CN109310662A - Linoleic acid and alpha-linolenic acid for reducing stress-induced cognitive decline/reduced neurogenesis in early life - Google Patents
Linoleic acid and alpha-linolenic acid for reducing stress-induced cognitive decline/reduced neurogenesis in early life Download PDFInfo
- Publication number
- CN109310662A CN109310662A CN201780037737.2A CN201780037737A CN109310662A CN 109310662 A CN109310662 A CN 109310662A CN 201780037737 A CN201780037737 A CN 201780037737A CN 109310662 A CN109310662 A CN 109310662A
- Authority
- CN
- China
- Prior art keywords
- life
- ala
- alimentation composition
- weight
- stress
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/201—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having one or two double bonds, e.g. oleic, linoleic acids
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
- A23L33/12—Fatty acids or derivatives thereof
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Mycology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pediatric Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
the present invention relates to a nutritional composition comprising Linoleic Acid (LA) and α -linolenic acid (ALA) in a weight ratio LA/ALA of 0.1 to 12, having a beneficial effect on preventing early-life stress-induced decline in cognitive function/preventing early-life stress-induced reduction of neurogenesis in a human subject.
Description
Technical field
The invention belongs to the field of alimentation composition, the alimentation composition is to the illness for reducing the induction of life early-life stress
With beneficial effect, such as to the life early-life stress induction for reducing life early-life stress, particularly human experimenter's experience
Cognition decline has the alimentation composition of beneficial effect.
Background technique
Known life early-life stress can have a negative impact to cognition in the whole life cycle of subject.By life morning
The cognition decline of phase stress-induced generally can not or only be remedied on limited extent.It is early interim in life, developmental people
The adjusting of class brain effect on environment is highly sensitive, therefore for remaining life, and the adaptation of any structure and function is all
It is programmed by the influence of these early stage environment.Direct correlation between life early-life stress and cognitive disorder is demonstrate,proved by clinical data
It is bright.This association is summarized in Trends in Neurosciences, 2013,36,621-631 by Lucassen et al..
Hippocampus is one of the brain region that a few remains able to generate new neuron in entire adult life.The mistake
Journey is referred to as adult neural.The neuron newly formed is most important to hippocampus function, and be related to hippocampus rely on inquiry learning and
The particular aspects of memory.Naninck et al. rolls up 25 (3): entitled " Chronic in 309-328 in Hippocampus (2015)
early life stress alters developmental and adult neurogenesis and impairs
In the article of cognitive function in mice ", the change of life early-life stress (ES) inducing neural generation is described
And the survival rate of the neuron of manhood formation reduces, and the neurogenesis and the cognitive disorder of manhood that change exist
It is functionally related.In brief, life early-life stress compromises the cognitive function of manhood and hippocampal neural occurs, also referred to as
" adult neural's generation ".Author indicate to want to know about the principle of the change of this life early-life stress induction for mental health and
Disease is very important, and should provide basis for following therapy intervention.
Summary of the invention
It is highly sensitive in the adjusting of life early stage, developmental human brain effect on environment, therefore for residue
For service life, the adaptation of any structure and function is programmed by the influence of these early stage environment.The present invention is intended to provide one
Kind influences brain structure and function by nutritional intervention, to mitigate the method due to the damage of life early-life stress.
Inventor surprisingly it has been found that, linoleic acid (LA) and alpha-linolenic acid (ALA) of the application comprising low LA/ALA weight ratio
Alimentation composition is effective in terms of the decrease of cognitive function of prevention life early-life stress induction.In object identification test,
Be subjected to the mouse performance of life early-life stress and feeding alimentation composition of the invention better than be subjected to it is identical stress but feeding have
There are the mouse of the alimentation composition of higher LA/ALA ratio, object space test and Mo Lisi water maze (Morris Water
Maze it) tests and is carried out in their manhood, this shows there is significant prevention effect to decrease of cognitive function.Therefore, people's will out
Material ground, by diet intervention, can prevent the negative effect of life early-life stress.
Inventor have further surprisingly found that application includes the linoleic acid (LA) and alpha-linolenic acid of low LA/ALA weight ratio
(ALA) alimentation composition is effective in terms of the nerve to occur reduction of prevention life early-life stress (ES) induction.It was found that using
Alimentation composition comprising low LA/ALA weight ratio carries out diet intervention, restores by the manhood after life early-life stress
Nerve to occur.Be subjected to it is identical stress but feeding with higher LA/ALA alimentation composition mouse compared with, be subjected to life morning
Phase stress and the mouse of feeding alimentation composition of the invention unexpected hippocampal cell survival is shown in its manhood
Phenomenon, this, which shows to reduce nerve to occur, has significant prevention effect.It therefore, unexpectedly, can be with by diet intervention
The negative effect for preventing life early-life stress.It can prevent life early-life stress from luring using low diet LA/ALA weight in life early stage
The damage led, especially prevents nerve to occur from reducing.
Specific embodiment
Therefore, the present invention relates to a kind of for preventing the decrease of cognitive function that life early-life stress induces in human experimenter
Method comprising to subject application comprising LA/ALA weight ratio be 0.1 to 12 linoleic acid (LA) and alpha-linolenic acid (ALA)
Alimentation composition.In one embodiment, the method for the decrease of cognitive function for preventing the induction of life early-life stress is
Non-medical method.
In other words, the present invention relates to a kind of for preventing the cognitive function that life early-life stress induces in human experimenter
The alimentation composition of decline, it includes linoleic acid (LA) and alpha-linolenic acid (ALA) that LA/ALA weight ratio is 0.1 to 12.
The present invention can also be expressed as linoleic acid (LA) and alpha-linolenic acid (ALA) in preparation for preventing in human experimenter
Purposes in the alimentation composition of the decrease of cognitive function of life early-life stress induction, the alimentation composition include LA/ALA weight
Amount is than the LA and ALA for 0.1 to 12.
The present invention can also be expressed as alimentation composition and recognize for prevent that life early-life stress in human experimenter induces
Know the purposes of function reduction, the alimentation composition includes the linoleic acid (LA) and α-flax that LA/ALA weight ratio is 0.1 to 12
Sour (ALA).
Subtract the invention further relates to a kind of for preventing the nerve to occur that life early-life stress (ES) induces in human experimenter
Few method comprising linoleic acid (LA) and α-flax to human experimenter's application comprising LA/ALA weight ratio for 0.1 to 12
The alimentation composition of sour (ALA).In one embodiment, subtract for preventing the nerve to occur of life early-life stress (ES) induction
Few method is non-medical procedures.
In other words, the present invention relates to a kind of for restoring mind in human experimenter in the manhood after life early-life stress
Method through occurring comprising the linoleic acid (LA) and α-for being 0.1 to 12 comprising LA/ALA weight ratio to human experimenter's application
The alimentation composition of linolenic acid (ALA).It in one embodiment, is non-doctor for restoring neurogenetic method in the manhood
Method.
In other words, the present invention relates to a kind of for preventing the nerve that life early-life stress (ES) induces in human experimenter
Reduced alimentation composition occurs, it includes linoleic acid (LA) and alpha-linolenic acid (ALA) that LA/ALA weight ratio is 0.1 to 12.
Again in other words, the present invention relates to a kind of for restoring in human experimenter in the manhood after life early-life stress
Neurogenetic alimentation composition, it includes linoleic acid (LA) and alpha-linolenic acid (ALA) that LA/ALA weight ratio is 0.1 to 12.
The present invention can also be expressed as linoleic acid (LA) and alpha-linolenic acid (ALA) in preparation for preventing in human experimenter
Purposes in the alimentation composition of the nerve to occur reduction of life early-life stress (ES) induction, the alimentation composition include LA/
The LA and ALA that ALA weight ratio is 0.1 to 12.
The present invention can also be expressed as linoleic acid (LA) and alpha-linolenic acid (ALA) in preparation for after life early-life stress
Manhood restore the purposes in human experimenter in neurogenetic alimentation composition, the alimentation composition includes LA/ALA
The LA and ALA that weight ratio is 0.1 to 12.
The present invention can also be expressed as alimentation composition and induce for preventing life early-life stress (ES) in human experimenter
Nerve to occur reduction purposes, the alimentation composition include LA/ALA weight ratio be 0.1 to 12 linoleic acid (LA) and α-
Linolenic acid (ALA).
The present invention can also be expressed as alimentation composition and restore human subjects for the manhood after life early-life stress
Neurogenetic purposes in person, the alimentation composition include the linoleic acid (LA) and α-Asia that LA/ALA weight ratio is 0.1 to 12
Numb acid (ALA).
In a preferred embodiment, life is prevented by hippocampal cell survival decline in prevention human experimenter
The nerve to occur of early-life stress (ES) induction is reduced.
In one aspect, the present invention relates to a kind of for preventing the sea that life early-life stress (ES) induces in human experimenter
The method of horse cell survival decline comprising the linoleic acid for being 0.1 to 12 comprising LA/ALA weight ratio to human experimenter's application
(LA) and the alimentation composition of alpha-linolenic acid (ALA).In one embodiment, the sea of prevention life early-life stress (ES) induction
The method of horse cell survival decline is non-medical procedures.
In other words, the present invention relates to a kind of for preventing the hippocampus that life early-life stress (ES) induces in human experimenter
The alimentation composition of cell survival decline, it includes linoleic acid (LA) and alpha-linolenic acid that LA/ALA weight ratio is 0.1 to 12
(ALA)。
The present invention can also be expressed as linoleic acid (LA) and alpha-linolenic acid (ALA) in preparation for preventing in human experimenter
Purposes in the alimentation composition of the hippocampal cell survival decline of life early-life stress (ES) induction, the alimentation composition include
The LA and ALA that LA/ALA weight ratio is 0.1 to 12.
The present invention can also be expressed as alimentation composition and induce for preventing life early-life stress (ES) in human experimenter
Hippocampal cell survival decline purposes, the alimentation composition include LA/ALA weight ratio be 0.1 to 12 linoleic acid (LA)
With alpha-linolenic acid (ALA).
All narrations below for method of the invention are equally applicable to purposes of the invention and are suitable for according to this
The composition used is invented, vice versa.
Alimentation composition
The alimentation composition applied according to the method for the present invention includes the linoleic acid (LA) that LA/ALA weight ratio is 0.1 to 12
With alpha-linolenic acid (ALA).The composition is referred to as " alimentation composition of the invention " or " alimentation composition ".
Alimentation composition of the invention can use and be suitable for administration to human experimenter, be preferably adapted for applying in life early stage
To any form of the nutrients of human experimenter.Alimentation composition of the invention can be added to the nutrition in normal diet
The human infant nutrition of replenishers (such as additive, hardening agent as normal diet), complete nutrient or suitable feeding infant
(such as infant formula or follow-up formula object).Preferably, alimentation composition is suitable for feeding infant and/or child.At one
In preferred embodiment, alimentation composition is selected from infant formula, follow-up formula object, growth dairy products and maternal nutritional supplement
Agent, most preferably alimentation composition are infant formulas.
According to the form of alimentation composition, it may be constructed complete nutrients or replenishers.Preferably, alimentation composition
It is complete nutrient.Preferably, composition contains lipid composition, digestible carbohydrate component and protein component.It
The ingredient of such as dietary fiber, minerals, vitamin, organic acid, nucleotide and flavoring agent can also be contained.Lipid composition is preferred
Every 100kcal composition 2.9 is provided to 6g lipid, protein component preferably provides every 100kcal composition 1.8 to 5.5g, closes
Every 100kcal composition 1.8 is to 2.5g suitablely, and digestible carbohydrate component preferably provides every 100kcal composition 9
To 14g.The amount of total calorie by from protein, lipid, digestible carbohydrate and indigestible oligosaccharide calorie
Summation determine.
Alimentation composition of the invention is usually enteral composition, i.e., for being administered orally.It is suitble to apply in liquid form
With.For example, composition may include other components dissolution or be suspended in water therein.Therefore, the composition suitably liquid
Or solid, or the form of stand-by water-reducible liquid concentrate, the solid is usually powder or tablet, can use liquid
Body suitably uses water or the liquid, aqueous redissolution of other food-grades, to obtain liquid composition.Preferably, liquid composition is viscous
Degree is lower than 100mPa.s, more suitably less than 60mPa.s, more suitably less than 35mPa.s, or even more suitably less than
6mPa.s, with 100s at 20 DEG C such as in Bu Shi (Brookfield) viscosimeter-1Shear rate measurement.In order to meet baby's
Heat demand, composition preferably comprise 45 to 200kcal/100ml liquid, and more preferable 60 to 90kcal/100ml liquid, even
More preferable 60 to 75kcal/100ml liquid.This heat density ensures the optimal proportion between water and heat consumption.This hair
The osmolarity of bright composition is preferably 150 to 420mOsmol/1, more preferable 260 to 360mOsmol/1.
Lipid
Alimentation composition includes lipid composition, the lipid group suitably known in the art for being suitable for human infant nutrition
Point.The lipid composition of this composition suitably provides every 100kcal composition 2.9 to 6.0g, and preferably 4 to 6g.When for liquid shape
When formula, alimentation composition preferably comprises every 100ml 2.1 to 6.5g lipid, more preferable every 100ml 3.0 to 4.0g.Lipid is preferred
The 30 to 60% of the total calorie of composition are provided.It is highly preferred that this composition includes to provide 35 to 55% rouge of total calorie
Matter, even further preferably, this composition includes to provide 40 to 50% lipid of total calorie.When for liquid form, such as
When as instant liquid, composition preferably comprises every 100ml 2.1 to 6.5g lipid, more preferable every 100ml 3.0 to 4.0g.?
In one embodiment, alimentation composition includes at least lipid of 15 weight %, based on the dry weight of composition.Based on dry weight
Meter, alimentation composition preferably comprise the lipid of 10 to 50 weight %, more preferable 12.5 to 40 weight %, and even more preferably 15 to 35
The lipid of weight %, the even more preferably lipid of 19 to 30 weight %.
It include lipid composition in alimentation composition include linoleic acid (LA) and alpha-linolenic acid (ALA).Herein,
" linoleic acid " or " LA " refers to linoleic acid chain and/or sub-oleoyl chain (18:2n6).Herein, " alpha-linolenic acid " or " ALA "
Refer to alpha-linolenic acid chain and/or α-linolenyl chain (18: 3n3).LA is preferably present in an amount sufficient, with promote healthy growth and
Development.Therefore, composition preferably comprises based on total fatty acids less than the LA of 20 weight %, preferably 5 to 15 weight %.It is preferred that
Ground, composition include the LA for being more than 5 weight % based on fatty acid, are preferably based on total fatty acids meter at least 10 weight %.It is preferred that
Ground, ALA is present in an amount sufficient, to promote healthy growth and development.Therefore, alimentation composition is preferably comprised based on total fatty acids
At least ALA of 0.5 weight % is counted, at least ALA of 1.0 weight % based on total fatty acids is preferably comprised.Preferably, composition packet
Containing at least ALA of 1.4 weight %, more preferably at least 1.5 weight % based on total fatty acids.Preferably, alimentation composition includes
Less than the ALA of 10 weight %, more preferably less than 5.0 weight %, based on total fatty acids.In one embodiment, nutrition group
The ALA that object includes at least LA of 10 weight % and at least 1 weight % is closed, the preferably weight of LA and 1 to 5 %'s of 10 to 20 weight %
ALA。
Surprisingly it has been found that compared with conventional nutrient composition, particularly conventional baby formulation, reduced LA/ALA
Weight ratio valuably influences subject by the cognition after life early-life stress, and prevents recognizing for life early-life stress induction
Know decline.The LA/ALA weight ratio of alimentation composition of the invention be 0.1 to 12, preferably 0.5 to 11, more preferably 0.8 to
10, more preferably 1 to 9, more preferably 1 to 8.
Lipid composition such as LA and ALA, and other components such as (LC-) PUFA being optionally present, can be used as free-fat
Acid, as a triglyceride, by triglyceride form, in the form of monoglyceride, with phospholipid form, or as above-mentioned a kind of or more
The mixture of kind provides.Preferably, alimentation composition includes triglycerides.Preferably, composition includes at least 70 weight %, more
The preferably at least triglycerides of 80 weight %, more preferably at least 85 weight %, the even more desirably at least glycerol three of 90 weight %
Ester, based on total lipid.Lipid can also include one of free fatty acid, monoglyceride and diglyceride or a variety of.
It has also been unexpectedly found that compared with conventional nutrient composition, particularly conventional baby formulation, reduced LA/
ALA weight ratio valuably influences subject and survives by the hippocampal cell after life early-life stress, and prevents life early stage and answer
The nerve to occur for swashing induction is reduced.The LA/ALA weight ratio of alimentation composition of the invention is 0.1 to 12, preferably 0.2 to 11,
Preferably 0.4 to 10, preferably 0.5 to 10, more preferably 0.6 to 10, more preferably 0.8 to 10, more preferably 1 to 8.
In a preferred embodiment, alimentation composition includes the triglycerides from plant fat.One into
In one step preferred embodiment, alimentation composition preferably additionally comprises phosphatide.Preferably, alimentation composition includes from inhuman
The phosphatide of mammalian milk.The presence of vegetable lipid is advantageously able to obtain optimal fatty acid profile, high how unsaturated rouge
Fat acid and closer human milk rouge.Use from ruminant cream, particularly individually cow's milk or other domestic ruminants
Lipid cannot provide best fatty acid profile.For example a large amount of saturated fatty acids of this not satisfactory fatty acid profile known are unhelpful
's.Preferably, this composition includes at least one, preferably at least two kinds of Lipid sources selected from the following: linseed oil (linseed
Oil), rapeseed oil (such as rape seed oil, Canola Oil and Canola oil), sage oil, perilla herb oil, purslane oil, more mandarin oil,
Seabuckthorn Oil, cannabis oil, sunflower oil, high oleic sunflower oil, safflower oil, high oleic safflower oil, olive oil, blackcurrant seed oil,
Blue dragonfly oil, coconut oil, palm oil and palm-kernel oil.Preferably, this composition include it is at least one, preferably at least two kinds selected from
Under Lipid sources: linseed oil, rape seed oil, coconut oil, sunflower oil and high oleic sunflower oil.Preferably, composition packet
Vegetable lipid containing 30 to the 99.5 weight % based on total lipid, more preferably based on 35 to 99 weight % of total lipid meter, even more
It is preferred that 40 to 95 weight %.
Preferably, alimentation composition includes from following fat or lipid: mammalian milk, more preferable ruminant
Cream, even more preferably cow's milk, goat dairy, sheep cream, buffalo's milk, yak milk, reinder cream and bactrian camel milk, most preferably cow's milk.Preferably,
Mammalian milk is not human milk.Therefore, in one embodiment, alimentation composition includes non-human mammal butterfat.It is preferred that
Ground, mammal butterfat component include at least triglycerides of 70 weight %, more preferably at least 90 weight %, and more preferably at least 97
Weight %.
Preferably, mammal butterfat is originated from butter, butter fat, cream and anhydrous milkfat, more preferable anhydrous milkfat and milk
Oil.The triglyceride levels of such butterfat Lipid sources are high.In addition, these Lipid sources are continuous fat phase or water in oil emulsion
The form of liquid.During preparing alimentation composition of the invention, it is capable of forming lipid globule using these butterfat sources, wherein often
A bead includes the mixture of plant fat and butterfat.
Preferably, alimentation composition includes the non-human mammal butterfat of 5 to the 70 weight % based on total lipid.At one
In embodiment, composition includes 10 to the 65 weight %, even more preferably 15 to 60 weight %, even more excellent based on total lipid
Select the non-human mammal butterfat of 25 to 55 weight %.Preferably, these butterfat are selected from butter, butter fat, cream and anhydrous lactitol
Rouge.Preferably, the ratio of plant fat and butterfat is 3/7 to 20/1.
Composition also may include non-plant lipid and non-dairy fat, such as the animal tallow other than butterfat, such as fish oil,
Egg lipid and microbial oil, algae oil, fungal oil or single cell oil.Preferably, the amount of non-plant non-dairy fat is base
In total lipid meter at most 10 weight %, more preferably up to 5 weight %.Preferably, the lipid packet in alimentation composition of the invention
Containing the adipose-derived of long-chain polyunsaturated fatty acid (LC-PUFA) is contained, it is selected from fish oil, marine product oil, algae oil, microorganism
Oil, single cell oil and egg lipid, in an amount of from 0.25 to the 10 weight % based on total lipid, preferably 0.5 to 10 weight %.
In an especially preferred embodiment, lipid is the form of lipid globule.When for liquid form, lipid is small
Ball emulsifies in water phase.Alternatively, lipid globule exists in powder form, the powder is suitable for water or another food-grade water phase
It redissolves.Usually and preferably, lipid globule includes core and surface.The core preferably comprises plant fat and butterfat, and preferably
Triglycerides comprising at least 80 weight %, more preferably at least 90 weight %, is more preferably substantially made of triglycerides.Not
Being present in all triglycerides lipids in composition must all be included in the core of lipid globule, but it is preferred most of in this way,
Preferably more than 50% weight, more preferably more than 70% weight are even more preferably more than 85 weight %, are even more preferably more than 95 weights
Measure %, the triglycerides lipid of most preferably greater than 98 weight % being present in composition is included in the core of lipid globule.
According to a preferred embodiment, mode diameter of the lipid globule based on volume is greater than 1.0 μm, preferably greater than
2.0 μm, preferably greater than 2.5 μm, more preferably greater than 3.0 μm.Preferably, mode diameter of the lipid globule based on volume is less than
6.0 μm, preferably smaller than 5.5 μm, more preferably less than 5.0 μm.Preferably, mode diameter of the lipid globule based on volume is 2 to 6
μm, preferably 2.0 to 6.0 μm, more preferable 2.5 to 6.0 μm, more preferable 3.0 to 6.0 μm, even more preferably 3.0 to 5.5 μm, even
More preferable 3.0 to 5.0 μm.Mode diameter refers to the peak value in the diameter being most commonly present based on total lipid volume, or diagram,
Using X- as diameter, using Y- as volume (%).Measure lipid globule volume and its size distribution appropriate method for example, by
The method recorded in Michalski et al, 2001, Lait 81:787-796, uses Malvern Particle Size Analyzer
(Malvern Instruments, Malvern, UK) is carried out.The specific surface area of lipid globule is the surface area of every weight lipid,
And reduce with the increase of bead size.Therefore, the specific surface area of lipid globule can be by the size distribution and rouge of lipid globule
The concentration and density of matter calculates.The preferred specific surface area of the lipid globule for including in alimentation composition is 0.5 to 15m2/ g lipid,
It is preferred that 1.0 to 10.0m2/ g, more preferable 1.5 to 8.0m2/ g, even more preferably 2.0 to 7.0m2/ g lipid.
Alimentation composition preferably comprises the phosphatide from (or " coming from ") non-human mammal cream.From non-human mammal
The phosphatide of cream includes glycerophosphatide and sphingomyelins.Phosphatide preferably is contained in the coating on lipid globule surface." coating " refers to
The outer surface layer of lipid globule includes phosphatide, and these phosphatide not actually exist in the core of lipid globule.Not it is present in
All phosphatide in alimentation composition must be all included in coating, but preferred most of such.It is preferably more than 30 weight %, excellent
Choosing is more than 50 weight %, more preferably more than 70 weight %, even more preferably more than 85 weight %'s, most preferably greater than 95 weight %
It is present in the phosphatide in composition included in the coating of lipid globule.
In one embodiment, alimentation composition includes at least phosphatide of 0.5 weight % based on total lipid.It is preferred that base
In the phosphatide of 0.5 to 20 weight % of total lipid meter, more preferably based on 0.5 to 10 weight % of total lipid meter, more preferable 1 to 10 weight
Measure the phosphatide of %, even more preferably 1.0 to 5 weight %, even more preferably 1.0 to 2.0 weight %.Preferably at least 80 weight %'s
Phosphatide be originated from non-human mammal cream, more preferably at least 90 weight %, even more desirably at least 95 weight % or 99 weight % or
It is preferred that all phosphatide are derived from non-human mammal cream.
Phosphatide preferably comprises sphingomyelins.Sphingomyelins has esterification at the phosphocholine or phosphoric acid second of the 1- hydroxyl of ceramide
Alcohol amine molecule.Preferably, sphingomyelins of the alimentation composition comprising 0.05 to the 10 weight % based on total lipid, more preferable 0.1 to 5
Weight %, even more preferably 0.2 to 2 weight %.Preferably, alimentation composition includes at least 15 weight % based on total phospholipids,
The more preferably at least sphingomyelins of 20 weight %.Preferably, the amount of sphingomyelins is lower than 50 weight %, based on total phospholipids.
Phosphatide preferably comprises glycerophosphatide.Glycerophosphatide is the lipoids formed by following substances: in main chain glycerol portion
The fatty acid being esterified on the hydroxyl on carbon -1 and carbon -2 divided, and the electronegative phosphoric acid connected by the carbon -3 of ester bond and glycerol
Group, and the choline group (phosphatidyl choline, PC), serine group (the phosphatidyl silk ammonia that are optionally connect with phosphate group
Acid, PS), ethanolamine group (phosphatidyl-ethanolamine, PE), (phosphatidyl is sweet for inisotol groups (phosphatidylinositols, PI) or glycerol group
Oil, PG).Preferably, alimentation composition contains PC, PS, PI and/or PE, more preferably at least contains PS.Preferably, nutrient combination
Object includes at least phosphatidylserine of 1 weight %, preferably at least 2 weight % based on total phospholipids.Preferably, phosphatidyl silk ammonia
The amount of acid is lower than 10 weight %, based on total phospholipids.
Phosphatide from non-human mammal cream includes the phosphatide separated from following substance: butterfat matter (milk
Lipid), cream lipid (cream lipid), cream serum lipids, butter serum lipid β serum lipid, whey lipid, cheese lipid
And/or buttermilk lipid.Preferably, phosphatide is obtained from cheese (milk cream).Phosphatide preferably originates from ox, mare, sheep, mountain
The cream of sheep, buffalo, horse and camel is most preferably originated from cow's milk.The lipid-soluble extract most preferably with separated from cow's milk.From non-
The suitable source of the phosphatide of people's mammalian milk is the part that can be separated from cream, is known as butterfat ball film (MFGM).Therefore, exist
It include the phosphatide in alimentation composition of the invention as MFGM offer in one embodiment.
Phosphatide is conveniently located on the surface of lipid globule, that is, is included in coating or outer layer.In one embodiment,
Lipid globule includes single layer, and it includes the phosphatide for being originated from butterfat.Determine the conjunction whether polar lipid is located on lipid globule surface
Suitable method is laser scanning microscopy or lens reflex type electronic microscopic method.Therefore, while the polarity for being originated from domestic animal cream is used
Lipid (especially phosphatide) and the triglycerides from vegetable lipid can manufacture the cladding with the coating for being more closely similar to human milk
Lipid globule, while providing optimal fatty acid profile.Obtain the lipid globule that there is such diameter and/or phosphatide to be coated
Method be disclosed in WO2010/0027258 and WO2010/0027259.
In one embodiment, alimentation composition includes at least the butyric acid chain and/or bytyry chain of 0.3 weight %
(BA), based on the poidometer of total fatty acids.In one embodiment, alimentation composition includes 0.3 to 4.0 weight %, preferably
The BA of 0.3 to 3 weight %, the poidometer based on total fatty acids.For being originated from the triglycerides of ruminant cream such as cow's milk, feature
It is the BA there are relatively high amount.It is not present in plant fat or fat rich in MCT as in coconut oil, and is being originated from cream
It is not also found in the polar lipid of rouge.It therefore, is fixed there are a kind of alternative of butterfat triglycerides in description composition
Adopted fatty acid profile, BA content is 0.3 to 4.0 weight %, based on total fatty acids.Total weight based on fatty acid, group
BA, preferably at least 0.5 weight %, more preferably at least 0.6 weight % that object preferably comprises at least 0.3 weight % are closed, more preferably extremely
Few 0.8 weight %.It is preferably based on the poidometer of total fatty acids, the weight % of the BA of composition is lower than 4 weight %, more preferably
Lower than 3 weight %, more preferably less than 2.5 weight %.
Preferably, alimentation composition includes at least 5 weight % medium chain fatty acid chains and/or fatty acyl based on total fatty acids
Base chain (MCFA), more preferably at least 7 weight %.In the context of the present invention, MCFA refers to a length of 8 to 12 carbon atoms of chain
Fatty acid chain and/or fatty acyl chain.The composition is advantageously comprised less than the MCFA of 15 weight % based on total fatty acids, more
Preferably smaller than 10 weight %.
Preferably, alimentation composition include based on total fatty acids the polyunsaturated fatty acid chain of 10 to 25 weight % and/
Or fatty acyl chain (PUFA).Amount greater than 25 weight %, which is higher than present in human milk, to be measured, and causes technical problem, such as nutrition
Stability in composition.
Preferably, alimentation composition includes long-chain polyunsaturated fatty acid chain and/or fatty acyl chain (LC-PUFA), more
It is preferred that n-3LC-PUFA.In the context of the present invention, PUFA containing at least 20 carbon atoms and has in fatty acyl chain
There are 2 or more unsaturated bonds.It is highly preferred that this composition includes eicosapentaenoic acid chain and/or eicosapentaenoic acyl group
Chain (20:5n3, EPA), clupanodonic acid chain and/or docosapentaenoic acyl chain (22: 5n3, DPA) and/or 22
Carbon acid chain and/or two dodecahexaene acyl chains (22:6n3, DHA), even more preferably DHA.Due to the DHA of low concentration,
DPA and/or EPA has been effective, and normal growth and development are important, therefore n-3LC-PUFA in alimentation composition
The content of (more preferable DHA) is preferably more than 5 weight % of total fatty acid content.Preferably, alimentation composition includes total fat
At least 0.15 weight % of acid content, preferably at least 0.35 weight %, more preferably at least 0.75 weight % n-3LC-PUFA (more
It is preferred that DHA).Alimentation composition preferably comprises at least LC-PUFA of 0.25 weight % based on total fatty acids.Preferably, nutrition
Lipid in composition include it is adipose-derived, it is described adipose-derived to include the 0.25 weight % to 5 weight % based on total fatty acids
LC-PUFA, wherein based on total fatty acids at least n-3LC-PUFA of 0.15 weight % be selected from DHA, EPA and DPA, more preferably
DHA 。
Due to n-6 fatty acid, especially chain of arachidonic acid and/or arachidonic acyl chain (20:4n6, ARA) and LA
As its precursor, acted on as its precursor with n-3 fatty acid, especially DHA and EPA and ALA on the contrary, therefore nutrient combination
Object preferably comprises the ARA of relatively small amount.N-6LC-PUFA content, more preferable ARA content are preferably more than 5 weight %, more preferably
No more than 2.0 weight %, more preferably no more than 0.75 weight %, even more preferably no more than 0.5 weight %, it is based on total fatty acids
Meter.Since in baby, ARA is important optimal functional film, especially nerve fiber film, therefore, n-6LC-PUFA,
It is preferred that the amount of ARA is preferably at least 0.02 weight %, more preferably at least 0.05 weight % based on total fatty acids, more preferably at least
0.1 weight %, more preferably at least 0.2 weight %.In the presence of preferred a small amount of ARA in the nutrients for being applied to 6 monthly ages baby below
In be it is particularly advantageous that this is because infant formula is usually unique source of nutrition for these babies.Preferably, n-
6LC-PUFA/n-3LC-PUFA weight ratio, more preferable ARA/DHA weight ratio are lower than 3, more preferably 2 or lower, even more preferably
It is 1 or lower.
Protein
Alimentation composition preferably comprises protein component.Protein component preferably provides the 5 to 15% of total calorie.It is preferred that
Ground, composition include to provide the protein of total calorie 6 to 12%.It is highly preferred that protein based on calorie to be lower than 9%
It is present in composition.Based on total calorie, human milk includes lesser amount of protein than cow's milk.Albumen in alimentation composition
Matter concentration is determined by the summation of protein, peptide and free amino acid.Based on dry weight, composition is preferably comprised less than 12 weight %
Protein, more preferable 9.6 to 12 weight %, even more preferably 10 to 11 weight %.Based on ready-to-drink liquid product, composition
Every 100ml is preferably comprised less than 1.5g protein, more preferably 1.2 to 1.5g, even more preferably 1.25 to 1.35g.
The source of protein component should be selected in this way, so that meeting the minimum requirements of essential amino acids content and ensuring to enable
The satisfied growth of people.It is therefore preferable that based on the milk protein such as protein source of whey, casein and its mixture, and
Protein based on soybean, potato or pea.Preferably, alimentation composition of the invention includes casein and lactalbumin.
Using lactalbumin, protein source is preferably based on acid whey or sweet whey, lactalbumin isolate or it is mixed
Object is closed, and may include α-lactalbumin and beta lactoglobulin.It is highly preferred that protein source is based on acid whey or sweet whey,
And from the wherein removing huge peptide of casein-sugar-(CGMP).Preferably, composition includes casein, and preferably it includes be based on dry weight
The meter at least casein of 3 weight %.Preferably, casein is complete and/or non-hydrolytic.For the present invention, protein packet
Include peptide and free amino acid.
Digestible carbohydrate
Preferably, alimentation composition includes digestible carbohydrate component.Digestible carbohydrate component preferably mentions
For the 30 to 80% of the total calorie of composition.Preferably, digestible carbohydrate component provides the 40 to 60% of total calorie.
When for liquid form, such as when as instant liquid, composition, which preferably comprises every 100ml 3.0 to 30g, can digest carbon aquation
Close object, more preferable 6.0 to 20g, even more preferably every 100ml 7.0 to 10.0g.Based on dry weight, this composition is preferably comprised
The digestible carbohydrate of 20 to 80 weight %, more preferable 40 to 65 weight %.
Preferred digestible carbohydrate source is lactose, glucose, sucrose, fructose, galactolipin, maltose, starch
And maltodextrin.Lactose is main digestible carbohydrate present in human milk.Lactose advantageously has low-glycemic.
This composition preferably comprises lactose.This composition preferably comprises digestible carbohydrate component, wherein at least 35 weight %, more
Preferably at least 50 weight %, more preferably at least 75 weight %, even more desirably at least 90 weight %, most preferably at least 95% weight
Digestible carbohydrate be lactose.Based on dry weight, this composition preferably comprises at least the lactose of 25 weight %, preferably extremely
Few 40 weight %.
Other components
In one embodiment, alimentation composition preferably comprises indigestible oligosaccharide.Preferably, this composition packet
The indigestible oligosaccharide for being 2 to 250, more preferable 3 to 60 containing the degree of polymerization (DP).Preferred indigestible oligosaccharide is selected from
Oligofructose, galactooligosaccharide and/or galactoronic acid oligosaccharides, more preferable galactooligosaccharide, most preferably trans- oligomeric gala
Sugar.In a preferred embodiment, composition includes the mixture of transgalactooligosac,harides and oligofructose.Suitably not
Digestible oligosaccharide is such as Vivinal GOS (FrieslandCampina DOMO), Raftilin HP or Raftilose
(Orafti)。
Preferably, composition includes the indigestible oligosaccharide of every 100ml 80mg to 2g, more preferable every 100ml 150mg
To 1.50g, even more preferably 300mg to 1g.Based on dry weight, composition preferably comprises 0.25 weight % to 20 weight %, more
It is preferred that 0.5 weight % to 10 weight %, even more preferably 1.5 weight % are to 7.5 weight %.
According to the international instruction of human infant nutrition, particularly infant formula, composition preferably comprises other compositions, such as
Vitamin, minerals.
Using
Inventor surprisingly it has been found that, alimentation composition of the invention prevention human experimenter in life early-life stress induction
Decrease of cognitive function in terms of be effective.Therefore, method of the invention is related to applying this in the life early stage of human experimenter
The alimentation composition of invention.When composition is liquid form, the preferred volume of daily administration is daily about 80 to 2500ml, more
Preferably from about 450 to 1000ml.
Inventor surprisingly it has been found that, alimentation composition of the invention prevention human experimenter in life early-life stress induction
Nerve to occur reduce aspect be effective.Therefore, method of the invention is related to applying this in the life early stage of human experimenter
The alimentation composition of invention.When composition is liquid form, the preferred volume of daily administration is daily about 80 to 2500ml, more
Preferably from about 450 to 1000ml.
In the context of the present invention, " prevention " can also referred to as " reduction ", " reduce ... risk or generation ",
" ... prevention " or " ... prophylactic treatment "." the cognitive function of prevention life early-life stress induction that the present invention uses
Decline " can also be expressed as " stimulating cognitive function after by life early-life stress " or " change after by life early-life stress
Kind cognitive function "." nerve to occur of prevention life early-life stress induction is reduced " that the present invention uses can also be expressed as " protection
From life early-life stress induction nerve to occur reduce " or " restoring nerve to occur after by life early-life stress " or "
By stimulating nerve to occur after life early-life stress " or " improving nerve to occur after by life early-life stress ".In addition, this hair
Bright " nerve to occur in manhood human experimenter " used can also be expressed as " adult neural's generation ".
In the context of the present invention, " life early stage (early life) " typically lasted for and including puberty, such as
It is the oldest to 18 years old, even more preferably maximum to 36 monthly ages more preferably up to 5 years old preferably at most to 12 years old, most preferably most
Greatly to 12 monthly ages.Life early stage further includes the antenatal stage of human experimenter, preferred the fetal state, more preferable third trimester of pregnancy
The fetal state.In one embodiment, life early stage is since birth.
Human experimenter is preferably selected from unborn fetus, baby, child, children, preadolescence teenager and teenager.?
In one further preferred embodiment, human experimenter be selected from unborn fetus, infants and young, be more preferably selected from baby and
The human experimenter that child, i.e. age are 0 to 36 month, most preferably human experimenter is baby, i.e. the age is 0 to 12 month.
Unborn fetus is preferably in third trimester of pregnancy.It is administered to unborn fetus by pregnant mother, and alimentation composition is excellent
Choosing uses the form of maternal nutritional replenishers.Since the lipid composition of mother's diet is embodied in her breast milk, alimentation composition
The form of breast feeding women's nutritional supplement can also be used.Particularly preferably maximum is to 36 monthly ages or even maximum to 12 monthly ages
Human experimenter because therefore brain plasticity highest is applied in this stage in general, in the early stage of survival
Alimentation composition is influenced with highest.
In a preferred embodiment, human experimenter is in the risk of experience life early-life stress or even locates
In the high risk of experience life early-life stress, or positive experience life early-life stress.This kind of reality in (height) risk subjects
Example is from subject below, i.e., the children of especially lower socio-economic status is (for example, from income level lower than average
Horizontal or education degree is low for example no more than the children of the family of senior middle school), it is the children of parent's separation or experience separation, double with parent
The isolated children in one of side, the children that parent both sides work, ignored children, aggrieved children, parent by pressure,
Children, depression children, sick children, underfed children and the children by violence of depression.Herein, " youngster
It is virgin " it include infants and young, it is preferable that and children are babies.
The particular subject of experience body pressure and/or stress is the baby of premature and small for gestational age infant (SGA).
Premature refers to before the standard gestational period terminates, therefore is opened from the last menstrual period of mother before mother's gestation 37 weeks
Before 37 weeks to begin, the baby of birth.Premature is also referred to as premature infant.SGA baby is birth weight lower than the pregnant age 10%
Baby.The reason of SGA, can be several；For example, term infant or premature can be born SGA, because they have been palaces
The subject of interior growth restriction (IUGR).Many prematures are also small for gestational age.Premature infant and/or SGA baby include low
Birth weight infant (LBW baby), very low birth weight baby (VLBW baby) and low birth weight baby (ELBW baby).
LBW baby is the baby that birth weight is lower than 2500g；The group includes the born SGA of term infant.VLBW and ELBW baby is almost always
Born premature labor, and it is defined as the baby that birth weight is respectively lower than 1500g or 1000g.Therefore, in method of the invention or
In one embodiment of purposes, human experimenter is premature, be born all is less than baby of gestational age or both.
Seem there are indications that the decrease of cognitive function that male subject is induced by a greater degree of life early-life stress,
Therefore human male subject may benefit more from current diet intervention.Therefore, in one embodiment, Ren Leishou
Examination person is male.
Therefore, when human experimenter be 18 years old or smaller when, preferably the age of human experimenter be lower than 12 years old, more preferably most
Greatly to 5 years old, even more preferably maximum to 36 monthly ages, most preferably maximum is usually administered nutrition group of the invention to 12 monthly ages
Close object.Although life usual earlier stops after puberty, cognition and/or neurogenetic beneficial effect may persistently be surpassed
Spend life early stage, such as until manhood or even more than manhood.Effect possibly even continues the entire service life of subject.Root
According to a preferred embodiment, the cognition decline and/or neurogenetic reduction for preventing the induction of life early-life stress are extended to
Manhood.Preferably, when subject has reached the manhood or when subject has reached 18 years old or the bigger age, or even 25 years old
Or it when bigger age, shows prevention decrease of cognitive function and/or nerve to occur is reduced.It is therefore preferable that nutrition of the invention
Composition has influence to the cognition of later stage of life and/or nerve to occur.Herein, what prevention life early-life stress induced recognizes
Know that function reduction and/or nerve to occur reduction are showed in later stage of life, preferably when subject reaches 5 years old.According to one
Preferred embodiment stops after applying alimentation composition of the invention, extends to cognition and/or neurogenetic beneficial effect
At least three moon, preferably at least 1 year, more preferably at least 5 years.The example of this influence to later stage of life --- it is the present invention
One particularly preferred embodiment --- it is that composition of the invention is administered to fetus, baby or child, most preferably applies
To baby, and the prevention effect of cognition decline and/or nerve to occur reduction to the induction of life early-life stress was at 5 years old or bigger
Age, more preferably at 12 years old or the bigger age, most preferably at 18 years old or the bigger age is observed.
Any known form can be used in life early-life stress.Typical pressure source includes psychological testis, physical stress source
With body pressure source.Life early-life stress can be the form of stress, body pressure, Metabolic stress or any combination thereof.
Exemplary pressure source includes the family (such as divorce, separation, recombination family) of rupture；With parent one or both separate (such as
Parent's imprisonment)；Mother's depression；Parent works；Lack parent's concern；By violence, maltreat (such as body, spirit, property), neglect
Depending on (such as mood, body), relatives dead (especially parent is dead), disease (such as spirit, body), malnutrition.At this
Wen Zhong, " parent " can also refer to " caretaker " or " guardian ".Most suitably, life early-life stress is selected from malnutritive, mother
It pressure, depression and maltreats.
The cognition decline of life early-life stress induction is a kind of cognition decline of specific type, many complexity with brain
Structure is related, such as cerebral cortex, cortex of frontal lobe, hypothalamus, hippocampus and nose week cortex.These structures in brain are being recognized and are being adjusted
It plays an important role in section stress reaction.For example, hippocampus contains, there are many stress hormone receptors, and are that height is plastic.Due to this
A little structures are developed rapidly behind last three months of gestation and birth, until about 16 years old or bigger, therefore they are to early-life stress
It is especially sensitive.
In a preferred embodiment, the cognitive function of decline preferably includes the hippocampus-dependent cognitive function of decline
Can, or the cognitive function of decline is preferably the hippocampus-dependent cognitive function of declining.In the context of the present invention, function is recognized
The particularly preferred embodiment of energy is (a) new object identification；(b) preference of new things；(c) pay attention to (change) environment；(d) non-
Space (object) memory；(e) spatial memory and (f) spatial reference memory, but also include new object identification and/or new object position
It sets or hippocampal-dependent memory (especially long term spatial memory).
In a preferred embodiment, neurogenetic subtract is prevented by the decline of prevention hippocampal cell survival
It is few.Alternatively, the invention further relates to apply alimentation composition of the invention by the life early stage in human experimenter to prevent to give birth to
The hippocampal cell for ordering early-life stress induction, which is survived, to be declined.It is used herein that " hippocampal cell of prevention life early-life stress induction is deposited
Decline living " can also be expressed as " stimulating hippocampal cell to survive after by life early-life stress " or " answer by life early stage
Improve hippocampal cell survival after swashing ".
Embodiment
Embodiment 1:
Such as Nainck et al., described in Hippocampus 2015,25:309-328, suffer a few nest female C57/BL6 mouse
By life early-life stress mode, the life early-life stress mode is made of limited nest/bedding material.Stress model is in every nest
Start within 2 days (PN2) after birth, continues to PN9.A few nest mouse are weaned in PN21.
Since PN2, offspring is by (lactating dam) contact experimental diet of sucking the breast, until PN42 is (male after wean
Offspring keeps respective diet).Terminate from PN42 to experiment, all male offsprings all identical AIN-93M diet of feeding.
It is formed according to American Nutrition Society (American Institute of Nutrition) dynamic for laboratory grinding tooth
The AIN93-G purified diet (Reeves 1993) of object, experimental diet are half with macronutrient and micronutrient composition
Diet is synthesized, and only different from linoleic acid (LA) and alpha linolenic acid (ALA) content in terms of fatty acid composition, referring to table 1.
In the manhood, using new object identification test, object space test and the test of Mo Lisi water maze to male offspring
Carry out cognitive performance test.These tests are widely used in behavioral neuroscience field.
Table 1: the fatty acid composition of experimental diet.
New object identification and the test of new object space
At the 120th day, new object identification test (ORT) is carried out to mouse.The test is the elder generation based on mouse to new things
Its preference come study to non-space object memory preference action process.In testing, mouse has to differentiate between new object and he
Before (known) object for exploring.In three days, mouse gets used to entering the test activity being made of rectangular plastic box
5 minute/day of place.On the day of training, mouse has 5 minutes to explore two identical objects (vial of 9.5cm high), these
Object is placed in 12cm apart and box apart from wall 11cm.On the day of the test after training for 24 hours, by an object
It is replaced with the new object (being made of yellow Lego Duplo building blocks) for being placed on identical position, and mouse is reintroduced back to work
Dynamic place 5 minutes, to explore new object and familiar objects.Each object the time it takes is explored in measurement, and calculate new object/
The ratio of the exploration time of familiar objects.As a result it is shown in Table 2.
Object space tests (OLT): the test is to study space object for the congenital curiosity of new position based on mouse
The action process of body memory.Test was carried out at PN 130 days.For OLT, playground and habit scheme and phase used in ORT
Together；Two completely new same object (whitening coffee cup) 12cm apart and apart from wall 11cm.On the day of training, mouse has
Explore object and its position within five minutes.On the day of test, after training for 24 hours, an object is moved in playground
New position, and mouse is reintroduced back to 5 minutes in playground and is explored.As previously mentioned, record explores the time spent simultaneously
Calculate new object/familiar objects detection time ratio.The results are shown in Table 2.
Table 2: new object/past heritage body (position) explores time scale
| Group | New object/past heritage body ratio in ORT | New object/past heritage body ratio in OLT |
| Control diet A | 2.5±0.46 | 1.4±0.19 |
| It stress diet A | 1.26±0.07 | 0.96±0.06 |
| Control diet B | 2.38±0.33 | 1.40±0.08 |
| It stress diet B | 2.02±0.18 | 1.61±0.22 |
As can be seen from Table 2, new object/past heritage body explores the ratio of time because of elder generation during ORT in the animal of feeding diet A
It is preceding to be reduced by early-life stress, this show animal cannot be distinguished object that they have seen and they see for the first time it is new
Object.In the animal of feeding diet B, there is no reduce the index because of Stress model.Two stress be between diet group
Difference have statistical significance, show diet B can prevent stress-induced cognitive performance damage, especially new things preference and
Non-space memory capability.
In the animal of feeding diet A, new object/past heritage body explores the ratio of time also because previously by morning during OLT
Phase stress and reduce, this shows that object in the position and the object for being moved to new position cannot be distinguished in animal.On the contrary,
In the animal of feeding diet B, this species diversity is not present.This shows that diet B can prevent the cognitive performance damage of stress-induced, special
It is not new things preference and spatial memory performance.
Mo Lisi water maze
Mouse also carries out the test of Mo Lisi water maze at PN 140, is also referred to as Mo Lisi water maze navigational duty,
This is a kind of behavior program for studying cognitive function, particularly Spatial learning and memory.In this experiment, animal is instructed
Practice, to find out hiding platform based on environmental cues.In brief, platform is just immersed in consolidating below the water surface in cylindrical tank
Positioning is set.Water tank has on wall in the fixed space prompted, these prompts can see from the water surface of water tank.Continuous 7 days, daily
Mouse is trained twice (intertrial interval 10 minutes), to find hiding platform.During each test, animal is put into water tank
In water, and platform must be found in 60 seconds.Between test, the initial position of animal not platform three quadrants it
Change between one.At the 8th day, platform is removed from pond, to carry out Single probe test, is spent wherein being recorded in target quadrant
Time.The test is known as probe test.As a result it is shown in Table 3.
Table 3: the time (%) spent in target quadrant in the probe test of Mo Lisi water maze.
| Group | Time (%) |
| Control diet A | 31.2±4.83 |
| It stress diet A | 26.8±3.67 |
| Control diet B | 34.6±5.56 |
| It stress diet B | 37.3±6.16 |
It can be inferred to from table 3, in the animal of feeding diet A, due to previously reducing by early-life stress in mesh
The percentage of time that spends in mark quadrant, this shows the position where animal forgets platform.However, contact diet B can be to prevent
Only stress-induced spends time-related damage in target quadrant.This shows cognitive performance, particularly long-term (space) memory
Performance makes moderate progress.
Embodiment 2
Use the bromo- 2 '-BrdU (BrdU of 5-；Sigma-Aldrich Chemie BV, Zwijndrecht, The
Netherlands) cell survival of born neuron of growing up is assessed.7 months after birth, to injection in mouse peritoneum
100mg/kg BrdU (10mg/ml is dissolved in+0.007M NaOH in Sterile Saline), continuous 4 days, 2 times a day.Last time is infused
Rear surrounding is penetrated, in P230 through heart perfusion to mouse.
Tissue collecting carries out as follows: by intraperitoneal injection amobarbital (, 120mg/kg) and small to anaesthetize
Mouse uses 0.9% salt water first, and then with 4% paraformaldehyde (PFA), (PB 0.1M, pH 7.4) is passed through in phosphate buffer
Heart perfusion.The brain being entirely perfused carefully is taken out, after fixing 24 hours in 0.1.M PB with 4%PFA at 4 DEG C, at 4 DEG C
Under be stored in the PB containing 0.01% sodium azide.It is before brain section, the brain of perfusion is molten in 0.1M PB in 30% sucrose
Cryoprotection in liquid.Then, the brain of freezing is cut into the coronal sections of 40 μ m-thicks, and 6 collateral series are divided by slicer
Column, and be stored in antifreezing agent (with 30% ethylene glycol, 20% glycerol, 50%0.05M PBS) at -20 DEG C.
Use the cell of immunohistochemistry's detection BrdU label.By brain section (from one of 6 parallel series)
(Superfrost Plus glass slide, Menzel, Braunschweig, Germany) is mounted on glass, then in 0.1M lemon
Microwave (Samsung M6235) thermal induction antigen retrieval 15min at about 95 DEG C is used in lemon phthalate buffer (pH 6.0)
(800 watts of lower 5min, 400 watts of lower 5min, 200 watts of lower 5min).Then, preassembled slice is handled with inhibition buffer
30min (1% bovine serum albumin(BSA) in TBS), then with the anti-BrdU (1: 200 of first antibody monoclonal rat；Accurate
Chemical and Scientific Corporation, OBT 0030) mixtures incubated (1% bovine serum albumin(BSA),
0.3%Triton X-100 in 0.05M TBS) in be incubated with for 24 hours.Then, will slice with the anti-rat of secondary antibody donkey,
488 conjugate of alexa fluor (1:1000, Invitrogen) is incubated with 2h, and is covered with the Vectashield containing DAPI
Lid.
In order to determine dentation gyrus (DG) particle region volume, use Stereoinvestigator software
(MicroBrightField, Germany) uses 20 times of magnifying powers on Zeiss Axiophot optical microscopy, before being eight
Boundary profile trace is arranged in fontanel, multiplied by 6 (correct parallel series) and multiplied by 40 μm (for the thickness of slice).For BrdU (40
Times object lens, Leica CTR5500) it is quantitative, in eight matched bregmas, carried out in the submicron particle region of DG and particle region
Cell count, and by the sum of the immunoreactive cell of each DG multiplied by 6.
As a result it is shown in figure.The figure shows the control group (hollow strips in left side) for not being subjected to early-life stress and it has been subjected to
The hippocampal cell survival rate of the diet A and diet B of the group (the filled black item on right side) of early-life stress, are measured as dentation gyrus
(DG) the BrdU cell marked in.Compared with diet B, for diet A, the hippocampal cell survival after being subjected to early-life stress is aobvious
Writing reduces.For diet B, the hippocampal cell after being subjected to early-life stress is survived, and is not subjected to early stage with for two kinds of diet
Stress after hippocampal cell survival it is identical.
From these results it can be concluded, nutritional intervention is carried out to reduction early-life stress with the diet of low LA/ALA ratio
Nerve to occur afterwards has prevention effect, or in other words, the nerve to occur that can prevent early-life stress induction is reduced.In addition,
It is sent out it may be concluded that carrying out nutritional intervention with the diet of low LA/ALA ratio and having restored the nerve of manhood after early-life stress
It is raw.
Claims (18)
1. linoleic acid (LA) and alpha-linolenic acid (ALA) are recognized in preparation for prevent that life early-life stress in human experimenter induces
Know the purposes in the alimentation composition of function reduction, the alimentation composition include the LA that LA/ALA weight ratio is 0.1 to 12 and
ALA。
2. purposes according to claim 1, wherein cognitive function includes hippocampus-dependent cognitive function, especially new object
Identification and/or new object space.
3. purposes according to claim 1 or 2, wherein cognitive function includes hippocampal-dependent memory.
4. linoleic acid (LA) and alpha-linolenic acid (ALA) are in preparation for preventing the mind that life early-life stress induces in human experimenter
Occurred the purposes in reduced alimentation composition, the alimentation composition include the LA that LA/ALA weight ratio is 0.1 to 12 and
ALA。
5. linoleic acid (LA) and alpha-linolenic acid (ALA) restore human subjects for the manhood after life early-life stress in preparation
Purposes in person in neurogenetic alimentation composition, the alimentation composition include the LA that LA/ALA weight ratio is 0.1 to 12
And ALA.
6. a kind of alimentation composition is used to restore nerve to occur in human experimenter in the manhood after life early-life stress,
The alimentation composition includes the linoleic acid (LA) and alpha-linolenic acid (ALA) that LA/ALA weight ratio is 0.1 to 12.
7. purposes according to any one of the preceding claims, wherein life early-life stress is selected from psychological stress, physiology is answered
Sharp, metabolic stress and combinations thereof.
8. purposes according to any one of the preceding claims, wherein human experimenter is unborn fetus, Ying Erhuo
Child.
9. purposes according to any one of the preceding claims is less than when wherein human experimenter is preemie, birth
Baby of gestational age or both is.
10. purposes according to any one of the preceding claims, wherein alimentation composition is infant nutrition, preferably baby
Formulation, follow-up formula object or growth dairy products.
11. purposes according to any one of the preceding claims, wherein LA/ALA weight ratio is 0.5 to 8.
12. purposes according to any one of the preceding claims, wherein alimentation composition includes lipid composition, protein group
Point and digestible carbohydrate component.
13. purposes according to any one of the preceding claims, wherein the cognitive function of prevention life early-life stress induction
Decline is showed in later stage of life, preferably when subject reaches 5 years old.
14. purposes according to any one of the preceding claims, wherein the nerve to occur of prevention life early-life stress induction
Reduction is showed in later stage of life.
15. purposes according to claim 14, wherein later stage of life is when human experimenter has arrived at the manhood.
16. linoleic acid (LA) and alpha-linolenic acid (ALA) are lured in preparation for preventing life early-life stress (ES) in human experimenter
Purposes in the alimentation composition for the hippocampal cell survival decline led, the alimentation composition include that LA/ALA weight ratio is 0.1
To 12 LA and ALA.
17. a kind of for preventing the method for the decrease of cognitive function that life early-life stress induces in human experimenter comprising to
The alimentation composition of linoleic acid (LA) and alpha-linolenic acid (ALA) that subject's application is 0.1 to 12 comprising LA/ALA weight ratio.
18. a kind of for preventing the method for the nerve to occur reduction that life early-life stress induces in human experimenter comprising to
The alimentation composition of linoleic acid (LA) and alpha-linolenic acid (ALA) that subject's application is 0.1 to 12 comprising LA/ALA weight ratio.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/NL2016/050271 WO2017183956A1 (en) | 2016-04-18 | 2016-04-18 | Linoleic acid and alpha-linolenic acid for use for reducing early-life stress induced cognitive decline |
| NLPCT/NL2016/050271 | 2016-04-18 | ||
| EP16188154 | 2016-09-09 | ||
| EP16188154.5 | 2016-09-09 | ||
| PCT/NL2017/050246 WO2017183970A1 (en) | 2016-04-18 | 2017-04-18 | Linoleic acid and alpha-li nolenic acid for use for reducing early-life stress induced cognitive decline/reduction in neurogenesis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109310662A true CN109310662A (en) | 2019-02-05 |
Family
ID=58639027
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201780037737.2A Pending CN109310662A (en) | 2016-04-18 | 2017-04-18 | Linoleic acid and alpha-linolenic acid for reducing stress-induced cognitive decline/reduced neurogenesis in early life |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP3445353A1 (en) |
| CN (1) | CN109310662A (en) |
| BR (1) | BR112018071493A2 (en) |
| RU (1) | RU2741495C2 (en) |
| WO (1) | WO2017183970A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024121222A1 (en) * | 2022-12-06 | 2024-06-13 | N.V. Nutricia | Infant formula for improving cognitive development |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1436048A (en) * | 2000-04-13 | 2003-08-13 | 艾博特公司 | Infant formulas containing long-chain polyunsaturated fatty acids and uses thereof |
| CN1842277A (en) * | 2003-06-24 | 2006-10-04 | 堪萨斯大学医学中心 | infant formula |
| CN101389227A (en) * | 2005-12-23 | 2009-03-18 | 纽崔西亚公司 | Nutritional composition for infants and young children for preventing obesity |
| CN101773223A (en) * | 2010-02-11 | 2010-07-14 | 圣元营养食品有限公司 | Infant food composite |
| CN102448328A (en) * | 2009-06-02 | 2012-05-09 | 雀巢产品技术援助有限公司 | Nutritional composition to support brain development and function in young children |
| CN102892300A (en) * | 2010-03-17 | 2013-01-23 | N·V·努特里奇亚 | Infant nutrition for improving fatty acid composition of brain membranes |
| WO2015086169A1 (en) * | 2013-12-12 | 2015-06-18 | Nestec S.A. | Synthetic milk compositions comprising polyunsaturated fatty acids (pufas) for promoting the healthy establishment of cognitive function in male and female infant and children |
| CN104825480A (en) * | 2007-06-26 | 2015-08-12 | N·V·努特里奇亚 | Improved memory in subjects with Mini-Mental State Examination values of 24-26 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1656839A1 (en) * | 2004-11-11 | 2006-05-17 | N.V. Nutricia | Nutrition containing lipid blend |
| AU2006327995B2 (en) * | 2005-12-23 | 2012-09-13 | N.V. Nutricia | Infant nutritional compositions for preventing obesity |
| WO2009002145A1 (en) * | 2007-06-26 | 2008-12-31 | N.V. Nutricia | Lipid composition for improving function of brain functioning |
| SI2554056T1 (en) | 2008-09-02 | 2020-02-28 | N.V. Nutricia | Nutritional compositions with large diameter lipid globules with a coating comprising phospholipids |
| JP6067558B2 (en) * | 2011-06-29 | 2017-01-25 | 日本水産株式会社 | How to reduce fear memory |
-
2017
- 2017-04-18 BR BR112018071493-3A patent/BR112018071493A2/en not_active Application Discontinuation
- 2017-04-18 EP EP17719941.1A patent/EP3445353A1/en not_active Withdrawn
- 2017-04-18 CN CN201780037737.2A patent/CN109310662A/en active Pending
- 2017-04-18 WO PCT/NL2017/050246 patent/WO2017183970A1/en not_active Ceased
- 2017-04-18 RU RU2018140486A patent/RU2741495C2/en active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1436048A (en) * | 2000-04-13 | 2003-08-13 | 艾博特公司 | Infant formulas containing long-chain polyunsaturated fatty acids and uses thereof |
| CN1842277A (en) * | 2003-06-24 | 2006-10-04 | 堪萨斯大学医学中心 | infant formula |
| CN101389227A (en) * | 2005-12-23 | 2009-03-18 | 纽崔西亚公司 | Nutritional composition for infants and young children for preventing obesity |
| CN104825480A (en) * | 2007-06-26 | 2015-08-12 | N·V·努特里奇亚 | Improved memory in subjects with Mini-Mental State Examination values of 24-26 |
| CN102448328A (en) * | 2009-06-02 | 2012-05-09 | 雀巢产品技术援助有限公司 | Nutritional composition to support brain development and function in young children |
| CN101773223A (en) * | 2010-02-11 | 2010-07-14 | 圣元营养食品有限公司 | Infant food composite |
| CN102892300A (en) * | 2010-03-17 | 2013-01-23 | N·V·努特里奇亚 | Infant nutrition for improving fatty acid composition of brain membranes |
| CN104351796A (en) * | 2010-03-17 | 2015-02-18 | N·V·努特里奇亚 | Infant nutrition for improving fatty acid composition of brain membranes |
| WO2015086169A1 (en) * | 2013-12-12 | 2015-06-18 | Nestec S.A. | Synthetic milk compositions comprising polyunsaturated fatty acids (pufas) for promoting the healthy establishment of cognitive function in male and female infant and children |
Non-Patent Citations (4)
| Title |
|---|
| ARTEMIS P. SIMOPOULOS: "Evolutionary Aspects of Diet: The Omega-6/Omega-3 Ratio and the Brain", 《MOL NEUROBIOL》 * |
| FENOGLIO ET AL: "Hippocampal neuroplasticity induced by early-life stress:Functional and molecular aspects", 《FRONT NEUROENDOCRINOL》 * |
| HUI GAO: "Long-Term Dietary Alpha-Linolenic Acid Supplement Alleviates Cognitive Impairment Correlate with Activating Hippocampal CREB Signaling in Natural Aging Rats", 《MOL NEUROBIOL》 * |
| JONATHAN Y. BERNARD ET AL: "The association between linoleic acid levels in colostrum and child cognition at 2 and 3 y in the EDEN cohort", 《PEDIATRIC RESEARCH》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| BR112018071493A2 (en) | 2019-02-19 |
| RU2018140486A3 (en) | 2020-07-14 |
| WO2017183970A1 (en) | 2017-10-26 |
| RU2018140486A (en) | 2020-05-19 |
| EP3445353A1 (en) | 2019-02-27 |
| RU2741495C2 (en) | 2021-01-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Bobiński et al. | Fatty acids of human milk–a review | |
| Lim et al. | An extraordinary degree of structural specificity is required in neural phospholipids for optimal brain function: n‐6 docosapentaenoic acid substitution for docosahexaenoic acid leads to a loss in spatial task performance | |
| De Giuseppe et al. | n-3 LC-PUFA supplementation: effects on infant and maternal outcomes | |
| ES2811549T3 (en) | Methods of maintaining or increasing cognitive growth or development | |
| EP2753190B1 (en) | Use of infant formula with cholesterol | |
| RU2761114C2 (en) | Infant formula for improving eating behaviour | |
| CN108366986A (en) | Infant formula with milk fat for promoting healthy growth | |
| EP2753191B1 (en) | Use of infant formula with large lipid globules | |
| AU2022204529B2 (en) | Nutritional composition for improving cell membranes | |
| Alshaikh et al. | The role of dietary fats in the development and prevention of necrotizing enterocolitis | |
| EP4068993B1 (en) | Infant formula with special lipid architecture for improving postnatal growth of infants born to overweight and obese mothers | |
| CN109310662A (en) | Linoleic acid and alpha-linolenic acid for reducing stress-induced cognitive decline/reduced neurogenesis in early life | |
| Anaizi | Fat facts: an overview of adipose tissue and lipids | |
| EP3599895B1 (en) | Infant formula for improved eating behaviour | |
| US11707080B2 (en) | Infant formula with special lipid architecture for improving postnatal growth of infants born by Caesarean section | |
| CN102438467A (en) | Stage 1 and Stage 2 Infant Formula | |
| CN114845570A (en) | Infant formula for reducing the risk of developing non-alcoholic fatty liver disease | |
| WO2017183956A1 (en) | Linoleic acid and alpha-linolenic acid for use for reducing early-life stress induced cognitive decline | |
| RU2822197C1 (en) | Infant formula with special fat structure for improving postnatal growth of infants born to overweight and obese mothers | |
| Chakrabarty et al. | Textbook of Nutrition in Health and | |
| NZ795279A (en) | Nutritional composition for improving cell membranes | |
| Kuratko et al. | Recent Developments in the | |
| BR112018007122B1 (en) | NON-THERAPEUTIC METHODS | |
| NZ621230B2 (en) | Use of infant formula with large lipid globules |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190205 |
|
| RJ01 | Rejection of invention patent application after publication |