Composition for improving cognitive decline and application thereof

Abstract

The invention relates to a composition for improving cognitive decline and application thereof, a mouse aging model is constructed through a D-galactose injection method, and then mice are randomly divided into a control group, a D-gal model group, a DHA group, and a DHA, folic acid and phosphatidylserine combined intervention group (n = 12). And testing. Test results show that the combined intervention of DHA, folic acid and phosphatidylserine has a certain improvement effect on the cognitive function of the brain of an aging model mouse, can improve the inflammatory response in hippocampus tissues and the expression conditions of neurotrophic factors and synaptic associated proteins, regulates the in-vivo antioxidant level, and has a good anti-aging effect. And the new object identification and spatial learning memory ability of the mouse is improved. Therefore, the invention provides a theoretical basis for improving cognition and realizing functional dairy product development and industrial production through combined intervention of DHA, folic acid and phosphatidylserine.

Description

Technical Field

[0001] The present invention belongs to the field of cognitive impairment, and in particular relates to a composition for improving cognitive decline and an application thereof. Background Art

[0002] With the rapid development of my country's economy and society, the number of elderly people in China has increased rapidly, and the trend of population aging has continued to accelerate. Among them, cognitive impairment has become a key factor affecting the quality of life of the elderly. Mild cognitive impairment has the risk of developing into dementia, forming irreversible neurological damage. Therefore, understanding the influencing factors and related biological processes of cognitive impairment and carrying out early prevention are of great significance for maintaining the cognitive function of the elderly and promoting healthy aging in China.

[0003] Precision nutritional intervention is an effective strategy to maintain cognitive function in the elderly, and dietary nutrition plays an important role in delaying cognitive decline and reducing the risk of cognitive impairment. Many studies have shown that DHA, folic acid and phosphatidylserine play a wide range of roles in preventing cognitive impairment. DHA delays cognitive decline through anti-inflammatory and antioxidant pathways; folic acid participates in homocysteine ​​metabolism and maintains the blood-brain barrier and synaptic function; phosphatidylserine can participate in neuronal membrane formation and signal transduction, and plays an important role in cognitive function. However, there is insufficient research on the combined intervention of DHA, folic acid and phosphatidylserine, and the effect on the development and application of functional dairy products is unknown. Therefore, this application studies the improvement effect of combined intervention of DHA, folic acid and phosphatidylserine on cognitive impairment. Summary of the invention

[0004] In view of the deficiencies of the prior art and actual needs, the purpose of the present invention is to improve cognitive decline.

[0005] The objective of the present invention is achieved through the following technical solutions:

[0006] The invention provides a composition consisting of DHA, folic acid and phosphatidylserine, which can improve cognitive function, wherein the ratio of DHA, folic acid and phosphatidylserine is 30:1:20.

[0007] Three behavioral experiments, namely novel object recognition, Y-maze and Morris water maze, proved that the combined intervention had a certain improvement effect on the learning and memory ability in the aging process.

[0008] The composition was verified to have the effect of improving cognitive function from multiple aspects such as oxidative stress, neuroinflammation, neurotrophic factors and synaptic protein changes.

[0009] The present invention provides an application of a composition in improving cognitive decline, wherein the cognitive decline may be caused by any one selected from neurotransmitter degradation, decreased neurotransmitter production and decreased neurotransmitter receptors.

[0010] The cognitive decline is at least one selected from the group consisting of lethargy, memory loss, amnesia, cognitive impairment, learning disability, attention loss, depression, hypotension, analgesia, anhidrosis and impaired discrimination.

[0011] The cognitive decline is caused by a neurodegenerative disease, and the neurodegenerative disease is at least one selected from the group consisting of Alzheimer's disease, dementia, Parkinson's disease, Huntington's disease, autosomal dominant cerebellar ataxia, narcolepsy, alcoholism, drug addiction, and hereditary sensory and autonomic neuropathy.

[0012] The present invention also provides application of the composition in functional formula milk powder for middle-aged and elderly people.

[0013] The present invention also provides the use of the above composition in the preparation of medicines, health foods and food additives. Compared with the prior art, the present invention has the following beneficial effects:

[0014] (1) This application found that the combined intervention of DHA, folic acid, and phosphatidylserine has a certain improvement effect on learning and memory ability in the aging process through three behavioral experiments: novel object recognition, Y maze, and Morris water maze;

[0015] (2) DHA, folic acid, and phosphatidylserine have antioxidant effects. Combined intervention can improve the body's antioxidant level by enhancing SOD enzyme activity, slowing down oxidative stress processes such as lipid peroxidation in the body, and maintaining neuronal connections and synaptic function to improve cognitive function;

[0016] (3) DHA, folic acid, and phosphatidylserine have anti-inflammatory effects. Combined intervention can downregulate the gene expression levels of proinflammatory cytokines IL-6, IL-1β, TNF-α, and inflammatory mediator JNK protein, reduce the damage to neurons caused by neuroinflammatory response, and maintain cognitive function;

[0017] (4) The combined intervention of DHA, folic acid, and phosphatidylserine can upregulate the gene expression levels of the neurotrophic factor BDNF and its receptor TrkB, which regulate the survival, differentiation, and function of nerve cells, enhance the neural signal transduction process in the hippocampus, and thus improve the cognitive function associated with aging.

[0018] (5) Combined intervention of DHA, folic acid, and phosphatidylserine can upregulate the gene expression levels of synapse-related proteins SNAP25, SYN, PSD95, and LIMK-1, thereby enhancing signal transmission between neurons and improving cognitive function by enhancing intersynaptic connectivity and plasticity. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 Animal experiment design.

[0020] Figure 2 Body weight of mice in each group after 8 weeks of intervention.

[0021] Figure 3 Brain organ index of mice in each group.

[0022] Figure 4 Movement trajectories of mice in each group in the novel object recognition experiment.

[0023] Figure 5 New object recognition experiment of mice in each group. Note: A is the number of explorations of new objects; B is the exploration time of new objects; C is the relative discrimination index.

[0024] Figure 6 Y-maze test of mice in each group. Note: A is the total number of entries into each arm; B is the number of entries into the novel arm C; C is the number of spontaneous alternations. D is the spontaneous alternation rate.

[0025] Figure 7 Morris water maze mouse's first swimming. Note: A is the mouse's first swimming distance; B is the mouse's first swimming speed.

[0026] Figure 8 Typical trajectories of Morris water maze for each group of mice.

[0027] Fig. 9 The latent escape period of mice in each group during the fixed-point navigation training. Note: During the fixed-point navigation period, A is the latent escape period of mice in each group in the first 5 days; B is the latent escape period of mice in each group on the 5th day.

[0028] Fig.10 The number and duration of each group of mice staying in the target quadrant during the spatial exploration period. Note: During the spatial exploration period, A, the number of times each group of mice stayed in the target quadrant; B, the duration of each group of mice staying in the target quadrant.

[0029] Fig.11 The number and time of each group of mice crossing the platform during the spatial exploration period. Note: During the spatial exploration period, A, the number of times each group of mice crossed the platform; B, the time each group of mice crossed the platform.

[0030] Fig.12 Effects of combined intervention of DHA, folic acid and phosphatidylserine on serum MDA content and SOD activity. Note: A is serum malondialdehyde (MDA) content; B is serum superoxide dismutase (SOD) activity.

[0031] Fig.13 Effects of combined intervention on the expression of IL-1β, IL-6, and TNF-α in the hippocampus. Note: A is the relative expression of IL-6 gene in the hippocampus of each group of mice; B is the relative expression of IL-1β gene in the hippocampus of each group of mice; C is the relative expression of TNF-α gene in the hippocampus of each group of mice.

[0032] Fig.14 Effect of combined intervention on JNK expression in hippocampus. Note: A and B are the relative expression of JNK protein in hippocampus of mice in each group; C is the relative expression of JNK gene in hippocampus of mice in each group.

[0033] Fig.15 Effects of combined intervention on the expression of BDNF and TrkB in the hippocampus. Note: A is the relative expression of BDNF gene in the hippocampus of mice in each group; B is the relative expression of TrkB gene in the hippocampus of mice in each group.

[0034] Fig.16 Effects of combined intervention on the expression of SNAP25, SYN, PSD95 and LIMK-1 in the hippocampus. Note: A is the relative expression of SNAP25 gene in the hippocampus of each group of mice; B is the relative expression of SYN gene in the hippocampus of each group of mice; C is the relative expression of PSD95 gene in the hippocampus of each group of mice; D is the relative expression of LIMK-1 gene in the hippocampus of each group of mice. DETAILED DESCRIPTION

[0035] The present invention will be described in detail below by way of examples. It should be understood that the following examples are only used to further explain and illustrate the content of the present invention in detail, and are not used to limit the present invention.

[0036] Example 1. Experimental design of the intervention of the composition to improve cognitive decline in mice

[0037] Male C57BL / 6N mice (SPF grade, 8 weeks old, weight 20.9-26.6 g) were purchased from Beijing Weitonglihua Experimental Animal Technology Co., Ltd. and raised in the SPF Animal Experiment Center of China Agricultural University at a constant temperature of (22±3)°C and humidity of (55±5)%. All animal experimental protocols followed the Guidelines for the Care and Use of Laboratory Animals and were approved by the Ethics Committee of the Animal Experiment Center of China Agricultural University. The experimental design and operation strictly complied with relevant regulations to reduce the pain of mice as much as possible.

[0038] In this experiment, mice were injected intraperitoneally with 300 mg / kg BW D-galactose solution D-gal for 8 weeks to establish the model ( Figure 1The mice were randomly divided into 4 groups: control group, D-gal model group, DHA group, and DHA, folic acid, and phosphatidylserine combined intervention group (n=12). After 1 week of free feeding and water adaptation, the mice were modeled and administered: the control group was intraperitoneally injected with 200 μL PBS solution and gavaged with 200 μL 1% bile salt solution every day, the D-gal model group was intraperitoneally injected with 300 mg / kg BW D-gal 200 μL and gavaged with 1% bile salt solution 200 μL every day, the DHA group was intraperitoneally injected with 300 mg / kg BW D-gal 200 μL and gavaged with 300 mg / kg BW DHA solution 200 μL every day, and the DHA, folic acid, and phosphatidylserine combined intervention group was intraperitoneally injected with 300 mg / kg BW D-gal 200 μL and gavaged with 300 mg / kg BW DHA, 10 mg / kg BW folic acid, and 200 mg / kg BW phosphatidylserine mixed solution 200 μL every day. The interval between modeling and administration in each group was more than 30 minutes, and the daily injection and gavage doses were adjusted according to the actual weight gain of the mice.

[0039] Example 2. Effect of the combination intervention on the learning and memory ability of aging mice

[0040] After 8 weeks of D-gal induction and drug intervention, compared with the control group, the mice in the D-gal model group, DHA group, and DHA, folic acid, and phosphatidylserine combined intervention group all showed decreased enthusiasm, reduced physical activity, dark fur, and slight hair loss. The weight of each group of mice was weighed and recorded every week during the modeling and drug administration period. It can be seen that the mice in each group were free to eat and drink water. With the extension of the intervention time, the weight of the mice gradually increased, and there was no significant difference in the weight of the mice in each group after 8 weeks, indicating that the mice in each group grew normally during the modeling intervention period ( Figure 2 ).

[0041] By weighing the brain tissue of each group of mice and calculating the brain organ index, we found that the organ index of the D-gal model group was significantly lower than that of the control group (p < 0.01). Compared with the D-gal model group, the brain organ index of the DHA group and the DHA, folic acid, and phosphatidylserine combined intervention group increased, but there was no significant difference. This shows that D-galactose induction for 8 weeks can lead to atrophy or degenerative changes in brain organs, while DHA, folic acid, and phosphatidylserine intervention have a certain improvement effect ( Figure 3 ).

[0042] From the action trajectory diagram of each group of mice during the experiment, it can be seen that ( Figure 4 ), compared with the control group mice, which showed a curious exploration of new objects, the D-gal model group mice showed a decreased interest in novel things. Figure 5It can be seen that the number of explorations of new objects by mice in the D-gal model group was significantly reduced compared with the control group (p < 0.05). Compared with the D-gal group, the number of explorations of new objects by mice in the DHA group and the combined intervention group of DHA, folic acid, and phosphatidylserine increased, but there was no significant difference. From the exploration time of new objects, it can be seen that compared with the control group, the exploration time of new objects by mice in the D-gal model group was significantly reduced (p < 0.001), while compared with the model group, the exploration time of new objects by mice in the DHA group and the combined intervention group of DHA, folic acid, and phosphatidylserine increased, and the combined intervention group had a significant difference (p < 0.01). According to the exploration time of familiar objects and new objects by mice in each group, the relative resolution index of mice in the D-gal model group was significantly reduced compared with the control group (p < 0.01), while compared with the model group, the relative resolution index of mice in the DHA group and the combined intervention group of DHA, folic acid, and phosphatidylserine increased significantly (p < 0.05). The novel object recognition experiment showed that the learning and memory ability of D-gal-induced mice was significantly reduced, while DHA, and the combined intervention of DHA, folic acid, and phosphatidylserine could improve the learning and memory ability of D-gal mice to a certain extent.

[0043] Depend on Figure 6The Y-maze experiment data showed that compared with the control group, the D-gal-induced mouse exploratory behavior was weakened, and the total number of entries into each arm was significantly reduced (p < 0.05). Compared with the D-gal model group, the total number of entries into each arm by the DHA group and the DHA, folic acid, and phosphatidylserine combined intervention group increased, and the DHA group had significant differences (p < 0.05). Mice have the instinct to explore new things, and the exploratory behavior of the novel arm effectively reflects the spatial working memory ability of mice. The number of times mice entered the C arm, i.e. the novel arm, showed that the number of entries into the novel arm by the D-gal model group mice was significantly reduced compared with the control group (p < 0.05), indicating that the learning and memory of D-gal mice was significantly reduced. Compared with the model group, the number of entries into the novel arm by the DHA group and the DHA, folic acid, and phosphatidylserine combined intervention group mice was significantly increased (p < 0.05), indicating that the learning and memory ability of the intervention group mice was significantly enhanced compared with the D-gal group mice. Spontaneous alternation is a key indicator reflecting the working memory ability of mice. The experimental results showed that the number of spontaneous alternations in the D-gal model group was significantly reduced compared with the control group (p < 0.05). Compared with the model group, the number of spontaneous alternations in the DHA group and the DHA, folic acid and phosphatidylserine combined intervention group was significantly increased (p < 0.05). Compared with the mice in the single DHA group, the number of spontaneous alternations in the combined intervention group was increased and had a significant difference (p < 0.05). This shows that DHA and the combined intervention of DHA, folic acid and phosphatidylserine significantly improved the spatial working memory ability of D-gal mice, and the improvement effect of the combined intervention was more significant. The results of spontaneous alternation rate showed that compared with the control group, the spontaneous alternation rate of D-gal mice was significantly reduced (p < 0.05). After DHA or combined intervention with DHA, folic acid and phosphatidylserine, the spontaneous alternation rate increased, and the combined intervention group increased significantly (p < 0.05). This indicates that the combined intervention of DHA, folic acid and phosphatidylserine can effectively improve the short-term spatial working memory ability of D-gal-induced aging mice, and to a certain extent improve the learning and memory ability of mice.

[0044] The Morris water maze test is a classic model for evaluating spatial learning and memory abilities. It tests the experimental animals' hippocampus-dependent spatial position learning and memory abilities by observing and recording the time and swimming trajectory of mice in finding an escape platform in a pool. It more objectively reflects the long-term memory and spatial memory of mice. Figure 7 The figure shows the swimming distance and swimming speed of each group of mice after they entered the water maze for the first time. It can be seen that there is no significant difference in the swimming distance and swimming speed of each group of mice, indicating that the motor ability and vision level of each group of mice in the water maze are normal. Figure 8The figure shows the typical trajectories of mice in the control group, D-gal model group, DHA group, and DHA, folic acid, and phosphatidylserine combined intervention group during spatial exploration in the water maze. From the spatial exploration trajectories of mice in each group, it can be seen that compared with the control group, the number of times the mice in the D-gal model group crossed the platform was significantly reduced, and the movement trajectory in the target quadrant where the escape platform was located was reduced; while the number of times the mice in the DHA group crossed the escape platform increased, the number of swimming times and exploration behaviors in the target quadrant increased, and the number of times they crossed the platform also increased. Similarly, compared with the D-gal model group, the number of swimming times and platform crossing times of mice in the DHA, folic acid, and phosphatidylserine combined intervention group increased. It can be seen that after the combined intervention of DHA, folic acid, and phosphatidylserine, the spatial exploration and swimming trajectories of mice were well improved.

[0045] In the Morris water maze 5-day navigation experiment, the escape latency is the time required for mice to find the escape platform in the third quadrant. The length of the escape latency can reflect the animal's spatial learning and memory ability to a certain extent. A short latency indicates that the mouse has good learning and memory ability. Fig. 9 (A) It can be seen that the escape latency of mice in each group decreased with the extension of the training days, indicating that the mice gradually learned and memorized the location of the escape platform during the positioning navigation. However, in the 5-day positioning navigation experiment, the escape latency of mice in the D-gal model group was higher than that of mice in other groups, indicating that the spatial learning and memory ability of D-gal-induced aging mice was poor. Starting from the third day of training, the escape latency of mice showed significant differences. The escape latency of mice in the D-gal model group was significantly prolonged compared with the control group (p < 0.05), while compared with the D-gal model group, the combined intervention of DHA, folic acid, and phosphatidylserine significantly shortened the escape latency of mice (p < 0.05). The results of the training on the fourth day showed that the escape latency of mice in the DHA group and the combined intervention group of DHA, folic acid, and phosphatidylserine was significantly lower than that in the D-gal model group (p < 0.05). Fig. 9 (B) shows the learning and memory of mice on the 5th day of navigation training. It can be seen that the latent escape period of mice in the D-gal model group was significantly prolonged compared with the control group (p < 0.01), while compared with the D-gal model group, DHA or the combined effect of DHA, folic acid, and phosphatidylserine can significantly shorten the escape latency of mice (p < 0.05). The results of navigation training show that the learning and memory ability of D-gal-induced aging mice is reduced, while the combined intervention of DHA, folic acid, and phosphatidylserine can significantly improve the spatial learning and memory ability of aging mice.

[0046] During the spatial exploration, the platform was removed, and the mouse's exploration behavior and platform crossing in the target quadrant where the original platform was located were observed and recorded. Fig.10As shown in the figure, compared with the D-gal model group, the target quadrant stay times of the other three groups of mice increased, and the target quadrant stay times of the control group, DHA, folic acid, phosphatidylserine combined intervention group mice increased significantly (p < 0.05). In terms of the target quadrant stay time, it can be seen that the target quadrant stay time of the D-gal group mice was shorter than that of the control group mice, and compared with the DHA, folic acid, phosphatidylserine combined intervention group, the target quadrant stay time of the D-gal group and DHA group mice was significantly reduced (p < 0.05). The above experimental results show that D-gal can reduce the spatial memory ability of mice, while the combined intervention of DHA, folic acid and phosphatidylserine can significantly improve the learning and memory ability of D-gal-induced aging mice.

[0047] The number of platform crossings reflects the learning and memory ability of mice. Within a certain period of time, the more frequently the mouse crosses the original platform position, the better the spatial learning and memory ability of the mouse. Fig.11 The results showed that the number of times and time that mice in the D-gal model group crossed the platform were significantly reduced compared with those in the control group (p < 0.05). Compared with the D-gal model group, the number of times and time that mice in the DHA group and the DHA, folic acid, and phosphatidylserine combined intervention group crossed the platform were increased, and the increase in the combined intervention group was significant (p < 0.05). This indicates that the combined intervention of DHA, folic acid, and phosphatidylserine can improve the spatial long-term memory ability of mice and effectively improve the cognitive decline of D-gal-induced aging mice.

[0048] In summary, the results show that: (1) Long-term injection of D-gal can accelerate aging, manifesting as thinning hair and decreased motor ability; (2) In the novel object recognition experiment, the combined intervention of DHA, folic acid, and phosphatidylserine can improve cognitive impairment and enhance the learning and memory ability of novel object recognition and environmental changes; (3) In the Y-maze experiment, the combined intervention of DHA, folic acid, and phosphatidylserine can improve cognitive function and improve short-term spatial learning and memory ability; (4) The Morris water maze experiment shows that the combined intervention of DHA, folic acid, and phosphatidylserine can delay cognitive decline and improve long-term spatial learning and memory ability. Behavioral experiments provide important evidence for our understanding that the combined intervention of DHA, folic acid, and phosphatidylserine improves learning and memory functions. The improvement of cognitive function by dietary nutrients may be due to their antioxidant and anti-inflammatory properties, and their effects need to be further explored at the molecular level.

[0049] Example 3. Improvement of hippocampal tissue in aged mice by intervention with the combination

[0050] The effect of combined intervention of DHA, folic acid and phosphatidylserine on the oxidative capacity of D-gal-induced aging mouse model was evaluated by measuring the MDA content and SOD activity in serum. The experimental results showed that the MDA content of D-gal model group mice was significantly higher than that of the control group, and the SOD activity was significantly lower than that of the control group (p < 0.05). Fig.12 (A) It can be seen that compared with the D-gal model group, the MDA content of mice in the DHA group, DHA, folic acid, and phosphatidylserine group decreased significantly (p < 0.05), indicating that DHA or the combined intervention of DHA, folic acid, and phosphatidylserine effectively improved the oxidative damage of D-gal-induced aging mice. At the same time, the serum MDA content of mice in the combined intervention group was significantly lower than that in the DHA intervention group (p < 0.05), indicating that the combined intervention has a better improvement effect. Fig.12 (B) It can be seen that compared with the D-gal model group, the serum SOD enzyme activity of mice in the DHA group, DHA, folic acid, and phosphatidylserine groups was significantly increased (p < 0.05), indicating that the combined intervention effectively increased the activity of serum SOD in mice. The above results show that D-gal induced a decrease in the serum SOD enzyme activity in mice, increased the level of oxidative stress in mice, and led to the accumulation of serum MDA. The combined intervention of DHA, folic acid, and phosphatidylserine can effectively reduce the accumulation of MDA by increasing the SOD enzyme activity in mice, enhancing the body's antioxidant level, and reducing lipid peroxidation in the body. The combined intervention can effectively reduce the oxidative stress response of D-gal-induced aging mice.

[0051] like Fig.13 As shown in the results, compared with the control group, the D-gal-induced model group showed significantly upregulated IL-1β, IL-6, and TNF-α gene expression levels in the proinflammatory cytokines IL-1β, IL-6, and TNF-α (p < 0.05), while compared with the D-gal model group, the DHA group and the combined intervention group of DHA, folic acid, and phosphatidylserine showed significant decreases (p < 0.05), and there was no significant difference in the gene expression of inflammatory factors between the combined intervention group and the control group. The experiment showed that D-gal induced an increase in the gene expression of IL-1β, IL-6, and TNF-α, and the combined intervention of DHA, folic acid, and phosphatidylserine could effectively improve the cognitive function of aging mice by slowing down the neuroinflammatory response of the mouse hippocampus.

[0052] like Fig.14The results of Western blot showed that compared with the control group, D-gal induction significantly increased the expression of JNK protein (p < 0.05), while DHA or DHA, folic acid, phosphatidylserine combined intervention reduced the expression of JNK protein in mice, and the JNK protein expression in the combined intervention group decreased more significantly, but there was no significant difference between the intervention group and the D-gal model group. In terms of JNK mRNA expression level, it can be seen that compared with the control group, the JNK gene expression level in the D-gal model group was significantly upregulated (p < 0.05), and compared with the D-gal model group, the JNK gene level was significantly downregulated after DHA or DHA, folic acid, phosphatidylserine combined intervention (p < 0.05), but there was no significant difference in the combined intervention group compared with the DHA group. The experimental results showed that there was consistency between the JNK gene expression level and protein expression. D-gal induction could significantly upregulate the JNK gene expression and increase the JNK protein expression, which was manifested as enhanced inflammatory response and cell apoptosis, resulting in impaired cognitive function in mice. The combined intervention of DHA, folic acid and phosphatidylserine can significantly downregulate gene expression, causing a downward trend in protein expression, effectively improving the inflammatory response of mice and improving cognitive function.

[0053] from Fig.15 (A) It can be seen that compared with the control group, the gene expression of BDNF in the hippocampus of the D-gal model group was significantly reduced (p < 0.05), while its gene expression was significantly upregulated after the combined intervention of DHA, folic acid and phosphatidylserine (p < 0.05). Fig.15 (B) It can be seen that compared with the control group, D-gal significantly downregulated the expression of TrkB receptor gene in hippocampal tissue (p < 0.05), while DHA or DHA, folic acid, phosphatidylserine combined intervention increased the expression of TrkB receptor gene, and the combined intervention group was significantly different from the D-gal model group (p < 0.05). The specific binding of BDNF and TrkB receptor can activate the signaling pathway and play an important role in neurogenesis. The experimental results show that the gene expression of the two is consistent, and D-gal induction significantly downregulated the gene expression of both, while the combined intervention of DHA, folic acid, and phosphatidylserine effectively upregulated the gene expression and effectively improved the cognitive function of mice.

[0054] Synaptic-related proteins SNAP25, SYN, PSD95, and LIMK-1 play important roles in neuronal function and synaptic plasticity, as can be seen from the gene expression levels ( Fig.16), compared with the control group, the mRNA expression of SNAP25, SYN, PSD95, and LIMK-1 in the D-gal model group was significantly downregulated (p < 0.05). Compared with the D-gal model group, the gene expression of SNAP25, SYN, PSD95, and LIMK-1 in the hippocampal tissue of the DHA group and the combined intervention group of DHA, folic acid, and phosphatidylserine showed an upward trend, and the gene expression of the combined intervention group was significantly upregulated compared with the D-gal model group (p < 0.05). The experimental results show that DHA or the combined intervention of DHA, folic acid, and phosphatidylserine can upregulate the expression level of synapse-related genes, but the upregulation of gene expression levels through combined intervention is significantly different, indicating that combined intervention can increase the expression of synapse-related genes, enhance its neuronal connection and synaptic plasticity, and improve the cognitive function of D-gal-induced aging mice.

[0055] In summary, the results show that: (1) the combined intervention of DHA, folic acid, and phosphatidylserine can improve serum SOD activity and enhance antioxidant capacity, reduce free radical reactions such as lipid peroxidation, reduce serum MDA content, reduce oxidative stress, and protect neurons from oxidative damage; (2) the combined intervention has an anti-inflammatory effect, can regulate neuroinflammatory response, reduce the expression of proinflammatory cytokines IL-6, IL-1β, TNF-α, and JNK, and reduce the impact of inflammatory damage on cognitive function; (3) the combined intervention may promote the synthesis and release of neurotrophic factors, increase the levels of BDNF and TrκB receptors in hippocampal tissue to slow down the development of cognitive function decline; (4) the combined intervention may affect synaptic structure and function by affecting the expression of synaptic-related proteins SNAP25, SYN, PSD95, and LIMK-1. The combined intervention may promote the release of neurotransmitters and synaptic transmission, thereby affecting the cognitive process associated with aging and improving cognitive function. In other words, DHA, folic acid, and phosphatidylserine can improve cognitive function from multiple aspects such as oxidative stress, neuroinflammation, neurotrophic factors, and changes in synaptic proteins.

[0056] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A composition, It is characterized in that It is composed of DHA, folic acid and phosphatidylserine, which can improve cognitive function.

2. The composition according to claim 1, It is characterized in that The ratio of DHA, folic acid and phosphatidylserine is 30:1:

20.

3. The composition according to claim 1, It is characterized in that Three behavioral experiments, namely novel object recognition, Y-maze and Morris water maze, proved that the combined intervention had a certain improvement effect on the learning and memory ability in the aging process.

4. The composition according to claim 1, It is characterized in that The composition can improve cognitive function from multiple aspects such as oxidative stress, neuroinflammation, neurotrophic factors and synaptic protein changes.

5. Use of a composition in improving cognitive decline, It is characterized in that The cognitive decline may be caused by any one selected from the group consisting of neurotransmitter degradation, decreased neurotransmitter production, and decreased neurotransmitter receptors.

6. The use according to claim 5, It is characterized in that The cognitive decline is at least one selected from the group consisting of lethargy, memory loss, amnesia, cognitive impairment, learning disability, attention loss, depression, hypotension, analgesia, anhidrosis and impaired discrimination.

7. The use according to claim 5, It is characterized in that The cognitive decline is caused by a neurodegenerative disease.

8. The use according to claim 5, It is characterized in that The neurodegenerative disease is at least one selected from the group consisting of Alzheimer's disease, dementia, Parkinson's disease, Huntington's disease, autosomal dominant cerebellar ataxia, narcolepsy, alcoholism, drug addiction, and hereditary sensory and autonomic neuropathy.

9. Use of the composition according to claim 1 in functional formula milk powder for middle-aged and elderly people.

10. Use of the composition according to claim 1 in the preparation of medicines, health foods and food additives.

Images