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Objective:To explore the effects and possible mechanisms of melatonin combined with enriched environment on the learning and memory ability of senescence-accelerated mouse prone 8(SAMP8).Methods:Forty-eight SAMP8 male mice aged 4 months were randomly divided into model group, enriched environment group, melatonin group and melatonin combined with enriched environment group (combined intervention group) by random number table method, with 12 mice in each group. Mice in the melatonin group and combined intervention group were subcutaneously injected with melatonin at a dose of 8 mg·kg -1·d -1, and the mice in the model group and the enriched environment group were given the same amount of normal saline instead.The mice in model group and melatonin group were raised in a standard environment, and the mice in enriched environment group and combined intervention group were raised in an enriched environment.The intervention lasted 28 days. The aging degree of mice was scored before and 28 days after the intervention. Morris water maze test was used to detect the learning and memory ability of mice. Nissl staining and TUNEL staining were used to observe the Nissl staining positive cells and apoptotic cells in the CA1 area of hippocampus.ELISA was used to detect the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the hippocampus of mice. Western blot was used to detect the levels of amyloid β-protein (Aβ) 1-42, microtubule-associated protein tau (tau) phosphorylated at threonine (Thr) 205 (Tau pT205), Toll-like receptor 4 (TLR4), and nuclear factor-κB (NF-κB) p65 protein in the hippocampus of mice. qRT-PCR was used to detect the levels of TLR4, NF-κB p65 mRNA in the hippocampus of mice. SPSS 22. 0 statistical software was used for repeated measure ANOVA, one-way ANOVA and LSD test. Results:(1) Aging score: after intervention, the aging scores of mice in the four groups were significantly different ( F=120.601, P<0.01). The aging scores of mice in the enriched environment group, melatonin group, and combined intervention group were lower than those in the model group (all P<0.05), while the aging score of mice in the combined intervention group was significantly lower than those in the enriched environment group and melatonin group (both P<0.05). (2) The results of the location navigation experiment showed that the time × group interaction effect of the escape latencies of mice in the four groups were significant ( F=30.524, P<0.001). From the 2nd to 4th day, the escape latencies of mice in the enriched environment group, melatonin group and combined intervention group were all lower than that in the model group (all P<0.05). The results of the space exploration experiment showed that the residence time in the target quadrant and the number of platform crossings of mice in the four groups were significantly different ( F=291.328, 113.482, both P<0.01). The residence time in the target quadrant ((29.45±1.70)s, (32.44±1.55)s, (37.48±0.84) s) and the number of platform crossings ((6.44±0.61) times, (7.16±0.70) times, (12.60±1.23) times) of mice in the enriched environment group, melatonin group and combined intervention group were higher than those in the model group ((15.07±1.28) s, (4.10±0.61) times), while the residence time in the target quadrant and the number of platform crossings of mice in the enriched environment group and the melatonin group were significantly lower than those in the combined intervention group (all P<0.05). (3) Nissl and TUNEL staining showed that the number of Nissl positive neurons in the hippocampal CA1 region of mice in the four groups were significantly different ( F=809.264, P<0.01), and the number of apoptotic cells in the hippocampal CA1 region were also significantly different ( F=1 060.583, P<0.01). The number of Nissl stained positive neurons in the hippocampal CA1 region of mice in the combined intervention group was more than those in the model group, enriched environment group, and melatonin group (all P<0.05), and the number of apoptotic cells were less than those in the model group, enriched environment group, and melatonin group (all P<0.05). (4) The results of ELISA assay showed that there were significantly different in the levels of IL-1β, IL-6 and TNF-α in the hippocampus of mice in the four groups ( F=152.887, 63.506, 432.026, all P<0.01). The contents of IL-1β, IL-6 and TNF-α in the hippocampus of mice in the enriched environment group, melatonin group, and combined intervention group were lower than those in the model group(all P<0.05). Among them, the contents of IL-1β, IL-6 and TNF-α in the hippocampus of mice in the enriched environment group and melatonin group were significantly higher than those in the combined intervention group (all P<0.05). (5) Western blot analysis showed that there were significantly different in the protein expression levels of Aβ1~42, tau pT205, TLR4, NF-κB p65 in the hippocampus of mice in the four groups ( F=122.349, 98.934, 201.635, 116.553, all P<0.01). The protein expression levels of Aβ1-42, tau pT205, TLR4, and NF-κB p65 in the hippocampus of mice in the enriched environment group, melatonin group, and combined intervention group were lower than those in the model group.Among them, the protein expression levels of Aβ1-42, tau pT205, TLR4, NF-κB p65 in the hippocampus of mice in the enriched environment group and melatonin group were significantly higher than those in the combined intervention group (all P<0.05). (6) qRT-PCR showed that the mRNA expression levels of TLR4 and NF-κB p65 in the hippocampus of mice in the four groups were significantly different ( F=42.913, 102.446, both P<0.01). The mRNA expression levels of TLR4 ((0.63±0.05), (0.55±0.04), (0.42±0.03)) and NF-κB p65 ((0.98±0.06), (0.82±0.04), (0.72±0.04)) in the hippocampus of mice in the enriched environment group, melatonin group and combined intervention group were lower than those in the model group ((0.74±0.07), (1.20±0.05)) (all P<0.05). Among them, the mRNA expression levels of TLR4 and NF-κB p65 in the hippocampus of mice in the enriched environment group and melatonin group were significantly higher than those in the combined intervention group (all P<0.05). Conclusion:Melatonin combined with enriched environment can improve the learning and memory ability and neuroinflammatory response of SAMP8 mice, and its mechanism may be related with the down-regulation of TLR4/NF-κB p65 signaling pathway.
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BACKGROUND@#Chronic noise exposure is one environmental hazard that is associated with genetic susceptibility factors that increase Alzheimer's disease (AD) pathogenesis. However, the comprehensive understanding of the link between chronic noise stress and AD is limited. Herein, we investigated the effects of chronic noise exposure on AD-like changes in senescence-accelerated mouse prone 8 (SAMP8).@*METHODS@#A total of 30 male SAMP8 mice were randomly divided into the noise-exposed group, the control group, and aging group (positive controls), and mice in the exposure group were exposed to 98 dB SPL white noise for 30 consecutive days. Transcriptome analysis and AD-like neuropathology of hippocampus were examined by RNA sequencing and immunoblotting. Enzyme-linked immunosorbent assay and real-time PCR were used to further determine the differential gene expression and explore the underlying mechanisms of chronic noise exposure in relation to AD at the genome level.@*RESULTS@#Chronic noise exposure led to amyloid beta accumulation and increased the hyperphosphorylation of tau at the Ser202 and Ser404 sites in young SAMP8 mice; similar observations were noted in aging SAMP8 mice. We identified 21 protein-coding transcripts that were differentially expressed: 6 were downregulated and 15 were upregulated after chronic noise exposure; 8 genes were related to AD. qPCR results indicated that the expression of Arc, Egr1, Egr2, Fos, Nauk1, and Per2 were significantly high in the noise exposure group. These outcomes mirrored the results of the RNA sequencing data.@*CONCLUSIONS@#These findings further revealed that chronic noise exposure exacerbated aging-like impairment in the hippocampus of the SAMP8 mice and that the protein-coding transcripts discovered in the study may be key candidate regulators involved in environment-gene interactions.
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Objective@#To evaluate the effect of acteoside on learning, memory and neurotransmitter in SAMP8 mice.@*Methods@#The 6-month-old rapidly aging SAMP8 mice were randomly divided into model group, namenda group, low-dose acteoside group(30 mg·kg-1 ·d-1), medium-dose acteoside group(60 mg·kg-1 ·d-1) and high-dose acteoside group(120 mg·kg-1 ·d-1) according to the digital table method, with 12 in each group.And 12 SAMR mice with the same age resistance were used as the control group.After 75 days of continuous intragastric administration, Morris water maze method and spontaneous activity experiment were used to investigate the effects of acteoside on learning, memory and anxiety of mice.The levels of neurotransmitters acetylcholine(ACh), serotonin(5-HT), norepinephrine(NE) and dopamine(DA) in mouse brain tissue(cortex and hippocampus) were detected by ELISA.@*Results@#(1)In the Morris water maze test, compared with the model group, the acteoside significantly reduced the escape latency of SAMP8 mice in training period.(2)In the experiment of autonomic activity, compared with the model group, the average speed and total distance of the low-dose acteoside group were significantly increased(t=15.0, 20.8, both P<0.05); the number of vertical movements and the average speed of the medium-dose acteoside group were significantly increased(t=15.8, 13.6, both P<0.05). The average speed and total distance of the high-dose acteoside group were remarkarbly increased(t=30.9, 29.7, both P<0.05), and the number of defecations in the mice of the lav-dose acteoside group, medium-dose acteoside group, high-dose acteoside group were((2.83±1.19)particles, (3.25±1.29)particles, (2.58±1.16)particles), they were obviously lower than that of the model group ((5.25±1.48) particles)(t=15.7, 20.1, 13.5, all P<0.01). (3)Simultaneously, the contents of ACh, NE and DA in the hippocampus and cortex of the model group were significantly lower than those in the normal group (hippocampus: t=10.3, 12.7, 13.2, all P<0.05; cortex: t=11.7, 10.5, 12.4, all P<0.05). Compared with the model group, the contents of ACh, NE, DA and 5-HT in the hippocampus and cortex of the low, medium and high doses of acteoside were significantly increased(hippocampus: t=31.4, 20.3, 10.7, 12.9, all P<0.05; cortex: t=33.7, 29.4, 14.5, 12.7, all P<0.05).@*Conclusion@#The acteoside can enhance the ability of spatial learning and memory of SAMP8 mice, and can regulate the depression and anxiety of animals.The mechanism may be related to the ACh content and the monoamine neurotransmitters increase in the brain.
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Objective To evaluate the effect of acteoside on learning,memory and neurotransmitter in SAMP8 mice. Methods The 6-month-old rapidly aging SAMP8 mice were randomly divided into model group,namenda group,low-dose acteoside group(30 mg·kg-1 ·d-1),medium-dose acteoside group(60 mg ·kg-1 ·d-1) and high-dose acteoside group(120 mg·kg-1 ·d-1 ) according to the digital table method, with 12 in each group. And 12 SAMR mice with the same age resistance were used as the control group. After 75 days of continuous intragastric administration,Morris water maze method and spontaneous activity experi-ment were used to investigate the effects of acteoside on learning,memory and anxiety of mice. The levels of neurotransmitters acetylcholine ( ACh), serotonin ( 5-HT ), norepinephrine ( NE ) and dopamine ( DA ) in mouse brain tissue(cortex and hippocampus) were detected by ELISA. Results (1) In the Morris water maze test,compared with the model group,the acteoside significantly reduced the escape latency of SAMP8 mice in training period. (2)In the experiment of autonomic activity,compared with the model group,the aver-age speed and total distance of the low-dose acteoside group were significantly increased(t=15. 0,20. 8,both P<0. 05);the number of vertical movements and the average speed of the medium-dose acteoside group were significantly increased(t=15. 8,13. 6,both P<0. 05). The average speed and total distance of the high-dose acteoside group were remarkarbly increased(t=30. 9,29. 7,both P<0. 05),and the number of defecations in the mice of the lav-dose acteoside group, medium-dose acteoside group, high-dose acteoside group were ((2. 83±1. 19)particles,(3. 25± 1. 29) particles,(2. 58± 1. 16) particles),they were obviously lower than that of the model group ((5. 25±1. 48) particles)(t=15. 7,20. 1,13. 5,all P<0. 01). (3) Simultaneously, the contents of ACh,NE and DA in the hippocampus and cortex of the model group were significantly lower than those in the normal group (hippocampus:t=10. 3,12. 7,13. 2,all P<0. 05;cortex:t=11. 7,10. 5,12. 4, all P<0. 05). Compared with the model group,the contents of ACh,NE,DA and 5-HT in the hippocampus and cortex of the low,medium and high doses of acteoside were significantly increased ( hippocampus: t=31. 4, 20. 3,10. 7,12. 9,all P<0. 05;cortex:t=33. 7,29. 4,14. 5,12. 7,all P<0. 05). Conclusion The ac-teoside can enhance the ability of spatial learning and memory of SAMP8 mice,and can regulate the depres-sion and anxiety of animals. The mechanism may be related to the ACh content and the monoamine neuro-transmitters increase in the brain.
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Objective To investigate the effects of Bushen Huoxue acupuncture method on the behavioral changes and the proliferation of endogenous neural stem cells (NSCs) in hippocampus of Alzheimer disease (AD) model mice. Methods 18 male SAMP8 mice, seven months old, were randomly divided into acupuncture group, non-acupoint control group, and model control group. And another age-matched 6 male SAMR1 mice were prepared as normal control group. Mice in acupuncture group were intervened by acupuncture method in the acupoints of "Shenshu", "Baihui", "Xuehai", and "Geshu". Mice in non-acupoint control group were treated by stimulating the fixed non-point under the bilateral rib, while mice in model control group and normal control group were raised without special treatment but administered the stimulation of catching with the same time and the same stimulus intensity. All treatrment lasted for 8 weeks. After the intervention, the learning and memory abilitities and brain hippocampus Brd U positive cells of all groups were detected. Results Compared with the nomal control group, mice in the model control group had longer escape latency and less time spent in former platform quadrant (P＜0.05); the number of Brd U positive cells decreased significantly (P＜0.05). Compared with the model control group and the non-acupoint control group, mice in the acupuncture group had shorter escape latency and more time spent in former platform quadrant (P＜0.05); the number of Brd U positive cells increased significantly (P＜0.05). Conclusion Bushen Huoxue acupuncture method can improve the learning and memory abilities of SAMP8 mice AD model by inducing the proliferation of hippocampal endogenous NSCs.
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Objective To observe the effects of Bushen Huoxue acupuncture method on amygdaloid protein expression in SAMP8; To explore the potential target protein for acupuncture treatment of Alzheimer disease (AD). Methods Thirty six-month-old male SAMP8 mice were randomly divided into acupuncture group and control group, 15 mice in each group. Acupuncture group selected Baihui (GV20), Shenshu (BL23), Geshu (BL17) and Xuehai (SP10) to intervene. The control group was given the same time to catch and stimulate. After 8 weeks, the amygdala was extracted and the differential expression protein spots were identified by proteomic techniques. Results Compared with control group, acupuncture group eventually identified 9 differential expression protein spots, of which 6 up-regulated and 3 down-regulated. According to the relevant information provided in the protein database, the main function of differential expression proteins involved in the mitochondrial energy metabolism, oxidative stress, and production of Aβ. Conclusion Bushen Huoxue acupuncture method can regulate multiple protein expressions in amygdala, suggesting that it may be through improving mitochondrial energy metabolism, oxidative stress, reducing production of Aβ to realize the potential therapeutic effects on AD.
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AIM To observe the effects of Qibao Meiran Oral Liquid (Polygoni multiflori Radix Praeparata,Angelicae sinensis Radix,Psoraleae Fructus,etc.) on learning and memory function,hippocampus tissue pathological morphology,SOD activity and carbonyl protein content in SAMP8 mice.METHODS Twenty-seven SAMP8 mice were randomly and equally divided into model control group,donepezil hydrochloride group and Qibao Meiran Oral Liquid group.Another nine SAMR1 mice were selected as normal control group.Mice were given successive intragastric administration for 60 days.On the 56th day,the passive avoidance test was adopted,and the learning and memory capacities were determined after 5 d;The pathological morphology was observed by HE staining;ELISA assay was used to detect the activity of SOD and the content of carbonyl protein in brain tissue.RESULTS Compared with the model control group,the escape latency of mice in the Qibao Meiran Oral Liquid group was significantly prolonged,and the number of errors decreased significantly (P ＜0.01);the pathological morphology of hippocampus tissue was significantly improved;SOD activity increased significantly,and carbonyl protein content decreased significantly (P ＜ 0.01).CONCLUSION Qibao Meiran Oral Liquid can not only improve the learning and memory function of SAMP8 mice,but also reduce the degree of hippocampus tissue degenerative disease.
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Objective:To study the metabolic mechanism of protective effect of waternut herb extract on primary Aβ SAMP8 damage of mouse hippocampal neurons by metabolic footprinting.Methods:MTT assay was used to determine the proliferation of primary hippocampal neurons in SAMP8 mice with Aβ damage,the effect for the first time on the basis of metabolic footprinting evaluation waternut herb extract.Focus on key metabolic pathways and related metabolic targets,mechanism of primary Aβ SAMP8 damage of mouse hippocampal neurons and pathogenesis of watemut herb extract.Results:MTT assay was used to measure the rate of cell proliferation.The results showed that the cell viability of the primary hippocampal neurons was significantly decreased in the Aβ SAMP8 mice.The study found that metabolic footprinting,compared with littermate wild-type mice,neuronal cell metabolism Aβ SAMP8 damage of mouse anomalies mainly concentrated in the metabolism of folic acid and taufine metabolism associated with nerve cells,by high-throughput mass spectrometric analysis and literature database retrieval to determine the 3 differential metabolites,respectively is L-disodoum alanine (L-Cysteic acid),dihydrofolate (Dihydrofolate),acid (Chorismate),the branch of small molecule metabolites through extract intervention after Amakusa callback trend obviously.Conclusion:the therapeutic effect of watemut herb extract on Aβ SAMP8 damage of mouse primary hippocampal neurons to a certain extent,3 biomarkers of this discovery may be a potential target of Aβ SAMP8 damage of mouse primary hippocampal neurons in the pathogenesis of waternut herb extract,given after these markers were callback trend in different degree,suggesting that watemut herb extract could regulate metabolism related enzymes and metabolic pathways to protect the purpose,to provide the experimental basis for the treatment of Alzheimer's disease watemut herb extract.
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This paper was aimed to compare the effect of Buzhong Yiqi decoction containing Hedysari Radix or Astragali Radix on anti-immunosenescence effects in spleen lymphocytes of senescence accelerated mouse 8 (SAMP8). The effect of the serums on the proliferation of spleen T lymphocytes in SAMP8 mice induced by ConA was tested by MTT. The effect of the serums on the T lymphocytes subsets of SAMP8 mice was measured by flow cytometry. ELISA was used to detect the level of IL-2 and IFN-γ in the culture supernatants of spleen lymphocytes. The effect of the serums on the expression of CD28 mRNA in spleen T lymphocytes was detected by fluorescent quantitative PCR. Western blot was used to detect the expression of CD28 protein in spleen T lymphocytes of SAMP8 mice. Both the serums of Buzhong Yiqi decoctions containing Hedysari Radix or Astragali Radix improved the proliferation of T lymphocytes in SAMP8 mice. Both the serums had no obvious effect on the differentiation of spleen T lymphocytes'subsets in SAMP8 mice. Both the serums increased the content of IL-2 and INF-γ in the culture supernatants of spleen lymphocytes. And for the content of IL-2, the serum of Buzhong Yiqi decoction with Hedysari Radix was better（P<0.05）. Both the serums improved the expression of CD28 mRNA in spleen T lymphocytes of SAMP8 mice. And the effect of Hedysari Radix group was better than that of Astragalus Radix group（P<0.05）. Both the serums improved the expression of CD28 protein in spleen T lymphocytes of SAMP8 mice. The role of the serums containing Buzhong Yiqi decoction with Astragalus Radix and the decoction with Hedysari Radix in anti-immunosenescence was through the effect of the CD28. And the effect of Hedysari Radix group was better than that of Astragalus Radix group on improved the expression of CD28 mRNA in T lymphocytes of SAMP8 mice. Astragalus Radix and Hedysari Radix could swap in the aspect of anti-immunosenescence.
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Objective To explore the role of histone H3 acetylation modification of brain derived neurotrophic factor (BDNF) in the pathogenesis of Alzheimer's disease (AD).Methods 2 months and 8 months SAMP8 mice were used as AD model.Morris water maze was used to detect the impairment of learning and memory.Western blot was used to detect BDNF protein expression in the hippocampus,and chromatin immunoprecipitation (CHIP) was applied to study the changes of histone H3 acetylation in different BDNF promoters.Results The results of water maze test showed that the time across the target quadrant in 8 months SAMP8 mice(0.9±0.4) was significant declined compared with that of 2 months SAMP8 mice(3.7 ± ±0.9) and 8 months SAMR1 mice (3.3±0.6)(all P＜0.05).Meanwhile,compared with 2 months SAMP8 mice ((23.9±4.0) s) and 8 months SAMR1 mice ((21.5± 2.3) s),target quadrant time in the 8 months SAMP8 mice((11.7±2.8) s) was also significantly reduced(both P＜0.05).The western blot showed the expression of BDNF in the hippocampus of 8 months SAMP8 mice was significantly decreased compared with that of 2 months SAMP8 mice and 8 months SAMR1 mice(P＜0.05).Lastly,CHIP assays showed that histone H3 acetylation of BDNF exon Ⅳ and Ⅵ in the hippocampus of 8 months SAMP8 mice were remarkably decreased(P＜0.05) compared with that of 2 months SAMP8 mice and 8 months SAMR1 mice.There was no significant change of histone H3 acetylation of BDNF exon Ⅰ and Ⅲ among all groups(P＞0.05).Conclusion Histone H3 acetylation of BDNF exon Ⅳ and Ⅵ is reduced during the development of AD,which may be the mechanism underlying the impairment of learning and memory in AD.
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Objective To observe the influence of oleanolic acid on the ethology of 9-month-old mice,the completeness of synapsis structure and the expression of cAMP-response element binding protein (CREB) in cortex and hippocampus.Methods Thirty 9-month-old healthy male SMAP8 mice were randomly divided into model group,oleanolic acid group and aricept group,and with 10 rats in each group,while 10 healthy male mice of the same age and species as normal group.Oleanolic acid group and aricept group were given intragastric administration with corresponding drugs,while the normal group and model group were given the same amount of physiological saline.4 weeks later,the ethology changes were observed by Morris water maze and morphology changes of hippocampus neurons were viewed by electron microscope and the expression of CREB was detected by Western Blot.Results (1)Morris water maze results suggested that compared with the normal group,the latency time in the model group mice was longer,which were ((83.33±4.96) s,(75.13±6.01) s,(71.75±7.77) s,(63.40± 8.93) s,(60.97±8.38) s),while compared with the model group,the latency time in the oleanolic acid group and the aricept group was remarkably shorter (P＜ 0.05),which were (75.97± 4.49) s,(64.98± 4.93) s,(64.16± 6.23) s,(53.47±5.99) s,(47.91±7.64) s and (71.30±7.65) s,(63.32±7.57) s,(59.82±4.69) s,(52.28±5.90) s,(46.22±7.27) s respectively.In the spatial probe trial,compared with tbe normal group,the crossing times of the model was less,while compared with the model one,the crossing times of the oleanolic acid group and the aricept group was more(P＜0.05).(2)Compared with the normal group,the number of synapses in the model group was smaller,in which the synaptic cleft was mixed with the front of synapses severely swollen,uninform synaptic vesicles and few clear outlines of mitochondrias.While the oleanolic acid group and the aricept group had clear synapses outlines with the front of synapses slightly swollen,intensive and uniform synaptic vesicles and clear mitochondrias with their cristae not easy to be seen.(3) The Western Blot showed that compared with the normal group,there was a decline in the CREB expression both in the cortex and hippocampus in the model group,while compared with the model group,there was a rise in the oleanolic acid group as well as the aricept group(P＜0.05).Conclusion Oleanolic acid can improve the learning and memorizing of model rats,which is possibly related to the increased expression of CREB protein to protect the synapses structure of model mice.
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Objective To observe cerebral hippocampus glucose metabolism using 18F-FDG micro-PET as an imaging technique in a normal group of mice, and model and electroacupuncture groups of SAMP8 mice with senile dementia (rapid aging mice). Method Four 6-month-old SAMR1 mice were picked at random out of the normal group and every four 6-month-old SAMP8 mice, out of the model and electroacupuncture groups respectively. Each of them was anesthetized by inhalation of 2% isoflurane and then given a bolus injection of radioactive tracer 18F-FDG 14.8~16.5 MBq through the tail vein. After one hour of the uptake, a PET scan was performed for 10 min. Hippocampus 18F-FDG uptake rate per gram of brain was calculated in every group of mice and the uptake rates were compared between the groups.Result The 18F-FDG uptake rate per gram of brain tissue was higher in the electroacupuncture group of mice than in the normal and model groups.Conclusion Electroacupuncture can markedly increase cerebral 18F-FDG uptake and the uptake rate per gram of brain tissue in SAMP8 mice. It may play a neuroprotective role through its influence on cerebral glucose metabolism.
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OBJECTIVE: To study the effect of modified wuzi-yanzong prescription(MWP) on brain gene expression profile in senescence accelerated mouse-prone/8 (SAMP8) mice and detect the mechanism of MWP treating dementia-related diseases. METHODS: Six SAMP8 mice were randomly divided into model group and MWP group on average, meanwhile three senescence accelerated mouse-resistance/1 (SAMR1) mice were chosen as the blank control group. The MWP group was intragastrically intervened by MWP 9 g · kg-1 · d-1, while model group and control goup were given equal volume of sodium carboxyl methyl cellulose, once a day. After 10 d, the mice in experiment were killed and seperated the whole brain. Brain RNA expression was analyzed using Illumina whole genome expression profiles. RESULTS: Compared with the model group, 293 differential genes were screened in the MWP group, including 179 up-regulated genes and 114 down-regulated genes. Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated 17 key targets about differentiation and proliferation of neural stem cells, including Notch pathway, Rap1/B-Raf/ERK pathway and related target proteins; 9 key targets about neural endocrine-immune (NEI) network, including follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, thyroid stimulating hormone (TSH), etc. CONCLUSION: The action mechanisms of MWP on brain in SAMP8 mouse involve the regulation of proliferation and differentiation of neural stem cells and NEI network.