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BACKGROUND:Exercise improves Alzheimer's disease,dementia,and age-related cognitive abilities.A potential mediator between exercise and these health benefits may be adult hippocampal neurogenesis.Therefore,it is of great significance to explore whether and how exercise affects the adult hippocampal neurogenesis process in Alzheimer's disease mice. OBJECTIVE:To observe the effect of aerobic exercise on adult hippocampal neurogenesis of Alzheimer's disease mice,and to explore whether aerobic exercise can promote their adult hippocampal neurogenesis. METHODS:Three-month-old wild-type(C57BL/6Jnju)and APP/PS1 double transgenic Alzheimer's disease mice were randomly divided into four groups:wild control group,wild exercise group,Alzheimer's disease control group and Alzheimer's disease exercise group,with 20 mice in each group.The control group did not do exercise,and the exercise group did aerobic exercise for 5 months.After exercise intervention,real-time PCR,immunofluorescence and western blot assay were used to detect the expression levels of DCX,Ki67,βIII-tubulin and NeuN in the hippocampal tissue of mice in each group. RESULTS AND CONCLUSION:The expressions of DCX,βIII-tubulin and NeuN in the hippocampal dentate gyrus in the Alzheimer's disease control group were significantly lower than those in the wild control group(P<0.05).The expressions of DCX,Ki67,βIII-tubulin and NeuN were significantly higher in the hippocampal dentate gyrus in the Alzheimer's disease exercise group than those in the Alzheimer's disease control group(P<0.05).It is indicated that long-term aerobic exercise intervention can strengthen the proliferation,migration and differentiation of neurons during adult hippocampal neurogenesis and significantly increase the number of neuronal precursor cells and new neurons in Alzheimer's disease mice.
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BACKGROUND:Patients with Alzheimer's disease mainly show cognitive and memory dysfunctions.Aerobic exercise can inhibit endoplasmic reticulum stress and improve cognitive function of the patients.However,whether aerobic exercise can inhibit endoplasmic reticulum stress dependent neuroinflammation is still unclear. OBJECTIVE:To explore the effect of aerobic exercise on neuroinflammation and cognitive impairment in a mouse model of Alzheimer's disease. METHODS:Fifty C57BL/6J wild-type male mouse mice were randomly divided into wild-type control and wild-type exercise groups,while another 50 APP/PS1 double transgenic male mice were randomly divided into Alzheimer's disease group and Alzheimer's disease exercise group,with 25 mice in each group.Mice in the wild-type exercise and Alzheimer's disease exercise groups received aerobic exercise training(treadmill training,45 min/d,12 m/min,5 d/wk,8 weeks in total).Mice in the wild-type control and Alzheimer's disease groups were placed on the quiet running platform.Morris water maze test was used to detect the cognitive ability of mice.Hematoxylin-eosin staining and Nissl staining were used to detect hippocampal tissue damage in mice.Thioflavin-S staining was used to detect β-amyloid content in hippocampal tissue.Immunohistochemistry was used to detect β-amyloid and p-Tau levels in hippocampal tissue.Immunofluorescence staining was used to detect the number of positive cells for neuroinflammation-related factors in hippocampal tissue.Western blot was used to detect p-IRE1,IRE1,p-PERK,PERK,ATF6,GRP78,Bip,Caspase-12,Iba-1,and GFAP protein levels. RESULTS AND CONCLUSION:Compared with the wild-type control group,escape latency was increased,the number of times they reached the previous platform and the time they stayed on the platform were decreased,β-amyloid and Tau levels,p-IRE1/IRE1,p-PERK/PERK,ATF6,GRP78,Bip,Caspase-12,Iba-1,and GFAP protein levels,Iba-1+,Iba-1+TNF-α+,Iba-1+IL-6+,Iba-1+IL-1β+,GFAP+,GFAP+TNF-α+,GFAP+IL-6+,GFAP+IL-1β+ positive cells in hippocampal tissue were increased,and Iba-1+IL-4+,Iba-1+IL-10+,GFAP+IL-4+,GFAP+IL-10+ positive cells were decreased in the Alzheimer's disease group(P＜0.05).Compared with Alzheimer's disease group,escape latency was decreased,the number of times they reached the previous platform and the time they stayed on the platform were increased,β-amyloid and Tau levels,p-IRE1/IRE1,p-PERK/PERK,ATF6,GRP78,Bip,Caspase-12,Iba-1,GFAP protein levels,Iba-1+,Iba-1+TNF-α+,Iba-1+IL-6+,Iba-1+IL-1β+,GFAP+,GFAP+TNF-α+,GFAP+IL-6+,and GFAP+IL-1β+ positive cells in hippocampal tissue were decreased,and Iba-1+IL-4+,Iba-1+IL-10+,GFAP+IL-4+,GFAP+IL-10+ positive cells were increased in the Alzheimer's disease exercise group(P＜0.05).To conclude,aerobic exercise can reduce cognitive impairment in Alzheimer's disease mice by inhibiting endoplasmic reticulum stress and neuroinflammation in hippocampal tissue.
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BACKGROUND:β-amyloid protein and Tau protein have adverse effects on the cognitive function of Alzheimer's disease patients,and Notch1 and Caspase-3 can regulate the expression of β-amyloid protein and Tau protein.It is not clear whether Notch1 and Caspase-3 mediate the process of aerobic exercise to improve the cognitive ability of Alzheimer's disease patients.At present,there is a lack of studies on the effect of long-term aerobic exercise on the expression of Notch1 and Caspase-3 in the hippocampus of Alzheimer's disease mice. OBJECTIVE:To observe the expression of Notch1 and Caspase-3 in the hippocampus of Alzheimer's disease mice undergoing long-term aerobic exercise and to investigate the effects of Notch1 and Caspase-3 in Alzheimer's disease mice. METHODS:Wild type and APP/PS1 double-transgenic Alzheimer's disease mice aged 3 months were randomly divided into four groups:wild control group,wild exercise group,Alzheimer's disease control group and Alzheimer's disease exercise group,with 20 mice in each group.Mice in the control groups were not subjected to exercise,while those in the exercise groups received aerobic exercise intervention for 5 months.After the exercise intervention,Morris water maze was used to detect the spatial learning and memory ability of mice.Real-time PCR,immunofluorescence and western blot were used to detect the expressions of Aβ1-42,Tau,Notch1 and Caspase-3 in the hippocampal tissues of mice in each group. RESULTS AND CONCLUSION:The spatial learning and memory ability of Alzheimer's mice was significantly worse than that of wild-type mice(P＜0.05).The spatial learning and memory ability of mice in the exercise groups were significantly better than that in the corresponding control groups(P＜0.05).The expressions of Aβ1-42,Tau,Notch1 and Caspase-3 in the hippocampus were significantly higher in the Alzheimer's disease control group than the wild control group(P＜0.05)and were significantly lower in the Alzheimer's disease exercise group than the Alzheimer's disease control group(P＜0.05).To conclude,long-term aerobic exercise can improve the spatial learning and memory ability of Alzheimer's disease mice,which may be related to the decreased expression of Notch1,Caspase-3,Aβ1-42 and Tau protein in the hippocampus of Alzheimer's disease mice.
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BACKGROUND:Abnormal Notch1 signaling pathway is mostly found in the brain of Alzheimer's disease patients,but the role of these signaling pathways in the pathogenesis of Alzheimer's disease has not been fully clarified.Long-term aerobic exercise can alter the expression of Notch1 by affecting the methylation rate of factors related to the Notch1 signaling pathway.However,it is not clear whether aerobic exercise affects hippocampal nerve cell proliferation and histopathological features of Alzheimer's disease mice through the Notch1 signaling pathway. OBJECTIVE:To observe the effects of aerobic exercise on the proliferation and histopathological features of hippocampal nerve cells in Alzheimer's disease mice after DAPT inhibited the Notch1 signaling pathway. METHODS:APP/PS1 double transgenic Alzheimer's disease mice aged 3 months were randomly divided into four groups:control group,exercise control group,inhibitor group,and exercise inhibitor group,with 20 mice in each group.The control group was fed naturally,and the exercise group received aerobic exercise intervention.Both natural feeding and exercise intervention lasted for 20 weeks.The mice were injected with solvent or Notch1 inhibitor at week 18.After 20 weeks,the brain tissue was collected,and Aβ1-42,Tau,Ki67,and Notch1 expression levels were detected by real-time PCR,immunofluorescence,and western blot assay. RESULTS AND CONCLUSION:Compared with the control group,the expressions of Ki67 and Notch1 in the dentate gyrus region of the hippocampus were significantly decreased in the inhibitor group(P<0.05),but there were no significant differences in Aβ1-42 and Tau.The expression of Ki67 in the dentate gyrus region of the hippocampus in the exercise control group was significantly higher than that in the control group,while the expressions of Aβ1-42,Tau,and Notch1 were significantly lower than those in the control group(P<0.05).The expressions of Aβ1-42,Tau,Ki67,and Notch1 in the dentate gyrus region of the hippocampus of the exercise inhibitor group were not significantly different from those of the inhibitor group.In conclusion,the Notch1 signaling pathway may mediate exercise to improve the proliferation and histopathological features of hippocampal nerve cells in Alzheimer's disease mice.
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Objective To observe the effect of aerobic exercises on the expression of synaptophysin (SYP)and postsynaptic density protein-95 (PSD-95) in the prefrontal lobe of brain-aging rats induced by D-galactose (D-gal) and to explore the underlying mechanism of aerobic exercises relieving learning and memory deficits in the brain-aging process.Methods Thirty-six 3-month-old male Sprage-Dawley rats were randomly divided into a saline control group (C),a D-gal control group (D),and a D-gal and aerobic exercises group (DE),each of 12.The rats in both group D and DE were injected D-gal (100 mg/kg body weight) abdominally every day for 6 consecutive weeks,while those in group C were injected the same amount of saline.Meanwhile,the rats in group DE had performed aerobic swimming for 1 hour daily,while the other two groups did not do any exercises.Then,the Morris Water Maze (MWM) test was performed to estimate the learning and memory abilities.The immunofluorescence technology,Western blotting and real-time PCR were used to determine the expression levels of SYP,PSD-95,SYP mRNA and PSD-95 mRNA in the prefrontal lobe.Results In the process of navigation training,all animals' escape latencies shortened gradually,indicating that each rat was able to learn to locate the submerged platform.The rats in group C and DE showed best performance on day 3 and no significant improvement was observed thereafter,whereas those in group D improved at a slower pace,and reached maximal performance on day 5.On the 2nd,3rd and 4th days of the navigation training,the average escape latency of group D was significantly longer than that of group C and group DE (P＜0.05),while on the 1st,5th and 6th days,there was no significant difference among the 3 groups.In the probe trial,rats in group D spent significantly less time in the target quadrant compared with both group C and DE (P＜0.05),and rats in group C and DE crossed where the platform was fixed significanlty more often than group D (P＜0.05).The expression levels of SYP and SYP mRNA in the prefrontal lobe of rats in group D were significantly lower than group C (P＜0.01),and group DE (P＜ 0.05).Compared with group C,the expression levels of PSD-95 and PSD mRNA in the prefrontal lobe of rats in group D declined significantly (P＜0.01).There was no significant difference in PSD-95 expression between group D and DE,but the level of PSD-95 protein molecule of group DE was significantly higher than that of group D (P＜0.05).Conclusions The aerobic exercises can ameliorate the deficits of SYP and PSD-95 expression in the frontal cortex of aging rats induced by D-gal to some extent,and improve their learning and memory abilities.