[Effect of mammalian target of rapamycin on cognitive dysfunction of Alzheimer's Disease via regulating Homer3].
Zhonghua Yi Xue Za Zhi
; 100(17): 1336-1340, 2020 May 05.
Article
em Zh
| MEDLINE
| ID: mdl-32375443
ABSTRACT
Objective:
To exploer the effect of mammalian target ofrapamycin(mTOR)on cognitive dysfunction of mice with Alzheimer's disease (AD) induced by amyloid ß(1-42) (Aß(1-42)) via observing the regulation effect of rapamycin on Homer3 in hippocampus.Methods:
The 32 mice were randomly divided into fourgroups sham group (the hippocampus of mice was injected with normal saline); AD group (the hippocampus of mice was injected with Aß(1-42)); DMSO group(AD mice induced by Aß(1-42) were intraperitoneally injected with dimethylsulfoxide for 14 days);RAPA group(AD mice induced by Aß(1-42) were intraperitoneally injected with rapamycin 1 mg/kg for 14 days). Morris maze and Y maze experiments to measuring cognitive function and immunowestern bloting detecting the expression of Aß(1-42), mTOR, p-mTOR and Homer3 in the hippocampus were conducted on each group of mice.Results:
Compared with sham group,the AD group showed significantly longer escape latency,shoter residence time of objective quadrant, less numbers of crossing of original platform, lower alternation ratio(P<0.05); Compared with DMSO group, RAPA group showed significantly shorter escape latency, longer residence time of objective quadrant, more numbers of crossing of original platform, more alternation ratio(P<0.05). The levels of Aß(1-42) and p-mTOR were increased, the levels of Homer3 were decreased in DMSO group mice's hippocampus compared with sham group(P<0.05); the levels of Aß(1-42) and p-mTOR were decreased,the levels of Homer3 were increased in RAPA group mice's hippocampus compared with DMSO group(P<0.05).Conclusion:
The inhibitor of mTOR rapamycin can improve the cognitive dysfunction of mice with AD induced by Aß(1-42) and reduce deposition of Aß(1-42) in the hippocampus, and the possible mechanism is rapamycin depressing the phosphorylation of mTOR as the same as Up-regulation the expression level of Homer3.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Doença de Alzheimer
/
Disfunção Cognitiva
Limite:
Animals
Idioma:
Zh
Ano de publicação:
2020
Tipo de documento:
Article