Effect of Metformin on Adult Hippocampal Neurogenesis: Comparison with Donepezil and Links to Cognition
Effect of Metformin on Adult Hippocampal Neurogenesis: Comparison with Donepezil and Links to Cognition
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DOI：
10.1007/s12031-017-0915-z
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发表时间：
2017-05-01
影响因子：
3.1
通讯作者：
Zahid, Saadia
中科院分区：
文献类型：
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作者：
Ahmed, Sara;Mahmood, Zahra;Zahid, Saadia
最近的研究发现，有证据表明，干扰海马成体神经发生有助于阿尔茨海默病（AD）的神经退行性变。支持AD是一种脑葡萄糖利用紊乱的代谢性疾病的证据意味着使用抗糖尿病药物作为替代治疗策略。本研究比较了二甲双胍和多奈哌齐在AlCl 3诱导的神经退行性变小鼠模型中的促神经发生潜力。进行Morris水迷宫任务和随后的NeuN免疫组织化学评价。分别通过qRT-PCR和SDS-PAGE确定神经发生标志物的表达和海马蛋白质组分析，然后通过ESI-QTOFF MS/MS鉴定。结果表明，与对照组相比，AlCl 3组的空间记忆受损和8种蛋白质的差异表达。有趣的是，二甲双胍治疗使蛋白质组谱和神经发生标志物的表达水平正常化，同时沿着空间记忆改善。此外，与多奈哌齐相比，二甲双胍治疗的小鼠表现出有丝分裂后NeuN阳性神经元的数量增加。这表明二甲双胍介导的成年海马神经发生的潜在分子机制可能对神经退行性疾病的治疗有影响。
Recent studies have uncovered evidence suggesting that interference with hippocampal adult neurogenesis contributes to neurodegeneration in Alzheimer's disease (AD). Evidence supporting that AD is a metabolic disease with derangements in brain glucose utilization implies the use of anti-diabetics as an alternate therapeutic strategy. The present study drew comparison between the pro-neurogenic potential of metformin and donepezil in AlCl3-induced mouse model of neurodegeneration. Morris water maze task and subsequent immunohistochemical evaluation for NeuN was conducted. Expression of neurogenesis markers and hippocampal proteome analysis was determined by qRT-PCR and SDS-PAGE, respectively, followed by ESI-QTOFF MS/MS identification. The results demonstrated impaired spatial memory and differential expression of eight proteins in the AlCl3 group as compared to the controls. Interestingly, treatment with metformin normalized the proteome profile and expression levels of neurogenesis markers along with improvement in the spatial memory. Moreover, as compared to donepezil, metformin-treated mice exhibited an enhanced number of post-mitotic NeuN-positive neurons. It is suggested that underlying molecular mechanisms of metformin-mediated adult hippocampal neurogenesis may have implications in treatment of neurodegenerative disorders.