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Effect of Metformin on Adult Hippocampal Neurogenesis: Comparison with Donepezil and Links to Cognition

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Abstract

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.

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Acknowledgements

This research was supported through MS student’s research grant by National University of Sciences and Technology (NUST), Islamabad, Pakistan. We also thank Prof. Dr. Thomas C Nugent, Jacobs University, Bremen, Germany, for proof reading the manuscript.

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Authors and Affiliations

  1. Neurobiology Research Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan

    Sara Ahmed, Zahra Mahmood, Aneela Javed & Saadia Zahid

  2. Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan

    Shoaib Naiyer Hashmi

  3. Department of Neurology, Clinical Dementia Center and DZNE, Georg-August University, University Medical Center Goettingen (UMG), Robert-Koch-Str. 40, 37075, Goettingen, Germany

    Inga Zerr & Saima Zafar

Authors
  1. Sara Ahmed
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  2. Zahra Mahmood
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  3. Aneela Javed
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  4. Shoaib Naiyer Hashmi
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  5. Inga Zerr
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  7. Saadia Zahid
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Correspondence to Saadia Zahid.

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Author’s Roles

*SZ, substantial contribution to conception and design of the study and finalization of the manuscript; SZ and IZ, MS/MS identification and data analysis. AJ and ZM, analysis of gene expression data, SNH, histological assessment; SA, all experimental work, analysis, data interpretation and drafting the article.

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Ahmed, S., Mahmood, Z., Javed, A. et al. Effect of Metformin on Adult Hippocampal Neurogenesis: Comparison with Donepezil and Links to Cognition. J Mol Neurosci 62, 88–98 (2017). https://doi.org/10.1007/s12031-017-0915-z

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  • DOI: https://doi.org/10.1007/s12031-017-0915-z

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