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Geldanamycin Reduces Aβ-Associated Anxiety and Depression, Concurrent with Autophagy Provocation

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Abstract

Neurodegenerative disorders are generally characterized by abnormal aggregation and deposition of specific proteins. Amyloid beta (Aβ)-associated neurodegenerative disorder is characterized by an oxidative damage that, in turn, leads to some behavioral changes before the establishment of dementia such as depression and anxiety. In the current study, we investigated the effect of heat shock protein 90 inhibitor geldanamycin (GA) administration 24 h before Aβ injection. In our experiment, 7 days after Aβ injection, elevated plus maze and forced swimming test were conducted to assess anxiety and depression-like behaviors. Levels of autophagy markers and malondialdehyde (MDA) and also activity of catalase in the hippocampus of rats were evaluated. Our behavioral analyses demonstrated that GA pretreatment can significantly decrease anxiety- and depression-like behaviors in Aβ-injected rats. Also, levels of autophagy markers including Atg12, Atg7, and LC3-II increased, while MDA level decreased and the activity of catalase increased in rats pretreated with GA compared to Aβ-injected rats. Thus, we assumed that GA, at least in part, ameliorated Aβ-mediated anxiety and depression by inducing autophagy and improving antioxidant defense system.

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Acknowledgments

This work is part of the PhD student’s thesis of N. Zare at the Shahid Beheshti University of Medical Sciences.

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The author declares that they have no conflict of interest.

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Authors and Affiliations

  1. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Nayereh Zare, Fariba Khodagholi, Shima Zareh Shahamati, Fereshteh Motamedi & Nader Maghsoudi

  2. NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Nayereh Zare, Fariba Khodagholi, Shima Zareh Shahamati, Fereshteh Motamedi & Nader Maghsoudi

  3. Medical Genomics Research Center and School of Advanced Sciences in Medicine, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran

    Solmaz Khalifeh

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  1. Nayereh Zare
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Correspondence to Nader Maghsoudi.

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Zare, N., Khalifeh, S., Khodagholi, F. et al. Geldanamycin Reduces Aβ-Associated Anxiety and Depression, Concurrent with Autophagy Provocation. J Mol Neurosci 57, 317–324 (2015). https://doi.org/10.1007/s12031-015-0619-1

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  • DOI: https://doi.org/10.1007/s12031-015-0619-1

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