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Involvement of Nrf2 in Development of Anxiety-Like Behavior by Linking Bcl2 to Oxidative Phosphorylation: Estimation in Rat Hippocampus, Amygdala, and Prefrontal Cortex

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Abstract

Anxiety-related disorders are complex illnesses that underlying molecular mechanisms of these complicated emotional disorders are poorly understood. Nuclear factor erythroid 2-related factor 2 (Nrf2) is the most important regulator of the antioxidant defense system. Its protective actions are not only limited to antioxidative transactivation, but also plays important roles in encountering various physiological and pathological stresses. In this study, we evaluated whether silencing of Nrf2 plays a role in development of anxiety-related behavior. In this regard, we exerted small interfering RNA (siRNA) targeting Nrf2 in dorsal third ventricle and subsequently examined the effect of this silencing on anxiety-related behavior along with supposed molecular mechanisms. Therefore, we evaluated apoptotic markers and mitochondrial electron transport chain (ETC) activity in three brain regions: hippocampus, amygdala, and prefrontal cortex. Based on our result, Nrf2-silenced rats exhibited greater anxiety-like behavior compared to control group. Furthermore, Nrf2 silencing increased activity of ETC complexes. Also, Bax/Bcl2 ratio of all mentioned areas of the brain and cleavage of caspase-3 in hippocampus increased in Nrf2 silenced group, however, with a distinct pattern.

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Acknowledgments

This work was supported financially by Iran National Science Foundation (INSF, grant number 91003013).

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Authors and Affiliations

  1. Department of Animal Physiology, Faculty of Biology, Kharazmi (Tarbiat Moallem) University, Tehran, Iran

    Solmaz Khalifeh & Shahrbanoo Oryan

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

    Hadi Digaleh, Fariba Khodagholi & Nader Maghsoudi

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

    Hadi Digaleh, Fariba Khodagholi & Nader Maghsoudi

  4. Neurophysiology Research Center, Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Fatemeh Shaerzadeh

  5. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad-Reza Zarrindast

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  1. Solmaz Khalifeh
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  2. Shahrbanoo Oryan
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Correspondence to Solmaz Khalifeh.

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Khalifeh, S., Oryan, S., Digaleh, H. et al. Involvement of Nrf2 in Development of Anxiety-Like Behavior by Linking Bcl2 to Oxidative Phosphorylation: Estimation in Rat Hippocampus, Amygdala, and Prefrontal Cortex. J Mol Neurosci 55, 492–499 (2015). https://doi.org/10.1007/s12031-014-0370-z

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  • DOI: https://doi.org/10.1007/s12031-014-0370-z

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