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Comparison of the Adulthood Chronic Stress Effect on Hippocampal BDNF Signaling in Male and Female Rats

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Abstract

Studies show that gender plays an important role in stress-related disorders, and women are more vulnerable to its effect. The present study was undertaken to investigate differences in the change in expression of brain-derived neurotrophic factor (BDNF), and its tyrosine intracellular kinase-activating receptor (TrkB) genes in the male and female rats’ hippocampus (HPC) under chronic mild repeated stress (CMRS) conditions. In this experiment, male and female Wistar rats were randomly divided into two groups: the CMRS and the control group. To induce stress, a repeated forced swimming paradigm was employed daily for adult male and female rats for 21 days. At the end of the stress phase, elevated plus maze (EPM) was used for measuring the stress behavioral effects. Serum corticosterone level was measured by ELISA. BDNF and TrkB gene methylation and protein expression in the HPC were detected using real-time PCR and Western blotting. Chronic stress in the adolescence had more effects on anxiety-like behavior and serum corticosterone concentration in female rats than males. Furthermore, stressed female rats had higher methylation levels and following reduced protein expression of BDNF but not TrkB compared to stressed male rats. These findings suggest that in exposure to a stressor, sex differences in BDNF methylation may be root cause of decreased BDNF levels in females and may underlie susceptibility to pathology development.

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Authors and Affiliations

  1. Physiology Research Center and Dept. of Physiology, Iran University of Medical Science, Tehran, Iran

    Somayeh Niknazar & Arezo Nahavandi

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

    Somayeh Niknazar & Ali Asghar Peyvandi

  3. Clinical Developmental Research Center, Loghman Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Hassan Peyvandi & Amin Shams Akhtari

  4. Biotechnology Research Center, Department of Molecular Medicine, Pasteur Institute of Iran, Tehran, Iran

    Mohsen Karimi

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  1. Somayeh Niknazar
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  2. Arezo Nahavandi
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Correspondence to Arezo Nahavandi.

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Niknazar, S., Nahavandi, A., Peyvandi, A.A. et al. Comparison of the Adulthood Chronic Stress Effect on Hippocampal BDNF Signaling in Male and Female Rats. Mol Neurobiol 53, 4026–4033 (2016). https://doi.org/10.1007/s12035-015-9345-5

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