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Time Course of Behavioral Alteration and mRNA Levels of Neurotrophic Factor Following Stress Exposure in Mouse

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Abstract

Stress is known to affect neurotrophic factor expression, which induces depression-like behavior. However, whether there are time-dependent changes in neurotrophic factor mRNA expression following stress remains unclear. In the present study, we tested whether chronic stress exposure induces long-term changes in depression-related behavior, serum corticosterone, and hippocampal proliferation as well as neurotrophic factor family mRNA levels, such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and ciliary neurotrophic factor (CNTF), in the mouse hippocampus. The mRNA level of neurotrophic factors (BDNF, NGF, NT-3, and CNTF) was measured using the real-time PCR. The serum corticosterone level was evaluated by enzyme-linked immunosorbent assay, and, for each subject, the hippocampal proliferation was examined by 5-bromo-2-deoxyuridine immunostaining. Mice exhibited depression-like behavior in the forced-swim test (FST) and decreased BDNF mRNA and hippocampal proliferation in the middle of the stress exposure. After 15 days of stress exposure, we observed increased immobility in the FST, serum corticosterone levels, and BDNF mRNA levels and degenerated hippocampal proliferation, maintained for at least 2 weeks. Anhedonia-like behavior in the sucrose preference test and NGF mRNA levels were decreased following 15 days of stress. NGF mRNA levels were significantly higher 1 week after stress exposure. The current data demonstrate that chronic stress exposure induces prolonged BDNF and NGF mRNA changes and increases corticosterone levels and depression-like behavior in the FST, but does not alter other neurotrophic factors or performance in the sucrose preference test.

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Acknowledgments

The authors are thankful to Dr. Yoshihisa Kitamura and Dr. Kenshi Takechi for their support.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Life Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama, 700-0005, Japan

    Naoya Hashikawa, Takumi Ogawa, Yusuke Sakamoto, Mami Ogawa, Yumi Matsuo & Narumi Hashikawa-Hobara

  2. Medicinal Drug Design, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama, Japan

    Yoshito Zamami

Authors
  1. Naoya Hashikawa
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  2. Takumi Ogawa
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  3. Yusuke Sakamoto
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  4. Mami Ogawa
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  5. Yumi Matsuo
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  6. Yoshito Zamami
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  7. Narumi Hashikawa-Hobara
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Correspondence to Narumi Hashikawa-Hobara.

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Hashikawa, N., Ogawa, T., Sakamoto, Y. et al. Time Course of Behavioral Alteration and mRNA Levels of Neurotrophic Factor Following Stress Exposure in Mouse. Cell Mol Neurobiol 35, 807–817 (2015). https://doi.org/10.1007/s10571-015-0174-x

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  • DOI: https://doi.org/10.1007/s10571-015-0174-x

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