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Glucocorticoid- and long-term stress-induced aberrant synaptic plasticity are mediated by activation of the glucocorticoid receptor

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Abstract

Long-term stress is known to cause aberrant synaptic plasticity and to impair learning and memory. Recent studies show that acute high concentration of glucocorticoids exerts similar effects to those of long-term stress. In the present study, we conducted an electrophysiological study, western blot analysis, and behavioral study to examine whether long-term stress and acute high concentration of corticosterone share common mechanisms. Acute corticosterone (1 μM) impaired LTP in the acute hippocampal slices, and this impairment was blocked by RU486, a glucocorticoid receptor (GR) antagonist. In the two-week restraint stress-treated rats, object recognition memory and hippocampal LTP were impaired and these impairments were restored by RU486 co-treatment. Moreover, the hippocampal BDNF level was also significantly reduced in the corticosterone- or long-term stress-treated hippocampus and restored by RU486 co-treatment. These results suggest that corticosterone and long-term stress induce aberrant synaptic plasticity, memory impairment, and reduction in the hippocampal BDNF level through GR activation. Taken together, we suggest that acute high concentration of glucocorticoid-induced LTP impairment study may be a good tool for screening the treatments for stress-induced psychiatric disorders including memory impairment.

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Acknowledgments

This research was supported by the Dong-A University research fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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The authors declare no conflict of interests.

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Authors and Affiliations

  1. Department of Medicinal Biotechnology, College of Natural Resources and Life Science, Dong-A University, 37 Nakdong-Daero 550beon-gil, Saha-Gu, Busan, 604-714, Republic of Korea

    Hye Jin Park & Dong Hyun Kim

  2. Department of Aquatic Biomedical Sciences, School of Marine Biomedical Science, College of Ocean Science, Jeju National University, Jeju, 690-756, Republic of Korea

    Seungheon Lee

  3. Department of Herbal Medicinal Pharmacology, College of Herbal Bio-industry, Daegu Haany University, Yugok-dong, Kyungsan, 712-715, Republic of Korea

    Ji Wook Jung

  4. Chonnam-Bristol Frontier Laboratory, Biomedical Research Institute, Chonnam National University Hospital, Jebong-ro, Gwangju, 501-757, Republic of Korea

    Byeong C. Kim

  5. Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, 130-701, Republic of Korea

    Jong Hoon Ryu

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  1. Hye Jin Park
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Park, H.J., Lee, S., Jung, J.W. et al. Glucocorticoid- and long-term stress-induced aberrant synaptic plasticity are mediated by activation of the glucocorticoid receptor. Arch. Pharm. Res. 38, 1204–1212 (2015). https://doi.org/10.1007/s12272-015-0548-0

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  • DOI: https://doi.org/10.1007/s12272-015-0548-0

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