Hashikawa, Naoya Okayama University of Science
Utaka, Yuta Okayama University of Science
Ogawa, Takumi Okayama University of Science
Tanoue, Ryo Okayama University of Science
Morita, Yuna Okayama University of Science
Yamamoto, Sayumi Okayama University of Science
Yamaguchi, Satoru Okayama University of Science
Kayano, Masafumi Okayama University of Science
Hashikawa-Hobara, Narumi Okayama University of Science
Heat shock proteins (HSPs) are stress-induced chaperones that are involved in neurological disease. Although increasingly implicated in behavioral disorders, the mechanisms of HSP action, and the relevant functional pathways, are still unclear. We examined whether oral administration of geranylgeranylacetone (GGA), a known HSP inducer, produced an antidepressant effect in a social defeat stress model of depression in mice. We also investigated the possible molecular mechanisms involved, particularly focusing on hippocampal neurogenesis and neurotrophic factor expression. In stressed mice, hippocampal HSP105 expression decreased. However, administration of GGA increased HSP105 expression and improved depression-like behavior, induced hippocampal cell proliferation, and elevated brain-derived neurotrophic factor (BDNF) levels in mouse hippocampus. Co-treatment with GGA and the BDNF receptor inhibitor K252a suppressed the antidepressant effects of GGA. HSP105 knockdown decreased BDNF mRNA levels in HT22 hippocampal cell lines and hippocampal tissue and inhibited the GGA-mediated antidepressant effect. These observations suggest that GGA administration is a therapeutic candidate for depressive diseases by increasing hippocampal BDNF levels via HSP105 expression.
American Association for the Advancement of Science
2017 © The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC)(https://creativecommons.org/licenses/by-nc/4.0/).
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sciadv_3_5_e1603014.pdf 1.24 MB