SCIENCE@home

HSP105 prevents depression-like behavior by increasing hippocampal brain-derived neurotrophic factor levels in mice

Naoya Hashikawa,Yuta Utaka,Takumi Ogawa,Ryo Tanoue,Yuna Morita,Sayumi Yamamoto,S. Yamaguchi,M. Kayano,Y. Zamami,Narumi Hashikawa-Hobara

Published 2017 in Science Advances

ABSTRACT

The gastric ulcer drug teprenone has central nervous system effects, specifically reducing depression-like behavior in mice. 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.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-44 of 44 references · Page 1 of 1

CITED BY

Showing 1-39 of 39 citing papers · Page 1 of 1