HSP105 prevents depression-like behavior by increasing hippocampal brain-derived neurotrophic factor levels in mice.
Level 5 - mechanism / opinion, no new human data
Bench and animal research (mice and cell lines)
PubMed 28580422 · doi:10.1126/sciadv.1603014
What was done
Mice subjected to a social defeat stress model of depression received oral geranylgeranylacetone (GGA), an inducer of heat shock proteins. Researchers evaluated depression-like behavior, hippocampal cell proliferation, and brain-derived neurotrophic factor (BDNF) levels. To delineate the mechanism, they tested co-treatment with the BDNF receptor inhibitor K252a and performed HSP105 knockdown experiments in HT22 hippocampal cell lines and hippocampal tissue.
What was found
The abstract reports directional findings without providing numerical values or effect sizes. Stress reduced hippocampal HSP105 expression, whereas GGA administration increased HSP105 expression, improved depression-like behavior, induced hippocampal cell proliferation, and elevated BDNF levels. The antidepressant effects of GGA were suppressed by K252a co-treatment and abolished by HSP105 knockdown, which also reduced BDNF mRNA expression.
Why it matters
The study identifies a mechanistic pathway linking heat shock protein 105 induction to BDNF upregulation and neurogenesis, highlighting a potential pharmacological target for depressive disorders.
Limits
The findings are limited to animal models and in vitro cell culture, lacking direct human clinical validation. The abstract reports no sample sizes, dosages, or quantitative statistical values.
Cited by
- supports Increased heat shock protein 105 in mice protected them from stress-induced depressive behaviors, correlated with increased BDNF.