Modulating expression of brain heat shock proteins by estrogen in ovariectomized mice model of aging

Heat shock proteins (HSPs) serve as molecular chaperones and endogenous cytoprotective factors. Two of the well-studied HSPs, HSP70, and HSP27 can be significantly induced in many areas of brain by a variety of stressors. A decrease in expression of brain HSPs has been documented in aged brain. Estrogen is well known as a neuroprotective hormone, and it has been reported that estrogen can regulate HSP70 and HSP27 expression in neuronal cells. In this study, the relationship between estrogen and heat stress-induced brain HSPs expression in young and aged ovariectomized (OVX) mice was investigated. Our results show that heat stress-induced levels of HSP70 proteins and mRNA transcripts was significantly lower in brain of aged (12 month) OVX mice, compared with young (2 month) OVX mice group. Estrogen supplementation (17β-estradiol 0.5 mg/kg for 7 days) restored heat stress-induced brain HSP70 expression and attenuated heat stress-induced brain DNA fragmentation, caspase 3 activation and mitochondrial leakage of cytochrome c and AIF in OVX mice. These results suggest that estrogen deficiency during aging down-regulates heat stress-induced brain HSP70 expression, which reveals a previously unknown link between estrogen deficiency and stress response elements.