Chronic stress has been shown to be associated clinically with formation of depression in patients and hormones are known to mediate certain clinical manifestations of mood disorders. Although the precise mechanisms underlying these effects remain to be elucidated, increasing data suggests that an alteration in neuroprotection and mitochondrial functions may play an important role. The primary objective of this study is to understand the mitochondrial functions regulated by hormones during chronic stress. Cortical neuronal cultures were established in order to determine the localization and function of glucocorticoid receptors in the mitochondria. Glucocorticoid levels in mitochondria were decreased after corticosterone (10-7M) treatment in cultured cortical neurons. In addition, mitochondrial oxidation function was enhanced after one day treatment of corticosterone (10-7M), determined by MitoTracker Red staining. Consistent with the enhancement of mitochondrial function, mitochondrially encoded gene cytochrome oxidase I (COXI) (has GRE in its promoter region) expression was also increased in mitochondria. We found that total Bag-1 protein expression was decreased in cell homogenates, however, Bag1 distribution in mitochondria was increased, suggesting an important role in regulating glucocorticoid effects in the mitochondria. In collaboration with Dr. Bruce McEwen's lab, we will use a well-established chronic-stress paradigm to study the function of glucocorticoid receptor in mitochondria in vivo by biochemical and immunocytochemical methods. These studies may provide additional insights on the mechanisms by which hormones regulate mitochondrial function and neuronal signaling. Furthermore, this research also has the potential to contribute to a more complete understanding of the mechanisms by which chronic stress and hormones regulate neuroplasticity and neuronal survival and to the future development of improved therapeutics.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Intramural Research (Z01)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
U.S. National Institute of Mental Health
United States
Zip Code