Hormetic effects of serum deprivation on androgen regulation of dopamine cell viability

Abstract

Hormesis is the beneficial response of treatments harmful at high concentrations but at low levels confer resistance, such as ischemic preconditioning and dietary restriction. Androgens have been shown to increase the vulnerability of dopamine neurons via an oxidative stress mechanism. In this study, we examined if serum deprivation alters androgens’ effects on oxidative stress in a dopaminergic cell line (N27 cells). N27 cells were exposed to tert‐butyl‐hydrogen peroxide (500uM) 24hrs prior to androgen exposure in either a serum‐free environment or charcoal‐stripped serum environment. Our results showed decreased neuronal vulnerability to oxidative stress in response to androgens in the serum‐free environment compared to the charcoal‐stripped environment. Indicating that serum deprivation had a hormetic effect on androgen regulation in dopamine neuronal viability. To determine underlying mechanisms, N27 cells in a serum‐free environment were exposed to androgens for varying time periods (0–48hrs) and imaged to determine morphology. Analysis showed increased neurite outgrowth after 2hrs of androgen exposure, indicating increased synaptic plasticity. These results suggest that serum deprivation can confer a hormetic effect on dopamine neuronal viability in response to androgens by increasing synaptic plasticity. Supported by NIH grants F32NS061417‐01 to RLC and AG022550 and AG027956 to MS.