Abstract/Summary

This study examined the neuroprotective properties of estrogen in the male brain, specifically focusing on its production and effects on the prefrontal cortex (PFC) during oxygen-glucose deprivation (OGD). This research addresses a knowledge gap regarding the role of estrogen in male neuroprotection, considering the lower systemic estrogen levels in males compared to females. PFC slices from adult male mice were incubated in artificial cerebrospinal fluid (ACSF) for 0 and 24 hrs. Elevated estrogen levels were detected in ACSF after 24 hrs, indicating active estrogen synthesis in male PFC. To explore the neuroprotective effects of estrogen during OGD, recordings were used to measure field excitatory postsynaptic potentials (fEPSPs) in PFC slices using a perforated multi-electrode array (pMEA). Slices were treated with 100 nM estrogen, 0.1% DMSO (vehicle), or estrogen + 1µM ICI 182,780 (GPER1 agonist and ERα/ERβ antagonist). During 10 min of OGD, fEPSP amplitude significantly decreased in DMSO-treated slices compared to estrogen-treated slices. Estrogen maintained the fEPSP amplitude during OGD. Estrogen + ICI 182,780 treatment did not alter the fEPSP amplitude, suggesting that GPER1 is involved in neuroprotection and not ERα or ERβ. Lastly, to explore the neuroprotective effects of estrogen during OGD on neuronal firing rate, slices were perfused with 100 nM of estrogen, and recordings were used to measure the firing rate. The application of estrogen did not affect the firing rate in the adult male mPFC; however, this was the first study to explore the firing rate of the adult PFC undergoing OGD using pMEA. The male PFC demonstrated a capacity for active estrogen synthesis. Estrogen exhibits neuroprotective properties in the male brain during OGD. The neuroprotective effects may be mediated, at least partially, by the GPER1 receptor. These findings suggest that estrogen may function as a neuroprotective steroid in the male brain, particularly during ischemic conditions, despite lower systemic estrogen levels than in females.