Research ReportDehydroepiandrosterone protects male and female hippocampal neurons and neuroblastoma cells from glucose deprivation

•DHEA is neuroprotective against glucose deprivation in human neuroblastoma cells.•DHEA is also neuroprotective in male and female mouse hippocampal neurons.•DHEA may exert neuroprotective actions at least one hour after neuronal injury.

Dehydroepiandrosterone (DHEA) modulates neurogenesis, neuronal function, neuronal survival and metabolism, enhancing mitochondrial oxidative capacity. Glucose deprivation and hypometabolism have been implicated in the mechanisms that mediate neuronal damage in neurological disorders, and some studies have shown that these mechanisms are sexually dimorphic. It was also demonstrated that DHEA is able to attenuate the hypometabolism that is related to some neurodegenerative diseases, eliciting neuroprotective effects in different experimental models of neurodegeneration. The aim of this study was to evaluate the effect of DHEA on the viability of male and female hippocampal neurons and SH-SY5Y neuroblastoma cells exposed to glucose deprivation. It was observed that after 12 h of pre-treatment, DHEA was able to protect SH-SY5Y cells from glucose deprivation for 6 h (DHEA 10−12, 10−8 and 10−6 M) and 8 h (DHEA 10−8 M). In contrast, DHEA was not neuroprotective against glucose deprivation for 12 or 24 h. DHEA (10−8 M) also protected SH-SY5Y cells when added together or even 1 h after the beginning of glucose deprivation (6 h). Furthermore, DHEA (10−8 M) also protected primary neurons from both sexes against glucose deprivation. In summary, our findings indicate that DHEA is neuroprotective against glucose deprivation in human neuroblastoma cells and in male and female mouse hippocampal neurons. These results suggest that DHEA could be a promising candidate to be used in clinical studies aiming to reduce neuronal damage in people from both sexes.