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Among the neuroactive steroids, dehydroepiandrosterone (3b-hydroxyandrost-5-ene17-one, [DHEA]) and its sulfated metabolite DHEA sulfate (DHEAS) have been shown to be potent modulators of neural function, including neurogenesis, neuronal growth and differentiation, and neuroprotection. Highlighting the potential health significance of DHEA and DHEAS in humans, serum concentrations decrease steadily with age, with lowest concentrations present at the time many diseases of aging and neurodegeneration become apparent. This temporal association has led to the suggestion that pathology associated with cognitive decline, age-related neurological disorders such as Alzheimer’s disease, dementia, amyotrophic lateral sclerosis (ALS), and adult onset schizophrenia may, in part at least, be attributed to decreased secretion of DHEA. Animal studies suggest neuroprotective functions for DHEA and DHEAS through reduction of glutamate-induced excitotoxicity. Reduced myelin loss and reactive gliosis after spinal cord injury by DHEA treatment also suggest a role for DHEA in the treatment of white matter pathologies such as multiple sclerosis. In this chapter, we discuss the physiological roles of DHEA and DHEAS in the central nervous system (CNS), their potential as neuroprotective hormones with reference to documented effects on excitotoxicity and oxidative stress, and their anti-glucocorticoid actions during chronic stress. The potential for metabolic derivatives of DHEA, such as estrogens and testosterone on brain function, and their contribution to neurodevelopment and neurodegenerative conditions are also discussed.

Dehydroepiandrosterone (DHEA) and DHEA Sulfate: Roles in Brain Function and Disease