Neurosteroids in the aging brain

Abstract

In addition to the important function neurosteroids play in neurodevelopment and as endogenous neuroprotectors, they play a pivotal role in the pathophysiology and management of memory and aging conditions. The relevance of neurosteroids to aging conditions is multifactorial and encompass changes of a variety of neurosteroid levels including DHEA, DHEA-S, pregnenolone, allopregnanolone, estradiaol and progesterone. Age-related decline in neurosteroid levels may induce a range of age-related neuronal dysfunction and degeneration due to loss of the neurosteroid protective and neurogenerative effect. Decreasing levels of neurosteroids with age may also leave the vulnerable brain unprotected against neurotoxic challenges and particularly predisposed to various age-related illnesses. These may include cardiovascular and metabolic diseases, immune disorders, malignancies, and neurological dysfunction. Since a variety of neurosteroids decrease in levels during the course of aging, it has frequently been suggested that replacement of these neurosteroids would either reduce or prevent age-related illness processes. While several studies have investigated administration of other neurosteroids, supplemental DHEA in particular has been hypothesized and observed by some to reverse many features of the aging process including memory, mood, energy levels and overall quality of life. However, the administration of DHEA to aging patients remains very controversial since many well-controlled studies remain inconclusive. A great need remains for development of improved evidence-based pharmaceutical compounds as technology improves and management of aging conditions advances with the possibility of safer more efficacious compounds based on neurosteroid activity. © 2008 Springer Netherlands.