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Pregnenolone sulfate enhances neurogenesis and PSA-NCAM in young and aged hippocampus

Mayoa, W.; Lemaire, V; Malaterre, J.; Rodriguez, J. J.; Cayre, M.; Stewart, M. G.; Kharouby, M.; Rougon, G.; Le Moal, M.; Piazza, P. V. and Abrous, D. N. (2005). Pregnenolone sulfate enhances neurogenesis and PSA-NCAM in young and aged hippocampus. Neurobiology of Aging, 26(1) pp. 103–114.

DOI (Digital Object Identifier) Link: http://dx.doi.org/10.1016/j.neurobiolaging.2004.03.013
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Abstract

Age-dependent cognitive impairments have been correlated with functional and structural modifications in the hippocampal formation. In particular, the brain endogenous steroid pregnenolone-sulfate (Preg-S) is a cognitive enhancer whose hippocampal levels have been linked physiologically to cognitive performance in senescent animals. However, the mechanism of its actions remains unknown. Because neurogenesis is sensitive to hormonal influences, we examined the effect of Preg-S on neurogenesis, a novel form of plasticity, in young and old rats. We demonstrate that in vivo infusion of Preg-S stimulates neurogenesis and the expression of the polysialylated forms of NCAM, PSA-NCAM, in the dentate gyrus of 3- and 20-month-old rats. These influences on hippocampal plasticity are mediated by the modulation of the gamma-aminobutyric acid receptor complex A (GABA(A)) receptors present on hippocampal neuroblasts. In vitro, Preg-S stimulates the division of adult-derived spheres suggesting a direct influence on progenitors. These data provide evidence that neurosteroids represent one of the local secreted signals controlling hippocampal neurogenesis. Thus, therapies which stimulate neurosteroidogenesis could preserve hippocampal plasticity and prevent the appearance of age-related cognitive disturbances

Item Type: Journal Article
ISSN: 0197-4580
Extra Information: Aging; Neurosteroid; Neurogenesis; PSA-NCAM; Hippocampus; Neurospheres
Academic Unit/Department: Science > Life, Health and Chemical Sciences
Interdisciplinary Research Centre: Biomedical Research Network (BRN)
Item ID: 12773
Depositing User: Astrid Peterkin
Date Deposited: 02 Jan 2009 01:46
Last Modified: 07 Mar 2014 15:05
URI: http://oro.open.ac.uk/id/eprint/12773
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