Pregnenolone sulfate enhances neurogenesis and PSA-NCAM in young and aged hippocampus.
Neurobiology of Aging. 2005-01-01; 26(1): 103-114
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1. Neurobiol Aging. 2005 Jan;26(1):103-14.
Pregnenolone sulfate enhances neurogenesis and PSA-NCAM in young and aged
Mayo W(1), Lemaire V, Malaterre J, Rodriguez JJ, Cayre M, Stewart MG, Kharouby M,
Rougon G, Le Moal M, Piazza PV, Abrous DN.
(1)Laboratoire de Psychobiologie des Comportements Adaptatifs, INSERM U588,
Domaine de Carreire, Rue Camille Saint-Saëns, 33077 Bordeaux, France.
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.
PMID: 15585350 [Indexed for MEDLINE]