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

Jose Rodriguez Arellano, W. Mayo, V. Lemaire, J. Malaterre, J. J. Rodriguez, M. Cayre, M. G. Stewart, M. Kharouby, G. Rougon, M. Le Moal, P. V. Piazza, D. N. Abrous

    Research output: Contribution to journalArticlepeer-review

    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 (GABAA) 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. © 2004 Elsevier Inc. All rights reserved.
    Original languageEnglish
    Pages (from-to)103-114
    Number of pages11
    JournalNeurobiology of Aging
    Volume26
    Issue number1
    DOIs
    Publication statusPublished - Jan 2005

    Keywords

    • Aging
    • Hippocampus
    • Neurogenesis
    • Neurospheres
    • Neurosteroid
    • PSA-NCAM

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