Pregnenolone reverses the age-dependent accumulation of glial fibrillary acidic protein within astrocytes of specific regions of the rat brain.

Although aged-related modifications of astrocytes have been frequently described, little is known so far about the signals responsible for these modifications. Since it is well demonstrated that astrocytes are highly responsive to a variety of steroids, we hypothesized that modifications of cerebral astrocytes may result from the age-related decrease of circulating steroids. In the present study, we investigated the effects of the chronic administration of pregnenolone (PREG), the precursor of all steroid hormones, on the age-related extension of astrocytic processes in various brain regions. In adult (2-3 month-old) and aged (22-24 month-old) rats, quantitative image analysis was used to estimate, within each region, the number of astrocyte cell bodies immunostained (IS) for S100, and the surface occupied by astrocytic cell bodies and processes IS for glial fibrillary acidic protein (GFAP). In all regions, the surface occupied by GFAP-IS structures was increased in the aged vs. the adult rats, whereas no significant modifications were observed in the number of S100-IS cell bodies. Chronic administration of PREG to aged rats induced a marked decrease in the surface occupied by GFAP-IS structures in the cortex, amygdala and thalamus, without any significant effect on the number of S100-IS cell bodies present in these regions. By contrast, PREG had no significant effect when administered to adult animals. These data suggest that decreased levels of circulating steroid hormones may be responsible for the age-dependent modifications of the astrocytes present in various brain regions, and that these modifications can be at least partly corrected by the administration of PREG.