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Gonadal hormones can influence the morphology and function of glial cells, particularly astrocytes. Here we explore the hypothesis that 17beta-estradiol (E2) exerts a positive effect on astrocytes within the region of the cholinergic neurons of the basal forebrain, an area heavily implicated in memory and attentional processes. Female rats were ovariectomized at 3 months of age and lesioned with the immunotoxin 192 IgG-saporin before receiving a subcutaneous pellet containing 0.25mg of estrogen or placebo, released over 60 days. The control, non-ovariectomized group was treated identically. At the end of the treatment, we used image analysis procedures to evaluate changes in the levels of glial fibrillary acidic protein (GFAP) expression in the area of the lesion. Infusion of the immunotoxin induced a slight increase in GFAP expression in some subjects, compared to the contralateral side. However, when differences within animals where factored in, GFAP expression in ovariectomized animals treated with E2 was undistinguishable from intact controls. By contrast, in ovariectomized animals treated with placebo, GFAP expression was significantly higher. These results suggest that E2 deprivation may exacerbate the effects of an immunotoxic lesion, and, more importantly, that E2 administration may contribute to structural recovery of lesioned cholinergic neurons by blocking GFAP expression in the area. These results are particularly relevant in the context of female aging and postmenopausal dementia, and further highlight other potential levels at which to design interventions to preserve an intact cholinergic system, which may be crucial to prevent Alzheimer's disease.

Over the last decade neuroscientists have accumulated a wealth of information confirming the trophic effects of 17beta-estradiol (E2) on a variety of brain regions, such as the effects on hippocampal spine density, as well as other measures of structural reorganization. Here, we explore the hypothesis that E2 exerts a positive trophic effect on the cholinergic neurons of the basal forebrain, an area heavily implicated in memory and attentional processes. Female rats were ovariectomized at 3 months of age and lesioned with the immunotoxin 192 IgG-saporin before receiving a subcutaneous pellet containing .25 mg of estrogen or placebo, released over 60 days. The control, non-ovariectomized group was treated identically. At the end of the treatment, the brains were histologically prepared and we used image analysis procedures to evaluate changes in the dendritic arborization of surviving cholinergic neurons. As expected, infusion of the immunotoxin induced a reduction in dendritic arborization in all subjects, but was significantly different from control values only in ovariectomized rats. When differences within animals were factored in, dendritic size in ovariectomized animals treated with E2 was undistinguishable from intact controls. By contrast, in ovariectomized animals treated with placebo, dendritic length remained significantly reduced. These results suggest that E2 can not only protect but also reverse structural neurodegenerative processes in cholinergic neurons. Our data is particularly relevant in the context of female aging and postmenopausal dementia, since preserving an intact cholinergic system may be crucial to prevent at least some of the cognitive decline that occurs in Alzheimer's disease.