Abstract
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.