Administration of the neuroactive steroid hormone estrogen has been shown to effect
cholinergic basal forebrain neuronal function. Antibodies directed against the estrogen
receptor alpha (ERalpha) revealed dark (type 1) and light (type 2) nuclear positive
neurons within the islands of Calleja, endopiriform nucleus, lateral septum, subfields
of the cholinergic basal forebrain, bed nucleus of the stria terminalis, striohypothalamic
region, medial preoptic region, periventricular, ventromedial, arcuate and tuberal
mammillary nuclei of the hypothalamus, reuniens and anterior medial thalamic nuclei,
amygdaloid complex, piriform cortex and subfornical organ. In contrast, only a few
scattered ERalpha labeled neurons were found in cortex and hippocampus. ERalpha stained
cell bodies were not seen in the striatum. Counts of ERalpha labeled neurons in intact
female rats revealed significantly more type 2 neurons within the basal forebrain
subfields. Quantitation of ERalpha immunoreactive neurons revealed a significant decrease
in the relative number of type 1 neurons within the medial septum (MS), horizontal
limb of the diagonal band (HDB) and substantia innominata/nucleus basalis (SI/NB)
following ovariectomy. Quantitation following choline acetyltransferease (ChAT) immunohistochemistry
revealed a significant decrease in the number of ChAT positive neurons within the
MS, HDB and SI/NB, but not VDB following ovariectomy. Following ovx, the percentage
of double labeled cholinergic basal forebrain neurons also declined significantly
within the MS, VDB, HDB and SI/NB. These observations suggest that estrogen effects
a subpopulation of cholinergic basal forebrain neurons and may provide insight into
the biologic actions of this steroid in Alzheimer's disease.