Estrogen receptor immunoreactivity in the adult primate brain: Neuronal distribution and association with p75, trkA, and choline acetyltransferase

The neuroactive steroid hormone, estrogen, has been implicated in both the prevention and treatment of Alzheimer's disease. Interactions between estro gen and neurotrophic systems may partially explain the beneficial effects o f estrogen therapy. Previous studies have identified estrogen binding sites colocalized with neurotrophin-related proteins and mRNA within the rodent brain. Extending these studies to a model more relevant to human systems, w e have mapped the distribution of estrogen receptor alpha (ER-alpha)-immuno reactive neurons in adult nonhuman primate brains. In addition, we used dou ble-label immunohistochemistry to examine colocalization of ER-alpha with t he low- and high-affinity neurotrophin receptors, p75 and trkA, and with th e cholinergic marker choline acetyltransferase. Large numbers of ER-alpha-i mmunoreactive cells were detected in several amygdaloid and hypothalamic nu clei. ER-alpha-labeled cells were also found in the lateral septum, nucleus of the stria terminals, subfornical organ, and periaqueductal gray. Only r are, scattered ER-alpha-immunoreactive cells were noted in the cholinergic basal forebrain. In contrast to rodents, no cells exhibited ER-alpha and p7 5 or ER-alpha and trkA double-labeling. However, ER-labeled neurons in the amygdala, a region containing putative nerve growth factor-producing cells and exhibiting a role in memory, were densely and specifically invested wit h cholinergic terminals projecting from the basal forebrain. Estrogen-label ed neurons were also present in the lateral septal nucleus, a system that r eceives hippocampal inputs and projects to the neurotrophin-sensitive media l septum. Thus, interactions between neurotrophin-sensitive neurons and ER- bearing neurons exist in the primate brain, providing a potential paracrine basis for estrogen-state modulation of vulnerability to Alzheimer's diseas e. (C) 1999 Wiley-Liss, Inc.