Effects of Estrogen Replacement Therapy on Cholinergic Basal Forebrain Neurons and Cortical Cholinergic Innervation in Young and Aged Ovariectomized Rhesus Monkeys

Katie Kompoliti, Yaping Chu, Ari Polish, Jeffrey A Roberts, Heather McKay, Elliott J. Mufson, Sue Leurgans, John Morrison, Jeffrey H. Kordower

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Estrogen modulates the function of cholinergic basal forebrain neurons in aged female rats. The present study tested the hypothesis that estrogen enhances the phenotype of cholinergic basal forebrain neurons and their cortical cholinergic innervation in young adult and aged ovariectomized rhesus monkeys. Sixteen monkeys (9 young and 7 aged) received two injections of estradiol cypionate or vehicle separated by 3 weeks. All monkeys were killed 1 day after the last injection. Quantitative immunofluorescence in the vertical limb of the diagonal band (VLDB) revealed enhanced optical density for choline acetyltransferase (ChAT) in both young and aged monkeys treated with estrogen. In contrast, optical density for low-affinity p75 neurotrophin receptor immunoreactivity in the VLDB did not change after estrogen treatment in either aged or young animals. Quantitative immunofluorescence for either ChAT or the low-affinity p75 neurotrophin receptor in the nucleus basalis Meynert failed to reveal differences between vehicle and estrogen treatment in either age group. Quantitative estimates of acetylcholinesterase (AChE) fiber density revealed that estrogen-treated aged monkeys but not their younger counterparts had decreased numbers of AChE-positive fibers in layer II of frontal, insular, and cingulate cortices. These data indicate that estrogen administered in a manner simulating natural hormonal cyclicity produces modest age-specific chemical phenotypic and regional changes in select neuronal subfields of the cholinergic basal forebrain and their cortical projection sites in nonhuman primates.

Original languageEnglish (US)
Pages (from-to)193-207
Number of pages15
JournalJournal of Comparative Neurology
Volume472
Issue number2
DOIs
StatePublished - Apr 26 2004

Keywords

  • AChE
  • ChAT-ir and p75-ir
  • Estradiol

ASJC Scopus subject areas

  • Neuroscience(all)

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