Effects of Estrogens on Choline-Acetyltransferase immunoreactivity and GAP-43 mRNA in the forebrain of young and aging male rats

FERRINI M; BISAGNO V; PIROLI G; GRILLO C; GONZALEZ DENISELLE MC; DE NICOLA AF

CELLULAR AND MOLECULAR NEUROBIOLOGY.

SPRINGER/PLENUM PUBLISHERS

Lugar: New York; Año: 2002 p. 289 - 301

0272-4340

1. Previous work demonstrated that estradiol (E2) treatment prevented the abnormalresponse to stress and the reduction of glucocorticoid receptors (GR) in hippocampus fromaging male rats. The mechanisms originating these effects were unknown.2. In the present work, we investigated the E2 effects on the cholinergic, growthassociatedprotein (GAP-43) expressing neurons of the medial septum (MS) and verticallimb of diagonal band of Broca (VDB). These areas project to the hippocampus, and maybe involved in the mentioned E2 effects in aging animals. Therefore, the response to E2 ofcholine-acetyltransferase (ChAT) in neurons and cell processes and GAP-43 mRNA as amarker of neurite outgrowth was studied in young and old male rats.3. Young (3?4 months) and old (18?20 months) male Sprague-Dawley rats remaineduntreated or were implanted s.c. with a 14 mg pellet of E2 benzoate during 6 weeks. Weused immoucytochemistry to determine ChAT and isotopic in situ hybridization to analyzeGAP-43 mRNA expression.4. Aging males showed a reduction in the number and length ofChAT-immunoreactivecell processes, but not in the number of positive neurons in MS and VDB. E2 reverted bothparameters in old rats to levels of young animals. Regarding basal levels of GAP-43mRNA,they were similar in old and young animals, but E2 treatment up-regulated GAP-43 mRNAexpression in MS and VDB of old animals only.5. Our data suggest that prolonged E2 treatment may affect hippocampal functionof aging male rats by regulating in part the plasticity of cholinergic, GAP-43 expressingneurones of the basal forebrain. Without discarding a direct E2 effect on the limbic tissue,effects on the cholinergic system may have a pronounced impact on the neuroendocrineand stress responses of the aging hippocampus