Fine structure of rat septohippocampal neurons. III. Recovery of choline acetyltransferase immunoreactivity after fimbria‐fornix transection

Abstract

Most cholinergic projection neurons in the medial septal nucleus (MS) lose their capability to synthesize choline acetyltransferase (ChAT) after axotomy by bilateral fimbria-fornix transection. We have recently shown that identified septohippocampal neurons survive axotomy up to 10 weeks and display fine-structural characteristics of cells in control rats. However, the fate and functional role of these neurons remained unclear. Here we describe observations made in rats which survived axotomy for 6 months. Adult Sprague-Dawley rats were subjected to bilateral transection of the fimbria-fornix system. In some animals septohippocampal projection neurons were labeled by the retrograde fluorescent tracer Fluoro-Gold (FG) prior to axotomy. After varying survival times following fimbria-fornix transection, the animals were fixed and sections of the septal region immunostained for ChAT. Three weeks postlesion, the number of ChAT-positive cells in the MS was reduced to 19% of control, suggesting a severe neuronal loss. However, 10 weeks and 6 months after axotomy this value increased to 28% and 54%, respectively. Fine-structural analysis of ChAT-positive neurons after 6 months survival revealed all characteristics of vital cells including normal input synapses. The majority of these cells could be identified as former septohippocampal projection neurons by the presence of FG. We conclude that many neurons in the MS have the capacity to restore their transmitter synthesis in a long-lasting process following axotomy.

Amyloid beta-protein reduces acetylcholine synthesis in a cell line derived from cholinergic neurons of the basal forebrain.

“…These results suggest that the AcCho content of septal cells may be the result of a balance between trophic factors and A,B, and that a shift in this balance could either enhance or suppress the synthesis of this neurotransmitter. This idea is consistent with the observations that down-regulation of the cholinergic phenotype can occur in vivo when cholinergic neurons are deprived of their targets and/or trophic factors (45)(46)(47)(48). Thus, we propose that a therapeutic strategy for AD may include the use of compounds (e.g., retinoids) and growth factors that prevent the suppression of AcCho synthesis caused by AP3.…”

Choline acetyltransferase detection in normal and denervated electrocyte from Electrophorus electricus (L.) using a Confocal Scanning Optical Microscopy Analysis

“…Likewise, the immunohistochemistry assay here used showed that the spatial distribution of the enzyme molecules is maintained. Our results strongly suggest that many cholinergic neurons survive the injury intact but shrink as recently described by Naumann et al (1994). Studies made by Falcato-Ribeiro and Chagas Filho (1975) on denervated muscles showed modifications in the protein profiles.…”

Preservation of nucleus basalis neurons containing choline acetyltransferase and the vesicular acetylcholine transporter in the elderly with mild cognitive impairment and early Alzheimer's disease

“…Moreover, there is evidence from experimental lesions in animals and from postmortem human studies Rinne et al, 1987;Allen et al, 1988;Vogels et al, 1990) to suggest that many cholinergic neurons shrink after injury or during the pathologic process rather than degenerate. Although controversial, down-regulation of ChAT could also account for the apparent loss of neurons observed in experimental paradigms and in AD (Perry et al, 1982;Naumann et al, 1994). Taken together, these observations suggest that cholinergic basal forebrain (CBF) neurons may be viable, albeit, dysregulated in AD.…”