Age-related vulnerability of developing cholinergic basal forebrain neurons following excitotoxic lesions of the hippocampus

Document Type

Article

Abstract

Previous studies have demonstrated that depleting the hippocampus of endogenous neurotrophins via excitotoxic lesions fails to alter the viability of adult cholinergic septal/diagonal band neurons. Since cholinergic basal forebrain neurons may be more vulnerable during development, we investigated whether excitotoxic lesions produced in neonatal animals alter the viability of these cells. Postnatal Day 7, 10, 14, and 28 rats pups received unilateral intrahippocampal injections of ibotenic acid and were sacrificed 4 weeks later. At 7, 10, and 14 days of age, significant reductions in the number of choline acetyltransferase (ChAT)- and p75 nerve growth factor receptor (NGFr)-immunoreactive neurons were observed within the medial septum ipsilateral to the hippocampal lesion. In contrast, rats receiving similar lesions on Day 28 failed to display a significant reduction in ChAT-immunoreactive medial septal neurons. The magnitude of ChAT-immunoreactive neuronal loss within the medial septum and the age at which the lesion was made were inversely correlated (r2 = 0.887), indicating that cholinergic septal neurons become less vulnerable to target removal as the cells develop. Similar results were observed in the vertical limb of the diagonal band although a small but significant loss of ChAT-immunoreactive neurons was seen in this structure ipsilateral to the hippocampal lesion when lesions were performed on Postnatal Day 28. At all age groups, many remaining cholinergic septal/diagonal band neurons appeared dystrophic with stunted fiber outgrowth. The present study demonstrates that unlike adult rats, removal of hippocampal target neurons during development alters the viability and morphology of cholinergic neurons of the medial septum and diagonal band. This suggests that target neurons which synthesize endogenous neurotrophins are needed for normal development of cholinergic basal forebrain neurons, but may not be required for the normal maintenance of the adult cell.

Medical Subject Headings

Aging (physiology); Animals; Animals, Newborn; Choline O-Acetyltransferase (metabolism); Female; Frontal Lobe (pathology, physiopathology); Hippocampus (drug effects, pathology, physiopathology); Ibotenic Acid (pharmacology); Male; Nerve Growth Factors (metabolism); Neurons (physiology); Neurotoxins (pharmacology); Parasympathetic Nervous System (pathology, physiopathology); Prosencephalon (pathology, physiopathology); Rats; Rats, Sprague-Dawley; Septum Pellucidum (pathology, physiopathology); Staining and Labeling

Publication Date

8-1-1994

Publication Title

Experimental neurology

ISSN

0014-4886

Volume

128

Issue

2

First Page

159

Last Page

71

PubMed ID

7521302

Digital Object Identifier (DOI)

10.1006/exnr.1994.1124

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