Quisqualic acid-induced lesion of the nucleus basalis of Meynert in young and aging rats: plasticity of surviving NGF receptor-positive cholinergic neurons.
Previous studies have demonstrated that cholinergic neurons in the adult rat forebrain, i.e., septal region, are able to respond and regenerate after damage followed by exogenous treatment with beta-nerve growth factor. Furthermore, it has been shown that an age-related loss of NGF-receptor (NGFr) immunoreactivity occurs in cholinergic septal neurons. Since the regenerative capacity of cholinergic neurons is of importance for potential therapeutic strategies during the course of age-related neurodegenerative diseases, we have compared NGFr positive neurons in young adult (3 months old) and in aging (18-24 months old) rats in their ability to produce a physiological plasticity response after surviving an excitotoxic lesion of the nucleus basalis of Meynert (NBM). In aging control rats, NGFr immunoreactivity within NBM neurons was significantly reduced, in analogy to data obtained earlier from studies about septal neurons in aged rats. After lesion with quisqualic acid, a severe cell loss as well as atrophy of remaining cholinergic neurons was observed in both groups. Investigation of the NBM at various times after the lesion demonstrated signs of axonal or dendritic sprouting and local regeneration, with a maximum seen 3 months after the lesion. No age-related differences in the response could be found. However, despite local fiber growth, no reinnervation of the frontal and parietal cortex could be noted, as demonstrated by acetylcholinesterase histochemistry. Our findings suggest that, despite a relatively early onset of NGFr decline during lifetime, cholinergic cells keep the capacity for a plastic response, although they ultimately fail to reinnervate the neocortex.(ABSTRACT TRUNCATED AT 250 WORDS)
Unger
J W
JW
Department of Anatomy, University of Munich, Germany.
Schmidt
Y
Y
D000110:Acetylcholinesterase / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D002470:Cell Survival; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D008297:Male; D009416:Nerve Regeneration; D009473:Neuronal Plasticity / Q000502:physiology*; D016548:Prosencephalon / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D016318:Quisqualic Acid; D051381:Rats; D017207:Rats, Sprague-Dawley; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D013377:Substantia Innominata / Q000378:metabolism / Q000473:pathology / Q000502:physiology*
D017475:Receptors, Nerve Growth Factor; D016318:Quisqualic Acid; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase