Nerve growth factor infusion in the primate brain reduces lesion- induced cholinergic neuronal degeneration

NGF is a protein that promotes survival, differentiation, and process extension of selected neuronal populations during development and, in some cases, in the mature organism. Previous lesion and aging studies in the rat have shown that intracerebroventricular NGF infusions can prevent degenerative...

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Bibliographic Details
Published in:The Journal of neuroscience 1990-11, Vol.10 (11), p.3604-3614
Main Authors: Tuszynski, MH, U, HS, Amaral, DG, Gage, FH
Format: Article
Language:English
Subjects:
Acetylcholinesterase - analysis
Anatomy
Animals
Biological and medical sciences
Brain - drug effects
Brain - physiology
Central nervous system
Choline O-Acetyltransferase - analysis
Fundamental and applied biological sciences. Psychology
Hippocampus - enzymology
Hippocampus - physiology
Macaca fascicularis
Nerve Degeneration - drug effects
Nerve Growth Factors - pharmacology
Neurons - enzymology
Neurons - physiology
Vertebrates: nervous system and sense organs
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Summary:NGF is a protein that promotes survival, differentiation, and process extension of selected neuronal populations during development and, in some cases, in the mature organism. Previous lesion and aging studies in the rat have shown that intracerebroventricular NGF infusions can prevent degenerative changes in basal forebrain cholinergic neurons. We sought to determine whether salutory effects of NGF occur in the primate brain. Cholinergic fibers of the septohippocampal projection in the primate were surgically transected, followed by infusion of either a vehicle or an NGF solution into the ventricular system for a 4-week period. Quantification of cholinergic neurons in the medial septal nucleus at the end of the infusion period demonstrated that only 45 +/- 5% of cholinergic neurons could be identified after fornix lesions in vehicle-infused animals, whereas 80 +/- 6% of neurons were visible in NGF-treated animals. Thus, NGF substantially reduced lesion-induced cholinergic neuronal degeneration in the adult primate brain. This finding may be relevant to the hypothesis that NGF has potential use as a cholinergic "neurotrophic-factor therapy," given that loss of basal forebrain cholinergic neurons is common in Alzheimer's disease.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.10-11-03604.1990