Long-term administration of mouse nerve growth factor to adult rats with partial lesions of the cholinergic septohippocampal pathway.
Nerve growth factor (NGF), a neurotrophic factor acting on cholinergic neurons of the basal forebrain, has been proposed as a treatment for Alzheimer's disease. Experimental support for its pharmacological use is derived from short-term studies showing that intraventricular administration of NGF during 2-4 weeks protects cholinergic cell bodies from lesion-induced degeneration, stimulates synthesis of choline acetyltransferase, and improves various behavioral impairments. To investigate the consequences of long-term NGF administration, we tested whether cholinergic cell bodies are protected from lesion-induced degeneration and whether cholinergic axons are stimulated to regrow into the denervated hippocampus following fimbrial transections. We found that intraventricular injections of NGF twice a week for 5 months to adult rats resulted in extended protection of cholinergic cell bodies from lesion-induced degeneration and did not produce obvious detrimental effects on the animals. NGF treatment mildly stimulated growth of cholinergic neurites within the 2-mm area directly adjacent to the fimbrial lesion but it failed to induce significant homotypic growth of cholinergic neurites into the deafferented hippocampus.
Junard
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Andrus Gerontology Center, University of Southern California, Los Angeles 90089.
Montero
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Hefti
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D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D003714:Denervation; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D007276:Injections, Intraventricular; D051379:Mice; D009410:Nerve Degeneration; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009434:Neural Pathways / Q000187:drug effects / Q000473:pathology; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor; D012688:Septum Pellucidum / Q000187:drug effects / Q000473:pathology*; D013997:Time Factors
D009414:Nerve Growth Factors; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D000110:Acetylcholinesterase