Nerve growth factor and cholinergic CNS neurons studied in organotypic brain slices. Implication in Alzheimer's disease?
Nerve growth factor (NGF) is a potent growth factor for cholinergic neurons. The aim of the present study was to investigate if NGF affects cholinergic neurons of the basal nucleus of Meynert (nBM) in organotypic brain slices. In single nBM slices cholinergic neurons rapidly degenerated when incubated without NGF. The number of remaining neurons was rescued by NGF application at any time point. When nBM slices were co-cultured with a cortex slice the number of cholinergic neurons was significantly increased pointing to a trophic influence of the cortex. Incubation with acetylcholine precursors did not affect the survival of cholinergic neurons. There was no significant difference when postnatal day 3 or day 10 nBM slices were cultured. In conclusion, NGF is the most potent growth factor for cholinergic neurons and is a promising candidate for treating Alzheimers disease, however, the delivery of NGF to the brain must the solved.
Humpel
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Laboratory of Psychiatry, Department of Psychiatry, University Hospital, Innsbruck, Austria. christian.humpel@uibk.ac.at
Weis
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D000105:Acetyl Coenzyme A / Q000494:pharmacology; D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D020532:Basal Nucleus of Meynert / Q000166:cytology*; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology*; D002794:Choline / Q000494:pharmacology; D002795:Choline O-Acetyltransferase / Q000032:analysis; D002799:Cholinergic Fibers / Q000737:chemistry* / Q000201:enzymology; D009410:Nerve Degeneration / Q000473:pathology; D020932:Nerve Growth Factor / Q000032:analysis / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology; D009924:Organ Culture Techniques; D051381:Rats
D018697:Nootropic Agents; D000105:Acetyl Coenzyme A; D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase; D002794:Choline