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Journal of Neuroscience, Vol 7, 244-251, Copyright © 1987 by Society for Neuroscience

ARTICLE

Increased beta-nerve growth factor messenger RNA and protein levels in neonatal rat hippocampus following specific cholinergic lesions

SR Whittemore, L Larkfors, T Ebendal, VR Holets, A Ericsson and H Persson

High levels of NGF have recently been detected in cerebral cortex and hippocampus, and it was suggested that NGF supports cholinergic, basal forebrain neurons. The present study directly examined whether NGF levels are altered in the neonatal hippocampus following cholinergic denervation by transection of the fimbria. Ten days after transection, hippocampal cholinergic innervation, as assessed by AChE histochemistry and CAT immunohistochemistry, was decreased, and both hippocampal NGF mRNA and protein were elevated about 50%. This indicates possible lesion-induced transcriptional control of neonatal hippocampal NGF levels. This increase was specific to lesions of cholinergic systems, as entorhinal cortex ablation, which removes other afferent fibers to the hippocampus, did not cause a similar increase. At 30 d after fimbria transection, hippocampal NGF mRNA and protein did not differ from control levels, but the decrease in AChE and CAT staining persisted. Peripheral sympathectomy carried out in the adult rat resulted in 2- to 5-fold increases in NGF protein levels in heart atrium and ventricle, as well as submandibular gland, with no concomitant increase in NGF mRNA. Therefore, the control of NGF levels in the adult PNS is probably posttranscriptional. Our results strongly suggest that NGF is involved in the regulation of central cholinergic neurons and is transiently elevated in the neonatal hippocampus following cholinergic lesion.

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