Altered NGF protein levels in different brain areas after immunolesion

J. Yu, R. G. Wiley, R. J. Perez-Polo

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    Abstract

    Nerve growth factor (NGF) provides critical trophic support to the cholinergic basal forebrain neurons that express high levels of the low- affinity NGF receptor (p75(NGFR)) in the adult rat brain. Intraventricular injection of 192 IgG-saporin, made by coupling the monoclonal antibody to p75(NGFR) 192 IgG to the cytotoxin saporin, selectively destroys the p75(NGFR)bearing neurons in the basal forebrain and was used here to examine the effects of selective cholinergic lesions on brain NGF protein levels. We showed that 192 IgG-saporin produced significant long-lasting elevation of NGF protein levels in the hippocampus, cortex, and olfactory bulb, with profound reductions of ChAT activities representing complete cholinergic deafferentations of these areas. NGF level was maintained in the basal forebrain, even though there was almost complete loss of p75(NGFR)- immunoreactive cells and significant decrease of ChAT activity. In addition, a mild glial response was observed in the basal forebrain, and most of the activated astroglia expressed NGF-like immunoreactivity there. The increases in NGF protein levels in the target areas of the basal forebrain were most likely due to loss of cholinergic basal forebrain neurons and retrograde transport of NGF from these areas. Glial-derived NGF is partially responsible for the maintained level of NGF in the basal forebrain after the loss of cholinergic neurons. The accumulation of NGF protein in the target areas may have some effects on synaptic rearrangement in denervated tissues.

    Original languageEnglish (US)
    Pages (from-to)213-223
    Number of pages11
    JournalJournal of Neuroscience Research
    Volume43
    Issue number2
    DOIs
    StatePublished - Feb 15 1996

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    Keywords

    • 192 IgG-saporin
    • choline acetyltransferase
    • glial fibrillary acid protein
    • immunohistochemistry
    • p75(NGFR)

    ASJC Scopus subject areas

    • Cellular and Molecular Neuroscience

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