ALTERED NGF PROTEIN-LEVELS IN DIFFERENT BRAIN-AREAS AFTER IMMUNOLESION

Nerve growth factor (NGF) provides critical trophic support to the cho linergic basal forebrain neurons that express high levels of the low-a ffinity NGF receptor (p75(NGFR)) in the adult rat brain, Intraventricu lar injection of 192 IgG-saporin, made by coupling the monoclonal anti body to p75(NGFR) 192 IgG to the cytotoxin saporin, selectively destro ys the p75(NGFR) bearing neurons in the basal forebrain and was used h ere to examine the effects of selective cholinergic lesions on brain N GF protein levels, We showed that 192 IgG-saporin produced significant long-lasting elevation of NGF protein levels in the hippocampus, cort ex, and olfactory bulb, with profound reductions of ChAT activities re presenting complete cholinergic deafferentations of these areas. NGF l evel was maintained in the basal forebrain, even though there was almo st complete loss of p75(NGFR)-immunoreactive cells and significant dec rease of ChAT activity, In addition, a mild glial response was observe d in the basal forebrain, and most of the activated astroglia expresse d NGF-like immunoreactivity there. The increases in NGF protein levels in the target areas of the basal forebrain were most likely due to lo ss of cholinergic basal forebrain neurons and retrograde transport of NGF from these areas, Glial-derived NGF is partially responsible for t he maintained level of NGF in the basal forebrain after the loss of ch olinergic neurons, The accumulation of NGF protein in the target areas may have some effects on synaptic rearrangement in denervated tissues . (C) 1996 Wiley-Liss, Inc.