Pharmacological characterization of nerve growth factor and/or monosialoganglioside GM1 effects on cholinergic markers in the adult lesioned brain.
The regulation of cholinergic markers by exogenous nerve growth factor (NGF) and/or monosialoganglioside GM1 (GM1) treatment was examined in various brain areas of unilaterally decorticated rats, with particular emphasis on the basal forebrain system. Treatment of decorticated rats, i.c.v. via a minipump, with various doses of NGF or GM1 for a period of 7 days prevented the lesion-induced decline in nucleus basalis magnocellularis choline acetyltransferase (ChAT) activity in a dose-dependent manner. These treatments also stimulated cortical ChAT activity as well as high-affinity choline uptake. Cholinergic markers in other brain areas studied were unaffected by the lesion or these treatments, except in the striatum in which exogenous NGF but not GM1 caused dose-dependent increases in ChAT activity and high-affinity choline uptake. Glutamic acid decarboxylase activity was unaffected by the lesion or treatments in all brain areas studied. Cotreatment of lesioned rats with GM1 did not affect NGF potency but did increase its maximal efficacy in the nucleus basalis magnocellularis and cortex, but not in the striatum. Treatment of cortically lesioned rats with maximal doses of GM1 and/or NGF did not differentially alter "soluble" or "membrane bound" forms of ChAT. In addition, choline uptake kinetic parameters also were affected similarly by these agents as evidenced by augmented Vmax and unaltered Km values. Distinct effects of NGF and GM1 were observed, however, in regard to the delay possible in treatment time onset. No significant alteration in NGF receptor density or affinity were noted in the remaining cortex of GM1-treated decorticated rats, suggesting that GM1 interacts with an alternative facet of NGF signal transduction to potentiate NGF effects on cholinergic markers.
Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada.
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Cuello
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002794:Choline / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D005732:Gangliosides / Q000494:pharmacology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017475:Receptors, Nerve Growth Factor / Q000187:drug effects
D005732:Gangliosides; D009414:Nerve Growth Factors; D017475:Receptors, Nerve Growth Factor; C025447:sialogangliosides; D005677:G(M1) Ganglioside; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; D002794:Choline