NICOTINE PREVENTS GLUTAMATE-INDUCED PROTEOLYSIS OF THE MICROTUBULE-ASSOCIATED PROTEIN MAP-2 AND GLUTAMATE NEUROTOXICITY IN PRIMARY CULTURESOF CEREBELLAR NEURONS

The aim of this work was to assess whether nicotine prevents glutamate neurotoxicity in primary cultures of cerebellar neurons, to try to id entify the receptor mediating the protective effect and to shed light on the step of the neurotoxic process which is prevented by nicotine. It is shown that nicotine prevents glutamate and NMDA neurotoxicity in primary cultures of cerebellar neurons. The protective effect of nico tine is not prevented by atropine, mecamylamine or dihydro-beta-erythr oidine, bur is slightly prevented by hexamethonium and completely prev ented by tubocurarine and alpha-bungarotoxin, indicating that the prot ective effect is mediated by activation of alpha 7 neuronal nicotinic receptors. Moreover, alpha-bungarotoxin potentiates glutamate neurotox icity, suggesting a tonic prevention of glutamate neurotoxicity by bas al activation of nicotinic receptors. Nicotine did not prevent glutama te-induced rise of free intracellular calcium nor depletion of ATP. Ni cotine prevents glutamate-induced proteolysis of the microtubule-assoc iated protein MAP-2 and disaggregation of the neuronal microtubular ne twork. The possible mechanism responsible for this prevention is discu ssed. (C) 1998 Elsevier Science Ltd. All rights reserved.