Effetti in vivo e in vitro di trattamenti cronici con farmaci nicotinici

Nicotine (nic) is an alkaloid contained in tobacco leaves that selectively binds neuronal acetylcholine receptors (nAChRs), a heterogeneous class of cationic channels with high Ca2+ permeability, which can play an important role in Ca2+-dependent events such as neurotransmitter release, regulation of second messanger cascades, cell survival and apoptosis. In our laboratory it has been shown that chronic exposure of primary cortical neurons to nic and nicotinic drugs, leads to change in number, subunit composition and function of nAChR subtypes, and it also changes the levels of ionotropic and metabotropic glutamate receptors. We found that chronic nicotinic drug exposure can change the localisation of these receptors in particular cell domains (cell surface or intracellular membanes) and/or their recruitment in membrane lipid microdomains (lipid rafts). It has been previously shown that nic can be neuroprotective in various neuronal models, involving different nAChR subtype(s) and intracellular pathways. In this study we analysed in primary cortical neurons, the neuroprotective effect of nic and nicotinic antagonists on glu-induced neurotoxicity. We found that chronic treatments with nic and homomeric alpha7-specific antagonists were neuroprotective whereas dihydro-beta-erythroidine, a heteromeric receptor specific antagonist, was not. Moreover, disruption of lipid rafts leads to loss of the neuroprotective effect of nic.