DISTRIBUTION OF NEURONAL NICOTINIC RECEPTOR SUBUNITS IN HUMAN BRAIN

Neuronal nicotinic acetylcholine receptors (nAchRs) are multimeric proteins constituted of two different subunits, alpha and beta, with different subtypes arrangement and different pharmacological and functional properties, nAchRs mediate neurotransmission in many central and peripheral synapses and appear to be affected in human degenerative disorders. We have studied the distribution of nAchR in human brain, particularly in the hippocampus and thalamus, by binding of H-3-nicotine and H-3-cytisine and by in situ hybridization with human alpha 3 and beta 2 nAchR subunits of mRNA. An alpha 3 probe shows a strong hybridization signal in the thalamus, while a beta 2 probe has a good signal at the level of the enthorinal cortex, hippocampus and in caudate and putamen. The alpha 3 and beta 2 mRNA localization is different from that described in other species. H-3-nicotine and H-3-cytisine binding were very similar in terms of anatomical distribution and comparable to the binding described in other animal species. The binding of the two ligands was distributed over the areas labeled by the alpha 3 and beta 2 probes and did not completely overlap with either of the subunits.