Comparison of the regional expression of nicotinic acetylcholine receptor alpha 7 mRNA and [I-125]alpha-bungarotoxin binding in human postmortem brain

Neuronal nicotinic acetylcholine receptors are expressed in the human central nervous system. A specific subtype of this receptor family, the alpha 7 nicotinic acetylcholine receptor, is thought to be the principal alpha-bungarotoxin (alpha BTX)-binding protein in mammalian brain. Although the expression of this receptor subtype has been characterized in rat, no study has specifically compared the expression of both the alpha 7 gene and the localization of BTX binding sites in human brain. Expression of alpha 7 mRNA and receptor protein in human postmortem brain tissue was examined by in situ hybridization and [I-125]-alpha-bungarotoxin autoradiography, respectively, with particular emphasis on regions associated with sensory processing. Regions with high levels of both alpha 7 gene expression and [I-125]-alpha BTX binding include the nucleus reticularis of the thalamus, the lateral and medial geniculate bodies, the basilar pontine nucleus, the horizontal limb of the diagonal band of Broca, the nucleus basalis of Meynert, and the inferior olivary nucleus. High-to-moderate levels of alpha 7 probe hybridization were also seen in the hippocampus and the cerebral cortex; however, there was a reduced or variable degree of [I-125]-alpha BTX binding in these regions compared with the level of probe hybridization. In most brain regions, [I-125]-alpha BTX binding was localized to neuronal cell bodies similar in morphology to those that exhibited alpha 7 hybridization, suggesting that the high-affinity [I-125]-alpha BTX binding sites in the human brain are likely to be principally composed of alpha 7 receptor subtypes. (C) 1997 Wiley-Liss, Inc.