DISTRIBUTION OF MESSENGER-RNA FOR THE ALPHA-4 SUBUNIT OF THE NICOTINIC ACETYLCHOLINE-RECEPTOR IN THE HUMAN FETAL BRAIN

Neuronal nicotinic acetylcholine receptors (nAChRs) present in the cen tral nervous system (CNS), are multimeric proteins constituted of two different subunits, alpha and beta, with different subtype arrangement s and different pharmacological and functional properties. By in situ hybridization, we studied the distribution of the mRNA for the alpha 4 subunit of nAChRs in brains of human 25-week old normal and fragile X fetuses. A strong hybridization signal was detected throughout the th alamus, cortex, pyramidal layer of the Ammon's hem, and the granular l ayer of the dentate gyrus. Several other areas including the claustrum , caudate nucleus, putamen, globus pallidus, subthalamic nucleus, subi culum, entorhinal cortex, and Purkinje cell layer displayed a low to m oderate radiosignal. With few exceptions, our data in the human brain agree those previously reported in the rat. Also, our data indicate th at the alpha 4 subunit mRNA is produced early in the development, in t he more differentiated cells, and in a site-specific manner. Additiona lly, the alpha 4 mRNA is produced in the brain of fragile X fetuses wi th the same pattern and same intensity than in the normal fetal brain suggesting that alpha 4 subunit mRNA production is not altered in the fragile X syndrome. High levels of alpha 4 subunit mRNA in human fetal brain support the hypothesis of a morphogenic role of nAChRs during t he early CNS development. (C) 1998 Elsevier Science B.V. All rights re served.