Distribution of mRNA for the alpha4 subunit of the nicotinic acetylcholine receptor in the human fetal brain

Abstract

Neuronal nicotinic acetylcholine receptors (nAChRs) present in the central nervous system (CNS), are multimeric proteins constituted of two different subunits, alpha and beta, with different subtype arrangements and different pharmacological and functional properties. By in situ hybridization, we studied the distribution of the mRNA for the alpha4 subunit of nAChRs in brains of human 25-week old normal and fragile X fetuses. A strong hybridization signal was detected throughout the thalamus, cortex, pyramidal layer of the Ammon's horn, and the granular layer of the dentate gyrus. Several other areas including the claustrum, caudate nucleus, putamen, globus pallidus, subthalamic nucleus, subiculum, entorhinal cortex, and Purkinje cell layer displayed a low to moderate radiosignal. With few exceptions, our data in the human brain agree those previously reported in the rat. Also, our data indicate that the alpha4 subunit mRNA is produced early in the development, in the more differentiated cells, and in a site-specific manner. Additionally, the alpha4 mRNA is produced in the brain of fragile X fetuses with the same pattern and same intensity than in the normal fetal brain suggesting that alpha4 subunit mRNA production is not altered in the fragile X syndrome. High levels of alpha4 subunit mRNA in human fetal brain support the hypothesis of a morphogenic role of nAChRs during the early CNS development.