REGIONAL DISTRIBUTION OF NICOTINIC RECEPTORS DURING PRENATAL DEVELOPMENT OF HUMAN BRAIN AND SPINAL-CORD

The development of nicotinic acetylcholine receptors (nAChRs) in brain s from human fetuses of 4-12 weeks,gestational age was studied. The ex pression of nAChR subunit mRNAs was analyzed using reverse transcripta se-polymerase chain reaction. Expression of alpha 3, alpha 4, alpha 5, alpha 7, beta 2, beta 3 and beta 4 mRNA were all detected in the pren atal spinal cord, medulla oblongata, pens, cerebellum: mesencephalon, subcortical forebrain and cortex during first trimester development. R elative quantification of mRNA showed that the highest levels for alph a 3, alpha 4 and alpha 7 were expressed in the spinal cord, alpha 5 wa s most abundant in the cortex and beta 3 was highest in the cerebellum . beta 4 seemed to be equally distributed in all regions whereas beta 2 was high in the cortex and cerebellum. A comparison of expression of nAChR subunit mRNAs in the cortex and cerebellum of prenatal and aged (54-81 years) brain showed that mRNA levels for alpha 4, alpha 5, alp ha 7, beta 2 and beta 4 were significantly higher in the prenatal cort ex and cerebellum than in aged brain, whereas the level of alpha 3 tra nscript was similar, and beta 3 significantly higher in aged cortex. S pecific binding of [H-3]-epibatidine to prenatal brain membranes was d etected as early as 4-5 weeks of gestation in the spinal cord, medulla oblongata, pens and subcortical forebrain. A positive correlation bet ween gestational age and [H-3]-epibatidine and [H-3]-cytisine binding was found in several brain regions. The highest specific binding of [H -3]-epibatidine and [H-3]-cytisine was detected in the spinal cord, pe ns and medulla oblongata and the lowest in the cortex. Saturation anal ysis of [H-3]-cytisine binding in both prenatal and aged brain were be st fit by a model for a single site, whereas binding data for [H-3]-ep ibatidine revealed two classes of binding sites. The early presence of nAChR proteins and gene transcripts shown in the present study sugges ts an important role for nAChRs in modulating dendritic outgrowth, est ablishment of neuronal connections and synaptogenesis during developme nt. (C) 1998 Elsevier Science B.V. All rights reserved.