Expression of alpha(2A) adrenoceptors during rat neocortical development

Norepinephrine has been suggested to play a neurotrophic role during develo pment and is present in the brain as early as embryonic day (E) 12. We have recently demonstrated that the alpha(2A) adrenoceptor subtype is widely ex pressed during times of neuronal migration and differentiation throughout t he developing brain. Here, we report the temporal and spatial expression pa ttern of alpha(2A) adrenoceptors in neocortex during late embryonic and ear ly postnatal development using in situ hybridization and receptor autoradio graphy. Functional a, receptors in embryonic rat cortex were also detected using agonist stimulated [S-35]GTP gamma S autoradiography, Both alpha(2A) mRNA and protein expression were strongly increased by E19 and E20, respect ively. The increased expression was in the cortical plate and intermediate and subventricular zones, corresponding to tiers of migrating and different iating neurons. This transient up-regulation of alpha(2A) adrenoceptors was restricted to the lateral neocortex. At E20, functional alpha(2) adrenocep tors were also detected in deep layers of lateral neocortex, During the fir st week of postnatal development, the expression of alpha(2A) mRNA and prot ein changed markedly, giving rise to a more mature pattern of anatomical di stribution. The temporal and spatial distribution of alpha(2A) adrenoceptor s in developing neocortex is consistent with expression of functional prote ins on migrating and differentiating layer IV to II neurons. These findings suggest that alpha(2A) receptors may mediate a neurotrophic effect of nore pinephrine during fetal cortical development. The early delineation of the lateral neocortex, which will develop into somatosensory and auditory corti ces, suggests an intrinsic regulation of alpha(2A) mRNA expression, (C) 199 9 John Wiley & Sons, Inc.