CATECHOLAMINERGIC REGULATION OF PROLIFERATION AND SURVIVAL IN RAT FOREBRAIN PARAVENTRICULAR GERMINAL CELLS

We have investigated the possible role of alpha(1)-adrenoreceptors in regulating the germination of progenitor cells cultured from embryonic rat neocortex. High binding levels of the alpha(1)-selective radiolig and (3)[H]prazosin were detected in the forebrain of the rat embryo at E13, and the greatest density of binding sites was localized to the v entricular and subventricular zones. Catecholamine-containing axon ter minals were present in these zones in the same period. Germinal neuroe pithelial cells retained specific (3)[H]prazosin binding in culture. a pproximate to 25% of cells in culture displayed complex intracellular Ca2+ transients in response to phenylephrine, many of which were aboli shed with the alpha(1B) antagonist, chloroethylclonidine. Cultures exh ibited concentration-dependent catecholamine stimulation of DNA synthe sis mediated by ct, receptors in serum-limited conditions. Neuroepithe lial cells were labelled via their ventricular processes by intraventr ivcular injection of Fast blue in E13 embryos prior to transfer of the neocortex to dissociated cell culture. Many of labelled cells were pr esent in culture in germinal foci. Some cells which migrated from thes e foci underwent apoptosis, as determined by TUNEL in situ hybridizati on. During a transitory period of up to 48 h in culture, alpha(1)-adre noreceptor activation by phenylephrine or noradrenaline increased the number of surviving cells. Apoptosis was observed in vivo in both vent ricular and subventricular zones of the neocortex from E13 to E15 in i ncreasing numbers. We propose that both the supply of noradrenaline to forebrain germinal cells, and the expression of alpha(1)-adrenorecept ors on their surface could act to determine whether they die or contin ue to proliferate.