INVOLVEMENT OF PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE-II VASOACTIVE-INTESTINAL-PEPTIDE 2 RECEPTOR IN MOUSE NEOCORTICAL ASTROCYTOGENESIS

At the end of neuronal migration, the neopallial germinative zone prod uces glial cells destined to colonize the upper layers of neocortex. H igh densities of binding sites for vasoactive intestinal peptide (VIP) have been found in the rodent germinative zone just after completion of neuronal migration, suggesting a possible role of VIP in neocortica l astrocytogenesis. In the present study, administration of a VIP anta gonist at embryonic days 17 and 18 to pregnant mice was followed by a dramatic depletion of astrocytes in the upper cortical layer of the of fspring. The depletion of astrocytes was dose-dependent, with a 42% re duction in the density of astrocytes observed with 50 mu g of antagoni st. The antagonist effect was reversed by cotreatment with VIP or pitu itary adenylate cyclase-activating polypeptide (PACAP), suggesting the involvement of a receptor common to these two neuropeptides. VIP anta gonist-induced inhibition of astrocytogenesis was also blocked by Po 2 5-1553, a long-acting cyclic VIP analogue selective for the PACAP II V IP2 receptor subclass. Our results demonstrate that VIP and/or PACAP p lay a crucial physiological role in neocortical astrocytogenesis, poss ibly through interaction with PACAP II VIP2 receptors.