Involvement of pituitary adenylate cyclase-activating polypeptide II vasoactive intestinal peptide 2 receptor in mouse neocortical astrocytogenesis

J Neurochem. 1998 May;70(5):2165-73. doi: 10.1046/j.1471-4159.1998.70052165.x.


At the end of neuronal migration, the neopallial germinative zone produces glial cells destined to colonize the upper layers of neocortex. High 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 neocortical astrocytogenesis. In the present study, administration of a VIP antagonist at embryonic days 17 and 18 to pregnant mice was followed by a dramatic depletion of astrocytes in the upper cortical layer of the offspring. The depletion of astrocytes was dose-dependent, with a 42% reduction in the density of astrocytes observed with 50 microg of antagonist. The antagonist effect was reversed by cotreatment with VIP or pituitary adenylate cyclase-activating polypeptide (PACAP), suggesting the involvement of a receptor common to these two neuropeptides. VIP antagonist-induced inhibition of astrocytogenesis was also blocked by Ro 25-1553, a long-acting cyclic VIP analogue selective for the PACAP II VIP2 receptor subclass. Our results demonstrate that VIP and/or PACAP play a crucial physiological role in neocortical astrocytogenesis, possibly through interaction with PACAP II VIP2 receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology*
  • Astrocytes / drug effects
  • Cell Count / drug effects
  • Cell Division / physiology
  • Cerebral Cortex / cytology*
  • Cerebral Cortex / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Mice
  • Neuropeptides / pharmacology
  • Neuropeptides / physiology*
  • Neurotensin / pharmacology
  • Peptide Fragments / pharmacology
  • Peptides, Cyclic / pharmacology
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Receptors, Vasoactive Intestinal Peptide / physiology*
  • Recombinant Fusion Proteins / pharmacology
  • Vasoactive Intestinal Peptide / analogs & derivatives
  • Vasoactive Intestinal Peptide / antagonists & inhibitors
  • Vasoactive Intestinal Peptide / pharmacology


  • Adcyap1 protein, mouse
  • Neuropeptides
  • Peptide Fragments
  • Peptides, Cyclic
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Vasoactive Intestinal Peptide
  • Recombinant Fusion Proteins
  • Ro 25-1553
  • pituitary adenylate cyclase-activating-peptide (1-38), pig
  • (VIP-neurotensin) hybrid antagonist
  • Vasoactive Intestinal Peptide
  • Neurotensin