VIP and PACAP 38 modulate ibotenate-induced neuronal heterotopias in the newborn hamster neocortex.
Intracerebral administration of ibotenate produces, through activation of N-methyl-D-aspartate (NMDA) receptors, neuronal heterotopias in the newborn hamster neocortex: high doses of ibotenate induce periventricular and subcortical neuronal heterotopias, while low doses of ibotenate produce intracortical heterotopias and molecular layer ectopias. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are closely related peptides with neurotrophic properties. They share common VPAC1 and VPAC2 receptors, which use cAMP as a second messenger. Previous studies have shown that VIP prevents excitotoxic neuronal death and exacerbates glutamate-induced c-fos neuronal expression. In order to gain new insight into the molecular control of neuronal migration, the present study examined the effects of VIP and PACAP on ibotenate-induced heterotopias in the newborn hamster. Co-treatment with VIP and a high dose of ibotenate produced a pattern of neuronal heterotopias similar to the one observed in animals treated with low doses of ibotenate alone. Pups co-injected with a low dose of ibotenate and a VIP antagonist displayed cortical dysgeneses similar to those observed in animals treated with high doses of ibotenate alone. The modulating effects of VIP on excitotoxin-induced heterotopias were mimicked by forskolin, PACAP, and by a specific VPAC2 receptor agonist but not by a VPAC1 agonist, and were blocked by a protein kinase A (PKA) inhibitor. Taken together, these data suggest that VIP and PACAP can attenuate ibotenate-induced heterotopias in newborn hamster and that this effect is mediated by the VPAC2 receptor utilizing the cAMP-PKA pathway.
Gressens
P
P
INSERM E 9935, H pital Robert-Debré, Paris, France.
Arquié
C
C
Hill
J M
JM
Marret
S
S
Sahir
N
N
Robberecht
P
P
Evrard
P
P
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001665:Binding Sites; D001927:Brain Diseases / Q000473:pathology*; D002828:Choristoma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D006224:Cricetinae; D004357:Drug Synergism; D007051:Ibotenic Acid; D008647:Mesocricetus; D019579:Neocortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009417:Nerve Tissue; D009479:Neuropeptides / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism / Q000494:pharmacology*
D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D007051:Ibotenic Acid; D014660:Vasoactive Intestinal Peptide