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Growth Factor Properties of VIP during Early Brain Development
Author(s) -
GRESSENS PIERRE,
PAINDAVEINE BÉNÉDICTE,
HILL JOANNA M.,
BRENNEMAN DOUGLAS E.,
EVRARD PHILIPPE
Publication year - 1997
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1997.tb46153.x
Subject(s) - library science , computer science
Vasoactive intestinal peptide (VIP), a 28 amino acid neuropeptide widely distributed in the mammalian nervous system, has potent growth-related actions that influence cell division, neuronal survival, and neurodifferentiation. To address the potential effects of VIP on embryonic growth, whole postimplantation embryo cultures were used. After a 4-hour incubation, VIP stimulated growth as assessed by the following increases from control: embryonic volume (63%), DNA (103%), and protein content (63%), as well as the number of cells in S-phase (490%). No apparent histological abnormalities are produced by VIP. To assess the in vivo function of VIP in early CNS growth, a VIP antagonist (VA) was injected i.p. between E9 and E11. VA induced a dose reduction of the DNA (84% of controls) and protein (80% of controls) contents of the E11 head and a decrease of E17 brain weight (87% of controls). In contrast, body growth was less affected by the antagonist. injections of VA for a longer period (E9 to E17) did not increase the severity of the microcephaly. By ex vivo autoradiography, GTP-sensitive VIP binding sites were detected in the germinative neuroepithelium between E9 and E11, but not between E13 and E15, during neuronal migration. These data demonstrate that VIP regulates mitogenic activity in the premigratory neuroepithelium. Although this effect is limited to a short ontogenic period, blockade of VIP by a specific antagonist induces a severe microcephaly.