Gressens P, Hill J M, Paindaveine B, Gozes I, Fridkin M, Brenneman D E
Laboratory of Experimental Neuropathology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
J Clin Invest. 1994 Nov;94(5):2020-7. doi: 10.1172/JCI117555.
Vasoactive intestinal peptide (VIP) has potent growth-related actions that influence cell mitosis, neuronal survival, and neurodifferentiation in cell culture. VIP can also produce dramatic growth in postimplantation mouse embryos in vitro, characterized by large increases in cell number. The goal of the present study was to assess the role of VIP on early nervous system development in vivo. Pregnant mice were treated with a specific antagonist to VIP. Prenatal administration of the antagonist early in development (E9-E11) produced severe microcephaly characterized by decreased embryonic brain weight with reduced DNA and protein content. The retardation of growth was disproportionally manifested in the brain compared with the body and was prevented by co-treatment with VIP. Identical treatment with the antagonist later in gestation had no detectable effect on embryonic growth. VIP receptors, which were restricted to the central nervous system during this stage of embryonic development, were increased in the neuroepithelium of antagonist-treated embryos while the number of cells in S-phase was significantly decreased. Thus, VIP regulates brain growth in vivo and inhibition of its action provides new insight into a molecular mechanism for microcephaly.
血管活性肠肽（VIP）具有强大的与生长相关的作用，可影响细胞培养中的细胞有丝分裂、神经元存活和神经分化。VIP还能使体外植入后的小鼠胚胎显著生长，其特征是细胞数量大幅增加。本研究的目的是评估VIP在体内早期神经系统发育中的作用。对怀孕小鼠给予VIP特异性拮抗剂进行处理。在发育早期（E9 - E11）产前给予拮抗剂会导致严重的小头畸形，表现为胚胎脑重量减轻，DNA和蛋白质含量降低。与身体相比，大脑生长迟缓表现得更为明显，而与VIP共同处理可预防这种情况。在妊娠后期用拮抗剂进行相同处理对胚胎生长没有可检测到的影响。在胚胎发育的这个阶段，VIP受体局限于中枢神经系统，在接受拮抗剂处理的胚胎的神经上皮中VIP受体增加，而处于S期的细胞数量显著减少。因此，VIP在体内调节大脑生长，抑制其作用为小头畸形的分子机制提供了新的见解。
