Hill J M, Agoston D V, Gressens P, McCune S K
Section on Developmental and Molecular Pharmacology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
J Comp Neurol. 1994 Apr 8;342(2):186-205. doi: 10.1002/cne.903420204.
The peptide neurotransmitter vasoactive intestinal peptide (VIP) has neurotrophic properties and influences neurobehavioral development. To assess the role of VIP during neural ontogeny, the present work traces the development of VIP mRNA with in situ hybridization and VIP receptors with in vitro autoradiography in rat central nervous system (CNS) from embryonic day 14 (E14) to the adult. VIP mRNA was not evident in the CNS until birth. Postnatally, it was expressed in several distinct brain regions, but its distribution bore little relation to that of VIP receptors. VIP receptors were present and expressed changing patterns of distribution throughout CNS development. The changing patterns were the result of 1) the transient appearance of GTP-insensitive VIP receptors in several regions undergoing mitosis or glial fasciculation and 2) the transient appearance of GTP-sensitive VIP receptors homogeneously distributed throughout the CNS during the first 2 postnatal weeks, the period of the brain growth spurt. At E14-16 VIP binding was dense throughout the brainstem and spinal cord, but limited in the rest of the brain. From E19 to postnatal day 14 (P14), while VIP binding was higher in germinal zones, it tended to be uniformly dense throughout the remainder of the brain. By P21 the adult pattern began to emerge; VIP binding was unevenly distributed and was related to specific cytoarchitectural sites. Since the expression of VIP in the CNS is limited to postnatal development but VIP receptors are abundant prenatally, we suggest that extraembryonic VIP may act upon prenatal VIP receptors to regulate ontogenic events in the brain.
肽类神经递质血管活性肠肽（VIP）具有神经营养特性，并影响神经行为发育。为了评估VIP在神经个体发育过程中的作用，本研究采用原位杂交技术追踪大鼠中枢神经系统（CNS）中从胚胎第14天（E14）到成年期VIP mRNA的发育情况，并用体外放射自显影技术追踪VIP受体的发育情况。VIP mRNA在出生前的CNS中并不明显。出生后，它在几个不同的脑区表达，但其分布与VIP受体的分布关系不大。VIP受体在整个CNS发育过程中都存在，并表现出不断变化的分布模式。这些变化的模式是由以下原因导致的：1）在几个正在进行有丝分裂或神经胶质束形成的区域中短暂出现对GTP不敏感的VIP受体；2）在出生后的前两周，即脑生长突增期，在整个CNS中均匀分布的对GTP敏感的VIP受体短暂出现。在E14 - 16时，VIP结合在整个脑干和脊髓中密集，但在大脑的其他部位有限。从E19到出生后第14天（P14），虽然VIP结合在生发区较高，但在大脑的其余部分趋于均匀密集。到P21时，成年模式开始出现；VIP结合分布不均，且与特定的细胞构筑部位有关。由于VIP在CNS中的表达仅限于出生后的发育阶段，但VIP受体在出生前就大量存在，我们认为胚胎外的VIP可能作用于出生前的VIP受体，以调节大脑中的个体发育事件。
