Picketts David J
Molecular Medicine Program, Ottawa Health Research Institute, and Department of Medicine, and Centre for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, Canada.
J Clin Invest. 2006 Jul;116(7):1828-32. doi: 10.1172/JCI29148.
Congenital hydrocephalus affects 0.1-0.3% of live births, with a high mortality rate (approximately 50%) in the absence of surgical intervention. Although the insertion of shunts alleviates the symptoms of the majority of congenital cases, the molecular basis of hydrocephalus and the mechanisms of cerebrospinal fluid (CSF) circulation remain largely unknown. Two important players are the subcommissural organ/Reissner's fiber (SCO/RF) complex and the ventricular ependymal (vel) cells that together facilitate the flow of the CSF through the narrow canals of the ventricular system. In this issue of the JCI, Lang et al. demonstrate that overexpression of the pituitary adenylate cyclase-activating polypeptide (PACAP) type I (PAC1) receptor gene results in abnormal development of the SCO and vel cells, leading to congenital hydrocephalus (see the related article beginning on page 1924). The ligand for the PAC1 receptor is the neuropeptide PACAP, which uncovers what the authors believe to be a novel role for this signaling cascade in the regulation of CSF circulation.
先天性脑积水影响0.1% - 0.3%的活产婴儿，在没有手术干预的情况下死亡率很高（约50%）。虽然分流管的植入缓解了大多数先天性病例的症状，但脑积水的分子基础和脑脊液（CSF）循环机制在很大程度上仍不清楚。两个重要的参与者是联合下器官/赖斯纳纤维（SCO/RF）复合体和脑室室管膜（vel）细胞，它们共同促进脑脊液通过脑室系统的狭窄管道流动。在本期《临床研究杂志》中，朗等人证明，垂体腺苷酸环化酶激活多肽（PACAP）I型（PAC1）受体基因的过表达导致SCO和vel细胞发育异常，从而导致先天性脑积水（见第1924页开始的相关文章）。PAC1受体的配体是神经肽PACAP，这揭示了作者认为该信号级联在脑脊液循环调节中的新作用。
