NGF effects on axonal growth in CNS white matter

超出所提供的空间。轴突再生现在已经被证明发生在中枢神经系统的区域，以前认为这是不可能的。这些成功再生的戏剧性例子来自于对神经突生长的促进剂和促进剂的影响的研究。神经元生长状态对再生成功的重要性已在视神经再生的研究中得到证实。总的来说，这些结果指出了通常刺激生长的因素在克服CNS白质的非允许特征中的重要性。这项工作将利用本实验室多年来发展的技术，评估NGF在刺激CNS内轴突生长中的作用。在星形胶质细胞特异性启动子（GFAP）的控制下过度表达NGF的转基因小鼠将用于CNS白色物质中轴突生长的体外和体内研究。将对这些小鼠中枢神经系统区域内交感神经轴突的生长进行体内研究，以确定NGF的异位表达对这些异常纤维生长的影响程度。此外，将进行组织切片培养研究，以确定外源性应用或转基因表达的NGF是否会改变CNS白色物质在支持轴突生长中的一般非允许性质。最后，我们将通过一系列移植和组织培养的方法研究p75（一种低亲和力的NGF受体）在中枢神经系统白色中对NGF反应性神经元轴突生长的调节作用，在转基因小鼠中，p75在NGF过表达的情况下是缺乏的。性能现场=

EXCEED THE SPACE PROVIDED. Axonal regenerationhas nowbeen demonstratedto occurin regionsof the CNS where it was formerly thoughtto be impossible. These dramaticexamplesof successfulregrowthhavecome from studiesin whichthe influenceof bothinhibitorsand promotersof neuritegrowthhave been examined. The importance of neuronalgrowthstate on regenerationsuccesshas recentlybeen demonstratedinstudiesof opticnerve regeneration. Collectively,these resultspointto the importanceof factorsthat normallystimulategrowthin overcomingthe non-permissivefeatures of CNS whitematter. The work proposedhere willtake advantage of techniquesthat have been developedinthis laboratoryover severalyears that permitassessmentof the role of NGF in stimulatingaxonalgrowthwithinthe CNS. Transgenicmice inwhich NGF is overexpressed underthe controlof an astrocyte-specificpromoter(GFAP), will be usedfor bothinvitroand invivo studies of axonalgrowth inCNS white matter. Invivostudiesof sympatheticaxonalgrowthwithinCNS regionsof such mice willbe carried outto determinethe extentto whichectopicexpressionof NGF modifiesthe growth of these aberrant fibers. In addition,tissuesectionculturestudieswillbe carriedoutto determinewhether NGF, either appliedexogenouslyor expressedtransgenically,willmodifythe generallynon-permissive natureof CNS white matterin supportingaxonalgrowth. Finally,the role of p75, the low-affinityNGF receptor,inmodifyingaxonalgrowthof NGF-responsiveneuronsinCNS white matterwillbe studiedthrough a seriesof transplantand tissuecultureapproachesusingtransgenicmiceinwhich p75 is deficientinthe presenceof NGF overexpression.The primarygoalis to studythe roleof neurotrophicfactorsin stimulating axonalregenerationwithinCNS white matter. PERFORMANCE SITE ========================================Section End===========================================