Mufson E J, Kroin J S, Sendera T J, Sobreviela T
Research Center for Brain Repair, Department of Neurological Sciences, Rush Presbyterian-Luke's Medical Center, Chicago, IL 60612, USA.
Prog Neurobiol. 1999 Feb;57(4):451-84. doi: 10.1016/s0301-0082(98)00059-8.
Neurotrophins play a crucial role in the maintenance, survival and selective vulnerability of various neuronal populations within the normal and diseased brain. Several families of growth promoting substances have been identified within the central nervous system (CNS) including the superfamily of nerve growth factor related neurotrophin factors, glial derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF). In addition, other non-neuronal growth factors such as fibroblast growth factor (FGF) have also been identified. This article reviews the trophic anatomy of these factors within the CNS. Intraventricular and intraparenchymal injections of exogenous nerve growth factor result in retrograde labeling mainly within the cholinergic basal forebrain. Distribution of brain derived neurotrophic factor (BDNF) following intraventricular injection is minimal due to the binding to the trkB receptor along the ventricular wall. In contrast, intraparenchymal injections of BDNF results in widespread retrograde transport throughout the CNS. BDNF has also been shown to be transported anterogradely within the CNS. Infusion of GDNF into the CNS results in retrograde transport limited to the nigrostriatal pathway. Hippocampal injections of NT-3 retrogradely label mainly basal forebrain neurons. Retrograde transport of radiolabeled CNTF has only been observed in sensory neurons of the sciatic nerve. Following intraventricular and intraparenchymal infusion of radiolabeled bFGF, retrograde neuronal labeling was found in the telecephalon, diencephalon, mesencephalon and pons. In contrast retrograde labeling for aFGF was found only in the hypothalamus and midbrain. Since select neurotrophins traffic anterogradely and retrogradely within the nervous system, these proteins could be used to treat neurological diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis.
神经营养因子在正常和患病大脑中各种神经元群体的维持、存活及选择性易损性方面发挥着关键作用。在中枢神经系统（CNS）中已鉴定出几类促进生长的物质，包括神经生长因子相关神经营养因子超家族、胶质细胞源性神经营养因子（GDNF）和睫状神经营养因子（CNTF）。此外，还鉴定出了其他非神经元生长因子，如成纤维细胞生长因子（FGF）。本文综述了这些因子在中枢神经系统中的营养解剖学。脑室内和脑实质内注射外源性神经生长因子主要导致胆碱能基底前脑内的逆行标记。脑室内注射脑源性神经营养因子（BDNF）后，由于其与脑室壁上的trkB受体结合，分布极少。相比之下，脑实质内注射BDNF会导致其在整个中枢神经系统中广泛逆行运输。BDNF也已被证明可在中枢神经系统中顺行运输。将GDNF注入中枢神经系统会导致逆行运输仅限于黑质纹状体通路。海马注射NT-3主要逆行标记基底前脑神经元。放射性标记的CNTF的逆行运输仅在坐骨神经的感觉神经元中观察到。在脑室内和脑实质内注入放射性标记的bFGF后，在端脑、间脑、中脑和脑桥中发现了逆行神经元标记。相比之下，aFGF的逆行标记仅在下丘脑和中脑中发现。由于特定的神经营养因子在神经系统中可顺行和逆行运输，这些蛋白质可用于治疗神经系统疾病，如阿尔茨海默病、帕金森病和肌萎缩侧索硬化症。
