Neuroprotection by neurotrophins and GDNF family members in the excitotoxic model of Huntington's disease
Neuroprotection by neurotrophins and GDNF family members in the excitotoxic model of Huntington's disease
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DOI：
10.1016/s0361-9230(01)00775-4
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发表时间：
2002-04-01
影响因子：
3.8
通讯作者：
Canals, JM
中科院分区：
文献类型：
--
作者：
Alberch, J;Pérez-Navarro, E;Canals, JM
亨廷顿病是一种神经退行性疾病，其特征在于处理舞蹈动作的纹状体投射神经元的选择性变性。了解这些神经元群体的特定营养需求可以实现神经保护治疗。因此，诱导内源性营养反应或外源性给予神经营养因子可能有助于预防或阻止疾病的进展。兴奋性毒性与亨廷顿病的病因有关，因为纹状体内注射谷氨酸受体激动剂可重现这种疾病的某些神经病理学特征。纹状体中谷氨酸受体的激活差异调节神经营养因子、胶质细胞系源性神经营养因子（GDNF）、neurturin及其受体在纹状体及其连接、皮质和黑质中的表达，显示出对兴奋性毒性损伤的选择性营养反应。在纹状体中移植经基因工程改造以释放神经营养因子的细胞已被用于研究神经营养因子和GDNF家族成员在亨廷顿病的兴奋毒性模型中的神经保护作用。神经营养因子（脑源性神经营养因子[BDNF]，神经营养因子-3和神经营养因子-4）保护纹状体投射神经元免受喹啉或红藻氨酸治疗。然而，GDNF家族成员表现出更特异的作用。Neurturin仅保护投射到苍白球外段的γ-氨基丁酸（GABA）/脑啡肽能神经元，而GDNF对投射到黑质腹侧部和苍白球内段的GABA/P物质阳性神经元发挥作用。总之，纹状体投射神经元的每个人口的营养需求是由于几个神经营养因子之间的复杂的相互作用，如神经营养因子和GDNF家族成员，可以修改，在不同的病理条件。此外，这些神经营养因子可能能够为基底神经节回路提供选择性保护，基底神经节回路在纹状体黑质退行性疾病如亨廷顿病或多系统萎缩中受到影响。(C)2002年爱思唯尔科技有限公司
Huntington's disease is a neurodegenerative disorder characterized by a selective degeneration of striatal projection neurons, which deal with choreic movements. Neuroprotective therapy could be achieved with the knowledge of the specific trophic requirements of these neuronal populations. Thus, the induction of endogenous trophic response or the exogenous administration of neurotrophic factors may help to prevent or stop the progression of the illness. Excitotoxicity has been implicated in the etiology of Huntington's disease, because intrastriatal injection of glutamate receptor agonists reproduces some of the neuropathological features of this disorder. Activation of glutamate receptors in the striatum differentially regulates the expression of neurotrophins, glial cell line-derived neurotrophic factor (GDNF), neurturin, and their receptors in the striatum and in its connections, cortex, and substantia nigra, showing a selective trophic response against excitotoxic insults. Transplantation of cells genetically engineered to release neurotrophic factors in the striatum has been used to study the neuroprotective effects of neurotrophin and GDNF family members in the excitotoxic model of Huntington's disease. Neurotrophins (brain-derived neurotrophic factor [BDNF], neurotrophin-3, and neurotrophin-4) protected striatal projection neurons against quinolinic or kainic acid treatment. However, GDNF family members showed a more specific action. Neurturin only protected gamma-aminobutyric acid (GABA)/enkephalinergic neurons that project to the external segment of the globus pallidus, whereas GDNF exerts its effects on GABA/substance P positive neurons, which project to the substantia nigra pars compacta and the internal segment of the globus pallidus. In conclusion, the trophic requirements of each population of striatal projection neurons are due to a complex interaction between several neurotrophic factors, such as neurotrophins and GDNF family members, which can be modified, in different pathological conditions. Moreover, these neurotrophic factors may be able to provide selective protection for basal ganglia circuits, which are affected in striatonigral degenerative disorders, such as Huntington's disease or multisystem atrophy. (C) 2002 Elsevier Science Inc.