Anderson K D, Panayotatos N, Corcoran T L, Lindsay R M, Wiegand S J
Regeneneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7346-51. doi: 10.1073/pnas.93.14.7346.
Huntington disease is a dominantly inherited, untreatable neurological disorder featuring a progressive loss of striatal output neurons that results in dyskinesia, cognitive decline, and, ultimately, death. Neurotrophic factors have recently been shown to be protective in several animal models of neurodegenerative disease, raising the possibility that such substances might also sustain the survival of compromised striatal output neurons. We determined whether intracerebral administration of brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3, or ciliary neurotrophic factor could protect striatal output neurons in a rodent model of Huntington disease. Whereas treatment with brain-derived neurotrophic factor, nerve growth factor, or neurotrophin-3 provided no protection of striatal output neurons from death induced by intrastriatal injection of quinolinic acid, an N-methyl-D-aspartate glutamate receptor agonist, treatment with ciliary neurotrophic factor afforded marked protection against this neurodegenerative insult.
亨廷顿舞蹈症是一种常染色体显性遗传的、无法治愈的神经紊乱疾病，其特征是纹状体输出神经元进行性丧失，最终导致运动障碍、认知衰退并致人死亡。最近研究表明，神经营养因子在几种神经退行性疾病的动物模型中具有保护作用，这增加了此类物质也可能维持受损纹状体输出神经元存活的可能性。我们研究了脑源性神经营养因子、神经生长因子、神经营养素-3或睫状神经营养因子的脑内给药是否能在亨廷顿舞蹈症的啮齿动物模型中保护纹状体输出神经元。虽然脑源性神经营养因子、神经生长因子或神经营养素-3治疗未能保护纹状体输出神经元免受纹状体内注射喹啉酸（一种N-甲基-D-天冬氨酸谷氨酸受体激动剂）诱导的死亡，但睫状神经营养因子治疗对这种神经退行性损伤提供了显著保护。
