DeGiorgio L A, DeGiorgio N, Volpe B T
Department of Neurology and Neuroscience, Cornell University Medical College at the Burke Medical Research Institute, White Plains, NY 10605, USA.
Neuroscience. 1999 Apr;90(1):79-85. doi: 10.1016/s0306-4522(98)00428-x.
Unilateral neurotoxin lesion of rat caudate-putamen and globus pallidus resulted in delayed, transneuronal degeneration of GABAergic substantia nigra pars reticulata neurons. To explore whether the disinhibition of endogenous glutamate excitatory input played a role in the degeneration of substantia nigra pars reticulata neurons, animals with unilateral striatal-pallidal lesions received three daily intraperitoneal injections of either dizocilpine maleate (MK-801, 1 or 10 mg/kg), an N-methyl-D-aspartate glutamate receptor blocker, or 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX, 30 mg/kg), an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor blocker, that began 24 h after the striatal-pallidal neurotoxin lesion. Drug treatment affected neither the volume of the initial lesion nor the volume of striatal-pallidal glial fibrillary acidic protein immunoreactivity. Neuron number in the substantia nigra pars reticulata ipsilateral to the lesioned striatopallidum was reduced on average by 37% in untreated control rats, in low dose MK-801, and NBQX-treated rats (P<0.0001). However, in animals treated with high doses of MK-801 there was no difference in the number of neurons in the substantia nigra pars reticulata ipsilateral or contralateral to the neurotoxin lesion. These data demonstrate that dose-related treatment with N-methyl-D-aspartate glutamate receptor blockers protects substantia nigra pars reticulata neurons, and suggests that glutamatergic mechanisms play a role in delayed transneuronal degeneration.
大鼠尾状核 - 壳核和苍白球的单侧神经毒素损伤导致黑质网状部GABA能神经元出现延迟性跨神经元变性。为探究内源性谷氨酸兴奋性输入的去抑制是否在黑质网状部神经元变性中起作用，患有单侧纹状体 - 苍白球损伤的动物在纹状体 - 苍白球神经毒素损伤后24小时开始，每天腹腔注射三次马来酸二氮卓（MK - 801，1或10 mg/kg），一种N - 甲基 - D - 天冬氨酸谷氨酸受体阻滞剂，或2,3 - 二羟基 - 6 - 硝基 - 7 - 氨磺酰基 - 苯并（f）喹喔啉（NBQX，30 mg/kg），一种α - 氨基 - 3 - 羟基 - 5 - 甲基 - 4 - 异恶唑丙酸受体阻滞剂。药物治疗既不影响初始损伤的体积，也不影响纹状体 - 苍白球胶质纤维酸性蛋白免疫反应性的体积。在未治疗的对照大鼠、低剂量MK - 801和NBQX治疗的大鼠中，与损伤的纹状体 - 苍白球同侧的黑质网状部神经元数量平均减少了37%（P<0.0001）。然而，在高剂量MK - 801治疗的动物中，神经毒素损伤同侧或对侧的黑质网状部神经元数量没有差异。这些数据表明，用N - 甲基 - D - 天冬氨酸谷氨酸受体阻滞剂进行剂量相关治疗可保护黑质网状部神经元，并表明谷氨酸能机制在延迟性跨神经元变性中起作用。
