Department of Life Sciences, National Chung Hsing University, Taiwan, ROC.
Behav Brain Res. 2010 Mar 17;208(1):38-46. doi: 10.1016/j.bbr.2009.11.006. Epub 2009 Nov 10.
Hyper-activation of glutamatergic activity and deficits in episodic memory has been observed in Parkinson's disease (PD). This study was intended to clarify the effects of D-cycloserine (DCS), a partial agonist of N-methyl-D-aspartate (NMDA) receptors, on neuroinflammation and deficits in episodic-like memory in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD animal model. Male Wistar rats were stereotaxically administered with MPTP into the substantia nigra pars compacta. Starting 1 day after the lesion, animals were treated daily with DCS (0, 5, or 10mg/kg/day; i.p.). Thirteen days after the MPTP lesion, the rats received the episodic-like memory test. Sham-operated rats exhibited episodic-like memory, recognizing objects' location and objects' temporal order. MPTP-lesioned rats exhibited deterioration in spatial memory and failed to recognize the temporal order of objects. Further, MPTP lesions resulted in dopaminergic degeneration and microglial activation in the brain, as well as cell loss in the hippocampal CA1 area. DCS treatment (10mg/kg/day) reversed the above neurodegeneration, neuroinflammation, and behavioral deficits. Taken together, these results suggest that NMDA receptors may be involved in cognitive deficits in PD and that the application of DCS in the treatment for dementia in PD is warranted.
谷氨酸能活动的过度激活和情景记忆缺陷已在帕金森病 (PD) 中观察到。本研究旨在阐明 D-环丝氨酸 (DCS)，一种 N-甲基-D-天冬氨酸 (NMDA) 受体部分激动剂，对 1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP) 诱导的 PD 动物模型中的神经炎症和情景记忆缺陷的影响。雄性 Wistar 大鼠通过立体定向将 MPTP 注入黑质致密部。在损伤后 1 天开始，动物每天接受 DCS（0、5 或 10mg/kg/天；ip）治疗。MPTP 损伤后 13 天，大鼠接受情景记忆测试。假手术大鼠表现出情景记忆，识别物体的位置和物体的时间顺序。MPTP 损伤大鼠表现出空间记忆恶化，无法识别物体的时间顺序。此外，MPTP 损伤导致大脑中多巴胺能神经元变性和小胶质细胞激活，以及海马 CA1 区的细胞丢失。DCS 治疗（10mg/kg/天）逆转了上述神经退行性变、神经炎症和行为缺陷。综上所述，这些结果表明 NMDA 受体可能参与 PD 的认知缺陷，并且在 PD 痴呆的治疗中应用 DCS 是合理的。
