School of Psychology, Chung Shan Medical University Hospital, Chung Shan Medical University, Taiwan, ROC.
Behav Brain Res. 2011 Jun 1;219(2):280-90. doi: 10.1016/j.bbr.2011.01.028. Epub 2011 Jan 22.
Glutamatergic dysfunction has been implicated in the neurodegeneration seen in Parkinson's disease (PD). Sub-chronic intraperitoneal injection with D-cycloserine (DCS), a partial agonist at the glycine binding site of the N-methyl-D-aspartate (NMDA) receptor, at dosages of 30, 100, or 200 mg/kg/day, was used to evaluate the role of NMDA receptors in neuronal and behavioral changes in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD rat model. Starting one day after intra-nigral infusion of MPTP, transient disturbance of motor function in the rotarod test was observed. This impairment spontaneously recovered to control levels 6 days after MPTP lesioning and DCS treatment facilitated recovery. MPTP lesioning also caused deficits in working memory and anxiety-like behavior in the T-maze and elevated plus-maze tests, respectively. Further, object recognition was disrupted in MPTP-lesioned rats, and interleukin-2 levels in the striatum, amygdala, and non-prefrontal cortex were increased, both changes being restored by DCS treatment. Furthermore, MPTP lesion-induced dopaminergic degeneration, microglial activation, and cell loss in the hippocampal CA1 area were all improved by DCS treatment. These results suggest that NMDA receptors are involved in PD-related neuronal and behavioral dysfunctions and that DCS may have clinical potential in the treatment of dementia associated with PD.
谷氨酸能功能障碍与帕金森病（PD）中的神经退行性变有关。亚慢性腹腔内注射 D-环丝氨酸（DCS），一种 N-甲基-D-天冬氨酸（NMDA）受体甘氨酸结合部位的部分激动剂，剂量为 30、100 或 200mg/kg/天，用于评估 NMDA 受体在 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的 PD 大鼠模型中神经元和行为变化中的作用。从 MPTP 纹状体输注后 1 天开始，在转棒试验中观察到运动功能短暂障碍。这种损伤在 MPTP 损伤后 6 天自发恢复到对照水平，DCS 治疗促进了恢复。MPTP 损伤还导致 T 迷宫和高架十字迷宫测试中工作记忆和焦虑样行为的缺陷，分别。此外，物体识别在 MPTP 损伤的大鼠中受到破坏，纹状体、杏仁核和非前额叶皮层中的白细胞介素 2 水平升高，这些变化都通过 DCS 治疗得到恢复。此外，DCS 治疗改善了 MPTP 损伤诱导的多巴胺能变性、小胶质细胞激活和海马 CA1 区的细胞丢失。这些结果表明，NMDA 受体参与 PD 相关的神经元和行为功能障碍，DCS 可能具有治疗与 PD 相关的痴呆的临床潜力。
