Department of Neurology, Chang-Hua Christian Hospital, Taiwan, ROC.
Pharmacol Biochem Behav. 2010 Apr;95(2):158-65. doi: 10.1016/j.pbb.2009.12.020. Epub 2010 Jan 11.
Emotional changes, impairment of object recognition, and neuroinflammation are seen in Parkinson's disease with dementia (PDD). Here, we show that bilateral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the rat substantia nigra pars compacta (SNc) of Wistar rats caused degeneration of nigrostriatal dopaminergic neurons, microglial activation in the SNc and hippocampus, and cell loss in the hippocampal CA1 area. With regard to behavior, an increase in anxiety-like behavior and impairment of object recognition were observed during the fourth week after MPTP lesioning. The behavioral changes were not caused by motor impairment, since the rats had already recovered from MPTP-induced catalepsy before the tests were performed. These findings show that MPTP-induced neuroinflammation and its consequences, for example, microglial activation and cell loss in the hippocampus, may be involved in dopaminergic degeneration-related behavioral deficits and suggest that, in addition to the dopaminergic system, the limbic system may also participate in the pathophysiology of PDD. MPTP-lesioned rats are therefore proposed as a useful tool for assessing the ability of pharmacological agents to prevent recognition deficits in PDD.
帕金森病伴痴呆（PDD）患者会出现情绪变化、认知障碍和神经炎症。在这里，我们发现将 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）双侧注入 Wistar 大鼠的黑质致密部（SNc）会导致黑质纹状体多巴胺能神经元变性、SNc 和海马中的小胶质细胞活化以及海马 CA1 区的细胞丢失。就行为而言，在 MPTP 损伤后第四周观察到焦虑样行为增加和物体识别受损。这些行为变化不是由运动障碍引起的，因为在进行测试之前，大鼠已经从 MPTP 引起的僵住中恢复过来。这些发现表明，MPTP 诱导的神经炎症及其后果，例如海马中的小胶质细胞活化和细胞丢失，可能与多巴胺能退行性变相关的行为缺陷有关，并表明除了多巴胺能系统之外，边缘系统也可能参与 PDD 的病理生理学。因此，MPTP 损伤大鼠被提议作为评估药物预防 PDD 认知障碍能力的有用工具。
