Song Guobin, Xi Guoping, Li Yanhua, Zhao Yijin, Qi Caixia, Song Lijuan, Xiao Baoguo, Ma Cungen
Institute of Brain Science, Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Shanxi Datong University, Datong, 037009, China.
Research Center of Neurobiology, The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Shanxi University of Chinese Medicine, Jinzhong, 030619, China.
Neurosci Lett. 2020 Apr 17;724:134869. doi: 10.1016/j.neulet.2020.134869. Epub 2020 Feb 27.
Animal models of Parkinson's disease (PD), a chronic and progressive neurodegenerative disease of the central nervous system (CNS), play a key role in investigating the pathogenesis and developing new therapeutic strategies of PD. However, this goal has been limited by certain weaknesses in the available animal models of PD, e.g., induction by either pro-inflammatory or neurotoxic reagents, or they are too time-/effort-consuming. Here, we report a double triggers, nasal induction of a PD mouse model that mimics the clinical, pathological features and pathogenesis of PD by intranasal (i.n.) administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) combined with lipopolysaccharide (LPS). After administration once every three days for 7 consecutive weeks, these mice displayed enhanced motor dysfunction, loss of dopaminergic neurons, α-synuclein accumulation, as well as activation of microglia and astrocytes in the substantia nigra pars compacta compared with mice that were administered MPTP or LPS alone. This study provides a novel and basic research tool for investigating the pathogenesis and therapeutic intervention of PD.
帕金森病（PD）是一种慢性进行性中枢神经系统（CNS）神经退行性疾病，其动物模型在研究PD的发病机制和开发新的治疗策略中发挥着关键作用。然而，这一目标受到现有PD动物模型某些弱点的限制，例如由促炎或神经毒性试剂诱导，或者它们太耗时/费力。在此，我们报告一种双触发、经鼻腔诱导的PD小鼠模型，该模型通过经鼻（i.n.）给予1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）与脂多糖（LPS）联合使用，模拟了PD的临床、病理特征和发病机制。连续7周每3天给药一次后，与单独给予MPTP或LPS的小鼠相比，这些小鼠表现出增强的运动功能障碍、多巴胺能神经元丧失、α-突触核蛋白积累，以及黑质致密部小胶质细胞和星形胶质细胞的激活。本研究为研究PD的发病机制和治疗干预提供了一种新颖的基础研究工具。
