Department of Anatomy, Zhongshan School of Medicine, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
Department of Anesthesiology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong 510317, P.R. China.
Int J Mol Med. 2019 Oct;44(4):1414-1424. doi: 10.3892/ijmm.2019.4288. Epub 2019 Jul 25.
The balance between glutamate (cortex and thalamus) and dopamine (substantia nigra) inputs on striatal neurons is of vital importance. Dopamine deficiency, which breaks this balance and leads to the domination of cortical glutamatergic inputs, plays an important role in Parkinson's disease (PD). However, the exact impact on striatal neurons has not been fully clarified. Thus, the present study aimed to characterize the influence of corticostriatal glutamatergic inputs on striatal neurons after decortication due to dopamine depletion in rats. 6‑Hydroxydopamine was injected into the right medial forebrain bundle to induce dopamine depletion, and/or ibotenic acid into the primary motor cortex to induce decortication. Subsequently, the grip strength test and Morris water maze task indicated that decortication significantly shortened the hang time and the latency that had been increased in the rats subjected to dopamine depletion. Golgi staining and electron microscopy analysis showed that the total dendritic length and dendritic spine density of the striatal neurons were decreased in the dopamine‑depleted rats, whereas decortication alleviated this damage. Immunohistochemistry analysis demonstrated that decortication decreased the number of caspase‑3‑positive neurons in the dopamine‑depleted rats. Moreover, reverse transcription‑quantitative PCR and western blot analyses showed that decortication offset the upregulation of caspase‑3 at both the protein and mRNA levels in the dopamine‑depleted rats. In conclusion, the present study demonstrated that a relative excess of cortical glutamate inputs had a substantial impact on the pathological processes of striatal neuron lesions in PD.
谷氨酸（皮质和丘脑）和多巴胺（黑质）输入对纹状体神经元的平衡至关重要。多巴胺缺乏打破了这种平衡，导致皮质谷氨酸能输入占主导地位，在帕金森病（PD）中发挥重要作用。然而，其对纹状体神经元的确切影响尚未完全阐明。因此，本研究旨在描述由于大鼠多巴胺耗竭导致去皮质后皮质纹状体谷氨酸能输入对纹状体神经元的影响。将 6-羟多巴胺注入右侧中脑束以诱导多巴胺耗竭，并且/或者将异硫氰酸酯注入初级运动皮层以诱导去皮质。随后，握力测试和 Morris 水迷宫任务表明，去皮质显著缩短了多巴胺耗竭大鼠的悬挂时间和潜伏期。高尔基染色和电子显微镜分析显示，多巴胺耗竭大鼠的纹状体神经元的总树突长度和树突棘密度降低，而去皮质减轻了这种损伤。免疫组织化学分析表明，去皮质减少了多巴胺耗竭大鼠中 caspase-3 阳性神经元的数量。此外，逆转录-定量 PCR 和 Western blot 分析显示，去皮质抵消了多巴胺耗竭大鼠 caspase-3 在蛋白和 mRNA 水平的上调。总之，本研究表明皮质谷氨酸输入的相对过剩对 PD 中纹状体神经元损伤的病理过程有重大影响。
