Blunt dopamine transmission due to decreased GDNF in the PFC evokes cognitive impairment in Parkinson's disease.
Blunt dopamine transmission due to decreased GDNF in the PFC evokes cognitive impairment in Parkinson's disease.
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DOI：
10.4103/1673-5374.355816
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发表时间：
2023-05
影响因子：
6.1
通讯作者：
Gao DS
中科院分区：
文献类型：
--
作者：
Tang CX;Chen J;Shao KQ;Liu YH;Zhou XY;Ma CC;Liu MT;Shi MY;Kambey PA;Wang W;Ayanlaja AA;Liu YF;Xu W;Chen G;Wu J;Li X;Gao DS
研究发现，胶质细胞源性神经营养因子的缺乏可能是帕金森病的主要危险因素。然而，还没有任何研究进行胶质细胞源性神经营养因子和帕金森病的认知能力之间的潜在关系。我们首先于2018年9月至2020年1月在徐州医科大学附属医院进行了一项回顾性病例对照研究，发现血清胶质细胞源性神经营养因子水平降低是帕金森病患者认知障碍的危险因素。然后，我们建立了1-甲基-4-苯基-1，2，3，6-四氢吡啶诱导的帕金森病小鼠模型，并分析了前额叶皮层胶质细胞源性神经营养因子，多巴胺传递和认知功能之间的潜在关系。我们的研究结果表明，减少胶质细胞源性神经营养因子在前额叶皮层减弱多巴胺的释放和传输，通过上调突触前膜的多巴胺转运蛋白的表达，从而导致锥体神经元的树突棘的损失和原始化和认知障碍。此外，磁共振成像数据显示，胶质细胞源性神经营养因子的长期缺乏降低了前额叶皮层与其他脑区之间的连通性，外源性胶质细胞源性神经营养因子显著改善了这种连通性。这些研究结果表明，减少胶质细胞源性神经营养因子在前额叶皮层导致神经可塑性变性的水平上的突触连接和电路，这导致认知功能障碍的帕金森病患者。
Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson’s disease. However, there have not been any studies conducted on the potential relationship between glial cell line-derived neurotrophic factor and cognitive performance in Parkinson’s disease. We first performed a retrospective case-control study at the Affiliated Hospital of Xuzhou Medical University between September 2018 and January 2020 and found that a decreased serum level of glial cell line-derived neurotrophic factor was a risk factor for cognitive disorders in patients with Parkinson’s disease. We then established a mouse model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analyzed the potential relationships among glial cell line-derived neurotrophic factor in the prefrontal cortex, dopamine transmission, and cognitive function. Our results showed that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex weakened dopamine release and transmission by upregulating the presynaptic membrane expression of the dopamine transporter, which led to the loss and primitivization of dendritic spines of pyramidal neurons and cognitive impairment. In addition, magnetic resonance imaging data showed that the long-term lack of glial cell line-derived neurotrophic factor reduced the connectivity between the prefrontal cortex and other brain regions, and exogenous glial cell line-derived neurotrophic factor significantly improved this connectivity. These findings suggested that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex leads to neuroplastic degeneration at the level of synaptic connections and circuits, which results in cognitive impairment in patients with Parkinson’s disease.
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影响因子：
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作者：
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通讯作者：
Lupica, Carl R.
影响因子：
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