Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (5): 1107-1117.doi: 10.4103/1673-5374.355816

Previous Articles     Next Articles

Blunt dopamine transmission due to decreased GDNF in the PFC evokes cognitive impairment in Parkinson’s disease

Chuan-Xi Tang1, #, Jing Chen2, #, Kai-Quan Shao1, Ye-Hao Liu1, Xiao-Yu Zhou1, 3, Cheng-Cheng Ma1, Meng-Ting Liu4, Ming-Yu Shi1, 5, Piniel Alphayo Kambey1, Wei Wang6, Abiola Abdulrahman Ayanlaja1, Yi-Fang Liu1, Wei Xu1, Gang Chen5, Jiao Wu1, Xue Li7, Dian-Shuai Gao1, *#br#   

  1. 1Department of Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu Province, China;  2Experinental Teaching Center of Morphology, Xuzhou Medical University, Xuzhou, Jiangsu Province, China;  3Department of Neurology, Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, Jiangsu Province, China; 4Department of Rehabilitation, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China;  5Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China;  6Department of Medicine, Jiangnan University, Wuxi, Jiangsu Province, China;  7Department of Nursing Care, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China
  • Online:2023-05-15 Published:2022-11-01
  • Contact: Dian-Shuai Gao, PhD, gds@xzhmu.edu.cn.
  • Supported by:
    The study was supported by the National Natural Science Foundation of China, Nos. 81971006 (to DSG), 82101263 (to CXT); Jiangsu Province Science Foundation for Youths, No. BK20210903 (to CXT); Research Foundation for Talented Scholars of Xuzhou Medical University, No. RC20552114 (to CXT); Science & Technology Program of Xuzhou, No. KC19016 (to JC); and Project of Xuzhou Medical University, No. 2018KJ06 (to JC).

PDF

82

Abstract: 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.

Key words: cognitive impairment, degree centrality, dendritic spine, dopamine transmission, dopamine transporter, glial cell line-derived neurotrophic factor, Parkinson’s disease, prefrontal cortex, synaptic plasticity