Sha Rong, Wu Mingzhe, Wang Pengfei, Chen Ziyuan, Lei Wei, Wang Shimiao, Gong Shun, Liang Guobiao, Zhao Rui, Tao Yingqun
Department of Neurosurgery, General Hospital of Northern Theater Command, Postgraduate Training Base of General Hospital of Northern Theater Command of Jinzhou Medical University, Shenyang, Liaoning, China.
Department of Forensic Pathology, China Medical University School of Forensic Medicine, Shenyang, Liaoning, China.
Transl Psychiatry. 2025 Jan 25;15(1):27. doi: 10.1038/s41398-025-03232-7.
Traumatic brain injury (TBI) is identified as a risk factor for Parkinson's disease (PD), which is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN). However, the precise mechanism by which chronic TBI initiates PD pathogenesis is not yet fully understood. In our present study, we assessed the chronic progression and pathogenesis of PD-like behavior at different intervals in TBI mice. More than half of the mice exhibited PD-like behavior at 6 months post injury. PD-like behavioral dysfunction and pathological changes were aggravated with the injured time extension in chronic phase of TBI. The loss of tyrosine hydroxylase positive (TH) neurons in the SN were partly associated with the accumulation of misfolded a-Synuclein and the cytoplasmic translocation of TDP-43 from nuclear. Moreover, the present of chronic inflammation was observed in SN of TBI mice, as evidenced by the enhancement of proinflammatory cytokines and reactive astrocytes and microgliosis post lesion. The enhanced phagocytosis of reactive microglia accounted for the reduction of dendrite spines. Our results revealed that chronic inflammation associated with the damage of TH neurons and the development of progressive PD-like pathology after chronic TBI in mice. Our study shed new light on the TBI-triggered molecular events on PD-like pathology. Additional research is required to have a deeper understanding of the molecular factors underlying the impairment of dopaminergic neurons following TBI.
创伤性脑损伤（TBI）被认为是帕金森病（PD）的一个风险因素，帕金森病是一种神经退行性疾病，其特征是黑质（SN）中多巴胺能神经元的丧失。然而，慢性创伤性脑损伤引发帕金森病发病机制的确切机制尚未完全清楚。在我们目前的研究中，我们评估了创伤性脑损伤小鼠在不同时间间隔内帕金森病样行为的慢性进展和发病机制。超过一半的小鼠在受伤后6个月表现出帕金森病样行为。在创伤性脑损伤的慢性期，帕金森病样行为功能障碍和病理变化随着损伤时间的延长而加重。黑质中酪氨酸羟化酶阳性（TH）神经元的丧失部分与错误折叠的α-突触核蛋白的积累以及TDP-43从细胞核向细胞质的转位有关。此外，在创伤性脑损伤小鼠的黑质中观察到慢性炎症的存在，损伤后促炎细胞因子、反应性星形胶质细胞和小胶质细胞增生的增强证明了这一点。反应性小胶质细胞吞噬作用的增强导致树突棘减少。我们的结果表明，慢性炎症与创伤性脑损伤后小鼠中TH神经元的损伤以及进行性帕金森病样病理的发展有关。我们的研究为创伤性脑损伤引发的帕金森病样病理的分子事件提供了新的线索。需要进一步的研究来更深入地了解创伤性脑损伤后多巴胺能神经元损伤的分子因素。
