Adolescent mice exposed to TBI developed PD-like pathology in middle age
Abstract 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...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-025-03232-7 |
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| author | Rong Sha Mingzhe Wu Pengfei Wang Ziyuan Chen Wei Lei Shimiao Wang Shun Gong Guobiao Liang Rui Zhao Yingqun Tao |
| author_facet | Rong Sha Mingzhe Wu Pengfei Wang Ziyuan Chen Wei Lei Shimiao Wang Shun Gong Guobiao Liang Rui Zhao Yingqun Tao |
| author_sort | Rong Sha |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-96abab58ffc747ada71143031e0b9d26 |
| institution | Kabale University |
| issn | 2158-3188 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj-art-96abab58ffc747ada71143031e0b9d262025-01-26T12:53:35ZengNature Publishing GroupTranslational Psychiatry2158-31882025-01-0115111410.1038/s41398-025-03232-7Adolescent mice exposed to TBI developed PD-like pathology in middle ageRong Sha0Mingzhe Wu1Pengfei Wang2Ziyuan Chen3Wei Lei4Shimiao Wang5Shun Gong6Guobiao Liang7Rui Zhao8Yingqun Tao9Department of Neurosurgery, General Hospital of Northern Theater Command, Postgraduate Training Base of General Hospital of Northern Theater Command of Jinzhou Medical UniversityDepartment of Forensic Pathology, China Medical University School of Forensic MedicineDepartment of Forensic Pathology, China Medical University School of Forensic MedicineKey Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical UniversityDepartment of Neurosurgery, General Hospital of Northern Theater Command, Postgraduate Training Base of General Hospital of Northern Theater Command of Jinzhou Medical UniversityDepartment of Neurosurgery, General Hospital of Northern Theater Command, Postgraduate Training Base of General Hospital of Northern Theater Command of Jinzhou Medical UniversityDepartment of Neurosurgery, General Hospital of Northern Theater Command, Postgraduate Training Base of General Hospital of Northern Theater Command of Jinzhou Medical UniversityDepartment of Neurosurgery, General Hospital of Northern Theater Command, Postgraduate Training Base of General Hospital of Northern Theater Command of Jinzhou Medical UniversityDepartment of Forensic Pathology, China Medical University School of Forensic MedicineDepartment of Neurosurgery, General Hospital of Northern Theater Command, Postgraduate Training Base of General Hospital of Northern Theater Command of Jinzhou Medical UniversityAbstract 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.https://doi.org/10.1038/s41398-025-03232-7 |
| spellingShingle | Rong Sha Mingzhe Wu Pengfei Wang Ziyuan Chen Wei Lei Shimiao Wang Shun Gong Guobiao Liang Rui Zhao Yingqun Tao Adolescent mice exposed to TBI developed PD-like pathology in middle age Translational Psychiatry |
| title | Adolescent mice exposed to TBI developed PD-like pathology in middle age |
| title_full | Adolescent mice exposed to TBI developed PD-like pathology in middle age |
| title_fullStr | Adolescent mice exposed to TBI developed PD-like pathology in middle age |
| title_full_unstemmed | Adolescent mice exposed to TBI developed PD-like pathology in middle age |
| title_short | Adolescent mice exposed to TBI developed PD-like pathology in middle age |
| title_sort | adolescent mice exposed to tbi developed pd like pathology in middle age |
| url | https://doi.org/10.1038/s41398-025-03232-7 |
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