| Autor: |
Sen‐Miao Li, Dian‐Dian Wang, Dan‐Hua Liu, Xiao‐Yan Meng, Zhizhong Wang, Xitong Guo, Qian Liu, Pei‐Pei Liu, Shu‐Ang Li, Songwei Wang, Run‐Zhou Yang, Yuming Xu, Longde Wang, Jian‐Sheng Kang |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
MedComm, Vol 5, Iss 6, Pp n/a-n/a (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2688-2663 |
| DOI: |
10.1002/mco2.568 |
| Popis: |
Abstract Parkinson's disease (PD) is a mitochondria‐related neurodegenerative disease characterized by locomotor deficits and loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Majority of PD research primarily focused on neuronal dysfunction, while the roles of astrocytes and their mitochondria remain largely unexplored. To bridge the gap and investigate the roles of astrocytic mitochondria in PD progression, we constructed a specialized optogenetic tool, mitochondrial‐targeted anion channelrhodopsin, to manipulate mitochondrial membrane potential in astrocytes. Utilizing this tool, the depolarization of astrocytic mitochondria within the SNc in vivo led to the accumulation of γ‐aminobutyric acid (GABA) and glutamate in SNc, subsequently resulting in excitatory/inhibitory imbalance and locomotor deficits. Consequently, in vivo calcium imaging and interventions of neurotransmitter antagonists demonstrated that GABA accumulation mediated movement deficits of mice. Furthermore, 1 h/day intermittent astrocytic mitochondrial depolarization for 2 weeks triggered spontaneous locomotor dysfunction, α‐synuclein aggregation, and the loss of DA neurons, suggesting that astrocytic mitochondrial depolarization was sufficient to induce a PD‐like phenotype. In summary, our findings suggest the maintenance of proper astrocytic mitochondrial function and the reinstatement of a balanced neurotransmitter profile may provide a new angle for mitigating neuronal dysfunction during the initial phases of PD. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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