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| Content Provider | frontiers |
|---|---|
| Author | Xue, Tao Wang, Shu Chen, Shujun Wang, Huizhi Liu, Chong Shi, Lin Bai, Yutong Zhang, Chunkui Han, Chunlei Zhang, Jianguo |
| Abstract | Background: Focal motor seizures that originate in the motor region are a considerable challenge because of the high risk of permanent motor deficits after resection. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a potential treatment for motor epilepsy that may enhance the antiepileptic actions of the substantia nigra pars reticulata (SNr). Orexin and its receptors have a relationship with both STN-DBS and epilepsy. We aimed to investigate whether and how STN inputs to the SNr regulate seizures and the role of the orexin pathway in this process. Methods: A penicillin-induced motor epileptic model in adult male C57BL/6J mice was established to evaluate the efficacy of STN-DBS in modulating seizure activities. Optogenetic and chemogenetic approaches were employed to regulate STN-SNr circuits. Selective orexin receptor type 1 and 2 antagonists were used to inhibit the orexin pathway. Results: First, we found that high-frequency ipsilateral or bilateral STN-DBS was effective in reducing seizure activity in the penicillin-induced motor epilepsy model. Second, inhibition of STN excitatory neurons and STN-SNr projections alleviates seizure activities, whereas their activation amplifies seizure activities. In addition, activation of the STN-SNr circuits also reversed the protective effect of STN-DBS on motor epilepsy. Finally, we observed that STN-DBS reduced the elevated expression of orexin and its receptors in the SNr during seizures and that using a combination of selective orexin receptor antagonists also reduced seizure activity. Conclusion: STN-DBS helps reduce motor seizure activity by inhibiting the STN-SNr circuit. Additionally, orexin receptor antagonists show potential in suppressing motor seizure activity and may be a promising therapeutic option in the future. |
| ISSN | 1662453X |
| DOI | 10.3389/fnins.2023.1157060 |
| Volume Number | 17 |
| Journal | Frontiers in Neuroscience |
| Language | English |
| Publisher Date | 2023-05-05 |
| Access Restriction | Open |
| Subject Keyword | Motor seizure Subthalamic Nucleus Substantia nigra pars reticulata Deep Brain Stimulation Orexin |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neuroscience |
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