TRPV1 translocated to astrocytic membrane to promote migration and inflammatory infiltration thus promotes epilepsy after hypoxic ischemia in immature brain
| Autor: | Meng-Liu Zeng, Jing-Jing Cheng, Guang-Tong Jiang, Xin Wang, Xiaohua He, Xing-Liang Yang, Shuo Kong, Wanhong Liu, Biwen Peng, Lin Shao, Tao-Xiang Chen, Wei-Lin Kong |
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| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_specialty
Immunology Central nervous system TRPV Cation Channels Inflammation Brain damage lcsh:RC346-429 Proinflammatory cytokine Mice Cellular and Molecular Neuroscience Epilepsy Cell Movement Internal medicine Animals Medicine lcsh:Neurology. Diseases of the nervous system Mice Knockout Neurons Glial fibrillary acidic protein biology business.industry Research General Neuroscience Brain medicine.disease TRPV1 Endocrinology medicine.anatomical_structure nervous system Neurology Astrocytes Hypoxia-Ischemia Brain Knockout mouse biology.protein Cytokines Tumor necrosis factor alpha medicine.symptom business HIBD |
| Zdroj: | Journal of Neuroinflammation Journal of Neuroinflammation, Vol 16, Iss 1, Pp 1-14 (2019) |
| ISSN: | 1742-2094 |
| Popis: | Background Neonatal hypoxic-ischemic brain damage (HIBD), a leading cause of neonatal mortality, has intractable sequela such as epilepsy that seriously affected the life quality of HIBD survivors. We have previously shown that ion channel dysfunction in the central nervous system played an important role in the process of HIBD-induced epilepsy. Therefore, we continued to validate the underlying mechanisms of TRPV1 as a potential target for epilepsy. Methods Neonatal hypoxic ischemia and oxygen-glucose deprivation (OGD) were used to simulate HIBD in vivo and in vitro. Primarily cultured astrocytes were used to assess the expression of TRPV1, glial fibrillary acidic protein (GFAP), cytoskeletal rearrangement, and inflammatory cytokines by using Western blot, q-PCR, and immunofluorescence. Furthermore, brain electrical activity in freely moving mice was recorded by electroencephalography (EEG). TRPV1 current and neuronal excitability were detected by whole-cell patch clamp. Results Astrocytic TRPV1 translocated to the membrane after OGD. Mechanistically, astrocytic TRPV1 activation increased the inflow of Ca2+, which promoted G-actin polymerized to F-actin, thus promoted astrocyte migration after OGD. Moreover, astrocytic TRPV1 deficiency decreased the production and release of pro-inflammatory cytokines (TNF, IL-6, IL-1β, and iNOS) after OGD. It could also dramatically attenuate neuronal excitability after OGD and brain electrical activity in HIBD mice. Behavioral testing for seizures after HIBD revealed that TRPV1 knockout mice demonstrated prolonged onset latency, shortened duration, and decreased seizure severity when compared with wild-type mice. Conclusions Collectively, TRPV1 promoted astrocyte migration thus helped the infiltration of pro-inflammatory cytokines (TNF, IL-1β, IL-6, and iNOS) from astrocytes into the vicinity of neurons to promote epilepsy. Our study provides a strong rationale for astrocytic TRPV1 to be a therapeutic target for anti-epileptogenesis after HIBD. |
| Databáze: | OpenAIRE |
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