Assessin' the Vexin' Connexin Between Severity of Epilepsy and Hippocampal Gliosis
| Autor: | Connor D. Courtney, Catherine A. Christian-Hinman |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
hippocampus
business.industry Gap junction Connexin Hippocampus temporal lobe epilepsy Hippocampal formation medicine.disease Current Literature in Basic Science gap junction Epilepsy gliosis astrocyte medicine.anatomical_structure Gliosis Medicine Neurology (clinical) medicine.symptom business Neuroscience Astrocyte |
| Zdroj: | Epilepsy Currents |
| ISSN: | 1535-7597 |
| Popis: | Constitutive Deletion of Astrocytic Connexins Aggravates Kainate-Induced Epilepsy Deshpande T, Li T, Henning L, Wu Z, Mueller JAL, Seifert G, Steinhäuser C, Bedner P. Glia. 2020. doi:10.1002/glia.23832The astroglial gap junctional network formed by connexin (Cx) channels plays a central role in regulating neuronal activity and network synchronization. However, its involvement in the development and progression of epilepsy is not yet understood. Loss of interastrocytic gap junction (GJ) coupling has been observed in the sclerotic hippocampus of patients with mesial temporal lobe epilepsy (MTLE) and in mouse models of MTLE, leading to the suggestion that it plays a causative role in the pathogenesis. To further elucidate this clinically relevant question, we investigated consequences of astrocyte disconnection on the time course and severity of kainate-induced MTLE with hippocampal sclerosis (HS) by comparing mice deficient for astrocytic Cx proteins with wild-type (WT) mice. Continuous telemetric EEG recordings and video monitoring performed over a period of 4 weeks after epilepsy induction revealed substantially higher seizure and interictal spike activity during the chronic phase in Cx deficient versus WT mice, while the severity of status epilepticus was not different. Immunohistochemical analysis showed that, despite the elevated chronic seizure activity, astrocyte disconnection did not aggravate the severity of HS. Indeed, the extent of CA1 pyramidal cell loss was similar between the experimental groupsx, while astrogliosis, granule cell dispersion, angiogenesis, and microglia activation were even reduced in Cx deficient as compared to WT mice. Interestingly, seizure-induced neurogenesis in the adult dentate gyrus was also independent of astrocytic Cxs. Together, our data indicate that constitutive loss of GJ coupling between astrocytes promotes neuronal hyperexcitability and attenuates seizure-induced histopathological outcomes. |
| Databáze: | OpenAIRE |
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