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Constitutive deletion of astrocytic connexins aggravates kainate‐induced epilepsy
Author(s) -
Deshpande Tushar,
Li Tingsong,
Henning Lukas,
Wu Zhou,
Müller Julia,
Seifert Gerald,
Steinhäuser Christian,
Bedner Peter
Publication year - 2020
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23832
Subject(s) - dentate gyrus , epileptogenesis , astrogliosis , epilepsy , astrocyte , hippocampal formation , neuroscience , biology , kainate receptor , hippocampal sclerosis , status epilepticus , neurogenesis , gliosis , granule cell , microglia , hippocampus , gap junction , pathology , glutamate receptor , medicine , ampa receptor , temporal lobe , central nervous system , microbiology and biotechnology , inflammation , immunology , receptor , biochemistry , intracellular
The 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 mice (WT). 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 groups, 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.