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Role of Impaired Astrocyte Gap Junction Coupling in Epilepto-Genesis
Version 1
: Received: 27 January 2023 / Approved: 30 January 2023 / Online: 30 January 2023 (02:07:39 CET)
A peer-reviewed article of this Preprint also exists.
Bedner, P.; Steinhäuser, C. Role of Impaired Astrocyte Gap Junction Coupling in Epileptogenesis. Cells 2023, 12, 1669. Bedner, P.; Steinhäuser, C. Role of Impaired Astrocyte Gap Junction Coupling in Epileptogenesis. Cells 2023, 12, 1669.
Abstract
The gap junction-coupled astroglial network plays a central role in the regulation of neuronal activity and synchronization, but its involvement in the pathogenesis of neuronal diseases is not yet understood. Here we present the current state of knowledge about the impact of impaired glial coupling in the development and progression of epilepsy and discuss whether astrocytes represent alternative therapeutic targets. We focus mainly on temporal lobe epilepsy (TLE), which is the most common form of epilepsy in adults, characterized by high therapy resistance. Functional data from TLE patients and corresponding experimental models point to a complete loss of astrocytic coupling, but preservation of the gap junction forming proteins connexin43 (Cx43) and connexin30 (Cx30) in hippocampal sclerosis. Several studies further indicate that astrocyte uncoupling represents a causal event in the initiation of TLE, as it occurs very early in epileptogenesis, clearly preceding dysfunctional changes in neurons. However, more research is needed to fully understand the role of gap junction channels in epilepsy and to develop safe and effective therapeutic strategies targeting astrocytes.
Keywords
astrocyte; gap junction coupling; connexin 43; connexin 30; hippocampus, epilepsy; ep-ileptogenesis; temporal lobe epilepsy
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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