Induced Overexpression of Connexin43 in Astrocytes Attenuates the Progression of Experimental Temporal Lobe Epilepsy.

Kherbouche, Oussama; Seifert, Gerald; Steinhäuser, Christian; Henning, Lukas; Bedner, Peter; Niemann, Pia; Geisen, Caroline; Henneberger, Christian; Fleischmann, Bernd K

doi:10.1007/s11064-025-04558-w

Journal Article

DZNE-2025-01093

Induced Overexpression of Connexin43 in Astrocytes Attenuates the Progression of Experimental Temporal Lobe Epilepsy.

Kherbouche, O. ; Henning, L. ; Niemann, P. ; Geisen, C. ; Seifert, G. ; Henneberger, C.DZNE* ; Fleischmann, B. K. ; Steinhäuser, C. ; Bedner, P.

2025
Springer Science + Business Media B.V Dordrecht [u.a.]

Neurochemical research 50(5), 303 (2025) [10.1007/s11064-025-04558-w]

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Please use a persistent id in citations: doi:10.1007/s11064-025-04558-w

Abstract: Astrocytic gap junctional communication plays a critical role in regulating neuronal activity and network synchronization, yet its precise contributions to brain function and the pathogenesis of neurological disorders remains incompletely understood. To address this, we generated a transgenic mouse line with inducible, astrocyte-specific overexpression of the gap junction protein connexin43 (Cx43). In these mice, hippocampal astrocytes exhibited markedly elevated Cx43 protein levels and a ~ 20% increase in intercellular gap junction coupling. Enhanced coupling was accompanied by a reduction in astrocytic cell volume and branching, without affecting passive membrane properties or astrocyte density in the hippocampus. Cx43 overexpression had no detectable impact on adult neurogenesis in the dentate gyrus, nor did it alter hippocampal synaptic efficacy or plasticity. Notably, in a mouse model of temporal lobe epilepsy with hippocampal sclerosis, astrocytic Cx43 overexpression attenuated chronic epileptic activity and the extent of sclerosis, supporting an antiepileptic role of the astroglial network. Collectively, these findings enhance our understanding of the functional relevance of astrocytic gap junction coupling in health and disease, with potential implications for the design of new treatment strategies.

Keyword(s): Animals (MeSH) ; Astrocytes: metabolism (MeSH) ; Connexin 43: biosynthesis (MeSH) ; Connexin 43: genetics (MeSH) ; Epilepsy, Temporal Lobe: metabolism (MeSH) ; Epilepsy, Temporal Lobe: pathology (MeSH) ; Mice, Transgenic (MeSH) ; Mice (MeSH) ; Disease Progression (MeSH) ; Hippocampus: metabolism (MeSH) ; Hippocampus: pathology (MeSH) ; Mice, Inbred C57BL (MeSH) ; Gap Junctions: metabolism (MeSH) ; Male (MeSH) ; Connexin 43 ; EEG ; Electrophysiology ; Gap junction coupling ; Hippocampal sclerosis ; Temporal lobe epilepsy ; Connexin 43

Classification:

ddc:610

Contributing Institute(s):

Synaptic and Glial Plasticity (AG Henneberger)

Research Program(s):

351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2025

Database coverage:
Medline

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