Neuron–glia interaction in epilepsy

Bedner, Peter; Steinhäuser, Christian

doi:10.1002/jnr.23800

Cited by 5 publications

(2 citation statements)

References 14 publications

(14 reference statements)

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“…Various membrane channels and transporters are altered in the epileptic brain, and experimental evidence increasingly highlights the crucial role of glia in the context of epileptogenesis, (reviewed in Bedner & Steinhäuser, 2016). NBCe1 may act as an acid extruder, enhance depolarization‐induced alkalinisation of astrocytes, and extracellular acidification, and thereby reduce susceptibility to epileptic seizures.…”

Section: Discussionmentioning

confidence: 99%

TGF‐β signaling directly regulates transcription and functional expression of the electrogenic sodium bicarbonate cotransporter 1, NBCe1 (SLC4A4), via Smad4 in mouse astrocytes

Khakipoor

Ophoven

Schrödl-Häußel

et al. 2017

Glia

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The electrogenic sodium bicarbonate cotransporter NBCe1 (SLC4A4) expressed in astrocytes regulates intracellular and extracellular pH. Here, we introduce transforming growth factor beta (TGF‐β) as a novel regulator of NBCe1 transcription and functional expression. Using hippocampal slices and primary hippocampal and cortical astrocyte cultures, we investigated regulation of NBCe1 and elucidated the underlying signaling pathways by RT‐PCR, immunoblotting, immunofluorescence, intracellular H(+) recording using the H(+) ‐sensitive dye 2′,7′‐bis‐(carboxyethyl)‐5‐(and‐6)‐carboxyfluorescein, mink lung epithelial cell (MLEC) assay, and chromatin immunoprecipitation. Activation of TGF‐β signaling significantly upregulated transcript, protein, and surface expression of NBCe1. These effects were TGF‐β receptor‐mediated and suppressed following inhibition of JNK and Smad signaling. Moreover, 4‐aminopyridine (4AP)‐dependent NBCe1 regulation requires TGF‐β. TGF‐β increased the rate and amplitude of intracellular H+ changes upon challenging NBCe1 in wild‐type astrocytes but not in cortical astrocytes from Slc4a4‐deficient mice. A Smad4 binding sequence was identified in the NBCe1 promoter and Smad4 binding increased after activation of TGF‐β signaling. The data show for the first time that NBCe1 is a direct target of TGF‐β/Smad4 signaling. Through activation of the canonical pathway TGF‐β acts directly on NBCe1 by binding of Smad4 to the NBCe1 promoter and regulating its transcription, followed by increased protein expression and transport activity.

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Section: Discussionmentioning

confidence: 99%

TGF‐β signaling directly regulates transcription and functional expression of the electrogenic sodium bicarbonate cotransporter 1, NBCe1 (SLC4A4), via Smad4 in mouse astrocytes

Khakipoor

Ophoven

Schrödl-Häußel

et al. 2017

Glia

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“…Additionally, astrocytes could regulate epileptogenesis by being involved in BBB breakdown and neuroinflammation [208]. Brain inflammation alters gap junction coupling and K + buffering, inducing disturbances that are fundamental in TLE [209]. All the previous changes described might be behind seizure intermittence [208,210].…”

Section: Astrocytes and Neuroinflammation In Epilepsymentioning

confidence: 99%

The Endocannabinoid System in Glial Cells and Their Profitable Interactions to Treat Epilepsy: Evidence from Animal Models

Egaña-Huguet

Soria-Gómez

Grandes

2021

IJMS

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Epilepsy is one of the most common neurological conditions. Yearly, five million people are diagnosed with epileptic-related disorders. The neuroprotective and therapeutic effect of (endo)cannabinoid compounds has been extensively investigated in several models of epilepsy. Therefore, the study of specific cell-type-dependent mechanisms underlying cannabinoid effects is crucial to understanding epileptic disorders. It is estimated that about 100 billion neurons and a roughly equal number of glial cells co-exist in the human brain. The glial population is in charge of neuronal viability, and therefore, their participation in brain pathophysiology is crucial. Furthermore, glial malfunctioning occurs in a wide range of neurological disorders. However, little is known about the impact of the endocannabinoid system (ECS) regulation over glial cells, even less in pathological conditions such as epilepsy. In this review, we aim to compile the existing knowledge on the role of the ECS in different cell types, with a particular emphasis on glial cells and their impact on epilepsy. Thus, we propose that glial cells could be a novel target for cannabinoid agents for treating the etiology of epilepsy and managing seizure-like disorders.

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Role of glutamate excitotoxicity and glutamate transporter EAAT2 in epilepsy: Opportunities for novel therapeutics development

Green

Santos

Fontana

2021

Biochemical Pharmacology

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Neuron–glia interaction in epilepsy

Cited by 5 publications

References 14 publications

TGF‐β signaling directly regulates transcription and functional expression of the electrogenic sodium bicarbonate cotransporter 1, NBCe1 (SLC4A4), via Smad4 in mouse astrocytes

TGF‐β signaling directly regulates transcription and functional expression of the electrogenic sodium bicarbonate cotransporter 1, NBCe1 (SLC4A4), via Smad4 in mouse astrocytes

The Endocannabinoid System in Glial Cells and Their Profitable Interactions to Treat Epilepsy: Evidence from Animal Models

Role of glutamate excitotoxicity and glutamate transporter EAAT2 in epilepsy: Opportunities for novel therapeutics development

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