5-HT/GABA interaction in epilepsy

Deidda, Gabriele; Crunelli, Vincenzo; Giovanni, Giuseppe Di

doi:10.1016/bs.pbr.2021.01.008

Cited by 11 publications

(14 citation statements)

References 158 publications

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“…Current research highlights the potential of modulating serotonergic transmission and targeting distinct serotonin (5‐HT) receptors in the treatment of epilepsy 20,30 . Consistently, 5‐HT is involved in different types of epilepsy, both in a preclinical and clinical setting 31 .…”

Section: Resultsmentioning

confidence: 99%

“…The following subtype receptors increase AC: 5‐HT 4 , 5‐HT 6 , and 5‐HT 7 , and thus causing excitation as well 36 . There is evidence that targeting different 5‐HT receptors and/or affecting 5‐HT metabolism and transport could be efficacious in the treatment of epilepsy and its comorbidities (eg, depression) 20,21,31,33,37,38 . In 2014, Gharedaghi and colleagues showed that stimulating 5‐HT 1 , 5‐HT 2 , or 5‐HT 3 receptor subtypes produce anticonvulsive effects.…”

Section: Resultsmentioning

confidence: 99%

“…Hence, it is not surprising that defects in serotonergic transmission have been related to numerous neurological diseases, such as epilepsy and depression. 20,[33][34][35] 5-HT-related research has exploded since the discovery in 1940-1950 resulting in successful approaches to characterize the different 5-HT receptor subtypes. Already by 1980; 5-HT 1-like , 5-HT 2 , and 5-HT 3 were characterized.…”

Section: -Ht Receptors and Epilepsymentioning

confidence: 99%

“…With this in mind, other studies have underlined that serotonergic receptors seem to be an interesting target for future ASMs 2,18,19 . In addition, ample preclinical and clinical evidence is available to suggest the importance of serotonergic neurotransmission in epilepsy, depression, headache, and sudden unexplained death in epilepsy patients (SUDEP) 18,20,–29 . Most compelling evidence of the 14 different serotonin receptors and its role in epilepsy have been reviewed by Gharedaghi and colleagues in 2014 18 …”

Section: Introductionmentioning

confidence: 99%

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Serotonin receptors in epilepsy: Novel treatment targets?

Sourbron

Lagae

2022

Epilepsia Open

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Despite the availability of over 30 antiseizure medications (ASMs), there is no “one size fits it all,” so there is a continuing search for novel ASMs. There are divergent data demonstrating that modulation of distinct serotonin (5‐hydroxytryptamine, 5‐HT) receptors subtypes could be beneficial in the treatment of epilepsy and its comorbidities, whereas only a few ASM, such as fenfluramine (FA), act via 5‐HT. There are 14 different 5‐HT receptor subtypes, and most epilepsy studies focus on one or a few of these subtypes, using different animal models and different ligands. We reviewed the available evidence of each 5‐HT receptor subtype using MEDLINE up to July 2021. Our search included medical subject heading (MeSH) and free terms of each “5‐HT subtype” separately and its relation to “epilepsy or seizures.” Most research underlines the antiseizure activity of 5‐HT1A,1D,2A,2C,3 agonism and 5‐HT6 antagonism. Consistently, FA, which has recently been approved for the treatment of seizures in Dravet syndrome, is an agonist of 5‐HT1D,2A,2C receptors. Even though each study focused on a distinct seizure/epilepsy type and generalization of different findings could lead to false interpretations, we believe that the available preclinical and clinical studies emphasize the role of serotonergic modulation, especially stimulation, as a promising avenue in epilepsy treatment.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: -Ht Receptors and Epilepsymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Serotonin receptors in epilepsy: Novel treatment targets?

Sourbron

Lagae

2022

Epilepsia Open

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“…Since GABAergic interneurons show severe impairments in DS pathophysiology [281,282], the modulation of GABAergic neurotransmission could play a role in DS treatment. Of importance, 5-HT 2A R agonism seems to facilitate GABAergic neurotransmission, which could explain the efficacy of 5-HT 2A R agonism for DS treatment [283] and other forms of epilepsy [284][285][286].…”

Section: Trazodone Tcb-2 and Lisuridementioning

confidence: 99%

Use of Zebrafish Models to Boost Research in Rare Genetic Diseases

Crouzier

Richard

Sourbron

et al. 2021

IJMS

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Rare genetic diseases are a group of pathologies with often unmet clinical needs. Even if rare by a single genetic disease (from 1/2000 to 1/more than 1,000,000), the total number of patients concerned account for approximatively 400 million peoples worldwide. Finding treatments remains challenging due to the complexity of these diseases, the small number of patients and the challenge in conducting clinical trials. Therefore, innovative preclinical research strategies are required. The zebrafish has emerged as a powerful animal model for investigating rare diseases. Zebrafish combines conserved vertebrate characteristics with high rate of breeding, limited housing requirements and low costs. More than 84% of human genes responsible for diseases present an orthologue, suggesting that the majority of genetic diseases could be modelized in zebrafish. In this review, we emphasize the unique advantages of zebrafish models over other in vivo models, particularly underlining the high throughput phenotypic capacity for therapeutic screening. We briefly introduce how the generation of zebrafish transgenic lines by gene-modulating technologies can be used to model rare genetic diseases. Then, we describe how zebrafish could be phenotyped using state-of-the-art technologies. Two prototypic examples of rare diseases illustrate how zebrafish models could play a critical role in deciphering the underlying mechanisms of rare genetic diseases and their use to identify innovative therapeutic solutions.

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