The diverse role of the raphe 5-HTergic systems in epilepsy.
5-HT
SSRI
epilepsy
epilepsy-associated comorbidities
raphe nuclei
sudden unexpected death in epilepsy (SUDEP)
Journal
Acta pharmacologica Sinica
ISSN: 1745-7254
Titre abrégé: Acta Pharmacol Sin
Pays: United States
ID NLM: 100956087
Informations de publication
Date de publication:
Nov 2022
Nov 2022
Historique:
received:
15
02
2022
accepted:
05
05
2022
pubmed:
26
5
2022
medline:
3
11
2022
entrez:
25
5
2022
Statut:
ppublish
Résumé
The raphe nuclei comprise nearly all of 5-hydroxytryptaminergic (5-HTergic) neurons in the brain and are widely acknowledged to participate in the modulation of neural excitability. "Excitability-inhibition imbalance" results in a variety of brain disorders, including epilepsy. Epilepsy is a common neurological disorder characterized by hypersynchronous epileptic seizures accompanied by many psychological, social, cognitive consequences. Current antiepileptic drugs and other therapeutics are not ideal to control epilepsy and its comorbidities. Cumulative evidence suggests that the raphe nuclei and 5-HTergic system play an important role in epilepsy and epilepsy-associated comorbidities. Seizure activities propagate to the raphe nuclei and induce various alterations in different subregions of the raphe nuclei at the cellular and molecular levels. Intervention of the activity of raphe nuclei and raphe 5-HTergic system with pharmacological or genetic approaches, deep brain stimulation or optogenetics produces indeed diverse and even contradictory effects on seizure and epilepsy-associated comorbidities in different epilepsy models. Nevertheless, there are still many open questions left, especially regarding to the relationship between 5-HTergic neural circuit and epilepsy. Understanding of 5-HTergic network in a circuit- and molecule-specific way may not only be therapeutically relevant for increasing the drug specificity and precise treatment in epilepsy, but also provide critical hints for other brain disorders with abnormal neural excitability. In this review we focus on the roles of the raphe 5-HTergic system in epilepsy and epilepsy-associated comorbidities. Besides, further perspectives about the complexity and diversity of the raphe nuclei in epilepsy are also addressed.
Identifiants
pubmed: 35614227
doi: 10.1038/s41401-022-00918-2
pii: 10.1038/s41401-022-00918-2
pmc: PMC9622810
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
2777-2788Informations de copyright
© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.
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