The effects of quercetin on the gene expression of the GABAA receptor α5 subunit gene in a mouse model of kainic acid-induced seizure

Abstract

The flavonoid quercetin has recently been reported to have neuroprotective effects, and the role of the gamma-aminobutyric acid A alpha 5 subunit (GABA α5) receptor has been determined in some nervous system disorders. The aim of this study was to identify the molecular mechanism of the effect of quercetin administered at anticonvulsive doses on the expression of the GABA α5 receptor gene in kainic acid (KA)-induced seizures in mice. The experimental animals were divided into four groups: control, KA, and KA + quercetin at 50 or 100 mg/kg, respectively. The results showed a dose-dependent reduction in the behavioral seizure score with quercetin pre-treatment in the KA mouse model. Two hours after the end of the 7-day treatment regimen, expression of the GABA α5 receptor gene in the hippocampus was found to be increased in the KA group, but this increase was reduced in the KA + quercetin 50 or 100 mg/kg treatment groups. These results suggest that expression of the GABA α5 receptor could be a mechanism for reducing seizure severity or may be a marker of seizure severity. Further studies are necessary to clarify quercetin's mechanism of action and the relation of GABA α5 receptor gene expression to seizure severity.

Dose-Dependent Behavioral and Antioxidant Effects of Quercetin and Methanolic and Acetonic Extracts fromHeterotheca inuloideson Several Rat Tissues following Kainic Acid-InducedStatus Epilepticus

“…Flavonoids have also been shown to exert anticonvulsive and antioxidant effects [41]. In a recent study, quercetin was found to decrease seizure activity in a mouse model of KA-induced seizure by modulating the gene expression of the GABA A receptor [42]. Another study also showed that flavonoids are neuroprotective agents that modulate GABA receptors in experimental models of epilepsy [43][44][45][46][47].…”

“…In recent years, several pharmacological activities of quercetin have been described, such as neuroprotective activity [54,55]. In addition, the effect of quercetin pretreatment on the gene expression of the beta subunits of γ-amino butyric acid receptor type A (GABA A ) has been studied in the context of seizures induced by KA, and the results showed that quercetin at a dose of 100 mg/kg modulated the expression of the β1 and β3 subunits of the GABA A receptor in the KA model [42]. Some studies have demonstrated new pharmacological effects of quercetin related to pain inhibition, cytokine production, and oxidative stress that lead to reductions in neuroinflammation; however, there is also evidence that quercetin metabolites reach the cerebrospinal fluid after peripheral treatment.…”

Perspective: Therapeutic Potential of Flavonoids as Alternative Medicines in Epilepsy

“…In that study, 20 mg/kg of quercetin administered 30 min before picrotoxin injection had anticonvulsant effects. Moreover, in another study with KA-induced model mice, it was shown that quercetin administration (50 and 100 mg/kg/d, intraperitoneally for 7 d) decreased seizure severity in a dose-dependent manner; in addition, it reduced the expression levels of the GABA A α 5 mRNA (111). Other studies have also reported an increase in GABA A α 5 expression in KA and pilocarpine models (112–114), suggesting that compensatory mechanisms are involved in disease pathogenesis (114).…”

Potential Therapeutic Targets of Quercetin and Its Derivatives: Its Role in the Therapy of Cognitive Impairment

“…Treatment with QC (50 mg and 100 mg/kg) reduced the KA-induced increase of GABAA α5 expression. According to these results, the expression of the GABAAα5 receptor could be a potential target of QC to reduce or to serve as a marker of seizure severity [86].…”