Modulation of the Expression of the GABAA Receptor β1 and β3 Subunits by Pretreatment with Quercetin in the KA Model of Epilepsy in Mice -The Effect of Quercetin on GABAA Receptor Beta Subunits-

  • Moghbelinejad, Sahar (Cellular and Molecular Research Center, Qazvin University of Medical Sciences) ;
  • Rashvand, Zahra (Cellular and Molecular Research Center, Qazvin University of Medical Sciences) ;
  • Khodabandehloo, Fatemeh (Department of Molecular Medicine, Qazvin University of Medical Sciences) ;
  • Mohammadi, Ghazaleh (Department of Molecular Medicine, Qazvin University of Medical Sciences) ;
  • Nassiri-Asl, Marjan (Cellular and Molecular Research Center, Qazvin University of Medical Sciences)
  • Received : 2016.04.07
  • Accepted : 2016.05.15
  • Published : 2016.06.30


Objectives: Quercetin is a flavonoid and an important dietary constituent of fruits and vegetables. In recent years, several pharmacological activities of quercetin, such as its neuroprotective activity and, more specifically, its anti-convulsant effects in animal models of epilepsy, have been reported. This study evaluated the role of quercetin pretreatment on gene expression of ${\gamma}$-amino butyric acid type A ($GABA_A$) receptor beta subunits in kainic acid (KA)-induced seizures in mice. Methods: The animals were divided into four groups: one saline group, one group in which seizures were induced by using KA (10 mg/kg) without quercetin pretreatment and two groups pretreated with quercetin (50 and 100 mg/kg) prior to seizures being induced by using KA. Next, the messenger ribonucleic acid (mRNA) levels of the $GABA_A$ receptor ${\beta}$ subunits in the hippocampus of each animal were assessed at 2 hours and 7 days after KA administration. Quantitative real-time polymerase chain reaction (RT-PCR) assay was used to detect mRNA content in hippocampal tissues. Results: Pretreatments with quercetin at doses of 50 and 100 mg/kg prevented significant increases in the mRNA levels of the ${\beta}_1$ and the ${\beta}_3$ subunits of the $GABA_A$ receptor at 2 hours after KA injection. Pretreatment with quercetin (100 mg/kg) significantly inhibited ${\beta}_1$ and ${\beta}_3$ gene expression in the hippocampus at 7 days after KA injection. But, this inhibitory effect of quercetin at 50 mg/kg on the mRNA levels of the ${\beta}_3$ subunit of the $GABA_A$ receptor was not observed at 7 days after KA administration. Conclusion: These results suggest that quercetin (100 mg/kg) modulates the expression of the $GABA_A$ receptor ${\beta}_1$ and ${\beta}_3$ subunits in the KA model of epilepsy, most likely to prevent compensatory responses. This may be related to the narrow therapeutic dose range for the anticonvulsant activities of quercetin.


Supported by : Qazvin University of Medical Sciences


  1. Schwarzer C, Tsunashima K, Wanzenbock C, Fuchs K, Sieghart W, Sperk G. GABA(A) receptor subunits in the rat hippocampus II: altered distribution in kainic acid-induced temporal lobe epilepsy. Neuroscience. 1997;80(4):1001-17.
  2. Sperk G, Schwarzer C, Tsunashima K, Kandlhofer S. Expression of GABA(A) receptor subunits in the hippocampus of the rat after kainic acid-induced seizures. Epilepsy Res. 1998;32(1-2):129-39.
  3. Tsunashima K, Schwarzer C, Kirchmailr E, Sieghart W, Sperk G. GABA(A) receptor subunits in the rat hippocampus III: altered messenger RNA expression in kainic acid-induced epilepsy. Neuroscience. 1997;80(4):1019-32.
  4. Sperk G. Kainic acid seizures in the rat. Prog Neurobiol. 1994;42(1):1-32.
  5. Drexel M, Kirchmair E, Sperk G. Changes in the expression of GABAA receptor subunit mRNAs in parahippocampal areas after kainic acid induced seizures. Front Neural Circuits. 2013;18:7-142.
  6. Lachance-Touchette P, Martin C, Poulin C, Gravel M, Carmant L, Cossette P. Screening of GABRB3 in French-Canadian families with idiopathic generalized epilepsy. Epilepsia. 2010;5(9):1894-7.
  7. Huang J, Zhu M, Tao Y, Wang S, Chen J, Sun W, et al. Therapeutic properties of quercetin on monosodium urate crystal-induced inflammation in rat. J Pharm Pharmacol. 2013;64(8):1119-27.
  8. Kawabata K, Mukai R, Ishisaka A. Quercetin and related polyphenols: new insights and implications for their bioactivity and bioavailability. Food Funct. 2015;6(5):1399-417.
  9. Boots AW, Drent M, de Boer VC, Bast A, Haenen GR. Quercetin reduces markers of oxidative stress and inflammation in sarcoidosis. Clin Nutr. 2011;30(4):506-12.
  10. Loke WM, Proudfoot JM, Stewart S, McKinley AJ, Needs PW, Kroon PA, et al. Metabolic transformation has a profound effect on anti-inflammatory activity of flavonoids such as quercetin: lack of association between antioxidant and lipoxygenase inhibitory activity. Biochem Pharmacol. 2008;75(5):1045-53.
  11. Yang T, Kong B, Gu JW, Kuang YQ, Cheng L, Yang WT, et al. Anti-apoptotic and anti-oxidative roles of quercetin after traumatic brain injury. Cell Mol Neurobiol. 2014;34(6):797-804.
  12. Beckmann DV, Carvalho FB, Mazzanti CM, Dos Santos RP, Andrades AO, Aiello G, et al. Neuroprotective role of quercetin in locomotor activities and cholinergic neurotransmission in rats experimentally demyelinated with ethidium bromide. Life Sci. 2014;103(2):79-87.
  13. Qu X, Qi D, Dong F, Wang B, Guo R, Luo M, et al. Quercetin improves hypoxia-ischemia induced cognitive deficits via promoting remyelination in neonatal rat. Brain Res. 2014;1553:31-40.
  14. Goutman JD, Waxemberg MD, Donate-Oliver F, Pomata PE, Calvo DJ. Flavonoid modulation of ionic currents mediated by GABA(A) and GABA(C) receptors. Eur J Pharmacol. 2003;461(2-3):79-87.
  15. Calero CI, Beltran Gonzalez AN, Gasulla J, Alvarez S, Evelson P, Calvo DJ. Quercetin antagonism of $GABAA_{{\rho}1}$ receptors is prevented by ascorbic acid through a redox-independent mechanism. Eur J Pharmacol. 2013;714(1-3):274-80.
  16. Nassiri-Asl M, Moghbelinejad S, Abbasi E, Yonesi F, Haghighi MR, Lotfizadeh M, et al. Effects of quercetin on oxidative stress and memory retrieval in kindled rats. Epilepsy Behav. 2013;28(2):151-5.
  17. Nassiri-Asl M, Hajiali F, Taghiloo M, Abbasi E, Mohseni F, Yousefi F. Comparison between the effects of quercetin on seizure threshold in acute and chronic seizure models. Toxicol Ind Health. 2016;32(5):936-44.

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