文献库 文献相关信息
- 题目:
- Increased GABA(B) receptor-mediated signaling reduces the susceptibility of fragile X knockout mice to audiogenic seizures.
- 作者:
- Pacey(Laura K K),Heximer(Scott P),Hampson(David R)
- 状态:
- 发布时间2009-06-25 , 更新时间 2013-11-21
- 期刊:
- Mol Pharmacol
- 摘要:
- Mice lacking the gene encoding fragile X mental retardation protein (FMR1) are susceptible to audiogenic seizures, and antagonists of the group I metabotropic glutamate receptors (mGluRs) have been shown to block seizures in FMR1 knockout mice. We investigated whether the G-protein-inhibitory activity of the regulator of G-protein signaling protein, RGS4, could also alter the susceptibility to audiogenic seizures in FMR1 mice. We were surprised to find that male FMR1/RGS4 double-knockout mice showed reduced susceptibility to audiogenic seizures compared with age-matched FMR1 mice. These data raised the intriguing possibility that loss of RGS4 increased signaling through another G-protein pathway that reduces seizure susceptibility in FMR1 mice. Indeed, administration of the GABA(B) receptor agonist baclofen to FMR1 mice inhibited seizures, whereas the GABA(B) receptor antagonist (3-aminopropyl)(cyclohexylmethyl)phosphinic acid (CGP 46381) increased seizure incidence in double-knockout mice but not in wild-type mice. Finally, audiogenic seizures could be induced in wild-type mice by coadministering CGP 46381 and the mGluR5-positive allosteric modulator 3-cyano-N-(1,2 diphenyl-1H-pyrazol-5-yl) benzamide. These data show for the first time that GABA(B) receptor-mediated signaling antagonizes the seizure-promoting effects of the mGluRs in FMR1 knockout mice and point to the potential therapeutic benefit of GABA(B) agonists for the treatment of fragile X syndrome.
- 语言:
- eng
- DOI:
- 10.1124/mol.109.056127
DataTable pData
微信公众号
关注微信订阅号，实时查看信息，关注医学生物学动态。
版权所有 © 2025.Genelibs 济南弘晖生物技术有限公司 鲁ICP备13024435号-2
