Altered expression of GABA(A) receptors (alpha 4, gamma 2 subunit), potassium chloride cotransporter 2 and astrogliosis in tremor rat hippocampus

作者：Mao, Xiaoyuan; Ma, Ping; Cao, Danfeng; Sun, Chunyan; Ji, Zhong; Min, Dongyu; Sun, Hongli; Xie, Ni; Cai, Jiqun^*; Cao, Yonggang

来源：Brain Research Bulletin, 2011, 86(5-6): 373-379.

DOI：10.1016/j.brainresbull.2011.09.002

• GABA receptor
• KCC2
• Astrocyte
• GFAP
• Tremor rat
• Epilepsy

Impaired GABAergic inhibitory neurotransmission plays an essential role in the pathogenesis of epilepsy. GABA(A) receptor (GABA(A)R), potassium chloride cotransporter 2 (KCC2) and astrocytes are of particular importance to GABAergic transmission and thus involved in the development of increased seizure susceptibility. The tremor rat (TRM: tm/tm), a genetic mutant discovered in a Kyoto-Wistar colony, can manifest both absence-like seizures and tonic convulsions without any external stimuli. So far, there are no reports that can elucidate the effects of GABA(A)R (alpha 4, gamma 2 subunit), KCC2 and astrocytes on TRMs. The present study was undertaken to detect the expressions of GABA(A)R alpha 4, GABA(A)R gamma 2 and KCC2 in TRMs hippocampus at mRNA and protein levels. In this work, mRNA and protein expressions of GABA(A)R alpha 4 were significantly elevated while GAB(A)AR gamma 2 and KCC2 were both evidently decreased in TRMs hippocampus by real-time RT-PCR and western blot, respectively. Furthermore, a dramatic elevation of KCC2 protein level was found after cerebroventricular injection with K252a to TRMs than that in the DMSO-treated TRMs. Besides, our present study also demonstrated that GFAP (a major component of astrocyte) immunoreactivity was much more intense in TRMs hippocampal CA1, CA3 and DG regions than that in control group with immnohistochemistry and confocal microscopic analyses. The protein expression of GFAP was also markedly elevated in TRMs hippocampus, suggesting that astrogliosis appeared in the TRM model. These data demonstrate that altered expressions of GABA(A)R (alpha 4, gamma 2) and KCC2 and astrogliosis observed in TRMs hippocampus may provide us good therapeutic targets for the treatment of genetic epilepsy.

• 出版日期2011-11-25
• 单位中国医科大学; 哈尔滨医科大学; 中国医学科学院北京协和医院; 中国医学科学院医学生物学研究所