Up-regulation of GABA transporters and GABA(A) receptor α1 subunit in tremor rat hippocampus.
The loss of GABAergic neurotransmission has been closely linked with epileptogenesis. The modulation of the synaptic activity occurs both via the removal of GABA from the synaptic cleft and by GABA transporters (GATs) and by modulation of GABA receptors. The tremor rat (TRM; tm/tm) is the parent strain of the spontaneously epileptic rat (SER; zi/zi, tm/tm), which exhibits absence-like seizure after 8 weeks of age. However, there are no reports that can elucidate the effects of GATs and GABA(A) receptors (GABARs) on TRMs. The present study was conducted to detect GATs and GABAR α1 subunit in TRMs hippocampus at mRNA and protein levels. In this study, total synaptosomal GABA content was significantly decreased in TRMs hippocampus compared with control Wistar rats by high performance liquid chromatography (HPLC); mRNA and protein expressions of GAT-1, GAT-3 and GABAR α1 subunit were all significantly increased in TRMs hippocampus by real time PCR and Western blot, respectively; GAT-1 and GABAR α1 subunit proteins were localized widely in TRMs and control rats hippocampus including CA1, CA3 and dentate gyrus (DG) regions whereas only a wide distribution of GAT-3 was observed in CA1 region by immunohistochemistry. These data demonstrate that excessive expressions of GAT-1 as well as GAT-3 and GABAR α1 subunit in TRMs hippocampus may provide the potential therapeutic targets for genetic epilepsy.
Mao
Xiaoyuan
X
Department of Pharmaceutical Toxicology, School of Pharmaceutical Science, China Medical University, Shenyang 110001, China.
Guo
Feng
F
Yu
Junling
J
Min
Dongyu
D
Wang
Zhanyou
Z
Xie
Ni
N
Chen
Tianbao
T
Shaw
Chris
C
Cai
Jiqun
J
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D050485:GABA Plasma Membrane Transport Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007696:Kindling, Neurologic; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000096:biosynthesis* / Q000235:genetics; D014202:Tremor / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000927:Anticonvulsants; D050485:GABA Plasma Membrane Transport Proteins; C546240:GABRA1 protein, human; D011963:Receptors, GABA-A; C493415:Slc6a1 protein, rat; C493417:Slc6a11 protein, rat; D005680:gamma-Aminobutyric Acid