Abnormal expressions of glutamate transporters and metabotropic glutamate receptor 1 in the spontaneously epileptic rat hippocampus.
Excessive glutamatergic neurotransmission is considered an underlying factor of epilepsy. The modulation of the synaptic activity occurs both by the removal of glutamate from the synaptic cleft and by excitatory amino acid transporters (EAATs) and by modulation of glutamate receptors. The spontaneously epileptic rat (SER), a double mutant (zi/zi, tm/tm), exhibits both tonic convulsions and absence-like seizures from the age of 8 weeks. However, there are no reports that can elucidate the effects of EAATs and metabotropic glutamate receptors (mGluRs) in SER. The present study was undertaken to detect EAATs (GLAST, GLT-1 and EAAC-1) and Group I metabotropic glutamate receptors (mGluR1) in SER hippocampus from both the level of mRNA and protein in SERs hippocampus compared with control Wistar rats. In this study, the glutamate concentration in SERs hippocampus was increased compared with that of control rats by high performance liquid chromatography; the mRNA expressions of GLAST and mGluR1 in SERs hippocampus were significantly lower than those in control rats hippocampus, whereas an abundant increase in mRNA for GLT-1 was observed by RT-PCR; EAAC-1 and mGluR1 protein in SERs and control rats were localized widely in the hippocampus including CA1, CA3 and dentate gyrus regions by immunohistochemistry; the number of GLAST and mGluR1-positive cells in the hippocampus of SERs were less than those in control rats, especially for CA3 and DG region; the protein expression of GLT-1 was up-regulated, but the protein expressions of GLAST and mGluR1 were down-regulated in SER hippocampus by western blot. Our data show that epileptogenesis in SER are associated with regulations of glutamate transporters and mGluR1, which might be potential targets for therapy in genetic epilepsy.
Department of Pharmaceutical Toxicology, School of Pharmaceutical Science, China Medical University, Heping District, Shenyang 110001, China.
Feng
F
Guo
Feng
F
Sun
Jun-Ling
JL
Yu
Qing-Hua
QH
Wang
Da-Yu
DY
Tu
Xiao-Yuan
XY
Mao
Rui
R
Liu
Kun-Can
KC
Wu
Ni
N
Xie
Li-Ying
LY
Hao
Ji-Qun
JQ
Cai
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism; D056654:CA3 Region, Hippocampal / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism; D004827:Epilepsy / Q000378:metabolism*; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D050580:Excitatory Amino Acid Transporter 3 / Q000378:metabolism; D050491:Glutamate Plasma Membrane Transport Proteins / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*
D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; C493398:Slc1a1 protein, rat; C493392:Slc1a3 protein, rat; C104077:metabotropic glutamate receptor type 1; D018698:Glutamic Acid