Effect of agonist on gamma-aminobutyric acid B receptor subunit expression in the hippocampus of epileptic rats

摘要

BACKGROUND:An amino acid imbalance has been considered to be responsible for epilepsy pathogenesis.Gamma-aminobutyric acid-B receptor(GABA_BR) inhibits voltage-sensitive calcium ion channels and GABA or glutamic acid(Glu) neurotransmitter release,which promotes or inhibits onset and development of epilepsy. OBJECTIVE:To explore the effect of baclofen on GBR1a and GBR2 mRNA expression in the hippocampus of epileptic rats following kainic acid(KA) induction,and to study the adaptability of GABA_BR subunits. DESIGN,TIME AND SETTING:A randomized,controlled,animal experiment based on molecular biology was performed at the Laboratory Research Center of Second Hospital Affiliated to Soochow University from November 2005 to March 2006. MATERIALS:KA was provided by Sigma,USA.In situ hybridization detection kit of GBR1a and GBR2 was provided by Wuhan Boster Biological Technology,China.GABA_BR agonist(baclofen) was provided by Sigma,USA. METHODS:Forty-four epileptic rats were randomly allocated to epileptic(n=28) and drug intervention(n=16) groups.The epileptic group was further divided into post-epileptic subgroups at different time points:6,12 hours,1,3,7,15,and 30 days(n=4).The drug intervention group was further divided into intervention controls subgroups at various time points:6 hours,1 day,and 3 days (n=4).Four additional rats were considered the normal control group and not modeled,but were injected with saline in the hippocampal CA3 region. MAIN OUTCOME MEASURES:GBR1a and GBR mRNA expression was detected in the right hippocampal CA1,CA3,and dentate gyrus(DG) areas of the control,epileptic,and interference groups at various time intervals according to in situ hybridization results. RESULTS:(1) During the early stage of epilepsy(6 and 12 hours),GBR1a and GBR2 mRNA expression was decreased,and expression was less than the control group at one day after KA induction(P<0.05).mRNA expression was increased in the DG,but was greater than the control group at day 3(P<0.05).Expression in the hippocampal CA1 and CA3 regions remained low(P<0.05),but gradually recovered to control levels.(2) The time points when subunit expression was decreased were prolonged following baclofen intervention,and expression was significantly greater than the epileptic group(P<0.05). CONCLUSION:Both mRNA expressions of GABA_BR subunits were up-regulated following decreased expression in the epileptic group,suggesting that the temporal lobe exhibited endogenous antiepileptic mechanisms during the early stages of epilepsy onset.Baclofen promoted mRNA expression of GBR1a and GBR2.