Involvement of GluA1-AMPAR-mediated LTP in time-dependent decline of cognitive function in rats with temporal lobe epilepsy
作者机构:Department of ElectrophysiologyWuhan Children’s Hospital(Wuhan Maternal and Child Healthcare Hospital)Tongji Medical CollegeHuazhong University of Science and TechnologyNo.100 of Hong Kong RoadJiang’an District430016 WuhanChina
出 版 物:《Acta Epileptologica》 (癫痫学报(英文))
年 卷 期:2021年第3卷第1期
页 面:7-14页
主 题:Cognitive impairment Temporal lobe epilepsy Long-term potentiation Hippocampus AMPA receptor
摘 要:Background:Cognitive impairment is one of the common comorbidities in patients with temporal lobe epilepsy(TLE),but the underlying mechanisms remain largely *** studies have found significant decay of hippocampal long-term potentiation(LTP)in TLE rats with cognitive *** the activation ofα-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors(AMPARs)is responsible for LTP formation and learning and memory,we investigated whether AMPARs are involved in the LTP inhibition and the TLE-associated cognitive ***:TLE rat model was established by intraperitoneal injection of lithium chloride-pilocarpine on postnatal day 21(P21).Learning and memory performance,hippocampal expression of membrane GluA1-AMPARs,and hippocampal LTP were tested by behavioral tests,western blotting,and field potential recording,respectively,at 1,5 and 13 weeks after induction of status epilepticu(SE).Finally,the effects of(S)-AMPA,an agonist of AMPARs,on LTP and cognitive function were ***:Results of behavioral tests revealed an time-dependent decline in the learning and memory of TLE rats when compared to the age-matched controls at week 5 and 13,rather than at week 1 after the induction of *** blotting showed that the hippocampal expression of membrane GluA1 was significantly decreased in a time-dependent manner in the TLE rats when compared to the age-matched controls at weeks 5 and 13,rather than at week 1 after the induction of ***,the hippocampal LTP was inhibited in a time-dependent manner in TLE rats at weeks 5 and 13,rather than at week 1 after the induction of ***,intra-hippocampal injection of(S)-AMPA ameliorated the deficits in learning as well as spatial and emotional memory in a dosedependent manner,and partially reversed the inhibition of CA1 LTP in the TLE rats at week 13 after the induction of ***:The reduced expression of hippocampal membrane GluA1 may be involved in LTP decay in CA1 and co