| 1 | Involvement of GluA1-AMPAR-mediated LTP in time-dependent decline of cognitive function in rats with temporal lobe epilepsy显示文摘Background:Cognitive impairment is one of the common comorbidities in patients with temporal lobe epilepsy(TLE),but the underlying mechanisms remain largely unknown.Previous studies have found significant decay of hippocampal long-term potentiation(LTP)in TLE rats with cognitive impairment.As 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 impairments.Methods: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 tested.Results: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 SE.Western 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 SE.Similarly,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 SE.Moreover,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 SE.Conclusions:The reduced expression of hippocampal membrane GluA1 may be involved in LTP decay in CA1 and cognition impairment in TLE rats. | Xiaoqing Luo Xiaoli Yu Jufang Liang Ruidi Sun Cheng Li Jun Jiang | 2021 | Acta Epileptologica2021，3，1： | 0 |
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