Post-ischemic long-term potentiation （i-LTP） is a pathological form of plasticity that was observed in glutamate receptor-mediated neurotransmission after stroke and may exert a detrimental effect via facilitating e...Post-ischemic long-term potentiation （i-LTP） is a pathological form of plasticity that was observed in glutamate receptor-mediated neurotransmission after stroke and may exert a detrimental effect via facilitating excitotoxic damage. The mechanism underlying i-LTP, however, remains less understood. By employing electrophysiological recording and immunofluorescence assay on hippocampal slices and cultured neurons, we found that protein kinase M（（PKMζ）, an atypical protein kinase C isoform, was involved in enhancing aminomethyl phosphonic acid （AMPA） receptor （AMPAR） expression after i-LTP induction. PKMζ knockdown attenuated postsynaptic expression of AMPA receptors and disrupted i-LTP. Consistently, we observed less neuronal death of cultured hippocampal cells with PKMζ knockdown. Meanwhile, these findings indicate that PKMζ plays an important role in i-LTP by regulating postsynaptic expression of AMPA receptors. This work adds new knowledge to the mechanism of i-LTP, and thus is helpful to find the potential target for clinical therapy of ischemic stroke.展开更多
基金supported by grants to W.L.From the Major State Basic Research Program of China(2013CB733801)the Priority Academic Program Development of Jiangsu Higher Education Institutions and the Open Research Fund of State Key Laboratory of Bioelectronics,Southeast University
文摘Post-ischemic long-term potentiation （i-LTP） is a pathological form of plasticity that was observed in glutamate receptor-mediated neurotransmission after stroke and may exert a detrimental effect via facilitating excitotoxic damage. The mechanism underlying i-LTP, however, remains less understood. By employing electrophysiological recording and immunofluorescence assay on hippocampal slices and cultured neurons, we found that protein kinase M（（PKMζ）, an atypical protein kinase C isoform, was involved in enhancing aminomethyl phosphonic acid （AMPA） receptor （AMPAR） expression after i-LTP induction. PKMζ knockdown attenuated postsynaptic expression of AMPA receptors and disrupted i-LTP. Consistently, we observed less neuronal death of cultured hippocampal cells with PKMζ knockdown. Meanwhile, these findings indicate that PKMζ plays an important role in i-LTP by regulating postsynaptic expression of AMPA receptors. This work adds new knowledge to the mechanism of i-LTP, and thus is helpful to find the potential target for clinical therapy of ischemic stroke.
