PKMζ knockdown disrupts post-ischemic long-term potentiation via inhibiting postsynaptic expression

来源 :The Journal of Biomedical Research | 被引量 : 0次 | 上传用户:lzxhno
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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 Mζ(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. 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 .y employed electrophysiological recording and immunofluorescence assay on hippocampal slices and cultured neurons, we found that protein kinase Mζ (PKMζ), an atypical protein kinase C isoform, was involved in enhancing aminomethyl phosphonic acid (AMPA) receptor (AMPAR) expression after i-LTP induction. PKMζ, knockdown of 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 t he potential target for clinical therapy of ischemic stroke.
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