title: PKMζ knockdown disrupts post-ischemic long-term potentiation via inhibiting postsynaptic expression of aminomethyl phosphonic acid receptors.
abstract: 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.
authors.affiliation: Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Cheng
authors.affiliation: Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Xiaoqiao
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.affiliation: Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
keywords: AMPA receptor; PKMζ; i-LTP; oxygen glucose deprivation