Low doses of Perampanel protect striatal and hippocampal neurons against in vitro ischemia by reversing the ischemia-induced alteration of AMPA receptor subunit composition

Paolo Calabresi, Petra Mazzocchetti, Andrea Mancini, Miriam Sciaccaluga, Alfredo Megaro, Laura Bellingacci, Massimiliano Di Filippo, Elena Nardi Cesarini, Michele Romoli, Nicolò Carrano, Fabrizio Gardoni, Alessandro Tozzi, Cinzia Costa

Risultato della ricerca: Contributo in rivistaArticolo in rivista

2 Citazioni (Scopus)

Abstract

Energy depletion caused by ischemic brain insults may result in persistent neuronal depolarization accompanied by hyper-stimulation of ionotropic glutamate receptors and excitotoxic phenomena, possibly leading to cell death. The use of glutamate receptor antagonists, such as the AMPARs antagonist Perampanel (PER), might be a pharmacological approach to counteract the excessive over-activation of glutamate receptors providing neuroprotective effects. Using electrophysiological and molecular analyses, we investigated the effect of PER against in vitro ischemia obtained by oxygen and glucose deprivation (OGD) in rat slices of two brain structures particularly sensitive to ischemic insults, the nucleus striatum and the hippocampus. We found that in these regions PER was able to avoid the OGD-induced neuronal suffering, at low doses not reducing basal excitatory synaptic transmission and not altering long-term potentiation (LTP) induction. Furthermore, in both the analysed regions, PER blocked the pathological form of LTP, namely ischemic LTP (iLTP). Finally, we hypothesized that the protective effect of PER against OGD was due to its capability to normalize the subunit synaptic localization and function of AMPAR altered after an ischemic insult. Taken together these findings support the idea that PER is a drug potentially effective to counteract in vivo ischemic damage.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaNeurobiology of Disease
DOI
Stato di pubblicazionePubblicato - 2020

Keywords

  • GluA1 AMPA receptor subunit
  • Hippocampus
  • Ischemic LTP
  • Neuroprotection
  • Oxygen and glucose deprivation
  • Striatum

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