Increased GABAergic inhibitory function against ischemic long-term potentiation in the CA1 region of the hippocampus

Ming Chia Chu, Jing Ying Lee, Hung Fu Lee, Kai Wen Chu, Han Fang Wu, Chi Wei Lee, Chia Hsien Lin, Chih Wei Tang, Hui Ching Lin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Potentiation of N-methyl-D-aspartate receptor (NMDAR)-mediated excitatory synaptic plasticity around 1 h after brief exposure to anoxia/aglycemia is called ischemic long-term potentiation (iLTP), which is considered a pathological form of synaptic response during the early phase of ischemic stroke. It is known that GABAergic inhibitory transmission is also an important molecular process involved in synaptic plasticity and learning memory. However, whether GABAergic transmission is involved in iLTP and early-phase plasticity in ischemic stroke remains unknown. In this study, iLTP was found to be induced in the hippocampal Schaffer-collateral pathway by exposure to oxygen glucose deprivation (OGD). Western blot analysis was conducted to analyze excitatory synaptic receptors and inhibitory synaptic receptors following OGD. The β3 subunit of the GABAA receptor (GABAAR) was markedly reduced, whereas the GluN2B subunit of the NMDAR was increased in the hippocampal area in the OGD group. Using extracellular recording, we demonstrated that application of GABAAR agonist midazolam could abolish the hippocampal iLTP. Moreover, midazolam had no significant effect on the increase in NMDAR subunit GluN2B, but ameliorated the reduction in the β3 subunit of GABAAR after OGD. In summary, our results indicated that hippocampal GABAAR reduction promoted synaptic potentiation after OGD. Activation of GABAergic inhibitory transmission function could inhibit iLTP; thus, modulation of GABAergic function is a protective treatment method in the acute phase of synaptic plasticity in ischemic stroke.

Original languageEnglish
Pages (from-to)491-496
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume526
Issue number2
DOIs
StatePublished - 28 May 2020

Keywords

  • GABAergic inhibitory transmission
  • Hippocampus
  • Ischemic long-term potentiation
  • NMDA receptor

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