Alpha-pinene and dizocilpine (MK-801) attenuate kindling development and astrocytosis in an experimental mouse model of epilepsy

Hiroshi Ueno, Atsumi Shimada, Shunsuke Suemitsu, Shinji Murakami, Naoya Kitamura, Kenta Wani, Yu Takahashi, Yosuke Matsumoto, Motoi Okamoto, Takeshi Ishihara

Research output: Contribution to journalArticlepeer-review

Abstract

Understanding the molecular and cellular mechanisms involved during the onset of epilepsy is crucial for elucidating the overall mechanism of epileptogenesis and therapeutic strategies. Previous studies, using a pentylenetetrazole (PTZ)-induced kindling mouse model, showed that astrocyte activation and an increase in perineuronal nets (PNNs) and extracellular matrix (ECM) molecules occurred within the hippocampus. However, the mechanisms of initiation and suppression of these changes, remain unclear. Herein, we analyzed the attenuation of astrocyte activation caused by dizocilpine (MK-801) administration, as well as the anticonvulsant effect of α-pinene on seizures and production of ECM molecules. Our results showed that MK-801 significantly reduced kindling acquisition, while α-pinene treatment prevented an increase in seizures incidences. Both MK-801 and α-pinene administration attenuated astrocyte activation by PTZ and significantly attenuated the increase in ECM molecules. Our results indicate that astrocyte activation and an increase in ECM may contribute to epileptogenesis and suggest that MK-801 and α-pinene may prevent epileptic seizures by suppressing astrocyte activation and ECM molecule production.

Original languageEnglish
Pages (from-to)102-114
Number of pages13
JournalIBRO Reports
Volume9
DOIs
Publication statusPublished - Dec 2020

Keywords

  • Epilepsy
  • Kindling
  • Pentylenetetrazol
  • Perineuronal nets
  • Wisteria floribunda

ASJC Scopus subject areas

  • Neuroscience(all)

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