Novel animal model of combined generalized and focal epilepsy

Iori Ohmori, Mamoru Ouchida, Masakazu Shinohara, Kiyoka Kobayashi, Saeko Ishida, Tomoji Mashimo

Research output: Contribution to journalArticlepeer-review

Abstract

Thioredoxin, encoded by Txn1, is a critical antioxidant that protects against oxidative damage by regulating the dithiol/disulfide balance of interacting proteins. We recently discovered the Adem rat, an epileptic rat harboring the Txn1-F54L mutation, characterized by wild running and vacuolar degeneration in the midbrain. This study aimed to characterize the classification of epilepsy in Adem rats. We performed simultaneous video-electroencephalographic recordings, magnetic resonance imaging, neurotransmitter measurements using gas chromatography–mass spectrometry (GC-MS), and immunohistochemistry. Adem rats exhibited absence, tonic, and focal seizures. The type of epilepsy was classified as combined generalized and focal epilepsy. Neurotransmitters in the midbrain and cortex were measured at 3 weeks of age, when neuronal cell death occurs in the midbrain. The results of GC-MS ruled out the dominance of the excitatory system in the midbrain and cortex of Adem rats. Activation of astrocytes and microglia was more pronounced at 5 weeks of age, at which time epileptic seizures occurred frequently. The underlying pathology in Adem rats remains unknown. However, glial cell activation and inflammation may play a significant role in the occurrence of epilepsy.

Original languageEnglish
JournalEpilepsia
DOIs
Publication statusAccepted/In press - 2022

Keywords

  • animal model
  • combined generalized and focal epilepsy
  • oxidative stress
  • thioredoxin

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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