Upregulation of lactate dehydrogenase A in a chronic model of temporal lobe epilepsy

Nagisa Sada, Shogo Suto, Mana Suzuki, Shoichiro Usui, Tsuyoshi Inoue

Research output: Contribution to journalArticlepeer-review

Abstract

The ketogenic diet treatment is effective for drug-resistant epilepsy. Because its antiepileptic effect is associated with lactate dehydrogenase (LDH), drug development is possible by targeting LDH enzymes. Seizures in rodent models are suppressed by inhibiting LDH; however, it remains unclear whether LDH in the brain is changed by seizures. In the present study, we examined the expression of LDH subunits (LDHA and LDHB) in a chronic model of temporal lobe epilepsy, in which seizures were induced by the microinjection of kainate into the mouse hippocampus. Using Western blot analyses, we found that LDHA expression was increased in the hippocampus of the chronic seizure model, whereas LDHB expression was not. Lactate levels in the hippocampus were also increased in this seizure model, suggesting elevated LDH enzymatic activities. Furthermore, the inhibition of LDHA suppressed spontaneous paroxysmal discharges in vivo in the chronic seizure model. In conclusion, our results show that chronic seizures increase LDHA, and conversely, the inhibition of LDHA suppresses seizures, which supports LDHA as a molecular target for the development of new antiepileptic drugs.

Original languageEnglish
Pages (from-to)e37-e42
JournalEpilepsia
Volume61
Issue number5
DOIs
Publication statusPublished - May 1 2020

Keywords

  • LDHA
  • chronic seizure model
  • drug-resistant epilepsy
  • ketogenic diet
  • lactate dehydrogenase

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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