Ketogenic diet regulates the antioxidant catalase via the transcription factor PPARγ2

Sara Knowles, Sarah Budney, Malavika Deodhar, Stephanie A. Matthews, Kristina A. Simeone, Timothy Simeone

Research output: Contribution to journalArticle

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Abstract

We have previously found that the transcription factor PPARγ2 contributes to the mechanism of action of the ketogenic diet (KD), an established treatment for pediatric refractory epilepsy. Among the wide-array of genes regulated by PPARγ, previous studies have suggested that antioxidants such as catalase may have prominent roles in KD neuroprotective and antiseizure effects. Here, we tested the hypothesis that the KD increases catalase through activation of PPARγ2, and that this action is part of the mechanism of antiseizure efficacy of the KD. We determined catalase mRNA and protein expression in hippocampal tissue from epileptic Kcna1−/− mice, Pparγ2+/+ mice and Pparγ2−/− mice. We found that a KD increases hippocampal catalase expression in Kcna1−/− and Pparγ2+/+ mice, but not Pparγ2−/− mice. Next, we determined whether catalase contributes to KD seizure protection. We found that the KD reduces pentylenetetrazole (PTZ)-induced seizures; however, pretreatment with a catalase inhibitor occluded KD effects on PTZ seizures. These results suggest that the KD regulates catalase expression through PPARγ2 activation, and that catalase may contribute to the KD antiseizure efficacy.

Original languageEnglish (US)
Pages (from-to)71-74
Number of pages4
JournalEpilepsy Research
Volume147
DOIs
StatePublished - Nov 1 2018

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Ketogenic Diet
Catalase
Transcription Factors
Antioxidants
Pentylenetetrazole
Seizures
Peroxisome Proliferator-Activated Receptors
Neuroprotective Agents
Epilepsy

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

Ketogenic diet regulates the antioxidant catalase via the transcription factor PPARγ2. / Knowles, Sara; Budney, Sarah; Deodhar, Malavika; Matthews, Stephanie A.; Simeone, Kristina A.; Simeone, Timothy.

In: Epilepsy Research, Vol. 147, 01.11.2018, p. 71-74.

Research output: Contribution to journalArticle

Knowles, Sara ; Budney, Sarah ; Deodhar, Malavika ; Matthews, Stephanie A. ; Simeone, Kristina A. ; Simeone, Timothy. / Ketogenic diet regulates the antioxidant catalase via the transcription factor PPARγ2. In: Epilepsy Research. 2018 ; Vol. 147. pp. 71-74.
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