Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
11030619 | Epilepsy Research | 2018 | 4 Pages |
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 Kcna1â/â mice, Pparγ2+/+ mice and Pparγ2â/â mice. We found that a KD increases hippocampal catalase expression in Kcna1â/â and Pparγ2+/+ mice, but not Pparγ2â/â 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.
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Authors
Sara Knowles, Sarah Budney, Malavika Deodhar, Stephanie A. Matthews, Kristina A. Simeone, Timothy A. Simeone,