TY - JOUR
T1 - Ketogenic diet regulates the antioxidant catalase via the transcription factor PPARγ2
AU - Knowles, Sara
AU - Budney, Sarah
AU - Deodhar, Malavika
AU - Matthews, Stephanie A.
AU - Simeone, Kristina A.
AU - Simeone, Timothy A.
N1 - Funding Information:
This work was supported by Citizens United for Research in Epilepsy Foundation (TAS) NIH NS085389 (TAS) and NIH NS072179 (KAS) . The project described was also supported by the National Center for Research Resources grant G20RR024001 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.
PY - 2018/11
Y1 - 2018/11
N2 - 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.
AB - 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.
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U2 - 10.1016/j.eplepsyres.2018.09.009
DO - 10.1016/j.eplepsyres.2018.09.009
M3 - Article
C2 - 30261354
AN - SCOPUS:85053748987
VL - 147
SP - 71
EP - 74
JO - Epilepsy Research
JF - Epilepsy Research
SN - 0920-1211
ER -