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 language | English (US) |
|---|---|
| Pages (from-to) | 71-74 |
| Number of pages | 4 |
| Journal | Epilepsy Research |
| Volume | 147 |
| DOIs | |
| State | Published - Nov 1 2018 |
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All Science Journal Classification (ASJC) codes
- Neurology
- Clinical Neurology
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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 journal › Article
}
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
PY - 2018/11/1
Y1 - 2018/11/1
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
VL - 147
SP - 71
EP - 74
JO - Epilepsy Research
JF - Epilepsy Research
SN - 0920-1211
ER -