| First Author | Knowles S | Year | 2018 |
| Journal | Epilepsy Res | Volume | 147 |
| Pages | 71-74 | PubMed ID | 30261354 |
| Mgi Jnum | J:294474 | Mgi Id | MGI:6456498 |
| Doi | 10.1016/j.eplepsyres.2018.09.009 | Citation | Knowles S, et al. (2018) Ketogenic diet regulates the antioxidant catalase via the transcription factor PPARgamma2. Epilepsy Res 147:71-74 |
| abstractText | We have previously found that the transcription factor PPARgamma2 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 PPARgamma, 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 PPARgamma2, 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, Ppargamma2(+/+) mice and Ppargamma2(-/-) mice. We found that a KD increases hippocampal catalase expression in Kcna1(-/-) and Ppargamma2(+/+) mice, but not Ppargamma2(-/-) 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 PPARgamma2 activation, and that catalase may contribute to the KD antiseizure efficacy. |
