title: Ketogenic diet-induced peroxisome proliferator-activated receptor-γ activation decreases neuroinflammation in the mouse hippocampus after kainic acid-induced seizures.
abstract: Similar to fasting, the ketogenic diet (KD) has anti-inflammatory effects and protects against excitotoxicity-mediated neuronal cell death. Recent studies have shown that peroxisome proliferator-activated receptor (PPAR)γ has anti-inflammatory effects in seizure animal models. However, the exact mechanisms underlying the anti-inflammatory effects of the KD have not been determined for seizures. Here we investigated the effect of the KD and acetoacetate (AA) on neuroinflammation in a seizure animal model and glutamate-treated HT22 cells, respectively. Mice were fed the KD for 4 weeks and sacrificed 2 or 6h after KA injection. The KD reduced hippocampal tumor necrosis factor alpha (TNF-α) levels and nuclear factor (NF)-κB translocation into the nucleus 2h after KA treatment. KD-induced PPARγ activation was decreased by KA in neurons as assessed by western blotting and immunofluorescence. Finally, the KD inhibited cyclooxygenase (COX)-2 and microsomal prostaglandin E(2) synthase-1 (mPGES-1) expression in the hippocampus 6h after KA treatment. AA treatment also protected against glutamate-induced cell death in HT22 cells by reducing TNF-α and PPARγ-mediated COX-2 expression. Thus, the KD may inhibit neuroinflammation by suppressing a COX-2-dependent pathway via activation of PPARγ by the KD or AA.
authors.affiliation: Department of Anatomy and Neurobiology, Institute of Health Sciences, Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine, Jinju, Gyeongnam, 660-751, Republic of Korea.
authors.forename: Eun Ae
authors.initials: EA
authors.lastname: Jeong
authors.forename: Byeong Tak
authors.initials: BT
authors.lastname: Jeon
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Shin
authors.forename: Nayoung
authors.initials: N
authors.lastname: Kim
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Lee
authors.forename: Hyun Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sang Soo
authors.initials: SS
authors.lastname: Kang
authors.forename: Gyeong Jae
authors.initials: GJ
authors.lastname: Cho
authors.forename: Wan Sung
authors.initials: WS
authors.lastname: Choi
authors.forename: Gu Seob
authors.initials: GS
authors.lastname: Roh
mesh_terms: D000090:Acetoacetates / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001835:Body Weight / Q000502:physiology; D039481:CD11b Antigen / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000276:immunology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D055423:Diet, Ketogenic; D004660:Encephalitis / Q000178:diet therapy* / Q000209:etiology / Q000276:immunology; D004827:Epilepsy / Q000139:chemically induced* / Q000150:complications / Q000178:diet therapy*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D018698:Glutamic Acid / Q000633:toxicity; D006624:Hippocampus / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000090:Acetoacetates; D039481:CD11b Antigen; D018690:Excitatory Amino Acid Agonists; D047495:PPAR gamma; D014409:Tumor Necrosis Factor-alpha; D018698:Glutamic Acid; C016635:acetoacetic acid; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D007608:Kainic Acid