Ketogenic diet-induced peroxisome proliferator-activated receptor-gamma 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)gamma 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 MD for 4 weeks and sacrificed 2 or 6 h after MA injection. The MD reduced hippocampal tumor necrosis factor alpha (TNF-alpha) levels and nuclear factor (NF)-kappa B translocation into the nucleus 2 h after KA treatment. MD-induced PPAR gamma 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 6 h after MA treatment. AA treatment also protected against glutamate-induced cell death in HT22 cells by reducing TNF-alpha and PPAR gamma-mediated COX-2 expression. Thus, the KD may inhibit neuroinflammation by suppressing a COX-2-dependent pathway via activation of PPAR gamma by the KD or AA. (C) 2011 Elsevier Inc. All rights reserved.