Protective Effect Of Beta-Hydroxybutyrate On Glutamate Induced Cell Death In Ht22 Cells

A ketogenic diet is a high-fat, adequate-protein, low-carbohydrate diet used in the treatment of paediatric epilepsy. However, little is known about the mechanism underlying its antiepileptic effect. Ketone bodies contain about 70% beta-hydroxybutyrate (BHB), a metabolic intermediate. Here, we sought to explore the protective effect of BHB on glutamate-induced toxicity in hippocampal neuronal HT22 cells and the underlying mechanisms. HT22 cells were pretreated with BHB, then exposed to glutamate. We examined cell viability, morphological characteristics of apoptosis, intracellular reactive oxygen species (ROS) levels, lipid peroxidation, and activation of the mitogen-activated protein kinase (MAPK) signal pathway. BHB significantly reduced the glutamate-decreased cell viability and inhibited HT22 cell death. Furthermore, BHB decreased ROS generation and alleviated lipid peroxidation. Exposure to glutamate strongly promoted the phosphorylation of c-Jun N-terminal kinase (JNK) and p38, and BHB reduced the glutamate-phosphorylated JNK and p38. MAPK signal pathways are essential for the neuroprotective effect of BHB on glutamate-induced toxicity in HT22 cells.