Beta-hydroxybutyric acid attenuates neuronal damage in epileptic mice

Abstract

β-Hydroxybutyric acid (BHBA) reportedly has neuroprotective and anti-oxidation properties. The present study aimed to investigate the protective effects of BHBA against epilepsy. C57BL/6 J mice were exposed to lithium chloride and pilocarpine to induce epilepsy and then were administrated with 300 mg/kg/day BHBA for 30 days. The learning impairment was evaluated via Morris Water Maze. Neuron loss and cell apoptosis were detected through Nissl staining and TUNEL staining. The levels of oxidative stress-related factors were determined by commercial kits. The protein expression levels of AMP-activated protein kinase (AMPK), p-AMPK, peroxisome proliferator-activated receptor alpha (PPARα), anti-apoptotic Bcl-2, and pro-apoptotic Bax were measured through Western blots. It was found BHBA improved epilepsy- caused learning deficiency and attenuated epilepsy-mediated neuron loss and cell apoptosis in the hippocampus. BHBA ameliorated oxidative stress via decreasing the levels of reactive oxygen species and malondialdehyde plus strengthening the activities of glutathione peroxidase and superoxide dismutase. BHBA also promoted the phosphorylation of AMPK and upregulated PPARα in the epileptic hippocampus. In conclusion, BHBA attenuates neuronal damage in epileptic mice, which is associated with its anti-apoptotic and anti-oxidative effects as well as the activation of AMPK and PPARα.