Propionate relieves pentylenetetrazol-induced seizures, consequent mitochondrial disruption, neuron necrosis and neurological deficits in mice

Abstract The present research was designed to evaluate the protective effects and underlying mechanisms of propionate, a bioactive food additive, on mitochondrial disruption, neuron necrosis and neurological deficits after epilepsy seizures. Epilepsy seizures was induced by repetitive injections of pentylenetetrazol at a dose of 37 mg per kg. Propionate (37.5, 50 and 75 mg/kg) as well as sodium valproate (300 mg/kg) were administrated intragastrically (i.g.) 1 hour before each PTZ injection and continued for 40 days. The influence of propionate was assessed by many biochemical assays and neurobehavioral experiments. The results of gas chromatography (GC) analysis indicated that increased concentration of propionate can be explored in hippocampus area of propionate + PTZ treated animals. Propionate decreased epilepsy seizure intensity, increased latency of seizures. Meanwhile, propionate treatment reversed the structure disruption of the mitochondria, improved ATP level and lessened 8-OHdG level in the brains of animals with seizures. In addition, we find propionate pretreated can increase activities of the antioxidant enzymes (CAT, SOD, as well as GSH-Px) in mitochondria. Additionally, propionate reduced neuronal loss in hippocampus and our results suggest that HIF-1α/ERK pathway and neuron necrosis exists potential linkage during epileptogenesis. Moreover, as a result, propionate administration can significantly improve the neurological function estimated by a battery of functional tests. In conclusion, treatment with propionate attenuates mitochondrial disruption, hippocampal apoptosis and neurological deficits in a mouse model of epilepsy seizures. Therefore, propionate, currently used as a food preservative, has a potential additional advantage of ameliorating epilepsy seizures.