Long-Term Effects of Zinc Deficiency and Zinc Supplementation on Developmental Seizure-Induced Brain Damage and the Underlying GPR39/ZnT-3 and MBP Expression in the Hippocampus.

We previously illustrated that long-term upregulated expression of ZnT-3 in the hippocampus of rats that underwent neonatal seizures was restored by pretreatment with a ketogenic diet. It was recently demonstrated that upregulated expression of ZnT-3 was associated with increased concentrations of intracellular free zinc ions in an model of glutamate-induced hippocampal neuronal excitotoxic damage. However, there is still a lack of research on the effects of different concentrations of zinc in the diet on developmental convulsive brain injury.

Reduction of Mitophagy-Related Oxidative Stress and Preservation of Mitochondria Function Using Melatonin Therapy in an HT22 Hippocampal Neuronal Cell Model of Glutamate-Induced Excitotoxicity.

Recent evidence indicates that autophagy-mediated mitochondrial homeostasis is crucial for oxidative stress-related brain damage and repair. The highest concentration of melatonin is in the mitochondria of cells, and melatonin exhibits well-known antioxidant properties. We investigated the impact and mechanism involved in mitochondrial function and the mitochondrial oxidative stress/autophagy regulator parameters of glutamate cytotoxicity in mouse HT22 hippocampal neurons.

Neuro-Behavioral Status and the Hippocampal Expression of Metabolic Associated Genes in Wild-Type Rat Following a Ketogenic Diet.

While a ketogenic diet (KD) is a well-established therapy for medically intractable epilepsy, clinical evidence of relevant adverse events of a KD has also been reported. We asked whether this kind of diet would have deleterious effects on wild-type brain function by evaluating KD-induced biochemical changes in the hippocampus as well as neurobehavioral changes occurring in wild-type rats. Fifty-four Sprague-Dawley rats were randomly assigned to three groups on postnatal day 28 (P28): wild-type rats fed with a KD qd (daily for 4 weeks, KD) or qod (every other day for 4 weeks, KOD), and wild-type rats fed with standard normal laboratory diet (ND).

Leptin-regulated autophagy plays a role in long-term neurobehavioral injury after neonatal seizures and the regulation of zinc/cPLA2 and CaMK II signaling in cerebral cortex.

Metabolic disorders play an important role in the pathogenesis of many neurological diseases. Recent evidence suggests that leptin levels in peripheral blood and brain are lower in patients with epilepsy. Leptin is an energy-regulating hormone that plays a neuroprotective role in neurodegenerative diseases and brain trauma.

Ketogenic diet change cPLA2/clusterin and autophagy related gene expression and correlate with cognitive deficits and hippocampal MFs sprouting following neonatal seizures.

Because the ketogenic diet (KD) was affecting expression of energy metabolism- related genes in hippocampus and because lipid membrane peroxidation and its associated autophagy stress were also found to be involved in energy depletion, we hypothesized that KD might exert its neuroprotective action via lipid membrane peroxidation and autophagic signaling. Here, we tested this hypothesis by examining the long-term expression of lipid membrane peroxidation-related cPLA2 and clusterin, its downstream autophagy marker Beclin-1, LC3 and p62, as well as its execution molecule Cathepsin-E following neonatal seizures and chronic KD treatment. On postnatal day 9 (P9), 48 Sprague-Dawley rats were randomly assigned to two groups: flurothyl-induced recurrent seizures group and control group.