ABSTRACT
Background: Epilepsy is one of the common neurological disorders affecting approximately 50 million people worldwide. Despite the recent introduction of new antiepileptic drugs, about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Early recognition of patients with drug-resistant epilepsy may help direct these patients to appropriate nonpharmacological treatment. Purpose: The possible use of serum microRNAs (miRNAs) as noninvasive biomarkers has been explored in various brain diseases, including epilepsy. In this study, we are aiming at analyzing the expression levels of circulating miRNA-153 and miRNA-199a in patients with generalized epilepsy and their correlation with drug resistance. Methods: Our study comprised 40 patients with generalized epilepsy and 20 healthy controls. 22 patients were drug-resistant and 18 patients were drug-responsive. The expression levels of miRNA-153 and -199a in serum were analyzed using quantitative real-time polymerase chain reaction. Data analysis was done by IBM SPSS Statistics 20.0. Results: The expression of miRNA-153 and -199a in serum was significantly downregulated in patients with generalized epilepsy compared with that of the healthy control (P < .001). Combined expression level of serum miRNA-153 and -199a had a sensitivity of 85% and a specificity of 90% in the diagnosis of generalized epilepsy. Furthermore, the expression levels of miRNA-153 and -199a were significantly decreased in drug-resistant patients compared to the drug-responsive group, and the combination of both markers gave the best results in differentiating between the two groups. Conclusion: We suggest that serum miRNAs-153 and -199a expression levels could be potential noninvasive biomarkers supporting the diagnosis of generalized epilepsy. Moreover, they could be used for the early detection of refractory generalized epilepsy.
ABSTRACT
BACKGROUND: Glutamate excitotoxicity and cyclic AMP-activated protein kinase (AMPK) are both recognized as important mediators in neurodegenerative disorders including Alzheimer's disease (AD). OBJECTIVES: To investigate whether oral or subcutaneous monosodium glutamate (MSG) neurotoxicity mimics some features of AD and whether these can be reversed by the AMPK activator Pioglitazone. METHODS: Male Wistar rats aged 5 weeks were administered oral or subcutaneous MSG for 10 days with or without daily oral Pioglitazone. Two additional groups given only saline orally or subcutaneously acted as controls. At age 10 weeks the rats were subjected to neurobehavioral testing, then sacrificed for measurement of AMPK, ß-amyloid and Fas ligand in the hippocampus. RESULTS: Oral and subcutaneous MSG both induced a lowering of hippocampal AMPK by 43% and 31% respectively (P<0.05 for both) and >2-fold increase in hippocampal Fas ligand, a mediator of apoptosis (P<0.001 for both). MSG treatment also induced a significant increase in ß-amyloid in the hippocampus by >4-fold and >5-fold in the oral and subcutaneous groups. This was associated with increased latency before crossing to the white half in the black-white alley and before the first rear in the holeboard test, suggesting increased anxiety. Pioglitazone decreased hippocampal ß-amyloid accumulation and Fas ligand, but did not ameliorate the neurobehavioural deficits induced by MSG. CONCLUSIONS: MSG treatment enhances ß-amyloid accumulation in the rat hippocampus. Our results suggest a role for AMPK reduction in mediating the neurotoxic effects of glutamate, including ß-amyloid accumulation.
