Crosstalk between miRNAs, high mobility group box-1 and complement system in epilepsy: relevance of response to valproic acid

Abstract

Abstract Background Epileptogenesis is a complex alteration of brain functions with subsequent development of seizures. Among the fundamental causes of epilepsy are immunological changes. Recently, the role of miRNAs in the pathogenesis of epilepsy has been raised. The current study investigated a possible link between serum levels of specific miRNAs, high mobility group box-1 (HMGB-1) and the complement system in epileptic patients and how valproate treatment can influence their levels. Results Serum levels of HMGB1, C3b and C1q were measured in 41 drug-naïve epileptic patients and 40 valproate-treated patients using enzyme-linked immunosorbent assay along with relative expressions of miRNA-129-5P, miRNA-146a and miRNA-155 by RT PCR. Serum samples of 41 healthy subjects were used as control. The serum level of the complement system C1q and C3 components was significantly elevated in epileptic patients. Valproate treatment was associated with a reduction of C1q and C3 levels. Epileptic patients, whether drug-naïve or valproate treated, had high serum levels of HMGB1, which was significantly reduced with valproate intake. Serum miRNAs-129-5P, 146a and 155 levels were significantly raised in all patients. Valproate intake was associated with a significant increase in miRNA-129-5P; in contrast, miRNA-146a and miRNA-155 showed decreased serum levels. Conclusion These results underlined the role of three circulating miRNAs as possible biological markers of epilepsy. These markers can provide a useful tool for early diagnosis and assessment of response to anti-seizure medications. Graphical Abstract