Effect of toxoplasma gondii infection on idiopathic epilepsy; the role of micro RNAs

Epilepsy is one of the most common disorders of the central nervous system. Although the exact cause of epilepsy remains unclear, inflammation is thought to play an important role in its pathogenesis. This inflammatory process may be associated with certain infections, particularly intracellular parasites. This study aimed to investigate Toxoplasma gondii infection, inflammation, and related microRNAs (miRNA-146a, miRNA-155, miRNA-26, miRNA-106b) in patients with idiopathic epilepsy. A total of 40 participants were equally divided into four groups: Group 1 (Epilepsy− / T. gondii−), Group 2 (Epilepsy+ / T. gondii−), Group 3 (Epilepsy− / T. gondii+), and Group 4 (Epilepsy+ / T. gondii+). Serum levels of HMGB1, NF-κB, TLR4, TNF-α, TRAF6, RAGE, and IL-1β were determined by ELISA. Gene expression levels of HMGB1, IL-1β, IL-10, IRAK1, IRAK2, TLR4, TNF-α, and RAGE, along with miRNA-146a, miRNA-155, miRNA-26, and miRNA-106b, were analyzed by RT-qPCR. HMGB1 levels were significantly higher in Group 4 compared to Groups 1 and 2, and in Group 3 compared to Groups 1 and 2 (p<0.05). NF-κB levels were highest in Group 4 (p<0.05), while TLR4 levels were highest in Group 3 (p<0.05). TNF-α and TRAF6 concentrations were highest in Group 4, followed by Groups 3, 2, and 1 (p<0.05). RAGE levels were significantly elevated in Groups 3 and 4 compared to Groups 1 and 2 (p<0.05). In gene expression analysis, IL-10 was highest in Group 2 (p<0.05), IL-1β was highest in Group 3 (p<0.05), and TLR4 was highest in Group 2 (p<0.05). IRAK1 and IRAK2 expression was highest in Group 4, while Group 3 also showed significantly higher expression than Groups 1 and 2 (p<0.05). RAGE mRNA expression did not differ significantly between groups (p>0.05). In microRNA analysis, miRNA-146a was elevated in infection groups, suggesting a potential role in regulating infection-induced inflammation. miRNA-155 and miRNA-106b levels were highest in Group 3 (p<0.05) and considered strong indicators of immune response to T. gondii infection. miRNA-26 levels did not differ significantly between groups (p>0.05). In conclusion, T. gondii infection, particularly when coexisting with epilepsy, appears to potentiate neuroinflammatory processes. Moreover, infection-related immune activation seems to be regulated by specific microRNAs. These findings provide an important molecular basis for the identification of novel therapeutic targets. Keywords: Toxoplasma gondii, epilepsy, neuroinflammation, ELISA, RT-qPCR, microRNA, cytokine.