Hippokampale MikroRNA-Expression bei der Entstehung epileptischer Toleranz im Rattenmodell

With a prevalence of 0.5-1% (approx. 400,000 to 800,000 people) and an incidence of 30.000 cases per year, epilepsy is one of the most common chronic neurological diseases world wide. Patients suffering from epilepsy sometimes experience considerable restrictions regarding their daily lives. Current therapeutic options include, above all, pharmacotherapy, which can cause severe side effects and, especially in the case of temporal lobe epilepsy, often proves ineffective in controlling seizures. Furthermore, such seizure suppressive medications are not disease modifying. Epileptic tolerance is a state of temporarily increased resistance to epileptic seizures and can be achieved through preconditioning. However, the underlying mechanisms of epileptic tolerance have not yet been fully understood. MiRNAs are short, non-coding ribonucleic acids which, by controlling the translation of mRNA, have a decisive influence on protein synthesis. Changes in miRNA expression have been shown in epilepsy and epileptic tolerance-related research. In the present study, changes in miRNA expression in the hippocampus under four different conditions (preconditioning, injury, tolerance, control) were investigated using the perforant pathway stimulation model. For this purpose, test animals were stimulated following different paradigms. After sequencing the miRNAs, a total of 21 miRNAs were found to be significantly upregulated and 15 miRNAs downregulated, of which ten miRNAs were exclusively upregulated and six miRNAs were downregulated in tolerance. The processes associated with these miRNAs primarily concern the regulation of apoptosis, morphology and the formation of axons, dendrites and synapses. Based on these findings further research is needed to investigate the specific mechanisms through which those miRNAs lead to epileptic tolerance and to explore their therapeutic potential.