Abstracts

Rationale: Increasing evidence supports the involvement of inflammatory and immune processes in temporal lobe epilepsy. MicroRNAs represent small regulatory RNA molecules that have been shown to act as negative regulators of gene expression controlling different biological processes, including immune-system homeostasis and function. Methods: We investigated the expression and cellular distribution of micro RNA-146a (miR-146a) in a rat model of temporal lobe epilepsy as well as in human temporal lobe epilepsy. MiR-146a analysis in rat hippocampus was performed by PCR and immunocytochemistry at 1 week and 3-4 months after induction of status epilepticus. Primary human cultures of astrocytes and glioma cell lines were used to study the regulation of miR-146a by inflammatory mediators. Results: Prominent up-regulation of miR-146a activation was evident at 1 week after status epilepticus and persisted in the chronic phase. The miR-146a expression was confirmed to be present in neurons and reactive astrocytes. In human temporal lobe epilepsy with hippocampal sclerosis, increased astroglial expression of miR-146a was observed mainly in regions where neuronal cell loss and reactive gliosis occurred. Increased glial and neuronal expression was also detected in specimens of focal cortical dysplasia. In human cultured astrocytes, as well as in the U373 human glioma cell line, miR-146a was induced by the pro-inflammatory cytokine interleukin-1?. Conclusions: The expression of miR-146a in reactive astrocytes supports the possible involvement of microRNAs in the modulation of the astroglial inflammatory response occurring in temporal lobe epilepsy and provides a target for future studies aimed at developing strategies against pro-epileptogenic inflammatory signaling.