Stress proteins and circulating miRNAs as biomarkers of hippocampal remodelling in drug-resistant temporal lobe epilepsy (DR-TLE)

Abstract

Among the mediators of stress response, Heat Shock Proteins (HSPs) play essential roles in cell survival, protein folding, trafficking and degradation [1]. In particular, HSPs alterations were associated with temporal lobe epilepsy (TLE) [2] and recently, specific microRNAs (miR- NA) have been proposed as regulators of HSPs expression [3].

The significance of HSP60 in hippocampus, derived from patients affected by drug resist- ant TLE with hippocampal sclerosis and associated controls, was investigated by immuno- histochemistry while circulating levels of this protein were detected by ELISA test. qRT-PCR was used to evaluate the expression levels of HSP60 and associated miRNA such as miR1 and miR206 in hippocampus. Moreover, miR-8071, miR-663, miR-146a and miR-124 expression levels associated with clinical features of TLE were also investigated. Our findings show that HSP60 is localized inside neurons somata and neuropil. Hsp60 expression levels were corre- lated to those of miR1 and miR206. Moreover, plasma Hsp60 levels in patients were higher than those of controls. Finally, circulating levels of miR-8071, miR-663, miR-146a and miR-124 decreased in TLE patients and were correlated to neuroinflammation and seizure recurrences.

Our work suggests that Hsp60 and associated miRNA levels are altered in relation to epi- leptogenesis and disease progression and may serve as a target for new therapeutic approaches in the management of TLE patients.

This work was supported by grants from Fondazione Epilessia LICE.