Inhibition of miRNA-129-2-3p increases risk of seizure induction in developing brain

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Year of publication 2019
Type Conference abstract
MU Faculty or unit

Central European Institute of Technology

Description Purpose: microRNAs (miRNAs/miR) are prominent regulators of gene expression playing important role in function and development of the brain. Changes in miRNA expression are associated with pathologies including epilepsy, where miRNAs are scrutinized as potential treatment agents with promising outcomes in animal models. miR-129-2-3p shows elevated level in both epileptic patients and animal models of epilepsy, hence we tested its effect on epilepsy induction in developing brain. Method: LNA-based inhibitor of miR-129-2-3p was intranasally administered to rats at postnatal (P) day 11 (n=6), controls (n=5) received saline. 24 hours later, cortical EEG electrodes were implanted to animals under isoflurane anesthesia. Subsequently, all animals received 35 mg/ml/kg of pilocarpine in a single dose (LiCl was administered at P11), followed by 3-hour long observation period with simultaneous EEG recording. Results: Due to exposure to isoflurane anesthesia shortly before the administration of pilocarpine, none of the control animals developed status epilepticus (SE), which is typical for P12 rats. Interestingly, five out of six rats treated with miR-129-2-3p inhibitor developed motor SE (Racine stage 3) despite being previously exposed to isoflurane. Conclusion: In concordance with our previous work showing that elevated levels of miR-129-2-3p are present in epilepsy stages, for which motor seizures are characteristic (acute stage of TLE in both adult and infantile rats and chronic stage in adult-onset TLE), these results suggest that miR-129-2-3p is a possible coping mechanism of the brain in presence of motor seizures. Hence, insight into miR-129-2-3p biology might shed light on the pathways involved in seizure origin. Acknowledgement This work was supported by GACR (GAP16-04726S and 19-11931S), The Ministry of Education, Youth and Sports of the Czech Republic under the National Sustainability Programme II, European Union’s Horizon 2020 grant programme (grant agreement No 692298) and research organization RVO: 67985823; project ERDF, OPPK Biomodels CZ.2.16/3.1.00/24017
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