Publication details

Inhibition of miRNA-129-2-3p increases risk and severity of seizures developing brain

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Year of publication 2019
Type Conference abstract
MU Faculty or unit

Central European Institute of Technology

Description Epilepsy is a severe neurological disorder characterized by recurrent seizures, which often starts in the infancy when the neuronal networks are not fully functional. Onset in the infancy changes the course of the epilepsy in both patients and animal models. These alterations might arise from impaired expression of microRNAs (miRNAs/miRs) - prominent regulators of gene expression playing important role in function and development of the brain. Altered expression of miRNAs have been associated with numerous types of epilepsy including most frequent temporal lobe epilepsy (TLE), making them a promising target of novel anti-epileptic therapeutics. miR-129-2-3p shows elevated level in both TLE patients and animal models. Our aim was to address miR-129-2-3p effect on epilepsy induction in developing brain. LNA-inhibitor of miR-129-2-3p was intranasally administered to rats at postnatal (P) day 11 (n=13), while controls (n=12) received saline. 24 hours later, cortical EEG electrodes were implanted under either isoflurane or ether anesthesia and status epilepticus (SE) was induced by pilocarpine with continuous EEG recording. Typically for P12 rats, controls exposed to isoflurane anesthesia before the administration of pilocarpine did not developed SE. Interestingly, five out of six rats treated with miR-129-2-3p inhibitor developed motor SE despite the isoflurane exposure. In animals with surgery performed under the ether anesthesia, pretreatment with miR-129-2-3p inhibitor prolonged duration of epileptic status and increased its severity. These results suggest that miR-129-2-3p may play role in the seizure coping mechanism of the brain and shed light on the pathways involved in seizure origin. Acknowledgement This work was supported by GACR (19-11931S), The Ministry of Education, Youth and Sports of the Czech Republic under the National Sustainability Programme II, research organization RVO: 67985823 and OPPK Biomodels CZ.2.16/3.1.00/24017
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