Unknown

Dataset Information

0

Inhibition of microRNA-129-2-3p protects against refractory temporal lobe epilepsy by regulating GABRA1.


ABSTRACT:

Background

Accumulating evidence demonstrates that certain microRNAs play critical roles in epileptogenesis. Our previous studies found microRNA (miR)-129-2-3p was induced in patients with refractory temporal lobe epilepsy (TLE). In this study, we aimed to explore the role of miR-129-2-3p in TLE pathogenesis.

Method

By bioinformatics, we predicted miR-129-2-3p may target the gene GABRA1 encoding the GABA type A receptor subunit alpha 1. Luciferase assay was used to investigate the regulation of miR-129-2-3p on GABRA1 3'UTR. The dynamic expression of miR-129-2-3p and GABRA1 mRNA and protein levels were measured in primary hippocampal neurons and a rat kainic acid (KA)-induced seizure model by quantitative reverse transcription-polymerase chain reaction (qPCR), Western blotting, and immunostaining. MiR-129-2-3p agomir and antagomir were utilized to explore their role in determining GABRA1 expression. The effects of targeting miR-129-2-3p and GABRA1 on epilepsy were assessed by electroencephalography (EEG) and immunostaining.

Results

Luciferase assay, qPCR, and Western blot results suggested GABRA1 as a direct target of miR-129-2-3p. MiR-129-2-3p level was significantly upregulated, whereas GABRA1 expression downregulated in KA-treated rat primary hippocampal neurons and KA-induced seizure model. In vivo knockdown of miR-129-2-3p by antagomir alleviated the seizure-like EEG findings in accordance with the upregulation of GABRA1. Furthermore, the seizure-suppressing effect of the antagomir was partly GABRA1 dependent.

Conclusions

The results suggested GABRA1 as a target of miR-129-2-3p in rat primary hippocampal neurons and a rat kainic acid (KA) seizure model. Silencing of miR-129-2-3p exerted a seizure-suppressing effect in rats. MiR-129-2-3p/GABRA1 pathway may represent a potential target for the prevention and treatment of refractory epilepsy.

SUBMITTER: Wang GY 

PROVIDER: S-EPMC8323041 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC4215559 | biostudies-literature
2010-06-11 | E-GEOD-6773 | biostudies-arrayexpress
| S-EPMC4415572 | biostudies-literature
| S-EPMC5897166 | biostudies-literature
| S-EPMC4596924 | biostudies-literature
2007-01-23 | GSE6773 | GEO
2007-01-23 | E-GEOD-6771 | biostudies-arrayexpress
2007-01-23 | E-GEOD-6834 | biostudies-arrayexpress
2014-12-04 | E-GEOD-63808 | biostudies-arrayexpress
| S-EPMC10846515 | biostudies-literature