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

Guan-Yu Wang1,2, Zhi-Lin Luan1,3, Ning-Wei Che1

  • 1Department of Neurosurgery, the Second Affiliated Hospital of Dalian Medical University, Dalian, China.

Brain and Behavior
|May 24, 2021
PubMed
Abstract

Insights

MicroRNA (miR)-129-2-3p targets GABRA1, a gene involved in epilepsy. Silencing miR-129-2-3p reduced seizures in a rat model, suggesting this pathway is a potential therapeutic target for refractory epilepsy.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • MicroRNAs (miRNAs) are increasingly recognized for their roles in epileptogenesis.
  • Previous research identified microRNA (miR)-129-2-3p as upregulated in patients with refractory temporal lobe epilepsy (TLE).

Purpose of the Study:

  • To investigate the role of miR-129-2-3p in the pathogenesis of temporal lobe epilepsy (TLE).
  • To explore the regulatory relationship between miR-129-2-3p and the GABRA1 gene.

Main Methods:

  • Bioinformatic analysis to predict miR-129-2-3p targets.
  • Luciferase assays to confirm direct targeting of GABRA1 3'UTR by miR-129-2-3p.
  • Quantitative reverse transcription-polymerase chain reaction (qPCR), Western blotting, and immunostaining to assess expression levels in primary hippocampal neurons and a kainic acid (KA)-induced seizure model.
  • In vivo experiments using miR-129-2-3p agomir and antagomir, with electroencephalography (EEG) and immunostaining to evaluate seizure activity and GABRA1 dependence.

Main Results:

  • GABRA1 was confirmed as a direct target of miR-129-2-3p.
  • miR-129-2-3p expression was significantly upregulated, while GABRA1 expression was downregulated in KA-treated neurons and the seizure model.
  • In vivo knockdown of miR-129-2-3p using an antagomir reduced seizure activity, correlating with GABRA1 upregulation.
  • The seizure-suppressing effect of the antagomir was partially dependent on GABRA1 levels.

Conclusions:

  • GABRA1 is a direct target of miR-129-2-3p in the context of epilepsy.
  • Silencing miR-129-2-3p demonstrates a seizure-suppressing effect in a rat model.
  • The miR-129-2-3p/GABRA1 pathway presents a potential therapeutic target for refractory epilepsy prevention and treatment.
Keywords:
GABRA1GABAA receptor subunit α1epilepsyhippocampus neuronkainic acid (KA)miR-129-2-3p

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