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Antagonist targeting microRNA-146a protects against lithium-pilocarpine-induced status epilepticus in rats by nuclear

Huilong Zhang1, Yun Qu2, Aihua Wang3

  • 1Department of Neurology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China.

Molecular Medicine Reports
|January 25, 2018
PubMed

Insights

MicroRNA-146a (miRNA-146a) and the nuclear factor-kappa B (NF-κB) pathway are implicated in epilepsy pathogenesis. Targeting these may offer new epilepsy treatments.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pathology

Background:

  • Epilepsy pathogenesis involves complex molecular mechanisms.
  • Nuclear factor-kappa B (NF-κB) signaling is a key pathway in epilepsy.
  • MicroRNAs (miRNAs) play regulatory roles in neurological disorders.

Purpose of the Study:

  • To investigate the expression of miRNA-146a, NF-κB pathway components, and inflammatory markers in an epilepsy rat model.
  • To explore the therapeutic potential of targeting miRNA-146a in epilepsy.

Main Methods:

  • Epilepsy model established in Sprague-Dawley rats using lithium-pilocarpine.
  • Expression levels of miRNA-146a, interleukins (IL-1β, IL-6), tumor necrosis factor-alpha (TNF-α), phosphorylated P65 (p-P65)/P65, B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X protein (Bax), and P-glycoprotein (P-gp) were quantified.
  • Techniques included reverse transcription-semi-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting.
  • Histopathological changes were assessed using hematoxylin and eosin staining.

Main Results:

  • MiRNA-146a expression was upregulated in epilepsy model rats, peaking at 7 days post-treatment.
  • Administration of a miRNA-146a antagonist significantly reduced pro-inflammatory cytokines (IL-1β, IL-6, TNF-α).
  • The antagonist also decreased P-gp and p-P65/P65 levels, while increasing the Bcl-2/Bax ratio, indicating reduced apoptosis.

Conclusions:

  • MiRNA-146a expression is elevated in epilepsy and influences key inflammatory and apoptotic pathways.
  • The NF-κB pathway and miRNA-146a represent promising therapeutic targets for epilepsy treatment.
Keywords:
miR-146aepilepsynuclear factor-κB pathwaypro‑inflammatory cytokines

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