MiR-125b-5p Inhibitor Might Protect Against Sevoflurane-induced Cognitive Impairments by Targeting LIMK1

Jun Xiong1, Huijun Wang2, Feng Mu1

  • 1Department of Anesthesiology, Sanbo Brain Hospital, Capital Medical University, Beijing City, 100093, China.

Abstract

Insights

Sevoflurane anesthesia can cause cognitive impairment by increasing miR-125b-5p. Inhibiting miR-125b-5p protects against this impairment by targeting LIMK1, improving learning and memory in rats.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Anesthesiology

Background:

  • Anesthesia exposure is linked to cognitive deficits.
  • MicroRNA-125b-5p (miR-125b-5p) is implicated in anesthesia-induced hippocampal apoptosis.
  • The specific role of miR-125b-5p in sevoflurane-induced cognitive impairment requires elucidation.

Purpose of the Study:

  • To investigate the role of miR-125b-5p in sevoflurane-induced cognitive impairments.
  • To explore the underlying molecular mechanisms involving LIM domain kinase 1 (LIMK1).

Main Methods:

  • Sevoflurane exposure in a rat model to induce cognitive impairment, assessed via Morris water maze (MWM) and HE staining.
  • Transfection with lentivirus-miR-125b-5p antagomiR to reduce miR-125b-5p levels.
  • Luciferase reporter assay to confirm miR-125b-5p and LIMK1 interaction.
  • Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and western blot to analyze gene and protein expression.

Main Results:

  • Sevoflurane exposure led to cognitive dysfunction and increased miR-125b-5p expression in rats and SH-SY5Y cells.
  • Reduced miR-125b-5p expression mitigated sevoflurane-induced hippocampal apoptosis and inflammation.
  • LIMK1 was identified as a direct target of miR-125b-5p; its inhibition reversed sevoflurane-induced apoptosis.
  • miR-125b-5p inhibition improved MWM performance and increased LIMK1 expression in rats.

Conclusions:

  • miR-125b-5p inhibition offers neuroprotection against sevoflurane-induced cognitive impairment.
  • The protective effect is mediated through the targeting of LIMK1.
  • This study highlights miR-125b-5p as a potential therapeutic target for managing anesthesia-related cognitive side effects.

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