Elevated microRNA-135b-5p relieves neuronal injury and inflammation in post-stroke cognitive impairment by targeting NR3C2

Int J Neurosci. 2022 Jan;132(1):58-66. doi: 10.1080/00207454.2020.1802265. Epub 2020 Aug 4.

Abstract

Purpose: Post-stroke cognitive impairment (PSCI) is a series of syndromes that meets the diagnostic criteria of cognitive impairment within 6 months after the clinical event of stroke. With the unpleasing treatment at present, this study aimed to investigate the role of microRNA (miR)-135b-5p in regulating mineralocorticoid receptor (NR3C2) in PSCI.

Methods: The rats were modeled via middle cerebral artery occlusion, and injected with miR-135b-5p agomir or antagomir to figure its role in post-stroke neurological deficits, neuronal injury, neuronal cell apoptosis, and inflammation via Behavioral tests, Nissl's staining, flow cytometry, and TUNEL staining. The expression of miR-135b-5p and NR3C2 in rats was detected by RT-qPCR and western blot analysis. The targeting relationship between miR-135b-5p and NR3C2 was verified by dual luciferase reporter gene assay.

Results: Highly expressed miR-135b-5p relieved post-stroke neurological deficits, focal cerebral ischemia-reperfusion (FCIR) neuron injury, and reduced neuronal apoptosis and inflammatory response after FCIR in PSCI rats. Poorly expressed miR-135b-5p and highly expressed NR3C2 were present in FCIR injury in PSCI rats. miR-135b-5p can direct target NR3C2 3'UTR.

Conclusion: The study highlights that up regulation of miR-135b-5p can reduce neuronal injury and inflammatory response in PSCI by targeting NR3C2, which might be helpful for PSCI treatment.

Keywords: Apoptosis; MicroRNA-135b-5p; Mineralocorticoid receptor; Neuronal injury; Post-stroke cognitive impairment; inflammatory factors.

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / metabolism*
  • Disease Models, Animal
  • MicroRNAs / metabolism*
  • Neuroinflammatory Diseases / etiology
  • Neuroinflammatory Diseases / metabolism*
  • Rats
  • Receptors, Mineralocorticoid / metabolism*
  • Reperfusion Injury / metabolism*
  • Stroke / complications*
  • Up-Regulation

Substances

  • MIRN135 microRNA, rat
  • MicroRNAs
  • Receptors, Mineralocorticoid