TLR2 deficiency attenuated chronic intermittent hypoxia-induced neurocognitive deficits

Int Immunopharmacol. 2020 Apr:81:106284. doi: 10.1016/j.intimp.2020.106284. Epub 2020 Feb 12.

Abstract

Chronic intermittent hypoxia (CIH) is the main symptom of obstructive sleep apnea syndrome (OSAS) and causes neural damage and cognitive deficits via neuroinflammation. Toll-like receptors (TLRs), especially TLR2, play an important role in neuroinflammation. However, the mechanisms by which TLR2 participates in CIH-induced cognitive deficits remain unclear. In this study, wild-type (WT) and TLR2 knock out (KO) mice were exposed to CIH for 8 weeks, and their social novelty discrimination, spatial learning and memory were severely compromised. Additionally, seriously damaged neurons and abnormally activated glia were observed in the CA1 and dentate gyrus (DG) areas of the hippocampus. Mechanistically, knocking out the TLR2 gene significantly alleviated these pathological changes and improved the behavioral performance. Together, these findings demonstrate that the TLR2-MyD88 signaling pathway might play an important role in CIH-induced cognitive deficits.

Keywords: Chronic intermittent hypoxia; Cognitive deficits; Neuroinflammation; Obstructive sleep apnea syndrome; TLR2.

MeSH terms

  • Animals
  • Apoptosis
  • Behavior, Animal
  • Cognitive Dysfunction / immunology
  • Cognitive Dysfunction / metabolism*
  • Disease Models, Animal
  • Humans
  • Hypoxia / immunology
  • Hypoxia / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurogenic Inflammation / immunology
  • Neurogenic Inflammation / metabolism*
  • Neurons / pathology*
  • Signal Transduction
  • Sleep Apnea, Obstructive / immunology
  • Sleep Apnea, Obstructive / metabolism*
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism*

Substances

  • Tlr2 protein, mouse
  • Toll-Like Receptor 2