Protective effects of taurine on heat Stress-Induced cognitive impairment through Npas4 and Lcn2

Int Immunopharmacol. 2024 Dec 25;143(Pt 1):113376. doi: 10.1016/j.intimp.2024.113376. Epub 2024 Oct 14.

Abstract

Heat stress (HS) induces various pathophysiological responses in the brain, encompassing neuroinflammation and cognitive impairments. Although taurine has been reported to possess anti-inflammatory and cognitive-enhancing properties, its role and mechanisms in HS-induced cognitive impairment remain unclear. This study supplemented mice exposed to HS with taurine to assess its effect on cognitive function in a HS-induced mouse model. The results revealed that taurine ameliorated cognitive deficits following HS in mice and mitigated HS-induced astrocyte and microglia activation as well as blood-brain barrier (BBB) damage in the hippocampus. Mechanistically, Mechanistically, transcriptome sequencing was employed to identify that taurine regulates neuronal PAS domain protein (Npas4) and lipocalin 2 (Lcn2) during HS. Taurine was found to modulate hippocampal inflammation and influence cognitive function by upregulating Npas4 and downregulating Lcn2 after HS. Subsequently, molecular docking and AnimalTFDB database calculations were conducted, revealing that taurine might regulate the expression of Npas4 and Lcn2 by modulating the regulatory transcription factors (TFs) RE1 silencing transcription factor (REST) and nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NFKB1). Our findings demonstrate that taurine enhances the recovery of cognitive function through Npas4 and Lcn2 following HS, providing a theoretical basis for the clinical application of taurine in preventing or treating HS-induced cognitive impairment.

Keywords: Cognitive impairment; Heat stress; Inflammation; Taurine; Transcription factor.

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Basic Helix-Loop-Helix Transcription Factors* / genetics
  • Basic Helix-Loop-Helix Transcription Factors* / metabolism
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Cognitive Dysfunction* / drug therapy
  • Cognitive Dysfunction* / etiology
  • Cognitive Dysfunction* / metabolism
  • Disease Models, Animal
  • Heat-Shock Response / drug effects
  • Hippocampus* / drug effects
  • Hippocampus* / metabolism
  • Lipocalin-2* / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Microglia / drug effects
  • Microglia / metabolism
  • Neuroinflammatory Diseases / drug therapy
  • Neuroinflammatory Diseases / immunology
  • Taurine* / pharmacology
  • Taurine* / therapeutic use

Substances

  • Taurine
  • Lipocalin-2
  • Lcn2 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Npas4 protein, mouse