TLR4 in circumventricular neural stem cells is a negative regulator for thermogenic pathways in the mouse brain

J Neuroimmunol. 2019 Jun 15:331:58-73. doi: 10.1016/j.jneuroim.2018.04.017. Epub 2018 May 3.

Abstract

Toll-like receptor 4 (TLR4) recognizes bacteria-derived lipopolysaccharide (LPS). In the present study, we found that intraperitoneal LPS activated nuclear factor-κ B (NF-κB) in TLR4-expressing neural stem cells (NSCs) in the circumventricular brain regions of mice. Intracerebroventricular preadministration of low-dose TLR4 inhibitors significantly augmented hyperthermia together with the inhibition of NF-κB activation in circumventricular NSCs of LPS-inflamed animals. Moreover, intracerebroventricular administration of high-dose TLR4 inhibitors induced hyperthermia and Fos activation in circumventricular NSCs and hypothalamic neurons. These results suggest that TLR4 on circumventricular NSCs functions as a central regulator for thermogenesis under inflamed and normal conditions.

Keywords: Circumventricular organs; Fever; Fos; Inflammation; NF-κB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Brain / drug effects
  • Brain / physiology*
  • Circumventricular Organs / cytology
  • Circumventricular Organs / drug effects
  • Circumventricular Organs / physiology*
  • Enzyme Inhibitors / pharmacology
  • Fever / chemically induced
  • Fever / physiopathology
  • Injections, Intraventricular
  • Lipopolysaccharides / toxicity
  • Male
  • Mice
  • Mice, Inbred ICR
  • Microglia / drug effects
  • Microglia / metabolism
  • NF-kappa B / metabolism
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Neural Stem Cells / drug effects*
  • Neural Stem Cells / physiology
  • Peptides / pharmacology
  • Proto-Oncogene Proteins c-fos / biosynthesis
  • Proto-Oncogene Proteins c-fos / genetics
  • Thermogenesis / drug effects
  • Thermogenesis / physiology*
  • Toll-Like Receptor 4 / antagonists & inhibitors
  • Toll-Like Receptor 4 / biosynthesis
  • Toll-Like Receptor 4 / physiology*

Substances

  • Enzyme Inhibitors
  • Lipopolysaccharides
  • NF-kappa B
  • Nerve Tissue Proteins
  • Peptides
  • Proto-Oncogene Proteins c-fos
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4