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.
Copyright © 2018 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Astrocytes / drug effects
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Astrocytes / metabolism
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Brain / drug effects
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Brain / physiology*
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Circumventricular Organs / cytology
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Circumventricular Organs / drug effects
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Circumventricular Organs / physiology*
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Enzyme Inhibitors / pharmacology
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Fever / chemically induced
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Fever / physiopathology
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Injections, Intraventricular
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Lipopolysaccharides / toxicity
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Male
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Mice
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Mice, Inbred ICR
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Microglia / drug effects
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Microglia / metabolism
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NF-kappa B / metabolism
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Nerve Tissue Proteins / biosynthesis
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Nerve Tissue Proteins / genetics
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Neural Stem Cells / drug effects*
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Neural Stem Cells / physiology
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Peptides / pharmacology
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Proto-Oncogene Proteins c-fos / biosynthesis
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Proto-Oncogene Proteins c-fos / genetics
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Thermogenesis / drug effects
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Thermogenesis / physiology*
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Toll-Like Receptor 4 / antagonists & inhibitors
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Toll-Like Receptor 4 / biosynthesis
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Toll-Like Receptor 4 / physiology*
Substances
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Enzyme Inhibitors
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Lipopolysaccharides
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NF-kappa B
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Nerve Tissue Proteins
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Peptides
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Proto-Oncogene Proteins c-fos
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Tlr4 protein, mouse
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Toll-Like Receptor 4