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.
Subject(s)
Brain/physiology , Circumventricular Organs/physiology , Neural Stem Cells/drug effects , Thermogenesis/physiology , Toll-Like Receptor 4/physiology , Animals , Astrocytes/drug effects , Astrocytes/metabolism , Brain/drug effects , Circumventricular Organs/cytology , Circumventricular Organs/drug effects , 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/physiology , Peptides/pharmacology , Proto-Oncogene Proteins c-fos/biosynthesis , Proto-Oncogene Proteins c-fos/genetics , Thermogenesis/drug effects , Toll-Like Receptor 4/antagonists & inhibitors , Toll-Like Receptor 4/biosynthesisABSTRACT
Evidence have been accumulated that continuous oligodendrogenesis occurs in the adult mammalian brain. The fornix, projection and commissure pathway of hippocampal neurons, carries signals from the hippocampus to other parts of the brain and has critical role in memory and learning. However, basic characterization of adult oligodendrogenesis in this brain region is not well understood. In the present study, therefore, we aimed to examine the proliferation and differentiation of oligodendrocyte progenitor cells (OPCs) and the effect of acute inflammatory stimulation on oligodendrogenesis in the fornix of adult mouse. We demonstrated the proliferation of OPCs and a new generation of mature oligodendrocytes by using bromodeoxyuridine and Ki67 immunohistochemistry. Oligodendrogenesis of adult fornix was also demonstrated by using oligodendrocyte transcription factor 2 transgenic mouse. A single systemic administration of lipopolysaccharide (LPS) attenuated proliferation of OPCs in the fornix together with reduced proliferation of hippocampal neural stem/progenitor cells. Time course analysis showed that a single administration of LPS attenuated the proliferation of OPCs during 24-48 h. On the other hand, consecutive administration of LPS did not suppress proliferation of OPCs. The treatment of LPS did not affect differentiation of OPCs into mature oligodendrocytes. Treatment of a microglia inhibitor minocycline significantly attenuated basal proliferation of OPCs under normal condition. In conclusion, the present study indicates that continuous oligodendrogenesis occurs and a single administration of LPS transiently attenuates proliferation of OPCs without changing differentiation in the fornix of the adult mouse brains.