Faculty Collaboration Database

Suprachiasmatic astrocytes modulate the circadian clock in response to TNF-α. J Immunol 2013 Nov 01;191(9):4656-64

Date

09/26/2013

Pubmed ID

24062487

Pubmed Central ID

PMC3811024

DOI

10.4049/jimmunol.1300450

Scopus ID

2-s2.0-84885987780 (requires institutional sign-in at Scopus site)   53 Citations

Abstract

The immune and the circadian systems interact in a bidirectional fashion. The master circadian oscillator, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, responds to peripheral and local immune stimuli, such as proinflammatory cytokines and bacterial endotoxin. Astrocytes exert several immune functions in the CNS, and there is growing evidence that points toward a role of these cells in the regulation of circadian rhythms. The aim of this work was to assess the response of SCN astrocytes to immune stimuli, particularly to the proinflammatory cytokine TNF-α. TNF-α applied to cultures of SCN astrocytes from Per2(luc) knockin mice altered both the phase and amplitude of PER2 expression rhythms, in a phase-dependent manner. Furthermore, conditioned media from SCN astrocyte cultures transiently challenged with TNF-α induced an increase in Per1 expression in NIH 3T3 cells, which was blocked by TNF-α antagonism. In addition, these conditioned media could induce phase shifts in SCN PER2 rhythms and, when administered intracerebroventricularly, induced phase delays in behavioral circadian rhythms and SCN activation in control mice, but not in TNFR-1 mutants. In summary, our results show that TNF-α modulates the molecular clock of SCN astrocytes in vitro, and also that, in response to this molecule, SCN astrocytes can modulate clock gene expression in other cells and tissues, and induce phase shifts in a circadian behavioral output in vivo. These findings suggest a role for astroglial cells in the alteration of circadian timing by immune activation.

Author List

Duhart JM, Leone MJ, Paladino N, Evans JA, Castanon-Cervantes O, Davidson AJ, Golombek DA

Author

Jennifer A. Evans PhD Assistant Professor in the Biomedical Sciences department at Marquette University

MESH terms used to index this publication - Major topics in bold

Animals
Astrocytes
Cell Line
Circadian Clocks
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
NIH 3T3 Cells
Period Circadian Proteins
Receptors, Tumor Necrosis Factor, Type I
Suprachiasmatic Nucleus
Tumor Necrosis Factor-alpha