Astrocyte-derived adenosine modulates increased sleep pressure during inflammatory response

Agnes Nadjar, Tamara Blutstein, Agnes Aubert, Sophie Laye, Philip G. Haydon
Glia. 2013-02-04; 61(5): 724-731
DOI: 10.1002/glia.22465

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1. Glia. 2013 May;61(5):724-31. doi: 10.1002/glia.22465. Epub 2013 Feb 4.

Astrocyte-derived adenosine modulates increased sleep pressure during
inflammatory response.

Nadjar A(1), Blutstein T, Aubert A, Laye S, Haydon PG.

Author information:
(1)Laboratory of Nutrition and Integrative Neurobiology, University of Bordeaux,
UMR 1286, Bordeaux, France.

Activation of the immune system elicits several behavioral changes collectively
called sickness. Among the behavioral changes, systemic infections induce an
increase in time spent in nonrapid-eye-movement (NREM) sleep and an increase of
slow wave activity (or « sleep pressure »). Using an inducible, astrocyte-specific
transgenic dominant negative SNARE (dnSNARE) mouse line we recently demonstrated
that gliotransmission plays an important role in sleep homeostasis through an
adenosine receptor 1 (A1R)-sensitive pathway. It has been hypothesized that
systemic infection, mimicked by peripheral administration of lipopolysaccharide
(LPS), increases sleeping behavior in part through upregulation of central
adenosine levels. Moreover, as a source of immunologically relevant factors,
astrocytes play a pivotal role in the central nervous system immune and
inflammatory responses. However, little is known about the role of astrocytes in
the CNS response to a peripheral immune challenge. We hypothesize that LPS
impacts sleep homeostasis through the modulation of astrocyte-derived adenosine
accumulation. We therefore used dnSNARE mice to determine whether astrocytes
contribute to the increased sleep pressure under immune challenge and whether
this is a result of changes in adenosine signaling. We demonstrate that
dnSNARE-mediated gliotransmission is required for the ability of LPS to elevate
sleep pressure as measured by the power of slow wave activity during NREM sleep.
Moreover, in agreement with a role of astrocyte-derived adenosine in modulating
sleep homeostasis, we find that intracerebroventricular infusion of the A1R
antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT) mimics this dnSNARE
phenotype. Taken together, our data demonstrate that astrocytic adenosine acting
through A1 receptors contributes to the modulation of sleep pressure by LPS.

Copyright © 2013 Wiley Periodicals, Inc.

DOI: 10.1002/glia.22465
PMID: 23378051 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus