CD40 activation induces NREM sleep and modulates genes associated with sleep homeostasis

Gast, Heidemarie; Müller, Andreas; Lopez, Martin; Meier, Daniel; Huber, Reto; Dechent, Frieder; Prinz, Marco; Emmenegger, Yann; Franken, Paul; Birchler, Thomas; Fontana, Adriano (2013). CD40 activation induces NREM sleep and modulates genes associated with sleep homeostasis. Brain, behavior, and immunity, 27(1), pp. 133-144. Elsevier 10.1016/j.bbi.2012.10.004

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The T-cell derived cytokine CD40 ligand is overexpressed in patients with autoimmune diseases. Through activation of its receptor, CD40 ligand leads to a tumor necrosis factor (TNF) receptor 1 (TNFR1) dependent impairment of locomotor activity in mice. Here we report that this effect is explained through a promotion of sleep, which was specific to non-rapid eye movement (NREM) sleep while REM sleep was suppressed. The increase in NREM sleep was accompanied by a decrease in EEG delta power during NREM sleep and by a decrease in the expression of transcripts in the cerebral cortex known to be associated with homeostatic sleep drive, such as Homer1a, Early growth response 2, Neuronal pentraxin 2, and Fos-like antigen 2. The effect of CD40 activation was mimicked by peripheral TNF injection and prevented by the TNF blocker etanercept. Our study indicates that sleep-wake dysregulation in autoimmune diseases may result from CD40 induced TNF:TNFR1 mediated alterations of molecular pathways, which regulate sleep-wake behavior.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology

UniBE Contributor:

Gast, Heidemarie


600 Technology > 610 Medicine & health








Valentina Rossetti

Date Deposited:

16 Jun 2014 12:56

Last Modified:

29 Oct 2015 12:08

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

Sickness behavior, Depression, Multiple sclerosis, Rheumatoid arthritis, Inflammatory bowel disease, AIDS, Human immunodeficiency virus (HIV), Brain endothelial cells, Microglia




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