Brain Behav Immun; co-auth: group Franken

Brain Behav Immun. 2012 Oct 13. pii: S0889-1591(12)00466-7. doi: 10.1016/j.bbi.2012.10.004. [Epub ahead of print]

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


Department of Neurology, Inselspital, University Hospital Berne, University of Bern, Bern, Switzerland.


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.

Copyright © 2012. Published by Elsevier Inc.