O'Keefe, S.M. and Beynon, A.L. and Davies, J.S. and Moynagh, Paul N. and Coogan, Andrew (2017) NF‐κB signalling is involved in immune‐modulation, but not basal functioning, of the mouse suprachiasmatic circadian clock. European Journal of Neuroscience, 45 (8). pp. 1111-1123. ISSN 1460-9568

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Abstract

Circadian rhythms are recurring near‐24 hour patterns driven by an endogenous circadian timekeeping system. The master pacemaker in this system is the hypothalamic suprachiasmatic nucleus (SCN). Recently interest has been drawn to how the SCN clock responds to immune system stimulation. A major signalling component in the immune system is nuclear factor (NF)‐κB. In the present study we examined the role of NF‐κB in SCN function. Whilst serum shocked fibroblasts showed rhythmic nuclear localisation of p65 and p65‐dependent transcription, there were no circadian changes in the SCN in expression of the NF‐κB components p65, c‐Rel, p‐IκB or p‐IKK. Chronic treatment with the NF‐κB inhibitor PDTC did not impact on circadian or diurnal rhythms. Phase‐shifting light pulses did not impact on SCN expression of p65, and PDTC treatment did not attenuate the behavioural or molecular response to light pulses. Peripheral treatment with lipopolysaccharide resulted in increased NF‐κB component expression in the SCN. In vitro experiments with SCN slice cultures showed that treatment with NF‐κB inhibitors did not markedly alter rhythmic changes in PER2::LUC expression. Further, SCN slices from nf‐κb::luc mice did not show any evidence for circadian rhythms in NF‐κB‐mediated transcription. Experiments utilising older mice (~16 months old) showed that SCN treatment in vitro with PDTC resulted in increased amplitude of rhythmic PER2::LUC expression, and LPS treatment resulted in altered PER2::LUC rhythm acrophase. Overall, we interpret our results as providing evidence for the involvement of NF‐κB in the suprachiasmatic circadian clock following immune stimulation, but not under basal conditions.

Item Type:	Article
Keywords:	ageing; circadian; neuroimmune; NF‐κB; PER2; suprachiasmatic;
Academic Unit:	Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Research Institutes > Human Health Institute
Item ID:	11045
Identification Number:	https://doi.org/10.1111/ejn.13553
Depositing User:	Professor Paul Moynagh
Date Deposited:	16 Sep 2019 15:43
Journal or Publication Title:	European Journal of Neuroscience
Publisher:	Wiley-Blackwell Publishing Ltd.
Refereed:	Yes
Funders:	Science Foundation Ireland (SFI)
URI:	https://onlinelibrary.wiley.com
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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