TY - JOUR
T1 - Sleeping sickness is a circadian disorder
AU - Rijo-Ferreira, Filipa
AU - Carvalho, Tânia
AU - Afonso, Cristina
AU - Sanches-Vaz, Margarida
AU - Costa, Rui M.
AU - Figueiredo, Luísa M.
AU - Takahashi, Joseph S.
N1 - Funding Information:
We thank Chryshanthi Joseph and Victoria Acosta Rodriguez for help during the implant surgeries of the telemetry system, Lisa Thomas for breeding the PER2::LUC mice and monitoring mice during the end of the phase test experiment, Marleen de Groot and Jennifer Mohawk for training in Clock Lab and LumiCycle software analysis, Vanessa Zuzarte-Luis and Jeremy Stubblefield for help during the 24-h tissue collections, Shin Yamazaki for guidance and discussions of the behavioral experiments, Yoga Chelliah for help in purifying VSG, Yan Li, Iza Kornblum, and Nelly Garduño for assistance during fibroblasts and explant experiments, and Nelly Garduño for monitoring mice infected with Plasmodium chabaudi. Research was supported by the Howard Hughes Medical Institute (J.S.T.), by HHMI International Early Career Scientist (55007419) to L.M.F., and by Fundação para a Ciência e Tecnologia (SFRH/BD/51286/2010) to F.R.-F. J.S.T. is an Investigator and F.R.-F. is an Associate in the Howard Hughes Medical Institute.
Publisher Copyright:
© 2017 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Sleeping sickness is a fatal disease caused by Trypanosoma brucei, a unicellular parasite that lives in the bloodstream and interstitial spaces of peripheral tissues and the brain. Patients have altered sleep/wake cycles, body temperature, and endocrine profiles, but the underlying causes are unknown. Here, we show that the robust circadian rhythms of mice become phase advanced upon infection, with abnormal activity occurring during the rest phase. This advanced phase is caused by shortening of the circadian period both at the behavioral level as well as at the tissue and cell level. Period shortening is T. brucei specific and independent of the host immune response, as co-culturing parasites with explants or fibroblasts also shortens the clock period, whereas malaria infection does not. We propose that T. brucei causes an advanced circadian rhythm disorder, previously associated only with mutations in clock genes, which leads to changes in the timing of sleep.
AB - Sleeping sickness is a fatal disease caused by Trypanosoma brucei, a unicellular parasite that lives in the bloodstream and interstitial spaces of peripheral tissues and the brain. Patients have altered sleep/wake cycles, body temperature, and endocrine profiles, but the underlying causes are unknown. Here, we show that the robust circadian rhythms of mice become phase advanced upon infection, with abnormal activity occurring during the rest phase. This advanced phase is caused by shortening of the circadian period both at the behavioral level as well as at the tissue and cell level. Period shortening is T. brucei specific and independent of the host immune response, as co-culturing parasites with explants or fibroblasts also shortens the clock period, whereas malaria infection does not. We propose that T. brucei causes an advanced circadian rhythm disorder, previously associated only with mutations in clock genes, which leads to changes in the timing of sleep.
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U2 - 10.1038/s41467-017-02484-2
DO - 10.1038/s41467-017-02484-2
M3 - Article
C2 - 29302035
AN - SCOPUS:85040219939
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 62
ER -