Clock gene expression during chronic inflammation induced by infection with Trypanosoma brucei brucei in rats.

Authors:
Michael T Sellix
Michael T Sellix
Florida State University
United States
Erin Davis
Erin Davis
University of Oklahoma Health Sciences Center
United States
Krister Kristensson
Krister Kristensson
Karolinska Institutet
Gene D Block
Gene D Block
University of Virginia
United States

J Biol Rhythms 2010 Apr;25(2):92-102

Swedish Medical Nanoscience Center, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.

African sleeping sickness is characterized by alterations in rhythmic functions. It is not known if the disease affects the expression of clock genes, which are the molecular basis for rhythm generation. We used a chronic rat model of experimental sleeping sickness, caused by the extracellular parasite Trypanosoma brucei brucei (Tb brucei), to study the effects on clock gene expression. In tissue explants of pituitary glands from Period1-luciferase (Per1-luc) transgenic rats infected with Tb brucei, the period of Per1-luc expression was significantly shorter. In explants containing the suprachiasmatic nuclei (SCN), the Per1-luc rhythms were flat in 21% of the tissues. We also examined the relative expression of Per1, Clock, and Bmal1 mRNA in the SCN, pineal gland, and spleen from control and infected rats using qPCR. Both Clock and Bmal1 mRNA expression was reduced in the pineal gland and spleen following Tb brucei infection. Infected rats were periodic both in core body temperature and in locomotor activity; however, early after infection, we observed a significant decline in the amplitude of the locomotor activity rhythm. In addition, both activity and body temperature rhythms exhibited decreased regularity and "robustness." In conclusion, although experimental trypanosome infection has previously been shown to cause functional disturbances in SCN neurons, only 21% of the SCN explants had disturbed Per1-luc rhythms. However, our data show that the infection overall alters molecular clock function in peripheral clocks including the pituitary gland, pineal gland, and spleen.

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http://dx.doi.org/10.1177/0748730409360963DOI Listing
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April 2010
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References

(Supplied by CrossRef)
Article in Physiol Rev
Freeman ME et al.
Physiol Rev 2000

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