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.

Download full-text PDF

Source
http://dx.doi.org/10.1177/0748730409360963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897063PMC
April 2010
12 Reads

Publication Analysis

Top Keywords

gland spleen
12
pineal gland
12
brucei brucei
12
infected rats
8
bmal1 mrna
8
clock bmal1
8
locomotor activity
8
sleeping sickness
8
clock gene
8
per1-luc rhythms
8
gene expression
8
body temperature
8
trypanosoma brucei
8
brucei
7
clock
6
expression
6
infection
5
mrna scn
4
scn pineal
4
gland
4

Similar Publications

Circadian profile of Per gene mRNA expression in the suprachiasmatic nucleus, paraventricular nucleus, and pineal body of aged rats.

J Neurosci Res 2001 Dec;66(6):1133-9

Department of Pharmacology and Brain Science, School of Human Sciences, Waseda University, 2-5879-15 Mikajima, Tokorozawa, Saitama 359-1192, Japan.

Aging alters circadian components such as the free-running period, the day-to-night activity ratio and photic entrainment in behavioral rhythms, and 2-deoxyglucose uptakes and neuronal firing in the suprachiasmatic nucleus (SCN). A core clock mechanism in the mouse SCN appears to involve a transcriptional feedback loop in which Period (Per) and Cryptochrome (Cry) genes play a role in negative feedback. The circadian rhythm systems include photic entrainment, clock oscillation, and outputs of clock information such as melatonin production. Read More

View Article
December 2001

Divergent roles of clock genes in retinal and suprachiasmatic nucleus circadian oscillators.

PLoS One 2012 11;7(6):e38985. Epub 2012 Jun 11.

Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, United States of America.

The retina is both a sensory organ and a self-sustained circadian clock. Gene targeting studies have revealed that mammalian circadian clocks generate molecular circadian rhythms through coupled transcription/translation feedback loops which involve 6 core clock genes, namely Period (Per) 1 and 2, Cryptochrome (Cry) 1 and 2, Clock, and Bmal1 and that the roles of individual clock genes in rhythms generation are tissue-specific. However, the mechanisms of molecular circadian rhythms in the mammalian retina are incompletely understood and the extent to which retinal neural clocks share mechanisms with the suprachiasmatic nucleus (SCN), the central neural clock, is unclear. Read More

View Article
November 2012

Daily torpor alters multiple gene expression in the suprachiasmatic nucleus and pineal gland of the Djungarian hamster (Phodopus sungorus).

Chronobiol Int 2006 ;23(1-2):269-76

Département de Neurobiologie des Rythme, Institut des Neurosciences Cellulaires et Intégratives, Université Louis Pasteur, IFR des Neurosciences de Strasbourg, France.

Circadian rhythms are still expressed in animals that display daily torpor, implying a temperature compensation of the pacemaker. Nevertheless, it remains unclear how the clock works in hypothermic states and whether torpor itself, as a temperature pulse, affects the circadian system. To reveal changes in the clockwork during torpor, we compared clock gene and neuropeptide expression by in situ hybridization in the suprachiasmatic nucleus (SCN) and pineal gland of normothermic and torpid Djungarian hamsters (Phodopus sungorus). Read More

View Article
August 2006

Effects of aging on central and peripheral mammalian clocks.

Proc Natl Acad Sci U S A 2002 Aug 29;99(16):10801-6. Epub 2002 Jul 29.

National Science Foundation Center for Biological Timing and Department of Biology, University of Virginia, Charlottesville, VA 22904-4328, USA.

Circadian organization changes with age, but we do not know the extent to which age-related changes are the result of alterations in the central pacemakers, the peripheral oscillators, or the coupling mechanisms that hold the system together. By using transgenic rats with a luciferase (luc) reporter, we assessed the effects of aging on the rhythm of expression of the Period 1 (Per1) gene in the suprachiasmatic nucleus (SCN) and in peripheral tissues. Young (2 months) and aged (24-26 months) Per1-luc transgenic rats, entrained to light-dark cycles, were killed, and tissues were removed and cultured. Read More

View Article
August 2002