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Featured ArticleResearch Articles, Neurobiology of Disease

Sleeping Sickness Disrupts the Sleep-Regulating Adenosine System

Filipa Rijo-Ferreira, Theresa E. Bjorness, Kimberly H. Cox, Alex Sonneborn, Robert W. Greene and Joseph S. Takahashi
Journal of Neuroscience 25 November 2020, 40 (48) 9306-9316; DOI: https://doi.org/10.1523/JNEUROSCI.1046-20.2020
Filipa Rijo-Ferreira
1Department of Neuroscience, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111
2Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111
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Theresa E. Bjorness
3Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111
4Research Service, VA North Texas Health Care System, Dallas, Texas 75216-7167
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Kimberly H. Cox
1Department of Neuroscience, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111
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Alex Sonneborn
1Department of Neuroscience, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111
3Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111
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Robert W. Greene
1Department of Neuroscience, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111
3Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111
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Joseph S. Takahashi
1Department of Neuroscience, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111
2Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111
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Abstract

Patients with sleeping sickness, caused by the parasite Trypanosoma brucei, have disruptions in both sleep timing and sleep architecture. However, the underlying cause of these sleep disturbances is not well understood. Here, we assessed the sleep architecture of male mice infected with T. brucei and found that infected mice had drastically altered sleep patterns. Interestingly, T. brucei-infected mice also had a reduced homeostatic sleep response to sleep deprivation, a response modulated by the adenosine system. We found that infected mice had a reduced electrophysiological response to an adenosine receptor antagonist and increased adenosine receptor gene expression. Although the mechanism by which T. brucei infection causes these changes remains to be determined, our findings suggest that the symptoms of sleeping sickness may be because of alterations in homeostatic adenosine signaling.

SIGNIFICANCE STATEMENT Sleeping sickness is a fatal disease that disrupts the circadian clock, causes disordered temperature regulation, and induces sleep disturbance. To examine the neurologic effects of infection in the absence of other symptoms, in this study, we used a mouse model of sleeping sickness in which the acute infection was treated but brain infection remained. Using this model, we evaluated the effects of the sleeping sickness parasite, Trypanosoma brucei, on sleep patterns in mice, under both normal and sleep-deprived conditions. Our findings suggest that signaling of adenosine, a neuromodulator involved in mediating homeostatic sleep drive, may be reduced in infected mice.

  • adenosine
  • homeostasis
  • sleep
  • sleeping sickness

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The Journal of Neuroscience: 40 (48)
Journal of Neuroscience
Vol. 40, Issue 48
25 Nov 2020
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Sleeping Sickness Disrupts the Sleep-Regulating Adenosine System
Filipa Rijo-Ferreira, Theresa E. Bjorness, Kimberly H. Cox, Alex Sonneborn, Robert W. Greene, Joseph S. Takahashi
Journal of Neuroscience 25 November 2020, 40 (48) 9306-9316; DOI: 10.1523/JNEUROSCI.1046-20.2020

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Sleeping Sickness Disrupts the Sleep-Regulating Adenosine System
Filipa Rijo-Ferreira, Theresa E. Bjorness, Kimberly H. Cox, Alex Sonneborn, Robert W. Greene, Joseph S. Takahashi
Journal of Neuroscience 25 November 2020, 40 (48) 9306-9316; DOI: 10.1523/JNEUROSCI.1046-20.2020
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Keywords

  • adenosine
  • homeostasis
  • sleep
  • sleeping sickness

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