Sleep and Rhythm Changes at the Time of Trypanosoma brucei Invasion of the Brain Parenchyma in the Rat

Abstract

Human African trypanosomiasis (HAT), or sleeping sickness, is a severe disease caused by Trypanosoma brucei (T.b.). The disease hallmark is sleep alterations. Brain involvement in HAT is a crucial pathogenetic step for disease diagnosis and therapy. In this study, a rat model of African trypanosomiasis was used to assess changes of sleep-wake, rest-activity, and body temperature rhythms in the time window previously shown as crucial for brain parenchyma invasion by T.b. to determine potential biomarkers of this event. Chronic radiotelemetric monitoring in Sprague-Dawley rats was used to continuously record electroencephalogram, electromyogram, rest-activity, and body temperature in the same animals before (baseline recording) and after infection. Rats were infected with T.b. brucei. Data were acquired from 1 to 20 d after infection (parasite neuroinvasion initiates at 11–13 d post-infection in this model), and were compared to baseline values. Sleep parameters were manually scored from electroencephalographic-electromyographic tracings. Circadian rhythms of sleep time, slow-wave activity, rest-activity, and body temperature were studied using cosinor rhythmometry. Results revealed alterations of most of the analyzed parameters. In particular, sleep pattern and sleep-wake organization plus rest-activity and body temperature rhythms exhibited early quantitative and qualitative alterations, which became marked around the time interval crucial for parasite neuroinvasion or shortly after. Data derived from actigrams showed close correspondence with those from hypnograms, suggesting that rest-activity could be useful to monitor sleep-wake alterations in African trypanosomiasis. (Author correspondence: [email protected])

Keywords:

• Actigram
• African trypanosomiasis
• Brain infection
• Circadian rhythms
• Electroencephalography
• Hypnogram
• Meningoencephalitis
• Polysomnography
• Sleeping sickness

ACKNOWLEDGMENTS

This study was supported by grants of the Wellcome Trust (grant number WT089992MA) and NIH/Fogarty (grant number 1R21NS064888-01A1). The authors thank Antonio Pozzo and Alessio Cangemi for their advice on spectral and statistical analyses.

Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.