Sleep disturbance in clinical and preclinical scrapie-infected sheep measured by polysomnography

Abstract

Neurodegenerative diseases are characterised by neuronal loss and abnormal deposition of pathological proteins in the nervous system. Among the most common neurodegenerative diseases are Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease and transmissible spongiform encephalopathies (TSEs). Sleep and circadian rhythm disturbances are one of the most common symptoms in patients with neurodegenerative diseases. Currently, one of the main objectives in the study of TSEs is to try to establish an early diagnosis, as clinical signs do not appear until the damage to the central nervous system is very advanced, which prevents any therapeutic approach. In this paper, we provide the first description of sleep disturbance caused by classical scrapie in clinical and preclinical sheep using polysomnography compared to healthy controls. Fifteen sheep classified into three groups, clinical, preclinical and negative control, were analysed. The results show a decrease in total sleep time as the disease progresses, with significant changes between control, clinical and pre-clinical animals. The results also show an increase in sleep fragmentation in clinical animals compared to preclinical and control animals. In addition, sheep with clinical scrapie show a total loss of Rapid Eye Movement sleep (REM) and alterations in Non Rapid Eyes Movement sleep (NREM) compared to control sheep, demonstrating more shallow sleep. Although further research is needed, these results suggest that prion diseases also produce sleep disturbances in animals and that polysomnography could be a diagnostic tool of interest in clinical and preclinical cases of prion diseases.

Keywords:

• Prion
• neurodegenerative diseases
• TSE
• sleep disorders
• sheep

Author contributions

The conception and design of the study were carried out by CA. data acquisition was carried out by DS and BM. Data analysis was carried out by JF, ES and DS. the writing of the manuscript was carried out by DS as well as the figures. All authors contributed with the writing of various parts of the paper and editing.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethical approval

All animal experiments were approved by the Ethics Committee for Animal Experiments of the University of Zaragoza (permit number PI17/21).

Data availability statement

The data presented in this study are available within the article text and figures.

Additional information

Funding

DS was supported by a doctoral grant from the Aragon Government. This research received no external funding neither to be published neither to be performed. This work was partially financed by reference group A19-20R funded by the Government of Aragón co-financed with FEDER 2014-2020 and the European Regional Development Fund (ERDF). This work was partially financed by reference group A05_20R Enfermedades Priónicas, Vectoriales y Zoonosis Emergentes.