Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (UMR5287)

Aquitaine Institute for Cognitive and Integrative Neuroscience



INCIA - UMR 5287- CNRS
Université de Bordeaux

Zone nord Bat 2 2ème étage
146, rue Léo Saignat
33076 Bordeaux cedex
France

Téléphone 05.57.57.15.51
Télécopie 05.56.90.14.21

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CNRS Ecole Pratique des Hautes Etudes Université de Bordeaux

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Neurocampus Unitéde Formation de Biologie

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Home > Latest publications

Neurophysiological and Behavioral Effects of Anti-Orexinergic Treatments in a Mouse Model of Huntington’s Disease. Neurotherapeutics. Volume 10, Number 3, 2019 Magali Cabanas, Maurice Garret et Yoon Cho

by Loïc Grattier - published on , updated on

Cabanas et al.
Huntington’s disease (HD) is associated with sleep and circadian disturbances in addition to hallmark motor and cognitive impairments. Electrophysiological studies on HD mouse models have revealed an aberrant oscillatory activity at the beta frequency, during sleep, that is associated with HD pathology. Moreover, HD animal models display an abnormal sleep–wake cycle and sleep fragmentation. In this study, we investigated a potential involvement of the orexinergic system dysfunctioning in sleep–wake and circadian disturbances and abnormal network (i.e., beta) activity in the R6/1 mouse model. We found that the age at which orexin activity starts to deviate from normal activity pattern coincides with that of sleep disturbances as well as the beta activity. We also found that acute administration of Suvorexant, an orexin 1 and orexin 2 receptor antagonist, was sufficient to decrease the beta power significantly and to improve sleep in R6/1 mice. In addition, a 5-day treatment paradigm alleviated cognitive deficits and induced a gain of body weight in female HD mice. These results suggest that restoring normal activity of the orexinergic system could be an efficient therapeutic solution for sleep and behavioral disturbances in HD.