Circadian rhythm disruption in a mouse model of Rett syndrome circadian disruption in RTT

Quan Li; Dawn H. Loh; Takashi Kudo; Danny Truong; Matthew Derakhshesh; Zoë MacDowell Kaswan; Cristina A. Ghiani; Rosemarie Tsoa; Yin Cheng; Yi E. Sun; Christopher S. Colwell

Neurobiology of Disease (May 2015)

Circadian rhythm disruption in a mouse model of Rett syndrome circadian disruption in RTT

Quan Li,
Dawn H. Loh,
Takashi Kudo,
Danny Truong,
Matthew Derakhshesh,
Zoë MacDowell Kaswan,
Cristina A. Ghiani,
Rosemarie Tsoa,
Yin Cheng,
Yi E. Sun,
Christopher S. Colwell

Affiliations

Quan Li: Laboratory of Circadian and Sleep Medicine, Department of Psychiatry, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles 90095-1759, USA; Department of Psychiatry, University of California, Los Angeles, Box 957332, 635 S. Charles E. Young Dr, Los Angeles, CA 90095-7332, USA; Molecular, Cellular and Integrative Physiology Program, University of California, Los Angeles, Los Angeles, CA 90095, USA
Dawn H. Loh: Laboratory of Circadian and Sleep Medicine, Department of Psychiatry, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles 90095-1759, USA
Takashi Kudo: Laboratory of Circadian and Sleep Medicine, Department of Psychiatry, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles 90095-1759, USA
Danny Truong: Laboratory of Circadian and Sleep Medicine, Department of Psychiatry, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles 90095-1759, USA
Matthew Derakhshesh: Laboratory of Circadian and Sleep Medicine, Department of Psychiatry, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles 90095-1759, USA
Zoë MacDowell Kaswan: Laboratory of Circadian and Sleep Medicine, Department of Psychiatry, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles 90095-1759, USA
Cristina A. Ghiani: Laboratory of Circadian and Sleep Medicine, Department of Psychiatry, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles 90095-1759, USA
Rosemarie Tsoa: Department of Psychiatry, University of California, Los Angeles, Box 957332, 635 S. Charles E. Young Dr, Los Angeles, CA 90095-7332, USA
Yin Cheng: Department of Psychiatry, University of California, Los Angeles, Box 957332, 635 S. Charles E. Young Dr, Los Angeles, CA 90095-7332, USA
Yi E. Sun: Department of Psychiatry, University of California, Los Angeles, Box 957332, 635 S. Charles E. Young Dr, Los Angeles, CA 90095-7332, USA; Corresponding authors.
Christopher S. Colwell: Laboratory of Circadian and Sleep Medicine, Department of Psychiatry, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles 90095-1759, USA; Corresponding authors.

Journal volume & issue: Vol. 77
pp. 155 – 164

Abstract

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Disturbances in the sleep/wake cycle are prevalent in patients with Rett syndrome (RTT). We sought to determine whether the circadian system is disrupted in a RTT model, Mecp2−/y mice. We found that MeCP2 mutants showed decreased strength and precision of daily rhythms of activity coupled with extremely fragmented sleep. The central circadian clock (suprachiasmatic nucleus) exhibited significant reduction in the number of neurons expressing vasoactive intestinal peptide (VIP) as well as compromised spontaneous neural activity. The molecular clockwork was disrupted both centrally in the SCN and in peripheral organs, indicating a general disorganization of the circadian system. Disruption of the molecular clockwork was observed in fibroblasts of RTT patients. Finally, MeCP2 mutant mice were vulnerable to circadian disruption as chronic jet lag accelerated mortality. Our finds suggest an integral role of MeCP2 in the circadian timing system and provides a possible mechanistic explanation for the sleep/wake distrubances observed in RTT patients. The work raises the possibility that RTT patients may benefit from a temporally structured environment.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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