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PMID: 22589743 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Loss of Gnas imprinting differentially affects REM/NREM sleep and cognition in mice.

PLoS genetics ·Vol. 8 ·No. 5 ·2012-00-00 ·Pages e1002706

Lassi G, Ball ST, Maggi S, Colonna G, Nieus T, Cero C, Bartolomucci A, Peters J, Tucci V

Abstract

It has been suggested that imprinted genes are important in the regulation of sleep. However, the fundamental question of whether genomic imprinting has a role in sleep has remained elusive up to now. In this work we show that REM and NREM sleep states are differentially modulated by the maternally expressed imprinted gene Gnas. In particular, in mice with loss of imprinting of Gnas, NREM and complex cognitive processes are enhanced while REM and REM-linked behaviors are inhibited. This is the first demonstration that a specific overexpression of an imprinted gene affects sleep states and related complex behavioral traits. Furthermore, in parallel to the Gnas overexpression, we have observed an overexpression of Ucp1 in interscapular brown adipose tissue (BAT) and a significant increase in thermoregulation that may account for the REM/NREM sleep phenotypes. We conclude that there must be significant evolutionary advantages in the monoallelic expression of Gnas for REM sleep and for the consolidation of REM-dependent memories. Conversely, biallelic expression of Gnas reinforces slow wave activity in NREM sleep, and this results in a reduction of uncertainty in temporal decision-making processes.

MeSH Terms
Adipose Tissue, Brown Alleles Animals Body Temperature Body Temperature Regulation/genetics,physiology Chromogranins Cognition/physiology DNA Methylation Electroencephalography Exons GTP-Binding Protein alpha Subunits, Gs/genetics,physiology Gene Expression Regulation Genomic Imprinting Ion Channels Mice Mitochondrial Proteins Sequence Deletion Sleep, REM/genetics,physiology Uncoupling Protein 1 Wakefulness
Chemicals
Chromogranins Ion Channels Mitochondrial Proteins Ucp1 protein, mouse Uncoupling Protein 1 Gnas protein, mouse GTP-Binding Protein alpha Subunits, Gs
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Lassi Glenda
Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy.
Ball Simon T
Maggi Silvia
Colonna Giovanni
Nieus Thierry
Cero Cheryl
Bartolomucci Alessandro
Peters Jo
Tucci Valter
Conflict of Interest

The authors have declared that no competing interests exist.

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Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
Published
2012-00-00
Epub
2012-00-10
Pages
e1002706
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC3349741
Subset
IM
Grants
Medical Research Council · MC_U142636336 · United Kingdom
NIDDK NIH HHS · P30 DK050456 · United States
NIDDK NIH HHS · NIH DK050456 · United States
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