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AMPK signaling linked to the schizophrenia-associated 1q21.1 deletion is required for neuronal and sleep maintenance

The human 1q21.1 deletion of ten genes is associated with increased risk of schizophrenia. This deletion involves the β-subunit of the AMP-activated protein kinase (AMPK) complex, a key energy sensor in the cell. Although neurons have a high demand for energy and low capacity to store nutrients, the...

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Autores principales: Nagy, Stanislav, Maurer, Gianna W., Hentze, Julie L., Rose, Morten, Werge, Thomas M., Rewitz, Kim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317821/
https://www.ncbi.nlm.nih.gov/pubmed/30566533
http://dx.doi.org/10.1371/journal.pgen.1007623
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author Nagy, Stanislav
Maurer, Gianna W.
Hentze, Julie L.
Rose, Morten
Werge, Thomas M.
Rewitz, Kim
author_facet Nagy, Stanislav
Maurer, Gianna W.
Hentze, Julie L.
Rose, Morten
Werge, Thomas M.
Rewitz, Kim
author_sort Nagy, Stanislav
collection PubMed
description The human 1q21.1 deletion of ten genes is associated with increased risk of schizophrenia. This deletion involves the β-subunit of the AMP-activated protein kinase (AMPK) complex, a key energy sensor in the cell. Although neurons have a high demand for energy and low capacity to store nutrients, the role of AMPK in neuronal physiology is poorly defined. Here we show that AMPK is important in the nervous system for maintaining neuronal integrity and for stress survival and longevity in Drosophila. To understand the impact of this signaling system on behavior and its potential contribution to the 1q21.1 deletion syndrome, we focused on sleep, an important role of which is proposed to be the reestablishment of neuronal energy levels that are diminished during energy-demanding wakefulness. Sleep disturbances are one of the most common problems affecting individuals with psychiatric disorders. We show that AMPK is required for maintenance of proper sleep architecture and for sleep recovery following sleep deprivation. Neuronal AMPKβ loss specifically leads to sleep fragmentation and causes dysregulation of genes believed to play a role in sleep homeostasis. Our data also suggest that AMPKβ loss may contribute to the increased risk of developing mental disorders and sleep disturbances associated with the human 1q21.1 deletion.
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spelling pubmed-63178212019-01-19 AMPK signaling linked to the schizophrenia-associated 1q21.1 deletion is required for neuronal and sleep maintenance Nagy, Stanislav Maurer, Gianna W. Hentze, Julie L. Rose, Morten Werge, Thomas M. Rewitz, Kim PLoS Genet Research Article The human 1q21.1 deletion of ten genes is associated with increased risk of schizophrenia. This deletion involves the β-subunit of the AMP-activated protein kinase (AMPK) complex, a key energy sensor in the cell. Although neurons have a high demand for energy and low capacity to store nutrients, the role of AMPK in neuronal physiology is poorly defined. Here we show that AMPK is important in the nervous system for maintaining neuronal integrity and for stress survival and longevity in Drosophila. To understand the impact of this signaling system on behavior and its potential contribution to the 1q21.1 deletion syndrome, we focused on sleep, an important role of which is proposed to be the reestablishment of neuronal energy levels that are diminished during energy-demanding wakefulness. Sleep disturbances are one of the most common problems affecting individuals with psychiatric disorders. We show that AMPK is required for maintenance of proper sleep architecture and for sleep recovery following sleep deprivation. Neuronal AMPKβ loss specifically leads to sleep fragmentation and causes dysregulation of genes believed to play a role in sleep homeostasis. Our data also suggest that AMPKβ loss may contribute to the increased risk of developing mental disorders and sleep disturbances associated with the human 1q21.1 deletion. Public Library of Science 2018-12-19 /pmc/articles/PMC6317821/ /pubmed/30566533 http://dx.doi.org/10.1371/journal.pgen.1007623 Text en © 2018 Nagy et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Nagy, Stanislav
Maurer, Gianna W.
Hentze, Julie L.
Rose, Morten
Werge, Thomas M.
Rewitz, Kim
AMPK signaling linked to the schizophrenia-associated 1q21.1 deletion is required for neuronal and sleep maintenance
title AMPK signaling linked to the schizophrenia-associated 1q21.1 deletion is required for neuronal and sleep maintenance
title_full AMPK signaling linked to the schizophrenia-associated 1q21.1 deletion is required for neuronal and sleep maintenance
title_fullStr AMPK signaling linked to the schizophrenia-associated 1q21.1 deletion is required for neuronal and sleep maintenance
title_full_unstemmed AMPK signaling linked to the schizophrenia-associated 1q21.1 deletion is required for neuronal and sleep maintenance
title_short AMPK signaling linked to the schizophrenia-associated 1q21.1 deletion is required for neuronal and sleep maintenance
title_sort ampk signaling linked to the schizophrenia-associated 1q21.1 deletion is required for neuronal and sleep maintenance
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317821/
https://www.ncbi.nlm.nih.gov/pubmed/30566533
http://dx.doi.org/10.1371/journal.pgen.1007623
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