Sleep deprivation impairs memory by attenuating mTORC1-dependent protein synthesis

Jennifer C Tudor; Emily J Davis; Lucia Peixoto; Mathieu E Wimmer; Erik van Tilborg; Alan J Park; Shane G Poplawski; Caroline W Chung; Robbert Havekes; Jiayan Huang; Evelina Gatti; Philippe Pierre; Ted Abel

doi:10.1126/scisignal.aad4949

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Sleep deprivation impairs memory by attenuating mTORC1-dependent protein synthesis

Journal article

Open access

Peer reviewed

Sleep deprivation impairs memory by attenuating mTORC1-dependent protein synthesis

Jennifer C Tudor, Emily J Davis, Lucia Peixoto, Mathieu E Wimmer, Erik van Tilborg, Alan J Park, Shane G Poplawski, Caroline W Chung, Robbert Havekes, Jiayan Huang, …

Science signaling, Vol.9(425), pp.ra41-ra41

04/26/2016

DOI: 10.1126/scisignal.aad4949

PMCID: PMC4890572

PMID: 27117251

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Abstract

Sleep deprivation is a public health epidemic that causes wide-ranging deleterious consequences, including impaired memory and cognition. Protein synthesis in hippocampal neurons promotes memory and cognition. The kinase complex mammalian target of rapamycin complex 1 (mTORC1) stimulates protein synthesis by phosphorylating and inhibiting the eukaryotic translation initiation factor 4E-binding protein 2 (4EBP2). We investigated the involvement of the mTORC1-4EBP2 axis in the molecular mechanisms mediating the cognitive deficits caused by sleep deprivation in mice. Using an in vivo protein translation assay, we found that loss of sleep impaired protein synthesis in the hippocampus. Five hours of sleep loss attenuated both mTORC1-mediated phosphorylation of 4EBP2 and the interaction between eukaryotic initiation factor 4E (eIF4E) and eIF4G in the hippocampi of sleep-deprived mice. Increasing the abundance of 4EBP2 in hippocampal excitatory neurons before sleep deprivation increased the abundance of phosphorylated 4EBP2, restored the amount of eIF4E-eIF4G interaction and hippocampal protein synthesis to that seen in mice that were not sleep-deprived, and prevented the hippocampus-dependent memory deficits associated with sleep loss. These findings collectively demonstrate that 4EBP2-regulated protein synthesis is a critical mediator of the memory deficits caused by sleep deprivation.

Eukaryotic Initiation Factors - metabolism

Immunohistochemistry

Phosphorylation

Protein Biosynthesis

Enzyme-Linked Immunosorbent Assay

Heat-Shock Proteins - metabolism

Mice, Inbred C57BL

Eukaryotic Initiation Factor-4E - metabolism

Memory Disorders - metabolism

Male

Cognition

Eukaryotic Initiation Factor-4G - metabolism

Sleep Deprivation - metabolism

Blotting, Western

Mechanistic Target of Rapamycin Complex 1 - metabolism

Nerve Tissue Proteins - metabolism

Hippocampus - metabolism

Animals

Statistics, Nonparametric

Puromycin - pharmacology

Cytoskeletal Proteins - metabolism

Mice

Neurons - metabolism

Real-Time Polymerase Chain Reaction

Details

Title: Subtitle: Sleep deprivation impairs memory by attenuating mTORC1-dependent protein synthesis
Creators: Jennifer C Tudor - Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA
Emily J Davis - Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA
Lucia Peixoto - Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA
Mathieu E Wimmer - Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA
Erik van Tilborg - Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA
Alan J Park - Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA
Shane G Poplawski - Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA
Caroline W Chung - Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA
Robbert Havekes - Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA
Jiayan Huang - Global Statistical Science, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA
Evelina Gatti - Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM U1104, CNRS UMR7280, 13288 Marseille, France. Institute for Research in Biomedicine (iBiMED) and Aveiro Health Sciences Program, University of Aveiro, 3810-193 Aveiro, Portugal
Philippe Pierre - Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM U1104, CNRS UMR7280, 13288 Marseille, France. Institute for Research in Biomedicine (iBiMED) and Aveiro Health Sciences Program, University of Aveiro, 3810-193 Aveiro, Portugal
Ted Abel - Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA. abele@sas.upenn.edu
Resource Type: Journal article
Publication Details: Science signaling, Vol.9(425), pp.ra41-ra41
DOI: 10.1126/scisignal.aad4949
PMID: 27117251
PMCID: PMC4890572
NLM abbreviation: Sci Signal
ISSN: 1945-0877
eISSN: 1937-9145
Publisher: United States
Grant note: P01 AG017628 / NIA NIH HHS F32 MH099730 / NIMH NIH HHS T32 NS007413 / NINDS NIH HHS R21 MH102703 / NIMH NIH HHS K12 GM081259 / NIGMS NIH HHS
Language: English
Date published: 04/26/2016
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984065822502771

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