Integrative Characterization of the R6/2 Mouse Model of Huntington's Disease Reveals Dysfunctional Astrocyte Metabolism

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Integrative Characterization of the R6/2 Mouse Model of Huntington's Disease Reveals Dysfunctional Astrocyte Metabolism. / Skotte, Niels H.; Andersen, Jens V.; Santos, Alberto; Aldana, Blanca I.; Willert, Cecilie W.; Nørremølle, Anne; Waagepetersen, Helle S.; Nielsen, Michael L.

In: Cell Reports, Vol. 23, No. 7, 2018, p. 2211-2224.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Skotte, NH, Andersen, JV, Santos, A, Aldana, BI, Willert, CW, Nørremølle, A, Waagepetersen, HS & Nielsen, ML 2018, 'Integrative Characterization of the R6/2 Mouse Model of Huntington's Disease Reveals Dysfunctional Astrocyte Metabolism', Cell Reports, vol. 23, no. 7, pp. 2211-2224. https://doi.org/10.1016/j.celrep.2018.04.052

APA

Skotte, N. H., Andersen, J. V., Santos, A., Aldana, B. I., Willert, C. W., Nørremølle, A., ... Nielsen, M. L. (2018). Integrative Characterization of the R6/2 Mouse Model of Huntington's Disease Reveals Dysfunctional Astrocyte Metabolism. Cell Reports, 23(7), 2211-2224. https://doi.org/10.1016/j.celrep.2018.04.052

Vancouver

Skotte NH, Andersen JV, Santos A, Aldana BI, Willert CW, Nørremølle A et al. Integrative Characterization of the R6/2 Mouse Model of Huntington's Disease Reveals Dysfunctional Astrocyte Metabolism. Cell Reports. 2018;23(7):2211-2224. https://doi.org/10.1016/j.celrep.2018.04.052

Author

Skotte, Niels H. ; Andersen, Jens V. ; Santos, Alberto ; Aldana, Blanca I. ; Willert, Cecilie W. ; Nørremølle, Anne ; Waagepetersen, Helle S. ; Nielsen, Michael L. / Integrative Characterization of the R6/2 Mouse Model of Huntington's Disease Reveals Dysfunctional Astrocyte Metabolism. In: Cell Reports. 2018 ; Vol. 23, No. 7. pp. 2211-2224.

Bibtex

@article{a4cfe24f19cb429fa1279e063a6c46cd,
title = "Integrative Characterization of the R6/2 Mouse Model of Huntington's Disease Reveals Dysfunctional Astrocyte Metabolism",
abstract = "Huntington's disease is a fatal neurodegenerative disease, where dysfunction and loss of striatal and cortical neurons are central to the pathogenesis of the disease. Here, we integrated quantitative studies to investigate the underlying mechanisms behind HD pathology in a systems-wide manner. To this end, we used state-of-the-art mass spectrometry to establish a spatial brain proteome from late-stage R6/2 mice and compared this with wild-type littermates. We observed altered expression of proteins in pathways related to energy metabolism, synapse function, and neurotransmitter homeostasis. To support these findings, metabolic 13C labeling studies confirmed a compromised astrocytic metabolism and regulation of glutamate-GABA-glutamine cycling, resulting in impaired release of glutamine and GABA synthesis. In recent years, increasing attention has been focused on the role of astrocytes in HD, and our data support that therapeutic strategies to improve astrocytic glutamine homeostasis may help ameliorate symptoms in HD.",
author = "Skotte, {Niels H.} and Andersen, {Jens V.} and Alberto Santos and Aldana, {Blanca I.} and Willert, {Cecilie W.} and Anne N{\o}rrem{\o}lle and Waagepetersen, {Helle S.} and Nielsen, {Michael L.}",
note = "Copyright {\circledC} 2018 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2018",
doi = "10.1016/j.celrep.2018.04.052",
language = "English",
volume = "23",
pages = "2211--2224",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "7",

}

RIS

TY - JOUR

T1 - Integrative Characterization of the R6/2 Mouse Model of Huntington's Disease Reveals Dysfunctional Astrocyte Metabolism

AU - Skotte, Niels H.

AU - Andersen, Jens V.

AU - Santos, Alberto

AU - Aldana, Blanca I.

AU - Willert, Cecilie W.

AU - Nørremølle, Anne

AU - Waagepetersen, Helle S.

AU - Nielsen, Michael L.

N1 - Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2018

Y1 - 2018

N2 - Huntington's disease is a fatal neurodegenerative disease, where dysfunction and loss of striatal and cortical neurons are central to the pathogenesis of the disease. Here, we integrated quantitative studies to investigate the underlying mechanisms behind HD pathology in a systems-wide manner. To this end, we used state-of-the-art mass spectrometry to establish a spatial brain proteome from late-stage R6/2 mice and compared this with wild-type littermates. We observed altered expression of proteins in pathways related to energy metabolism, synapse function, and neurotransmitter homeostasis. To support these findings, metabolic 13C labeling studies confirmed a compromised astrocytic metabolism and regulation of glutamate-GABA-glutamine cycling, resulting in impaired release of glutamine and GABA synthesis. In recent years, increasing attention has been focused on the role of astrocytes in HD, and our data support that therapeutic strategies to improve astrocytic glutamine homeostasis may help ameliorate symptoms in HD.

AB - Huntington's disease is a fatal neurodegenerative disease, where dysfunction and loss of striatal and cortical neurons are central to the pathogenesis of the disease. Here, we integrated quantitative studies to investigate the underlying mechanisms behind HD pathology in a systems-wide manner. To this end, we used state-of-the-art mass spectrometry to establish a spatial brain proteome from late-stage R6/2 mice and compared this with wild-type littermates. We observed altered expression of proteins in pathways related to energy metabolism, synapse function, and neurotransmitter homeostasis. To support these findings, metabolic 13C labeling studies confirmed a compromised astrocytic metabolism and regulation of glutamate-GABA-glutamine cycling, resulting in impaired release of glutamine and GABA synthesis. In recent years, increasing attention has been focused on the role of astrocytes in HD, and our data support that therapeutic strategies to improve astrocytic glutamine homeostasis may help ameliorate symptoms in HD.

U2 - 10.1016/j.celrep.2018.04.052

DO - 10.1016/j.celrep.2018.04.052

M3 - Journal article

C2 - 29768217

VL - 23

SP - 2211

EP - 2224

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 7

ER -

ID: 196714652