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Distinct Basal Metabolism in Three Mouse Models of Neurodevelopmental Disorders

Prevalence of metabolic disturbances is higher among individuals with neurodevelopmental disorders (NDDs), yet this association has been largely overlooked. Investigation into human disease remains challenging, as a complete pathophysiological understanding relies on accurate modeling and highly con...

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Autores principales: Menzies, Caitlin, Naz, Shama, Patten, David, Alquier, Thierry, Bennett, Brian M., Lacoste, Baptiste
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Society for Neuroscience 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174051/
https://www.ncbi.nlm.nih.gov/pubmed/33820803
http://dx.doi.org/10.1523/ENEURO.0292-20.2021
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author Menzies, Caitlin
Naz, Shama
Patten, David
Alquier, Thierry
Bennett, Brian M.
Lacoste, Baptiste
author_facet Menzies, Caitlin
Naz, Shama
Patten, David
Alquier, Thierry
Bennett, Brian M.
Lacoste, Baptiste
author_sort Menzies, Caitlin
collection PubMed
description Prevalence of metabolic disturbances is higher among individuals with neurodevelopmental disorders (NDDs), yet this association has been largely overlooked. Investigation into human disease remains challenging, as a complete pathophysiological understanding relies on accurate modeling and highly controlled variables. Genetically engineered mouse models are widely used to gain insight into the biology of human NDDs, but research focus has been on behavioral and neurophysiological abnormalities. Such models not only allow for evaluating usefulness in reproducing human features, including similarities and discrepancies with rodent phenotypes, but they also represent a unique opportunity to observe and quantify novel anomalies. Here, we present the first characterization and comparison of basal metabolism in three mouse models of NDDs, namely, Down syndrome (DS; Dp(16)Yey/+ mice), 16p11.2 deletion syndrome (16pDel; 16p11.2(df/+) mice), and fragile X syndrome [FXS; Fmr1 knock-out (KO) mice] and their wild-type (WT) counterparts. Using the Comprehensive Lab Animal Monitoring System (CLAMS) coupled to EchoMRI, as well as quantification of key plasma metabolites by liquid chromatography mass spectrometry (LC-MS), our in vivo study reveals that each mouse model expresses a unique metabolic signature that is sex-specific, independent of the amount of food consumed and minimally influenced by physical activity. In particular, we identify striking differences in body composition, respiratory exchange ratio (RER), caloric expenditure (CE), and concentrations of circulating plasma metabolites related to mitochondrial function. Providing novel insight into NDD-associated metabolic alterations is an essential prerequisite for future preclinical and clinical interventions.
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spelling pubmed-81740512021-06-03 Distinct Basal Metabolism in Three Mouse Models of Neurodevelopmental Disorders Menzies, Caitlin Naz, Shama Patten, David Alquier, Thierry Bennett, Brian M. Lacoste, Baptiste eNeuro Research Article: New Research Prevalence of metabolic disturbances is higher among individuals with neurodevelopmental disorders (NDDs), yet this association has been largely overlooked. Investigation into human disease remains challenging, as a complete pathophysiological understanding relies on accurate modeling and highly controlled variables. Genetically engineered mouse models are widely used to gain insight into the biology of human NDDs, but research focus has been on behavioral and neurophysiological abnormalities. Such models not only allow for evaluating usefulness in reproducing human features, including similarities and discrepancies with rodent phenotypes, but they also represent a unique opportunity to observe and quantify novel anomalies. Here, we present the first characterization and comparison of basal metabolism in three mouse models of NDDs, namely, Down syndrome (DS; Dp(16)Yey/+ mice), 16p11.2 deletion syndrome (16pDel; 16p11.2(df/+) mice), and fragile X syndrome [FXS; Fmr1 knock-out (KO) mice] and their wild-type (WT) counterparts. Using the Comprehensive Lab Animal Monitoring System (CLAMS) coupled to EchoMRI, as well as quantification of key plasma metabolites by liquid chromatography mass spectrometry (LC-MS), our in vivo study reveals that each mouse model expresses a unique metabolic signature that is sex-specific, independent of the amount of food consumed and minimally influenced by physical activity. In particular, we identify striking differences in body composition, respiratory exchange ratio (RER), caloric expenditure (CE), and concentrations of circulating plasma metabolites related to mitochondrial function. Providing novel insight into NDD-associated metabolic alterations is an essential prerequisite for future preclinical and clinical interventions. Society for Neuroscience 2021-04-15 /pmc/articles/PMC8174051/ /pubmed/33820803 http://dx.doi.org/10.1523/ENEURO.0292-20.2021 Text en Copyright © 2021 Menzies et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article: New Research
Menzies, Caitlin
Naz, Shama
Patten, David
Alquier, Thierry
Bennett, Brian M.
Lacoste, Baptiste
Distinct Basal Metabolism in Three Mouse Models of Neurodevelopmental Disorders
title Distinct Basal Metabolism in Three Mouse Models of Neurodevelopmental Disorders
title_full Distinct Basal Metabolism in Three Mouse Models of Neurodevelopmental Disorders
title_fullStr Distinct Basal Metabolism in Three Mouse Models of Neurodevelopmental Disorders
title_full_unstemmed Distinct Basal Metabolism in Three Mouse Models of Neurodevelopmental Disorders
title_short Distinct Basal Metabolism in Three Mouse Models of Neurodevelopmental Disorders
title_sort distinct basal metabolism in three mouse models of neurodevelopmental disorders
topic Research Article: New Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174051/
https://www.ncbi.nlm.nih.gov/pubmed/33820803
http://dx.doi.org/10.1523/ENEURO.0292-20.2021
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