PT  - JOURNAL ARTICLE
AU  - Menzies, Caitlin
AU  - Naz, Shama
AU  - Patten, David
AU  - Alquier, Thierry
AU  - Bennett, Brian M.
AU  - Lacoste, Baptiste
TI  - Distinct Basal Metabolism in Three Mouse Models of Neurodevelopmental Disorders
AID  - 10.1523/ENEURO.0292-20.2021
DP  - 2021 Mar 01
TA  - eneuro
PG  - ENEURO.0292-20.2021
VI  - 8
IP  - 2
4099  - http://www.eneuro.org/content/8/2/ENEURO.0292-20.2021.short
4100  - http://www.eneuro.org/content/8/2/ENEURO.0292-20.2021.full
SO  - eNeuro2021 Mar 01; 8
AB  - 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; 16p11.2df/+ 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.