title: Chronic Maternal Low-Protein Diet in Mice Affects Anxiety, Night-Time Energy Expenditure and Sleep Patterns, but Not Circadian Rhythm in Male Offspring.
abstract: Offspring of murine dams chronically fed a protein-restricted diet have an increased risk for metabolic and neurobehavioral disorders. Previously we showed that adult offspring, developmentally exposed to a chronic maternal low-protein (MLP) diet, had lower body and hind-leg muscle weights and decreased liver enzyme serum levels. We conducted energy expenditure, neurobehavioral and circadian rhythm assays in male offspring to examine mechanisms for the body-weight phenotype and assess neurodevelopmental implications of MLP exposure. C57BL/6J dams were fed a protein restricted (8%protein, MLP) or a control protein (20% protein, C) diet from four weeks before mating until weaning of offspring. Male offspring were weaned to standard rodent diet (20% protein) and single-housed until 8-12 weeks of age. We examined body composition, food intake, energy expenditure, spontaneous rearing activity and sleep patterns and performed behavioral assays for anxiety (open field activity, elevated plus maze [EPM], light/dark exploration), depression (tail suspension and forced swim test), sociability (three-chamber), repetitive (marble burying), learning and memory (fear conditioning), and circadian behavior (wheel-running activity during light-dark and constant dark cycles). We also measured circadian gene expression in hypothalamus and liver at different Zeitgeber times (ZT). Male offspring from separate MLP exposed dams had significantly greater body fat (P = 0.03), less energy expenditure (P = 0.004), less rearing activity (P = 0.04) and a greater number of night-time rest/sleep bouts (P = 0.03) compared to control. MLP offspring displayed greater anxiety-like behavior in the EPM (P<0.01) but had no learning and memory deficit in fear-conditioning assay (P = 0.02). There was an effect of time on Per1, Per 2 and Clock circadian gene expression in the hypothalamus but not on circadian behavior. Thus, transplacental and early developmental exposure of dams to chronic MLP reduces food intake and energy expenditure, increases anxiety like behavior and disturbs sleep patterns but not circadian rhythm in adult male offspring.
authors.affiliation: Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, TX, United States of America.|Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX, United States of America.
authors.forename: Randy F
authors.initials: RF
authors.lastname: Crossland
authors.affiliation: Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, TX, United States of America.|Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX, United States of America.
authors.forename: Alfred
authors.initials: A
authors.lastname: Balasa
authors.affiliation: Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, TX, United States of America.|Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX, United States of America.
authors.forename: Rajesh
authors.identifier: http://orcid.org/0000-0001-8841-570X
authors.initials: R
authors.lastname: Ramakrishnan
authors.affiliation: Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, TX, United States of America.|Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX, United States of America.|Interdepartmental Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX, United States of America.
authors.forename: Sangeetha K
authors.initials: SK
authors.lastname: Mahadevan
authors.affiliation: USDA/Agricultural Research Service Children's Nutrition Research Center, Houston, TX, United States of America.
authors.forename: Marta L
authors.initials: ML
authors.lastname: Fiorotto
authors.affiliation: Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, TX, United States of America.|Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX, United States of America.|Interdepartmental Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX, United States of America.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States of America.
authors.forename: Ignatia B
authors.initials: IB
authors.lastname: Van den Veyver
mesh_terms: D000273:Adipose Tissue; D000818:Animals; D001007:Anxiety / Q000209:etiology*; D001522:Behavior, Animal; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D018753:Diet, Protein-Restricted / Q000009:adverse effects*; D004734:Energy Metabolism; D005260:Female; D015870:Gene Expression; D007031:Hypothalamus / Q000502:physiology; D008099:Liver / Q000502:physiology; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D008810:Mice, Inbred C57BL; D012890:Sleep / Q000502:physiology*