title: Moderate developmental undernutrition: Impact on growth and cognitive function in youth and old age.
abstract: Low weight at birth is a common adverse developmental effect reported in human populations and animal toxicity studies. Epidemiological evidence links low birth weight to a syndrome of metabolic changes that increase later risk for obesity, type 2 diabetes, hypertension, and cardiovascular disease. The present study used a four-treatment cross-over experimental design to evaluate the selective impact of early nutritional deficiency on metabolism and brain function across the lifespan of male Sprague Dawley rats. Undernutrition was induced prenatally by restricting maternal food intake to 50% of ad lib from GD3 to birth. Postnatal undernutrition was induced by fostering pups at birth to naïve dams in large (n=16) litters as opposed to small (n=8) control litters. Body weights were monitored in the early neonatal period, in early adulthood beginning at 5months and through to senescence at 21months of age. In contrast to recent reports, no increase in the prevalence of obesity was seen in animals born to food restricted dams and reared under ad lib feeding conditions. Behavioral tests of locomotion, learning and memory were performed in young, middle-aged, and aged animals. No effects of pre or postnatal nutritional history were detected. Age-dependent reductions in locomotor activity were detected, as well as deficits in spatial learning as measured in the Morris water maze and in context fear conditioning. These findings indicate that moderate fetal undernutrition followed by neonatal adequate nutrition does not appear to lead to obesity or neurological dysfunction in young adulthood or old age.
authors.affiliation: Toxicity Assessment Division, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA. gilbert.mary@epa.gov <gilbert.mary@epa.gov>
authors.forename: M E
authors.initials: ME
authors.lastname: Gilbert
authors.forename: R
authors.initials: R
authors.lastname: MacPhail
authors.forename: J
authors.initials: J
authors.lastname: Baldwin
authors.forename: V C
authors.initials: VC
authors.lastname: Moser
authors.forename: N
authors.initials: N
authors.lastname: Chernoff
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects*; D003213:Conditioning, Psychological / Q000187:drug effects; D018592:Cross-Over Studies; D005239:Fear / Q000187:drug effects / Q000523:psychology; D005260:Female; D048070:Fetal Nutrition Disorders / Q000503:physiopathology; D005865:Gestational Age; D007858:Learning / Q000187:drug effects*; D008297:Male; D044342:Malnutrition / Q000503:physiopathology*; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013037:Spatial Behavior / Q000187:drug effects