Gestational and early postnatal protein malnutrition disrupts neurodevelopment in rhesus macaques.

Abstract

Adequate nutrition during gestation is critical for fetal development, and deficits in protein are associated with neurological and behavioral impairments in offspring placing a significant burden on global health. Fetal and neonatal longitudinal magnetic resonance assessments of brain development spanning mid-gestation to 11months of age were conducted in rhesus macaque (Macaca mulatta) (n= 22; 9 females) generated from an established nonhuman primate model of gestational protein reduction to ascertain the neurodevelopmental effects of reduced maternal protein intake. Structural abnormalities were identified in two reduced diet groups, in addition to age-dependent whole-brain volume deficits in the most severely reduced (50% vs. 33% reduction) protein cohort, primarily restricted to gray matter structures; i.e. cortical/subcortical gray matter and the cerebellum. Diffusion-weighted imaging revealed widespread postnatal reductions in white matter fractional anisotropy, concentrated in the corpus callosum for both reduced protein levels relative to control diet. Despite extensive neurodevelopmental alterations detectable by longitudinal imaging, early behavioral assessments conducted at 1month revealed minor perturbations. These results highlight differential impacts of reduced maternal and infant protein intake on gray and white matter formation and organization, with potential implications for early motor development.