Gestational and early postnatal protein malnutrition disrupts neurodevelopment in rhesus macaques

Area of Science:

• Neuroscience
• Developmental Biology
• Nutritional Science

Background:

• Maternal nutrition during gestation is crucial for fetal neurodevelopment.
• Protein deficits in pregnancy are linked to offspring neurological and behavioral impairments.
• Gestational protein reduction models in nonhuman primates offer insights into human neurodevelopmental effects.

Purpose of the Study:

• To investigate the neurodevelopmental effects of reduced maternal protein intake on fetal and neonatal brain development in rhesus macaques.
• To identify structural and organizational changes in gray and white matter resulting from maternal protein restriction.
• To correlate observed neuroimaging findings with early behavioral assessments.

Main Methods:

• Longitudinal fetal and neonatal magnetic resonance imaging (MRI) assessments from mid-gestation to 11 months of age.
• Utilized a nonhuman primate model (Macaca mulatta) with established gestational protein reduction diets (33% and 50% reduction).
• Employed diffusion-weighted imaging to assess white matter integrity (fractional anisotropy) and structural MRI for gray matter analysis.

Main Results:

• Structural abnormalities were observed in both protein-reduced groups compared to controls.
• Age-dependent whole-brain volume deficits, primarily in gray matter (cortical/subcortical, cerebellum), were noted in the 50% protein reduction cohort.
• Postnatal diffusion-weighted imaging revealed widespread reductions in white matter fractional anisotropy, particularly in the corpus callosum, for both reduced protein groups.

Conclusions:

• Reduced maternal protein intake during gestation leads to significant structural and organizational alterations in offspring brain development, affecting both gray and white matter.
• Neuroimaging detects substantial neurodevelopmental changes, even when early behavioral assessments show only minor perturbations.
• These findings underscore the critical role of adequate maternal protein intake for normal brain formation and organization, with potential implications for early motor development.