White matter microglia morphological changes with aging in guinea pig offspring born growth restricted

Abstract

Fetal growth restriction is implicated in the programming of later-life neurodegeneration. We hypothesized that growth restricted offspring would show accelerated changes to microglial white matter morphology, relative to controls. Control guinea pig sows were fed ad libitum, while maternal nutrient restriction sows received 70% of control diet switched to 90% from mid-gestation. Offspring were sacrificed at [~]26 days (neonate) or [~]110 days (adult) postpartum. Coronal brain sections from the frontal cortex were subject to IBA1-staining for microglial detection and analyzed by machine learning software. At birth, total body weight of growth restricted offspring was reduced relative to control (p<0.0001) with postnatal catch-up growth observed. Microglial density was reduced in the corpus callosum of control (p<0.05) and growth restricted (p=0.13) adults, relative to neonates. Adults from both groups showed greater IBA1-positive area in the cingulum and periventricular white matter (p<0.05) and increased microglial fractal dimension in the corpus callosum (p<0.10) and periventricular white matter (p<0.05), relative to neonates. At the timepoints studied, we report age-related changes in white matter microglial morphology. However, maternal nutrient restriction leading to fetal growth restriction in guinea pigs does not appear to exacerbate these white matter microglia morphological changes as a marker for later-life neurodegeneration.