Brain Structural Networks in Mouse Exposed to Chronic Maternal Undernutrition

Abstract

Brain structural connectivity is known to be altered in cases of intrauterine growth restriction and premature birth, although the specific effect of maternal nutritional restriction, a common burden in human populations, has not been assessed yet. Here we analyze the effects of maternal undernutrition during pregnancy and lactation by establishing three experimental groups of female mice divided according to their diet: control (Co), moderate calorie-protein restriction (MCP) and severe protein restriction (SP). Nutritionally restricted dams gained relatively less weight during pregnancy and the body weight of the offspring was also affected by maternal undernutrition, showing global growth restriction. We performed magnetic resonance imaging (MRI) of the offspring's brains after weaning and analyzed their connectivity patterns using complex graph theory. In general, changes observed in the MCP group were more subtle than in SP. Results indicated that brain structures were not homogeneously affected by early nutritional stress. In particular, the growth of central brain regions, such as the temporo-parietal cortex, and long integrative myelinated tracts were relatively preserved, while the frequency of short tracts was relatively reduced. We also found a differential effect on network parameters: network degree, clustering, characteristic path length and small-worldness remained mainly unchanged, while the rich-club index was lower in nutritionally restricted animals. Rich-club decrease reflects an impairment in the structure by which brain regions with large number of connections tend to be more densely linked among themselves. Overall, the findings presented here support the hypothesis that chronic nutritional stress produces long-term changes in brain structural connectivity.