Maternal Nutrition and the Developing Brain (2014-2015)
Postpartum depression is a serious and highly prevalent mental health disorder with significant implications for women and their children. Research is inconclusive about the root causes; however, growing evidence suggests that diet plays a critical role. This project team explored the potential role of maternal nutrition on maternal behavior and offspring brain development. Specifically, a component of Western diet that tends to be higher in overweight and obese individuals, the branched chain amino acids (BCAA) leucine, isoleucine and valine, were examined in both human and animal studies. This work is based on rat studies confirming that exposure to these BCAAs induces behavioral signs of anxiety and depression, and their presence is exacerbated by a high-fat diet. Emerging clinical evidence that suggests the BCAA signature may be a potential biomarker for postpartum depression. However, the impact of a high-fat diet /- BCAA on pregnant animals and their offspring with the goal of translating findings to human studies to develop clinical interventions had never been explored.
This project team investigated the impact of diet manipulation in pregnant mice on maternal and offspring brain, gastrointestinal, immune and behavioral outcomes. Because alterations in maternal nutrition may impact offspring development either through changes in biochemical pathways during pregnancy OR via changes in maternal behavior following the birth of offspring (particularly in the context of depression), or both, the team carefully assessed changes in maternal care in the weeks after birth, in addition to collecting peripheral and central tissues for metabolomics, neurochemistry and inflammatory analyses. Coincident with the rodent studies, team members collected and analyzed data from ongoing clinical studies with early postpartum women in Durham and surrounding areas. The team was able to collect and compare maternal blood samples from both the mouse and human studies, in which members could correlate the BCAA signature and metabolomics information to behavioral outcomes in both species.
The study uncovered interesting differences in the development of mice exposed to varying maternal diets. Maternal BCAA supplementation was associated with decreased weight. Maternal HFD was associated with increased fasting blood glucose, increased anxiety-like behavior and increased activity in male offspring; increased anxiety-like behavior and altered context-dependent reward learning in females; and with a reduction of microglial markers at P1 in both sexes. Microglia are critical mediators of synaptic refinement and pruning, and early microglial function has wide-ranging implications for network formation and later-life cognition. Previous studies have found higher expression of microglial markers in males than in females perinatally, and this has been linked to male susceptibility to early-onset disorders such as autism. Similarly, the team found disparate effects of maternal diet on male and female groups, with males most vulnerable to metabolic and behavioral changes.
Team members plan to continue the project with molecular and histological data from multiple timepoints; with analysis of serum levels of BCAA, serotonin and corticosterone; and with analysis of maternal as well as offspring outcomes. They will synthesize these data with a clinical study of postpartum women, which will examine many of the same response variables to produce a translational, interdisciplinary understanding of the impact of diet on maternal and child health.
Summer 2014 - Spring 2015
Jessica L. Bolton, Melanie G. Wiley, Bailey Ryan, Samantha Truong, Melva Strait, Dana Creighton Baker, Nancy Y. Yang, Olga Ilkayeva, Thomas M. O’Connell, Shelley W. Wroth, Cristina L. Sanchez, Geeta Swamy, Christopher Newgard, Cynthia Kuhn, Staci D. Bilbo, Leigh Ann Simmons. 2017. “Perinatal western-type diet and associated gestational weight gain alter postpartum maternal mood.” Brain and Behavior.
This Team in the News
See earlier related team, Environmental Justice and the Early-life Origin of Health Disparities: Why Mom Matters (2013-2014).
My participation on our project team was an integral part of my dissertation work, which may not have been funded without the critical support of Bass Connections. I was able to get involved in translational research, which shaped my decision to continue in this type of research. Recently I began a postdoctoral fellowship in translational research at the University of California-Irvine focusing on the effects of early-life stress on the developing brain. —Jessica Bolton
/faculty/staff Team Members
Staci Bilbo, Arts & Sciences-Psychology and Neuroscience*
Leigh Ann Simmons, School of Nursing*
/graduate Team Members
Jessica Bolton, Psychology-PHD
Danielle Pipher, Nursing-PHD
/undergraduate Team Members
Dominic Le, Biology (BS)
Sean Sweat, Economics (BS)
Katherine West, Biology (BS)