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- College of Human Ecology: Nutritional Science
1. Maternal choline supplementation (research using animal models): We have found that supplementing the maternal diet during pregnancy and lactation significantly improves attention, spatial cognition, and emotion regulation in a mouse model of Down syndrome. A more circumscribed improvement in attention was also seen in the Wildtype littermates. I am currently involved in a collaborative study with investigators at Rush University Medical Center and NYU to elucidate the underlying neural mechanisms. We have found that maternal choline suppmentation (MCS) improves spatial cognition in the Ts65Dn mice which is mediated, at least in part, by protection of medial septal cholinergic neurons, which atrophy in these mice with the onset of Alzheimer-like neuropathology. We have also found that MCS increases adult hippocampal neurogenesis in the Ts65Dn mice, and that this correlates with the improved spatial cognition of these mice. Furthermore we have found evidence for improved neurotrophin function in these trisomic mice, which may contribute to the protection of BFCN neurons in these mice, and subsequently their improved cognitive functioning. The results of these studies will have implications for minimizing cognitive and affective function in individuals who have Down syndrome as well as provide new information concerning the mechanism by which perinatal choline supplementation exerts lifelong benefits on cognitive functioning in normal rodents. These findings will have important clinical implications for identifying the choline intake during pregnancy and lactation that is optimal for cognitive functioning throughout the lifespan. These collaborative studies linking behavioral and neural changes are in progress.
2. Maternal choline supplementation (research with human subjects): We are currently assessing cognitive and affective functioning in 7 year children whose mothers participated in a randomized controlled trial of maternal choline supplementation during either the last trimester of pregnancy or the first 3 months postnatally. Maternal choline intake was completely controlled at either 480 mg/day or 930 mg/day during these periods of time. Preliminary analyses indicate that the children born to mothers consuming the higher choline intake during the last trimester of pregnancy performed significantly better (v. 480 mg/d) on tests of attention, memory, and problem solving. This is the first evidence demonstrating that higher maternal choline intake during pregnancy improves offspring cognition during the school-age years, a time when neurobehavioral tests predict later academic outcomes and adult functioning. This study is a collaboration with several DNS colleagues (Drs. Caudill, Canfield, and Finkelstein). .
3. Dr Paul Soloway and I are planning to investigate whether the lasting cognitive benefits of maternal choline supplementation in the Ts65Dn mouse model of Down syndrome and normal littermates are mediated by epigenetics effects due to choline's role as a methyl donor. These studies will also help ascertain possible adverse effects of MCS on other systems (e.g., cancer).
4. I am collaborating on a project with collaborators at UC Santa Cruz and the University of Illinois to investigate the lasting cognitive and neural effects of early developmental exposure to Manganese. We have found evidence for attentional and fine motor dysfunction in the rats exposed early in life, and have found evidence for catecholaminergic alterations in these same animals. Importantly treatment with methylphenidate (Ritalin) completely normalized the fine motor dysfunction in the manganese exposed animals. We are planning future studies to further explore the mechanisms underlying these areas of dysfunction and test potential therapies.