This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Little is known about how nutrient availability during development modulates genomic, neural, physiological, and behavioral responses to stress in adults to alter the onset or course of neuropsychiatric disorders, like depression. The present project uses rats to examine whether there is protection against depressive systems precipitated by stress in adults treated with prenatal choline supplementation. Also under investigation is the possibility that there is enhanced vulnerability to stress and depressive symptoms with prenatal choline deficiency. To address these aims, pregnant rats are treated with diets supplemented, sufficient, or deficient in choline. Offspring are reared into adulthood and assessed in rodent models of depression that entail acutely traumatic or chronic unpredictable stress. We expect that prenatal choline supplementation will attenuate behavioral outcomes such as despair, anhedonia, cognitive deficits, and anxiety, while prenatal choline deficiency will worsen them. We are also measuring levels of stress hormones and examining patterns of gene expression and function in the hippocampus, amygdala, and prefrontal cortex, three brain regions implicated in depression and well known for their importance in mediating stress responses. We, again, expect that prenatal supplementation will prevent stress-induced alterations in molecular markers of genomic function, while prenatal deficiency will accentuate them. Emerging data from studies in humans show that there are genetic factors that produce individual requirements for choline and inadequate intake of choline has profound implications for health. This research is a crucial expansion into the realm of mental health to determine whether choline may also modulate an individual's depression risk and outcomes.
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