The overall goal of this study is to characterize the neurochemical correlates of the improved memory performance in rats treated perinatally with supplemental choline. Choline is a precursor of the neurotransmitter acetylcholine (ACh) in cholinergic neurons and cholinergic mechanisms are important in memory processes. In addition, choline is a precursor of phosphatidylcholine (PC), sphingomyelin and plasmenylcholine; phospholipids which are collectively the most abundant components of all biological membranes. Thus choline administration may alter either cholinergic neurotransmission or membrane events or both. Our studies to date indicate that perinatal choline supplementation alters the development of brain cholinergic system. We propose to vary the supply of choline (using choline-sufficient; and choline-supplemented treatment protocols) to male and female rats during defined periods of brain development [embryonic (E) days E12-17, postnatal (P) days P1-P15, days P16-P30, and days E12-P30] and to measure indices of cholinergic neurotransmission and of membrane turnover as a function development [from embryonic day 17 to late adulthood (30 months of age)]. Specifically we shall determine: 1) the developmental changes in the concentrations of water-soluble and lipid-soluble metabolites of choline in brain regions: 2) ACh release in vivo using the microdialysis technique; 3) ACh synthesis and release using in vitro brain preparations; 4) the ACh-evoked phosphatidylinositol turnover; and 5) PC turnover. The studies will provide new information on the cholinergic system and on membrane phospholipid turnover during brain development and aging. The biochemical correlates of memory enhancement in aged rats associated with perinatal choline will be established. This information will help to develop perinatal nutritional strategies which could enhance memory in aged humans.
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