An important goal of biomedical science is the design of treatments which prevent memory loss associated with aging. We have observed that administration of choline to rats during tow specific perinatal periods results in enhances performance on memory tests which persists throughout animals' lifetime. These behavioral changes are accompanied by neuroanatomical and neurochemical modifications of the brain. We have also described several mechanisms which lead to maintenance of high plasma choline concentrations early in the development of animals and humans. We hypothesize that, during critical perinatal periods availability of choline influences the anatomical and biochemical organization of developing brain. These organizational changes influence memory performance in adult and aged animals. Choline administration may alter either cholinergic neurotransmission or membrane events or both. Choline is a precursor of a neurotransmitter acetylcholine in cholinergic neurons and cholinergic mechanisms are in memory processes. In addition choline is a precursor of phosphatidylcholine, sphingomyelin and plasmenylcholine; phospholipids which collectively are the most abundant components of all biological membranes. The overall goal of this study is to characterize the physiological processes which underlie the long-term memory enhancement associated with perinatal choline treatments and to further characterize the factors which influence choline availability to brain during the perinatal period. We propose to supplement male and female rats with choline 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 correlate behavioral measurements with: function of cholinergic neurons and membrane turnover; changes in the anatomy of the brain; and the effects of genetic sex and of gonadal steroids. In order to fully characterize these processes throughout animals life, these measurements will be made in animals between the embryonic day 17 and 30 months of age. The studies will provide new information on brain development and aging. The biochemical physiological and anatomical correlates of memory enhancement in aged rates associated with perinatal choline will be established. The ultimate goal of our studies is to relate our results to the aged- associated changes in memory in humans, and to develop perinatal nutritional strategies which could benefit people.
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