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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
3P01AG009525-02S1
Application #
3091279
Study Section
Aging Review Committee (AGE)
Project Start
1991-03-01
Project End
1993-12-09
Budget Start
1992-03-01
Budget End
1993-12-09
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Boston University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Blusztajn, Jan Krzysztof; Slack, Barbara E; Mellott, Tiffany J (2017) Neuroprotective Actions of Dietary Choline. Nutrients 9:
Mellott, Tiffany J; Huleatt, Olivia M; Shade, Bethany N et al. (2017) Perinatal Choline Supplementation Reduces Amyloidosis and Increases Choline Acetyltransferase Expression in the Hippocampus of the APPswePS1dE9 Alzheimer's Disease Model Mice. PLoS One 12:e0170450
Tosto, Giuseppe; Monsell, Sarah E; Hawes, Stephen E et al. (2016) Progression of Extrapyramidal Signs in Alzheimer's Disease: Clinical and Neuropathological Correlates. J Alzheimers Dis 49:1085-93
Blusztajn, Jan Krzysztof; Mellott, Tiffany J (2013) Neuroprotective actions of perinatal choline nutrition. Clin Chem Lab Med 51:591-9
Cheatham, Carol L; Goldman, Barbara Davis; Fischer, Leslie M et al. (2012) Phosphatidylcholine supplementation in pregnant women consuming moderate-choline diets does not enhance infant cognitive function: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr 96:1465-72
Blusztajn, Jan Krzysztof; Mellott, Tiffany J (2012) Choline nutrition programs brain development via DNA and histone methylation. Cent Nerv Syst Agents Med Chem 12:82-94
Wong-Goodrich, Sarah J E; Tognoni, Christina M; Mellott, Tiffany J et al. (2011) Prenatal choline deficiency does not enhance hippocampal vulnerability after kainic acid-induced seizures in adulthood. Brain Res 1413:84-97
Lopez-Coviella, Ignacio; Mellott, Tiffany J; Schnitzler, Aletta C et al. (2011) BMP9 protects septal neurons from axotomy-evoked loss of cholinergic phenotype. PLoS One 6:e21166
Carey, Robyn M; Blusztajn, Jan K; Slack, Barbara E (2011) Surface expression and limited proteolysis of ADAM10 are increased by a dominant negative inhibitor of dynamin. BMC Cell Biol 12:20
Resseguie, Mary E; da Costa, Kerry-Ann; Galanko, Joseph A et al. (2011) Aberrant estrogen regulation of PEMT results in choline deficiency-associated liver dysfunction. J Biol Chem 286:1649-58

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