The ability to remember and use information accurately is very important, and impairments of visuospatial memory profoundly disrupt an individual's life. These observations motivate research to understand the brain mechanisms involved in normal memory processing, and the types of lifespan developmental changes that produce memory dysfunctions and amnesia. At the same time it is of critical importance to understand the early developmental stages that brain and behavior processes go through and humans has demonstrated that modification of frontal and temporal lobe structures, particularly the hippocampus and frontal cortex, produce behavioral changes that have some of the basic characteristics of an amnesic syndrome. The purpose of the present proposal is to investigate further our recent findings that indicate the potential for organizational changes in these same structures that subserve visuospatial memory by exposing the developing nervous system to choline supplementation. Such perinatal choline supplementation has produced relatively permanent changes in the spatial ability of subjects treated during specified periods (embryonic days 12-17 and postnatal day 15-30). The behavioral changes have been interpreted as reflecting an increase in memory capacity and precision. The major question is to determine if there are any negative consequences of these treatments that might be revealed by the recruitment of normal aging processes. In this regard, we will investigate the three possibilities that perinatal choline supplementation either has a) a positive effect on the accuracy of visuospatial memory is a function of aging, b) a neutral effect on visuospatial memory as a function of aging, or c) a negative effect on the accuracy of visuospatial memory as a function of aging. These behavioral data will stimulate additional studies of the of the anatomical and neurochemical basis of these effects.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
1P01AG009525-01
Application #
3802931
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Boston University
Department
Type
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
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
Wong-Goodrich, Sarah J E; Glenn, Melissa J; Mellott, Tiffany J et al. (2011) Water maze experience and prenatal choline supplementation differentially promote long-term hippocampal recovery from seizures in adulthood. Hippocampus 21:584-608
McGowan, Patrick O; Hope, Thomas A; Meck, Warren H et al. (2011) Impaired social recognition memory in recombination activating gene 1-deficient mice. Brain Res 1383:187-95

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