Age-related Declines in Exploratory Behavior and Markers of Hippocampal Plasticity Are Attenuated by Prenatal Choline Supplementation in Rats

Supplemental choline in the maternal diet produces a lasting enhancement in memory in offspring that resists age-related decline and is accompanied by neuroanatomical, neurophysiological and neurochemical changes in the hippocampus. The present study was designed to examine: 1) if prenatal choline supplementation alters behaviors that contribute to risk or resilience in cognitive aging, and 2) whether, at old age (25 months), prenatally choline-supplemented rats show evidence of preserved hippocampal plasticity. A longitudinal design was used to look at exploration of an open field, with and without objects, at 1 and 24 months of age in male and female rats whose mothers were fed a diet supplemented with choline (SUP; 5 mg/kg choline chloride) or not supplemented (CON; 1.1 mg/kg choline chloride) on embryonic days 12-17. Aging caused a significant decline in open field exploration that was more pronounced in males but interest in novel objects was maintained in both sexes. Prenatal choline supplementation attenuated, but did not prevent age-related decline in exploration in males and increased object exploration in young females. Following behavioral assessment, rats were euthanized to assess markers of hippocampal plasticity. Aged SUP males and females had more newly proliferated cells in the hippocampal dentate gyrus and protein levels of vascular endothelial growth factor (VEGF) and neurotrophin-3 (NT-3) were significantly elevated in female SUP rats in comparison to all other groups. Taken together, these findings provide the first evidence that prenatal choline supplementation causes changes in exploratory behaviors over the lifespan and preserves some features of hippocampal plasticity that can be seen even at 2 years of age.