[Abstract Title]. - Society for Neuroscience

Topic: F.02.j. Learning and memory: Pharmacology
Support: AG009525
Title: Prenatal choline supplementation enhances depolarization-evoked expression of genes
implicated in neural plasticity
Authors: *T. J. MELLOTT, J. M. DAVISON, V. P. KOVACHEVA, J. K. BLUSZTAJN;
Dept Pathol, Boston Univ. Sch. Med., Boston, MA
Abstract: Normal development and function of the brain requires the availability of fundamental
nutrients, such as choline, during the period of embryonic and fetal growth. Choline is an
essential nutrient whose intake during the second half of fetal development can produce longlasting
cognitive effects. The mechanism by which choline influences learning and memory
remains unclear; however, it may involve changes in the levels of factors responsible for
neuronal growth and survival within the brain. We have previously shown that prenatal choline
supplementation increases levels of brain derived neurotrophic factor (BNDF) in the
hippocampus and enhances activation of signaling molecules, specifically those induced during
learning and memory (MAPK, CREB). Depolarization-evoked BDNF expression has been
shown to involve methyl-CpG-binding protein 2 (MeCP2) phosphorylation and its dissociation
from the methylated binding site on the BDNF promoter. In this study, we found a timedependent
increase in MeCP2 phosphorylation, demethylation of a specific CpG in the BDNF
promoter, and BDNF mRNA expression following stimulation of hippocampal slices from
control animals with a depolarizing concentration of potassium (45 mM KCl). Using
hippocampal slices derived from rats that were exposed to choline supplementation, a control
amount of choline, or choline deficiency via the maternal diet on embryonic days 12-17, we
measured the mRNA levels of BDNF, as well as NMDA receptor subunit 2B (NR2B), in
hippocampal slices following stimulation with either a depolarizing concentration of potassium
or insulin-like growth factor 2 (IGF2, 0.1 nM). Hippocampal slices from prenatally cholinesupplemented
rats had the highest basal levels of BDNF mRNA and were most responsive to
depolarization and IGF2 stimulation. Basal levels and depolarization-evoked NR2B mRNA
levels were the lowest in hippocampal slices from prenatally choline-deficient animals. IGF2
stimulation increased NR2B mRNA expression only in hippocampal slices from prenatally
choline-supplemented rats. Therefore, we are currently examining MeCP2 phosphorylation in
response to depolarization and the methylation status of the respective promoters to possibly
explain differences in BDNF expression, as well as NR2B expression, between the groups of
animals whose mothers consumed different amounts of choline during pregnancy. Elevated
levels of BDNF and NR2B, both implicated in learning and memory processes, in prenatally
choline supplemented animals may be in part responsible for the cognitive enhancement
observed in these animals.
Disclosures: T.J. Mellott , None; J.M. Davison, None; J.K. Blusztajn, None; V.P.
Kovacheva, None.