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Prenatal choline availability modulates hippocampal and cerebral cortical gene expression

Tiffany J. Mellott^*, Maximillian T. Follettie, Veronica Diesl, Andrew A. Hill, Ignacio Lopez-Coviella^*, and Jan Krzysztof Blusztajn^*,,1

^* Department of Pathology and Laboratory Medicine and

Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts, USA;

Biological Technologies, Wyeth Research, Cambridge, Massachusetts, USA

¹Correspondence: Department of Pathology and Laboratory Medicine, Boston University School of Medicine, 715 Albany St., Rm. L804, Boston, MA 02118 USA. E-mail: jbluszta{at}bu.edu

An increased supply of the essential nutrient choline during fetal development [embryonic day (E) 11–17] in rats causes life-long improvements in memory performance, whereas choline deficiency during this time impairs certain aspects of memory. We analyzed mRNA expression in brains of prenatally choline-deficient, choline-supplemented, or control rats of various ages [postnatal days (P) 1 to 34 for hippocampus and E16 to P34 for cortex] using oligonucleotide microarrays and found alterations in gene expression levels evoked by prenatal choline intake that were, in most cases, transient occurring during the P15-P34 period. We selected a subset of genes, encoding signaling proteins, and verified the microarray data by reverse transcriptase-polymerase chain reaction analyses. Prenatally choline-supplemented rats had the highest expression of calcium/calmodulin (CaM)-dependent protein kinase (CaMK) I and insulin-like growth factor (IGF) II (Igf2) in the cortex and of the transcription factor Zif268/EGR1 in the cortex and hippocampus. Prenatally choline deficient rats had the highest expression of CaMKIIß, protein kinase Cß2, and GABA_B receptor 1 isoforms c and d in the hippocampus. Similar changes in the expression of the proteins encoded by these genes were observed using immunoblot analyses. These data show that the prenatal supply of choline causes multiple modifications in the developmental patterns of expression of genes known to influence learning and memory and provide molecular correlates for the cognitive changes evoked by altered availability of choline in utero.—Mellott, T. J., Follettie, M. T., Diesl, V., Hill, A. A., Lopez-Coviella, I., and Blusztajn, J. K. Prenatal choline availability modulates hippocampal and cerebral cortical gene expression.

Key Words: microarray • memory • nutrition • development • pregnancy

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