| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Nutrition, School of Public Health and School of Medicine, University of North Carolina at Chapel Hill, North Carolina, USA
1Correspondence: Department of Nutrition, School of Public Health and School of Medicine, University of North Carolina at Chapel Hill, North Carolina, 27599-7461 USA. E-mail: steven_zeisel{at}unc.edu
The availability of choline during critical periods of fetal development alters hippocampal development and affects memory function throughout life. Choline deficiency during fetal development reduces proliferation and migration of neuronal precursor cells in the mouse fetal hippocampus and these changes are associated with modifications in the protein levels of some cell cycle regulators and early differentiation markers. We fed C57 BL/6 mouse dams diets deficient or normal in choline content from days 12 to 17 of pregnancy, and then collected fetal brains on embryonic day 17. Using laser-capture micro-dissection we harvested cells from the ventricular and subventricular zones of Ammon’s horn and from the prime germinal zone of the dentate gyrus (hippocampus). In the ventricular and subventricular zones from the choline-deficient group, we observed increased protein levels for kinase-associated phosphatase (Kap) and for p15INK4b (two cell cycle inhibitors). In the dentate gyrus, we observed increased levels of calretinin (an early marker of neuronal differentiation). In fetal brain from mothers fed a choline-deficient diet, DNA global methylation was decreased in the ventricular and subventricular zones of Ammon’s horn. We also observed decreased gene-specific DNA methylation of the gene (Cdkn3) that encodes for Kap, correlating with increased expression of this protein. This was not the case for p15INK4b or calretinin (Cdkn2b and Calb2, respectively). These data suggest that choline deficiency-induced changes in gene methylation could mediate the expression of a cell cycle regulator and thereby alter brain development.
Key Words: Cdkn3 • Kap • Cdkn2b • p15INK4b • Calb2 • calretinin • fetal brain • DNA methylation • choline deficiency • hippocampus
This article has been cited by other articles:
|
|
 |
|
  K.-A. da Costa, K. S. Rai, C. N. Craciunescu, K. Parikh, M. G. Mehedint, L. M. Sanders, A. McLean-Pottinger, and S. H. Zeisel Dietary Docosahexaenoic Acid Supplementation Modulates Hippocampal Development in the Pemt-/- Mouse J. Biol. Chem., January 8, 2010; 285(2): 1008 - 1015. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. G. Mehedint, M. D. Niculescu, C. N. Craciunescu, and S. H. Zeisel Choline deficiency alters global histone methylation and epigenetic marking at the Re1 site of the calbindin 1 gene FASEB J, January 1, 2010; 24(1): 184 - 195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H Zeisel Epigenetic mechanisms for nutrition determinants of later health outcomes Am. J. Clinical Nutrition, May 1, 2009; 89(5): 1488S - 1493S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. P. Kovacheva, J. M. Davison, T. J. Mellott, A. E. Rogers, S. Yang, M. J. O'Brien, and J. K. Blusztajn Raising gestational choline intake alters gene expression in DMBA-evoked mammary tumors and prolongs survival FASEB J, April 1, 2009; 23(4): 1054 - 1063. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H Zeisel Importance of methyl donors during reproduction Am. J. Clinical Nutrition, February 1, 2009; 89(2): 673S - 677S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Davison, T. J. Mellott, V. P. Kovacheva, and J. K. Blusztajn Gestational Choline Supply Regulates Methylation of Histone H3, Expression of Histone Methyltransferases G9a (Kmt1c) and Suv39h1 (Kmt1a), and DNA Methylation of Their Genes in Rat Fetal Liver and Brain J. Biol. Chem., January 23, 2009; 284(4): 1982 - 1989. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Oresic, S. Simell, M. Sysi-Aho, K. Nanto-Salonen, T. Seppanen-Laakso, V. Parikka, M. Katajamaa, A. Hekkala, I. Mattila, P. Keskinen, et al. Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes J. Exp. Med., December 22, 2008; 205(13): 2975 - 2984. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Veenema, C. Solis, R. Li, W. Wang, C. V Maletz, C. M Abratte, and M. A Caudill Adequate Intake levels of choline are sufficient for preventing elevations in serum markers of liver dysfunction in Mexican American men but are not optimal for minimizing plasma total homocysteine increases after a methionine load Am. J. Clinical Nutrition, September 1, 2008; 88(3): 685 - 692. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. V. Konstantinova, G. S. Tell, S. E. Vollset, O. Nygard, O. Bleie, and P. M. Ueland Divergent Associations of Plasma Choline and Betaine with Components of Metabolic Syndrome in Middle Age and Elderly Men and Women J. Nutr., May 1, 2008; 138(5): 914 - 920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Solis, K. Veenema, A. A. Ivanov, S. Tran, R. Li, W. Wang, D. J. Moriarty, C. V. Maletz, and M. A. Caudill Folate Intake at RDA Levels Is Inadequate for Mexican American Men with the Methylenetetrahydrofolate Reductase 677TT Genotype J. Nutr., January 1, 2008; 138(1): 67 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. P. Kovacheva, T. J. Mellott, J. M. Davison, N. Wagner, I. Lopez-Coviella, A. C. Schnitzler, and J. K. Blusztajn Gestational Choline Deficiency Causes Global and Igf2 Gene DNA Hypermethylation by Up-regulation of Dnmt1 Expression J. Biol. Chem., October 26, 2007; 282(43): 31777 - 31788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H Zeisel Nutrigenomics and metabolomics will change clinical nutrition and public health practice: insights from studies on dietary requirements for choline Am. J. Clinical Nutrition, September 1, 2007; 86(3): 542 - 548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Resseguie, J. Song, M. D. Niculescu, K.-A. da Costa, T. A. Randall, and S. H. Zeisel Phosphatidylethanolamine N-methyltransferase (PEMT) gene expression is induced by estrogen in human and mouse primary hepatocytes FASEB J, August 1, 2007; 21(10): 2622 - 2632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D Niculescu, K.-A. da Costa, L. M Fischer, and S. H Zeisel Lymphocyte gene expression in subjects fed a low-choline diet differs between those who develop organ dysfunction and those who do not Am. J. Clinical Nutrition, July 1, 2007; 86(1): 230 - 239. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Brown and M. Szyf Epigenetic Programming of the rRNA Promoter by MBD3 Mol. Cell. Biol., July 1, 2007; 27(13): 4938 - 4952. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Mellott, M. T. Follettie, V. Diesl, A. A. Hill, I. Lopez-Coviella, and J. K. Blusztajn Prenatal choline availability modulates hippocampal and cerebral cortical gene expression FASEB J, May 1, 2007; 21(7): 1311 - 1323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Niculescu, R. Wu, Z. Guo, K. A. da Costa, and S. H. Zeisel Diethanolamine Alters Proliferation and Choline Metabolism in Mouse Neural Precursor Cells Toxicol. Sci., April 1, 2007; 96(2): 321 - 326. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
