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Nutritional Neurosciences

Choline Availability During Embryonic Development Alters Progenitor Cell Mitosis in Developing Mouse Hippocampus^1,2

Department of Nutrition, School of Public Health and School of Medicine, University of North Carolina, Chapel Hill, NC 27599-7400

³To whom correspondence should be addressed. E-mail: steven_zeisel{at}unc.edu.

Previously, we reported that dietary choline influences development of the hippocampus in fetal rat brain. It is important to know whether similar effects of choline occur in developing fetal mouse brain because interesting new experimental approaches are now available using several transgenic mouse models. Timed-pregnant mice were fed choline-supplemented (CS), control (CT) or choline-deficient (CD) AIN-76 diet from embryonic day 12 to 17 (E12–17). Fetuses from CD dams had diminished concentrations of phosphocholine and phosphatidylcholine in their brains compared with CT or CS fetuses (P < 0.05). When we analyzed fetal hippocampus on day E17 for cells with mitotic phase–specific expression of phosphorylated histone H3, we detected fewer labeled cells at the ventricular surface of the ventricular zone in the CD group (14.8 ± 1.9) compared with the CT (30.7 ± 1.9) or CS (36.6 ± 2.6) group (P < 0.05). At the same time, we detected more apoptotic cells in E17 hippocampus using morphology in the CD group (11.8 ± 1.4) than in CT (5.6 ± 0.6) or CS (4.2 ± 0.7) group (P < 0.05). This was confirmed using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin anti-digoxigenin fluorescein conjugate antibody nick end-labeling (TUNEL) and activated caspase-3 immunoreactivity. We conclude that the dietary availability of choline to the mouse dam influences progenitor cell proliferation and apoptosis in the fetal brain.

KEY WORDS: • choline • phosphatidylcholine • brain development • mice • hippocampus

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