Abstract
Choline dehydrogenase (CHDH) catalyzes the conversion of choline to betaine. Betaine is an osmolyte and an important methyl‐group donor. Previously, increased availability of choline to fetal brain resulted in increased hippocampal neurogenesis. The proposed mechanism involved epigenetic changes in genes that regulate cell proliferation. To determine if the effects of choline on neurogenesis are mediated by conversion to betaine and then donation of a methyl‐group for the methylation of DNA, we studied brain development in the Chdh−/− mouse. These animals cannot use choline as a methyl‐donor, and were expected to have abnormal hippocampal neurogenesis in the fetal brain. Chdh+/− breeding pairs fed AIN‐76A diet with 1.1 g/kg choline chloride were time‐mated. At embryonic day 17 (E17) of pregnancy fetal brain and liver were collected, and either fixed for immunohistochemistry (IHC) or frozen for gene expression and choline metabolite measures. Proliferation of neural progenitor cells in the subventricular region of the Chdh−/−and Chdh+/+ littermate control hippocampus was assessed using IHC for the mitosis marker phosphorylated histone 3. Apoptosis in this brain region was assessed by fluorescent TUNEL staining. We assessed developmental differences in Chdh mRNA expression; in E17 fetal liver expression was 46% lower than in adult liver (p < 0.01); in E17 whole fetal brain expression was 74% lower than in adult adult brain (p < 0.01). Preliminary results show no difference in neurogenesis between the genotypes. Measurements of apoptosis and choline metabolites are pending. These findings will help elucidate if choline modulates brain development via donation of methyl‐groups.Grant Funding Source: Agriculture and Food Research Initiative Grant no. 2010–65200‐20354 from the USDA National Institute of Food and Agriculture.
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