Untitled

Albright, Craig D.; Tsai, Amy Y.; Mar, Mei Heng; Zeisel, Steven H.

doi:10.1023/a:1022411510636

Cited by 32 publications

(6 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, choline availability during development can influence cell division, migration and differentiation of hippocampal cells (Albright et al, 1999; Albright et al, 2005; Albright et al, 1998), leading to long-lasting increases in cell size and basal dendritic arborization in CA1 pyramidal neurons (Li et al, 2004). But more importantly, perinatal choline supplementation leads to long-lasting changes in hippocampal plasticity that continue throughout the lifespan.…”

Section: Discussionmentioning

confidence: 99%

Choline supplementation mitigates trace, but not delay, eyeblink conditioning deficits in rats exposed to alcohol during development

Thomas

Tran

2011

Hippocampus

View full text Add to dashboard Cite

Children exposed to alcohol prenatally suffer from a range of physical, neuropathological and behavioral alterations, referred to as Fetal Alcohol Spectrum Disorders (FASD). Both the cerebellum and hippocampus are affected by alcohol exposure during development, which may contribute to behavioral and cognitive deficits observed in children with FASD. Despite the known neuropathology associated with prenatal alcohol exposure, many pregnant women continue to drink (heavy drinkers, in particular), creating a need to identify effective treatments for their children who are adversely affected by alcohol. We previously reported that choline supplementation can mitigate alcohol’s effects on cognitive development, specifically on tasks which depend on the functional integrity of the hippocampus. The present study examined whether choline supplementation could differentially mitigate ethanol’s effects on trace eyeblink classical conditioning (a hippocampal-dependent task) and delay eyeblink classical conditioning (a cerebellar-dependent task). Long-Evans rats were exposed to 5.25 g/kg/day alcohol via gastric intubation from postnatal days (PD) 4-9, a period of brain development equivalent to late gestation in humans. A sham-intubated control group was included. From PD 10-30, subjects received subcutaneous injections of 100 mg/kg choline chloride or vehicle. Beginning on PD 32-34, subjects were trained on either delay or trace eyeblink conditioning. Performance of subjects exposed to alcohol was significantly impaired on both tasks, as indicated by significant reductions in percentage and amplitude of conditioned eyeblink responses, an effect that was attenuated by choline supplementation on the trace, but not delay conditioning task. Indeed, ethanol-exposed subjects treated with choline performed at control levels on the trace eyeblink conditioning task. There were no significant main or interactive effects of sex. These data indicate that choline supplementation can significantly reduce the severity of trace eyeblink conditioning deficits associated with early alcohol exposure, even when administered after the alcohol insult is complete. These findings have important implications for the treatment of fetal alcohol spectrum disorders.

show abstract

Section: Discussionmentioning

confidence: 99%

Choline supplementation mitigates trace, but not delay, eyeblink conditioning deficits in rats exposed to alcohol during development

Thomas

Tran

2011

Hippocampus

View full text Add to dashboard Cite

show abstract

“…Low choline was associated with increased expression of genes which inhibit cell cycling (CDKN3; p15Ink4B; p27Kip1) in the neural progenitor cells of the fetal hippocampus [9, 10]. Also, lower choline was associated with increased expression of genes and proteins that mark the differentiation of progenitor cells into mature neurons (calretinin, TOAD) [6, 11–13]. Lower choline decreased the expression of proteins that drive neuronal migration (netrin) and decreased the rate at which neuronal precursor cells in the subventricular region migrated to the dentate gyrus region of the hippocampus after undergoing mitosis [6–8, 14].…”

Section: Choline and Fetal Progenitor Cellsmentioning

confidence: 99%

The supply of choline is important for fetal progenitor cells

Zeisel

2011

Seminars in Cell & Developmental Biology

Self Cite

View full text Add to dashboard Cite

Fetal progenitor cells proliferate, migrate, differentiate and undergo apoptosis at specific times during fetal development. Choline is needed by these cells for membrane synthesis and for methylation. There is growing evidence that this nutrient also modulates epigenetic regulation of gene expression in both neuronal and endothelial progenitor cells, thereby modifying brain development. It is likely that these mechanisms explain why, in rodent models, maternal dietary intake of choline influences both angiogenesis and neurogenesis in fetal hippocampus, and results in life-long changes in memory function. This also may explain why women eating diets low in choline have a greater risk of having a baby with a birth defect. Choline is mainly found in foods that contain fat and cholesterol, and intake of such foods has diminished in response dietary advice from nutritionists and physicians. Forty years ago, diets commonly contained choline-rich foods but now women in the USA tend to eat diets low in choline content. Premenopausal women normally may require less choline in their diet than do men and postmenopausal women, because estrogen induces the gene for the enzyme catalyzing endogenous biosynthesis of the choline-containing phospholipid phosphatidylcholine. However, many women have a single nucleotide polymorphism (SNP) that blocks the induction of endogenous biosynthesis, thereby making them require more dietary choline. When these women eat diets low in choline, the supply of this nutrient to the fetus is likely to be inadequate, and may perturb progenitor cell proliferation, migration, differentiation and apoptosis.

show abstract

“…Low choline availability to the fetal brain results in decreased production of the receptor for EGF [52]. Similarly, low maternal choline intake results in premature differentiation of neural progenitors in the fetal hippocampus [54,55,56,57]. This area of the brain is important for memory function.…”

Section: Choline Epigenetics and Fetal Developmentmentioning

confidence: 99%

Choline, Other Methyl-Donors and Epigenetics

2017

View full text Add to dashboard Cite

Choline dietary intake varies such that many people do not achieve adequate intakes. Diet intake of choline can modulate methylation because, via betaine homocysteine methyltransferase (BHMT), this nutrient (and its metabolite, betaine) regulate the concentrations of S-adenosylhomocysteine and S-adenosylmethionine. Some of the epigenetic mechanisms that modify gene expression without modifying the genetic code depend on the methylation of DNA or of histones; and diet availability of choline and other methyl-group donors influences both of these methylations. Examples of methyl-donor mediated epigenetic effects include the changes in coat color and body weight in offspring when pregnant agouti mice are fed high choline, high methyl diets; the changes in tail kinking in offspring when pregnant Axin(Fu) mice are fed high choline, high methyl diets; the changes in Cdkn3 methylation and altered brain development that occurs in offspring when pregnant rodents are fed low choline diets. When choline metabolism is disrupted by deleting the gene Bhmt, DNA methylation is affected (especially in a region of chromosome 13), expression of specific genes is suppressed, and liver cancers develop. Better understanding of how nutrients such as choline and methyl-donors influence epigenetic programs has importance for our understanding of not only developmental abnormalities but also for understanding the origins of chronic diseases.

show abstract

Untitled

Cited by 32 publications

References 50 publications

Choline supplementation mitigates trace, but not delay, eyeblink conditioning deficits in rats exposed to alcohol during development

Choline supplementation mitigates trace, but not delay, eyeblink conditioning deficits in rats exposed to alcohol during development

The supply of choline is important for fetal progenitor cells

Choline, Other Methyl-Donors and Epigenetics

Contact Info

Product

Resources

About