Choline Availability During Embryonic Development Alters Progenitor Cell Mitosis in Developing Mouse Hippocampus

Craciunescu, Corneliu N.; Albright, Craig D.; Mar, Mei Heng; Song, Jun; Zeisel, Steven H.

doi:10.1093/jn/133.11.3614

Cited by 157 publications

(165 citation statements)

References 42 publications

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“…Intrauterine choline deficiency has been shown to result in structural defects in the hippocampus of rats [36] and mice [37][38][39]. Choline availability altered the timing, genesis, migration and differentiation of progenitor neuronal-type cells in the fetal hippocampus.…”

Section: Betaine Supplementation To Lactating Dams Increases Betaine mentioning

confidence: 99%

Betaine rescue of an animal model with methylenetetrahydrofolate reductase deficiency

Schwahn

Laryea

Chen

et al. 2004

Biochemical Journal

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MTHFR (methylenetetrahydrofolate reductase) catalyses the synthesis of 5-methyltetrahydrofolate, the folate derivative utilized in homocysteine remethylation to methionine. A severe deficiency of MTHFR results in hyperhomocysteinaemia and homocystinuria. Betaine supplementation has proven effective in ameliorating the biochemical abnormalities and the clinical course in patients with this deficiency. Mice with a complete knockout of MTHFR serve as a good animal model for homocystinuria; early postnatal death of these mice is common, as with some neonates with low residual MTHFR activity. We attempted to rescue Mthfr−/− mice from postnatal death by betaine supplementation to their mothers throughout pregnancy and lactation. Betaine decreased the mortality of Mthfr−/− mice from 83 % to 26 % and significantly improved somatic development from postnatal day 1, compared with Mthfr−/− mice from unsupplemented dams. Biochemical evaluations demonstrated higher availability of betaine in suckling pups, decreased accumulation of homocysteine, and decreased flux through the trans-sulphuration pathway in liver and brain of Mthfr−/− pups from betaine-supplemented dams. We observed disturbances in proliferation and differentiation in the cerebellum and hippocampus in the knockout mice; these changes were ameliorated by betaine supplementation. The dramatic effects of betaine on survival and growth, and the partial reversibility of the biochemical and developmental anomalies in the brains of MTHFR-deficient mice, emphasize an important role for choline and betaine depletion in the pathogenesis of homocystinuria due to MTHFR deficiency.

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Section: Betaine Supplementation To Lactating Dams Increases Betaine mentioning

confidence: 99%

Betaine rescue of an animal model with methylenetetrahydrofolate reductase deficiency

Schwahn

Laryea

Chen

et al. 2004

Biochemical Journal

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“…Surprisingly, netrin-1 and DCC showed similar changes in the CD and CS groups. This is in contrast to mitotic inhibition, apoptosis, and cell proliferation in fetal developing hippocampus which do not track in the same direction in the CD and CS groups [2][3][4]7,14], suggesting not only that each of these components of neurogenesis has a different choline dose-response, but also that the consequences of netrin-DCC signaling for precursor cell migration are dependent on additional molecular interactions. For example, recent reports suggest a critical role for cyclic nucleotides in regulating the response to guidance cues.…”

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confidence: 97%

Maternal dietary choline availability alters the balance of netrin-1 and DCC neuronal migration proteins in fetal mouse brain hippocampus

Albright¹,

Mar²,

Craciunescu³

et al. 2005

Developmental Brain Research

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Alterations in maternal dietary choline availability during days 12-17 of pregnancy led to an increase in the level of immunoreactive netrin-1 and a decrease in the level of DCC protein in the developing fetal mouse brain hippocampus compared with controls. Changes in the expression of cell migration cues during development could account for some of the lifelong consequences of maternal dietary choline availability for cognitive and memory processes. KeywordsBrain development; Chemoattraction; Choline; Hippocampus; Pregnancy Maternal dietary choline availability during pregnancy plays a critical role in the establishment and lifelong functioning of cognitive and memory processes in rodent offspring. The underlying choline-sensitive physiological and biochemical processes (e.g., threshold for longterm potentiation; cholinergic activity) affecting temporal and spatial memory in offspring are beginning to be understood [13,20,22]. However, the neuroanatomical basis for these behavioral changes is less well understood.The neuroanatomical development of the fetal hippocampus is influenced by the proliferation, survival, and migration of precursor cells generated in the ventricular zone. We previously showed that, depending on the availability of maternal dietary choline, precursor cells in ventricular zone undergo proliferation and commit to differentiate into neuronal cell types (e.g., calretinin-containing cells) [8] known to regulate memory, or undergo apoptosis. We previously described how choline availability affects pro-apoptotic signal transduction in neuronal-type cells [18,28] and hepatocytes [1,4,6,7,9]. We are beginning to understand how maternal dietary choline availability during pregnancy affects not only the generation, but also the targeted migration of precursor neuronal-type cells in the fetal hippocampus [2,3,14]. Targeted migration of precursor cells in the developing nervous system is regulated in part by interactions between the binding of netrin-1, a secreted glycoprotein, and to DCC, a transmembrane receptor [16,17]. These interactions can exert repulsive and attractive effects on precursor-type cells in the developing nervous system [19,21]. In addition to steering the migration of precursor cells in developing brain, interactions between netrin and DCC have also been implicated in apoptosis signaling [15]. In order to better understand the neuroanatomical basis for the effects of maternal dietary choline on the establishment of an functioning of cognitive and memory processes in rodent offspring, we investigated whether choline availability in the diet of pregnant mice alters the localization of netrin-1 and DCC proteins that are known to direct the migration of precursor cells in developing brain.Timed-pregnant C57BL/6 mice (Jackson Lab., Bar Harbor, ME) obtained on days 4-9 of gestation were maintained in a climate-controlled environment and exposed to a 12-h light/ dark cycle daily. The animals were provided with AIN-76A diet containing 1.1 g/kg choline chloride (Dyets, Bethlehem,...

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“…The cholinergic cells of the hippocampus are related to the learning and memory capabilities of the brain (Ragozzino et al, 1996;Das, 2003). Choline supplementation during the gestational period increases the sensibility of hippocampus neurons to stimulus (López et al, 1992), increases the concentration of acetylcholine at the frontal cortex and hippocampus (Jones et al, 1999), regulates the cellular cycle and neuronal apoptosis during brain development (Craciunescu et al, 2003) and increases the size of cholinergic hippocampus neurons (Loy et al, 1991). Acetylcholine, like other neurotransmitters, plays an important role in neurite outgrowth, growth cone motility, target cell selection and synaptogenesis (Spencer et al, 1998;Weiss et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Supplementing female rats with DHA-lysophosphatidylcholine increases docosahexaenoic acid and acetylcholine contents in the brain and improves the memory and learning capabilities of the pups.

Valenzuela¹,

Nieto²,

Sanhueza³

et al. 2009

Grasas y Aceites

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DHA has been established. We propose that DHAcontaining lysophosphatidylcholine (DHA-LPC), obtained from DHA-rich eggs may be a suitable form of DHA and choline (the precursor of acetylcholine) supplementation. We evaluated the effectiveness of DHA-LPC to increase DHA and acetylcholine concentration in the brain of pups born from female rats supplemented with DHA-LPC before and during pregnancy. We also evaluated the effect of DHA supplementation on learning and memory capabilities of pups through the Skinner test for operant conditioning. Female Wistar rats received 40-day supplementation of DHA-LPC (8 mg DHA/kg b.w/daily.), before and during pregnancy. After delivery, plasma, erythrocyte, liver, and adipose tissue DHA and plasma choline were analyzed. Brains from 60 day-old pups separated into frontal cortex, cerebellum, striatum, hippocampus, and occipital cortex, were assessed for DHA, acetylcholine, and acetylcholine transferase (CAT) activity. Pups were subjected to the Skinner box test. DHA-LPC supplementation produces higher choline and liver DHA contents in the mother's plasma and increases the pups' DHA and acetylcholine in the cerebellum and hippocampus. CAT was not modified by supplementation. The Skinner test shows that pups born from DHA-LPC supplemented mothers exhibit better scores of learning and memory than the controls. Conclusion: DHA-LPC may be an adequate form for DHA supplementation during the perinatal period. KEY-WORDS: Brain acetylcholine -Choline -DHA supplementation -Lysophospholipids -Skinner box test.

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Choline Availability During Embryonic Development Alters Progenitor Cell Mitosis in Developing Mouse Hippocampus

Cited by 157 publications

References 42 publications

Betaine rescue of an animal model with methylenetetrahydrofolate reductase deficiency

Betaine rescue of an animal model with methylenetetrahydrofolate reductase deficiency

Maternal dietary choline availability alters the balance of netrin-1 and DCC neuronal migration proteins in fetal mouse brain hippocampus

Supplementing female rats with DHA-lysophosphatidylcholine increases docosahexaenoic acid and acetylcholine contents in the brain and improves the memory and learning capabilities of the pups.

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