Neurochemical and behavioral effects of diet related perinatal folic acid restriction

Middaugh, Lawrence D.; Grover, Thomas A.; Blackwell, Luke; Zemp, John W.

doi:10.1016/0091-3057(76)90027-7

Cited by 20 publications

(15 citation statements)

References 13 publications

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“…Alternatively, excessive maternal dietary supplementation of folic acid resulted in reduced global methylation in placental tissue of Wistar albino rats (31). Multiple sources have suggested that maternal folic acid inadequacy may predispose offspring to a secondary metabolic stressor and would thus lead to abnormal behaviors such as reduced locomotor activity and increased conditioned escape response (27,29). These findings provide evidence that confirm findings from epidemiological data and further suggest that offspring of maternal folic acid deficiencies may lead to altered methylation profiles in offspring.…”

Section: Methylationsupporting

confidence: 76%

“…For example, metabolism of the free form of folate, 5-methylTHF, is intimately involved with the synthesis of methionine, an amino acid critical in DNA methylation and repair. It has been reported that SAM, a global methyl donor, is reduced in the livers and brains of mouse pups of their mothers subjected to a dietary folic acid deficiency, and interestingly, this reduction was exacerbated after a shock stressor (27), suggesting that these pups have reduced DNA methylation due to a dietary folic acid deficiency. A similar study using rats found similar results in the Purkinje cells of the cerebellum (28), which may imply disrupted motor coordination.…”

Section: Methylationmentioning

confidence: 99%

“…Other behavioral deficits have been documented as early as 1951, where offspring of folic acid deficient dams exhibited reduced maze learning ability (36). Also, in 1976, a study using 35 day old mice demonstrated that folic acid deficient dams bore offspring that scored significantly lower on locomotor activity and conditioned escape behavior (27). Most recently, visual and spatial short term memory impairments (37) as a result of maternal MTHFR or folic acid deficiencies have been reported in wild-type offspring, possibly as result of increased maternal homocysteine levels.…”

Section: Animal Behaviormentioning

confidence: 99%

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Impact of Maternal Folate Deficiencies on Early Neurological Development: A Narrative Review

Emmerson¹,

Jadavji²

2016

J Pediatr Rev

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Context: Folates are B-vitamins that cannot be generated de novo and are therefore obtained from the diet. In the brain, these vitamins are involved in nucleotide synthesis, DNA repair, lipid metabolism, methylation and neurotransmitter synthesis. It is well established that adequate levels of maternal folates are required for closure of the neural tube within the first month of pregnancy, however, it is not clear whether maternal folates are needed throughout pregnancy for brain development and whether they influence offspring neurological function after birth. The aim of this review is to outline current literature from epidemiological and animal model studies that shows maternal supplementation of folates throughout pregnancy does indeed affect offspring neurological function after birth. Evidence Acquisition: A Medline search was performed using the following mesh terms, maternal-fetal exchange, folic acid, offspring neurologic manifestations, methylenetetrahydrofolate reductase (MTHFR), embryology, and behavior. Results: The studies described in the present review have reported that maternal deficiencies in folates during pregnancy result in changes in behavior as well as in blood and brain tissue in offspring, including altered methylation, including reduced levels of the global methyl donor S-adenosylmethionine (SAM), and increased levels of oxidative stress. Conclusions:The data summarized here outlines the importance of adequate levels of folates throughout pregnancy to facilitate appropriate neurological development of offspring after birth.

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Section: Methylationsupporting

confidence: 76%

Section: Methylationmentioning

confidence: 99%

Section: Animal Behaviormentioning

confidence: 99%

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Impact of Maternal Folate Deficiencies on Early Neurological Development: A Narrative Review

Emmerson¹,

Jadavji²

2016

J Pediatr Rev

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“…In rats, the concentrations of many folate-dependent enzymes were substantially higher during early development than adult levels [23]. Dams and developing pups fed with diets eliminating folic acid 1 week prior to birth were less viable and had lower brain weights, lower activity level, and lower level of S-adenosyl-L-methionine concentrations in brain tissue of surviving offspring than animals reared on normal diets [24]. Ferguson et al examined whether gestational dietary folate deficiency not producing severe NTDs could lead to other functional impairments in mice [25].…”

Section: Discussionmentioning

confidence: 99%

New Perspective on Impact of Folic Acid Supplementation during Pregnancy on Neurodevelopment/Autism in the Offspring Children – A Systematic Review

et al. 2016

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It has been conclusively established that folic acid supplementation prior to and during early pregnancy (up to 12 weeks of gestation) can prevent neural tube defects (NTDs). We hypothesized that folate effects may extend from neuro-structural defects to alterations in neuro-behavioural and emotional skills including autism spectrum disorders (ASDs) and other developmental disorders. The objective of this review was to comprehensively evaluate evidence on the impact of folic acid on neurodevelopment other than NTDs. We conducted an online search of relevant literature compiled by the National Library of Medicine from Medline and EMBASE (searched on Dec 31, 2014: http://www.ncbi.nlm.nih.gov/entrez/query/fcgi and http://www.elsevier.com/online-tools/embase). We first created 3 files (search restricted to English literature) using the following key words: 1) folate or folic acid (171322 papers identified by this search); 2) maternal or pregnancy or pregnant or gestation or gestational or prenatal or antenatal or periconception or periconceptional (1349219 papers identified by this search); and 3) autism or autism spectrum disorders or developmental delay or development or neurodevelopment or mental or cognitive or language or personal-social or gross motor or fine motor or behaviour or intellectual or intelligence or Bayley Scale (8268145 papers identified by this search). We then merged the 3 files and reviewed the papers that addressed these three issues simultaneously. A total of 22 original papers that examined the association between folic acid supplementation in human pregnancy and neurodevelopment/autism were identified after the screening, with 15 studies showing a beneficial effect of folic acid supplementation on neurodevelopment/autism, 6 studies showed no statistically significant difference, while one study showed a harmful effect in > 5 mg folic acid supplementation/day during pregnancy. Folic acid supplementation in pregnancy may have beneficial effects on the neurodevelopment of children beyond its proven effect on NTDs.

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“…But in that case, those of the mother remained low, indicating that folate transfer to the litter prevailed on the maintenance of maternal stores (29). Fetal folate stores are known to be an essential factor of a normal postnatal development (25), in mammals in general (26) and especially in the human spe cies (24,28), first of all in the case of prema turity (13,35). They are built in utero (31), even at the mother's expense as was pointed out by Strelling (34) and Grossowicz et al…”

Section: Discussionmentioning

confidence: 99%

Effects of Diets with or without Folic Acid, with or without Methionine, on Fetus Development, Folate Stores and Folic Acid-Dependent Enzyme Activities in the Rat

Courcy¹,

Bujoli²

1981

Neonatology

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Wistar female rats fed, since mating, with diets lacking either methionine, replaced in this case by homocystine (HF), or folic acid (MO), or both (HO). With diets lacking either one of the two factors, fetal weights remained in the range of the controls. When both factors were absent from the diet (HO), underweight fetuses were observed on day 20. In the offspring of folic acid-deficient mothers (MO), only folyloligoglutamates were lowered; total ones remained near control level. Switching HO females to a folic acid-supplemented diet from day 16 to 20 of pregnancy restored fetal weight and folates to the control level. The activity of folico-dependent enzymes of the whole fetal body or liver varied in parallel to fetal weight. We conclude from these data that: (1) methionine has a protective effect on folates in MO groups; (2) when folic acid is present in a diet containing homocystine but no methionine (MF), endogenous methionine synthesis is sufficient to cover maternal and fetal needs; (3) when the vitamin is also withdrawn (HO), methionine synthesis is no more adequate and fetal underdevelopment appears.

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Neurochemical and behavioral effects of diet related perinatal folic acid restriction

Cited by 20 publications

References 13 publications

Impact of Maternal Folate Deficiencies on Early Neurological Development: A Narrative Review

Impact of Maternal Folate Deficiencies on Early Neurological Development: A Narrative Review

New Perspective on Impact of Folic Acid Supplementation during Pregnancy on Neurodevelopment/Autism in the Offspring Children – A Systematic Review

Effects of Diets with or without Folic Acid, with or without Methionine, on Fetus Development, Folate Stores and Folic Acid-Dependent Enzyme Activities in the Rat

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