Folic Acid Deficiency During Late Gestation Decreases Progenitor Cell Proliferation and Increases Apoptosis in Fetal Mouse Brain

Craciunescu, Corneliu N.; Brown, Elliott C.; Mar, Mei Heng; Albright, Craig D.; Nadeau, Marie; Zeisel, Steven H.

doi:10.1093/jn/134.1.162

Cited by 160 publications

(134 citation statements)

References 48 publications

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“…Choline and folate metabolism intersect at pathways for methyl-group donation (see discussion above) and it is reasonable to hypothesize that methylation reactions are the mechanism they share that influences neural tube closure. As discussed below, folate deficiency and choline deficiency have similar effects on stem cell proliferation and apoptosis in the brain (31,32).…”

Section: Choline and Brain Development In Uteromentioning

confidence: 99%

Choline: Critical Role During Fetal Development and Dietary Requirements in Adults

2006

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Choline is an essential nutrient needed for the structural integrity and signaling functions of cell membranes; for normal cholinergic neurotransmission; for normal muscle function; for lipid transport from liver; and it is the major source of methyl groups in the diet. Choline is critical during fetal development, when it influences stem cell proliferation and apoptosis, thereby altering brain and spinal cord structure and function and influencing risk for neural tube defects and lifelong memory function. Choline is derived not only from the diet, but from de novo synthesis as well. Though many foods contain choline, there is at least a twofold variation in dietary intake in humans. When deprived of dietary choline, most men and postmenopausal women developed signs of organ dysfunction (fatty liver or muscle damage), while less than half of premenopausal women developed such signs. Aside from gender differences, there is significant variation in the dietary requirement for choline that can be explained by very common genetic polymorphisms.

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Section: Choline and Brain Development In Uteromentioning

confidence: 99%

Choline: Critical Role During Fetal Development and Dietary Requirements in Adults

2006

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“…However, it is unclear if this mechanism contributes to AED-induced behavioral teratogenesis. Folate deficiency during pregnancy reduces neurogenesis and increases apoptosis [34], but folate nutritional status during pregnancy has not been shown to impact neurodevelopment [35]. As discussed below, there is mounting evidence that AED-induced apoptosis is the most likely candidate for the behavioral deficits.…”

Section: Proposed Mechanismsmentioning

confidence: 99%

Cognitive/behavioral teratogenetic effects of antiepileptic drugs

Meador

Baker

Cohen

et al. 2007

Epilepsy & Behavior

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The majority of children of mothers with epilepsy are normal, but they are at increased risk for developmental delay. Antiepileptic drugs (AEDs) appear to play a role. Our current knowledge is reviewed, including research design issues and recommendations for future research. In animals, exposure of the immature brain to some AEDs can produce widespread neuronal apoptosis and behavioral deficits. The risks of AEDs in humans are less clear, but recent studies raise concerns, especially for valproate. There is a critical need for well-designed systematic research to improve our understanding of AED effects on the fetal brain. KeywordsAntiepileptic drugs; Anticonvulsant drugs; Pregnancy; Teratogenesis; Development; Cognition; Behavior Animal studies on behavioral effects of in utero AED exposureAnimal studies have demonstrated that in utero antiepileptic drug (AED) exposure can produce behavioral as well as anatomical defects, which can occur at dosages lower than those required to produce somatic malformations [1,2]. Gestational or neonatal exposure to benzodiazepines can affect brain chemistry and behavior causing hyperactivity or learning deficits [3,4]. Despite the common use of carbamazepine in humans, very few neurobehavioral studies in animals have been conducted with this AED. In utero carbamazepine exposure did not produce hyperexcitability in primates [5]. Perinatal phenobarbital exposure in rats reduces brain weight [6]. Mice exposed prenatally to phenobarbital have neuronal deficits, reduced brain weight, and impaired development of reflexes, open-field activity, schedule-controlled behavior, spatial learning, and cate-cholamine brain levels [7][8][9][10][11][12]. Gestational or neonatal exposure to phenytoin reduces brain weight [13,14], alters neuronal membranes in the hippocampus [15], delays neurodevelopment [16], and impairs spatial learning and motor coordination [17][18][19][20][21][22][23][24][25]. Hyperactivity has been observed in rats and primates following prenatal exposure to phenytoin [5,23,25]. Gestational primidone in rats produces learning deficits and reduces open-field activity [26]. In utero valproate exposure can alter neuronal membranes [27], decrease brain weight in mice [28], and result in adverse neurobehavioral effects [29,30].

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“…It has been reported also that deficiency diet of some methyl donors (Zinc, folic acid or choline) during gestational and lactation phase in mice causes memory defects in their offspring, neuronal apoptosis increasing and decreasing of cell proliferation [58] [59] [60] [61].…”

Section: Discussionmentioning

confidence: 99%

Methyl Donors Supplementation Attenuates the Adverse Effects of Maternal High Fructose Diet of Offspring Emotional and Cognitive Behaviors

Coulibaly¹,

Mesfioui²,

Ouichou³

et al. 2017

OJEMD

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Free Fatty acid is an end-product of hepatic metabolism of fructose. Most of past studies have demonstrated significant relationship between gestational high fat diet and metabolic and physiology outcomes in offspring. However, there is a scarce of data extended to the effects of high fructose diet-fed dams on juveniles' progeny. Therefore, the present experiment was designed to examine the later effects of maternal high fructose diet intake during pregnancy and lactation on juvenile offspring rats emotional behaviors and memory abilities. We tested whether methyl donors supplemented to that high fructose diet could reverse the adverse effects. We found at two months of age, anxiety-like behavior and depression-like behavior were elevated in off springs of mother fed to high fructose diet and a sex difference effect with males were more affected than females. In addition, behavioral outcomes indicated that the high fructose diet also impaired spatial working and recognition memories in the Y-maze and object recognition test respectively. Blood glucose intolerance increased significantly in juvenile males rats of dams fed with high fructose diet when compared to females. However, a supplementation of the maternal diet with methyl donors attenuated all these changes. Our study suggested a controlled fructose diet supplemented to methyl donors during critical period of brain developing (in utero and pre-weaning stage), otherwise that could induced irreversible detrimental effects on offspring behavior and cognitive health.

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Folic Acid Deficiency During Late Gestation Decreases Progenitor Cell Proliferation and Increases Apoptosis in Fetal Mouse Brain

Cited by 160 publications

References 48 publications

Choline: Critical Role During Fetal Development and Dietary Requirements in Adults

Choline: Critical Role During Fetal Development and Dietary Requirements in Adults

Cognitive/behavioral teratogenetic effects of antiepileptic drugs

Methyl Donors Supplementation Attenuates the Adverse Effects of Maternal High Fructose Diet of Offspring Emotional and Cognitive Behaviors

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