Choline Supplementation Modifies the Effects of Developmental Alcohol Exposure on Immune Responses in Adult Rats

Baker, Jessica A.; Breit, Kristen R.; Bodnar, Tamara S.; Weinberg, Joanne; Thomas, Jennifer D.

doi:10.3390/nu14142868

Cited by 11 publications

(11 citation statements)

References 85 publications

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“…Choline could also reprogram anti-inflammatory responses with the activation of INFg and TNFa [ 33 , 34 ] in females ( Figure 6 ). In this regard, there is evidence that prenatal choline supplementation mitigates fetal alcohol-exposure-induced pro-inflammatory responses in the adult rat hippocampus [ 35 ]. Thus, the role of prenatal choline in neuroinflammation deserves further analysis.…”

Section: Discussionmentioning

confidence: 99%

Sex-Specific Effects of Early-Life Iron Deficiency and Prenatal Choline Treatment on Adult Rat Hippocampal Transcriptome

et al. 2023

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Background: Fetal-neonatal iron deficiency (ID) causes long-term neurocognitive and affective dysfunctions. Clinical and preclinical studies have shown that early-life ID produces sex-specific effects. However, little is known about the molecular mechanisms underlying these early-life ID-induced sex-specific effects on neural gene regulation. Objective: To illustrate sex-specific transcriptome alterations in adult rat hippocampus induced by fetal-neonatal ID and prenatal choline treatment. Methods: Pregnant rats were fed an iron-deficient (4 mg/kg Fe) or iron-sufficient (200 mg/kg Fe) diet from gestational day (G) 2 to postnatal day (P) 7 with or without choline supplementation (5 g/kg choline) from G11–18. Hippocampi were collected from P65 offspring of both sexes and analyzed for changes in gene expression. Results: Both early-life ID and choline treatment induced transcriptional changes in adult female and male rat hippocampi. Both sexes showed ID-induced alterations in gene networks leading to enhanced neuroinflammation. In females, ID-induced changes indicated enhanced activity of oxidative phosphorylation and fatty acid metabolism, which were contrary to the ID effects in males. Prenatal choline supplementation induced the most robust changes in gene expression, particularly in iron-deficient animals where it partially rescued ID-induced dysregulation. Choline supplementation also altered hippocampal transcriptome in iron-sufficient rats with indications for both beneficial and adverse effects. Conclusions: This study provided unbiased global assessments of gene expression regulated by iron and choline in a sex-specific manner, with greater effects in female than male rats. Our new findings highlight potential sex-specific gene networks regulated by iron and choline for further investigation.

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Section: Discussionmentioning

confidence: 99%

Sex-Specific Effects of Early-Life Iron Deficiency and Prenatal Choline Treatment on Adult Rat Hippocampal Transcriptome

et al. 2023

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“…These neuroprotective effects are consistent with other studies that have shown that MCS lessens the adverse cognitive effects of various developmental insults, including models of various neurological disorders (e.g., Down syndrome. Alzheimer's disease, autism), toxicant exposure (e.g., alcohol), and other environmental influences (e.g., prenatal stress) 28,29,[94][95][96][97][98][99][30][31][32][33][90][91][92][93] . For example, MCS has been shown to lessen the functional deficits produced by developmental alcohol exposure in both rodent models 28,35,96,[98][99][100] , and humans 36,101 .…”

Section: Discussionmentioning

confidence: 99%

“…Alzheimer's disease, autism), toxicant exposure (e.g., alcohol), and other environmental influences (e.g., prenatal stress) 28,29,[94][95][96][97][98][99][30][31][32][33][90][91][92][93] . For example, MCS has been shown to lessen the functional deficits produced by developmental alcohol exposure in both rodent models 28,35,96,[98][99][100] , and humans 36,101 . And of particular interest to the present study, MCS has been shown to lessen the attentional dysfunction, as well as to normalize behavioral reactivity to committing an error or not receiving an expected reward in a mouse model of Down syndrome 33 .…”

Section: Discussionmentioning

confidence: 99%

Maternal choline supplementation lessens the behavioral dysfunction produced by developmental manganese exposure in a rodent model of ADHD

Howard

Beaudin

Strupp

et al. 2023

Preprint

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Background: Studies in children and adolescents have associated early developmental manganese (Mn) exposure with inattention, impulsivity, hyperactivity, and fine motor deficits, and our rodent studies of early life Mn exposure have recapitulated many of these outcomes, demonstrating causality. There are currently no recognized therapies/interventions other than exposure prevention to mitigate the neurotoxic effects of developmental Mn exposure. One possible preventive treatment is to supplement the maternal diet with additional choline during pregnancy. Maternal choline supplementation (MCS) has been shown to improve offspring cognitive function in humans and animal models, and lessens dysfunction caused by various developmental insults. Objectives: Determine whether MCS during pregnancy and lactation protects against Mn-induced impairments in attention, impulse control, learning, behavioral reactivity, and sensorimotor function. Methods: Starting at gestational day 3 (G3), pregnant dams were given standard diet or diet with additional choline (4x the level in standard diets) throughout gestation and lactation until offspring were weaned on PND 21. Pups were exposed orally to 0 or 50 mg Mn/kg/day during early postnatal life (PND 1-21). In adulthood, animals were tested in the five-choice serial reaction time task and the Montoya staircase task, to assess impulsivity, focused and selective attention, behavioral reactivity to errors or omission of an expected reward, and sensorimotor function. Results: MCS intervention was partially effective in protecting against the Mn-induced deficits, with the degree of benefit varying with the specific domain of function. Specifically, MCS lessens differences between Mn and control animals in attentional function and reactivity to committing an error or not receiving an expected reward. MCS does not protect against Mn-induced sensorimotor dysfunction. Finally, in the absence of Mn exposure, MCS produces lasting benefits in attentional function and reactivity to errors. Conclusions: MCS was partially effective in alleviating Mn-induced deficits: MCS normalized Mn exposed animals in the domains of attentional function and behavioral reactivity. These findings have implications for understanding the molecular mechanisms by which both MCS and Mn produce lasting cognitive changes, and provide further evidence that MCS benefits offspring. These findings, taken with evidence from other studies demonstrating the benefit of MCS to offspring and the fact that ~90% of women consume less than the adequate intake (AI) of choline, inform the recommendation that MCS should be considered for pregnant women.

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“…Choline could also reprogram anti-inflammatory responses with an activation of INFg and TNFa [33, 34] in females (Figure 6). In this regard, there is evidence that prenatal choline supplementation mitigates fetal alcohol-exposure induced pro-inflammatory responses in the adult rat hippocampus [35]. Thus, the role of prenatal choline supplementation in neuroinflammation deserves further analyses.…”

Section: Discussionmentioning

confidence: 99%

Sex-Specific Effects of Early-Life Iron Deficiency and Prenatal Choline Treatment on Adult Rat Hippocampal Transcriptome

Liu

Fredrickson

Gisslen³

et al. 2022

Preprint

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Background: Fetal-neonatal iron deficiency (ID) causes long-term neurocognitive and affective dysfunctions. Clinical and preclinical studies showed that early-life ID produced sex-specific effects. However, little is known about molecular mechanisms behind the sex-specific effects of early-life ID on neural gene regulation. Objective: To illustrate sex-specific transcriptome alteration in adult rat hippocampus induced by fetal-neonatal ID and prenatal choline treatment. Methods: Pregnant rats were fed iron-deficient (4 mg/kg Fe) or iron-sufficient (200 mg/kg Fe) diet from gestational day (G) 2 to postnatal day (P) 7 with or without choline supplementation (5 g/kg choline) from G11-18. Hippocampi were collected from P65 offspring of both sexes and analyzed for changes in gene expression. Results: Both early-life ID and choline treatment induced more transcriptional changes in female rat hippocampus than males with a less than 10 percent overlap between sexes. While both sexes showed alterations in gene networks related to increased risks of neurocognitive disorders, males also showed enhanced anti-inflammatory activities in response to ID, contrary to activated pro-inflammatory responses in females. Prenatal choline treatment to ID animals partially rescued ID-induced dysregulations in males but showed less effects in females. However, choline treatment to iron-sufficient rats showed more negative effects on the regulation of genes associated with cognition and affective behaviors, especially in females. Conclusions: This study provided unbiased global assessments of gene expression regulated by iron and choline in a sex-specific manner, with greater negative effects in female than male rats. Our new findings highlight potential sex-specific gene networks for further investigation.

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Choline Supplementation Modifies the Effects of Developmental Alcohol Exposure on Immune Responses in Adult Rats

Cited by 11 publications

References 85 publications

Sex-Specific Effects of Early-Life Iron Deficiency and Prenatal Choline Treatment on Adult Rat Hippocampal Transcriptome

Sex-Specific Effects of Early-Life Iron Deficiency and Prenatal Choline Treatment on Adult Rat Hippocampal Transcriptome

Maternal choline supplementation lessens the behavioral dysfunction produced by developmental manganese exposure in a rodent model of ADHD

Sex-Specific Effects of Early-Life Iron Deficiency and Prenatal Choline Treatment on Adult Rat Hippocampal Transcriptome

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