Sex-Specific Effects of Early-Life Iron Deficiency and Prenatal Choline Treatment on Adult Rat Hippocampal Transcriptome
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PROVIDER: PRJNA953771 | ENA |
REPOSITORIES: ENA
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Project description:Fetal-neonatal iron deficiency (ID) causes long-term and sex specific neurocognitive and affective dysfunctions. This study aims to illustrate sex- specific transcriptome alterations in adult rat hippocampus induced by fetal-neonatal ID and prenatal choline treatment.
2023-04-10 | GSE229266 | GEO
Project description:Background: Iron deficiency (ID) during the fetal-neonatal period results in long-term neurodevelopmental impairments associated with pervasive hippocampal gene dysregulation. Prenatal choline supplementation partially normalizes these effects, suggesting an interaction between iron and choline in hippocampal transcriptome regulation. To understand the regulatory mechanisms, we investigated epigenetic marks of genes that are poised to be activated (ATAC-seq) or repressed (H3K9me3 ChIP-seq) in iron-repleted adult rats having experienced fetal-neonatal ID exposure with or without prenatal choline supplementation. Results: Fetal-neonatal ID was induced by limiting maternal iron intake from gestational day (G) 2 through postnatal day (P) 7. Half of the pregnant dams were given supplemental choline (5.0 g/kg) from G11-18. This resulted in 4 groups at P65 (Iron-sufficient [IS], Formerly Iron-deficient [FID], IS with choline [ISch], and FID with choline [FIDch]). Hippocampi were collected from P65 iron-repleted male offspring and analyzed for chromatin accessibility and H3K9me3 enrichment. 22% and 24% of differentially transcribed genes in FID- and FIDch-groups, respectively, exhibited significant differences in chromatin accessibility, whereas 1.7% and 13% exhibited significant differences in H3K9me3 enrichment. These changes mapped onto gene networks regulating synaptic plasticity, neuroinflammation, and reward circuits. Motif analysis of differentially modified genomic sites revealed significantly stronger choline effects than early-life ID and identified multiple epigenetically modified transcription factor binding sites. Conclusions: This study reveals genome-wide, stable epigenetic changes and epigenetically modifiable gene networks associated with specific chromatin marks in the hippocampus, and lays a foundation to further elucidate iron-dependent epigenetic mechanisms that underlie the long-term effects of fetal-neonatal ID, choline, and their interactions.
2024-03-14 | GSE244207 | GEO
Project description:Background: Iron deficiency (ID) during the fetal-neonatal period results in long-term neurodevelopmental impairments associated with pervasive hippocampal gene dysregulation. Prenatal choline supplementation partially normalizes these effects, suggesting an interaction between iron and choline in hippocampal transcriptome regulation. To understand the regulatory mechanisms, we investigated epigenetic marks of genes that are poised to be activated (ATAC-seq) or repressed (H3K9me3 ChIP-seq) in iron-repleted adult rats having experienced fetal-neonatal ID exposure with or without prenatal choline supplementation. Results: Fetal-neonatal ID was induced by limiting maternal iron intake from gestational day (G) 2 through postnatal day (P) 7. Half of the pregnant dams were given supplemental choline (5.0 g/kg) from G11-18. This resulted in 4 groups at P65 (Iron-sufficient [IS], Formerly Iron-deficient [FID], IS with choline [ISch], and FID with choline [FIDch]). Hippocampi were collected from P65 iron-repleted male offspring and analyzed for chromatin accessibility and H3K9me3 enrichment. 22% and 24% of differentially transcribed genes in FID- and FIDch-groups, respectively, exhibited significant differences in chromatin accessibility, whereas 1.7% and 13% exhibited significant differences in H3K9me3 enrichment. These changes mapped onto gene networks regulating synaptic plasticity, neuroinflammation, and reward circuits. Motif analysis of differentially modified genomic sites revealed significantly stronger choline effects than early-life ID and identified multiple epigenetically modified transcription factor binding sites. Conclusions: This study reveals genome-wide, stable epigenetic changes and epigenetically modifiable gene networks associated with specific chromatin marks in the hippocampus, and lays a foundation to further elucidate iron-dependent epigenetic mechanisms that underlie the long-term effects of fetal-neonatal ID, choline, and their interactions.
2024-03-14 | GSE244206 | GEO
Project description:BackgroundFetal-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.ObjectiveTo illustrate sex-specific transcriptome alterations in adult rat hippocampus induced by fetal-neonatal ID and prenatal choline treatment.MethodsPregnant 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.ResultsBoth 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.ConclusionsThis 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.
| S-EPMC10055746 | biostudies-literature
Project description:Women are twice as likely to have Alzheimer’s disease (AD) than men and multiparity has been suggested to be a risk factor for dementia. The present study evaluated whether the lack of certain nutrients during pregnancy influences cognition while pregnant and in old age in mouse model. Non-targeted NMR analysis revealed significantly lower levels of numerous plasma nutrients and metabolites including choline and its derivatives on gestation day 7 compared to day 1. Novel object recognition and Morris Water Maze tests revealed impaired cognition in pregnant mice compared to nonpregnant controls. Choline deprivation worsened the cognitive impairment during pregnancy and choline supplementation alleviated it. Furthermore, choline availability during pregnancy affected cognition and general health in old age, with mice given a choline-deficient diet during pregnancy performed more poorly. RNA-Seq analysis indicates lasting effect of choline intake during pregnancy on hippocampal gene signatures in old age. Choline deprivation was associated with more upregulation of proinflammatory genes, whereas choline supplementation showed upregulation of neuroprotective genes such as Prl, Gh, and hemoglobin (Hba and Hbb subunits). Together the study shows that choline supplement benefits women’s cognitive health during pregnancy and at the old age.
2025-09-04 | GSE293570 | GEO
Project description:This study reveals a novel mechanism linking social isolation to anxiety through a glucocorticoid (GC)-driven, ventral hippocampal (vHip)-specific iron-α-synuclein (α-Syn) axis. Social isolation activates glucocorticoid receptors (GRs) in vHip pyramidal neurons, which upregulate transferrin receptor 1 (TfR1) to promote iron accumulation. Elevated iron induces α-Syn overexpression, thereby enhancing presynaptic glutamate release and neuronal hyperexcitability in the vHip; this ultimately drives anxiety-like behaviors. Gain-of-function/loss-of-function experiments confirm that TfR1 and α-Syn are essential for this pathway, while intranasal iron chelation or α-Syn inhibition rescues both neural and behavioral abnormalities. These findings establish the GR-TfR1-α-Syn axis as a therapeutic target for social stress-related anxiety, which bridges metallobiology and psychiatric pathophysiology.
2025-06-12 | GSE299293 | GEO
Project description:To determine the physiological roles of NCOA4 and NCOA4-mediated ferritinophagy in hippocampal neurons, NCOA4 was depleted using siRNA and desferrioxamine (DFO; 100 µM, 24 h) was added to restrict iron availability. Cells were treated for NCOA4 depletion, iron restriction, or both, and then the transcriptome profiles acquired from RNA-seq were compared with those of control (scramble siRNA-treated) cells.
2022-12-30 | GSE211931 | GEO
Project description:Eubacterium limosum ATCC 8486 makes acetate and butyrate from various substrates and is found in the human intestine. The proteome of choline -grown Eubacterium limosum was obtained in order to identify enzymes required for growth on choline, in particular to identify components that are unique to growth on choline in comparison to other substrates for acetogenesis, such as lactic acid, L-carnitine, or proline betaine. Choline is converted to trimethylamine (TMA) by certain members of the gut microbiome. Subsequent liver metabolism of TMA is now tied to progression of cardiovascular disease. Demethylation of choline is observed during growth of Eubacterium limosum on this substrate, and does not produce TMA. Choline demethylation by organisms like Eubacterium limosum could lessen TMA production in the gut, thereby lessening the propensity towards atherosclerosis caused by metabolism of TMA in the body. This proteome led to discovery of a phosphocholine:tetrahydrofolate methyltransferase system. The key choline demethylating enzyme is a member of the widespread TMA methyltransferase protein superfamily.
2025-06-16 | PXD033467 | Pride
Project description:Effects of prenatal valproic acid exposure on hippocampal gene expression after birth
| PRJNA748711 | ENA
Project description:prenatal stress response, genetic modification Background: Prenatal stress (PS) exposure has been shown to increase the risk for emotional disorders in later life. Furthermore, the serotonin transporter (5-HTT) genotype is suggested to exert a modulating effect on the association between early life stress and the risk for depression. In the present study, we use a 5-HTT x PS paradigm to investigate whether the effects of PS are dependent upon the 5-HTT genotype. Methods: The effects of PS on cognition, anxiety- and depression-related behaviour were examined using a maternal restraint stress paradigm of PS in C57BL6 wild-type (WT) and heterozygous (+/-) 5-HTT knockout mice. Additionally, in the female offspring, a genome-wide hippocampal gene expression screening was performed. Results: 5-HTT +/- offspring showed enhanced memory performance and signs of reduced anxiety as compared to WT offspring. Conversely, exposure of 5-HTT +/- mice to PS was associated with altered stress-responsivity and increased depressive-like behaviour, particularly in female offspring. Further, 5-HTT genotype, PS and their interaction differentially affected the expression of numerous genes and related pathways within the female hippocampus. Specifically, MAPK and neurotrophin signalling were regulated by both the 5-HTT +/- genotype and PS exposure, whereas cytokine and Wnt signalling were affected in a 5-HTT genotype x PS manner, indicating a gene x environment interaction at the molecular level. Conclusions: The long-term behavioural effects of PS in C57BL6 mice are partly dependent on the 5-HTT genotype. Further, hippocampal gene expression profiles suggest that distinct molecular mechanisms mediate the behavioural effects of the 5-HTT genotype, PS exposure, and their interaction. total samples analysed are 12
2011-12-12 | E-GEOD-26025 | biostudies-arrayexpress