Maternal hematopoietic TNF, via milk chemokines, programs hippocampal development and memory
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Shifra Klein
PROVIDER: E-GEOD-52069 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:TNF is a proinflammatory cytokine with established roles in host defense and immune system organogenesis. Here we report a novel physiological function of TNF that extends its effect beyond the host into the developing offspring. A partial/complete maternal TNF-deficit, specifically in hematopoietic cells, resulted in reduced milk levels of chemokines IP-10, MCP-1/-3/-5, and MIP-1β, which in turn, augmented offspring postnatal hippocampal proliferation, leading to improved adult spatial memory. These effects were reproduced by the postpartum administration of a clinically used anti-TNF agent. Chemokines, fed to suckling pups of TNF-deficient mothers, restored both postnatal proliferation and adult spatial memory to normal levels. This work identifies a TNF-dependent “lactrocrine” pathway that programs offspring hippocampal development and memory. The level of ambient TNF is known to be downregulated by physical activity/exercise and adaptive stress; thus, we propose that the maternal TNF-milk chemokine pathway evolved to promote offspring adaptation to post-weaning environmental challenges/competition.
2013-12-01 | GSE52069 | GEO
Project description:Maternal hematopoietic TNF, via milk chemokines, programs hippocampal development and memory
| PRJNA226614 | ENA
Project description:By successfully tracking individual maternal food intake and milk investment, we show that offspring gain more milk from their own mother, particularly when partner mothers are unrelated and when offspring born second experience strong competition from older pups. Unrelated partner mothers are less efficient, requiring more energy than sisters to rear communal broods of equivalent mass. Further, while unrelated partners provide more equal (but not proportional) investment in the brood, individual fitness gains from investment are much greater and more equal between sisters. Our results show that cryptic kin discrimination in maternal investment provides a strong selective advantage for the choice of close relatives as communal rearing partners, reducing costs and potential exploitation of effort when partners were closely matched.
2023-06-27 | PXD019586 | Pride
Project description:By successfully tracking individual maternal food intake and milk investment, we show that offspring gain more milk from their own mother, particularly when partner mothers are unrelated and when offspring born second experience strong competition from older pups. Unrelated partner mothers are less efficient, requiring more energy than sisters to rear communal broods of equivalent mass. Further, while unrelated partners provide more equal (but not proportional) investment in the brood, individual fitness gains from investment are much greater and more equal between sisters. Our results show that cryptic kin discrimination in maternal investment provides a strong selective advantage for the choice of close relatives as communal rearing partners, reducing costs and potential exploitation of effort when partners were closely matched.
2023-06-27 | PXD019578 | Pride
Project description:Maternal 5-HT1A-receptor (R) is required for the timely development of the hippocampus and the establishment of emotional behaviors in Swiss-Webster (SW) mice. A partial and/or complete loss of maternal 5-HT1AR results in delayed ventral dentate granule cell (v-DGC) development and subsequent anxiety-like phenotype in the wild-type offspring by a non-genetic, presumably epigenetic mechanism. Here we tested v-DGCs for genome-wide DNA methylation changes elicited by the receptor deficient maternal environment. We identified a set of hypomethylated regions in the offspring of receptor deficient mothers. A significant fraction of these maternal-differentially methylated regions (m-DMRs) mapped to strong CpG islands, sequences that are typically not methylated or if methylated, resistant to environmental-induced changes. Many m-DMRs mapped to exons and some were associated with expression changes. Their hypomethylation was due to an arrest in de novo methylation and, to a lesser extent, to demethylation during postnatal life indicating that the perturbation in methylation coincides with the developmental delay in DGC maturation in the offspring of receptor deficient mothers. Inhibiting methylation in differentiating neurons impaired their maturation further suggesting a link between de novo methylation and neuronal differentiation. These data suggest that methylation at specific exonic CpG-islands may contribute to the mechanism through which maternal 5-HT1AR modulates hippocampal development and consecutively the level of anxiety in the SW offspring. Reduced 5-HT1AR-binding has been reported in individuals, particularly in association with anxiety/depression, including peri/postpartum depression. Therefore, maternal receptor deficit may contribute, via a non-genetic mechanism, to the high prevalence and heritability of anxiety disorders in human. Examined transcriptomes of 5HT1A wild type offspring with 5HT1A wild type/heterozygous mother or 5HT1A KO offspring with 5HT1A of heterozygous/knock out mother
2013-02-04 | E-GEOD-35838 | biostudies-arrayexpress
Project description:Maternal 5-HT1A-receptor (R) is required for the timely development of the hippocampus and the establishment of emotional behaviors in Swiss-Webster (SW) mice. A partial and/or complete loss of maternal 5-HT1AR results in delayed ventral dentate granule cell (v-DGC) development and subsequent anxiety-like phenotype in the wild-type offspring by a non-genetic, presumably epigenetic mechanism. Here we tested v-DGCs for genome-wide DNA methylation changes elicited by the receptor deficient maternal environment. We identified a set of hypomethylated regions in the offspring of receptor deficient mothers. A significant fraction of these maternal-differentially methylated regions (m-DMRs) mapped to strong CpG islands, sequences that are typically not methylated or if methylated, resistant to environmental-induced changes. Many m-DMRs mapped to exons and some were associated with expression changes. Their hypomethylation was due to an arrest in de novo methylation and, to a lesser extent, to demethylation during postnatal life indicating that the perturbation in methylation coincides with the developmental delay in DGC maturation in the offspring of receptor deficient mothers. Inhibiting methylation in differentiating neurons impaired their maturation further suggesting a link between de novo methylation and neuronal differentiation. These data suggest that methylation at specific exonic CpG-islands may contribute to the mechanism through which maternal 5-HT1AR modulates hippocampal development and consecutively the level of anxiety in the SW offspring. Reduced 5-HT1AR-binding has been reported in individuals, particularly in association with anxiety/depression, including peri/postpartum depression. Therefore, maternal receptor deficit may contribute, via a non-genetic mechanism, to the high prevalence and heritability of anxiety disorders in human. Examined 4 samples: 5HT1A wild type offspring with 5HT1A wild type/heterozygous mother or 5HT1A KO offspring with 5HT1A of heterozygous/knock out mother
2013-02-04 | E-GEOD-35854 | biostudies-arrayexpress
Project description:Maternal 5-HT1A-receptor (R) is required for the timely development of the hippocampus and the establishment of emotional behaviors in Swiss-Webster (SW) mice. A partial and/or complete loss of maternal 5-HT1AR results in delayed ventral dentate granule cell (v-DGC) development and subsequent anxiety-like phenotype in the wild-type offspring by a non-genetic, presumably epigenetic mechanism. Here we tested v-DGCs for genome-wide DNA methylation changes elicited by the receptor deficient maternal environment. We identified a set of hypomethylated regions in the offspring of receptor deficient mothers. A significant fraction of these maternal-differentially methylated regions (m-DMRs) mapped to strong CpG islands, sequences that are typically not methylated or if methylated, resistant to environmental-induced changes. Many m-DMRs mapped to exons and some were associated with expression changes. Their hypomethylation was due to an arrest in de novo methylation and, to a lesser extent, to demethylation during postnatal life indicating that the perturbation in methylation coincides with the developmental delay in DGC maturation in the offspring of receptor deficient mothers. Inhibiting methylation in differentiating neurons impaired their maturation further suggesting a link between de novo methylation and neuronal differentiation. These data suggest that methylation at specific exonic CpG-islands may contribute to the mechanism through which maternal 5-HT1AR modulates hippocampal development and consecutively the level of anxiety in the SW offspring. Reduced 5-HT1AR-binding has been reported in individuals, particularly in association with anxiety/depression, including peri/postpartum depression. Therefore, maternal receptor deficit may contribute, via a non-genetic mechanism, to the high prevalence and heritability of anxiety disorders in human. Comparison of methylation patterns in ventral Dentate Gyrus cells of wild type mice versus 5HT1A receptor knockouts, as well as the effect of the maternal 5HT1A genotype
2013-02-04 | E-GEOD-35815 | biostudies-arrayexpress
Project description:Maternal health and diet can have important consequences for offspring nutrition and metabolic health. Signals are communicated from the mother to the infant during lactation through milk via macronutrients, hormones and bioactive molecules. In this study we designed experiments to probe the mother-milk-infant triad in the condition of normal maternal health and upon exposure to high fat diet (HFD) with or without concurrent metformin exposure. We examined maternal characteristics, milk composition and offspring metabolic parameters on postnatal day 16, prior to offspring beginning to wean. We found that lactational HFD increased maternal adipose tissue, mammary gland adipocytes, and altered milk lipid composition causing a higher amount of n-6 long chain fatty acids and lower n-3. Offspring of HFD dams were heavier with more body fat during suckling. Metformin exposure decreased maternal glucose and several amino acids. Offspring of met dams were smaller during suckling. Gene expression in the lactating mammary glands was impacted to a greater extent by metformin but both metformin and HFD altered genes related to muscle contraction, indicating that these genes may be more susceptible to lactational stressors. Our study demonstrates the impact of common maternal exposures during lactation on milk composition, mammary gland function and offspring growth with metformin having little capacity to recuse from the effects of a maternal HFD during lactation.
2021-06-04 | GSE176118 | GEO
Project description:Early-life exposure to high-fat diet (HF) can program metabolic and cognitive alterations in adult offspring. Although the hippocampus plays a crucial role in memory and metabolic homeostasis, few studies reported the impact of maternal HF on this structure. We assessed the effects of maternal HF during lactation on physiological, metabolic and cognitive parameters in young adult offspring mice. To identify early-programming mechanisms in hippocampus, we developed a multi-omics strategy in male and female offspring. Maternal HF induced a transient increased body weight at weaning, a mild glucose intolerance only in 3-month-old male mice with no change in plasma metabolic parameters in adult male and female offspring. Behavioral alterations revealed by Barnes maze test were observed both in 6-month-old male and female mice. Multi-omics strategy unveiled sex-specific transcriptomic and proteomic modifications in the hippocampus of adult offspring. These studies, that were confirmed by regulon analysis, showing that, although genes whose expression was modified by maternal HF were different between sexes, the main pathways affected were similar with mitochondria and synapses as main hippocampal targets of maternal HF. The effects of maternal HF reported here may help to better characterize sex-dependent molecular pathways involved in cognitive disorders and neurodegenerative diseases.
2024-01-26 | PXD045639 | Pride
Project description:Maternal care is associated with long-term effects on behavior and epigenetic programming of the NR3C1 (GLUCOCORTICOID RECEPTOR) gene in the hippocampus of both rats and humans. However, epigenetic changes at a single gene promoter are unlikely to account for the range of responses to the early life environment and the persistent change in expression of hundreds of additional genes in adult rats in response to differences in maternal care. Here we show that natural variations in maternal care are associated with coordinate changes in DNA methylation, chromatin, and gene expression spanning over a hundred kilobase pairs in the hippocampus of adult rats. The offspring of high compared to low maternal care mothers show epigenetic changes in promoters, exons, and gene ends and higher transcriptional activity across many genes, suggesting that a broad epigenetic regulation of gene expression may form part of a coordinated response to early maternal care. We obtained hippocampal samples from adult offspring of rat mothers that differed in the frequency of pup licking/grooming in the first week of life. Using custom-designed microarrays with probes tiling the 7 million base pair region of rat chromosome 18 centered at the NR3C1 gene at 100 bp spacing, we obtained DNA methylation and H3K9 acetylation profiles by ChIP-on-chip. Each profile was generated in triplicate, each type of profile from 3 high frequency and 3 low frequency mothers.
2011-03-09 | E-GEOD-20714 | biostudies-arrayexpress