Cranial radiotherapy profoundly affects glia without inducing widespread cellular senescence
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PROVIDER: PRJNA1195931 | ENA |
REPOSITORIES: ENA
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Project description:Background More than 70% of cancer patients who underwent cranial radiotherapy have cognitive problems, suggesting that they might undergo accelerated brain aging due to the cancer treatment. Radiotherapy is known to induce cellular senescence in tumors and in various cell types in vitro. Therefore, we hypothesized that cranial radiotherapy induces cellular senescence in the brain. Methods We treated male C57BL/6 mice with various dosages of (fractionated) CT-guided cranial radiotherapy. The brains were analyzed for various senescence and glial markers using immunohistochemistry, histochemistry, Cosmx SMI and RT-qPCR. To contextualize the findings regarding cranial radiotherapy in young animals and assess whether these changes parallel natural aging, we studied the brains from 77-week-old female mice, which is considered middle-aged to old representing early aging. Results Surprisingly, we found no increase in markers for cellular senescence in the brain after cranial radiotherapy. However, we did detect profound changes in different types of glia. In early-aged mice we again did not detect an increase in senescence markers, but we observed the same directionality in the effects on glia. These effects on glia were milder compared to those upon cranial radiotherapy. Conclusion Overall, cellular senescence in the healthy brain seems a rather uncommon phenomenon and not induced upon cranial radiotherapy, but profound changes in different types of glia were detected upon cranial radiotherapy.
2025-06-17 | GSE283863 | GEO
Project description:Cranial and craniospinal irradiation are the oldest central nervous system prophylaxis treatments considered for pediatric patients with lymphoblastic leukemia (ALL). However, survivors of childhood ALL that received cranial radiotherapy are at increased risk for deficits in neurocognitive skills. The continuous and dynamic response of normal tissue after irradiation has been identified as one of the causative factors for cognitive changes after cranial radiation therapy. The aim of our study was to investigate the radiation effects on social behavior and neuronal morphology in the hippocampus of adult mice. Twenty-one-day-old male C57BL/6 mice were irradiated with the small-animal radiation research platform (SARRP). Animals were given a single 10-Gy dose of radiation of X-ray cranial radiation. One month following irradiation, animals underwent behavioral testing in the Three-Chamber Sociability paradigm. Radiation affected social discrimination during the third stage eliciting an inability to discriminate between the familiar and stranger mouse, while sham successfully spent more time exploring the novel stranger. Proteomic analysis revealed dysregulation of metabolic and signaling pathways associated with neurocognitive dysfunction such as mitochondrial dysfunction, Rac 1 signaling, and synaptogenesis signaling. We observed significant decreases in mushroom spine density in the Cornu Ammonis 2 of the hippocampus, which is associated sociability processing.
2022-02-15 | PXD017596 | Pride
Project description:Radiotherapy is a highly effective tool for the treatment of brain cancer. However, radiation also causes detrimental effects in the healthy tissue, leading to neurocognitive sequelae that compromise the quality of life of brain cancer survivors. Despite the recognition of this serious complication, no satisfactory solutions exist at present. Here we investigated the effects of intranasal administration of human mesenchymal stem cell (hMSCs) as a neuroprotective strategy for cranial radiation in mice. Our results demonstrated that intranasally delivered hMSCs promote radiation-induced brain injury repair, improving neurological function. The molecular analysis revealed that hMSC administration reduces persistent activation of damage-induced c-AMP response element-binding signaling in the irradiated neurogenic niches. Furthermore, hMSC treatment did not compromise survival of glioma-bearing mice. Our findings encourage the therapeutic use of hMSCs as an effective and non-invasive approach to prevent neurological complications of radiotherapy, improving the quality of life of brain tumor survivors.
2019-06-21 | GSE115735 | GEO
Project description:To identify the gene expression profile of enteric glia and assess the transcriptional similarity between enteric and extraenteric glia, we performed RNA sequencing analysis on PLP1-expressing cells in the mouse intestine. This analysis shows that enteric glia are transcriptionally unique and distinct from other cell types in the nervous system. Enteric glia express many genes characteristic of the myelinating glia, Schwann cells and oli- godendrocytes, although there is no evidence of myelination in the murine ENS. Total RNA expression profiles of PLP1 expressing enteric glial cells (GFP+) and non-glial cells (GFP-negative) were obtained from the ileum and colon of juvenile PLP1-eGFP transgenic mice.
2015-09-01 | E-GEOD-72560 | biostudies-arrayexpress
Project description:This manuscript is about our recent work on investigating the effective mechanism of Zinc oxide Nanoparticles on the malformation of craniofacial skeleton. Briefly, we focused on addressing the phenotype of destroyed cranial neural crest cells’ development where the effect of oxidant stress was explored when developing early embryos were exposed to Zinc oxide Nanoparticles during the embryogenesis.
2021-10-19 | GSE121507 | GEO
Project description:We employ RNA-seq of FACS sorted cell populations to identify genes that are enriched in cranial neural crest in relationship to the trunk. Transcriptional profiling of delaminating cranial and trunk neural crest subpopulations.
2016-06-24 | E-GEOD-75125 | biostudies-arrayexpress
Project description:TWIST1, a basic helix-loop-helix transcription factor is essential for the development of cranial mesoderm and cranial neural crest-derived craniofacial structures. Our previous work showed that, in the absence of TWIST1, some cells within the cranial mesoderm adopt an abnormal epithelial configuration. Here, we show by transcriptome analysis that loss of TWIST1 in the cranial mesoderm is accompanied by a reduction in the expression of genes that are associated with cell-extracellular matrix interactions and the acquisition of mesenchymal characteristics. By comparing the transcriptional profiles of cranial mesoderm-specific Twist1 loss-of-function mutant and control mouse embryos, we identified a set of genes that are both TWIST1-dependent and predominantly expressed in the mesoderm. By ChIP-seq in a cell line model of a TWIST1-dependent mesenchymal state, we identified, among the downstream genes, three direct transcriptional targets of TWIST1: Ddr2, Pcolce and Tgfbi. Our findings show that the mesenchymal properties of the cranial mesoderm is likely to be regulated by a network of TWIST1 targets genes that influence the extracellular matrix and cell-matrix interactions, and collectively they are required for the morphogenesis of the craniofacial structures. Cranial neural crest and cranial mesoderm cells were isolated by flow sorting of GFP reporter-labelled cells collected from heads of E9.5 mouse embryos. Three replicates were independently isolated and hybridized to Illumina mouse WG v 2.0 chips
2016-08-23 | E-GEOD-80335 | biostudies-arrayexpress
Project description:TWIST1, a basic helix-loop-helix transcription factor is essential for the development of cranial mesoderm and cranial neural crest-derived craniofacial structures. Our previous work showed that, in the absence of TWIST1, some cells within the cranial mesoderm adopt an abnormal epithelial configuration. Here, we show by transcriptome analysis that loss of TWIST1 in the cranial mesoderm is accompanied by a reduction in the expression of genes that are associated with cell-extracellular matrix interactions and the acquisition of mesenchymal characteristics. By comparing the transcriptional profiles of cranial mesoderm-specific Twist1 loss-of-function mutant and control mouse embryos, we identified a set of genes that are both TWIST1-dependent and predominantly expressed in the mesoderm. By ChIP-seq in a cell line model of a TWIST1-dependent mesenchymal state, we identified, among the downstream genes, three direct transcriptional targets of TWIST1: Ddr2, Pcolce and Tgfbi. Our findings show that the mesenchymal properties of the cranial mesoderm is likely to be regulated by a network of TWIST1 targets genes that influence the extracellular matrix and cell-matrix interactions, and collectively they are required for the morphogenesis of the craniofacial structures. For microarray analysis of CM-CKO embryos, embryo heads of four genotypes were collected at E8.5 (5-7 somites) and E9.5 (18- 20 somites): CM-CKO (Twist1flox/del; Mesp1Cre/+), CM-Het (Twist1flox/wt; Mesp1Cre/+), Het (Twist1flox/del; Mesp1+/+) and Control (Twist1flox/wt; Mesp1+/+). Sample sizes for E8.5 embryos were as follows: Control, n=4 CM-CKO, n=4; Het, n=3; CM-Hets, n=3).
2016-08-23 | E-GEOD-80334 | biostudies-arrayexpress
Project description:Proteins exhibit dynamics in their expression level in response to intracellular and extracellular signals. Regulation of protein turnover allows cells to rapidly and efficiently remodel their proteomes. It is known that proteins can show very different turnover rates in different tissue of the same organism, but little is known about protein turnover rates in different brain cell types. We used a dynamic SILAC approach to determine protein half-lives in primary hippocampal cultures (containing a mixture of neurons and glia cells) as well as in neuron-enriched and glia-enriched cultures. We determined the protein half-lives for over 5100 proteins and found half-lives ranging from <1 to > 20 days with a median half-life of 5.4 days in mixed cultures. Membrane proteins as a group were shorter-lived and mitochondrial proteins, surprisingly, were longer-lived. Proteins in glia possessed significantly shorter half-lives than the same proteins in neurons. The presence of glia sped up or slowed down the half-lives of neuronal proteins. Our results demonstrate that both the cell-type of origin as well as the nature of the extracellular environment have potent influences on protein turnover.
2018-06-05 | PXD008596 | Pride
Project description:Small RNA-seq of HH9- chick embryo cranial midbrain region
2022-08-17 | GSE171616 | GEO