Comparative proteomic profiling reveals aberrant cell proliferation in the brain of embryonic Ts1Cje, a mouse model of Down syndrome

Ishihara, Keiichi; Kanai, Setsuko; Sago, Haruhiko; Yamakawa, Kazuhiro; Akiba, Suminori

doi:10.1016/j.neuroscience.2014.09.039

Cited by 16 publications

(14 citation statements)

References 49 publications

(61 reference statements)

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“…In contrast, our previous study has shown that genes that are overexpressed in the brain of neonatal Ts1Cje mice are primarily located on the trisomic region, and that very few genes are differentially expressed outside the trisomic region . We also showed the disturbed expression of proteins in the prenatal brain—but not the neonatal brain—of Ts1Cje mice in a comparative proteomics analysis . These observations may indicate that different changes in the expression of genes coded in the disomic region are induced by the overexpression of genes encoded in the trisomic region in the brain of Ts1Cje mice during prenatal and postnatal life.…”

Section: Discussioncontrasting

confidence: 82%

Perturbation of the immune cells and prenatal neurogenesis by the triplication of the Erg gene in mouse models of Down syndrome

et al. 2019

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Some mouse models of Down syndrome (DS), including Ts1Cje mice, exhibit impaired prenatal neurogenesis with yet unknown molecular mechanism. To gain insights into the impaired neurogenesis, a transcriptomic and flow cytometry analysis of E14.5 Ts1Cje embryo brain was performed. Our analysis revealed that the neutrophil and monocyte ratios in the CD45-positive hematopoietic cells were relatively increased, in agreement with the altered expression of inflammation/immune-related genes, in Ts1Cje embryonic brain, whereas the relative number of brain macrophages was decreased in comparison to wild-type mice. Similar upregulation of inflammationassociated mRNAs was observed in other DS mouse models, with variable trisomic region lengths. We used genetic manipulation to assess the contribution of Erg, a trisomic gene in these DS models, known to regulation hemato-immune cells. The perturbed proportions of immune cells in Ts1Cje mouse brain were restored in Ts1Cje-Erg +/+/Mld2 mice, which are disomic for functional Erg but otherwise trisomic on a Ts1Cje background. Moreover, the embryonic neurogenesis defects observed in Ts1Cje cortex were reduced in Ts1Cje-Erg +/+/Mld2 embryos. Our findings suggest that Erg gene triplication contributes to the dysregulation of the homeostatic proportion of the populations of immune cells in the embryonic brain and decreased prenatal cortical neurogenesis in the prenatal brain with DS.Brain Pathology 30 (2020) 75-91Brain Pathology 30 (2020) 75-91

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Section: Discussioncontrasting

confidence: 82%

Perturbation of the immune cells and prenatal neurogenesis by the triplication of the Erg gene in mouse models of Down syndrome

et al. 2019

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“…A literature search on proteomic studies shows that this protein and other ribosomal stalk proteins tend to be increased, coupled with an increased level of energy metabolism proteins [50,51,52]. A reduction in the level of 60S acidic ribosomal protein P0 in the EE group is apparently associated with a reduction in energy metabolism.…”

Section: Discussionmentioning

confidence: 99%

Alteration of Energy Metabolism and Antioxidative Processing in the Hippocampus of Rats Reared in Long-Term Environmental Enrichment

Kang

Choi²,

Kim³

et al. 2016

Dev Neurosci

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Environmental enrichment (EE) is a typical experimental method that promotes levels of novelty and complexity that enhance experience-dependent neuroplasticity and cognitive behavior function in laboratory animals. Early EE is associated with resilience in the face of later-life challenges. Since increased synaptic activity enhances endogenous neuronal antioxidant defenses, we hypothesized that long-term EE beginning at an early stage may alter the levels of oxidative stress. We investigated global protein expression and oxidative stress in hippocampal proteins from rats nurtured for a 6-month EE beginning in the prenatal period. The analysis of protein expression was carried out using 2-dimensional gel electrophoresis with matrix-associated laser desorption ionization time-of-flight mass spectrometry. Proteins with altered expression were involved in energy metabolism (phosphoglycerate mutase 1, α-enolase isoform 1, adenylate kinase 1, and triose phosphate isomerase) and antioxidant enzymes (superoxide dismutase 1, glutathione S-transferase ω type 1, peroxiredoxin 5, DJ-1, and glial maturation factor β). Using Western blot assays, some of the proteins with altered expression and NADPH oxidase 2 were confirmed to be decreased. Further confirmation was demonstrated with attenuated expression of 7,8-dihydro-8-oxo-deoxyguanine, a DNA oxidative stress marker, in the hippocampus of EE group rats. Our data demonstrate that a long-term EE program beginning in the prenatal and early postnatal phase of development modulates energy metabolism and reduced oxidant stress possibly through enhanced synaptic activity. We provide evidence that EE can be developed as a tool to protect the brain from oxidative stress-induced injury.

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“…A number of proteins associated with proteolysis, energy metabolism, the cytoskeleton, and cell proliferation that are coded in disomic genes were found to be dysregulated in humans and mice with DS (Table 2) [29,30,31], although proteins, which were differentially expressed in both human and mouse brain with DS, have not yet been identified in these proteomic analysis. For instance, ubiquitin carboxyl-terminal hydrolase isozyme L1 (Uchl1) coded on an euploid gene showed a decreased expression in the brain of a 141G6 mouse carrying a yeast artificial chromosome (YAC), which contains HSA21 genes, Down syndrome critical region gene 3 ( Dscr3 ), phosphatidylinositol glycan anchor biosynthesis, class P ( Pigp ), ripply transcriptional repressor 3 ( Ripply3 ), and tetratricopeptide repeat domain 3 ( Ttc3 ), as well as neurons differentiated from ES cells carrying an extra HSA21 [32,31].…”

Section: Comparative Proteomics In the Ds Brainmentioning

confidence: 99%

“…As no proteins were found to be differentially expressed in the Ts1Cje mouse brain during neonatal and postnatal life by 2D-electrophoresis-based proteomics [30], these other ‘-omics’ approaches are thought to be particularly useful.…”

Section: Other ‘-Omics’ Analysesmentioning

confidence: 99%

A Comprehensive Diverse ‘-omics’ Approach to Better Understanding the Molecular Pathomechanisms of Down Syndrome

Ishihara

Akiba

2017

Brain Sciences

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Diverse ‘-omics’ technologies permit the comprehensive quantitative profiling of a variety of biological molecules. Comparative ‘-omics’ analyses, such as transcriptomics and proteomics, are powerful and useful tools for unraveling the molecular pathomechanisms of various diseases. As enhanced oxidative stress has been demonstrated in humans and mice with Down syndrome (DS), a redox proteomic analysis is useful for understanding how enhanced oxidative stress aggravates the state of individuals with oxidative stress-related disorders. In this review, ‘-omics’ analyses in humans with DS and mouse models of DS are summarized, and the molecular dissection of this syndrome is discussed.

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Comparative proteomic profiling reveals aberrant cell proliferation in the brain of embryonic Ts1Cje, a mouse model of Down syndrome

Cited by 16 publications

References 49 publications

Perturbation of the immune cells and prenatal neurogenesis by the triplication of the Erg gene in mouse models of Down syndrome

Perturbation of the immune cells and prenatal neurogenesis by the triplication of the Erg gene in mouse models of Down syndrome

Alteration of Energy Metabolism and Antioxidative Processing in the Hippocampus of Rats Reared in Long-Term Environmental Enrichment

A Comprehensive Diverse ‘-omics’ Approach to Better Understanding the Molecular Pathomechanisms of Down Syndrome

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