The neurite outgrowth inhibitory myelin protein Nogo-A has been well studied in the context of central nervous system (CNS) injury and disease. We studied the effects of the application of neutralizing anti-Nogo-A antibodies (11C7 and 7B12) in intact CNS tissue in vitro using rat organotypic hippocampal slice cultures. This study had the purpose of elucidating the role of Nogo-A in the adult intact CNS and determining the consequences of its neutralization through antibody application.
Neutralization of the membrane protein Nogo-A enhances growth and reactive sprouting in established organotypic hippocampal slice cultures.
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View SamplesNogo-A localized on myelin adaxonal membrane in the adult CNS is well known for its role as neurite outgrowth inhibitor following a lesion. Nogo-A KO mice show enhanced regenerative/compensatory fiber growth following CNS lesion. However, changes undergoing in their intact CNS have not been studied. Moreover, Nogo-A in the intact adult CNS in also expressed in some neuronal subpopulations, e.g. in the hippocampus, olfactory bulbs and dorsal root ganglia.
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Sex, Specimen part
View SamplesRecent attempts to increase endogenous disease resistance of plants by overexpression of anti-fungal transgenes have shown a potential of this method. However, it has also been shown that such improvements are usually small. One of the obvious reasons for this low anti-fungal effect might be the regulation of endogenous genes in parallel. In this project, we will study the effect of anti-fungal transgenes on the endogenous gene expression. Such effects might relate to substantial equivalence which is a biosafety issue of concern to the public.
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Specimen part, Treatment
View SamplesActivation of A Disintegrin and A Metalloprotease Domain17 (ADAM17) is involved in nephropathy, but the role of this metalloprotease and its inhibitor TIMP3 in diabetic kidney disease is unclear. We used microarray profiling to find genes differentially expressed in the 2 genotypes which could explain the more severe diabetic kidney disease features observed in T3-/- mice compared to the WT littermates.
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Sex, Specimen part
View SamplesTranscriptome analysis of post-mortem brain tissue specimens from three brain regions (BRs), entorinal, temporal and frontal cortices, of 71 Japanese brain-donor subjects to identify genes relevant to the expansion of neurofibrillary tangles. In total, 213 brain tissue specimens (= 71 subjects 3 BRs) were involved in this study. The spreading of neurofibrillary tangles (NFTs), intraneuronal aggregates of highly phosphorylated microtubule-associated protein tau, across the human brain is correlated with the cognitive severity of Alzheimers disease (AD). To identify genes relevant to NFT expansion defined by the Braak stage, we conducted exon array analysis with an exploratory sample set consisting of 213 human post-mortem brain tissue specimens from the entorinal, temporal and frontal cortices of 71 brain-donor subjects: Braak NFT stages 0 (N = 13), III (N = 20), IIIIV (N = 19) and VVI (N = 19). We identified eight genes, RELN, PTGS2, MYO5C, TRIL, DCHS2, GRB14, NPAS4 and PHYHD1, associated with the Braak stage. The expression levels of three genes, PHYHD1, MYO5C and GRB14, exhibited reproducible association on real-time quantitative PCR analysis. In another sample set, including control subjects (N = 30) and patients with late-onset AD (N = 37), dementia with Lewy bodies (N = 17) and Parkinson disease (N = 36), the expression levels of two genes, PHYHD1 and MYO5C, were obviously associated with late-onset AD. Proteinprotein interaction network analysis with a public database revealed that PHYHD1 interacts with MYO5C via POT1, and PHYHD1 directly interacts with amyloid beta-peptide 42. It is thus likely that functional failure of PHYHD1 and MYO5C could lead to AD development.
Genes associated with the progression of neurofibrillary tangles in Alzheimer's disease.
Sex, Specimen part, Subject
View SamplesExcessive inflammation within the central nervous system is injurious, but an immune response is also required for its repair. Macrophages are versatile cells that adopt different properties depending upon their microenvironment. Exposing macrophages to interleukin-4 and -13 (IL4/IL13) has incurred interest for their reparative properties. Unexpectedly, while macrophages exposed to the classic pro-inflammatory signals (interferon-γ/lipopolysaccharide, IFN/LPS) killed neurons and oligodendrocytes in culture, the addition of LPS to IL4/IL13-treated macrophages profoundly elevated IL10, repair metabolites (lactate, ornithine), glucose metabolism and the oligodendrocyte-trophic heparin-binding epidermal growth factor (HBEGF); cells did not display pro-inflammatory or neurotoxic features.
No associated publication
Specimen part, Treatment
View SamplesDuring development, lineage specification is controlled by several signaling pathways involving various transcription factors (TFs). Here, we studied the RE1-silencing transcription factor (REST) and identified an important role of this TF in cardiac differentiation. Using mouse embryonic stem cells (ESC) to model development, we analyzed the effect of REST knock-out on the ability to these cells to differentiate into the cardiac lineage. Detailed analysis of specific lineage markers expression showed selective down-regulation of endoderm markers in REST-null cells, thus contributing to a loss of cardiogenic signals.
A Role for RE-1-Silencing Transcription Factor in Embryonic Stem Cells Cardiac Lineage Specification.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Alternative generation of CNS neural stem cells and PNS derivatives from neural crest-derived peripheral stem cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm.
Cell line, Treatment
View SamplesAnalysis of the expression of KH2 embryonic stem cells inducibly expressing V5 tagged Sox17 protein. Results provide information on the endodermal gene expression program activated after Sox17 expression in ES cells.
Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm.
Cell line, Treatment
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