Comparison of adult intact naive C57Bl/6 Nogo-A KO versus WT spinal cord
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE11276 | GEO | 2010/11/01
SECONDARY ACCESSION(S): PRJNA106677
REPOSITORIES: GEO
Similar Datasets
Project description:Nogo-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. We compared the intact adult CNS (spinal cord) of Nogo-A KO mice in order to identify: potential compensating molecules which could be interesting new inhibitory neurite outgrowth candidates, possible molecules involved in the up to now not yet clarified downstream signalling pathway of Nogo-A, additional new functions for myelin or neuronal Nogo-A in the intact adult CNS. Keywords: gene expression, Nogo-A KO, spinal cord, adult, naive, unlesioned Spinal cords from 3 adult C57Bl/6 wild type and Nogo-A KO mice have been explanted. Total RNA has been extracted and processed for hybridization on Mouse 430 2.0 Affymetrix GeneChips. Following scanning and first analysis with MAS 5.0, further analysis was performed by GeneSpring 7.2 (Silicon Genetics, Redwood City, CA). A present call filter (2 out of 3 present calls in at least one out of the different studied conditions) was applied. Normalization was run per chip as well as per gene to the median of the control replicates. Data were statistical restricted through a 1-way Anova (p=0.05). A final threshold of =1.2 folds of increase or decrease in the expression level of each single transcript was applied. Regulated transcripts have been assigned to functional categories according to GeneOntology as well as literature and database mining (Pubmed and Bioinformatics Harvester EMBL Heidelberg).
2010-11-01 | E-GEOD-11276 | biostudies-arrayexpress
Project description: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. In vitro cultures treated with anti-Nogo-A antibody showed an elicited growth response. The results also gave indications that hippocampal circuitry might be altered due to the regulation at the synaptic and neurotransmission level.
2008-11-12 | GSE12483 | GEO
Project description: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. In vitro cultures treated with anti-Nogo-A antibody showed an elicited growth response. The results also gave indications that hippocampal circuitry might be altered due to the regulation at the synaptic and neurotransmission level. Experiment Overall Design: Nogo-A function in the intact CNS tissue is not well known, but its neutralization in vivo produced a transitory growth response of Purkinje axons and of the corticospinal tract in intact adult rats (Buffo et al., 2000; Bareyre et al., 2002; Gianola et al., 2003). Nogo-A is relatively highly expressed in oligodendrocytes and some neurons of the hippocampus (Huber et al., 2002; Meier et al., 2003; Gil et al., 2006; Trifunovski et al., 2006). Organotypic hippocampal slice cultures are a good in vitro model to study hippocampal function and structure (Stoppini et al., 1991; 1993; Bahr, 1995; Gahwiler et al., 1997; Hakkoum et al., 2006). They mature in vitro and retain many in vivo features from a structural and functional perspective. We chose this model to study the effects of acute Nogo-A neutralization, using two function blocking monoclonal antibodies, 11C7 and 7B12 (Oertle et al., 2003; Wiessner et al., 2003; Liebscher et al., 2005), exclusively targeted against the Nogo-A specific region. Hippocampal slices from P7 Wistar rats were cultured for 21 DIV. Control untreated cultures where cultured for additional 5days for a total of 26DIV, while control IgG, and 11C7 and 7B12 were added to 21DIV cultures which were then further cultured for 5days, changing medium every 2 days. All the conditions were repeated in triplicates with separate cultures from different animals. For each condition and experimental replicate 24 cultures were pooled together before being processed for RNA extraction. Data analysis was performed by GeneSpring 7.2 (Silicon Genetics, Agilent, CA, US) comparing 11C7 and 7B12 treated samples versus Not treated and IgG treated, as controls. A present call filter (2 out of 3 present calls in at least one out of the 3 experimental replicates) was applied. Normalization was run per chip as well as per gene to the median of the control replicates. Data were statistical restricted through a 1-way Anova (pâ?¤0.05). A final threshold of â?¥1.2 fold of increase or decrease in the expression level of each single transcript was applied. Regulated transcripts have been assigned to functional categories according to GeneOntology as well as literature and database mining (Pubmed; Bioinformatics Harvester EMBL Heidelberg; Rat Genome Database).
2008-11-15 | E-GEOD-12483 | biostudies-arrayexpress
Project description:We screened nine genetically diverse inbred mouse strains for differences in axonal growth of adult dorsal root ganglion (DRG) neurons on CNS myelin. Naïve DRG neurite outgrowth on myelin was very limited, but preconditioning the neurons by a prior sciatic nerve crush increased axonal growth substantially across all strains, with by far the greatest change in neurons from CAST/Ei mice. Three independent in vivo CNS injury models revealed greater capacity for CNS axonal regeneration in CAST/Ei than C57BL/6 mice. Full-genome expression profiling of naïve and pre-conditioned DRGs across all strains revealed Activin-βA (Inhba) as the transcript whose expression most closely correlated with axonal growth on myelin. In vitro and in vivo gain- and loss-of-function experiments confirmed that Activin promotes axonal growth in the CNS. Substantial regeneration is possible, therefore, in the injured mammalian CNS when Activin signaling is intrinsically high, as in CAST/Ei or when extrinsically modulated in other strains. 9 strains, 4 replicates per strain, 2 conditions (naïve and axotomy) = 72 samples. 2 samples were excluded because technical outliers (AJ_AX5D_1 and AJ_NAIVE_4 excluded from the normalized data but included in the raw data)
2015-05-14 | E-GEOD-55424 | biostudies-arrayexpress
Project description:We screened nine genetically diverse inbred mouse strains for differences in axonal growth of adult dorsal root ganglion (DRG) neurons on CNS myelin. Naïve DRG neurite outgrowth on myelin was very limited, but preconditioning the neurons by a prior sciatic nerve crush increased axonal growth substantially across all strains, with by far the greatest change in neurons from CAST/Ei mice. Three independent in vivo CNS injury models revealed greater capacity for CNS axonal regeneration in CAST/Ei than C57BL/6 mice. Full-genome expression profiling of naïve and pre-conditioned DRGs across all strains revealed Activin-βA (Inhba) as the transcript whose expression most closely correlated with axonal growth on myelin. In vitro and in vivo gain- and loss-of-function experiments confirmed that Activin promotes axonal growth in the CNS. Substantial regeneration is possible, therefore, in the injured mammalian CNS when Activin signaling is intrinsically high, as in CAST/Ei or when extrinsically modulated in other strains.
2015-05-14 | GSE55424 | GEO
Project description:Comparison of adult intact naive C57Bl/6 Nogo-A KO versus WT spinal cord
| PRJNA106677 | ENA
Project description:Adult CNS Myelin Enhances Axonal Outgrowth From Neural Stem Cells
| PRJNA386927 | ENA
Project description:After injury to the central nervous system (CNS), both neuron-intrinsic limitations on regenerative responses and inhibitory factors in the injured CNS environment restrict regenerative axon growth. Instances of successful axon regrowth offer opportunities to identify features that differentiate these situations from that of the normal adult CNS. One such opportunity is provided by the kinase inhibitor RO48, which dramatically enhances neurite outgrowth of neurons in vitro and substantially increased contralateral sprouting of corticospinal tract neurons when infused intraventricularly following unilateral pyramidotomy. The authors present here a transcriptomic deconvolution of RO48-associated axon growth, with the goal of identifying transcriptional regulators associated with axon growth in the CNS. Through the use of RNA sequencing (RNA-seq) and transcription factor binding site enrichment analysis, the authors identified a list of transcription factors putatively driving differential gene expression during RO48-induced neurite outgrowth of rat hippocampal neurons in vitro. The 82 transcription factor motifs identified in this way included some with known association to axon growth regulation, such as Jun, Klf4, Myc, Atf4, Stat3, and Nfatc2, and many with no known association to axon growth. A phenotypic loss-of-function screen was carried out to evaluate these transcription factors for their roles in neurite outgrowth; this screen identified several potential outgrowth regulators. Subsequent validation suggests that the Forkhead box (Fox) family transcription factor Foxp2 restricts neurite outgrowth, while FoxO subfamily members Foxo1 and Foxo3a promote neurite outgrowth. The authors’ combined transcriptomic-phenotypic screening strategy therefore allowed identification of novel transcriptional regulators of neurite outgrowth downstream of a multitarget kinase inhibitor.
2023-06-19 | GSE234696 | GEO
Project description:Combining proteomics and systems biology analyses, we demonstrated that neonatal microglial cells derived from two different CNS locations (cortex and spinal cord) displayed different phenotypes upon different physiological or pathological conditions. These cells also exhibited great variability in terms of both cellular and small extracellular vesicles (sEVs) protein contents and levels. Bioinformatics data analysis showed that the cortical microglia had anti-inflammatory and neurogenesis/tumorigenesis properties, while the spinal cord microglia was rather involved in inflammatory response process. Of interest, while both sEVs microglia sources enhanced growth of DRGs axons, only the spinal cord-derived sEVs microglia under LPS stimulation significantly attenuated glioma proliferation. These results were confirmed through neurite outgrowth assays in DRGs cell line and glioma proliferation analysis in 3D spheroid cultures. Results from these in vitro assays indicated that the microglia localized at different CNS regions can ensure different biological functions. Together, these works indicate that neonatal microglia locations regulate their physiological and pathological functional fates, and could explain the high prevalence of brain vs. spinal cord glioma in adults.
2020-05-26 | PXD016093 | Pride
Project description:The adult central nervous system (CNS) has a limited capacity for self-repair. Severed CNS axons typically do not regrow. There is an unmet need for treatments specifically designed to enhance neuronal viability, facilitate CNS axon regeneration, and ultimately restore lost neurological functions to individuals with traumatic CNS injury, multiple sclerosis, and stroke, among other disorders. Here we demonstrate that both mouse and human bone marrow (BM) neutrophils upregulate markers of alternative activation, and acquire the ability to promote neurite outgrowth, following polarization with a combination of recombinant interleukin-4 (IL-4) and granulocyte-colony stimulating factor (G-CSF). Moreover, adoptively transferring IL-4/G-CSF polarized BM neutrophils into experimental models of CNS injury resulted in significant axon regeneration within the optic nerve and spinal cord. The findings reported in this paper hold significant implications for the future development of autologous myeloid cell-based therapies that may bring us closer to effective solutions for reversing CNS damage.
2023-12-01 | GSE244934 | GEO