Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Timecourse expression data from sciatic nerve distal stump of C57BL/6 and C57BL/6 OlaHsd-Wlds mice.

ABSTRACT: Wallerian degeneration (WD) involves the fragmentation of axonal segments disconnected from their cell bodies, segmentation of the myelin sheath, and removal of debris by Schwann cells and immune cells. The removal and downregulation of myelin-associated inhibitors of axonal regeneration and synthesis of growth factors by these two cell types are critical responses to successful nerve repair. Here, we analyzed the transcriptome of the sciatic nerve of mice carrying the Wallerian degeneration slow (WldS) mutant gene, a gene that confers axonal protection in the distal stump after injury, therefore causing significant delays in WD, neuroinflammation, and axonal regeneration. 56 C57BL6 mice and 56 C57BL/6 OlaHsd-Wlds mice were anesthetized with isoflurane and underwent a microcrush lesion of their left sciatic nerve at the mid-thigh level (exept naive mice, t0). At 0, 3, 7 and 14 days post-injury, mice were anesthetized and killed by cervical dislocation. Sciatic nerves were collected and conective tissue removed. A 4-mm long sciatic nerve segment was taken from the nerve distal stump, starting at 1 mm distal from the lesion up to 5 mm distal. Distal nerve stumps were pooled by group and RNA extracted. Samples were hybridized to GeneChip® Mouse Genome 430 2.0 Array (Affymetrix). Biological replicate was done.

ORGANISM(S): Mus musculus

SUBMITTER: Ezequiel Calvo

PROVIDER: E-GEOD-22291 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Transcriptional profiling of the injured sciatic nerve of mice carrying the Wld(S) mutant gene: identification of genes involved in neuroprotection, neuroinflammation, and nerve regeneration.

Barrette Benoit B Calvo Ezéquiel E Vallières Nicolas N Lacroix Steve S

Brain, behavior, and immunity 20100803 8

Wallerian degeneration (WD) involves the fragmentation of axonal segments disconnected from their cell bodies, segmentation of the myelin sheath, and removal of debris by Schwann cells and immune cells. The removal and downregulation of myelin-associated inhibitors of axonal regeneration and synthesis of growth factors by these two cell types are critical responses to successful nerve repair. Here, we analyzed the transcriptome of the sciatic nerve of mice carrying the Wallerian degeneration slo ...[more]

PMID: 20688153

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Project description:To shed light on the early processes of immune response to peripheral nerve injury, we first used genome-wide transcriptional profiling and bioinformatics (Ingenuity, NextBio) pathway analyses of the proximal (P; regenerating) and distal (D; degenerating) nerve stumps at day 1 in the sciatic nerve axotomy model in rats. We identified a number of specific immunomodulatory genes and pathways that were regulated shortly post-injury in both the P and D segments, including all members of the interleukin (IL), chemokine, tumor necrosis factor (TNF), matrix metalloproteinase (MMP), toll-like receptor (TLR), tissue inhibitor of metalloproteinase (TIMP), ion channel and myosin families. Immunomodulatory calcium-binding S100A8 and S100A9 were the top up-regulated genes in both the D and P segments. In cultured Schwann cells stimulated with the purified S100A8/A9 heterodimer we recorded a high level of similarity of the activated genes and pathways with that of the injured nerve, especially in the activation of the chemokine and cytokine gene networks that support agranulocyte and granulocyte chemotaxis, adhesion, transmigration and rolling signaling pathways. We also confirmed activation of multiple cell death related gene networks supporting TNFR1, natural killer cell receptor and death receptor apoptosis signaling in the D stump, and the gluconeogenesis/glycolysis and cytoskeletal motility signaling in the P stump, corroborated by activation of ERK, PI3K and JNK kinase pathways. As compared to the D segment, multiple additional pathways were more efficiently upregulated in the P stump, including the IL-6 and -17, MMP-9, calcium, activated agranulocyte, leukocyte rolling and glutathione-mediated detoxification signaling pathways. These data suggest that shortly after nerve injury, upregulation of S100A8/A9 is responsible for the expression and release of chemokines and cytokines by Schwann cells, necessary to generate the initial chemotactic gradient and guide the hematogenous immune cells into the injury site. Gene expression profiling of total RNAs extracted from injured and non-injured rat sciatic nerves, and primary rat Schwann cells stimulated with S100A8/A9 proteins

Dataset Information

Timecourse expression data from sciatic nerve distal stump of C57BL/6 and C57BL/6 OlaHsd-Wlds mice.

Publications

Transcriptional profiling of the injured sciatic nerve of mice carrying the Wld(S) mutant gene: identification of genes involved in neuroprotection, neuroinflammation, and nerve regeneration.

Similar Datasets

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