Expression changes and bioinformatic analysis of Wallerian degeneration after sciatic nerve injury in rat

Abstract

Wallerian degeneration (WD) remains an important research topic. Many genes are differentially expressed during the process of WD, but the precise mechanisms responsible for these differentiations are not completely understood. In this study, we used microarrays to analyze the expression changes of the distal nerve stump at 0, 1, 4, 7, 14, 21 and 28 days after sciatic nerve injury in rats. The data revealed 6 076 differentially-expressed genes, with 23 types of expression, specifically enriched in genes associated with nerve development and axonogenesis, cytokine biosynthesis, cell differentiation, cytokine/chemokine production, neuron differentiation, cytokinesis, phosphorylation and axon regeneration. Kyoto Encyclopedia of Genes and Genomes pathway analysis gave findings related mainly to the MAPK signaling pathway, the Jak-STAT signaling pathway, the cell cycle, cytokine-cytokine receptor interaction, the p53 signaling pathway and the Wnt signaling pathway. Some key factors were NGF, MAG, CNTF, CTNNA2, p53, JAK2, PLCB1, STAT3, BDNF, PRKC, collagen II, FGF, THBS4, TNC and c-Src, which were further validated by real-time quantitative PCR, Western blot, and immunohistochemistry. Our findings contribute to a better understanding of the functional analysis of differentially-expressed genes in WD and may shed light on the molecular mechanisms of nerve degeneration and regeneration.

The Calcium-binding Proteins S100A8 and S100A9 Initiate the Early Inflammatory Program in Injured Peripheral Nerves

“…Although both the degenerative and regenerative processes generally begin immediately after most types of nerve injury, axotomy entails a prolonged lag period in the regenerative process and staggered neurite growth (for up to 4 weeks in rats) (3,4,6). Overall, our data confirm and extend the findings by us and others of the early transcriptional response to peripheral nerve injury, characterized by disintegration of the axonal cytoskeleton, immune response, and cell death unfolding in the D segment (26,29,31,32) and cell proliferation, migration, axon guidance, and regeneration in the P segment proximal to nerve injury (33,47). Our results offer additional comparative insights into the specific rapid cell responses and activation of gene families and pathways that are favorable for chemotaxis, adhesion, and extravasation of myeloid cells in the D and P segments within the first day of peripheral nerve axotomy.…”

“…4F). Overall, these findings support and extend the observations made by others, which focused mainly on either the individual P or D changes or on later time points post-axotomy (25)(26)(27)(28)(29)(30)(31)(32)(33).…”

“…Here we first confirmed and expanded the transcriptional profiling studies in peripheral nerves (25)(26)(27)(28)(29)(30)(31)(32)(33). Using comparative genome-wide transcriptional profiling and subsequent bioinformatics (Ingenuity, NextBio) analyses in the P and D stumps on day 1 post-axotomy, we recorded early gene expression changes in the severed sciatic nerve in rats.…”

miR-9 inhibits Schwann cell migration by targeting CTHRC1 following sciatic nerve injury

“…Following peripheral nerve injury, mature differentiated Schwann cells undergo significant phenotypic modulation, in particular shedding their myelin sheaths and dedifferentiating to a progenitor/stem-cell-like state (Freidin et al, 2009). The dedifferentiated Schwann cells can replenish lost or damaged tissue through proliferation and migration, and can produce a favorable environment for axonal outgrowth through clearing myelin debris and forming cellular conduits or corridors (called bands of Buengner) to guide the directional growth of axons (Parrinello et al, 2010;Yao et al, 2013). Furthermore, many previous studies have described that the phenotypic modulation of Schwann cells is governed by activation of a regulatory network, including the transcription factors Sox2, Sox10, Krox20/Egr2, Oct6/SCIP, Brn2, NFATc4 (Ghislain and Charnay 2006;Kao et al, 2009;Parrinello et al, 2010).…”

Regeneración de las lesiones críticas del nervio periférico con factores de crecimiento. Estudio experimental

“…Ya Cajal observó que la segmentación de la vaina de mielina tiende a ocurrir en las segmentaciones de Schmidt-Lanterman (Cajal SR, 1905;Cajal SR, 1928). Esta fragmentación de la vaina de mielina, está asociada con hipertrofia e hiperplasia de las células de Schwann, (Bradley & Adsbury, 1970 (Yao et al, 2013).…”