Differential gene expression in proximal and distal nerve segments of rats with sciatic nerve injury during Wallerian degeneration

Abstract

Wallerian degeneration is a subject of major interest in neuroscience. A large number of genes are differentially regulated during the distinct stages of Wallerian degeneration: transcription factor activation, immune response, myelin cell differentiation and dedifferentiation. Although gene expression responses in the distal segment of the sciatic nerve after peripheral nerve injury are known, differences in gene expression between the proximal and distal segments remain unclear. In the present study in rats, we used microarrays to analyze changes in gene expression, biological processes and signaling pathways in the proximal and distal segments of sciatic nerves undergoing Wallerian degeneration. More than 6,000 genes were differentially expressed and 20 types of expression tendencies were identified, mainly between proximal and distal segments at 7–14 days after injury. The differentially expressed genes were those involved in cell differentiation, cytokinesis, neuron differentiation, nerve development and axon regeneration. Furthermore, 11 biological processes were represented, related to responses to stimuli, cell apoptosis, inflammatory response, immune response, signal transduction, protein kinase activity, and cell proliferation. Using real-time quantitative PCR, western blot analysis and immunohistochemistry, microarray data were verified for four genes: aquaporin-4, interleukin 1 receptor-like 1, matrix metalloproteinase-12 and periaxin. Our study identifies differential gene expression in the proximal and distal segments of a nerve during Wallerian degeneration, analyzes dynamic biological changes of these genes, and provides a useful platform for the detailed study of nerve injury and repair during Wallerian degeneration.

Ingenuity Pathway Analysis of Gene Expression Profiles in Distal Nerve Stump following Nerve Injury: Insights into Wallerian Degeneration

“…Up-regulated MMP9 stimulates the recruitment and migration of macrophages, mediates the differentiation of myelinating Schwann cells, and thus benefits nerve regeneration (Shubayev et al, 2006; Kim et al, 2012). Our earlier studies also demonstrated that two other members of the MMP family, MMP7 and MMP12, were kept up-regulated following nerve injury (Jiang et al, 2014; Qin et al, 2016). All these results highlight the central roles of the MMP family in nerve regeneration.…”

“…Certainly, the gene expression patterns and activated biological processes in the distal nerve stump showed different characteristics compared to those in the proximal nerve stump. There has been a previous study which compared the differentially gene expressions in proximal and distal nerves after nerve injury (Jiang et al, 2014). It should be known that the proximal and the distal nerve stumps may share many common genes but have different spatiotemporal expression patterns after nerve injury.…”

“…For example, Gene Ontology analysis suggested that differentially expressed genes in the distal nerve stump could be mainly divided into functional groups with regulatory functions, including cell communication, cell transport, and transcriptional regulation (Bosse et al, 2006). Biological processes, such as response to stimulus, inflammatory response, immune response, cell proliferation, migration, and apoptosis, axon guidance, myelination, signal transduction, and protein kinase activity, were also investigated (Jiang et al, 2014). Despite these findings, it is still required to further investigate the molecular changes of Wallerian degeneration from a genetic perspective.…”

Miconazole alleviates peripheral nerve crush injury by mediating a macrophage phenotype change through the NF‐κB pathway

“…Complex correlations between Schwann cells, macrophages, and axons during nervous demyelinating and myelin regeneration (Jiang, Li, et al, 2014;McLean & Verge, 2016;Niemi et al, 2013). Complex correlations between Schwann cells, macrophages, and axons during nervous demyelinating and myelin regeneration (Jiang, Li, et al, 2014;McLean & Verge, 2016;Niemi et al, 2013).…”

“…In addition, the inflammation plays a key role in a series of pathological reaction of neurological disease. Complex correlations between Schwann cells, macrophages, and axons during nervous demyelinating and myelin regeneration (Jiang, Li, et al, 2014;McLean & Verge, 2016;Niemi et al, 2013). Inflammatory response is a hallmark of demyelinating pathology.…”