Dataset Information

Microarray and qPCR Analyses of Wallerian Degeneration in Rat Sciatic Nerves.

ABSTRACT: Wallerian degeneration occurs immediately following injury to mammal peripheral nerves. To better understand the molecular events occurring during Wallerian degeneration, a rat model of sciatic nerve transection was used to assess differentially expressed genes at 0.5, 1, 6, 12, 24 h, 4 days, 1, 2, 3, and 4 weeks post nerve injury (PNI). Hierarchical clustering, Euclidean distance matrix, and principal component analysis (PCA) collectively suggested three distinct phases within the post-injury period of 4 weeks. Gene ontology (GO) analysis suggested that phase I (0-6 h PNI), phase II (6-24 h PNI), and phase III (4 days to 4 weeks) were associated with acute response to injury, preformation of Wallerian degeneration, and complete execution of Wallerian degeneration, respectively. Critical signaling pathways and transcriptional factor networks responsible for the regulation of Wallerian degeneration were further identified and integrated using Kyoto Enrichment of Genes and Genomes (KEGG) pathway analysis and Ingenuity Pathway Analysis (IPA), respectively. Our results may help to elucidate some molecular mechanisms of gene regulation associated with Wallerian degeneration that occurs after traumatic injury to peripheral nerve axons in mammals.

SUBMITTER: Yi S

PROVIDER: S-EPMC5301003 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Microarray and qPCR Analyses of Wallerian Degeneration in Rat Sciatic Nerves.

Yi Sheng S Tang Xin X Yu Jun J Liu Jie J Ding Fei F Gu Xiaosong X

Frontiers in cellular neuroscience 20170210

Wallerian degeneration occurs immediately following injury to mammal peripheral nerves. To better understand the molecular events occurring during Wallerian degeneration, a rat model of sciatic nerve transection was used to assess differentially expressed genes at 0.5, 1, 6, 12, 24 h, 4 days, 1, 2, 3, and 4 weeks post nerve injury (PNI). Hierarchical clustering, Euclidean distance matrix, and principal component analysis (PCA) collectively suggested three distinct phases within the post-injury p ...[more]

PMID: 28239339

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Project description:BackgroundThe progressive nature of Wallerian degeneration has long been controversial. Conflicting reports that distal stumps of injured axons degenerate anterogradely, retrogradely, or simultaneously are based on statistical observations at discontinuous locations within the nerve, without observing any single axon at two distant points. As axon degeneration is asynchronous, there are clear advantages to longitudinal studies of individual degenerating axons. We recently validated the study of Wallerian degeneration using yellow fluorescent protein (YFP) in a small, representative population of axons, which greatly improves longitudinal imaging. Here, we apply this method to study the progressive nature of Wallerian degeneration in both wild-type and slow Wallerian degeneration (WldS) mutant mice.ResultsIn wild-type nerves, we directly observed partially fragmented axons (average 5.3%) among a majority of fully intact or degenerated axons 37-42 h after transection and 40-44 h after crush injury. Axons exist in this state only transiently, probably for less than one hour. Surprisingly, axons degenerated anterogradely after transection but retrogradely after a crush, but in both cases a sharp boundary separated intact and fragmented regions of individual axons, indicating that Wallerian degeneration progresses as a wave sequentially affecting adjacent regions of the axon. In contrast, most or all WldS axons were partially fragmented 15-25 days after nerve lesion, WldS axons degenerated anterogradely independent of lesion type, and signs of degeneration increased gradually along the nerve instead of abruptly. Furthermore, the first signs of degeneration were short constrictions, not complete breaks.ConclusionsWe conclude that Wallerian degeneration progresses rapidly along individual wild-type axons after a heterogeneous latent phase. The speed of progression and its ability to travel in either direction challenges earlier models in which clearance of trophic or regulatory factors by axonal transport triggers degeneration. WldS axons, once they finally degenerate, do so by a fundamentally different mechanism, indicated by differences in the rate, direction and abruptness of progression, and by different early morphological signs of degeneration. These observations suggest that WldS axons undergo a slow anterograde decay as axonal components are gradually depleted, and do not simply follow the degeneration pathway of wild-type axons at a slower rate.

Project description:Sensory and motor nerve fibers of peripheral nerves have different anatomies and regeneration functions after injury. To gain a clear understanding of the biological processes behind these differences, we used a labeling technique termed isobaric tags for relative and absolute quantitation to investigate the protein profiles of spinal nerve tissues from Sprague-Dawley rats. In response to Wallerian degeneration, a total of 626 proteins were screened in sensory nerves, of which 368 were upregulated and 258 were downregulated. In addition, 637 proteins were screened in motor nerves, of which 372 were upregulated and 265 were downregulated. All identified proteins were analyzed using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of bioinformatics, and the presence of several key proteins closely related to Wallerian degeneration were tested and verified using quantitative real-time polymerase chain reaction analyses. The differentially expressed proteins only identified in the sensory nerves were mainly relevant to various biological processes that included cell-cell adhesion, carbohydrate metabolic processes and cell adhesion, whereas differentially expressed proteins only identified in the motor nerves were mainly relevant to biological processes associated with the glycolytic process, cell redox homeostasis, and protein folding. In the aspect of the cellular component, the differentially expressed proteins in the sensory and motor nerves were commonly related to extracellular exosomes, the myelin sheath, and focal adhesion. According to the Kyoto Encyclopedia of Genes and Genomes, the differentially expressed proteins identified are primarily related to various types of metabolic pathways. In conclusion, the present study screened differentially expressed proteins to reveal more about the di?erences and similarities between sensory and motor nerves during Wallerian degeneration. The present findings could provide a reference point for a future investigation into the differences between sensory and motor nerves in Wallerian degeneration and the characteristics of peripheral nerve regeneration. The study was approved by the Ethics Committee of the Chinese PLA General Hospital, China (approval No. 2016-x9-07) in September 2016.

Dataset Information

Microarray and qPCR Analyses of Wallerian Degeneration in Rat Sciatic Nerves.

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Microarray and qPCR Analyses of Wallerian Degeneration in Rat Sciatic Nerves.

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