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Chromatin Immunoprecipitation from Dorsal Root Ganglia Tissue following Axonal Injury
Published on: July 20, 2011
Patterns of gene expression reveal a temporally orchestrated wound healing response in the injured spinal cord
Margaret J Velardo1, Corinna Burger, Philip R Williams
1Department of Neuroscience, McKnight Brain Institute of the University of Florida, Gainesville, Florida 32610-0244, USA. velardo@mbi.ufl.edu
Abstract:
Spinal cord injury (SCI) induces a progressive pathophysiology affecting cell survival and neurological integrity via complex and evolving molecular cascades whose interrelationships are not fully understood. The present experiments were designed to: (1) determine potential functional interactions within transcriptional expression profiles obtained after a clinically relevant SCI and (2) test the consistency of transcript expression after SCI in two genetically and immunologically diverse rat strains characterized by differences in T cell competence and associated inflammatory responses. By interrogating Affymetrix U34A rat genome GeneChip microarrays, we defined the transcriptional expression patterns in midcervical contusion lesion sites between 1 and 90 d postinjury of athymic nude (AN) and Sprague Dawley (SD) strains. Stringent statistical analyses detected significant changes in 3638 probe sets, with 80 genes differing between the AN and SD groups. Subsequent detailed functional categorization of these transcripts unveiled an overall tissue remodeling response that was common to both strains. The functionally organized gene profiles were temporally distinct and correlated with repair indices observed microscopically and by magnetic resonance microimaging. Our molecular and anatomical observations have identified a novel, longitudinal perspective of the post-SCI response, namely, that of a highly orchestrated tissue repair and remodeling repertoire with a prominent cutaneous wound healing signature that is conserved between two widely differing rat strains. These results have significant bearing on the continuing development of cellular and pharmacological therapeutics directed at tissue rescue and neuronal regeneration in the injured spinal cord.
Insights
Spinal cord injury triggers complex molecular changes. This study reveals a conserved, orchestrated tissue repair process with a wound healing signature in different rat strains after injury.
Area of Science:
- Neuroscience
- Molecular Biology
- Genomics
Background:
- Spinal cord injury (SCI) involves complex molecular cascades impacting cell survival and neurological function.
- Understanding these molecular interactions is crucial for developing effective therapeutics.
Purpose of the Study:
- To investigate functional interactions within transcriptional profiles post-SCI.
- To assess transcript expression consistency across genetically diverse rat strains (athymic nude and Sprague Dawley) with varying immune responses.
Main Methods:
- Utilized Affymetrix U34A rat genome GeneChip microarrays to analyze gene expression at SCI lesion sites (1-90 days post-injury).
- Employed stringent statistical analyses to identify significant transcriptional changes and inter-strain gene expression differences.
- Performed functional categorization of differentially expressed genes.
Main Results:
- Identified 3638 significantly changed probe sets and 80 genes differing between rat strains.
- Unveiled a common, overall tissue remodeling response across both strains.
- Observed temporally distinct gene expression profiles correlated with microscopic and MRI-based repair indices.
Conclusions:
- Characterized a novel, longitudinal perspective of the post-SCI response as a highly orchestrated tissue repair and remodeling process.
- Highlighted a conserved cutaneous wound healing signature in the injured spinal cord across different rat strains.
- Findings provide insights for developing cellular and pharmacological therapies for spinal cord repair and neuronal regeneration.
