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Controlled Cortical Impact Model for Traumatic Brain Injury
Published on: August 5, 2014
Peripheral nerve injury is accompanied by chronic transcriptome-wide changes in the mouse prefrontal cortex
Sebastian Alvarado1, Maral Tajerian, Magali Millecamps
1Department of Pharmacology and Therapeutics, McGill University, Faculty of Medicine, 3655 Promenade Sir William Osler, Montréal, Québec H3G 1Y6, Canada.
Molecular Pain
|April 20, 2013
Summary
Peripheral nerve injury causes long-term gene expression changes in the brain's prefrontal cortex (PFC). These alterations may explain chronic pain and associated behaviors, persisting long after the initial injury.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Peripheral nerve injury can lead to chronic pain, hypersensitivity, and affective/cognitive disturbances.
- The prefrontal cortex (PFC) is implicated in pain comorbidities like depression and anxiety.
- Previous research showed PFC epigenetic reprogramming after nerve injury, linked to pain reduction.
Purpose of the Study:
- To investigate if peripheral nerve injury triggers persistent, long-lasting gene expression changes in the PFC.
- To determine if these gene expression changes alter functional networks, explaining chronic pain behaviors.
Main Methods:
- Utilized the Spared Nerve Injury (SNI) model in male CD1 mice.
- Performed transcriptome-wide sequencing (RNAseq) six months post-surgery.
- Validated key gene expression changes using RT-QPCR.
Main Results:
- Identified 1147 differentially regulated transcripts in the PFC of nerve-injured mice compared to controls.
- Observed significant alterations in biological processes including neurological disease, skeletal muscular disorders, behavior, and psychological disorders.
- Validated changes in genes related to chronic pain and neuronal plasticity (e.g., NMDA receptor, GFAP, SCN1A).
Conclusions:
- Demonstrated long-term alterations in brain gene expression following peripheral nerve injury using an unbiased approach.
- Proposed that these gene expression changes are maintained as a 'memory' of the initial injury.
- These findings offer a potential molecular explanation for persistent neuropathic pain and related behavioral changes.
