Chronic Regulation of miR-124-3p in the Perilesional Cortex after Experimental and Human TBI

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• MicroRNAs (miRNAs) are key gene regulators, and their dysregulation is implicated in Traumatic Brain Injury (TBI).
• miR-124-3p is a brain-enriched miRNA associated with post-TBI pathologies like neuroinflammation.

Purpose of the Study:

• To investigate the changes in miR-124-3p expression in the perilesional cortex following TBI.
• To identify miR-124-3p targets and assess their relevance in the TBI context.
• To determine if miR-124-3p downregulation in TBI is conserved in human brain tissue.

Main Methods:

• Quantitative reverse transcription PCR (RT-qPCR) to measure miR-124-3p and target gene expression in rat brain tissue.
• In situ hybridization to localize miR-124-3p expression in rat and human brain samples.
• Messenger RNA sequencing (mRNA-Seq) to identify global changes in miR-124-3p targets.

Main Results:

• miR-124-3p was significantly downregulated in the perilesional cortex of rats at 7 days and 3 months post-TBI.
• The miR-124-3p target, Stat3, was upregulated at 7 days post-TBI.
• mRNA-Seq identified hundreds of downregulated and upregulated miR-124-3p targets.
• Human autopsy samples showed reduced miR-124-3p expression in cortical neurons after TBI.

Conclusions:

• TBI induces persistent downregulation of miR-124-3p in the perilesional cortex.
• This miRNA dysregulation may play a role in the neurodegenerative and neuroinflammatory processes following TBI.
• Findings in rats translate to human TBI patients, highlighting miR-124-3p as a potential therapeutic target.