Circular Ribonucleic Acid Expression Profile in Mouse Cortex after Traumatic Brain Injury

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Traumatic brain injury (TBI) leads to significant mortality and morbidity due to complex secondary injury mechanisms.
• Circular RNAs (circRNAs), a class of post-transcriptional regulators, are widely expressed in the brain and may play a role in TBI.
• Understanding circRNA expression profiles in TBI is crucial for elucidating secondary injury pathways.

Purpose of the Study:

• To investigate the expression profile and functional significance of circRNAs in the mouse cortex following controlled cortical impact (CCI) induced TBI.
• To identify differentially expressed circRNAs and analyze their associated biological processes and molecular pathways.
• To explore potential circRNA-mediated regulatory networks, including circRNA-mRNA interactions and microRNA (miRNA) sponging.

Main Methods:

• Deep RNA sequencing (RNA-seq) and bioinformatic analysis were employed to profile circRNAs in mouse cortex post-CCI.
• Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on differentially expressed circRNAs.
• circRNA-mRNA interaction networks and competitive endogenous RNA (ceRNA) analysis were conducted to predict regulatory relationships.
• Quantitative real-time polymerase chain reaction (qRT-PCR) was used for validation of selected circRNAs.

Main Results:

• A total of 19,794 circRNAs were identified, with 191 differentially expressed (98 upregulated, 93 downregulated) after CCI.
• GO and KEGG analyses indicated that altered circRNAs are involved in inflammation, cell death, and tissue repair.
• A circRNA-miRNA-mRNA interaction network revealed potential regulatory pathways, including circRNA_16895 targeting the FcγR-mediated phagocytosis pathway via miRNA.
• Four circRNAs were validated using qRT-PCR, confirming the RNA-seq findings.

Conclusions:

• Aberrantly expressed circRNAs play significant roles in the molecular mechanisms underlying TBI.
• The identified circRNAs and their associated pathways represent potential therapeutic targets for TBI treatment.
• This study provides a foundation for further research into the functional roles of circRNAs in TBI pathogenesis.