Dexmedetomidine alleviates postoperative cognitive dysfunction through circular RNA in aged rats

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Postoperative cognitive dysfunction (POCD) is a common complication with unclear underlying mechanisms.
• Circular RNAs (circRNAs) are implicated in various diseases, but their role in POCD is largely unknown.

Purpose of the Study:

• To investigate the therapeutic effects of dexmedetomidine (Dex) on POCD.
• To identify the role of circRNAs and associated pathways in Dex-mediated POCD treatment.

Main Methods:

• Morris water maze test and HE staining for behavioral and pathological assessment.
• RNA sequencing to identify differentially expressed circRNAs and their target genes.
• Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.
• Quantitative real-time polymerase chain reaction (qRT-PCR) for validation.

Main Results:

• Dex treatment significantly improved cognitive function and reduced hippocampal pathology in POCD rats.
• RNA sequencing identified 164 differentially expressed circRNAs between POCD and Dex groups.
• Target genes of differentially expressed circRNAs are enriched in apoptosis, cell adhesion, and inflammatory response pathways, including P53 and NF-κB signaling.
• circ-Shank3 was identified as a key circRNA involved in Dex's therapeutic effect on POCD.

Conclusions:

• Dexmedetomidine exerts therapeutic effects on POCD by regulating circRNA expression, particularly circ-Shank3.
• The P53 and NF-κB signaling pathways are crucial mediators of Dex's action in improving POCD.
• circRNAs represent potential therapeutic targets for clinical drug development in POCD treatment.