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Whole transcriptome sequencing reveals dexmedetomidine-improves postoperative cognitive dysfunction in rats via
Fumou Deng1, Lily Cai2, Bin Zhou1
11Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, No.1 Minde Road, Donghu District, Nanchang, Jiangxi China.
3 Biotech
|April 21, 2020
Summary
Dexmedetomidine (Dex) improves postoperative cognitive dysfunction (POCD) in rats by regulating long non-coding RNAs (lncRNAs). The study identified lncRNA LOC102546895 as a key player in POCD, targeting Npas4 to modulate microglial activity.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Postoperative cognitive dysfunction (POCD) is a significant concern.
- Dexmedetomidine (Dex) shows potential in mitigating POCD.
- The molecular mechanisms underlying Dex's effect on POCD require further elucidation, particularly concerning long non-coding RNAs (lncRNAs).
Purpose of the Study:
- To investigate the role and mechanism of Dex-regulated lncRNAs in improving POCD in a rat model.
- To identify specific lncRNAs involved in the therapeutic effects of Dex on POCD.
- To explore the downstream targets and pathways influenced by these lncRNAs.
Main Methods:
- Establishment of a rat model for POCD and Dex treatment.
- Behavioral assessment using the Morris water maze test.
- Hippocampal lncRNA sequencing, quantitative reverse transcription PCR (qRT-PCR), and competing endogenous RNA (ceRNA) network construction.
- Analysis of inflammatory cytokines (ELISA) and microglial cell activity (CCK-8 assay, flow cytometry).
Main Results:
- Dex treatment alleviated cognitive deficits and reduced neuronal injury in POCD rats.
- Dex significantly downregulated inflammatory cytokines TNF-α and IL-1β.
- A total of 60 differentially expressed lncRNAs were identified; lncRNA LOC102546895 was highlighted for its role in inhibiting microglial proliferation and promoting apoptosis, potentially via targeting Npas4.
Conclusions:
- Dexmedetomidine effectively alleviates POCD in rats.
- Dex alters the hippocampal lncRNA expression profile in POCD rats.
- Dex-regulated lncRNA LOC102546895 may be a crucial mediator in Dex's therapeutic effects on POCD by targeting Npas4 and influencing microglial function.
