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Stereotactic Injection of MicroRNA-expressing Lentiviruses to the Mouse Hippocampus CA1 Region and Assessment of the Behavioral Outcome
Published on: June 10, 2013
Expression of microRNA induced by postoperative delirium-like behavior is associated with long-term default mode
Yang Liu1,2, Huiru Feng1, Huiqun Fu1
1Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Aims:
Resting state functional magnetic resonance imaging (rs-fMRI) has been widely used in studying default mode network (DMN) changes in postoperative delirium (POD). Reproducibility and interpretability of the analyzing results remain insufficiently studied.
Methods:
Delirium-like behavior was induced by tibial fixation surgery under isoflurane anesthesia. Firstly, we evaluated delirium-like behavior and inflammatory responses in hippocampus and systemic level. Then the expressions of microRNA (miRNA) and target gene were sequenced and validated. Afterwards the functional connectivity (FC) in DMN was analyzed. Finally, results were correlated with DMN changes.
Results:
POD-like behavior caused significant changes of miR-34b-5p, miR-328-5p, and miR-3505 in miRNA level and Nos1, Tubb3, and Gys1 in the gene level. The FC in left and right hippocampus (L-Hip and R-Hip) and right auditory cortex (R-AC) was found significantly changed. Significant correlations were found in FCL-Hip/R-AC and FCR-Hip/R-AC for miR-34b-5p and miR-3505, as well as Nos1 and Tubb3. For miR-328-5p, no significant correlations were found.
Conclusion:
Our study demonstrates that POD-like behavior induced significant miRNA and gene expression changes were associated with hippocampus related long-term FC disruption in DMN. The results increased reproducibility and interpretability for standardized rs-fMRI data analysis, as well as providing potential targets for postoperative delirium treatment.
Insights
Postoperative delirium (POD) is linked to changes in brain connectivity and specific microRNA and gene expressions. This study enhances the understanding and reproducibility of analyzing these default mode network (DMN) changes.
Area of Science:
- Neuroscience
- Genetics
- Medical Imaging
Background:
- Resting-state functional magnetic resonance imaging (rs-fMRI) is crucial for studying default mode network (DMN) alterations in postoperative delirium (POD).
- The reproducibility and interpretability of rs-fMRI analyses for POD require further investigation.
Purpose of the Study:
- To investigate the relationship between delirium-like behavior, microRNA (miRNA) and gene expression changes, and DMN functional connectivity (FC) alterations in a rodent model.
- To enhance the reproducibility and interpretability of rs-fMRI data analysis in the context of POD.
Main Methods:
- Induction of delirium-like behavior via tibial fixation surgery and isoflurane anesthesia.
- Evaluation of behavioral and inflammatory responses, followed by miRNA and target gene sequencing.
- Analysis of DMN functional connectivity (FC) using rs-fMRI and correlation with molecular changes.
Main Results:
- Delirium-like behavior altered specific miRNAs (miR-34b-5p, miR-328-5p, miR-3505) and genes (Nos1, Tubb3, Gys1).
- Significant changes in FC were observed in the hippocampus and auditory cortex.
- Correlations were found between FC in hippocampus-auditory cortex pathways and specific miRNAs/genes (miR-34b-5p, miR-3505, Nos1, Tubb3).
Conclusions:
- POD-induced miRNA and gene expression changes are associated with long-term DMN functional connectivity disruption, particularly involving the hippocampus.
- The findings improve reproducibility and interpretability of rs-fMRI analysis for POD.
- Identified molecular changes offer potential therapeutic targets for postoperative delirium.
