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Updated: Aug 18, 2026
A Mouse Model of Orthopedic Surgery to Study Postoperative Cognitive Dysfunction and Tissue Regeneration
Published on: February 27, 2018
Elevation of miR-146a Inhibits BTG2/BAX Expression to Ameliorate Postoperative Cognitive Dysfunction Following
Lei Mao1,2, Qingcui Zeng2,3, Wenjie Su1,2
1Department of Anesthesiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Qingyang District, Chengdu, 610072, Sichuan Province, People's Republic of China.
Abstract:
It has been reported that the gut microbiome modulates postoperative cognitive dysfunction (POCD), and that administration of probiotics (VSL#3) may effectively relieve POCD. In this study, we aimed to identify the underlying mechanism of VSL#3 in POCD. A mouse model of POCD was constructed in adult male C57BL/6 mice, which were then treated with VSL#3. VSL#3 exerted a protective role against POCD and resultant neuronal apoptosis. The expression of miR-146a was found to be downregulated in hippocampal tissues of POCD mice, while VSL#3 could restore its expression. Loss- and gain-function approaches were conducted to determine the roles of microRNA (miR)-146a, B-cell translocation gene 2 (BTG2), and Bcl-2-associated X protein (Bax) in post-operative effects on cognitive function and neuronal apoptosis. The levels of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) were measured to determine oxidative stress in brain tissue. The dual-luciferase reporter gene assay identified that miR-146a could target BTG2 and negatively regulate its expression. BTG2 knockdown suppressed neuronal apoptosis and contributed to shortened time of latency, prolonged time of mice spent in the target quadrant, and reduced oxidative stress through downregulating Bax expression. Finally, VSL#3 treatment upregulated the expression of miR-146a to block BTG2/Bax axis and consequently inhibited neuronal apoptosis and reduced oxidative stress in POCD mice. Taken together, the study suggested that miR-146a-mediated suppression of BTG2/Bax contributed to the protective role of probiotics treatment against POCD.
Insights
Probiotics (VSL#3) protect against postoperative cognitive dysfunction (POCD) by upregulating miR-146a, which suppresses the BTG2/Bax pathway, reducing neuronal apoptosis and oxidative stress.
Area of Science:
- Neuroscience
- Microbiology
- Molecular Biology
Background:
- Gut microbiome influences postoperative cognitive dysfunction (POCD).
- Probiotic VSL#3 shows potential in alleviating POCD.
- Underlying mechanisms of probiotic intervention in POCD require elucidation.
Purpose of the Study:
- To investigate the protective mechanism of VSL#3 against POCD.
- To identify the role of microRNA (miR)-146a, BTG2, and Bax in POCD.
- To explore the impact of VSL#3 on oxidative stress and neuronal apoptosis in POCD.
Main Methods:
- Established a mouse model of POCD and treated with VSL#3.
- Utilized loss- and gain-of-function studies for miR-146a, BTG2, and Bax.
- Assessed oxidative stress markers (ROS, MDA, SOD) and neuronal apoptosis.
- Performed dual-luciferase reporter assays to confirm miR-146a targeting of BTG2.
Main Results:
- VSL#3 treatment protected against POCD, reducing neuronal apoptosis.
- miR-146a expression was downregulated in POCD mice but restored by VSL#3.
- miR-146a directly targeted BTG2, inhibiting its expression; BTG2 knockdown reduced apoptosis and oxidative stress via Bax downregulation.
- VSL#3 upregulated miR-146a, inhibiting the BTG2/Bax axis, thereby reducing neuronal apoptosis and oxidative stress.
Conclusions:
- VSL#3 exerts neuroprotective effects against POCD.
- The miR-146a/BTG2/Bax pathway is a key mechanism in VSL#3's protective role.
- Targeting the miR-146a-mediated suppression of BTG2/Bax offers a therapeutic strategy for POCD.
