Postoperative cognitive dysfunction (POCD) is a prevalent neurological complication following surgery, particularly in elderly patients, characterized by memory deficits, attention impairments, and executive dysfunction. Despite its clinical significance, effective therapeutic strategies remain limited. Recent evidence highlights the gut-brain axis as a key modulator of neurocognitive outcomes, with emerging data indicating that probiotics such as VSL#3 may mitigate POCD through modulation of microbial communities and downstream molecular pathways. This study investigates the underlying mechanisms by which VSL#3 exerts neuroprotective effects in a mouse model of POCD.
A total of 156 adult male C57BL/6 mice were subjected to exploratory splenectomy under anesthesia to induce POCD, followed by either no treatment, daily intragastric administration of VSL#3, or additional genetic interventions targeting miR-146a, BTG2, or Bax. Behavioral assessments via Morris water maze revealed that mice in the Surgery group exhibited significantly prolonged escape latency and reduced time spent in the target quadrant compared to Control and VSL#3-only groups. Notably, VSL#3-treated mice showed markedly improved cognitive performance, suggesting protective effects against POCD. Immunohistochemical analysis using NeuN staining demonstrated a significant loss of hippocampal neurons in the Surgery group, which was partially preserved in the VSL#3 + Surgery cohort. TUNEL assay confirmed increased neuronal apoptosis in the surgical group, attenuated by VSL#3 administration.
Molecular analyses revealed that miR-146a expression was significantly downregulated in the hippocampus of POCD mice.Saccharocin Cancer VSL#3 treatment restored miR-146a levels, correlating with improved cognitive function. Functional studies using anti-miR-146a lentiviral vectors demonstrated that inhibition of miR-146a abolished the beneficial effects of VSL#3, resulting in worsened cognitive deficits and increased neuronal apoptosis. Conversely, overexpression of miR-146a mimicked the protective effects of VSL#3. Dual-luciferase reporter assays confirmed that miR-146a directly targets the 3′-UTR of BTG2 mRNA, leading to its translational repression. RT-qPCR and immunoblotting validated that BTG2 expression was elevated in POCD mice and suppressed by both VSL#3 and miR-146a overexpression.CALB1 Antibody Technical Information
Further investigation revealed that BTG2 positively regulates Bax, a pro-apoptotic protein.PMID:35022763 Knockdown of BTG2 using shRNA reduced Bax expression, decreased oxidative stress markers (ROS and MDA), enhanced SOD activity, and protected against neuronal death. These effects were reversed upon Bax overexpression, confirming the BTG2/Bax axis as a critical mediator of neuronal damage in POCD. Finally, in vivo experiments combining VSL#3 with Bax overexpression demonstrated that restoring Bax expression negated the neuroprotective benefits of VSL#3, underscoring the importance of this pathway.
In conclusion, this study establishes that VSL#3 alleviates POCD by upregulating miR-146a, which subsequently suppresses BTG2 and downstream Bax expression, thereby inhibiting neuronal apoptosis and reducing oxidative stress. These findings highlight miR-146a as a promising therapeutic target for preventing postoperative cognitive decline and suggest that probiotic intervention may be a viable strategy to preserve brain health in vulnerable surgical populations.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com