Lactobacillus mucosae Reduces Neuronal Oxidative Stress in Alzheimer's Disease via the Regulation of CB2 Signaling.

BACKGROUND: The probiotic Lactobacillus mucosae has been widely shown to have many positive effects. However, its neuroprotective effects and underlying mechanism in Alzheimer's disease (AD) remain elusive. METHODS: Male APP/PS1 mice were treated for 4 weeks with L. mucosae WMU007, followed by the evaluation of cognitive function, neuronal damage, amyloid-β (Aβ) deposition, and Tau phosphorylation. RNA-seq coupled with Gene Ontology (GO) enrichment analysis implicated L. mucosae WMU007 in modulating oxidative stress in this AD model. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and qPCR were performed to identify the specific mechanism by which this probiotic suppresses oxidative stress in the pathogenesis of AD. In addition, we quantified the levels of classical oxidative stress markers, such as superoxide dismutase 2 (SOD2) and glutathione peroxidase 4 (GPX4). We also examined the expression of cannabinoid receptor type 2 (CB2) and its key downstream regulators in the redox pathway, namely nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1), in both animal and cellular models. RESULTS: Our results showed that treatment with L. mucosae WMU007 significantly decreased cognitive impairment, neuronal damage, Aβ deposits, and Tau phosphorylation in APP/PS1 mice. Activation of CB2 was identified as the key mechanism by which L. mucosae WMU007 reduces oxidative stress in AD. In addition, L. mucosae WMU007 reduced oxidative stress and increased the levels of CB2 pathway-related proteins in vivo and in vitro. CONCLUSIONS: These results indicate that L. mucosae WMU007 confers neuroprotection in AD by targeting CB2-mediated oxidative pathways, highlighting its therapeutic potential as a novel probiotic intervention.