Lee_2025_J.Microbiol.Biotechnol_35_e2411013

Leuconostoc mesenteroides H40 (H40), originally isolated from kimchi, has been shown to exhibit probiotic characteristics and a neuroprotective effect in SH-SY5Y cells. In this study, we investigated the modulatory effects of heat-killed H40 (H-H40) in a scopolamine-induced (1 mg/kg/day) mouse model of cognitive impairment. H-H40 at either 1 x 10(8) or 1 x 10(9) CFU/day alleviated scopolamine-induced cognitive impairment in the novel object recognition and Y-maze tests. Neuroinflammatory cytokines, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, inducible NO synthase (iNOS), and cyclooxygenase (COX)-2 were all found to be decreased by H-H40 treatment. Moreover, changes in neurotransmitter levels and synaptic plasticity were further confirmed through measurement of acetylcholinesterase, acetylcholine, choline acetyltransferase, and brain-derived neurotrophic factor (BDNF) levels. H-H40 increased beta-secretase levels, but decreased amyloid-beta levels. In addition, the antioxidant effects of catalase and GPx were demonstrated. Overall, our results showed that H-H40 exerts positive cognitive effects by anti-inflammatory and antioxidant activities in a mouse model of scopolamine-induced cognitive impairment. H-H40 could be used as a prophylactic functional food for improving cognition.