Combined Lactobacillus plantarum Supplementation and Aerobic Training Mitigate Cognitive and Behavioral Impairments in Ovariectomized Rats.

BACKGROUND: Menopause, modeled by ovariectomy (OVX) in rodents, causes cognitive decline and emotional disturbances due to estrogen withdrawal. While probiotics and aerobic exercise independently show beneficial effects, their combined contribution remains poorly characterized. This study investigated whether concurrent administration of Lactobacillus plantarum and aerobic exercise alleviates cognitive and behavioral deficits in OVX rats. METHODS: Fifty female Wistar rats (9-12 weeks old) were randomly allocated into five groups (n=10/group): Sham, OVX+PBS, OVX+Exercise (Exe), OVX+L. plantarum, and OVX+ Exe+ L. plantarum. Following a 16-day postoperative recovery, L. plantarum (1.5 × 108 CFU/mL) was administered via oral gavage (1 mL/day, 5 days/week), and treadmill training was performed for five weeks. Neurobehavioral outcomes were assessed via three-chamber social interaction, elevated plus-maze, forced swim test, Barnes maze test, novel object recognition, and marble-burying tests. Molecular changes were evaluated using ELISA for pro-inflammatory cytokines and RT-qPCR for Bdnf and Ntrk2 expression. Data were analyzed by one- or two-way ANOVA followed by Tukey's post hoc test (P < 0.05). RESULTS: OVX rats exhibited significant cognitive impairment, social withdrawal, and increased obsessive-compulsive-like behavior (p<0.05). While either intervention alone produced moderate effects, their combined application (OVX+Exe+ L. plantarum) yielded the greatest improvement, significantly attenuating anxiety and restoring social and cognitive performance to levels comparable to the Sham group (P > 0.05). Furthermore, the combined intervention significantly downregulated pro-inflammatory cytokines and upregulated hippocampal Bdnf and Ntrk2 expression. CONCLUSIONS: Combined L. plantarum and aerobic exercise effectively counteract the neurobehavioral and molecular sequelae of hormonal deficiency in post-menopausal models, suggesting that integrating psychobiotics with physical activity is a potent non-pharmacological strategy for managing menopause-related cognitive and behavioral challenges.