Abstract

Social isolation (SI) is associated with cognitive decline and dementia, with mitochondrial dysfunction and ferroptosis as potential underlying mechanisms. This study aimed to investigate the effects of SI-induced stress on cognitive function, mitochondrial function, and ferroptosis. SI-induced mice exhibited anxiety, depressive-like behavior, cognitive decline, increased levels of oxidative stress, mitochondrial dysfunction, and ferroptosis. Two-month-old male C57BL/6 mice were subjected to 8 weeks of SI, lactoferrin intervention was administered to evaluate its therapeutic effects in SI-induced cognitive dysfunction. Treatment with milk-derived lactoferrin mitigated these effects, improving cognitive function and reducing markers of oxidative stress, mitochondrial damage, and ferroptosis. Overall, our findings demonstrated that lactoferrin alleviates the adverse effects of SI. These findings underscore the molecular mechanisms by which LF improves cognitive function.