Development of Anxiolytic and Depression-like Behavior in Mice Infected with Mycobacterium lepraemurium.

[Display omitted] • Murine leprosy is a chronic mycobacterial disease that does not infect the nervous system, however alterations in the prefrontal cortex, ventral hippocampus and amygdala have been associated with neurocognitive impairment. • Murine-leprosy infection elicited a suppressive immune response with high levels of IL-10 and IL-4 and spleno-hepatomegaly. • Chronic infection induces BBB disruption and neuroinflammation. • Murine leprosy atrophy the adrenal glands and increase levels of epinephrine, norepinephrine and corticosterone. • The immunosuppressive environment generated by the infection may affect the nervous and endocrine system integrity and function. Murine leprosy is a systemic infectious disease of mice caused by Mycobacterium lepraemurium (MLM) in which the central nervous system (CNS) is not infected; nevertheless, diseased animals show measurable cognitive alterations. For this reason, in this study, we explored the neurobehavioral changes in mice chronically infected with MLM. BALB/c mice were infected with MLM, and 120 days later, the alterations in mice were evaluated based on immunologic, histologic, endocrine, neurochemical, and behavioral traits. We found increases in the levels of IL-4 and IL-10 associated with high bacillary loads. We also found increase in the serum levels of corticosterone, epinephrine, and norepinephrine in the adrenal gland, suggesting neuroendocrine deregulation. Mice exhibited depression-like behavior in the tail suspension and forced swimming tests and anxiolytic behavior in the open field and elevated plus maze tests. The neurobehavioral alterations of mice were correlated with the histologic damage in the prefrontal cortex, ventral hippocampus, and amygdala, as well as with a blood–brain barrier disruption in the hippocampus. These results reveal an interrelated response of the neuroimmune-–endocrinological axis in unresolved chronic infections that result in neurocognitive deterioration. [ABSTRACT FROM AUTHOR]