Abstract

Chronic toxoplasmosis has been increasingly associated with behavior disorders, including depression-like behaviors, while the underlying mechanisms remain poorly understood. In this study, we demonstrated that chronic toxoplasmosis induced depression-like behaviors in mice, which were observed together with neuroinflammation, neuronal injury, and suppression of the BDNF–TrkB pathway. Treatment with the TrkB agonist 7,8-DHF alleviated these behavioral deficits by restoring BDNF–TrkB signaling, preserving neuronal function, and reducing neuroinflammation through inhibition of NF-κB and MAPK pathways. Additionally, 7,8-DHF also reduced astrocyte overactivation and protected blood–brain barrier structure integrity. These findings highlight that disruption of BDNF–TrkB signaling contributes to T. gondii -induced behavioral abnormalities and that targeting this pathway may represent a promising therapeutic strategy against neuroinflammation and neuronal damage associated with chronic infection. Graphical Chronic PRU strain infection induces neuroinflammation and suppresses BDNF–TrkB signaling, leading to neuronal injury and depression-like behaviors. 7,8-DHF exerts dual neuroprotective effects by directly restoring BDNF–TrkB signaling and indirectly alleviating neuroinflammation via inhibition of the NF-κB and MAPK pathways. This dual mechanism preserves BBB integrity and alleviates behavioral deficits in infected mice.