Exploring the interplay of chronic toxoplasmosis and NMDAR dysfunction: Insights into schizophrenia-like behaviors and therapeutic potential.

Chronic infection with Toxoplasma gondii and ketamine treatment both produce schizophrenia-like symptoms in mice, including hyperactivity, anxiety, and memory problems. Both conditions also lowered antioxidant enzyme levels and increased lipid peroxidation in the brain, along with reduced expression of NMDA receptor subunits NR1 and NR2A. Treatment with sulfadiazine-trimethoprim partially reversed the NMDA receptor downregulation but did not correct all behavioral changes. The findings highlight a link between chronic toxoplasmosis, NMDA receptor dysfunction, and schizophrenia-like behaviors, suggesting potential targets for treating cognitive and neurological impairments.

Study at a glance

Abstract

Chronic toxoplasmosis has been strongly implicated in the development of psychosis and schizophrenia. Additionally, the understanding of schizophrenia has been significantly reshaped by insights into N-methyl-D-aspartate receptor (NMDAR) hypofunction. This study aimed to compare the behavioral, antioxidant, and NMDAR changes in mice subjected to Toxoplasma gondii infection and those treated with ketamine to induce schizophrenia-like symptoms. Sixty male BALB/c mice were divided into six groups: toxoplasmosis (TOXO) (infected), ketamine-induced schizophrenia (KET), TOXO+KET, TOXO+sulfadiazine-trimethoprim treatment (SDT), TOXO+KET+SDT, and control (CON) (uninfected). After 10 weeks post-infection, behavioral tests were conducted, brain antioxidant status and lipid peroxidation were analyzed, and NMDA-NR1/NR2A expressions were assessed. TOXO and KET induced distinct behaviors: hyperlocomotion, anxiety, and memory impairment. Antioxidant enzyme levels decreased, and lipid peroxidation increased in TOXO and schizophrenic mice brains. NMDAR downregulation, especially NR-1 and NR2A, was evident due to T. gondii and ketamine. Sulfadiazine-trimethoprim ameliorated NMDAR downregulation, but not all of the behavioral alterations. Further studies are needed to elucidate specific NMDAR subunit roles in toxoplasmosis-induced pathophysiology, offering potential therapeutic insights. This investigation highlights the intricate relationship between chronic toxoplasmosis, NMDAR dysfunction, and schizophrenia-like behaviors. Insights gained could pave the way for innovative interventions targeting both cognitive and neurological impairments associated with these conditions.