Neuroinflammation and schizophrenia: The role of Toxoplasma gondii infection and astrocytic dysfunction

Abstract

Obligate intracellular pathogens such as the protozoan Toxoplasma gondii exploit host cell mechanisms to facilitate their survival and replication. While T. gondii can infect any nucleated mammalian cell, it exhibits a particular affinity for central nervous system cells, including neurons, astrocytes, and microglia. Among these, astrocytes play a pivotal role in maintaining neuroimmune balance, and their infection by T. gondii induces structural and functional alterations. Emerging evidence suggests that these changes may contribute to the pathophysiology of schizophrenia (SCZ). Although a direct causal link between T. gondii-induced astrocytic dysfunction and SCZ remains unproven, infection has been associated with increased kynurenic acid production, elevated dopamine levels, and heightened inflammatory cytokines—all of which are implicated in SCZ pathology. Additionally, T. gondii infection disrupts crucial neurobiological processes, including N-methyl-d-aspartate receptor signaling, blood-brain barrier integrity, and gray matter volume, further aligning with SCZ-associated neuropathology. This review underscores the need for targeted research into T. gondii-mediated astrocytic dysfunction as a potential factor in SCZ development. Understanding the mechanistic links between T. gondii infection, astrocytic alterations, and psychiatric disorders may open new avenues for therapeutic interventions.