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

Everett, Abigail; Elsheikha, Hany M

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.

Citation

Everett, A., & Elsheikha, H. M. (2025). Neuroinflammation and schizophrenia: The role of Toxoplasma gondii infection and astrocytic dysfunction. Journal of Neuroimmunology, 403, Article 578588. https://doi.org/10.1016/j.jneuroim.2025.578588

• Journal Article Type: Article
• Acceptance Date: Mar 16, 2025
• Online Publication Date: Mar 19, 2025
• Publication Date: Jun 15, 2025
• Deposit Date: Mar 27, 2025
• Publicly Available Date: Mar 27, 2025
• Journal: Journal of Neuroimmunology
• Print ISSN: 0165-5728
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 403
• Article Number: 578588
• DOI: https://doi.org/10.1016/j.jneuroim.2025.578588
• Keywords: Toxoplasma gondii; Schizophrenia; Astrocytes; Infection; Neuroinflammation; Immune response
• Public URL: https://nottingham-repository.worktribe.com/output/47003869
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0165572825000682?via%3Dihub
• Additional Information: This article is maintained by: Elsevier; Article Title: Neuroinflammation and schizophrenia: The role of Toxoplasma gondii infection and astrocytic dysfunction; Journal Title: Journal of Neuroimmunology; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.jneuroim.2025.578588; Content Type: article; Copyright: © 2025 The Authors. Published by Elsevier B.V.