Epigenetic Manipulation of Psychiatric Behavioral Disorders Induced by Toxoplasma gondii

Abstract

Toxoplasma gondii is known to have a complex life cycle and infect almost all kinds of warm-blooded animals around the world. The brain of the host could be persistently infected by cerebral cysts, and a variety of psychiatric disorders such as schizophrenia and suicide have been reported to be related with latent toxoplasmosis. The infected animals showed fear reduction and a tendency to be preyed upon. However, the mechanism of this “parasites manipulation” effects have not been elucidated. Here, we reviewed the recent infection prevalence of toxoplasmosis and the evidence of mental and behavioral disorders induced by T. gondii and discussed the related physiological basis including dopamine dysregulation and gamma-aminobutyric acid (GABA) pathway and the controversial opinion of the necessity for cerebral cysts existence. Based on the recent advances, we speculated that the neuroendocrine programs and neurotransmitter imbalance may play a key role in this process. Simultaneously, studies in the evaluation of the expression pattern of related genes, long noncoding RNAs (lncRNAs), and mRNAs of the host provides a new point for understanding the mechanism of neurotransmitter dysfunction induced by parasite manipulation. Therefore, we summarized the animal models, T. gondii strains, and behavioral tests used in the related epigenetic studies and the responsible epigenetic processes; pinpointed opportunities and challenges in future research including the causality evidence of human psychiatric disorders, the statistical analysis for rodent-infected host to be more vulnerable preyed upon; and identified responsible genes and drug targets through epigenetics.

Modulation of autophagy as a therapeutic strategy for Toxoplasma gondii infection

“…It is noteworthy that T. gondii infection is related to psychiatric disorders in some subclinical cases, as numerous studies have shown the correlation between schizophrenia and T. gondii infection ( Xiao et al., 2018 ). Chronic toxoplasmosis is an significant risk factor for schizophrenia, which might be attributed to the dysregulation of neuroendocrine and the neurotransmitter imbalance caused by chronic neuroinflammation, while psychiatric disorders also increase the exposure risk of T. gondii ( Yin et al., 2022 ).…”

Label-free quantitative proteomics analyses of mouse astrocytes provides insight into the host response mechanism at different developmental stages ofToxoplasma gondii

“…Neuroendocrine programs and neurotransmitter imbalance may act as the physiological basis for T. gondii induced psychiatric and behavioral disorders [71] .…”

“…Neuroendocrine programs and neurotransmitter imbalance may act as the physiological basis for T. gondii induced psychiatric and behavioral disorders [71] . Glutamate (GLU) is the most abundant neurotransmitter in the brain, and its excitability plays a crucial role in brain structure and function.…”

Biological Factors Underpinning Suicidal Behaviour: An Update

“…T. gondii infecting patients with behavioural disorders could possibly induce a “behavioural manipulation” in the host (e.g., reduction of fear, as revealed in animals with induced infection with T. gondii ). This affects the host transcription elements through epigenetic modifications and induction of special effectors (such as the Toxoplasma E2F4-associated EZH2-inducing Gene Regulator), resulting in a change in the host gene expression at both transcriptional and post-translational levels [ 120 ].…”