Persistent toxoplasma infection of the brain induced neurodegeneration associated with activation of complement and microglia

Research output: Contribution to journalArticle

Abstract

Toxoplasma gondii, a common neurotropic parasite, is increasingly being linked to neuropsychiatric disorders, including schizophrenia, Alzheimer's disease, and Parkinson's disease. However, the pathogenic mechanisms underlying these associations are not clear. Toxoplasma can reside in the brain for extensive periods in the form of tissue cysts, and this process requires a continuous immune response to prevent the parasite's reactivation. Because neuroinflammation may promote the onset and progression of neurodegenerative diseases, we investigated neurodegeneration-associated pathological changes in a mouse model of chronic Toxoplasma infection. Under conditions of high-grade chronic infection, we documented the presence of neurodegeneration in specific regions of the prefrontal cortex, namely, the anterior cingulate cortex (ACC) and somatomotor cortex (SC). Neurodegeneration occurred in both glutamatergic and GABAergic neurons. Neurons that showed signs of degeneration expressed high levels of CX3CL1, were marked by profoundly upregulated complement proteins (e.g., C1q and C3), and were surrounded by activated microglia. Our findings suggest that chronic Toxoplasma infection leads to cortical neurodegeneration and results in CX3CL1, complement, and microglial interactions, which are known to mediate the phagocytic clearance of degenerating neurons. Our study provides a mechanistic explanation for the link between Toxoplasma infection and psychiatric disorders.

Original languageEnglish (US)
Article numbere00139
JournalInfection and Immunity
Volume87
Issue number8
DOIs
StatePublished - Jan 1 2019

Fingerprint

Complement Activation
Toxoplasma
Microglia
Brain
Infection
Parasites
Neurons
GABAergic Neurons
Complement C3
Gyrus Cinguli
Prefrontal Cortex
Neurodegenerative Diseases
Parkinson Disease
Psychiatry
Cysts
Schizophrenia
Alzheimer Disease
Complement System Proteins

Keywords

  • Complement
  • CX3CL1
  • Microglia
  • Neurodegeneration
  • Neuroinflammation
  • Toxoplasma gondii

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

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title = "Persistent toxoplasma infection of the brain induced neurodegeneration associated with activation of complement and microglia",
abstract = "Toxoplasma gondii, a common neurotropic parasite, is increasingly being linked to neuropsychiatric disorders, including schizophrenia, Alzheimer's disease, and Parkinson's disease. However, the pathogenic mechanisms underlying these associations are not clear. Toxoplasma can reside in the brain for extensive periods in the form of tissue cysts, and this process requires a continuous immune response to prevent the parasite's reactivation. Because neuroinflammation may promote the onset and progression of neurodegenerative diseases, we investigated neurodegeneration-associated pathological changes in a mouse model of chronic Toxoplasma infection. Under conditions of high-grade chronic infection, we documented the presence of neurodegeneration in specific regions of the prefrontal cortex, namely, the anterior cingulate cortex (ACC) and somatomotor cortex (SC). Neurodegeneration occurred in both glutamatergic and GABAergic neurons. Neurons that showed signs of degeneration expressed high levels of CX3CL1, were marked by profoundly upregulated complement proteins (e.g., C1q and C3), and were surrounded by activated microglia. Our findings suggest that chronic Toxoplasma infection leads to cortical neurodegeneration and results in CX3CL1, complement, and microglial interactions, which are known to mediate the phagocytic clearance of degenerating neurons. Our study provides a mechanistic explanation for the link between Toxoplasma infection and psychiatric disorders.",
keywords = "Complement, CX3CL1, Microglia, Neurodegeneration, Neuroinflammation, Toxoplasma gondii",
author = "Ye Li and Severance, {Emily G} and Viscidi, {Raphael P} and Yolken, {Robert H} and Jian-Chun Xiao",
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T1 - Persistent toxoplasma infection of the brain induced neurodegeneration associated with activation of complement and microglia

AU - Li, Ye

AU - Severance, Emily G

AU - Viscidi, Raphael P

AU - Yolken, Robert H

AU - Xiao, Jian-Chun

PY - 2019/1/1

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