Persistent Toxoplasma Infection of the Brain Induced Neurodegeneration Associated with Activation of Complement and Microglia.
Infect Immun
; 87(8)2019 08.
Article
em En
| MEDLINE
| ID: mdl-31182619
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Toxoplasmose
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Microglia
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Ativação do Complemento
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Doenças Neurodegenerativas
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article