Cerebral Organoids Derived from a Parkinson's Patient Exhibit Unique Pathogenesis from Chikungunya Virus Infection When Compared to a Non-Parkinson's Patient

与非帕金森病患者相比,来自帕金森病患者的脑类器官表现出基孔肯雅病毒感染的独特发病机制

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作者:Emily M Schultz, TyAnthony J Jones, Sibei Xu, Dana D Dean, Bernd Zechmann, Kelli L Barr

Background

Arboviruses of medical and veterinary significance have been identified on all seven continents, with every human and animal population at risk for exposure. Like arboviruses, chronic neurodegenerative diseases, like Alzheimer's and Parkinson's disease, are found wherever there are humans. Significant differences in baseline gene and protein expression have been determined between human-induced pluripotent stem cell lines derived from non-Parkinson's disease individuals and from individuals with Parkinson's disease. It was hypothesized that these inherent differences could impact cerebral organoid responses to viral infection. (2)

Conclusions

The differential antiviral response of Parkinson's organoids compared with non-Parkinson's organoids highlights the need for more research in neurotropic infections in a neurologically compromised host.

Methods

In this study, cerebral organoids from a non-Parkinson's and Parkinson's patient were infected with Chikungunya virus and observed for two weeks. (3)

Results

Parkinson's organoids lost mass and exhibited a differential antiviral response different from non-Parkinson's organoids. Neurotransmission data from both infected non-Parkinson's and Parkinson's organoids had dysregulation of IL-1, IL-10, and IL-6. These cytokines are associated with mood and could be contributing to persistent depression seen in patients following CHIKV infection. Both organoid types had increased expression of CXCL10, which is linked to demyelination. (4) Conclusions: The differential antiviral response of Parkinson's organoids compared with non-Parkinson's organoids highlights the need for more research in neurotropic infections in a neurologically compromised host.

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