Sex-dimorphic neuroprotective effect of CD163 in an α-synuclein mouse model of Parkinson’s disease

Sara A. Ferreira; Conghui Li; Ida H. Klæstrup; Zagorka Vitic; Rikke K. Rasmussen; Asger Kirkegaard; Gitte U. Toft; Cristine Betzer; Pia Svendsen; Poul H. Jensen; Yonglun Luo; Anders Etzerodt; Søren K. Moestrup; Marina Romero-Ramos

doi:10.1038/s41531-023-00606-w

Sex-dimorphic neuroprotective effect of CD163 in an α-synuclein mouse model of Parkinson’s disease

Sara A. Ferreira, Conghui Li, Ida H. Klæstrup, Zagorka Vitic, Rikke K. Rasmussen, Asger Kirkegaard, Gitte U. Toft, Cristine Betzer, Pia Svendsen, Poul H. Jensen, Yonglun Luo, Anders Etzerodt, Søren K. Moestrup, Marina Romero-Ramos

Research output: Contribution to journal › Article › peer-review

Abstract

Alpha-synuclein (α-syn) aggregation and immune activation represent hallmark pathological events in Parkinson’s disease (PD). The PD-associated immune response encompasses both brain and peripheral immune cells, although little is known about the immune proteins relevant for such a response. We propose that the upregulation of CD163 observed in blood monocytes and in the responsive microglia in PD patients is a protective mechanism in the disease. To investigate this, we used the PD model based on intrastriatal injections of murine α-syn pre-formed fibrils in CD163 knockout (KO) mice and wild-type littermates. CD163KO females revealed an impaired and differential early immune response to α-syn pathology as revealed by immunohistochemical and transcriptomic analysis. After 6 months, CD163KO females showed an exacerbated immune response and α-syn pathology, which ultimately led to dopaminergic neurodegeneration of greater magnitude. These findings support a sex-dimorphic neuroprotective role for CD163 during α-syn-induced neurodegeneration.

Original language	English
Article number	164
Journal	npj Parkinson's Disease
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41531-023-00606-w
State	Published - 1 Dec 2023
Externally published	Yes

ASJC Scopus subject areas

Neurology
Clinical Neurology
Cellular and Molecular Neuroscience

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Ferreira, S. A., Li, C., Klæstrup, I. H., Vitic, Z., Rasmussen, R. K., Kirkegaard, A., Toft, G. U., Betzer, C., Svendsen, P., Jensen, P. H., Luo, Y., Etzerodt, A., Moestrup, S. K., & Romero-Ramos, M. (2023). Sex-dimorphic neuroprotective effect of CD163 in an α-synuclein mouse model of Parkinson’s disease. npj Parkinson's Disease, 9(1), Article 164. https://doi.org/10.1038/s41531-023-00606-w

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title = "Sex-dimorphic neuroprotective effect of CD163 in an α-synuclein mouse model of Parkinson{\textquoteright}s disease",

abstract = "Alpha-synuclein (α-syn) aggregation and immune activation represent hallmark pathological events in Parkinson{\textquoteright}s disease (PD). The PD-associated immune response encompasses both brain and peripheral immune cells, although little is known about the immune proteins relevant for such a response. We propose that the upregulation of CD163 observed in blood monocytes and in the responsive microglia in PD patients is a protective mechanism in the disease. To investigate this, we used the PD model based on intrastriatal injections of murine α-syn pre-formed fibrils in CD163 knockout (KO) mice and wild-type littermates. CD163KO females revealed an impaired and differential early immune response to α-syn pathology as revealed by immunohistochemical and transcriptomic analysis. After 6 months, CD163KO females showed an exacerbated immune response and α-syn pathology, which ultimately led to dopaminergic neurodegeneration of greater magnitude. These findings support a sex-dimorphic neuroprotective role for CD163 during α-syn-induced neurodegeneration.",

author = "Ferreira, {Sara A.} and Conghui Li and Kl{\ae}strup, {Ida H.} and Zagorka Vitic and Rasmussen, {Rikke K.} and Asger Kirkegaard and Toft, {Gitte U.} and Cristine Betzer and Pia Svendsen and Jensen, {Poul H.} and Yonglun Luo and Anders Etzerodt and Moestrup, {S{\o}ren K.} and Marina Romero-Ramos",

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doi = "10.1038/s41531-023-00606-w",

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Ferreira, SA, Li, C, Klæstrup, IH, Vitic, Z, Rasmussen, RK, Kirkegaard, A, Toft, GU, Betzer, C, Svendsen, P, Jensen, PH, Luo, Y, Etzerodt, A, Moestrup, SK & Romero-Ramos, M 2023, 'Sex-dimorphic neuroprotective effect of CD163 in an α-synuclein mouse model of Parkinson’s disease', npj Parkinson's Disease, vol. 9, no. 1, 164. https://doi.org/10.1038/s41531-023-00606-w

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T1 - Sex-dimorphic neuroprotective effect of CD163 in an α-synuclein mouse model of Parkinson’s disease

AU - Ferreira, Sara A.

AU - Li, Conghui

AU - Klæstrup, Ida H.

AU - Vitic, Zagorka

AU - Rasmussen, Rikke K.

AU - Kirkegaard, Asger

AU - Toft, Gitte U.

AU - Betzer, Cristine

AU - Svendsen, Pia

AU - Jensen, Poul H.

AU - Luo, Yonglun

AU - Etzerodt, Anders

AU - Moestrup, Søren K.

AU - Romero-Ramos, Marina

PY - 2023/12/1

Y1 - 2023/12/1

N2 - Alpha-synuclein (α-syn) aggregation and immune activation represent hallmark pathological events in Parkinson’s disease (PD). The PD-associated immune response encompasses both brain and peripheral immune cells, although little is known about the immune proteins relevant for such a response. We propose that the upregulation of CD163 observed in blood monocytes and in the responsive microglia in PD patients is a protective mechanism in the disease. To investigate this, we used the PD model based on intrastriatal injections of murine α-syn pre-formed fibrils in CD163 knockout (KO) mice and wild-type littermates. CD163KO females revealed an impaired and differential early immune response to α-syn pathology as revealed by immunohistochemical and transcriptomic analysis. After 6 months, CD163KO females showed an exacerbated immune response and α-syn pathology, which ultimately led to dopaminergic neurodegeneration of greater magnitude. These findings support a sex-dimorphic neuroprotective role for CD163 during α-syn-induced neurodegeneration.

AB - Alpha-synuclein (α-syn) aggregation and immune activation represent hallmark pathological events in Parkinson’s disease (PD). The PD-associated immune response encompasses both brain and peripheral immune cells, although little is known about the immune proteins relevant for such a response. We propose that the upregulation of CD163 observed in blood monocytes and in the responsive microglia in PD patients is a protective mechanism in the disease. To investigate this, we used the PD model based on intrastriatal injections of murine α-syn pre-formed fibrils in CD163 knockout (KO) mice and wild-type littermates. CD163KO females revealed an impaired and differential early immune response to α-syn pathology as revealed by immunohistochemical and transcriptomic analysis. After 6 months, CD163KO females showed an exacerbated immune response and α-syn pathology, which ultimately led to dopaminergic neurodegeneration of greater magnitude. These findings support a sex-dimorphic neuroprotective role for CD163 during α-syn-induced neurodegeneration.

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Sex-dimorphic neuroprotective effect of CD163 in an α-synuclein mouse model of Parkinson’s disease

Abstract

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