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

被引：5

作者：

Ferreira, Sara A. ^{[1
,2
]}

Li, Conghui ^{[3
]}

Klaestrup, Ida H. ^{[1
,2
]}

Vitic, Zagorka ^{[1
,2
]}

Rasmussen, Rikke K. ^{[1
]}

Kirkegaard, Asger ^{[1
,2
]}

Toft, Gitte U. ^{[1
,2
]}

Betzer, Cristine ^{[1
,2
]}

Svendsen, Pia ^{[1
,4
]}

Jensen, Poul H. ^{[1
,2
]}

Luo, Yonglun ^{[1
,2
,5
]}

Etzerodt, Anders ^{[1
]}

Moestrup, Soren K. ^{[1
,4
]}

Romero-Ramos, Marina ^{[1
,2
]}

机构：

[1] Aarhus Univ, Dept Biomed, Aarhus, Denmark

[2] Aarhus Univ, Danish Res Inst Translat Neurosci DANDRITE, Aarhus, Denmark

[3] Univ Copenhagen, Dept Biol, Copenhagen, Denmark

[4] Univ Southern Denmark, Dept Mol Med, Odense, Denmark

[5] Aarhus Univ Hosp, Steno Diabet Ctr Aarhus, Aarhus, Denmark

来源：

NPJ PARKINSONS DISEASE | 2023年 / 9卷 / 01期

关键词：

COREGULATED GENE; MICROGLIA; RECEPTOR; PATHOLOGY; MICE; TRANSMISSION; ASSOCIATION; ACTIVATION; HEMOGLOBIN; EXPRESSION;

D O I：

10.1038/s41531-023-00606-w

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Alpha-synuclein (alpha-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 alpha-syn pre-formed fibrils in CD163 knockout (KO) mice and wild-type littermates. CD163KO females revealed an impaired and differential early immune response to alpha-syn pathology as revealed by immunohistochemical and transcriptomic analysis. After 6 months, CD163KO females showed an exacerbated immune response and alpha-syn pathology, which ultimately led to dopaminergic neurodegeneration of greater magnitude. These findings support a sex-dimorphic neuroprotective role for CD163 during alpha-syn-induced neurodegeneration.

引用

页数：21

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