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

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  • Sara A. Ferreira
  • Li, Conghui
  • 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
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.
OriginalsprogEngelsk
Artikelnummer164
Tidsskriftnpj Parkinson's Disease
Vol/bind9
Udgave nummer1
Antal sider21
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
We are grateful to Xiaoyu Zhou for her help with the transcriptomic data processing, to the FACS core facility for the technical help with the FACSAria III high-speed cell sorter, and to the Imaging core facility for technical support with the Upright Widefield Slide Scanner microscope. Funding support for the research covered in this article was provided by the Bjarne Saxhof Fund administered through the Danish Parkinson’s Foundation (M.R.-R.), the Novo Nordisk Foundation (DEO, NNF17OC0028806, M.R.-R.) and Independent Research Fund Denmark (9039-00217B, M.R.-R.). The Lundbeck Foundation grants R223-2015-4222 and R248-2016-2518 for the Danish Research Institute of Translational Neuroscience-DANDRITE (P.H.J. and C.B.). S.A.F. was a recipient of a PhD fellowship from the Graduate School at the Health Faculty, Aarhus University, when performing the experiments described here.

Funding Information:
We are grateful to Xiaoyu Zhou for her help with the transcriptomic data processing, to the FACS core facility for the technical help with the FACSAria III high-speed cell sorter, and to the Imaging core facility for technical support with the Upright Widefield Slide Scanner microscope. Funding support for the research covered in this article was provided by the Bjarne Saxhof Fund administered through the Danish Parkinson’s Foundation (M.R.-R.), the Novo Nordisk Foundation (DEO, NNF17OC0028806, M.R.-R.) and Independent Research Fund Denmark (9039-00217B, M.R.-R.). The Lundbeck Foundation grants R223-2015-4222 and R248-2016-2518 for the Danish Research Institute of Translational Neuroscience-DANDRITE (P.H.J. and C.B.). S.A.F. was a recipient of a PhD fellowship from the Graduate School at the Health Faculty, Aarhus University, when performing the experiments described here.

Publisher Copyright:
© 2023, The Author(s).

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