Sex-dimorphic neuroprotective effect of CD163 in an α-synuclein mouse model of Parkinson's disease.
Sara A FerreiraConghui LiIda H KlæstrupZagorka ViticRikke K RasmussenAsger KirkegaardGitte U ToftCristine BetzerPia SvendsenPoul Henning JensenYonglun LuoAnders EtzerodtSøren K MoestrupMarina Romero-RamosPublished in: NPJ Parkinson's disease (2023)
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.
Keyphrases
- immune response
- mouse model
- wild type
- nk cells
- end stage renal disease
- chronic kidney disease
- oxidative stress
- multiple sclerosis
- adipose tissue
- metabolic syndrome
- newly diagnosed
- spinal cord injury
- type diabetes
- toll like receptor
- peripheral blood
- cancer therapy
- neuropathic pain
- resting state
- insulin resistance
- functional connectivity
- high fat diet induced