Objective: To explore the pathogenicity of exosomes derived from Parkinson’s disease (PD) patients’ serum and healthy control’s serum in vivo and verify the prion-like propagation of human derived exosomes in animals.

Background: Extracellular α-synuclein has been proposed as a medium for induction of pathological process. And exosomal vehicles is partly associated with extracellular α-synuclein. We suppose exosome α-synuclein from patients serve as carriers for interneuronal disease transmission. And currently, few studies pay attention to the effect of human serum derived exosomes in vivo.

Methods: Exosomes from PD patients and healthy controls were isolated, and then injected into the tail vein of the balb/c mouse and the immune deficient mouse NOD-SCID, exosomes were also intrastriatally injected into the balb/c mouse simultaneously. The behaviors and key molecules such as pathological form of α-synuclein were analysed.

Results: Exosomes were confirmed by Western blotting, transmission electron microscopy (TEM) and Nanosight. The tail vein injected PD patients’ serum derived exosomes induced bradykinesia in mice, which is more pronounced in NOD/SCID mice, but not obvious in stereotactic models. Additionally, a slight weight loss in all of these three mice was observed after exposure to PD serum derived exosomes. In stark contrast, these phenomena were not shown on animals subjected to exosomes derived from healthy control’s serum. In principle, different forms of α-synuclein in exosomes derived from the PD patients and healthy controls were discovered. With the aid of IVIS, we confirm that DIR labeled exosomes is able to cross the blood-brain barrier. Ascended α-synuclein expression and decreased levels of TH in the substantia nigra compacta (SNpc) were verified by Western blotting and immnofluorescence. By utilizing the H&E staining method, we observed distorted neuronal morphology in the SNpc of the mice treated with PD patients’ serum derived exosomes.

Conclusions: Serum-derived exosomes from PD patients contains pathogenic species of α-synuclein which may induce behavioral changes as well as some pathological profiles mimic PD in mice.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/exosomes-injection-to-reproduce-a-mouse-model-of-parkinsons-disease-a-preliminary-report/