Fig. 8

αSyn aggregates preferentially co-localized within astrocytes but not in SN-resident DA neurons in line M20 mice injected with human WT αSyn fibrils. Representative immunofluorescence staining showing co-localization of pSer129 immunoreactive αSyn pathology (red) in the TH immunopositive DA neurons (green) or GFAP (green) immunopositive astrocytes in the SN region of human αSyn fibril injected M20 mice. In both cohorts of M20 mice injected in the IC or the CPu (a-b: Cohorts 1 and 3 respectively), astrocytes laden with pSer129-αSyn were present in abundance (arrows) while none of these LB type inclusions were identified within the TH-immunopositive DA neurons. Additionally, many cell body inclusions or neurites were present in populations that were not immunopositive for TH (arrowheads). Of note, the astrocytes with resident αSyn pathology resemble hypermorphic reactive state and co-localized with p62, an indicator of decreased autophagic flux (c). PBS injected mice represents the control mice (c). Cell nuclei were stained with DAPI (blue). The 3-color merged panel has been magnified (right panel) to visualize the localization of astrocytic pSer129 αSyn pathology in the SN. n = 3–5/cohort; Scale bar, 500 μm (all panels except right panel); 200 μm (merged panel, right)