biostudies-literatureUcar BAustrian Science Fund FWF163https://www.ebi.ac.uk/biostudies/studies/S-EPMC8961638biostudies-literatureUnknown12(2)The accumulation of α-synuclein (α-syn) in the brain plays a role in synucleinopathies and it is hypothesized to spread in a prion-like fashion between connected brain regions. In the present study, we aim to investigate this spreading in well-characterized sagittal organotypic whole brain slices taken from postnatal wild type (WT) and transgenic mice overexpressing human α-syn under the promoter of proteolipid protein (PLP). Collagen hydrogels were loaded with monomers of human α-syn, as well as human and mouse pre-formed fibrils (PFFs), to allow local application and slow release. The spreading of α-syn was evaluated in different brain regions by immunohistochemistry for total α-syn and α-syn phosphorylated at the serine129 position (α-syn-P). The application of human and mouse PFFs of αBiomoleculesSpreading of Aggregated α-Synuclein in Sagittal Organotypic Mouse Brain Slices.PMC8961638P32558-BStefanova NUcar BHumpel CfalseSpreading of Aggregated α-Synuclein in Sagittal Organotypic Mouse Brain Slices.The accumulation of α-synuclein (α-syn) in the brain plays a role in synucleinopathies and it is hypothesized to spread in a prion-like fashion between connected brain regions. In the present study, we aim to investigate this spreading in well-characterized sagittal organotypic whole brain slices taken from postnatal wild type (WT) and transgenic mice overexpressing human α-syn under the promoter of proteolipid protein (PLP). Collagen hydrogels were loaded with monomers of human α-syn, as well as human and mouse pre-formed fibrils (PFFs), to allow local application and slow release. The spreading of α-syn was evaluated in different brain regions by immunohistochemistry for total α-syn and α-syn phosphorylated at the serine129 position (α-syn-P). The application of human and mouse PFFs of α2022-01-01T00:00:00Z2022 Jan2025-04-19T13:00:32.979Z2025-04-19T13:00:32.979ZS-EPMC89616383520466410.3390/biom12020163