Transcriptomic analysis of early stage of alpha-synuclein accummulation in Parkinson's disease mouse model

The gene expression changes in dopaminergic neurons in PD mouse model has not been able to study due to lack of an approach in the collection of viable neurons from mouse brains. We utilized the established Ddc-hKO1 knock in mice and improved neural dissociation protocol accompanied with FACS to faciliate the collection of viable dopaminergic neurons. We performed intranigral injection with pre-formed alpha-synuclein fibril with G51D mutation on Snca to induce Lewy body-like structure accumulation. Dopaminergic neurons rom midbrain were collected at 7 weeks and 12 weeks post injection to reflect the early stage of PD progression. 2 brains were pooled as a single biological replicate. We performed gene ontology analysis using DAVID and GSEA analysis with pre-ranked in fold change. Both analysis shows that lipid metabolism associated gene sets were enriched in up-regulated genes in 7 weeks post-injection but remained unchange in expression in 12 weeks post-injection. Meanwhile, protein post-translational modifications related gene sets were enriched in up-regulated genes at 12 weeks post-injection but remained unchanged at 7 weeks post-injection. We showed that Fabp1 expression of was up-regulated in hKO1(+) cells and up-regulation of FABP1 in VTA & SNc region was confirmed by immunofluorescence staining.