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

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.