D-087 | Cell-type specific transcriptional profiles by snRNAseq in the 6-OHDA mouse model of Parkinson’s disease and levodopa induced dyskinesia.

Disorders of the Nervous System
Author: Bárbara Martínez | Email: barbarafmartinezm@gmail.com

Bárbara Martínez^1°, Chang Li^2°, Yogita Sharma^2°,  Jenny Johansson^2°, Anna Hammarberg^2°, Claudio Schuster^3°, Marcelo Marti^3°,  Juan Ferrario^1°, Angela Cenci^2°, Melina P. Bordone^1°

^1° Instituto de Biociencias, Biotecnología y Biología Traslacional (iB3), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, CABA, Argentina.
^2° Department Experimental Medical, Science, Wallenberg Neuroscience Center,Lund University, Lund, Sweden
^3° IQUIBICEN-FCEN-UBA

The striatum is a complex brain region essential for motor function and the key structure involved in levodopa (L-DOPA)-induced dyskinesia (LID), the main side effect of Parkinson’s disease treatment. The aim was to perform a comprehensive transcriptome analysis with cell-type resolution using single nuclei RNA sequencing from striata of intact and hemiparkinsonian mice with or without LID. cDNA libraries from 8500 nuclei/sample were prepared and sequenced using a droplet-based RNA sequencing technology. Data was preprocessed following a standardized pipeline to obtain a single expression matrix for downstream analysis. Good quality nuclei were integrated, clustered and annotated based on well-known genetic markers for striatal cellular types. Using DESeq2 we performed a pseudobulk analysis to obtain differentially expressed genes (DEGs) for each cluster and comparison. DEGs were then used for a gene ontology analysis on biological processes. Notably, in the dyskinetic state the upregulated DEGs in dSPN were associated with lipid metabolism and cytoskeleton reorganization while in iSPN with K+ transport, membrane potential and actin-cytoskeleton organization. Some but minor changes were seen in astrocytes and other cell types that will be discussed in the poster. These results provide new insights into the complex molecular adaptations of the striatal circuitry in LID and allow us to identify cell functions involved in LID which can emerge as possible therapeutic targets.