Differential expression of synaptic proteins in unilateral 6-OHDA lesioned rat model-A comparative proteomics approach

Parkinson's disease (PD) is characterized as a movement disorder due to lesions in the basal ganglia. As the major input region of the basal ganglia, striatum plays a vital role in coordinating movements. It receives afferents from the cerebral cortex and projects afferents to the internal segment of the globus pallidus and substantia nigra pars reticulate. Additionally, accumulating evidences support a role for synaptic dysfunction in PD. Therefore, the present study explores the changes in protein abundance involved in synaptic disorders in unilateral lesioned 6-OHDA rat model. Based on ¹⁸O/¹⁶O-labeling technique, striatal proteins were separated using online 2D-LC, and identified by nano-ESI-quadrupole-TOF. A total of 370 proteins were identified, including 76 significantly differentially expressed proteins. Twenty-two downregulated proteins were found in composition of vesicle, ten of which were involved in neuronal transmission and recycling across synapses. These include N-ethylmaleimide-sensitive fusion protein attachment receptor proteins (SNAP-25, syntaxin-1A, syntaxin-1B, VAMP2), synapsin-1, septin-5, clathrin heavy chain 1, AP-2 complex subunit beta, dynamin-1, and endophilin-A1. Moreover, MS result for syntaxin-1A was confirmed by Western blot analysis. Overall, these synaptic changes induced by neurotoxin may serve as a reference for understanding the functional mechanism of striatum in PD.