MicroRNAs alteration and unique distribution in the soma and synapses of substantia nigra in Parkinsons disease

Abstract

Parkinsons disease (PD) is the second most common neurodegenerative condition after Alzheimers. Abnormal accumulation of alpha-synuclein (-syn) aggregates disrupts the balance of dopaminergic (DA-ergic) synapse components, interfering with dopamine transmission and leading to synaptic dysfunction and neuronal loss in PD. However exact molecular mechanism underlying DA-ergic neuronal cell loss in the SNpc in not known. MicroRNAs (miRNAs) are observed in various compartments of neural elements including cell bodies, nerve terminals, mitochondria, synaptic vesicles and synaptosomes. However, miRNAs expression and cellular distribution are unknown in the soma and synapse compartment in PD and healthy state. To address this void of information, we isolated synaptosomes and cytosolic fractions (soma) from post-mortem brains of PD-affected individuals and unaffected controls (UC) and processed for miRNA sequencing analysis. A group of miRNAs were significantly altered (p 2-fold) in their expressions in different comparisons: 1. UC synaptosome vs UC cytosol, 2. PD synaptosome vs PD cytosol, 3. PD synaptosome vs UC synaptosome, 4. PD cytosol vs UC cytosol. Our study unveiled some potential miRNAs in PD and their alteration and unique distribution in the soma and synapses of SNpc in PD and controls. Further, gene ontology enrichment analysis showed the involvement of deregulated miRNAs in several molecular function and cellular components: synapse assembly formation, cell junction organization, cell projections, mitochondria, Calcium ion binding and protein binding activities.