A microRNA microarray analysis of C.elegans Parkinsons disease models

MicroRNAs (miRNAs) play an important role in human brain development and maintenance. To search for miRNAs potentially involved with molecular mechanisms in the pathogenesis of Parkinsons disease (PD), we utilized miRNA microarrays to identify expression changes of 115 annotated Caenorhabditis elegans (C.elegans) miRNAs in human α-synuclein A53T transgenic, dopamine deficient catecholamine transporter gene cat-1 mutant and parkin gene pdr-1 mutant C.elegans strains. Twelve miRNAs were found regulated differentially in α-synuclein transgenic C. elegans, five in cat-1 mutants and three in pdr-1 mutants. The family of miR64/65 appeared co-under-expressed in α-synuclein and cat-1 strains and members of let-7 family co-under-expressed (except miR-241 over-expressed) in a-synuclein and pdr-1 strains. Class H serpentine receptor (srh) family of G-protein-coupled receptor genes were computationally identified to be highly over-represented target candidates for regulated miRNAs.These results indicate that miRNAs are misregulated in C. elegans PD models and suggest a role for these molecules in the disease pathogenesis. Two color NCode microRNA microrarrays were used (Invitrogen) to measure miRNA expression changes in human alpha-synuclein trangenic, cat-1 mutant, and pdr-1 mutant C.elegans strains. The experiment contains four independent biological replicates (worm populations)/strain. Strain N2 was used as reference channel, also prepared from four independently isolated small RNA samples.