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Global microRNA Expression Profiling of Caenorhabditis elegans Parkinson's Disease Models

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Abstract

MicroRNAs (miRNAs) play an important role in human brain development and maintenance. To search for miRNAs that may be involved in the pathogenesis of Parkinsons disease (PD), we utilized miRNA microarrays to identify potential gene expression changes in 115 annotated miRNAs in PD-associated Caenorhabditis elegans models that either overexpress human A53T α-synuclein or have mutations within the vesicular catecholamine transporter (cat-1) or parkin (pdr-1) ortholog. Here, we show that 12 specific miRNAs are differentially regulated in the animals overexpressing α-synuclein, five in cat-1, and three in the pdr-1 mutants. The family of miR-64 and miR-65 are co-underexpressed in the α-synuclein transgenic and cat-1 strains, and members of let-7 family co-underexpressed in the α-synuclein and pdr-1 strains; mdl-1 and ptc-1 genes are target candidates for miR-64 and miR-65 and are overexpressed in α-synuclein transgenic as well as miR-64/65 (tm3711) knockout animals. These results indicate that miRNAs are differentially expressed in C. elegans PD models and suggest a role for these molecules in disease pathogenesis.

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Acknowledgements

We thank the Finnish Graduate School of Neurosciences (FGSN), the Saastamoinen Foundation, and the Sigrid Juselius Foundation for their financial support. This study was supported in part by NIH ES014459 and MHRP W81XWH-05-1-0239 to RN. We thank Petri Pehkonen and Antti Kurronen for advice in computer analysis and Markus Storvik, Vuokko Aarnio, and Julia Vistbakka for fruitful discussions. We thank Dr. Shohei Mitani (Tokyo Women’s Medical University) for providing djr-1.1 and pink-1, and miR-64/65 (tm3711) mutant strains. Some strains used in this study were obtained from the C. elegans Genetics Center, which is funded by the NIH.

Authors' contributions

SA planned and performed the experiments and wrote the manuscript. MR, LH, KL, JV, and ML performed experiments. GW planned and performed experiments and helped write the manuscript. RN provided critical reagents, guided the study, and helped write the manuscript.

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Authors and Affiliations

  1. Department of Biosciences, Kuopio University, Kuopio, Finland

    Suvi Asikainen, Martina Rudgalvyte, Liisa Heikkinen, Kristiina Louhiranta, Merja Lakso & Garry Wong

  2. Department of Neurobiology, A.I.Virtanen Institute for Molecular Sciences, Kuopio University, P.O. Box 1627, 70211, Kuopio, Finland

    Suvi Asikainen, Martina Rudgalvyte, Liisa Heikkinen, Kristiina Louhiranta, Merja Lakso & Garry Wong

  3. Department of Pharmacology and Toxicology, Center for Environmental Health, Stark Neuroscience Research Institute, Indiana University School of Medicine, 635 Barnhill Drive, MS 549, Indianapolis, IN, 46202-5120, USA

    Richard Nass

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  1. Suvi Asikainen
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Correspondence to Garry Wong or Richard Nass.

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Supplementary Table 1

All miRNAs detected in the microarray experiment (DOCX 22 kb)

Supplementary Table 2

miRNAs missing from the NCode miRNA microarray platform (DOCX 15 kb)

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Asikainen, S., Rudgalvyte, M., Heikkinen, L. et al. Global microRNA Expression Profiling of Caenorhabditis elegans Parkinson's Disease Models. J Mol Neurosci 41, 210–218 (2010). https://doi.org/10.1007/s12031-009-9325-1

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