miR-196a Ameliorates Cytotoxicity and Cellular Phenotype in Transgenic Huntington's Disease Monkey Neural Cells

• Type of Material: Article
• Authors: Tanut Kunkanjanawan, Emory University; Richard L. Carter, Emory University; Melinda S. Prucha, Emory University; Jinjing Yang, Emory University; Rangsun Parnpai, Suranaree University of Technology; Anthony Chan, Emory University
• Language: English
• Date: 2016-09-15
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2016 Kunkanjanawan et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0162788
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 11
• Issue: 9
• Start Page: e0162788
• End Page: e0162788
• Grant/Funding Information: YNPRC is supported by the Office of Research and Infrastructure Program (ORIP)/OD P51OD11132.; This study is supported in part by grant awarded by the NINDS (NS084163) and the ORIP/NIH (OD010930; Transgenic Huntington’s Disease Monkey Resource) to AWSC.; Transgenic HD monkey brain tissues and NPCs were provided by the Transgenic Huntington’s disease monkey resource (THDMR) sponsored by the ORIP/NIH (OD010930).
• Keywords: ACTIVATED RECEPTOR-GAMMA; MicroRNAs; Cytotoxicity; NONCODING RNAS; Hyperexpression techniques; CAG REPEATS; MUTANT HUNTINGTIN; Neurons; Gene expression; DYSREGULATION; DYSFUNCTION; Apoptosis; Huntington disease; Mitochondria; Science & Technology; Multidisciplinary Sciences; MODEL; PLURIPOTENT STEM-CELLS
• Research Categories: Health Sciences, General; Biology, Genetics; Biology, Neuroscience

Abstract

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by the expansion of polyglutamine (polyQ) tract that leads to motor, cognitive and psychiatric impairment. Currently there is no cure for HD. A transgenic HD nonhuman primate (HD-NHP) model was developed with progressive development of clinical and pathological features similar to human HD, which suggested the potential preclinical application of the HD-NHP model. Elevated expression of miR-196a was observed in both HD-NHP and human HD brains. Cytotoxicity and apoptosis were ameliorated by the overexpression of miR-196a in HD-NHP neural progenitor cells (HD-NPCs) and differentiated neural cells (HD-NCs). The expression of apoptosis related gene was also down regulated. Mitochondrial morphology and activity were improved as indicated by mitotracker staining and the upregulation of CBP and PGC-1α in HD-NPCs overexpressing miR-196a. Here we demonstrated the amelioration of HD cellular phenotypes in HD-NPCs and HD-NCs overexpressing miR-196a. Our results also suggested the regulatory role of miR-196a in HD pathogenesis that may hold the key for understanding molecular regulation in HD and developing novel therapeutics.