@article{27305e99ada043a3ae137b43970ea92d,
title = "MicroRNA profiling reveals marker of motor neuron disease in ALS models",
abstract = "Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by the loss of motor neurons (MNs) in the brain and spinal cord, leading to fatally debilitating weakness. Because this disease predominantly affects MNs, we aimed to characterize the distinct expression profile of that cell type to elucidate underlying disease mechanisms and to identify novel targets that inform on MN health during ALS disease time course. Micron RNAs (miRNAs) are short, noncoding RNAs that can shape the expression profile of a cell and thus often exhibit cell-type-enriched expression. To determine MN-enriched miRNA expression, we used Cre recombinase-dependent miRNA tagging and affinity purification in mice. By defining the in vivo miRNA expression of MNs, all neurons, astrocytes, and microglia, we then focused on MN-enriched miRNAs via a comparative analysis and found that they may functionally distinguish MNs postnatally from other spinal neurons. Characterizing the levels of the MN-enriched miRNAs in CSF harvested from ALS models of MN disease demonstrated that one miRNA (miR-218) tracked with MN loss and was responsive to an ALS therapy in rodent models. Therefore, we have used cellular expression profiling tools to define the distinct miRNA expression of MNs, which is likely to enrich future studies of MN disease. This approach enabled the development of a novel, drug-responsive marker of MN disease in ALS rodents.",
keywords = "ALS, MiRAP, MicroRNAs, Motor neuron, Motor neuron disease, TRAP",
author = "Hoye, {Mariah L.} and Koval, {Erica D.} and Wegener, {Amy J.} and Hyman, {Theodore S.} and Chengran Yang and O{\textquoteright}Brien, {David R.} and Miller, {Rebecca L.} and Tracy Cole and Schoch, {Kathleen M.} and Tao Shen and Tomonori Kunikata and Richard, {Jean Philippe} and Gutmann, {David H.} and Maragakis, {Nicholas J.} and Kordasiewicz, {Holly B.} and Dougherty, {Joseph D.} and Miller, {Timothy M.}",
note = "Funding Information: This work was supported by Project5 for ALS (T.M.M.); the National Institute of Neurological Disorders and Stroke–National Institutes of Health (Grants K08NS074194 and R01NS078398 to T.M.M., Grant F31NS077781 to E.D.K., and Grant F31NS092340 to M.L.H.); the Robert Packard Center for ALS Research (T.M.M.); the University of Missouri Spinal Cord Injury and Disease Research Program (T.M.M.); and the Hope Center for Neurological Disorders. J.D.D. is supported in part by a NARSAD Independent Investigator grant from the Brain and Behavior Research Foundation. This work was also supported by access to equipment made possible by the Hope Center for Neurological Disorders and the Departments of Neurology and Psychiatry at Washington University School of Medicine. Data from the NikonA1Rsi confocal microscope were obtained in part through the use of Washington University Center for Cellular Imaging supported by Washington University School of Medicine, the Children{\textquoteright}s Discovery Institute of Washington University and St. Louis Children{\textquoteright}s Hospital, the Foundation for Barnes-Jewish Hospital, and the National Institute for Neurological Disorders and Stroke–National Institutes of Health (Grant NS086741). We thank Gregory F. Wu and Conrad C. Weihl for helpful comments and critique on this work; Pak Chan (Stanford University) for providing the hSOD1 WT rats; Klaus-Armin Nave (Max Planck Institute) for the Cnp1 Cre mouse; the Division of Neuropathology, Department of Pathology and Immunology, for assistance with autopsy tissue acquisition; Amber Salter for help with statistical analyses; and Elena Fisher for assistance with manuscript preparation. Washington University has filed patents regarding miRNA as biomarkers and therapeutic targets for ALS. The authors declare no other competing financial interests. Publisher Copyright: {\textcopyright} 2017 the authors.",
year = "2017",
month = may,
day = "31",
doi = "10.1523/JNEUROSCI.3582-16.2017",
language = "English (US)",
volume = "37",
pages = "5574--5586",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "22",
}