title: Decrease of mRNA Editing after Spinal Cord Injury is Caused by Down-regulation of ADAR2 that is Triggered by Inflammatory Response.
abstract: We recently showed that spinal cord injury (SCI) leads to a decrease in mRNA editing of serotonin receptor 2C (5-HT2CR) contributing to post-SCI spasticity. Here we study post-SCI mRNA editing and global gene expression using massively parallel sequencing. Evidence is presented that the decrease in 5-HT2CR editing is caused by down-regulation of adenosine deaminase ADAR2 and that editing of at least one other ADAR2 target, potassium channel Kv1.1, is decreased after SCI. Bayesian network analysis of genome-wide transcriptome data indicates that down-regulation of ADAR2 (1) is triggered by persistent inflammatory response to SCI that is associated with activation of microglia and (2) results in changes in neuronal gene expression that are likely to contribute both to post-SCI restoration of neuronal excitability and muscle spasms. These findings have broad implications for other diseases of the Central Nervous System and could open new avenues for developing efficacious antispastic treatments.
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Antonio Fabio
authors.initials: AF
authors.lastname: Di Narzo
authors.affiliation: 1] The Friedman Brain Institute and Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA [2] James J. Peters VA Medical Center, Bronx, NY.
authors.forename: Alexey
authors.initials: A
authors.lastname: Kozlenkov
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Ge
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Centre for Neuroscience, Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Leo
authors.initials: L
authors.lastname: Sanelli
authors.affiliation: Centre for Neuroscience, Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Zacnicte
authors.initials: Z
authors.lastname: May
authors.affiliation: Centre for Neuroscience, Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Li
authors.affiliation: Centre for Neuroscience, Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Karim
authors.initials: K
authors.lastname: Fouad
authors.affiliation: James J. Peters VA Medical Center, Bronx, NY.
authors.forename: Christopher
authors.initials: C
authors.lastname: Cardozo
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Eugene V
authors.initials: EV
authors.lastname: Koonin
authors.affiliation: Centre for Neuroscience, Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: David J
authors.initials: DJ
authors.lastname: Bennett
authors.affiliation: 1] The Friedman Brain Institute and Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA [2] James J. Peters VA Medical Center, Bronx, NY.
authors.forename: Stella
authors.initials: S
authors.lastname: Dracheva
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001499:Bayes Theorem; D015536:Down-Regulation; D005260:Female; D051662:Kv1.1 Potassium Channel / Q000235:genetics / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D017393:RNA Editing / Q000502:physiology*; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology
chemical_list: C489293:Kcna1 protein, rat; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D051662:Kv1.1 Potassium Channel; C000602621:Adarb1 protein, rat; D000243:Adenosine Deaminase