title: Acute spinal cord injury persistently reduces R/G RNA editing of AMPA receptors.
abstract: Spinal cord injury (SCI) triggers a complex ischemic and inflammatory reaction, involving activation of neurotransmitter systems, in particular glutamate, culminating in cell death. We hypothesized that SCI might lead to alteration in the RNA editing of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors that govern critical determinants of neuronal survival. To this end, we examined the molecular changes set in motion by SCI that affect the channel properties of AMPA receptors. SCI strongly reduced the level of AMPA receptor R/G editing, involving not only the site of the lesion but also adjacent areas of the cord spared by the lesion. The effects, with changes for some subunits and loci, were observed as long as 30 days after lesioning and may correlate with a partial decrease in enzymatic activity of adenosine deaminase acting on RNA 2 (ADAR2), as deduced from the analysis of ADAR2 self-editing. The reduced editing at the R/G site of glutamate receptor subunits (GluRs) is likely to reduce post-synaptic excitatory responses to glutamate, thus limiting the progression of cell death; however, prolonged suppression of GluR function in later stages may hinder synaptic plasticity. These observations provide the first direct evidence of the potential contribution of RNA editing to excitatory neural injury and recovery after SCI.
authors.affiliation: Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnologies, University of Brescia, Brescia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Barbon
authors.forename: Fabio
authors.initials: F
authors.lastname: Fumagalli
authors.forename: Luca
authors.initials: L
authors.lastname: Caracciolo
authors.forename: Laura
authors.initials: L
authors.lastname: Madaschi
authors.forename: Elena
authors.initials: E
authors.lastname: Lesma
authors.forename: Cristina
authors.initials: C
authors.lastname: Mora
authors.forename: Stephana
authors.initials: S
authors.lastname: Carelli
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Slotkin
authors.forename: Giorgio
authors.initials: G
authors.lastname: Racagni
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Di Giulio
authors.forename: Alfredo
authors.initials: A
authors.lastname: Gorio
authors.forename: Sergio
authors.initials: S
authors.lastname: Barlati
mesh_terms: D000243:Adenosine Deaminase / Q000096:biosynthesis / Q000235:genetics; D017398:Alternative Splicing; D000818:Animals; D009043:Motor Activity; D017393:RNA Editing; D012333:RNA, Messenger / Q000096:biosynthesis; D016601:RNA-Binding Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000096:biosynthesis / Q000235:genetics*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018091:Receptors, AMPA; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase