Acute spinal cord injury persistently reduces R/G RNA editing of AMPA receptors.
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.
Barbon
Alessandro
A
Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnologies, University of Brescia, Brescia, Italy.
Fumagalli
Fabio
F
Caracciolo
Luca
L
Madaschi
Laura
L
Lesma
Elena
E
Mora
Cristina
C
Carelli
Stephana
S
Slotkin
Theodore A
TA
Racagni
Giorgio
G
Di Giulio
Anna Maria
AM
Gorio
Alfredo
A
Barlati
Sergio
S
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
D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018091:Receptors, AMPA; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase