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Acute spinal cord injury persistently reduces R/G RNA editing of AMPA receptors
Author(s) -
Barbon Alessandro,
Fumagalli Fabio,
Caracciolo Luca,
Madaschi Laura,
Lesma Elena,
Mora Cristina,
Carelli Stephana,
Slotkin Theodore A.,
Racagni Giorgio,
Di Giulio Anna Maria,
Gorio Alfredo,
Barlati Sergio
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.06767.x
Subject(s) - ampa receptor , rna editing , neuroscience , glutamate receptor , excitatory postsynaptic potential , long term depression , biology , synaptic plasticity , lesion , receptor , inhibitory postsynaptic potential , rna , chemistry , microbiology and biotechnology , biochemistry , medicine , pathology , gene
J. Neurochem. (2010) 114 , 397–407. 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 α‐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.