Embryonic alteration of motoneuronal morphology induces hyperexcitability in the mouse model of amyotrophic lateral sclerosis
Neurobiology of Disease. 2013-06-01; 54: 116-126
DOI: 10.1016/j.nbd.2013.02.011
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1. Neurobiol Dis. 2013 Jun;54:116-26. doi: 10.1016/j.nbd.2013.02.011. Epub 2013 Mar
4.
Embryonic alteration of motoneuronal morphology induces hyperexcitability in the
mouse model of amyotrophic lateral sclerosis.
Martin E(1), Cazenave W, Cattaert D, Branchereau P.
Author information:
(1)Univ. Bordeaux, INCIA, UMR 5287, F-33400 Talence, France.
Erratum in
Neurobiol Dis. 2013 Jul;55:63.
Although amyotrophic lateral sclerosis (ALS) is an age-dependent fatal
neurodegenerative disease in which upper and lower motoneurons (MNs) are targeted
for death in adults, increasing lines of evidence indicate that MNs display
physiological and morphological abnormalities during postnatal development, long
before disease onset. Here, using transgenic mice overexpressing the G93A
mutation of the human Cu/Zn superoxide dismutase gene (SOD1), we show that
SOD1(G93A) embryonic lumbar E17.5 MNs already expressed abnormal morphometric
parameters, including a deep reduction of their terminal segments length.
Whole-cell patch-clamp recordings from acute spinal cord preparations were made
to characterize functional changes in neuronal activity. SOD1(G93A) E17.5 MNs
displayed hyperexcitability compared to wild-type MNs. Finally, we performed
realistic simulations in order to correlate morphometric and electrophysiological
changes observed in embryonic SOD1(G93A) MNs. We found that the reduced dendritic
elongation mainly accounted for the hyperexcitability observed in SOD1(G93A) MNs.
Altogether, our results emphasize the remarkable early onset of abnormal neural
activity in the commonly used animal model for ALS, and suggest that embryonic
morphological changes are the primary compensatory mechanisms, the physiological
adjustments being only secondary to morphological alterations.
Copyright © 2013. Published by Elsevier Inc.
DOI: 10.1016/j.nbd.2013.02.011
PMID: 23466698 [Indexed for MEDLINE]