Reduction in the motoneuron inhibitory/excitatory synaptic ratio in an early-symptomatic mouse model of amyotrophic lateral sclerosis.

Brain Pathology
Carmen R SunicoBernardo Moreno-López

Abstract

Excitotoxicity is a widely studied mechanism underlying motoneuron degeneration in amyotrophic lateral sclerosis (ALS). Synaptic alterations that produce an imbalance in the ratio of inhibitory/excitatory synapses are expected to promote or protect against motoneuron excitotoxicity. In ALS patients, motoneurons suffer a reduction in their synaptic coverage, as in the transition from the presymptomatic (2-month-old) to early-symptomatic (3-month-old) stage of the hSOD1(G93A) mouse model of familial ALS. Net synapse loss resulted from inhibitory bouton loss and excitatory synapse gain. Furthermore, in 3-month-old transgenic mice, remaining inhibitory but not excitatory boutons attached to motoneurons showed reduction in the active zone length and in the spatial density of synaptic vesicles in the releasable pool near the active zone. Bouton degeneration/loss seems to be mediated by bouton vacuolization and by mechanical displacement due to swelling vacuolated dendrites. In addition, chronic treatment with a nitric oxide (NO) synthase inhibitor avoided inhibitory loss but not excitatory gain. These results indicate that NO mediates inhibitory loss occurring from the pre- to early-symptomatic stage of hSOD1(G93A) mice. This work co...Continue Reading

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Citations

Dec 31, 2010·Molecular Neurobiology·Bernardo Moreno-LópezDavid González-Forero
Sep 1, 2012·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Renzo MancusoXavier Navarro
Nov 5, 2011·Nature Reviews. Neurology·Laura FerraiuoloPamela J Shaw
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Aug 24, 2019·Nature Communications·Victoria García-MoralesBernardo Moreno-López
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Jan 29, 2021·Neuropathology and Applied Neurobiology·Ángela Gento-CaroBernardo Moreno-López

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