Neuroprotective effects of violacein in a model of inherited amyotrophic lateral sclerosis

Author:

Olivera-Bravo Silvia,Bolatto Carmen,Otero Damianovich Gabriel,Stancov Matías,Cerri Sofía,Rodríguez Paola,Boragno Daniela,Hernández Mir Karina,Cuitiño María Noel,Larrambembere Fernanda,Isasi Eugenia,Alem Diego,Canclini Lucía,Marco Marta,Davyt Danilo,Díaz-Amarilla Pablo

Abstract

AbstractAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive death of motor neurons and muscle atrophy, with defective neuron-glia interplay and emergence of aberrant glial phenotypes having a role in disease pathology. Here, we have studied if the pigment violacein with several reported protective/antiproliferative properties may control highly neurotoxic astrocytes (AbAs) obtained from spinal cord cultures of symptomatic hSOD1G93A rats, and if it could be neuroprotective in this ALS experimental model. At concentrations lower than those reported as protective, violacein selectively killed aberrant astrocytes. Treatment of hSOD1G93A rats with doses equivalent to the concentrations that killed AbAs caused a marginally significant delay in survival, partially preserved the body weight and soleus muscle mass and improved the integrity of the neuromuscular junction. Reduced motor neuron death and glial reactivity was also found and likely related to decreased inflammation and matrix metalloproteinase-2 and -9. Thus, in spite that new experimental designs aimed at extending the lifespan of hSOD1G93A rats are needed, improvements observed upon violacein treatment suggest a significant therapeutic potential that deserves further studies.

Funder

IIBCE - Ministry of Education and Culture

PEDECIBA

Agencia Nacional de Investigación e Innovación

UdelaR

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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