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TitleLimited effect of chronic valproic acid treatment in a mouse model of Machado-Joseph disease
Author(s)Esteves, Sofia
Silva, Sara Carina Duarte
Naia, Luana
Carvalho, Andreia Alexandra Neves
Castro, Andreia Cristiana Teixeira
Rego, Ana Cristina
Fernandes, Anabela Silva
Maciel, P.
Issue date21-Oct-2015
PublisherPublic Library of Science (PLOS)
JournalPLoS ONE
CitationEsteves, S., Duarte-Silva, S., Naia, L., Neves-Carvalho, A., Teixeira-Castro, A., Rego, A. C., ... & Maciel, P. (2015). Limited effect of chronic valproic acid treatment in a mouse model of Machado-Joseph disease. PloS one, 10(10), e0141610
Abstract(s)Machado-Joseph disease (MJD) is an inherited neurodegenerative disease, caused by a CAG repeat expansion within the coding region of ATXN3 gene, and which currently lacks effective treatment. In this work we tested the therapeutic efficacy of chronic treatment with valproic acid (VPA) (200mg/kg), a compound with known neuroprotection activity, and previously shown to be effective in cell, fly and nematode models of MJD. We show that chronic VPA treatment in the CMVMJD135 mouse model had limited effects in the motor deficits of these mice, seen mostly at late stages in the motor swimming, beam walk, rotarod and spontaneous locomotor activity tests, and did not modify the ATXN3 inclusion load and astrogliosis in affected brain regions. However, VPA chronic treatment was able to increase GRP78 protein levels at 30 weeks of age, one of its known neuroprotective effects, confirming target engagement. In spite of limited results, the use of another dosage of VPA or of VPA in a combined therapy with molecules targeting other pathways, cannot be excluded as potential strategies for MJD therapeutics
Publisher version
AccessOpen access
Appears in Collections:ICVS - Artigos em revistas internacionais / Papers in international journals

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