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Title: Cuprizone-Induced Neurotoxicity in Human Neural Cell Lines Is Mediated by a Reversible Mitochondrial Dysfunction: Relevance for Demyelination Models
Author: Martínez-Pinilla, Eva
Rubio, Nuria
Villar-Conde, Sandra
Navarro Brugal, Gemma
Valle, Eva del
Tolivia, Jorge
Franco Fernández, Rafael
Navarro, Ana
Keywords: Malalties neurodegeneratives
Fisiologia patològica
Metabolisme cel·lular
Neurodegenerative Diseases
Pathological physiology
Cell metabolism
Issue Date: 22-Feb-2021
Publisher: MDPI
Abstract: Suitable in vivo and in vitro models are instrumental for the development of new drugs aimed at improving symptoms or progression of multiple sclerosis (MS). The cuprizone (CPZ)-induced murine model has gained momentum in recent decades, aiming to address the demyelination component of the disease. This work aims at assessing the differential cytotoxicity of CPZ in cells of different types and from different species: human oligodendroglial (HOG), human neuroblastoma (SH-SY5Y), human glioblastoma (T-98), and mouse microglial (N-9) cell lines. Moreover, the effect of CPZ was investigated in primary rat brain cells. Cell viability was assayed by oxygen rate consumption and by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-based (MTT) method. Our results demonstrated that CPZ did not cause death in any of the assayed cell models but affected mitochondrial function and aerobic cell respiration, thus compromising cell metabolism in neural cells and neuron-glia co-cultures. In this sense, we found differential vulnerability between glial cells and neurons as is the case of the CPZ-induced mouse model of MS. In addition, our findings demonstrated that reduced viability was spontaneous reverted in a time-dependent manner by treatment discontinuation. This reversible cell-based model may help to further investigate the role of mitochondria in the disease, and study the molecular intricacies underlying the pathophysiology of the MS and other demyelinating diseases. Keywords: neurodegenerative diseases, copper chelator, pathophysiology, cell metabolism, glia
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It is part of: Brain Sciences, 2021
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ISSN: 2076-3425
Appears in Collections:Articles publicats en revistes (Bioquímica i Fisiologia)
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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