Microglial Neuroinflammation-Independent Reversal of Demyelination of Corpus Callosum by Arsenic in a Cuprizone-Induced Demyelinating Mouse Model.
Mol Neurobiol
; 61(9): 6822-6841, 2024 Sep.
Article
de En
| MEDLINE
| ID: mdl-38353925
ABSTRACT
Demyelination is the loss of myelin in CNS, resulting in damaged myelin sheath. Oxidative stress and neuroinflammation play a key role in inducing demyelinating diseases like MS; hence, controlling oxidative stress and neuroinflammation is important. Cuprizone (CPZ), a copper chelator, generates oxidative stress and neuroinflammation, thereby inducing demyelination. Therefore, the CPZ-induced demyelinating mouse model (CPZ model) is widely used in research. The present study was intended to unravel a mechanism of inhibition of demyelination by arsenic in a CPZ model, which is otherwise known for its toxicity. We investigated an alternative mechanism of inhibition of demyelination by arsenic through the reversal of SOD1 activity employing in silico analysis, analytical chemistry techniques, and in vitro and in vivo experiments. In vivo experiments showed protection of body weight, survivability, and myelination of the corpus callosum in CPZ and arsenic-co-exposed animals, where neuroinflammation was apparently not involved. In vitro experiments revealed that arsenic-mediated reversal of impaired SOD1 activity leads to reduced cellular ROS levels and better viability of primary oligodendrocytes. Reversal of SOD1 activity was also observed in the corpus callosum tissue isolated from experimental animals. In silico and analytical chemistry studies revealed that similar to copper, arsenic can potentially bind to CPZ and thereby make the copper freely available for SOD1 activity. Suitable neurobehavior tests further validated the protective effect of arsenic. Taken together, the present study revealed that arsenic protects oligodendrocytes and demyelination of corpus callosum by reversing CPZ-induced impaired SOD1 activity.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Arsenic
/
Maladies démyélinisantes
/
Microglie
/
Corps calleux
/
Cuprizone
/
Modèles animaux de maladie humaine
Limites:
Animals
Langue:
En
Journal:
Mol Neurobiol
/
Mol. Neurobiol
/
Molecular Neurobiology
Sujet du journal:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Année:
2024
Type de document:
Article
Pays d'affiliation:
Inde
Pays de publication:
États-Unis d'Amérique