dc.contributor.author
Ulshöfer, Rebecca
dc.contributor.author
Bros, Helena
dc.contributor.author
Hauser, Anja Erika
dc.contributor.author
Niesner, Raluca Aura
dc.contributor.author
Paul, Friedemann
dc.contributor.author
Malla, Bimala
dc.contributor.author
Infante-Duarte, Carmen
dc.date.accessioned
2023-03-24T12:57:33Z
dc.date.available
2023-03-24T12:57:33Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/38556
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-38272
dc.description.abstract
In neuroinflammatory and neurodegenerative disorders such as multiple sclerosis, mitochondrial damage caused by oxidative stress is believed to contribute to neuroaxonal damage. Previously, we demonstrated that exposure to hydrogen peroxide (H2O2) alters mitochondrial morphology and motility in myelinated axons and that these changes initiate at the nodes of Ranvier, where numerous sodium channels are located. Therefore, we suggested that mitochondrial damage may lead to ATP deficit, thereby affecting the efficiency of the sodium-potassium ATPase and eventually leading to sodium overload in axons. The increased intra-axonal sodium may revert the axonal sodium-calcium exchangers and thus may lead to a pathological calcium overload in the axoplasm and mitochondria. Here, we used the explanted murine ventral spinal roots to investigate whether modulation of sodium or calcium influx may prevent mitochondrial alterations in myelinated axons during exogenous application of H2O2 inducing oxidative stress. For that, tetrodotoxin, an inhibitor of voltage-gated sodium ion channels, and ruthenium 360, an inhibitor of the mitochondrial calcium uniporter, were applied simultaneously with hydrogen peroxide to axons. Mitochondrial shape and motility were analyzed. We showed that inhibition of axonal sodium influx prevented oxidative stress-induced morphological changes (i.e., increase in circularity and area and decrease in length) and preserved mitochondrial membrane potential, which is crucial for ATP production. Blocking mitochondrial calcium uptake prevented decrease in mitochondrial motility and also preserved membrane potential. Our findings indicate that alterations of both mitochondrial morphology and motility in the contexts of oxidative stress can be counterbalanced by modulating intramitochondrial ion concentrations pharmacologically. Moreover, motile mitochondria show preserved membrane potentials, pointing to a close association between mitochondrial motility and functionality.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
Oxidative Stress
en
dc.subject
Multiple sclerosis (MS)
en
dc.subject
central nervous system (CNS)
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Preventing Axonal Sodium Overload or Mitochondrial Calcium Uptake Protects Axonal Mitochondria from Oxidative Stress-Induced Alterations
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
6125711
dcterms.bibliographicCitation.doi
10.1155/2022/6125711
dcterms.bibliographicCitation.journaltitle
Oxidative Medicine and Cellular Longevity
dcterms.bibliographicCitation.originalpublishername
Hindawi
dcterms.bibliographicCitation.volume
2022
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
35663200
dcterms.isPartOf.issn
1942-0900
dcterms.isPartOf.eissn
1942-0994