Show simple item record

dc.contributor.authorSimoes, Rui
dc.contributor.authorCunha-Oliveira, Teresa
dc.contributor.authorKovarova, Jaromira
dc.contributor.authorNeuzil, Jiri
dc.contributor.authorOliveira, Paulo J
dc.contributor.authorPereira, Francisco B
dc.date.accessioned2021-01-29T00:35:16Z
dc.date.available2021-01-29T00:35:16Z
dc.date.issued2019
dc.identifier.issn0014-2972
dc.identifier.urihttp://hdl.handle.net/10072/401530
dc.description.abstractBackground: Neuronal calcium and ATP homeostasis is regulated through alterations in mitochondria fusion/fission events and anterograde and retrograde transport in neurons. Mitochondrial dynamics form an interactome that ultimately controls mitochondrial quality, quantity and metabolism. Our objective is to show that alterations in this interactome lead to point‐of‐no‐return situations characterized as first signs of progressive neurodegeneration. Material and methods: Differentiated human SH‐SY5Y neuroblastoma cells were treated with non‐lethal concentrations of either rotenone (31.25, 62.5, 125 and 250 nM) or 6‐hydroxydopamine (6.25, 12.5, 25 and 50 μmol/L). Cell viability was determined by measuring cell mass, metabolic activity and [ATP] using SRB, resazurin, and CellTiter‐Glo Luminescent Cell Viability assays, respectively, after 96 hours treatment. At earlier time points, before changes on cell viability occurred, cells were labelled with different fluorescent dyes, imaged under a Nikon Ti‐E‐H‐TIRF microscope. Mann‐Whitney's test was used for comparison of two‐mean values of controls and treated cells. Results: In a dose‐dependent manner, rotenone and 6‐hydroxydopamine decreased cell area and number of neuronal processes, leading to the loss of neuronal architecture. Under the same treatment conditions, neuronal mitochondria showed decreased axonal transport (velocities, time and length of movement) along with other dynamic events like fusion/fission cycles that are correlated to mitochondrial shape alterations. Conclusions: Alterations in mitochondrial metabolism and dynamics lead to neuronal cell morphology modifications and neurodegeneration that can ultimately drive cell death. Characterization and prevention of these changes, prior to the escalation to point‐of‐no‐return situations, may be the answer to diagnosis and to design therapeutic interventions to prevent cell death in neurodegenerative diseases.
dc.languageEnglish
dc.publisherWiley
dc.publisher.urihttps://onlinelibrary.wiley.com/doi/10.1111/eci.13109
dc.relation.ispartofconferencenamethe 53rd Annual Scientific Meeting of the European Society for Clinical Investigation
dc.relation.ispartofconferencetitleEuropean Journal of Clinical Investigation
dc.relation.ispartofdatefrom2019-05-22
dc.relation.ispartofdateto2019-05-24
dc.relation.ispartofpagefrom180
dc.relation.ispartofpageto181
dc.relation.ispartofvolume49
dc.subject.fieldofresearchClinical sciences
dc.subject.fieldofresearchcode3202
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsMedicine, General & Internal
dc.subject.keywordsMedicine, Research & Experimental
dc.subject.keywordsGeneral & Internal Medicine
dc.titleEarly mitochondrial metabolism and dynamics changes as predictors of neurodegeneration and neuronal cell death
dc.typeConference output
dc.type.descriptionE3 - Conferences (Extract Paper)
dcterms.bibliographicCitationSimoes, R; Cunha-Oliveira, T; Kovarova, J; Neuzil, J; Oliveira, PJ; Pereira, FB, Early mitochondrial metabolism and dynamics changes as predictors of neurodegeneration and neuronal cell death, European Journal of Clinical Investigation, 2019, 49, pp. 180-181
dc.date.updated2021-01-29T00:33:06Z
gro.hasfulltextNo Full Text
gro.griffith.authorNeuzil, Jiri


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

  • Conference outputs
    Contains papers delivered by Griffith authors at national and international conferences.

Show simple item record