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Rui Simoes. Picture.

Rui Simoes

Rui Simöes, Guest researcher

Rui Simoes. Picture.

Early mitochondrial metabolism and dynamics changes as predictors of neurodegeneration and neuronal cell death

Author

  • Rui Simoes
  • Teresa Cunha-Oliveira
  • Paulo Oliveira
  • Francisco Pereira

Summary, in English

Background: 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.

Publishing year

2019

Language

English

Pages

180-181

Publication/Series

European Journal of Clinical Investigation

Volume

49

Issue

51

Document type

Conference paper: abstract

Publisher

Wiley-Blackwell

Conference name

53rd Annual Scientific Meeting of European Society for Clinical Investigation

Conference date

2019-05-22 - 2019-05-24

Conference place

Coimbra, Portugal

Status

Published

ISBN/ISSN/Other

  • ISSN: 0014-2972