PUBLICATION
Real-time visualization of oxidative stress-mediated neurodegeneration of individual spinal motor neurons in vivo
- Authors
- Formella, I., Svahn, A.J., Radford, R.A.W., Don, E.K., Cole, N.J., Hogan, A., Lee, A., Chung, R.S., Morsch, M.
- ID
- ZDB-PUB-180908-11
- Date
- 2018
- Source
- Redox Biology 19: 226-234 (Journal)
- Registered Authors
- Chung, Roger, Cole, Nicholas, Don, Emily, Formella, Isabel, Morsch, Marco, Svahn, Adam
- Keywords
- Microscopy, Motor neurons, Optogenetics, Oxidative stress, Zebrafish
- MeSH Terms
-
- Animals
- Apoptosis
- Cell Death
- Motor Neurons/cytology
- Motor Neurons/pathology*
- Neurodegenerative Diseases/metabolism
- Neurodegenerative Diseases/pathology
- Optogenetics/methods
- Oxidative Stress*
- Reactive Oxygen Species/metabolism
- Single-Cell Analysis/methods*
- Spinal Cord/cytology
- Spinal Cord/metabolism
- Spinal Cord/pathology*
- Zebrafish
- PubMed
- 30193184 Full text @ Redox Biol.
Citation
Formella, I., Svahn, A.J., Radford, R.A.W., Don, E.K., Cole, N.J., Hogan, A., Lee, A., Chung, R.S., Morsch, M. (2018) Real-time visualization of oxidative stress-mediated neurodegeneration of individual spinal motor neurons in vivo. Redox Biology. 19:226-234.
Abstract
Generation of reactive oxygen species (ROS) has been shown to be important for many physiological processes, ranging from cell differentiation to apoptosis. With the development of the genetically encoded photosensitiser KillerRed (KR) it is now possible to efficiently produce ROS dose-dependently in a specific cell type upon green light illumination. Zebrafish are the ideal vertebrate animal model for these optogenetic methods because of their transparency and efficient transgenesis. Here we describe a zebrafish model that expresses membrane-targeted KR selectively in motor neurons. We show that KR-activated neurons in the spinal cord undergo stress and cell death after induction of ROS. Using single-cell resolution and time-lapse confocal imaging, we selectively induced neurodegeneration in KR-expressing neurons leading to characteristic signs of apoptosis and cell death. We furthermore illustrate a targeted microglia response to the induction site as part of a physiological response within the zebrafish spinal cord. Our data demonstrate the successful implementation of KR mediated ROS toxicity in motor neurons in vivo and has important implications for studying the effects of ROS in a variety of conditions within the central nervous system, including aging and age-related neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping