PUBLICATION
Mitochondrion to endoplasmic reticulum apposition length in zebrafish embryo spinal progenitors is unchanged in response to perturbations associated with Alzheimer's disease
- Authors
- Newman, M., Halter, L., Lim, A., Lardelli, M.
- ID
- ZDB-PUB-170622-2
- Date
- 2017
- Source
- PLoS One 12: e0179859 (Journal)
- Registered Authors
- Lardelli, Michael, Newman, Morgan
- Keywords
- Embryos, Zebrafish, Alzheimer's disease, Sodium azides, Mitochondria, Morpholino, Spinal cord, Fibroblasts
- MeSH Terms
-
- Alzheimer Disease/metabolism
- Alzheimer Disease/pathology
- Amyloid Precursor Protein Secretases/antagonists & inhibitors
- Amyloid Precursor Protein Secretases/metabolism
- Animals
- Body Size/drug effects
- Diamines/toxicity
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/drug effects
- Endoplasmic Reticulum/drug effects
- Endoplasmic Reticulum/metabolism*
- Humans
- Mice
- Microscopy, Electron, Transmission
- Mitochondria/drug effects
- Mitochondria/metabolism*
- Oligonucleotides, Antisense/metabolism
- Presenilin-1/antagonists & inhibitors
- Presenilin-1/genetics
- Presenilin-1/metabolism
- Presenilin-2/antagonists & inhibitors
- Presenilin-2/genetics
- Presenilin-2/metabolism
- Sodium Azide/toxicity
- Spine/cytology
- Stem Cells/cytology
- Stem Cells/metabolism
- Thiazoles/toxicity
- Zebrafish
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 28636676 Full text @ PLoS One
Citation
Newman, M., Halter, L., Lim, A., Lardelli, M. (2017) Mitochondrion to endoplasmic reticulum apposition length in zebrafish embryo spinal progenitors is unchanged in response to perturbations associated with Alzheimer's disease. PLoS One. 12:e0179859.
Abstract
Mutations in the human genes PRESENILIN1 (PSEN1), PRESENILIN2 (PSEN2) and AMYLOID BETA A4 PRECURSOR PROTEIN (APP) have been identified in familial Alzheimer's disease (AD). The length of mitochondrion-endoplasmic reticulum (M-ER) appositions is increased in Psen1-/-/Psen2-/- double knockout murine embryonic fibroblasts and in fibroblasts from AD-affected individuals. Development of an easily accessible, genetically manipulable, in vivo system for studying M-ER appositions would be valuable so we attempted to manipulate M-ER apposition length in zebrafish (Danio rerio) embryos. We injected fertilized zebrafish eggs with antisense morpholino oligonucleotides (MOs) that inhibit expression of zebrafish familial AD gene orthologues psen1 and psen2. Furthermore, we treated zebrafish embryos with DAPT (a highly specific γ-secretase inhibitor) or with sodium azide (to mimic partially hypoxic conditions). We then analyzed M-ER apposition in an identified, presumably proliferative neural cell type using electron microscopy. Our analysis showed no significant differences in M-ER apposition lengths at 48 hours post fertilization (hpf) between psen1 & psen2 MO co-injected embryos, embryos treated with DAPT, or sodium azide, and control embryos. Instead, the distribution of M-ER apposition lengths into different length classes was close to identical. However, this indicates that it is feasible to reproducibly measure M-ER size distributions in zebrafish embryos. While our observations differ from those of murine and human studies, this may be due to differences in cellular differentiation and metabolic state, cell age, or species-specific responses. In particular, by focusing on a presumably proliferative embryonic cell type, we may have selected a cell heavily already reliant on anaerobic glycolysis and less responsive to factors affecting M-ER apposition. Future examination of more differentiated, more secretory cell types may reveal measurable responses of M-ER apposition to environmental and genetic manipulation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping