Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/106570
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Type: Journal article
Title: Mitochondrion to endoplasmic reticulum apposition length in zebrafish embryo spinal progenitors is unchanged in response to perturbations associated with Alzheimer’s disease
Author: Newman, M.
Halter, L.
Lim, A.
Lardelli, M.
Citation: PLoS ONE, 2017; 12(6):e0179859-1-e0179859-17
Publisher: Public Library of Science (PLoS)
Issue Date: 2017
ISSN: 1932-6203
1932-6203
Statement of
Responsibility: 
Morgan Newman, Lena Halter, Anne Lim, Michael Lardelli
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.
Keywords: Spine; Endoplasmic Reticulum; Mitochondria; Stem Cells; Embryo, Nonmammalian; Animals; Zebrafish; Humans; Mice; Alzheimer Disease; Sodium Azide; Diamines; Thiazoles; Zebrafish Proteins; Oligonucleotides, Antisense; Microscopy, Electron, Transmission; Body Size; Amyloid Precursor Protein Secretases; Presenilin-1; Presenilin-2
Description: Published: June 21, 2017
Rights: Copyright: © 2017 Newman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
RMID: 0030071649
DOI: 10.1371/journal.pone.0179859
Grant ID: http://purl.org/au-research/grants/nhmrc/1061006
Appears in Collections:Genetics publications

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