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Aneuploidy is linked to neurological phenotypes through oxidative stress

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dc.contributor.authorIslam, A.
dc.contributor.authorShaukat, Z.
dc.contributor.authorHussain, R.
dc.contributor.authorRicos, M.G.
dc.contributor.authorDibbens, L.M.
dc.contributor.authorGregory, S.L.
dc.date.issued2024
dc.description.abstractAneuploidy, having an aberrant genome, is gaining increasing attention in neurodegenerative diseases. It gives rise to proteotoxic stress as well as a stereotypical oxidative shift which makes these cells sensitive to internal and environmental stresses. A growing body of research from numerous laboratories suggests that many neurodegenerative disorders, especially Alzheimer’s disease and frontotemporal dementia, are characterised by neuronal aneuploidy and the ensuing apoptosis, which may contribute to neuronal loss. Using Drosophila as a model, we investigated the effect of induced aneuploidy in GABAergic neurons. We found an increased proportion of aneuploidy due to Mad2 depletion in the third-instar larval brain and increased cell death. Depletion of Mad2 in GABAergic neurons also gave a defective climbing and seizure phenotype. Feeding animals an antioxidant rescued the climbing and seizure phenotype. These findings suggest that increased aneuploidy leads to higher oxidative stress in GABAergic neurons which causes cell death, climbing defects, and seizure phenotype. Antioxidant feeding represents a potential therapy to reduce the aneuploidy-driven neurological phenotype.
dc.identifier.citationJournal of Molecular Neuroscience, 2024; 74(2, article no. 50):1-11
dc.identifier.doi10.1007/s12031-024-02227-1
dc.identifier.issn0895-8696
dc.identifier.issn1559-1166
dc.identifier.urihttps://hdl.handle.net/11541.2/38663
dc.language.isoen
dc.publisherSpringer
dc.relation.fundingAustralianGovernment Research Training Program (AGRTP)
dc.rightsCopyright 2024 The author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. (http://creativecommons.org/licenses/by/4.0/)
dc.source.urihttps://doi.org/10.1007/s12031-024-02227-1
dc.subjectneurological phenotypes
dc.subjectoxidative stress
dc.subjectGABAergic neuron
dc.subjectBrain
dc.subjectAnimals
dc.subjectDrosophila
dc.subjectDrosophila melanogaster
dc.subjectSeizures
dc.subjectAneuploidy
dc.subjectDrosophila Proteins
dc.subjectAntioxidants
dc.subjectPhenotype
dc.subjectGABAergic Neurons
dc.titleAneuploidy is linked to neurological phenotypes through oxidative stress
dc.typeJournal article
pubs.publication-statusPublished
ror.fileinfo12285689410001831 13285739510001831 Open Access Published Version
ror.mmsid9916856224701831

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