A New Synuclein-Transgenic Mouse Model for Early Parkinson's Reveals Molecular Features of Preclinical Disease.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsHendrickx, Diana M
Schmit, Kristopher J
MetadataShow full item record
AbstractUnderstanding Parkinson's disease (PD), in particular in its earliest phases, is important for diagnosis and treatment. However, human brain samples are collected post-mortem, reflecting mainly end-stage disease. Because brain samples of mouse models can be collected at any stage of the disease process, they are useful in investigating PD progression. Here, we compare ventral midbrain transcriptomics profiles from α-synuclein transgenic mice with a progressive, early PD-like striatal neurodegeneration across different ages using pathway, gene set, and network analysis methods. Our study uncovers statistically significant altered genes across ages and between genotypes with known, suspected, or unknown function in PD pathogenesis and key pathways associated with disease progression. Among those are genotype-dependent alterations associated with synaptic plasticity and neurotransmission, as well as mitochondria-related genes and dysregulation of lipid metabolism. Age-dependent changes were among others observed in neuronal and synaptic activity, calcium homeostasis, and membrane receptor signaling pathways, many of which linked to G-protein coupled receptors. Most importantly, most changes occurred before neurodegeneration was detected in this model, which points to a sequence of gene expression events that may be relevant for disease initiation and progression. It is tempting to speculate that molecular changes similar to those changes observed in our model happen in midbrain dopaminergic neurons before they start to degenerate. In other words, we believe we have uncovered molecular changes that accompany the progression from preclinical to early PD.
CitationMol Neurobiol. 2020 Sep 30. doi: 10.1007/s12035-020-02085-z. Epub ahead of print.
AffiliationHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- rAAV2/7 vector-mediated overexpression of alpha-synuclein in mouse substantia nigra induces protein aggregation and progressive dose-dependent neurodegeneration.
- Authors: Oliveras-Salvá M, Van der Perren A, Casadei N, Stroobants S, Nuber S, D'Hooge R, Van den Haute C, Baekelandt V
- Issue date: 2013 Nov 25
- Depopulation of dense α-synuclein aggregates is associated with rescue of dopamine neuron dysfunction and death in a new Parkinson's disease model.
- Authors: Wegrzynowicz M, Bar-On D, Calo' L, Anichtchik O, Iovino M, Xia J, Ryazanov S, Leonov A, Giese A, Dalley JW, Griesinger C, Ashery U, Spillantini MG
- Issue date: 2019 Oct
- Alterations in the nigrostriatal system following conditional inactivation of α-synuclein in neurons of adult and aging mice.
- Authors: Ninkina N, Tarasova TV, Chaprov KD, Roman AY, Kukharsky MS, Kolik LG, Ovchinnikov R, Ustyugov AA, Durnev AD, Buchman VL
- Issue date: 2020 Jul
- Human α-synuclein overexpression in a mouse model of Parkinson's disease leads to vascular pathology, blood brain barrier leakage and pericyte activation.
- Authors: Elabi O, Gaceb A, Carlsson R, Padel T, Soylu-Kucharz R, Cortijo I, Li W, Li JY, Paul G
- Issue date: 2021 Jan 13
- Intracerebral Administration of a Ligand-ASO Conjugate Selectively Reduces α-Synuclein Accumulation in Monoamine Neurons of Double Mutant Human A30P*A53T*α-Synuclein Transgenic Mice.
- Authors: Pavia-Collado R, Cóppola-Segovia V, Miquel-Rio L, Alarcón-Aris D, Rodríguez-Aller R, Torres-López M, Paz V, Ruiz-Bronchal E, Campa L, Artigas F, Montefeltro A, Revilla R, Bortolozzi A
- Issue date: 2021 Mar 13