Altered dopamine release and monoamine transporters in Vps35 p.D620N knock-in mice

NPJ Parkinson's Disease
Stefano CataldiM Farrer

Abstract

Vacuolar protein sorting 35 (VPS35) is a core component of the retromer trimer required for endosomal membrane-associated protein trafficking. The discovery of a missense mutation, Vps35 p.D620N implicates retromer dysfunction in the pathogenesis of Parkinson's disease (PD). We have characterized a knock-in mouse with a Vps35 p.D620N substitution (hereafter referred to as VKI) at 3 months of age. Standardized behavioral testing did not observe overt movement disorder. Tyrosine hydroxylase (TH)-positive nigral neuron counts and terminal expression in striata were comparable across genotypes. Fast scan cyclic voltammetry revealed increased dopamine release in VKI striatal slices. While extracellular dopamine collected via striatal microdialysis of freely moving animals was comparable across genotypes, the ratio of dopamine metabolites to dopamine suggests increased dopamine turnover in VKI homozygous mice. Western blot of striatal proteins revealed a genotype-dependent decrease in dopamine transporter (DAT) along with an increase in vesicular monoamine transporter 2 (VMAT2), albeit independent of changes in other synaptic markers. The reduction in DAT was further supported by immunohistochemical analysis. The data show that the d...Continue Reading

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Citations

Jan 27, 2019·The Journal of Comparative Neurology·Deanna L Benson, George W Huntley
Feb 28, 2019·Movement Disorders : Official Journal of the Movement Disorder Society·Matthew J Farrer, Jordan Follett
Jul 8, 2020·Journal of Neuroscience Research·Vania Macías-CalvioMaría-Paz Marzolo
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Jan 11, 2020·Frontiers in Neurology·Simona Eleuteri, Alberto Albanese
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Apr 24, 2020·Cellular and Molecular Neurobiology·Jenny SassoneBarbara Garavaglia
Sep 26, 2020·Frontiers in Molecular Neuroscience·Naila Kuhlmann, Austen J Milnerwood
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Dec 11, 2020·NPJ Parkinson's Disease·Meghan L BucherTeresa G Hastings
Mar 7, 2021·NPJ Parkinson's Disease·Mengfei BuHabibeh Khoshbouei
Mar 5, 2021·Brain Research·Jordan Follett, Matthew J Farrer
May 4, 2021·Annals of Neurology·Dongbing LaiTatiana Foroud
Jun 22, 2021·Journal of Parkinson's Disease·Meir Schechter, Ronit Sharon
Sep 17, 2021·Essays in Biochemistry·Zhe YangRohan D Teasdale

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Methods Mentioned

BETA
transgenic
genotyping
PCR
Profiler

Software Mentioned

G power
ANY
Ensemble
Invilog Voltammetry system
Cell Profiler
ClampEx
Ensembl
Prism
maze
Image J

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