The Gene Expression of Proteins Involved in Intercellular Signaling and Neurodegeneration in the Substantia Nigra in a Mouse Subchronic Model of Parkinson’s Disease

Given the limited access to clinical material for studying the pathogenesis of Parkinson’s disease (PD), these studies should be carried out on experimental models. We have recently developed a subchronic model of the progressive development of PD with a gradual transition from the preclinical (asym...

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Main Authors: Anna Kolacheva, Ekaterina Pavlova, Alyona Bannikova, Vsevolod Bogdanov, Dmitry Troshev, Michael Ugrumov
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/3/3027
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author Anna Kolacheva
Ekaterina Pavlova
Alyona Bannikova
Vsevolod Bogdanov
Dmitry Troshev
Michael Ugrumov
author_facet Anna Kolacheva
Ekaterina Pavlova
Alyona Bannikova
Vsevolod Bogdanov
Dmitry Troshev
Michael Ugrumov
author_sort Anna Kolacheva
collection DOAJ
description Given the limited access to clinical material for studying the pathogenesis of Parkinson’s disease (PD), these studies should be carried out on experimental models. We have recently developed a subchronic model of the progressive development of PD with a gradual transition from the preclinical (asymptomatic) stage to the clinical (symptomatic) one. The aim of this study was to evaluate changes in the expression of a wide range of genes in the substantia nigra (SN), the central link in the regulation of motor function, in mice in our subchronic model of PD. We have found changes in the expression of a number of genes encoding enzymes involved in the synthesis and degradation of dopamine as well as proteins involved in the vesicular cycle, axonal transport, protein degradation in the proteasome system, neuroinflammation, and cell death in the SN of our mouse model of the clinical stage of PD. Similar changes in gene expression were previously demonstrated in patients (postmortem), indicating good reproducibility of PD in our model. Further analysis of the gene expression in the SN of mice has shown that the expression of some genes also changes in the model of the preclinical stage, when dopaminergic neurons have not yet died. Thus, this study opens up broad prospects for further evaluation of the molecular mechanisms of PD pathogenesis and the development of a test system for drug screening.
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spelling doaj.art-982eef65065f40f899ea81e3ecaa730f2023-11-16T17:06:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01243302710.3390/ijms24033027The Gene Expression of Proteins Involved in Intercellular Signaling and Neurodegeneration in the Substantia Nigra in a Mouse Subchronic Model of Parkinson’s DiseaseAnna Kolacheva0Ekaterina Pavlova1Alyona Bannikova2Vsevolod Bogdanov3Dmitry Troshev4Michael Ugrumov5Koltzov Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilova Street, 119334 Moscow, RussiaKoltzov Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilova Street, 119334 Moscow, RussiaKoltzov Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilova Street, 119334 Moscow, RussiaKoltzov Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilova Street, 119334 Moscow, RussiaKoltzov Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilova Street, 119334 Moscow, RussiaKoltzov Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilova Street, 119334 Moscow, RussiaGiven the limited access to clinical material for studying the pathogenesis of Parkinson’s disease (PD), these studies should be carried out on experimental models. We have recently developed a subchronic model of the progressive development of PD with a gradual transition from the preclinical (asymptomatic) stage to the clinical (symptomatic) one. The aim of this study was to evaluate changes in the expression of a wide range of genes in the substantia nigra (SN), the central link in the regulation of motor function, in mice in our subchronic model of PD. We have found changes in the expression of a number of genes encoding enzymes involved in the synthesis and degradation of dopamine as well as proteins involved in the vesicular cycle, axonal transport, protein degradation in the proteasome system, neuroinflammation, and cell death in the SN of our mouse model of the clinical stage of PD. Similar changes in gene expression were previously demonstrated in patients (postmortem), indicating good reproducibility of PD in our model. Further analysis of the gene expression in the SN of mice has shown that the expression of some genes also changes in the model of the preclinical stage, when dopaminergic neurons have not yet died. Thus, this study opens up broad prospects for further evaluation of the molecular mechanisms of PD pathogenesis and the development of a test system for drug screening.https://www.mdpi.com/1422-0067/24/3/3027Parkinson’s diseasemodeling of Parkinson’s diseasedopaminergic neuronssubstantia nigraneurodegenerationgene expression
spellingShingle Anna Kolacheva
Ekaterina Pavlova
Alyona Bannikova
Vsevolod Bogdanov
Dmitry Troshev
Michael Ugrumov
The Gene Expression of Proteins Involved in Intercellular Signaling and Neurodegeneration in the Substantia Nigra in a Mouse Subchronic Model of Parkinson’s Disease
International Journal of Molecular Sciences
Parkinson’s disease
modeling of Parkinson’s disease
dopaminergic neurons
substantia nigra
neurodegeneration
gene expression
title The Gene Expression of Proteins Involved in Intercellular Signaling and Neurodegeneration in the Substantia Nigra in a Mouse Subchronic Model of Parkinson’s Disease
title_full The Gene Expression of Proteins Involved in Intercellular Signaling and Neurodegeneration in the Substantia Nigra in a Mouse Subchronic Model of Parkinson’s Disease
title_fullStr The Gene Expression of Proteins Involved in Intercellular Signaling and Neurodegeneration in the Substantia Nigra in a Mouse Subchronic Model of Parkinson’s Disease
title_full_unstemmed The Gene Expression of Proteins Involved in Intercellular Signaling and Neurodegeneration in the Substantia Nigra in a Mouse Subchronic Model of Parkinson’s Disease
title_short The Gene Expression of Proteins Involved in Intercellular Signaling and Neurodegeneration in the Substantia Nigra in a Mouse Subchronic Model of Parkinson’s Disease
title_sort gene expression of proteins involved in intercellular signaling and neurodegeneration in the substantia nigra in a mouse subchronic model of parkinson s disease
topic Parkinson’s disease
modeling of Parkinson’s disease
dopaminergic neurons
substantia nigra
neurodegeneration
gene expression
url https://www.mdpi.com/1422-0067/24/3/3027
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