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Modeling of the Progressive Degradation of the Nigrostriatal Dopaminergic System in Mice to Study the Mechanisms of Neurodegeneration and Neuroplasticity in Parkinson’s Disease

The fight against neurodegenerative diseases, including Parkinson’s disease (PD), is among the global challenges of the 21st century. The low efficiency of therapy is due to the late diagnosis and treatment of PD, which take place when there is already significant degradation of the nigrostriatal do...

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Autores principales: Kolacheva, Anna, Bannikova, Alyona, Pavlova, Ekaterina, Bogdanov, Vsevolod, Ugrumov, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820573/
https://www.ncbi.nlm.nih.gov/pubmed/36614126
http://dx.doi.org/10.3390/ijms24010683
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author Kolacheva, Anna
Bannikova, Alyona
Pavlova, Ekaterina
Bogdanov, Vsevolod
Ugrumov, Michael
author_facet Kolacheva, Anna
Bannikova, Alyona
Pavlova, Ekaterina
Bogdanov, Vsevolod
Ugrumov, Michael
author_sort Kolacheva, Anna
collection PubMed
description The fight against neurodegenerative diseases, including Parkinson’s disease (PD), is among the global challenges of the 21st century. The low efficiency of therapy is due to the late diagnosis and treatment of PD, which take place when there is already significant degradation of the nigrostriatal dopaminergic system, a key link in the regulation of motor function. We have developed a subchronic mouse model of PD by repeatedly administering 1–methyl–4–phenyl–1,2,3,6–tetrahydropyridine (MPTP) at gradually increasing doses with a 24 h interval between injections, a period comparable to the time of MPTP metabolism and elimination from the body. This model reproduces the main hallmarks of PD: progressive degeneration of dopaminergic neurons; the appearance of motor disorders with a 70–80% decrease in the level of dopamine in the striatum; an increase in dopamine turnover in the striatum to compensate for dopamine deficiency. When comparing the degradation of the nigrostriatal dopaminergic system and motor disorders in mice in the acute and subchronic models of PD, it has turned out that the resistance of dopaminergic neurons to MPTP increases with its repeated administration. Our subchronic model of PD opens up broad prospects for studying the molecular mechanisms of PD pathogenesis and developing technologies for early diagnosis and preventive treatment.
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spelling pubmed-98205732023-01-07 Modeling of the Progressive Degradation of the Nigrostriatal Dopaminergic System in Mice to Study the Mechanisms of Neurodegeneration and Neuroplasticity in Parkinson’s Disease Kolacheva, Anna Bannikova, Alyona Pavlova, Ekaterina Bogdanov, Vsevolod Ugrumov, Michael Int J Mol Sci Article The fight against neurodegenerative diseases, including Parkinson’s disease (PD), is among the global challenges of the 21st century. The low efficiency of therapy is due to the late diagnosis and treatment of PD, which take place when there is already significant degradation of the nigrostriatal dopaminergic system, a key link in the regulation of motor function. We have developed a subchronic mouse model of PD by repeatedly administering 1–methyl–4–phenyl–1,2,3,6–tetrahydropyridine (MPTP) at gradually increasing doses with a 24 h interval between injections, a period comparable to the time of MPTP metabolism and elimination from the body. This model reproduces the main hallmarks of PD: progressive degeneration of dopaminergic neurons; the appearance of motor disorders with a 70–80% decrease in the level of dopamine in the striatum; an increase in dopamine turnover in the striatum to compensate for dopamine deficiency. When comparing the degradation of the nigrostriatal dopaminergic system and motor disorders in mice in the acute and subchronic models of PD, it has turned out that the resistance of dopaminergic neurons to MPTP increases with its repeated administration. Our subchronic model of PD opens up broad prospects for studying the molecular mechanisms of PD pathogenesis and developing technologies for early diagnosis and preventive treatment. MDPI 2022-12-30 /pmc/articles/PMC9820573/ /pubmed/36614126 http://dx.doi.org/10.3390/ijms24010683 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kolacheva, Anna
Bannikova, Alyona
Pavlova, Ekaterina
Bogdanov, Vsevolod
Ugrumov, Michael
Modeling of the Progressive Degradation of the Nigrostriatal Dopaminergic System in Mice to Study the Mechanisms of Neurodegeneration and Neuroplasticity in Parkinson’s Disease
title Modeling of the Progressive Degradation of the Nigrostriatal Dopaminergic System in Mice to Study the Mechanisms of Neurodegeneration and Neuroplasticity in Parkinson’s Disease
title_full Modeling of the Progressive Degradation of the Nigrostriatal Dopaminergic System in Mice to Study the Mechanisms of Neurodegeneration and Neuroplasticity in Parkinson’s Disease
title_fullStr Modeling of the Progressive Degradation of the Nigrostriatal Dopaminergic System in Mice to Study the Mechanisms of Neurodegeneration and Neuroplasticity in Parkinson’s Disease
title_full_unstemmed Modeling of the Progressive Degradation of the Nigrostriatal Dopaminergic System in Mice to Study the Mechanisms of Neurodegeneration and Neuroplasticity in Parkinson’s Disease
title_short Modeling of the Progressive Degradation of the Nigrostriatal Dopaminergic System in Mice to Study the Mechanisms of Neurodegeneration and Neuroplasticity in Parkinson’s Disease
title_sort modeling of the progressive degradation of the nigrostriatal dopaminergic system in mice to study the mechanisms of neurodegeneration and neuroplasticity in parkinson’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820573/
https://www.ncbi.nlm.nih.gov/pubmed/36614126
http://dx.doi.org/10.3390/ijms24010683
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