Substantia nigra alterations in mice modeling Parkinson’s disease
Parkinson’s disease (PD) is an age-related neurodegenerative pathology of the central nervous system. The well-known abnormalities characteristic of PD are dysfunctions in the nigrostriatal system including the substantia nigra of the midbrain and the striatum. Moreover, in PD persons, alpha-synucle...
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Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
2024-11-01
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| Series: | Вавиловский журнал генетики и селекции |
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| Online Access: | https://vavilov.elpub.ru/jour/article/view/4347 |
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| author | I. N. Rozhkova S. V. Okotrub E. Yu. Brusentsev T. A. Rakhmanova D. A. Lebedeva V. S. Kozeneva N. A. Shavshaeva N. V. Khotskin S. Ya. Amstislavsky |
| author_facet | I. N. Rozhkova S. V. Okotrub E. Yu. Brusentsev T. A. Rakhmanova D. A. Lebedeva V. S. Kozeneva N. A. Shavshaeva N. V. Khotskin S. Ya. Amstislavsky |
| author_sort | I. N. Rozhkova |
| collection | DOAJ |
| description | Parkinson’s disease (PD) is an age-related neurodegenerative pathology of the central nervous system. The well-known abnormalities characteristic of PD are dysfunctions in the nigrostriatal system including the substantia nigra of the midbrain and the striatum. Moreover, in PD persons, alpha-synucleinopathy is associated with abnormalities in the dopaminergic brain system. To study the mechanisms of this pathology, genetic models in mice have been designed. Transgenic mice of the B6.Cg-Tg(Prnp-SNCA*A53T)23Mkle/J strain (referred to as B6.Cg-Tg further in the text) possess the A53T mutation in the human alpha-synuclein SNCA gene. The density of neurons in the prefrontal cortex, hippocampus, substantia nigra and striatum in B6.Cg-Tg mice was assessed in our previous work, but the dopaminergic system was not studied there, although it plays a key role in the development of PD. The aim of the current study was to investigate motor coordination and body balance, as well as dopaminergic neuronal density and alpha-synuclein accumulation in the substantia nigra in male B6.Cg-Tg mice at the age of six months. Wild-type mice of the same sex and age, siblings of the B6.Cg-Tg mice from the same litters, lacking the SNCA gene with the A53T mutation, but expressing murine alpha-synuclein, were used as controls (referred to as the wild type further in the text). Motor coordination and body balance were assessed with the rota-rod test; the density of dopaminergic neurons and accumulation of alpha-synuclein in the substantia nigra were evaluated by the immunohistochemical method. There was no difference between B6.Cg-Tg mice and WT siblings in motor coordination and body balance. However, accumulation of alpha-synuclein and a decrease in the number of dopaminergic neurons in the substantia nigra were found in the B6.Cg-Tg mouse strain. Thus, the mice of the B6.Cg-Tg strain at the age of six months have some symptoms of the onset of PD, such as the accumulation of mutant alpha-synuclein and a decrease in the number of dopaminergic neurons in the substantia nigra. Taken together, the results obtained in our work qualify the B6.Cg-Tg strain as a pertinent model for studying the early stage of human PD already at the age of six months. |
| format | Article |
| id | doaj-art-2ec1edd50a5b4a0996a2252d85ea20e5 |
| institution | Kabale University |
| issn | 2500-3259 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders |
| record_format | Article |
| series | Вавиловский журнал генетики и селекции |
| spelling | doaj-art-2ec1edd50a5b4a0996a2252d85ea20e52025-02-01T09:58:13ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592024-11-0128774475110.18699/vjgb-24-821509Substantia nigra alterations in mice modeling Parkinson’s diseaseI. N. Rozhkova0S. V. Okotrub1E. Yu. Brusentsev2T. A. Rakhmanova3D. A. Lebedeva4V. S. Kozeneva5N. A. Shavshaeva6N. V. Khotskin7S. Ya. Amstislavsky8Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesParkinson’s disease (PD) is an age-related neurodegenerative pathology of the central nervous system. The well-known abnormalities characteristic of PD are dysfunctions in the nigrostriatal system including the substantia nigra of the midbrain and the striatum. Moreover, in PD persons, alpha-synucleinopathy is associated with abnormalities in the dopaminergic brain system. To study the mechanisms of this pathology, genetic models in mice have been designed. Transgenic mice of the B6.Cg-Tg(Prnp-SNCA*A53T)23Mkle/J strain (referred to as B6.Cg-Tg further in the text) possess the A53T mutation in the human alpha-synuclein SNCA gene. The density of neurons in the prefrontal cortex, hippocampus, substantia nigra and striatum in B6.Cg-Tg mice was assessed in our previous work, but the dopaminergic system was not studied there, although it plays a key role in the development of PD. The aim of the current study was to investigate motor coordination and body balance, as well as dopaminergic neuronal density and alpha-synuclein accumulation in the substantia nigra in male B6.Cg-Tg mice at the age of six months. Wild-type mice of the same sex and age, siblings of the B6.Cg-Tg mice from the same litters, lacking the SNCA gene with the A53T mutation, but expressing murine alpha-synuclein, were used as controls (referred to as the wild type further in the text). Motor coordination and body balance were assessed with the rota-rod test; the density of dopaminergic neurons and accumulation of alpha-synuclein in the substantia nigra were evaluated by the immunohistochemical method. There was no difference between B6.Cg-Tg mice and WT siblings in motor coordination and body balance. However, accumulation of alpha-synuclein and a decrease in the number of dopaminergic neurons in the substantia nigra were found in the B6.Cg-Tg mouse strain. Thus, the mice of the B6.Cg-Tg strain at the age of six months have some symptoms of the onset of PD, such as the accumulation of mutant alpha-synuclein and a decrease in the number of dopaminergic neurons in the substantia nigra. Taken together, the results obtained in our work qualify the B6.Cg-Tg strain as a pertinent model for studying the early stage of human PD already at the age of six months.https://vavilov.elpub.ru/jour/article/view/4347miceparkinson’s diseasemotor coordinationdopaminergic brain systemalpha-synuclein |
| spellingShingle | I. N. Rozhkova S. V. Okotrub E. Yu. Brusentsev T. A. Rakhmanova D. A. Lebedeva V. S. Kozeneva N. A. Shavshaeva N. V. Khotskin S. Ya. Amstislavsky Substantia nigra alterations in mice modeling Parkinson’s disease Вавиловский журнал генетики и селекции mice parkinson’s disease motor coordination dopaminergic brain system alpha-synuclein |
| title | Substantia nigra alterations in mice modeling Parkinson’s disease |
| title_full | Substantia nigra alterations in mice modeling Parkinson’s disease |
| title_fullStr | Substantia nigra alterations in mice modeling Parkinson’s disease |
| title_full_unstemmed | Substantia nigra alterations in mice modeling Parkinson’s disease |
| title_short | Substantia nigra alterations in mice modeling Parkinson’s disease |
| title_sort | substantia nigra alterations in mice modeling parkinson s disease |
| topic | mice parkinson’s disease motor coordination dopaminergic brain system alpha-synuclein |
| url | https://vavilov.elpub.ru/jour/article/view/4347 |
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