Modeling Parkinson's disease‐related symptoms in alpha‐synuclein overexpressing mice
Abstract Background Intracellular deposition of alpha‐synuclein (α‐syn) as Lewy bodies and Lewy neurites is a central event in the pathogenesis of Parkinson's disease (PD) and other α‐synucleinopathies. Transgenic mouse models overexpressing human α‐syn, are useful research tools in preclinical...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-07-01
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| Series: | Brain and Behavior |
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| Online Access: | https://doi.org/10.1002/brb3.2628 |
| _version_ | 1817971270375964672 |
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| author | Agata Aniszewska Joakim Bergström Martin Ingelsson Sara Ekmark‐Lewén |
| author_facet | Agata Aniszewska Joakim Bergström Martin Ingelsson Sara Ekmark‐Lewén |
| author_sort | Agata Aniszewska |
| collection | DOAJ |
| description | Abstract Background Intracellular deposition of alpha‐synuclein (α‐syn) as Lewy bodies and Lewy neurites is a central event in the pathogenesis of Parkinson's disease (PD) and other α‐synucleinopathies. Transgenic mouse models overexpressing human α‐syn, are useful research tools in preclinical studies of pathogenetic mechanisms. Such mice develop α‐syn inclusions as well as neurodegeneration with a topographical distribution that varies depending on the choice of promoter and which form of α‐syn that is overexpressed. Moreover, they display motor symptoms and cognitive disturbances that to some extent resemble the human conditions. Purpose One of the main motives for assessing behavior in these mouse models is to evaluate the potential of new treatment strategies, including their impact on motor and cognitive symptoms. However, due to a high within‐group variability with respect to such features, the behavioral studies need to be applied with caution. In this review, we discuss how to make appropriate choices in the experimental design and which tests that are most suitable for the evaluation of PD‐related symptoms in such studies. Methods We have evaluated published results on two selected transgenic mouse models overexpressing wild type (L61) and mutated (A30P) α‐syn in the context of their validity and utility for different types of behavioral studies. Conclusions By applying appropriate behavioral tests, α‐syn transgenic mouse models provide an appropriate experimental platform for studies of symptoms related to PD and other α‐synucleinopathies. |
| first_indexed | 2024-04-13T20:44:42Z |
| format | Article |
| id | doaj.art-a606ebf0f1954c5a8d104cce47e36bc1 |
| institution | Directory Open Access Journal |
| issn | 2162-3279 |
| language | English |
| last_indexed | 2024-04-13T20:44:42Z |
| publishDate | 2022-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Brain and Behavior |
| spelling | doaj.art-a606ebf0f1954c5a8d104cce47e36bc12022-12-22T02:30:44ZengWileyBrain and Behavior2162-32792022-07-01127n/an/a10.1002/brb3.2628Modeling Parkinson's disease‐related symptoms in alpha‐synuclein overexpressing miceAgata Aniszewska0Joakim Bergström1Martin Ingelsson2Sara Ekmark‐Lewén3Department of Public Health and Caring Sciences Molecular Geriatrics Uppsala University Uppsala SwedenDepartment of Public Health and Caring Sciences Molecular Geriatrics Uppsala University Uppsala SwedenDepartment of Public Health and Caring Sciences Molecular Geriatrics Uppsala University Uppsala SwedenDepartment of Public Health and Caring Sciences Molecular Geriatrics Uppsala University Uppsala SwedenAbstract Background Intracellular deposition of alpha‐synuclein (α‐syn) as Lewy bodies and Lewy neurites is a central event in the pathogenesis of Parkinson's disease (PD) and other α‐synucleinopathies. Transgenic mouse models overexpressing human α‐syn, are useful research tools in preclinical studies of pathogenetic mechanisms. Such mice develop α‐syn inclusions as well as neurodegeneration with a topographical distribution that varies depending on the choice of promoter and which form of α‐syn that is overexpressed. Moreover, they display motor symptoms and cognitive disturbances that to some extent resemble the human conditions. Purpose One of the main motives for assessing behavior in these mouse models is to evaluate the potential of new treatment strategies, including their impact on motor and cognitive symptoms. However, due to a high within‐group variability with respect to such features, the behavioral studies need to be applied with caution. In this review, we discuss how to make appropriate choices in the experimental design and which tests that are most suitable for the evaluation of PD‐related symptoms in such studies. Methods We have evaluated published results on two selected transgenic mouse models overexpressing wild type (L61) and mutated (A30P) α‐syn in the context of their validity and utility for different types of behavioral studies. Conclusions By applying appropriate behavioral tests, α‐syn transgenic mouse models provide an appropriate experimental platform for studies of symptoms related to PD and other α‐synucleinopathies.https://doi.org/10.1002/brb3.2628alpha‐synucleinbehavioral testethologyParkinson´s diseasetransgenic mouse modelstranslational research |
| spellingShingle | Agata Aniszewska Joakim Bergström Martin Ingelsson Sara Ekmark‐Lewén Modeling Parkinson's disease‐related symptoms in alpha‐synuclein overexpressing mice Brain and Behavior alpha‐synuclein behavioral test ethology Parkinson´s disease transgenic mouse models translational research |
| title | Modeling Parkinson's disease‐related symptoms in alpha‐synuclein overexpressing mice |
| title_full | Modeling Parkinson's disease‐related symptoms in alpha‐synuclein overexpressing mice |
| title_fullStr | Modeling Parkinson's disease‐related symptoms in alpha‐synuclein overexpressing mice |
| title_full_unstemmed | Modeling Parkinson's disease‐related symptoms in alpha‐synuclein overexpressing mice |
| title_short | Modeling Parkinson's disease‐related symptoms in alpha‐synuclein overexpressing mice |
| title_sort | modeling parkinson s disease related symptoms in alpha synuclein overexpressing mice |
| topic | alpha‐synuclein behavioral test ethology Parkinson´s disease transgenic mouse models translational research |
| url | https://doi.org/10.1002/brb3.2628 |
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