Single-cell analysis of gene expression in the substantia nigra pars compacta of a pesticide-induced mouse model of Parkinson’s disease
Exposure to pesticides in humans increases the risk of Parkinson’s disease (PD), but the mechanisms remain poorly understood. To elucidate these pathways, we dosed C57BL/6J mice with a combination of the pesticides maneb and paraquat. Behavioral analysis revealed motor deficits consistent with PD. S...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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De Gruyter
2022-09-01
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| Series: | Translational Neuroscience |
| Subjects: | |
| Online Access: | https://doi.org/10.1515/tnsci-2022-0237 |
| _version_ | 1818027252339703808 |
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| author | Khan Arshad H. Lee Lydia K. Smith Desmond J. |
| author_facet | Khan Arshad H. Lee Lydia K. Smith Desmond J. |
| author_sort | Khan Arshad H. |
| collection | DOAJ |
| description | Exposure to pesticides in humans increases the risk of Parkinson’s disease (PD), but the mechanisms remain poorly understood. To elucidate these pathways, we dosed C57BL/6J mice with a combination of the pesticides maneb and paraquat. Behavioral analysis revealed motor deficits consistent with PD. Single-cell RNA sequencing of substantia nigra pars compacta revealed both cell-type-specific genes and genes expressed differentially between pesticide and control, including Fam241b, Emx2os, Bivm, Gm1439, Prdm15, and Rai2. Neurons had the largest number of significant differentially expressed genes, but comparable numbers were found in astrocytes and less so in oligodendrocytes. In addition, network analysis revealed enrichment in functions related to the extracellular matrix. These findings emphasize the importance of support cells in pesticide-induced PD and refocus our attention away from neurons as the sole agent of this disorder. |
| first_indexed | 2024-12-10T04:44:57Z |
| format | Article |
| id | doaj.art-0df58243033844f48db502426f4cbd26 |
| institution | Directory Open Access Journal |
| issn | 2081-6936 |
| language | English |
| last_indexed | 2024-12-10T04:44:57Z |
| publishDate | 2022-09-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Translational Neuroscience |
| spelling | doaj.art-0df58243033844f48db502426f4cbd262022-12-22T02:01:45ZengDe GruyterTranslational Neuroscience2081-69362022-09-0113125526910.1515/tnsci-2022-0237Single-cell analysis of gene expression in the substantia nigra pars compacta of a pesticide-induced mouse model of Parkinson’s diseaseKhan Arshad H.0Lee Lydia K.1Smith Desmond J.2Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Box 951735, 23-151 A CHS, Los Angeles, CA 90095-1735, United States of AmericaDepartment of Obstetrics and Gynecology, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095-6928, United States of AmericaDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Box 951735, 23-151 A CHS, Los Angeles, CA 90095-1735, United States of AmericaExposure to pesticides in humans increases the risk of Parkinson’s disease (PD), but the mechanisms remain poorly understood. To elucidate these pathways, we dosed C57BL/6J mice with a combination of the pesticides maneb and paraquat. Behavioral analysis revealed motor deficits consistent with PD. Single-cell RNA sequencing of substantia nigra pars compacta revealed both cell-type-specific genes and genes expressed differentially between pesticide and control, including Fam241b, Emx2os, Bivm, Gm1439, Prdm15, and Rai2. Neurons had the largest number of significant differentially expressed genes, but comparable numbers were found in astrocytes and less so in oligodendrocytes. In addition, network analysis revealed enrichment in functions related to the extracellular matrix. These findings emphasize the importance of support cells in pesticide-induced PD and refocus our attention away from neurons as the sole agent of this disorder.https://doi.org/10.1515/tnsci-2022-0237basal gangliamanebparaquatneurodegenerationscrna-seq |
| spellingShingle | Khan Arshad H. Lee Lydia K. Smith Desmond J. Single-cell analysis of gene expression in the substantia nigra pars compacta of a pesticide-induced mouse model of Parkinson’s disease Translational Neuroscience basal ganglia maneb paraquat neurodegeneration scrna-seq |
| title | Single-cell analysis of gene expression in the substantia nigra pars compacta of a pesticide-induced mouse model of Parkinson’s disease |
| title_full | Single-cell analysis of gene expression in the substantia nigra pars compacta of a pesticide-induced mouse model of Parkinson’s disease |
| title_fullStr | Single-cell analysis of gene expression in the substantia nigra pars compacta of a pesticide-induced mouse model of Parkinson’s disease |
| title_full_unstemmed | Single-cell analysis of gene expression in the substantia nigra pars compacta of a pesticide-induced mouse model of Parkinson’s disease |
| title_short | Single-cell analysis of gene expression in the substantia nigra pars compacta of a pesticide-induced mouse model of Parkinson’s disease |
| title_sort | single cell analysis of gene expression in the substantia nigra pars compacta of a pesticide induced mouse model of parkinson s disease |
| topic | basal ganglia maneb paraquat neurodegeneration scrna-seq |
| url | https://doi.org/10.1515/tnsci-2022-0237 |
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