Spatiotemporal Up-Regulation of Mu Opioid Receptor 1 in Striatum of Mouse Model of Huntington’s Disease Differentially Affecting Caudal and Striosomal Regions
The striatum of humans and other mammals is divided into macroscopic compartments made up of a labyrinthine striosome compartment embedded in a much larger surrounding matrix compartment. Anatomical and snRNA-Seq studies of the Huntington’s disease (HD) postmortem striatum suggest a preferential dec...
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Frontiers Media SA
2021
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| Online Access: | https://hdl.handle.net/1721.1/129663 |
| _version_ | 1826192600449679360 |
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| author | Morigaki, Ryoma Lee, Jannifer Yoshida, Tomoko Wuethrich, Christian Hu, Dan Crittenden, Jill R Friedman, Alexander Kubota, Yasuo Graybiel, Ann M |
| author2 | McGovern Institute for Brain Research at MIT |
| author_facet | McGovern Institute for Brain Research at MIT Morigaki, Ryoma Lee, Jannifer Yoshida, Tomoko Wuethrich, Christian Hu, Dan Crittenden, Jill R Friedman, Alexander Kubota, Yasuo Graybiel, Ann M |
| author_sort | Morigaki, Ryoma |
| collection | MIT |
| description | The striatum of humans and other mammals is divided into macroscopic compartments made up of a labyrinthine striosome compartment embedded in a much larger surrounding matrix compartment. Anatomical and snRNA-Seq studies of the Huntington’s disease (HD) postmortem striatum suggest a preferential decline of some striosomal markers, and mRNAs studies of HD model mice concur. Here, by immunohistochemical methods, we examined the distribution of the canonical striosomal marker, mu-opioid receptor 1 (MOR1), in the striatum of the Q175 knock-in mouse model of HD in a postnatal time series extending from 3 to 19 months. We demonstrate that, contrary to the loss of many markers for striosomes, there is a pronounced up-regulation of MOR1 in these Q175 knock-in mice. We show that in heterozygous Q175 knock-in model mice [~192 cytosine-adenine-guanine (CAG) repeats], this MOR1 up-regulation progressed with advancing age and disease progression, and was particularly remarkable at caudal levels of the striatum. Given the known importance of MOR1 in basal ganglia signaling, our findings, though in mice, should offer clues to the pathogenesis of psychiatric features, especially depression, reinforcement sensitivity, and involuntary movements in HD. |
| first_indexed | 2024-09-23T09:24:09Z |
| format | Article |
| id | mit-1721.1/129663 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T09:24:09Z |
| publishDate | 2021 |
| publisher | Frontiers Media SA |
| record_format | dspace |
| spelling | mit-1721.1/1296632022-09-26T11:23:24Z Spatiotemporal Up-Regulation of Mu Opioid Receptor 1 in Striatum of Mouse Model of Huntington’s Disease Differentially Affecting Caudal and Striosomal Regions Morigaki, Ryoma Lee, Jannifer Yoshida, Tomoko Wuethrich, Christian Hu, Dan Crittenden, Jill R Friedman, Alexander Kubota, Yasuo Graybiel, Ann M McGovern Institute for Brain Research at MIT Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences The striatum of humans and other mammals is divided into macroscopic compartments made up of a labyrinthine striosome compartment embedded in a much larger surrounding matrix compartment. Anatomical and snRNA-Seq studies of the Huntington’s disease (HD) postmortem striatum suggest a preferential decline of some striosomal markers, and mRNAs studies of HD model mice concur. Here, by immunohistochemical methods, we examined the distribution of the canonical striosomal marker, mu-opioid receptor 1 (MOR1), in the striatum of the Q175 knock-in mouse model of HD in a postnatal time series extending from 3 to 19 months. We demonstrate that, contrary to the loss of many markers for striosomes, there is a pronounced up-regulation of MOR1 in these Q175 knock-in mice. We show that in heterozygous Q175 knock-in model mice [~192 cytosine-adenine-guanine (CAG) repeats], this MOR1 up-regulation progressed with advancing age and disease progression, and was particularly remarkable at caudal levels of the striatum. Given the known importance of MOR1 in basal ganglia signaling, our findings, though in mice, should offer clues to the pathogenesis of psychiatric features, especially depression, reinforcement sensitivity, and involuntary movements in HD. NIH/NIMH (Grant R01-MH060379) 2021-02-03T21:17:59Z 2021-02-03T21:17:59Z 2020-12 2020-09 Article http://purl.org/eprint/type/JournalArticle 1662-5129 https://hdl.handle.net/1721.1/129663 Morigaki, Ryoma et al. "Spatiotemporal Up-Regulation of Mu Opioid Receptor 1 in Striatum of Mouse Model of Huntington’s Disease Differentially Affecting Caudal and Striosomal Regions." Frontiers in Neuroanatomy 14 (December 2020): 608060 © 2020 Morigaki et al. https://doi.org/10.3389/fnana.2020.608060 Frontiers in Neuroanatomy Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Frontiers Media SA Frontiers |
| spellingShingle | Morigaki, Ryoma Lee, Jannifer Yoshida, Tomoko Wuethrich, Christian Hu, Dan Crittenden, Jill R Friedman, Alexander Kubota, Yasuo Graybiel, Ann M Spatiotemporal Up-Regulation of Mu Opioid Receptor 1 in Striatum of Mouse Model of Huntington’s Disease Differentially Affecting Caudal and Striosomal Regions |
| title | Spatiotemporal Up-Regulation of Mu Opioid Receptor 1 in Striatum of Mouse Model of Huntington’s Disease Differentially Affecting Caudal and Striosomal Regions |
| title_full | Spatiotemporal Up-Regulation of Mu Opioid Receptor 1 in Striatum of Mouse Model of Huntington’s Disease Differentially Affecting Caudal and Striosomal Regions |
| title_fullStr | Spatiotemporal Up-Regulation of Mu Opioid Receptor 1 in Striatum of Mouse Model of Huntington’s Disease Differentially Affecting Caudal and Striosomal Regions |
| title_full_unstemmed | Spatiotemporal Up-Regulation of Mu Opioid Receptor 1 in Striatum of Mouse Model of Huntington’s Disease Differentially Affecting Caudal and Striosomal Regions |
| title_short | Spatiotemporal Up-Regulation of Mu Opioid Receptor 1 in Striatum of Mouse Model of Huntington’s Disease Differentially Affecting Caudal and Striosomal Regions |
| title_sort | spatiotemporal up regulation of mu opioid receptor 1 in striatum of mouse model of huntington s disease differentially affecting caudal and striosomal regions |
| url | https://hdl.handle.net/1721.1/129663 |
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