A Comprehensive Phenotype of Non-motor Impairments and Distribution of Alpha-Synuclein Deposition in Parkinsonism-Induced Mice by a Combination Injection of MPTP and Probenecid
Parkinson’s disease (PD) is characterized by non-motor symptoms as well as motor deficits. The non-motor symptoms rarely appear individually and occur simultaneously with motor deficits or independently. However, a comprehensive research on the non-motor symptoms using an experimental model of PD re...
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2020.599045/full |
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| author | Na-Ra Han Na-Ra Han Yu-Kang Kim Yu-Kang Kim Sora Ahn Tae-Yeon Hwang Tae-Yeon Hwang Hyejung Lee Hi-Joon Park Hi-Joon Park |
| author_facet | Na-Ra Han Na-Ra Han Yu-Kang Kim Yu-Kang Kim Sora Ahn Tae-Yeon Hwang Tae-Yeon Hwang Hyejung Lee Hi-Joon Park Hi-Joon Park |
| author_sort | Na-Ra Han |
| collection | DOAJ |
| description | Parkinson’s disease (PD) is characterized by non-motor symptoms as well as motor deficits. The non-motor symptoms rarely appear individually and occur simultaneously with motor deficits or independently. However, a comprehensive research on the non-motor symptoms using an experimental model of PD remains poorly understood. The aim of the current study is to establish a chronic mouse model of PD mimicking the comprehensive non-motor symptoms of human PD by injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and probenecid (MPTP/p). The non-motor and motor symptoms were evaluated by performing buried food, short-term olfactory memory, hot plate, open field, tail suspension, Y maze, novel object recognition, bead expulsion, one-h stool collection, rotarod, rearing, catalepsy, and akinesia tests after 10 injections of MPTP/p into mice. The expression levels of α-synuclein, glial fibrillary acidic protein (GFAP), tyrosine hydroxylase (TH) or DJ-1 were analyzed by Western blotting or immunostaining. MPTP/p-treated mice achieved to reproduce the key features of non-motor symptoms including olfactory deficit, thermal hyperalgesia, anxiety, depression, cognitive decline, and gastrointestinal dysfunction in addition to motor deficits. The MPTP/p-treated mice also showed the high levels of α-synuclein and low levels of TH and DJ-1 in striatum, substantia nigra, olfactory bulb, hippocampus, amygdala, prefrontal cortex, locus coeruleus, or colon. In addition, the expression levels of phosphorylated-α-synuclein and GFAP were elevated in the striatum and substantia nigra in the MPTP/p-treated mice. Taken together, our study clarifies that the chronic MPTP/p-treated mice have a variety of non-motor dysfunctions as well as motor abnormalities by α-synuclein overexpression and dopaminergic depletion. Therefore, the study of comprehensive phenotypes of non-motor symptoms in one PD model would advance in-depth understandings of neuropathological alternations and contribute to future strategies for PD treatment. |
| first_indexed | 2024-12-16T10:07:23Z |
| format | Article |
| id | doaj.art-fe074255cb334776840dc12c835231d3 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-16T10:07:23Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-fe074255cb334776840dc12c835231d32022-12-21T22:35:39ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652021-01-011210.3389/fnagi.2020.599045599045A Comprehensive Phenotype of Non-motor Impairments and Distribution of Alpha-Synuclein Deposition in Parkinsonism-Induced Mice by a Combination Injection of MPTP and ProbenecidNa-Ra Han0Na-Ra Han1Yu-Kang Kim2Yu-Kang Kim3Sora Ahn4Tae-Yeon Hwang5Tae-Yeon Hwang6Hyejung Lee7Hi-Joon Park8Hi-Joon Park9Integrative Parkinson’s Disease Research Group, Acupuncture and Meridian Science Research Center, Kyung Hee University, Seoul, South KoreaDepartment of Anatomy & Information Sciences, College of Korean Medicine, Kyung Hee University, Seoul, South KoreaIntegrative Parkinson’s Disease Research Group, Acupuncture and Meridian Science Research Center, Kyung Hee University, Seoul, South KoreaDepartment of Anatomy & Information Sciences, College of Korean Medicine, Kyung Hee University, Seoul, South KoreaIntegrative Parkinson’s Disease Research Group, Acupuncture and Meridian Science Research Center, Kyung Hee University, Seoul, South KoreaIntegrative Parkinson’s Disease Research Group, Acupuncture and Meridian Science Research Center, Kyung Hee University, Seoul, South KoreaDepartment of Meridian & Acupoints, College of Korean Medicine, Kyung Hee University, Seoul, South KoreaDepartment of Meridian & Acupoints, College of Korean Medicine, Kyung Hee University, Seoul, South KoreaIntegrative Parkinson’s Disease Research Group, Acupuncture and Meridian Science Research Center, Kyung Hee University, Seoul, South KoreaDepartment of Anatomy & Information Sciences, College of Korean Medicine, Kyung Hee University, Seoul, South KoreaParkinson’s disease (PD) is characterized by non-motor symptoms as well as motor deficits. The non-motor symptoms rarely appear individually and occur simultaneously with motor deficits or independently. However, a comprehensive research on the non-motor symptoms using an experimental model of PD remains poorly understood. The aim of the current study is to establish a chronic mouse model of PD mimicking the comprehensive non-motor symptoms of human PD by injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and probenecid (MPTP/p). The non-motor and motor symptoms were evaluated by performing buried food, short-term olfactory memory, hot plate, open field, tail suspension, Y maze, novel object recognition, bead expulsion, one-h stool collection, rotarod, rearing, catalepsy, and akinesia tests after 10 injections of MPTP/p into mice. The expression levels of α-synuclein, glial fibrillary acidic protein (GFAP), tyrosine hydroxylase (TH) or DJ-1 were analyzed by Western blotting or immunostaining. MPTP/p-treated mice achieved to reproduce the key features of non-motor symptoms including olfactory deficit, thermal hyperalgesia, anxiety, depression, cognitive decline, and gastrointestinal dysfunction in addition to motor deficits. The MPTP/p-treated mice also showed the high levels of α-synuclein and low levels of TH and DJ-1 in striatum, substantia nigra, olfactory bulb, hippocampus, amygdala, prefrontal cortex, locus coeruleus, or colon. In addition, the expression levels of phosphorylated-α-synuclein and GFAP were elevated in the striatum and substantia nigra in the MPTP/p-treated mice. Taken together, our study clarifies that the chronic MPTP/p-treated mice have a variety of non-motor dysfunctions as well as motor abnormalities by α-synuclein overexpression and dopaminergic depletion. Therefore, the study of comprehensive phenotypes of non-motor symptoms in one PD model would advance in-depth understandings of neuropathological alternations and contribute to future strategies for PD treatment.https://www.frontiersin.org/articles/10.3389/fnagi.2020.599045/fullParkinson’s diseasenon-motor symptomsα-synuclein1-methyl-4-phenyl-123 |
| spellingShingle | Na-Ra Han Na-Ra Han Yu-Kang Kim Yu-Kang Kim Sora Ahn Tae-Yeon Hwang Tae-Yeon Hwang Hyejung Lee Hi-Joon Park Hi-Joon Park A Comprehensive Phenotype of Non-motor Impairments and Distribution of Alpha-Synuclein Deposition in Parkinsonism-Induced Mice by a Combination Injection of MPTP and Probenecid Frontiers in Aging Neuroscience Parkinson’s disease non-motor symptoms α-synuclein 1-methyl-4-phenyl-1 2 3 |
| title | A Comprehensive Phenotype of Non-motor Impairments and Distribution of Alpha-Synuclein Deposition in Parkinsonism-Induced Mice by a Combination Injection of MPTP and Probenecid |
| title_full | A Comprehensive Phenotype of Non-motor Impairments and Distribution of Alpha-Synuclein Deposition in Parkinsonism-Induced Mice by a Combination Injection of MPTP and Probenecid |
| title_fullStr | A Comprehensive Phenotype of Non-motor Impairments and Distribution of Alpha-Synuclein Deposition in Parkinsonism-Induced Mice by a Combination Injection of MPTP and Probenecid |
| title_full_unstemmed | A Comprehensive Phenotype of Non-motor Impairments and Distribution of Alpha-Synuclein Deposition in Parkinsonism-Induced Mice by a Combination Injection of MPTP and Probenecid |
| title_short | A Comprehensive Phenotype of Non-motor Impairments and Distribution of Alpha-Synuclein Deposition in Parkinsonism-Induced Mice by a Combination Injection of MPTP and Probenecid |
| title_sort | comprehensive phenotype of non motor impairments and distribution of alpha synuclein deposition in parkinsonism induced mice by a combination injection of mptp and probenecid |
| topic | Parkinson’s disease non-motor symptoms α-synuclein 1-methyl-4-phenyl-1 2 3 |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2020.599045/full |
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