Noncanonical Roles of hα-syn (A53T) in the Pathogenesis of Parkinson’s Disease: Synaptic Pathology and Neuronal Aging
The motor and nonmotor symptoms of PD involve several brain regions. However, whether α-syn pathology originating from the SNc can directly lead to the pathological changes in distant cerebral regions and induce PD-related symptoms remains unclear. Here, AAV9-synapsin-mCherry-human SNCA (A53T) was i...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2020/6283754 |
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| author | Qing-Jun Wang An-Di Chen Hai-Chao Chen Dong-Xin Wang Yi-Ting Cai Jie Yin Yu-Hong Jing Li-Ping Gao |
| author_facet | Qing-Jun Wang An-Di Chen Hai-Chao Chen Dong-Xin Wang Yi-Ting Cai Jie Yin Yu-Hong Jing Li-Ping Gao |
| author_sort | Qing-Jun Wang |
| collection | DOAJ |
| description | The motor and nonmotor symptoms of PD involve several brain regions. However, whether α-syn pathology originating from the SNc can directly lead to the pathological changes in distant cerebral regions and induce PD-related symptoms remains unclear. Here, AAV9-synapsin-mCherry-human SNCA (A53T) was injected into the unilateral SNc of mice. Motor function and olfactory sensitivity were evaluated. Our results showed that AAV9-synapsin-mCherry-human SNCA was continuously expressed in SNc. The animals showed mild motor and olfactory dysfunction at 7 months after viral injection. The pathology in SNc was characterized by the loss of dopaminergic neurons accompanied by ER stress. In the striatum, hα-syn expression was high, CaMKβ-2 and NR2B expression decreased, and active synapses reduced. In the olfactory bulb, hα-syn expression was high, and aging cells in the mitral layer increased. The results suggested that hα-syn was transported in the striatum and OB along the nerve fibers that originated from the SNc and induced pathological changes in the distant cerebral regions, which contributed to the motor and nonmotor symptoms of PD. |
| format | Article |
| id | doaj-art-b34726d91f3647f1adcae40465f0a721 |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-b34726d91f3647f1adcae40465f0a7212025-02-03T01:01:26ZengWileyNeural Plasticity2090-59041687-54432020-01-01202010.1155/2020/62837546283754Noncanonical Roles of hα-syn (A53T) in the Pathogenesis of Parkinson’s Disease: Synaptic Pathology and Neuronal AgingQing-Jun Wang0An-Di Chen1Hai-Chao Chen2Dong-Xin Wang3Yi-Ting Cai4Jie Yin5Yu-Hong Jing6Li-Ping Gao7Institute of Anatomy and Histology & Embryology, Neuroscience, School of Basic Medical Sciences, Lanzhou University, Lanzhou, ChinaInstitute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, ChinaInstitute of Anatomy and Histology & Embryology, Neuroscience, School of Basic Medical Sciences, Lanzhou University, Lanzhou, ChinaInstitute of Anatomy and Histology & Embryology, Neuroscience, School of Basic Medical Sciences, Lanzhou University, Lanzhou, ChinaInstitute of Anatomy and Histology & Embryology, Neuroscience, School of Basic Medical Sciences, Lanzhou University, Lanzhou, ChinaInstitute of Anatomy and Histology & Embryology, Neuroscience, School of Basic Medical Sciences, Lanzhou University, Lanzhou, ChinaInstitute of Anatomy and Histology & Embryology, Neuroscience, School of Basic Medical Sciences, Lanzhou University, Lanzhou, ChinaInstitute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, ChinaThe motor and nonmotor symptoms of PD involve several brain regions. However, whether α-syn pathology originating from the SNc can directly lead to the pathological changes in distant cerebral regions and induce PD-related symptoms remains unclear. Here, AAV9-synapsin-mCherry-human SNCA (A53T) was injected into the unilateral SNc of mice. Motor function and olfactory sensitivity were evaluated. Our results showed that AAV9-synapsin-mCherry-human SNCA was continuously expressed in SNc. The animals showed mild motor and olfactory dysfunction at 7 months after viral injection. The pathology in SNc was characterized by the loss of dopaminergic neurons accompanied by ER stress. In the striatum, hα-syn expression was high, CaMKβ-2 and NR2B expression decreased, and active synapses reduced. In the olfactory bulb, hα-syn expression was high, and aging cells in the mitral layer increased. The results suggested that hα-syn was transported in the striatum and OB along the nerve fibers that originated from the SNc and induced pathological changes in the distant cerebral regions, which contributed to the motor and nonmotor symptoms of PD.http://dx.doi.org/10.1155/2020/6283754 |
| spellingShingle | Qing-Jun Wang An-Di Chen Hai-Chao Chen Dong-Xin Wang Yi-Ting Cai Jie Yin Yu-Hong Jing Li-Ping Gao Noncanonical Roles of hα-syn (A53T) in the Pathogenesis of Parkinson’s Disease: Synaptic Pathology and Neuronal Aging Neural Plasticity |
| title | Noncanonical Roles of hα-syn (A53T) in the Pathogenesis of Parkinson’s Disease: Synaptic Pathology and Neuronal Aging |
| title_full | Noncanonical Roles of hα-syn (A53T) in the Pathogenesis of Parkinson’s Disease: Synaptic Pathology and Neuronal Aging |
| title_fullStr | Noncanonical Roles of hα-syn (A53T) in the Pathogenesis of Parkinson’s Disease: Synaptic Pathology and Neuronal Aging |
| title_full_unstemmed | Noncanonical Roles of hα-syn (A53T) in the Pathogenesis of Parkinson’s Disease: Synaptic Pathology and Neuronal Aging |
| title_short | Noncanonical Roles of hα-syn (A53T) in the Pathogenesis of Parkinson’s Disease: Synaptic Pathology and Neuronal Aging |
| title_sort | noncanonical roles of hα syn a53t in the pathogenesis of parkinson s disease synaptic pathology and neuronal aging |
| url | http://dx.doi.org/10.1155/2020/6283754 |
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