Amelioration of olfactory dysfunction in a mouse model of Parkinson’s disease via enhancing GABAergic signaling
Abstract Background Olfactory dysfunction is among the earliest non-motor symptoms of Parkinson’s disease (PD). As the foremost pathological hallmark, α-synuclein initiates the pathology in the olfactory pathway at the early stage of PD, particularly in the olfactory epithelium (OE) and olfactory bu...
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| Format: | Article |
| Language: | English |
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BMC
2023-06-01
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| Series: | Cell & Bioscience |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13578-023-01049-9 |
| _version_ | 1797811294834786304 |
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| author | Xing-Yang Liu Ke Wang Xian-Hua Deng Yi-Hua Wei Rui Guo Sui-Feng Liu Yi-Fan Zhu Jia-Jun Zhong Jing-Yuan Zheng Meng-Dan Wang Qiu-Hong Ye Jian-Quan He Kai-Hang Guo Jun-Rong Zhu Shu-Qiong Huang Ze-Xu Chen Chong-Shan Lv Lei Wen |
| author_facet | Xing-Yang Liu Ke Wang Xian-Hua Deng Yi-Hua Wei Rui Guo Sui-Feng Liu Yi-Fan Zhu Jia-Jun Zhong Jing-Yuan Zheng Meng-Dan Wang Qiu-Hong Ye Jian-Quan He Kai-Hang Guo Jun-Rong Zhu Shu-Qiong Huang Ze-Xu Chen Chong-Shan Lv Lei Wen |
| author_sort | Xing-Yang Liu |
| collection | DOAJ |
| description | Abstract Background Olfactory dysfunction is among the earliest non-motor symptoms of Parkinson’s disease (PD). As the foremost pathological hallmark, α-synuclein initiates the pathology in the olfactory pathway at the early stage of PD, particularly in the olfactory epithelium (OE) and olfactory bulb (OB). However, the local neural microcircuit mechanisms underlying olfactory dysfunction between OE and OB in early PD remain unknown. Results We observed that odor detection and discrimination were impaired in 6-month-old SNCA-A53T mice, while their motor ability remained unaffected. It was confirmed that α-synuclein increased and accumulated in OB but not in OE. Notably, the hyperactivity of mitral/tufted cells and the excitation/inhibition imbalance in OB were found in 6-month-old SNCA-A53T mice, which was attributed to the impaired GABAergic transmission and aberrant expression of GABA transporter 1 and vesicular GABA transporter in OB. We further showed that tiagabine, a potent and selective GABA reuptake inhibitor, could reverse the impaired olfactory function and GABAergic signaling in OB of SNCA-A53T mice. Conclusions Taken together, our findings demonstrate potential synaptic mechanisms of local neural microcircuit underlying olfactory dysfunction at the early stage of PD. These results highlight the critical role of aberrant GABAergic signaling of OB in early diagnosis and provide a potential therapeutic strategy for early-stage PD. |
| first_indexed | 2024-03-13T07:21:32Z |
| format | Article |
| id | doaj.art-c34f41dbf0de4dbf91248e78e67e5a0c |
| institution | Directory Open Access Journal |
| issn | 2045-3701 |
| language | English |
| last_indexed | 2024-03-13T07:21:32Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj.art-c34f41dbf0de4dbf91248e78e67e5a0c2023-06-04T11:39:33ZengBMCCell & Bioscience2045-37012023-06-0113112010.1186/s13578-023-01049-9Amelioration of olfactory dysfunction in a mouse model of Parkinson’s disease via enhancing GABAergic signalingXing-Yang Liu0Ke Wang1Xian-Hua Deng2Yi-Hua Wei3Rui Guo4Sui-Feng Liu5Yi-Fan Zhu6Jia-Jun Zhong7Jing-Yuan Zheng8Meng-Dan Wang9Qiu-Hong Ye10Jian-Quan He11Kai-Hang Guo12Jun-Rong Zhu13Shu-Qiong Huang14Ze-Xu Chen15Chong-Shan Lv16Lei Wen17State Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Xiang’an Hospital, School of Medicine, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Xiang’an Hospital, School of Medicine, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Xiang’an Hospital, School of Medicine, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Xiang’an Hospital, School of Medicine, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Xiang’an Hospital, School of Medicine, Xiamen UniversityZhongshan Hospital, School of Medicine, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Xiang’an Hospital, School of Medicine, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Xiang’an Hospital, School of Medicine, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Xiang’an Hospital, School of Medicine, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Xiang’an Hospital, School of Medicine, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Xiang’an Hospital, School of Medicine, Xiamen UniversityZhongshan Hospital, School of Medicine, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Xiang’an Hospital, School of Medicine, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Xiang’an Hospital, School of Medicine, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Xiang’an Hospital, School of Medicine, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Xiang’an Hospital, School of Medicine, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Xiang’an Hospital, School of Medicine, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Xiang’an Hospital, School of Medicine, Xiamen UniversityAbstract Background Olfactory dysfunction is among the earliest non-motor symptoms of Parkinson’s disease (PD). As the foremost pathological hallmark, α-synuclein initiates the pathology in the olfactory pathway at the early stage of PD, particularly in the olfactory epithelium (OE) and olfactory bulb (OB). However, the local neural microcircuit mechanisms underlying olfactory dysfunction between OE and OB in early PD remain unknown. Results We observed that odor detection and discrimination were impaired in 6-month-old SNCA-A53T mice, while their motor ability remained unaffected. It was confirmed that α-synuclein increased and accumulated in OB but not in OE. Notably, the hyperactivity of mitral/tufted cells and the excitation/inhibition imbalance in OB were found in 6-month-old SNCA-A53T mice, which was attributed to the impaired GABAergic transmission and aberrant expression of GABA transporter 1 and vesicular GABA transporter in OB. We further showed that tiagabine, a potent and selective GABA reuptake inhibitor, could reverse the impaired olfactory function and GABAergic signaling in OB of SNCA-A53T mice. Conclusions Taken together, our findings demonstrate potential synaptic mechanisms of local neural microcircuit underlying olfactory dysfunction at the early stage of PD. These results highlight the critical role of aberrant GABAergic signaling of OB in early diagnosis and provide a potential therapeutic strategy for early-stage PD.https://doi.org/10.1186/s13578-023-01049-9Parkinson’s diseaseOlfactory dysfunctionGABAergic signalingExcitation/inhibition imbalance |
| spellingShingle | Xing-Yang Liu Ke Wang Xian-Hua Deng Yi-Hua Wei Rui Guo Sui-Feng Liu Yi-Fan Zhu Jia-Jun Zhong Jing-Yuan Zheng Meng-Dan Wang Qiu-Hong Ye Jian-Quan He Kai-Hang Guo Jun-Rong Zhu Shu-Qiong Huang Ze-Xu Chen Chong-Shan Lv Lei Wen Amelioration of olfactory dysfunction in a mouse model of Parkinson’s disease via enhancing GABAergic signaling Cell & Bioscience Parkinson’s disease Olfactory dysfunction GABAergic signaling Excitation/inhibition imbalance |
| title | Amelioration of olfactory dysfunction in a mouse model of Parkinson’s disease via enhancing GABAergic signaling |
| title_full | Amelioration of olfactory dysfunction in a mouse model of Parkinson’s disease via enhancing GABAergic signaling |
| title_fullStr | Amelioration of olfactory dysfunction in a mouse model of Parkinson’s disease via enhancing GABAergic signaling |
| title_full_unstemmed | Amelioration of olfactory dysfunction in a mouse model of Parkinson’s disease via enhancing GABAergic signaling |
| title_short | Amelioration of olfactory dysfunction in a mouse model of Parkinson’s disease via enhancing GABAergic signaling |
| title_sort | amelioration of olfactory dysfunction in a mouse model of parkinson s disease via enhancing gabaergic signaling |
| topic | Parkinson’s disease Olfactory dysfunction GABAergic signaling Excitation/inhibition imbalance |
| url | https://doi.org/10.1186/s13578-023-01049-9 |
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