A selective degeneration of cholinergic neurons mediated by NRADD in an Alzheimer's disease mouse model
Cholinergic neurons in the basal forebrain constitute a major source of cholinergic inputs to the forebrain, modulate diverse functions including sensory processing, memory and attention, and are vulnerable to Alzheimer's disease (AD). Recently, we classified cholinergic neurons into two distin...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Cell Insight |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772892722000578 |
| _version_ | 1811190053502713856 |
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| author | Lanfang Li Bing Zhang Xiaomei Tang Quntao Yu Aodi He Youming Lu Xinyan Li |
| author_facet | Lanfang Li Bing Zhang Xiaomei Tang Quntao Yu Aodi He Youming Lu Xinyan Li |
| author_sort | Lanfang Li |
| collection | DOAJ |
| description | Cholinergic neurons in the basal forebrain constitute a major source of cholinergic inputs to the forebrain, modulate diverse functions including sensory processing, memory and attention, and are vulnerable to Alzheimer's disease (AD). Recently, we classified cholinergic neurons into two distinct subpopulations; calbindin D28K-expressing (D28K+) versus D28K-lacking (D28K−) neurons. Yet, which of these two cholinergic subpopulations are selectively degenerated in AD and the molecular mechanisms underlying this selective degeneration remain unknown. Here, we reported a discovery that D28K+ neurons are selectively degenerated and this degeneration induces anxiety-like behaviors in the early stage of AD. Neuronal type specific deletion of NRADD effectively rescues D28K+ neuronal degeneration, whereas genetic introduction of exogenous NRADD causes D28K− neuronal loss. This gain- and loss-of-function study reveals a subtype specific degeneration of cholinergic neurons in the disease progression of AD and hence warrants a novel molecular target for AD therapy. |
| first_indexed | 2024-04-11T14:45:03Z |
| format | Article |
| id | doaj.art-5f580e537776431b847d8530f67a57dd |
| institution | Directory Open Access Journal |
| issn | 2772-8927 |
| language | English |
| last_indexed | 2024-04-11T14:45:03Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Insight |
| spelling | doaj.art-5f580e537776431b847d8530f67a57dd2022-12-22T04:17:43ZengElsevierCell Insight2772-89272022-12-0116100060A selective degeneration of cholinergic neurons mediated by NRADD in an Alzheimer's disease mouse modelLanfang Li0Bing Zhang1Xiaomei Tang2Quntao Yu3Aodi He4Youming Lu5Xinyan Li6Institute for Brain Research, Wuhan Center of Brain Science, Huazhong University of Science and Technology, Wuhan, 430030, China; Department of Pathophysiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, ChinaInstitute for Brain Research, Wuhan Center of Brain Science, Huazhong University of Science and Technology, Wuhan, 430030, China; Department of Pathophysiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, ChinaInstitute for Brain Research, Wuhan Center of Brain Science, Huazhong University of Science and Technology, Wuhan, 430030, China; Department of Pathophysiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, ChinaInstitute for Brain Research, Wuhan Center of Brain Science, Huazhong University of Science and Technology, Wuhan, 430030, China; Department of Pathophysiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, ChinaInstitute for Brain Research, Wuhan Center of Brain Science, Huazhong University of Science and Technology, Wuhan, 430030, China; Department of Anatomy, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, ChinaDepartment of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 4030030, China; Institute for Brain Research, Wuhan Center of Brain Science, Huazhong University of Science and Technology, Wuhan, 430030, China; Department of Pathophysiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, ChinaInstitute for Brain Research, Wuhan Center of Brain Science, Huazhong University of Science and Technology, Wuhan, 430030, China; Department of Anatomy, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Corresponding author. Institute for Brain Research, Wuhan Center of Brain Science, Huazhong University of Science and Technology, Wuhan, 430030, China.Cholinergic neurons in the basal forebrain constitute a major source of cholinergic inputs to the forebrain, modulate diverse functions including sensory processing, memory and attention, and are vulnerable to Alzheimer's disease (AD). Recently, we classified cholinergic neurons into two distinct subpopulations; calbindin D28K-expressing (D28K+) versus D28K-lacking (D28K−) neurons. Yet, which of these two cholinergic subpopulations are selectively degenerated in AD and the molecular mechanisms underlying this selective degeneration remain unknown. Here, we reported a discovery that D28K+ neurons are selectively degenerated and this degeneration induces anxiety-like behaviors in the early stage of AD. Neuronal type specific deletion of NRADD effectively rescues D28K+ neuronal degeneration, whereas genetic introduction of exogenous NRADD causes D28K− neuronal loss. This gain- and loss-of-function study reveals a subtype specific degeneration of cholinergic neurons in the disease progression of AD and hence warrants a novel molecular target for AD therapy.http://www.sciencedirect.com/science/article/pii/S2772892722000578Alzheimer's diseaseD28KCholinergic neuronsAnxiety-like behaviorNRADD |
| spellingShingle | Lanfang Li Bing Zhang Xiaomei Tang Quntao Yu Aodi He Youming Lu Xinyan Li A selective degeneration of cholinergic neurons mediated by NRADD in an Alzheimer's disease mouse model Cell Insight Alzheimer's disease D28K Cholinergic neurons Anxiety-like behavior NRADD |
| title | A selective degeneration of cholinergic neurons mediated by NRADD in an Alzheimer's disease mouse model |
| title_full | A selective degeneration of cholinergic neurons mediated by NRADD in an Alzheimer's disease mouse model |
| title_fullStr | A selective degeneration of cholinergic neurons mediated by NRADD in an Alzheimer's disease mouse model |
| title_full_unstemmed | A selective degeneration of cholinergic neurons mediated by NRADD in an Alzheimer's disease mouse model |
| title_short | A selective degeneration of cholinergic neurons mediated by NRADD in an Alzheimer's disease mouse model |
| title_sort | selective degeneration of cholinergic neurons mediated by nradd in an alzheimer s disease mouse model |
| topic | Alzheimer's disease D28K Cholinergic neurons Anxiety-like behavior NRADD |
| url | http://www.sciencedirect.com/science/article/pii/S2772892722000578 |
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