Neuroplastin 65 deficiency reduces amyloid plaque formation and cognitive deficits in an Alzheimer’s disease mouse model
IntroductionAlzheimer’s disease (AD) is characterized by increasing cognitive dysfunction, progressive cerebral amyloid beta (Aβ) deposition, and neurofibrillary tangle aggregation. However, the molecular mechanisms of AD pathologies have not been completely understood. As synaptic glycoprotein neur...
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2023.1129773/full |
| _version_ | 1797833134932230144 |
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| author | Dan-Dan Wu Jie Cheng Ya-Ni Zheng Yu-Tong Liu Shuang-Xin Hou Li-Fen Liu Liang Huang Liang Huang Qiong-Lan Yuan Qiong-Lan Yuan |
| author_facet | Dan-Dan Wu Jie Cheng Ya-Ni Zheng Yu-Tong Liu Shuang-Xin Hou Li-Fen Liu Liang Huang Liang Huang Qiong-Lan Yuan Qiong-Lan Yuan |
| author_sort | Dan-Dan Wu |
| collection | DOAJ |
| description | IntroductionAlzheimer’s disease (AD) is characterized by increasing cognitive dysfunction, progressive cerebral amyloid beta (Aβ) deposition, and neurofibrillary tangle aggregation. However, the molecular mechanisms of AD pathologies have not been completely understood. As synaptic glycoprotein neuroplastin 65 (NP65) is related with synaptic plasticity and complex molecular events underlying learning and memory, we hypothesized that NP65 would be involved in cognitive dysfunction and Aβ plaque formation of AD. For this purpose, we examined the role of NP65 in the transgenic amyloid precursor protein (APP)/presenilin 1 (PS1) mouse model of AD.MethodsNeuroplastin 65-knockout (NP65–/–) mice crossed with APP/PS1 mice to get the NP65-deficient APP/PS1 mice. In the present study, a separate cohort of NP65-deficient APP/PS1 mice were used. First, the cognitive behaviors of NP65-deficient APP/PS1 mice were assessed. Then, Aβ plaque burden and Aβ levels in NP65-deficient APP/PS1 mice were measured by immunostaining and western blot as well as ELISA. Thirdly, immunostaining and western blot were used to evaluate the glial response and neuroinflammation. Finally, protein levels of 5-hydroxytryptamin (serotonin) receptor 3A and synaptic proteins and neurons were measured.ResultsWe found that loss of NP65 alleviated the cognitive deficits of APP/PS1 mice. In addition, Aβ plaque burden and Aβ levels were significantly reduced in NP65-deficient APP/PS1 mice compared with control animals. NP65-loss in APP/PS1 mice resulted in a decrease in glial activation and the levels of pro- and anti-inflammatory cytokines (IL-1β, TNF-α, and IL-4) as well as protective matrix YM-1 and Arg-1, but had no effect on microglial phenotype. Moreover, NP65 deficiency significantly reversed the increase in 5-hydroxytryptamine (serotonin) receptor 3A (Htr3A) expression levels in the hippocampus of APP/PS1 mice.DiscussionThese findings identify a previously unrecognized role of NP65 in cognitive deficits and Aβ formation of APP/PS1 mice, and suggest that NP65 may serve as a potential therapeutic target for AD. |
| first_indexed | 2024-04-09T14:18:40Z |
| format | Article |
| id | doaj.art-9bac1456c73f4f96871f38f95adb8b89 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-09T14:18:40Z |
| publishDate | 2023-05-01 |
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| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-9bac1456c73f4f96871f38f95adb8b892023-05-05T05:15:45ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-05-011710.3389/fncel.2023.11297731129773Neuroplastin 65 deficiency reduces amyloid plaque formation and cognitive deficits in an Alzheimer’s disease mouse modelDan-Dan Wu0Jie Cheng1Ya-Ni Zheng2Yu-Tong Liu3Shuang-Xin Hou4Li-Fen Liu5Liang Huang6Liang Huang7Qiong-Lan Yuan8Qiong-Lan Yuan9Department of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Radiology, University of Nebraska Medical Center, Omaha, NE, United StatesDepartment of Neurobiology, Shanghai Pudong Hospital, Fudan University, Shanghai, ChinaDepartment of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Human Anatomy, Histology and Embryology, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Human Anatomy, Histology and Embryology, Tongji University School of Medicine, Shanghai, ChinaIntroductionAlzheimer’s disease (AD) is characterized by increasing cognitive dysfunction, progressive cerebral amyloid beta (Aβ) deposition, and neurofibrillary tangle aggregation. However, the molecular mechanisms of AD pathologies have not been completely understood. As synaptic glycoprotein neuroplastin 65 (NP65) is related with synaptic plasticity and complex molecular events underlying learning and memory, we hypothesized that NP65 would be involved in cognitive dysfunction and Aβ plaque formation of AD. For this purpose, we examined the role of NP65 in the transgenic amyloid precursor protein (APP)/presenilin 1 (PS1) mouse model of AD.MethodsNeuroplastin 65-knockout (NP65–/–) mice crossed with APP/PS1 mice to get the NP65-deficient APP/PS1 mice. In the present study, a separate cohort of NP65-deficient APP/PS1 mice were used. First, the cognitive behaviors of NP65-deficient APP/PS1 mice were assessed. Then, Aβ plaque burden and Aβ levels in NP65-deficient APP/PS1 mice were measured by immunostaining and western blot as well as ELISA. Thirdly, immunostaining and western blot were used to evaluate the glial response and neuroinflammation. Finally, protein levels of 5-hydroxytryptamin (serotonin) receptor 3A and synaptic proteins and neurons were measured.ResultsWe found that loss of NP65 alleviated the cognitive deficits of APP/PS1 mice. In addition, Aβ plaque burden and Aβ levels were significantly reduced in NP65-deficient APP/PS1 mice compared with control animals. NP65-loss in APP/PS1 mice resulted in a decrease in glial activation and the levels of pro- and anti-inflammatory cytokines (IL-1β, TNF-α, and IL-4) as well as protective matrix YM-1 and Arg-1, but had no effect on microglial phenotype. Moreover, NP65 deficiency significantly reversed the increase in 5-hydroxytryptamine (serotonin) receptor 3A (Htr3A) expression levels in the hippocampus of APP/PS1 mice.DiscussionThese findings identify a previously unrecognized role of NP65 in cognitive deficits and Aβ formation of APP/PS1 mice, and suggest that NP65 may serve as a potential therapeutic target for AD.https://www.frontiersin.org/articles/10.3389/fncel.2023.1129773/fullneuroplastin 65Alzheimer’s diseaseamyloid plaquesneuroinflammation5-hydroxytryptamine receptor 3A subunitglial activation |
| spellingShingle | Dan-Dan Wu Jie Cheng Ya-Ni Zheng Yu-Tong Liu Shuang-Xin Hou Li-Fen Liu Liang Huang Liang Huang Qiong-Lan Yuan Qiong-Lan Yuan Neuroplastin 65 deficiency reduces amyloid plaque formation and cognitive deficits in an Alzheimer’s disease mouse model Frontiers in Cellular Neuroscience neuroplastin 65 Alzheimer’s disease amyloid plaques neuroinflammation 5-hydroxytryptamine receptor 3A subunit glial activation |
| title | Neuroplastin 65 deficiency reduces amyloid plaque formation and cognitive deficits in an Alzheimer’s disease mouse model |
| title_full | Neuroplastin 65 deficiency reduces amyloid plaque formation and cognitive deficits in an Alzheimer’s disease mouse model |
| title_fullStr | Neuroplastin 65 deficiency reduces amyloid plaque formation and cognitive deficits in an Alzheimer’s disease mouse model |
| title_full_unstemmed | Neuroplastin 65 deficiency reduces amyloid plaque formation and cognitive deficits in an Alzheimer’s disease mouse model |
| title_short | Neuroplastin 65 deficiency reduces amyloid plaque formation and cognitive deficits in an Alzheimer’s disease mouse model |
| title_sort | neuroplastin 65 deficiency reduces amyloid plaque formation and cognitive deficits in an alzheimer s disease mouse model |
| topic | neuroplastin 65 Alzheimer’s disease amyloid plaques neuroinflammation 5-hydroxytryptamine receptor 3A subunit glial activation |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2023.1129773/full |
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