miR-132 regulates the expression of synaptic proteins in APP/PS1 transgenic mice through C1q
Cognitive impairment in Alzheimer’s disease (AD) is usually accompanied by synaptic loss in both the hippocampus and neocortex. In the early stage of AD, amyloid β-induced synapse changes is the main reason, while in the later stage, the accumulation of Tau protein promotes synapse degeneration as t...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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PAGEPress Publications
2019-05-01
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| Series: | European Journal of Histochemistry |
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| Online Access: | https://ejh.it/index.php/ejh/article/view/3008 |
| _version_ | 1811245887951732736 |
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| author | Nan Xu Ang-Di Li Li-Li Ji Yao Ye Zhen-Yu Wang Lei Tong |
| author_facet | Nan Xu Ang-Di Li Li-Li Ji Yao Ye Zhen-Yu Wang Lei Tong |
| author_sort | Nan Xu |
| collection | DOAJ |
| description | Cognitive impairment in Alzheimer’s disease (AD) is usually accompanied by synaptic loss in both the hippocampus and neocortex. In the early stage of AD, amyloid β-induced synapse changes is the main reason, while in the later stage, the accumulation of Tau protein promotes synapse degeneration as the key factor leading to dementia. MicroRNA (miRNA) is closely related to the expression changes of many AD-related genes. One of the most abundant brain-enriched miRNAs is miR-132, which has been shown to regulate both neuron morphogenesis and plasticity. It has been reported that miR-132 is significantly reduced in the brains of Alzheimer’s patients. Genetic deletion of miR-132 in mice promotes Aβ deposition, leading to impaired memory and enhanced Tau pathology, but how the miRNA-mediated gene expression dysregulation contributes to AD pathology remains unclear. Here we found the possible downstream target of miR-132 by in silico analysis, namely C1q. C1q is the primary protein of classical complement cascade, which is highly expressed in the synaptic regions of the central nervous system in Alzheimer’s patients. However, it is not clear whether miR-132 plays a role in AD through regulating C1q. To address this question, the APP/PS1 transgenic mice were transfected with miR-132 and given C1 inhibitors. Behavior tests were conducted to assess memory and cognitive abilities seven days after administration. In addition, we analyzed the expression of PSD95, Synapsin-1 and phosphorylated (p)-Synapsin. We found that the expression levels of the synaptic proteins treated with miR-132 or C1INH were significantly increased compared with the AD group. Further RT-qPCR result suggested that miR-132 might regulate C1q expression in AD. |
| first_indexed | 2024-04-12T14:45:54Z |
| format | Article |
| id | doaj.art-2545080a45de455faa69a42dc7d6a44b |
| institution | Directory Open Access Journal |
| issn | 1121-760X 2038-8306 |
| language | English |
| last_indexed | 2024-04-12T14:45:54Z |
| publishDate | 2019-05-01 |
| publisher | PAGEPress Publications |
| record_format | Article |
| series | European Journal of Histochemistry |
| spelling | doaj.art-2545080a45de455faa69a42dc7d6a44b2022-12-22T03:28:38ZengPAGEPress PublicationsEuropean Journal of Histochemistry1121-760X2038-83062019-05-0163210.4081/ejh.2019.3008miR-132 regulates the expression of synaptic proteins in APP/PS1 transgenic mice through C1qNan Xu0Ang-Di Li1Li-Li Ji2Yao Ye3Zhen-Yu Wang4Lei Tong5Department of Anatomy, College of Basic Medical Sciences, China Medical University, ShenyangDepartment of Anatomy, College of Basic Medical Sciences, China Medical University, ShenyangDepartment of Anatomy, College of Basic Medical Sciences, China Medical University, ShenyangDepartment of Anatomy, College of Basic Medical Sciences, China Medical University, ShenyangChina Medical University, College of Basic Medical Sciences, Department of AnatomyDepartment of Anatomy, College of Basic Medical Sciences, China Medical University, ShenyangCognitive impairment in Alzheimer’s disease (AD) is usually accompanied by synaptic loss in both the hippocampus and neocortex. In the early stage of AD, amyloid β-induced synapse changes is the main reason, while in the later stage, the accumulation of Tau protein promotes synapse degeneration as the key factor leading to dementia. MicroRNA (miRNA) is closely related to the expression changes of many AD-related genes. One of the most abundant brain-enriched miRNAs is miR-132, which has been shown to regulate both neuron morphogenesis and plasticity. It has been reported that miR-132 is significantly reduced in the brains of Alzheimer’s patients. Genetic deletion of miR-132 in mice promotes Aβ deposition, leading to impaired memory and enhanced Tau pathology, but how the miRNA-mediated gene expression dysregulation contributes to AD pathology remains unclear. Here we found the possible downstream target of miR-132 by in silico analysis, namely C1q. C1q is the primary protein of classical complement cascade, which is highly expressed in the synaptic regions of the central nervous system in Alzheimer’s patients. However, it is not clear whether miR-132 plays a role in AD through regulating C1q. To address this question, the APP/PS1 transgenic mice were transfected with miR-132 and given C1 inhibitors. Behavior tests were conducted to assess memory and cognitive abilities seven days after administration. In addition, we analyzed the expression of PSD95, Synapsin-1 and phosphorylated (p)-Synapsin. We found that the expression levels of the synaptic proteins treated with miR-132 or C1INH were significantly increased compared with the AD group. Further RT-qPCR result suggested that miR-132 might regulate C1q expression in AD.https://ejh.it/index.php/ejh/article/view/3008miR-132Alzheimer's diseasesynapseC1q |
| spellingShingle | Nan Xu Ang-Di Li Li-Li Ji Yao Ye Zhen-Yu Wang Lei Tong miR-132 regulates the expression of synaptic proteins in APP/PS1 transgenic mice through C1q European Journal of Histochemistry miR-132 Alzheimer's disease synapse C1q |
| title | miR-132 regulates the expression of synaptic proteins in APP/PS1 transgenic mice through C1q |
| title_full | miR-132 regulates the expression of synaptic proteins in APP/PS1 transgenic mice through C1q |
| title_fullStr | miR-132 regulates the expression of synaptic proteins in APP/PS1 transgenic mice through C1q |
| title_full_unstemmed | miR-132 regulates the expression of synaptic proteins in APP/PS1 transgenic mice through C1q |
| title_short | miR-132 regulates the expression of synaptic proteins in APP/PS1 transgenic mice through C1q |
| title_sort | mir 132 regulates the expression of synaptic proteins in app ps1 transgenic mice through c1q |
| topic | miR-132 Alzheimer's disease synapse C1q |
| url | https://ejh.it/index.php/ejh/article/view/3008 |
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