Pramlintide improves cognitive function in Alzheimer’s disease mice through antioxidant stress and PI3K/Akt pathway
Objective To investigate the effect of pramlintide, a pancreatic amyloid peptide analog, on learning and memory of Alzheimer’s disease (AD) mice through antioxidant stress, and to determine the expression of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Methods The...
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Editorial Office of Journal of Army Medical University
2025-08-01
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| Series: | 陆军军医大学学报 |
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| Online Access: | http://aammt.tmmu.edu.cn/html/202505072.html |
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| author | LIU Yating LU Jing FENG Xiangqian |
| author_facet | LIU Yating LU Jing FENG Xiangqian |
| author_sort | LIU Yating |
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| description | Objective To investigate the effect of pramlintide, a pancreatic amyloid peptide analog, on learning and memory of Alzheimer’s disease (AD) mice through antioxidant stress, and to determine the expression of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Methods The APP/PS1 mice were divided into a pramlintide treatment group (intraperitoneal injection of 0.5 μmol/L per day for 10 weeks) and an AD group (same dose of PBS), with 5 mice in each group. The learning and memory abilities were detected with water maze test, the pathological changes of the hippocampus were observed with HE staining and immunohistochemistry, the morphological characteristics of dendritic spines in hippocampus were observed after Golgi staining, and the ultrastructure of hippocampal neurons was observed through transmission electron microscopy (TEM). The content of malondialdehyde (MDA) and the level of superoxide dismutase (SOD) in the hippocampal tissue were detected by biochemical assay, and the levels of inflammatory factors IL-6, TNF-α and IL-1β were determined with ELISA. Western blotting was applied to measure the expression of PI3K/Akt signaling pathway related proteins in the hippocampus. In the cell experiment, SH-SY5Y cells were added with Aβ 1-42 to establish a cell model of AD. After the cells were treated with pramlintide, the levels of oxidative stress and inflammatory response were detected, and cell apoptosis was detected by immunofluorescence. Results The animal experiments showed that pramlintide treatment resulted in significantly shortened escape latency (P<0.01), increased platform crossings (P<0.01), and prolonged time to exploring hidden platform (P<0.01). In the hippocampal tissue of the pramlintide treatment group, HE staining displayed hippocampal neurons in high density and neat arrangement (P<0.05), immunohistochemical results showed significantly reduced Aβ protein (P<0.01), Golgi staining results demonstrated more dendritic spines (P<0.05), TEM revealed almost intact neuronal mitochondrial structure, with reduced vacuolization and clear and identifiable morphology. When compared with the AD group, the levels of oxidative stress and inflammatory response were decreased (P<0.01), and the relative expression of p-PI3K/PI3K and p-Akt/Akt proteins was increased (P<0.01) in the treatment group. In cell experiments, the levels of oxidative stress and inflammatory response were decreased in AD cell model after pramlintide treatment (P<0.01), and the results of immunofluorescence showed that cell apoptosis was declined (P<0.01). Conclusion Pramlintide can improve the cognitive function, reduce the hippocampal deposition of Aβ, reduce oxidative stress and inflammatory response, alleviate the pathological changes of neuronal ultrastructure, and enhance the expression of PI3K/Akt signaling pathway in AD mice.
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| format | Article |
| id | doaj-art-d69b3ac935c34e17b8b6002b1606aaef |
| institution | Kabale University |
| issn | 2097-0927 |
| language | zho |
| publishDate | 2025-08-01 |
| publisher | Editorial Office of Journal of Army Medical University |
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| series | 陆军军医大学学报 |
| spelling | doaj-art-d69b3ac935c34e17b8b6002b1606aaef2025-08-26T11:40:48ZzhoEditorial Office of Journal of Army Medical University陆军军医大学学报2097-09272025-08-0147161862187110.16016/j.2097-0927.202505072Pramlintide improves cognitive function in Alzheimer’s disease mice through antioxidant stress and PI3K/Akt pathwayLIU Yating0LU Jing1FENG Xiangqian2Department of Neurology， the First Affiliated Hospital of Bengbu Medical University， Bengbu， AnhuiDepartment of Neurology， the First Affiliated Hospital of Bengbu Medical University， Bengbu， AnhuiDepartment of Neurology， the First Affiliated Hospital of Bengbu Medical University， Bengbu， AnhuiObjective To investigate the effect of pramlintide, a pancreatic amyloid peptide analog, on learning and memory of Alzheimer’s disease (AD) mice through antioxidant stress, and to determine the expression of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Methods The APP/PS1 mice were divided into a pramlintide treatment group (intraperitoneal injection of 0.5 μmol/L per day for 10 weeks) and an AD group (same dose of PBS), with 5 mice in each group. The learning and memory abilities were detected with water maze test, the pathological changes of the hippocampus were observed with HE staining and immunohistochemistry, the morphological characteristics of dendritic spines in hippocampus were observed after Golgi staining, and the ultrastructure of hippocampal neurons was observed through transmission electron microscopy (TEM). The content of malondialdehyde (MDA) and the level of superoxide dismutase (SOD) in the hippocampal tissue were detected by biochemical assay, and the levels of inflammatory factors IL-6, TNF-α and IL-1β were determined with ELISA. Western blotting was applied to measure the expression of PI3K/Akt signaling pathway related proteins in the hippocampus. In the cell experiment, SH-SY5Y cells were added with Aβ 1-42 to establish a cell model of AD. After the cells were treated with pramlintide, the levels of oxidative stress and inflammatory response were detected, and cell apoptosis was detected by immunofluorescence. Results The animal experiments showed that pramlintide treatment resulted in significantly shortened escape latency (P<0.01), increased platform crossings (P<0.01), and prolonged time to exploring hidden platform (P<0.01). In the hippocampal tissue of the pramlintide treatment group, HE staining displayed hippocampal neurons in high density and neat arrangement (P<0.05), immunohistochemical results showed significantly reduced Aβ protein (P<0.01), Golgi staining results demonstrated more dendritic spines (P<0.05), TEM revealed almost intact neuronal mitochondrial structure, with reduced vacuolization and clear and identifiable morphology. When compared with the AD group, the levels of oxidative stress and inflammatory response were decreased (P<0.01), and the relative expression of p-PI3K/PI3K and p-Akt/Akt proteins was increased (P<0.01) in the treatment group. In cell experiments, the levels of oxidative stress and inflammatory response were decreased in AD cell model after pramlintide treatment (P<0.01), and the results of immunofluorescence showed that cell apoptosis was declined (P<0.01). Conclusion Pramlintide can improve the cognitive function, reduce the hippocampal deposition of Aβ, reduce oxidative stress and inflammatory response, alleviate the pathological changes of neuronal ultrastructure, and enhance the expression of PI3K/Akt signaling pathway in AD mice. http://aammt.tmmu.edu.cn/html/202505072.htmlalzheimer’s diseasepramlintideislet amyloid polypeptidepi3k/akt pathwayantioxidant stressinflammatory response |
| spellingShingle | LIU Yating LU Jing FENG Xiangqian Pramlintide improves cognitive function in Alzheimer’s disease mice through antioxidant stress and PI3K/Akt pathway 陆军军医大学学报 alzheimer’s disease pramlintide islet amyloid polypeptide pi3k/akt pathway antioxidant stress inflammatory response |
| title | Pramlintide improves cognitive function in Alzheimer’s disease mice through antioxidant stress and PI3K/Akt pathway |
| title_full | Pramlintide improves cognitive function in Alzheimer’s disease mice through antioxidant stress and PI3K/Akt pathway |
| title_fullStr | Pramlintide improves cognitive function in Alzheimer’s disease mice through antioxidant stress and PI3K/Akt pathway |
| title_full_unstemmed | Pramlintide improves cognitive function in Alzheimer’s disease mice through antioxidant stress and PI3K/Akt pathway |
| title_short | Pramlintide improves cognitive function in Alzheimer’s disease mice through antioxidant stress and PI3K/Akt pathway |
| title_sort | pramlintide improves cognitive function in alzheimer s disease mice through antioxidant stress and pi3k akt pathway |
| topic | alzheimer’s disease pramlintide islet amyloid polypeptide pi3k/akt pathway antioxidant stress inflammatory response |
| url | http://aammt.tmmu.edu.cn/html/202505072.html |
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