Peripheral mitochondrial transplantation alleviates diabetes-associated cognitive dysfunction by suppressing cuproptosis
Mitochondrial dysfunction and neuronal impairment are hallmark features of Diabetes-Associated Cognitive Dysfunction (DACD), mitochondrial transplantation is also a therapeutic intervention for DACD. However, the precise mechanism underlying its therapeutic effects are not fully elucidated. Given th...
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Elsevier
2025-03-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923025000577 |
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| author | Juan Hu Qiao Li Shiqiu Jiang Yingying Deng Lan Yang Mengyu Du Shuxuan He Fuxing Xu Chaoying Yan Wei Gao Yansong Li Yaomin Zhu |
| author_facet | Juan Hu Qiao Li Shiqiu Jiang Yingying Deng Lan Yang Mengyu Du Shuxuan He Fuxing Xu Chaoying Yan Wei Gao Yansong Li Yaomin Zhu |
| author_sort | Juan Hu |
| collection | DOAJ |
| description | Mitochondrial dysfunction and neuronal impairment are hallmark features of Diabetes-Associated Cognitive Dysfunction (DACD), mitochondrial transplantation is also a therapeutic intervention for DACD. However, the precise mechanism underlying its therapeutic effects are not fully elucidated. Given that imbalances in copper homeostasis and cuproptosis are associated with various neurodegenerative disorders and diabetic myocardial damage, we hypothesize a role for cuproptosis in the pathogenesis of DACD. We further propose that therapeutic peripheral mitochondrial transplantation may ameliorate DACD by reducing processes of cuproptosis. In this research, the study delved into the expression levels of cuproptosis-associated proteins FDX1, LIAS, and DLAT, as well as the copper content in both type 2 diabetes mellitus (T2DM) mice and primary neuronal cells exposed to high glucose and palmitic acid (HG/Pal). Furthermore, the cognitive capabilities of the mice were evaluated using a series of behavioral tests. The findings revealed that in primary neurons exposed to HG/Pal, the expression of copper levels was elevated, and the levels of FDX1, LIAS, and DLAT were reduced. Post-transplantation of platelet-derived mitochondria (Mito-Plt), a significant reversal of these biomarkers was noted, coincident with an improvement in cognitive deficits in T2DM mice. Significantly, the cuproptosis agonist elesclomol (ES) aggravated these alterations. In summary, the findings collectively suggest a causal connection between DACD and the development of cuproptosis in neurons. The use of exogenous Mito-Plt presents a promising therapeutic approach, capable of rescuing neurons from cuproptosis and thereby potentially alleviating DACD. |
| format | Article |
| id | doaj-art-18bfd749f898481aae2144fda036e944 |
| institution | Kabale University |
| issn | 1873-2747 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj-art-18bfd749f898481aae2144fda036e9442025-02-10T04:33:31ZengElsevierBrain Research Bulletin1873-27472025-03-01222111245Peripheral mitochondrial transplantation alleviates diabetes-associated cognitive dysfunction by suppressing cuproptosisJuan Hu0Qiao Li1Shiqiu Jiang2Yingying Deng3Lan Yang4Mengyu Du5Shuxuan He6Fuxing Xu7Chaoying Yan8Wei Gao9Yansong Li10Yaomin Zhu11Department of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China; The Second Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, ChinaDepartment of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China; Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, ChinaDepartment of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, ChinaDepartment of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, ChinaDepartment of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, ChinaDepartment of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China; Department of Anesthesiology, Zhongnan Hospital, Wuhan University, East Lake Road, Wuhan, Hubei 430071, ChinaDepartment of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China; Department of Anesthesiology, The Second Affiliated Hospital of Air Force Medical University, Xi'an, Shaanxi 710038, ChinaDepartment of Anesthesiology, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi 030013, ChinaDepartment of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, ChinaDepartment of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, ChinaDepartment of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China; Correspondence to: Department of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi province 710061, China.Department of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China; Correspondence to: Department of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi province 710061, China.Mitochondrial dysfunction and neuronal impairment are hallmark features of Diabetes-Associated Cognitive Dysfunction (DACD), mitochondrial transplantation is also a therapeutic intervention for DACD. However, the precise mechanism underlying its therapeutic effects are not fully elucidated. Given that imbalances in copper homeostasis and cuproptosis are associated with various neurodegenerative disorders and diabetic myocardial damage, we hypothesize a role for cuproptosis in the pathogenesis of DACD. We further propose that therapeutic peripheral mitochondrial transplantation may ameliorate DACD by reducing processes of cuproptosis. In this research, the study delved into the expression levels of cuproptosis-associated proteins FDX1, LIAS, and DLAT, as well as the copper content in both type 2 diabetes mellitus (T2DM) mice and primary neuronal cells exposed to high glucose and palmitic acid (HG/Pal). Furthermore, the cognitive capabilities of the mice were evaluated using a series of behavioral tests. The findings revealed that in primary neurons exposed to HG/Pal, the expression of copper levels was elevated, and the levels of FDX1, LIAS, and DLAT were reduced. Post-transplantation of platelet-derived mitochondria (Mito-Plt), a significant reversal of these biomarkers was noted, coincident with an improvement in cognitive deficits in T2DM mice. Significantly, the cuproptosis agonist elesclomol (ES) aggravated these alterations. In summary, the findings collectively suggest a causal connection between DACD and the development of cuproptosis in neurons. The use of exogenous Mito-Plt presents a promising therapeutic approach, capable of rescuing neurons from cuproptosis and thereby potentially alleviating DACD.http://www.sciencedirect.com/science/article/pii/S0361923025000577CuproptosisMitochondrial transplantationDiabetes-associated cognitive dysfunction (DACD) |
| spellingShingle | Juan Hu Qiao Li Shiqiu Jiang Yingying Deng Lan Yang Mengyu Du Shuxuan He Fuxing Xu Chaoying Yan Wei Gao Yansong Li Yaomin Zhu Peripheral mitochondrial transplantation alleviates diabetes-associated cognitive dysfunction by suppressing cuproptosis Brain Research Bulletin Cuproptosis Mitochondrial transplantation Diabetes-associated cognitive dysfunction (DACD) |
| title | Peripheral mitochondrial transplantation alleviates diabetes-associated cognitive dysfunction by suppressing cuproptosis |
| title_full | Peripheral mitochondrial transplantation alleviates diabetes-associated cognitive dysfunction by suppressing cuproptosis |
| title_fullStr | Peripheral mitochondrial transplantation alleviates diabetes-associated cognitive dysfunction by suppressing cuproptosis |
| title_full_unstemmed | Peripheral mitochondrial transplantation alleviates diabetes-associated cognitive dysfunction by suppressing cuproptosis |
| title_short | Peripheral mitochondrial transplantation alleviates diabetes-associated cognitive dysfunction by suppressing cuproptosis |
| title_sort | peripheral mitochondrial transplantation alleviates diabetes associated cognitive dysfunction by suppressing cuproptosis |
| topic | Cuproptosis Mitochondrial transplantation Diabetes-associated cognitive dysfunction (DACD) |
| url | http://www.sciencedirect.com/science/article/pii/S0361923025000577 |
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