AdipoRon attenuates depression-like behavior in T2DM mice via inhibiting inflammation and regulating autophagy
Adiponectin, an adipocyte-derived adipokine, exerts anti-inflammatory effects in the brain, but its specific function in type 2 diabetes mellitus(T2DM) has not been elucidated. Based on the common physiological and pathological mechanisms of T2DM and depression, this study revealed the protective ef...
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Elsevier
2025-05-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923025001200 |
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| author | Wenyan Zhao Yahong Li Yuliang Zhou Jinying Zhao Yanyu Lu Zhipeng Xu |
| author_facet | Wenyan Zhao Yahong Li Yuliang Zhou Jinying Zhao Yanyu Lu Zhipeng Xu |
| author_sort | Wenyan Zhao |
| collection | DOAJ |
| description | Adiponectin, an adipocyte-derived adipokine, exerts anti-inflammatory effects in the brain, but its specific function in type 2 diabetes mellitus(T2DM) has not been elucidated. Based on the common physiological and pathological mechanisms of T2DM and depression, this study revealed the protective effect of AdipoRon on T2DM-related depressive behavior and its molecular biological mechanism in vivo. Our results showed that AdipoRon treatment enhanced the sucrose consumption of T2DM mice in sucrose preference experiment, reduced the immobility time in the forced swimming experiment, and increased the total movement distance and cross times in the open field experiment. AdipoRon treatment inhibited the apoptosis of hippocampal cells, increased the number of synapses in the prefrontal cortex and hippocampus, and enhanced the density of dendritic spines in CA1 region of T2DM mice. AdipoRon could reduce NLRP3, ASC and IL-1β levels in the hippocampus and prefrontal cortex, increase the ratio of p-AMPK/AMPK and decrease p-mTOR/mTOR expression in T2DM mice. Furthermore, AdipoRon treatment increased the ratio of LC3II/LC3I and the expression of AdipoR1 in the prefrontal cortex and hippocampus of T2DM mice. All of these findings support the idea that AdipoRon reduces neuroinflammation and stimulates autophagy in T2DM mice via activating the AdipoR1/AMPK/mTOR pathway. AdipoRon may be a novel therapeutic agent for T2DM complicated depression. |
| format | Article |
| id | doaj-art-e9c8023e1e504fd683f2b07d4413c7aa |
| institution | DOAJ |
| issn | 1873-2747 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj-art-e9c8023e1e504fd683f2b07d4413c7aa2025-08-20T02:50:45ZengElsevierBrain Research Bulletin1873-27472025-05-0122411130810.1016/j.brainresbull.2025.111308AdipoRon attenuates depression-like behavior in T2DM mice via inhibiting inflammation and regulating autophagyWenyan Zhao0Yahong Li1Yuliang Zhou2Jinying Zhao3Yanyu Lu4Zhipeng Xu5Department of Neuropsychology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China; Department of Neurology,Tangdu Hospital, Air Force Medical University, Xi'an, Shanxi, ChinaDepartment of Applied Psychology, South-Central Minzu University, Wuhan, Hubei, ChinaDepartment of Neuropsychology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, ChinaDepartment of Neuropsychology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, ChinaDepartment of Applied Psychology, South-Central Minzu University, Wuhan, Hubei, ChinaDepartment of Neuropsychology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China; Corresponding author.Adiponectin, an adipocyte-derived adipokine, exerts anti-inflammatory effects in the brain, but its specific function in type 2 diabetes mellitus(T2DM) has not been elucidated. Based on the common physiological and pathological mechanisms of T2DM and depression, this study revealed the protective effect of AdipoRon on T2DM-related depressive behavior and its molecular biological mechanism in vivo. Our results showed that AdipoRon treatment enhanced the sucrose consumption of T2DM mice in sucrose preference experiment, reduced the immobility time in the forced swimming experiment, and increased the total movement distance and cross times in the open field experiment. AdipoRon treatment inhibited the apoptosis of hippocampal cells, increased the number of synapses in the prefrontal cortex and hippocampus, and enhanced the density of dendritic spines in CA1 region of T2DM mice. AdipoRon could reduce NLRP3, ASC and IL-1β levels in the hippocampus and prefrontal cortex, increase the ratio of p-AMPK/AMPK and decrease p-mTOR/mTOR expression in T2DM mice. Furthermore, AdipoRon treatment increased the ratio of LC3II/LC3I and the expression of AdipoR1 in the prefrontal cortex and hippocampus of T2DM mice. All of these findings support the idea that AdipoRon reduces neuroinflammation and stimulates autophagy in T2DM mice via activating the AdipoR1/AMPK/mTOR pathway. AdipoRon may be a novel therapeutic agent for T2DM complicated depression.http://www.sciencedirect.com/science/article/pii/S0361923025001200AdipoRonNLRP3DepressionT2DMAutophagy |
| spellingShingle | Wenyan Zhao Yahong Li Yuliang Zhou Jinying Zhao Yanyu Lu Zhipeng Xu AdipoRon attenuates depression-like behavior in T2DM mice via inhibiting inflammation and regulating autophagy Brain Research Bulletin AdipoRon NLRP3 Depression T2DM Autophagy |
| title | AdipoRon attenuates depression-like behavior in T2DM mice via inhibiting inflammation and regulating autophagy |
| title_full | AdipoRon attenuates depression-like behavior in T2DM mice via inhibiting inflammation and regulating autophagy |
| title_fullStr | AdipoRon attenuates depression-like behavior in T2DM mice via inhibiting inflammation and regulating autophagy |
| title_full_unstemmed | AdipoRon attenuates depression-like behavior in T2DM mice via inhibiting inflammation and regulating autophagy |
| title_short | AdipoRon attenuates depression-like behavior in T2DM mice via inhibiting inflammation and regulating autophagy |
| title_sort | adiporon attenuates depression like behavior in t2dm mice via inhibiting inflammation and regulating autophagy |
| topic | AdipoRon NLRP3 Depression T2DM Autophagy |
| url | http://www.sciencedirect.com/science/article/pii/S0361923025001200 |
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