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Neuronal CCL2 responds to hyperglycaemia and contributes to anxiety disorders in the context of diabetes

文献类型：期刊论文

作者Pan, Kaijun1,5; Gao, Yanan1,5; Zong, Haichao5; Zhang, Yongmei5; Qi, Yingbei5; Wang, Hanlin5; Chen, Wengang1,5; Zhou, Ting5; Zhao, Jinwen5; Yin, Tao5
刊名NATURE METABOLISM
出版日期2025-05-01
卷号7期号:5页码:39
DOI10.1038/s42255-025-01281-2
通讯作者Zang, Yi(yzang@lglab.ac.cn) ; Li, Jia(jli@simm.ac.cn)
英文摘要Anxiety disorders are frequently observed in patients with diabetes and can be associated with several diabetes-related factors. Here we determine that hyperglycaemia is a major cause for the development of anxiety disorders through a C-C motif chemokine ligand 2 (CCL2)-dependent mechanism. By adopting complementary strategies, we demonstrate that neuron-specific (not peripheral) CCL2 mediates anxiety-like behaviours in streptozotocin-induced diabetic mice. Mechanistically, high glucose levels induce Tonicity-responsive enhancer-binding protein (TonEBP)-dependent CCL2 expression in neurons, leading to microglial activation in a paracrine manner. Similar phenotypes are also observed in high-fat diet-induced diabetic mice, independent of insulin signalling. Furthermore, we reveal that neuronal CCL2 in the medial prefrontal cortex and ventral hippocampus synergistically induces anxiety-like behaviours, indicating brain region-specific effects on diabetic mice. Finally, we confirm that the neuronal TonEBP-CCL2 axis and inflammatory pathways are both upregulated in patients with diabetes. Conclusively, neuronal CCL2 is specifically increased by hyperglycaemia and contributes to anxiety disorders, providing additional insights into the link between diabetes and mental health disorders.
WOS关键词ENHANCER-BINDING PROTEIN ; BLOOD-BRAIN-BARRIER ; MONOCYTE CHEMOATTRACTANT PROTEIN-1 ; TONICITY-INDUCED EXPRESSION ; TRANSCRIPTION FACTOR TONEBP ; CELLULAR-DISTRIBUTION ; OSMOPROTECTIVE GENES ; GLYCEMIC CONTROL ; MOOD DISORDERS ; TYPE-2
资助项目National Natural Science Foundation of China (National Science Foundation of China)[21937002] ; National Natural Science Foundation of China[2018ZX09711002-007-002] ; National Science & Technology Major Project 'Key New Drug Creation and Manufacturing Program' grant[2021000003] ; Shanghai Municipal Commission of Science and Technology[19JC1416300] ; Shanghai Science and Technology Development Fund
WOS研究方向Endocrinology & Metabolism
语种英语
WOS记录号WOS:001482122500001
出版者NATURE PORTFOLIO
源URL[http://119.78.100.183/handle/2S10ELR8/317602]  
专题中国科学院上海药物研究所
通讯作者Zang, Yi; Li, Jia
作者单位1.China Pharmaceut Univ, Metab Dis Res Ctr, Jiangsu Key Lab Drug Screening, Nanjing, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.Univ Chinese Acad Sci, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou, Peoples R China
4.Lingang Lab, Shanghai, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Pan, Kaijun,Gao, Yanan,Zong, Haichao,et al. Neuronal CCL2 responds to hyperglycaemia and contributes to anxiety disorders in the context of diabetes[J]. NATURE METABOLISM,2025,7(5):39.
APA Pan, Kaijun.,Gao, Yanan.,Zong, Haichao.,Zhang, Yongmei.,Qi, Yingbei.,...&Li, Jia.(2025).Neuronal CCL2 responds to hyperglycaemia and contributes to anxiety disorders in the context of diabetes.NATURE METABOLISM,7(5),39.
MLA Pan, Kaijun,et al."Neuronal CCL2 responds to hyperglycaemia and contributes to anxiety disorders in the context of diabetes".NATURE METABOLISM 7.5(2025):39.

入库方式： OAI收割

来源：上海药物研究所

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