华中科技大学同济医学院张果、美国爱因斯坦医学院蔡东升等研究人员合作发现，抑制小胶质细胞Tak1能够逆转长期肥胖相关的脑血管功能障碍。2020年5月25日，《自然—神经科学》在线发表了这一成果。

Title: Reversal of prolonged obesity-associated cerebrovascular dysfunction by inhibiting microglial Tak1

Author: Qing Shen, Zhuo Chen, Faming Zhao, Susu Pan, Tingting Zhang, Xueer Cheng, Lei Zhang, Shanshan Zhang, Junxia Qi, Juxue Li, Dongsheng Cai, Guo Zhang

Issue&Volume: 2020-05-25

Abstract: Prolonged obesity is associated with cerebrovascular dysfunction; however, the underlying mechanisms remain largely unclear. In the present study, using a prolonged obesity mouse model that suffers from basilar artery (BA) abnormalities, we find that microglial transforming growth factor β-activated kinase 1 (Tak1) is over-activated in the brainstem. Both pharmacological inhibition primarily in the brainstem and genetic microglia-selective deletion of Tak1 ameliorated BA vascular dysfunction. Conversely, microglia-specific activation of Tak1 in the brainstem was sufficient to cause an impairment in BA function in chow-fed mice. Mechanistically, Tak1 activation leads to increased interleukin-18 (IL-18) production, whereas blockade of IL-18 receptor in the brain helped protect against cerebrovascular dysfunction despite prolonged obesity. Microglia-selective deletion of Tak1 also protects against ischemic stroke in prolonged obesity. Taken together, these findings provide evidence that microglial Tak1 in the brain, and particularly the brainstem, contributes to the pathogenesis of obesity-associated cerebrovascular dysfunction.

DOI: 10.1038/s41593-020-0642-6

Source: https://www.nature.com/articles/s41593-020-0642-6