Studies have demonstrated that a functional network of meningeal lymphatic vessels exists in the brain.However,it is unknown whether lymphatic vessels could also extend deep into the brain parenchyma and whether the v...Studies have demonstrated that a functional network of meningeal lymphatic vessels exists in the brain.However,it is unknown whether lymphatic vessels could also extend deep into the brain parenchyma and whether the vessels could be regulated by stressful life events.We used tissue clearing techniques,immunostaining,light-sheet whole-brain imaging,confocal imaging in thick brain sections and flow cytometry to demonstrate the existence of lymphatic vessels deep in the brain parenchyma.Chronic unpredictable mild stress or chronic corticosterone treatment was used to examine the regulation of brain lymphatic vessels by stressful events.Western blotting and coimmunoprecipitation were used to provide mechanistic insights.We demonstrated the existence of lymphatic vessels deep in the brain parenchyma and characterized their features in the cortex,cerebellum,hippocampus,midbrain,and brainstem.Furthermore,we showed that deep brain lymphatic vessels can be regulated by stressful life events.Chronic stress reduced the length and areas of lymphatic vessels in the hippocampus and thalamus but increased the diameter of lymphatic vessels in the amygdala.No changes were observed in prefrontal cortex,lateral habenula,or dorsal raphe nucleus.Chronic corticosterone treatment reduced lymphatic endothelial cell markers in the hippocampus.Mechanistically,chronic stress might reduce hippocampal lymphatic vessels by down-regulating vascular endothelial growth factor C receptors and up-regulating vascular endothelial growth factor C neutralization mechanisms.Our results provide new insights into the characteristic features of deep brain lymphatic vessels,as well as their regulation by stressful life events.展开更多
Dear Editor,The ion channel transient receptor potential melastatin-like 7(TRPM7)has a serine-threonineα-kinase domain(M7CK)on its intracellular C-terminal[1,2].In cell lines,M7CK is cleaved and translocated to the n...Dear Editor,The ion channel transient receptor potential melastatin-like 7(TRPM7)has a serine-threonineα-kinase domain(M7CK)on its intracellular C-terminal[1,2].In cell lines,M7CK is cleaved and translocated to the nucleus to regulate a variety of cellular processes including cell proliferation and survival[3].In neuroblastoma cells.展开更多
Dear Editor,Following an emotionally intensive and fearful traumatic event,some individuals develop anxiety disorders such as post-traumatic stress disorder (PTSD)[1].Cognitive therapy is used as an effective therapy ...Dear Editor,Following an emotionally intensive and fearful traumatic event,some individuals develop anxiety disorders such as post-traumatic stress disorder (PTSD)[1].Cognitive therapy is used as an effective therapy to suppress fearful and/or traumatic memories;however,it fails in almost half of the anxious patients,resulting in the return of fearful memories [2].展开更多
Learning and memory are fundamental brain functions affected by dietary and environmental factors. Magnesium is essential for maintaining normal body and brain functions. Here,
基金This work was supported by the Natural Science Foundation(NSF)of China(31970942 and 81573408 to N.A.)Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJLab,and Shanghai Center for Brain Science and Brain-Inspired Technology.
文摘Studies have demonstrated that a functional network of meningeal lymphatic vessels exists in the brain.However,it is unknown whether lymphatic vessels could also extend deep into the brain parenchyma and whether the vessels could be regulated by stressful life events.We used tissue clearing techniques,immunostaining,light-sheet whole-brain imaging,confocal imaging in thick brain sections and flow cytometry to demonstrate the existence of lymphatic vessels deep in the brain parenchyma.Chronic unpredictable mild stress or chronic corticosterone treatment was used to examine the regulation of brain lymphatic vessels by stressful events.Western blotting and coimmunoprecipitation were used to provide mechanistic insights.We demonstrated the existence of lymphatic vessels deep in the brain parenchyma and characterized their features in the cortex,cerebellum,hippocampus,midbrain,and brainstem.Furthermore,we showed that deep brain lymphatic vessels can be regulated by stressful life events.Chronic stress reduced the length and areas of lymphatic vessels in the hippocampus and thalamus but increased the diameter of lymphatic vessels in the amygdala.No changes were observed in prefrontal cortex,lateral habenula,or dorsal raphe nucleus.Chronic corticosterone treatment reduced lymphatic endothelial cell markers in the hippocampus.Mechanistically,chronic stress might reduce hippocampal lymphatic vessels by down-regulating vascular endothelial growth factor C receptors and up-regulating vascular endothelial growth factor C neutralization mechanisms.Our results provide new insights into the characteristic features of deep brain lymphatic vessels,as well as their regulation by stressful life events.
基金supported by the National Natural Science Foundation of China(31970942 and 81573408)the Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)the ZJ Lab,and Shanghai Center for Brain Science and Brain-Inspired Technology.
文摘Dear Editor,The ion channel transient receptor potential melastatin-like 7(TRPM7)has a serine-threonineα-kinase domain(M7CK)on its intracellular C-terminal[1,2].In cell lines,M7CK is cleaved and translocated to the nucleus to regulate a variety of cellular processes including cell proliferation and survival[3].In neuroblastoma cells.
基金supported by grants from the National Natural Science Foundation of China (31970942 and 81573408)a Fudan University-Shanghai Institute of Materia Medica Chinese Academy of Science joint grant (FU-SIMM20174015)+2 种基金a Shanghai Municipal Science and Technology Major Project (2018SHZDZX01)ZJLaba Natural Science Foundation of Shanghai grant(16ZR1403200)。
文摘Dear Editor,Following an emotionally intensive and fearful traumatic event,some individuals develop anxiety disorders such as post-traumatic stress disorder (PTSD)[1].Cognitive therapy is used as an effective therapy to suppress fearful and/or traumatic memories;however,it fails in almost half of the anxious patients,resulting in the return of fearful memories [2].
文摘Learning and memory are fundamental brain functions affected by dietary and environmental factors. Magnesium is essential for maintaining normal body and brain functions. Here,
