Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-i...Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet known.In the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of action.In vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial polarization.Lipopolysaccharide,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were administered.RNA-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of dexamethasone.The Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our hypothesis.High-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain injury.Thus dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in vivo.Glucocorticoid receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain injury.Additionally,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is the GR/JAK1/STAT3 pathway.Overactivation of glucocorticoid receptor by high-dose dexamethasone reduced the expression of M2 microglia,which plays an antiinflammatory role.In contrast,inhibiting the activation of glucocorticoid receptor reduced the number of apoptotic glia and neurons and decreased the loss of dendritic spines after traumatic brain injury.Dexamethasone may exe rt its neurotoxic effects by inhibiting M2 microglia through the GR/JAK1/STAT3 signaling pathway.展开更多
Objective: This study explored the effects of Health Qigong exercise on depression and anxiety in patients withParkinson’s disease (PD). Methods: A total of 42 volunteers who met the inclusion criteria were recruited...Objective: This study explored the effects of Health Qigong exercise on depression and anxiety in patients withParkinson’s disease (PD). Methods: A total of 42 volunteers who met the inclusion criteria were recruited andrandomly allocated into the experimental group and the control group. The experimental group carried out60-minute sessions of Health Qigong exercise five times a week for 12 weeks while the control group did not performany regular physical exercise. Data on cognitive impairment, psychomotor retardation, somatic anxiety,weight loss and sleep disorders, the sum score of the 17-item Hamilton Depression Rating Scale (HDRS-17), stateanxiety, trait anxiety as well as the sum score of the State-Trait Anxiety Inventory (STAI) were collected for threerepeated measurements (baseline, 6, and 12 weeks). Results: Significant differences were observed in depression,state anxiety, trait anxiety, cognitive impairment and psychomotor retardation in the experimental group but nodifference in somatic anxiety, weight loss and sleep disorders. Conclusion: Health Qigong exercise can pose positivepsychological effects and alleviate the depression and anxiety in patients with Parkinson’s disease. It can beapplied as an accessible supplement to the existent drug treatment for PD.展开更多
基金supported by research grants from the Ningbo Science and Technology Plan Project,No.2022Z143hezuo(to BL)the National Natural Science Foundation of China,No.82201520(to XD)。
文摘Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet known.In the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of action.In vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial polarization.Lipopolysaccharide,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were administered.RNA-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of dexamethasone.The Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our hypothesis.High-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain injury.Thus dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in vivo.Glucocorticoid receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain injury.Additionally,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is the GR/JAK1/STAT3 pathway.Overactivation of glucocorticoid receptor by high-dose dexamethasone reduced the expression of M2 microglia,which plays an antiinflammatory role.In contrast,inhibiting the activation of glucocorticoid receptor reduced the number of apoptotic glia and neurons and decreased the loss of dendritic spines after traumatic brain injury.Dexamethasone may exe rt its neurotoxic effects by inhibiting M2 microglia through the GR/JAK1/STAT3 signaling pathway.
文摘Objective: This study explored the effects of Health Qigong exercise on depression and anxiety in patients withParkinson’s disease (PD). Methods: A total of 42 volunteers who met the inclusion criteria were recruited andrandomly allocated into the experimental group and the control group. The experimental group carried out60-minute sessions of Health Qigong exercise five times a week for 12 weeks while the control group did not performany regular physical exercise. Data on cognitive impairment, psychomotor retardation, somatic anxiety,weight loss and sleep disorders, the sum score of the 17-item Hamilton Depression Rating Scale (HDRS-17), stateanxiety, trait anxiety as well as the sum score of the State-Trait Anxiety Inventory (STAI) were collected for threerepeated measurements (baseline, 6, and 12 weeks). Results: Significant differences were observed in depression,state anxiety, trait anxiety, cognitive impairment and psychomotor retardation in the experimental group but nodifference in somatic anxiety, weight loss and sleep disorders. Conclusion: Health Qigong exercise can pose positivepsychological effects and alleviate the depression and anxiety in patients with Parkinson’s disease. It can beapplied as an accessible supplement to the existent drug treatment for PD.
