OBJECTIVE Chronic stress is one of the important factors in the development of many mental and neurological diseases,and cause damage to the central nervous system,affect animal emotions and damage the immune function...OBJECTIVE Chronic stress is one of the important factors in the development of many mental and neurological diseases,and cause damage to the central nervous system,affect animal emotions and damage the immune function of the body.The purpose of this study was to investigate the effects of LW-AFC which extracting from traditional Chinese medicine prescription Liuwei Dihuang decoctionon the anxiety-like behaviorand immune dysfunction abnormalities caused by chronic stress,and whether immune intervention affect the action of LW-AFC.METHODS Male BALB/c mice were subcutaneously injected with corticosterone(25 mg·kg^-1)for 28 d to establish a chronic stress model.Cyclophos⁃phamide(Cy,80 mg·kg^-1)was injected continuously for the initial three days,followed by once a week,LW-AFC(1.6 g·kg^-1)was given continuously for 28 d.Then investigate the emotion changes by open field and elevated plus maze tests,and detected the lymphocyte proliferation,lymphocyte subsets in peripheral blood,microglia and astrocyte expression,and inflammatory cytokines in peripheral blood and brain tissue.RESULTS The mice showed obvious depressive-like behaviorafter 28 d of continuous corticosterone injection.LW-AFC could significantly improve the anxietybehavior induced by corticosterone injection,but LW-AFC could not improve the anxietybehavior of mice by Cy intervention.The expression of glial cells in hippocampus of corticosterone-induced mice showed an upward trend,and the activation of microglia and astrocytes have significantly increase in corticosterone and Cy injected mice.LW-AFC significantly decreased the activation of microglia and astrocytes in corticosterone-induced mice with Cy intervention.This suggested that LW-AFC can reduce the damage of stress on the immune function of central nervous system under immunosuppres⁃sive state.Furthermore,LW-AFC could significantly up-regulate the proliferation of splenic lymphocyte stimulated by LPS and ConA,up-regulate the proportion of CD3+CD8+cells,reduce the proportion of CD4+/CD8+cells,decrease the secretion of inflammatory factors IL-6 and MCP-1 in plasma,and increase the level of anti-inflammatory factor IL-10 in plasma of mice induced by chronic corticosteroneinjection.While LW-AFC could promote the inflammatory factors TNF-α and IL-6in plasma,inhibit the secretion of anti-inflammatory factor IL-10 and inflammatory cytokine MCP-1 in hippocampus of corticosterone-induced mice with Cy intervention.CONCLUSION LW-AFC can improve anxiety-likebehavior induced by chronic stress,the Cy intervention affects the alleviation of anxiety-like behavior by LW-AFC as well as the regulation of immune function.The regulation of immune function might be the main way for LW-AFC to improve the function of central nervous system.展开更多
Pyridaben(PY)is a widely used organochlorine acaricide,which can be detected in the peripheral blood of pregnant women.Available evidence suggests that PY has reproductive toxicity.However,it remains uncertain whether...Pyridaben(PY)is a widely used organochlorine acaricide,which can be detected in the peripheral blood of pregnant women.Available evidence suggests that PY has reproductive toxicity.However,it remains uncertain whether prenatal PY exposure impacts neurobehavioral development in offspring.Here,we administered PY to pregnant mice at a dose of 0.5 and 5 mg kg^(-1)day^(-1)via gavage and observed anxietylike behaviors in PY offspring aged five weeks.We then integrated the metabolome and transcriptome of the offspring's brain to explore the underlying mechanism.Metabolome data indicated that the vitamin B6 metabolism pathway was significantly affected,and the pyridoxal 50-phosphate(PLP)concentration and the active form of vitamin B6 was significantly reduced.Moreover,the transcriptome data showed that both PLP generation-related Pdxk and anxiety-related Gad1 were significantly down-regulated.Meanwhile,there was a decreasing trend in the concentration of GABA in the hippocampal DG region.Next,we supplemented PLP at a dose of 20 mg kg^(-1)day^(-1)to the PY offspring via intraperitoneal injection at three weeks.We found up-regulated expression of Pdxk and Gad1 and restored anxiety-like behaviors.This study suggests that prenatal exposure to PY can disrupt vitamin B6 metabolism,reduce the concentration of PLP,down-regulate the expression levels of Pdxk and Gad1,inhibit the production of GABA,and ultimately lead to anxiety-like behaviors in offspring.展开更多
Structural plasticity is critical for the functional diversity of neurons in the brain.Experimental autoimmune encephalomyelitis(EAE)is the most commonly used model for multiple sclerosis(MS),successfully mimicking it...Structural plasticity is critical for the functional diversity of neurons in the brain.Experimental autoimmune encephalomyelitis(EAE)is the most commonly used model for multiple sclerosis(MS),successfully mimicking its key pathological features(inflammation,demyelination,axonal loss,and gliosis)and clinical symptoms(motor and non-motordysfunctions).Recentstudieshave demonstrated the importance of synaptic plasticity in EAE pathogenesis.In the present study,we investigated the features of behavioral alteration and hippocampal structural plasticity in EAE-affected mice in the early phase(11 days post-immunization,DPI)and chronic phase(28DPI).EAE-affected mice exhibited hippocampus-related behavioral dysfunction in the open field test during both early and chronic phases.Dendritic complexity was largely affected in the cornu ammonis 1(CA1)and CA3 apical and dentate gyrus(DG)subregions of the hippocampus during the chronic phase,while this effect was only noted in the CA1 apical subregion in the early phase.Moreover,dendritic spine density was reduced in the hippocampal CA1 and CA3 apical/basal and DG subregions in the early phase of EAE,but only reduced in the DG subregion during the chronic phase.Furthermore,mRNA levels of proinflammatory cytokines(Il1β,Tnfα,and Ifnγ)and glial cell markers(Gfap and Cd68)were significantly increased,whereas the expression of activity-regulated cytoskeletonassociated protein(ARC)was reduced during the chronic phase.Similarly,exposure to the aforementioned cytokines in primary cultures of hippocampal neurons reduced dendritic complexity and ARC expression.Primary cultures of hippocampal neurons also showed significantly reduced extracellular signal-regulated kinase(ERK)phosphorylation upon treatment with proinflammatory cytokines.Collectively,these results suggest that autoimmune neuroinflammation alters structural plasticity in the hippocampus,possibly through the ERK-ARC pathway,indicating that this alteration may be associated with hippocampal dysfunctions in EAE.展开更多
BACKGROUND Acute pancreatitis(AP)and recurring AP are serious health care problems causing excruciating pain and potentially lethal outcomes due to sepsis.The validated caerulein-(CAE)induced mouse model of acute/recu...BACKGROUND Acute pancreatitis(AP)and recurring AP are serious health care problems causing excruciating pain and potentially lethal outcomes due to sepsis.The validated caerulein-(CAE)induced mouse model of acute/recurring AP produces secondary persistent hypersensitivity and anxiety-like behavioral changes for study.AIM To determine efficacy of acetyl-L-carnitine(ALC)to reduce pain-related behaviors and brain microglial activation along the pain circuitry in CAE-pancreatitis.METHODS Pancreatitis was induced with 6 hly intraperitoneal(i.p.)injections of CAE(50μg/kg),3 d a week for 6 wk in male C57BL/6J mice.Starting in week 4,mice received either vehicle or ALC until experiment’s end.Mechanical hypersensitivity was assessed with von Frey filaments.Heat hypersensitivity was determined with the hotplate test.Anxiety-like behavior was tested in week 6 using elevated plus maze and open field tests.Microglial activation in brain was quantified histologically by immunostaining for ionized calcium-binding adaptor molecule 1(Iba1).RESULTS Mice with CAE-induced pancreatitis had significantly reduced mechanical withdrawal thresholds and heat response latencies,indicating ongoing pain.Treatment with ALC attenuated inflammation-induced hypersensitivity,but hypersensitivity due to abdominal wall injury caused by repeated intraperitoneal injections persisted.Animals with pancreatitis displayed spontaneous anxiety-like behavior in the elevated plus maze compared to controls.Treatment with ALC resulted in increased numbers of rearing activity events,but time spent in“safety”was not changed.After all the abdominal injections,pancreata were translucent if excised at experiment’s end and opaque if excised on the subsequent day,indicative of spontaneous healing.Post mortem histopathological analysis performed on pancreas sections stained with Sirius Red and Fast Green identified wide-spread fibrosis and acinar cell atrophy in sections from mice with CAE-induced pancreatitis that was not rescued by treatment with ALC.Microglial Iba1 immunostaining was significantly increased in hippocampus,thalamus(intralaminar nuclei),hypothalamus,and amygdala of mice with CAE-induced pancreatitis compared to naïve controls but unchanged in the primary somatosensory cortex compared to naïves.CONCLUSION CAE-induced pancreatitis caused increased pain-related behaviors,pancreatic fibrosis,and brain microglial changes.ALC alleviated CAE-induced mechanical and heat hypersensitivity but not abdominal wall injury-induced hypersensitivity caused by the repeated injections.展开更多
Objective: Electroacupuncture (EA) in the treating principle of “soothing the liver and regulating the kidney” was applied to intervion the rats with post-traumatic stress disorder (PTSD), and its effect on anxiety-...Objective: Electroacupuncture (EA) in the treating principle of “soothing the liver and regulating the kidney” was applied to intervion the rats with post-traumatic stress disorder (PTSD), and its effect on anxiety-like behavior, spatial learning and memory ability, and expressions of synaptophysin (SYN) and postsynaptic dense 95 (PSD95) in hippocampus of rats were observed to explore the underlying mechanism.Methods: Twenty-four male SD rats were randomly divided into control group, model group, and EA group, with 8 rats in each group. There was no intervention in the control group. The rest 16 rats were prepared for modeling. The single-prolonged stress & shock (SPS&S) method was used to establish the PTSD models. There was no intervention in the model group after modeling. In the EA group, “Bǎihuì (百会GV20)”“ Shéntíng (神庭GV24)”“Gānshū (肝俞BL18)”“Shènshū (肾俞BL23)” were manipulated with EA stimulation, intensity 1 mA, frequency 2/100 Hz, disperse-dense wave, and treatment was performed once a day, 20 min each time, for a total of 21 days. Open field test, elevated plus maze and Morris water maze tests were used to observe the behavioral differences of rats in each group. Immunohistochemical method was used to observe the differences of positive expressions of proteins SYN and PSD95 in hippocampus.Results: In the open field test, compared with the control group, the total traveling distance, the percentage of the time spent in the central cell and the numbers of the central cells crossing in the model group were all decreased (all P < 0.05). Compared with the model group, these indicators in the EA group were significantly all increased (all P < 0.05). In the elevated plus maze test, compared with the control group, the percentages of open arm staying time and entering times in the model group were both decreased (both P < 0.05). Compared with the model group, these indicators in the EA group were both significantly increased (both P < 0.05). The results of Morris water maze test showed that compared with the control group, the escape latency time and travelled distance of rats in the model group were all increased from day1 to day 4 (all P < 0.05), and the percentage of staying time in the target quadrant was decreased (P < 0.05). Compared with the model group, the escape latency time and travelled distance of EA group were both significantly shortened (both P < 0.05), and the percentage of staying time in the target quadrant was significantly increased (P < 0.05). The immunohistochemical results showed that, compared with the control group, the positive expressions of SYN and PSD95 in the hippocampus of the model group were significantly down-regulated (both P < 0.05). Compared with the model group, the positive expressions of SYN and PSD95 in the hippocampus of the EA group were significantly up-regulated (both P < 0.05).Conclusions: EA in the treating principle of “soothing the liver and regulating the kidney” can effectively relieve anxiety-like behavior and improve spatial learning and memory ability of rats with PTSD, and the mechanism is related to the up-regulation of the expressions of SYN and PSD95 in the hippocampus.展开更多
Background:The effectiveness of acupuncture for insomnia and insomnia-related anxiety and depression has been widely investigated in clinical trials.However,whether higher dosage(more frequent)acupuncture can bring gr...Background:The effectiveness of acupuncture for insomnia and insomnia-related anxiety and depression has been widely investigated in clinical trials.However,whether higher dosage(more frequent)acupuncture can bring greater responses(a greater size of effect)is less understood.Objective:This study is designed to investigate whether a five-times weekly(5 Ts/w)electroacupuncture(EA)treatment is better than a three-times weekly(3 Ts/w)EA in alleviating sleep deprivation,and sleep disturbance-induced cognitive dysfunctions and negative emotions in rats through four various behavioral te sts.Methods:Forty-six male Sprague-Dawley rats were randomly divided into control group(n=10),model group(n=12),EA-3 Ts/w group(n=12),and EA-5 Ts/w group(n=12).Except for the control group,the other three groups were established as chronic sleep deprivation models via the modified multi-platform water environment methodology.Then,rats in both EA-3 Ts/w group and EA-5 Ts/w group received corresponding dosage of EA therapy,respectively.After modeling and interventions,all four groups received four behavioral tests as follows:(1)sleep behavioral monitoring and evaluation was achieved by Comprehensive Lab Animal Monitoring System(CLAMS).(2)Cognitive functions were assessed by Novel Object Recognition(NOR)test.(3)Depressive-like behaviors was evaluated by Open-Field(OF)test.(4)Anxietylike behaviors was appraised by Elevated Plus-Maze(EPM)test.After finishing the behavioral tests,the hippocampus of each rat was removed and its synaptic structure changes were observed under electron microscope.Results:(1)CLAMS:two EA groups derived more sleep time within 24 h than the model group(both P<0.05),and no statistical differences was found between these two EA groups(P>0.05).(2)NOR test:NOR ratio in the EA-3 Ts/w group was higher than that of the model group(P<0.05)but lower than that of either the control group(P<0.05)or the EA-5 Ts/w group(P<0.05).(3)OF test:the difference of horizontal movements between the EA-3 Ts/w group and the EA-5 Ts/w group was not significant(P>0.05),although both of them were lower than that of the control group(both P<0.05)but higher than that of the model group(P<0.05).(4)EPM test:no significant decline of open-arm total time(OT)was found in EA-3 Ts/w group(P>0.05)but was found in both the model group(P<0.05)and the EA-5 Ts/w group(P<0.05)compared to the control group.Conclusion:(1)Five-week EA treatment can partially mitigate cognitive dysfunctions,anxiety-like behaviors,and depressive behaviors in rats with sleep deprivation,and this effect might be associated with the repairs on mitochondrial damage in hippocampal neurons.(2)There is insufficient evidence supporting 3 Ts/w EA treatment is less effective than 5 Ts/w EA treatment in mitigating sleep deprivation symptoms and depressive behaviors induced by sleep deprivation among rats.(3)5 Ts/w EA treatment might be more effective than 3 Ts/w EA treatment in attenuating sleep deprivation-induced cognitive impairments while it might further increase rat’s anxiety-like behaviors at the same time.展开更多
基金National Natural Science Foundation of China(81473191)National Key Research and Development Program(2016YFC1306300)
文摘OBJECTIVE Chronic stress is one of the important factors in the development of many mental and neurological diseases,and cause damage to the central nervous system,affect animal emotions and damage the immune function of the body.The purpose of this study was to investigate the effects of LW-AFC which extracting from traditional Chinese medicine prescription Liuwei Dihuang decoctionon the anxiety-like behaviorand immune dysfunction abnormalities caused by chronic stress,and whether immune intervention affect the action of LW-AFC.METHODS Male BALB/c mice were subcutaneously injected with corticosterone(25 mg·kg^-1)for 28 d to establish a chronic stress model.Cyclophos⁃phamide(Cy,80 mg·kg^-1)was injected continuously for the initial three days,followed by once a week,LW-AFC(1.6 g·kg^-1)was given continuously for 28 d.Then investigate the emotion changes by open field and elevated plus maze tests,and detected the lymphocyte proliferation,lymphocyte subsets in peripheral blood,microglia and astrocyte expression,and inflammatory cytokines in peripheral blood and brain tissue.RESULTS The mice showed obvious depressive-like behaviorafter 28 d of continuous corticosterone injection.LW-AFC could significantly improve the anxietybehavior induced by corticosterone injection,but LW-AFC could not improve the anxietybehavior of mice by Cy intervention.The expression of glial cells in hippocampus of corticosterone-induced mice showed an upward trend,and the activation of microglia and astrocytes have significantly increase in corticosterone and Cy injected mice.LW-AFC significantly decreased the activation of microglia and astrocytes in corticosterone-induced mice with Cy intervention.This suggested that LW-AFC can reduce the damage of stress on the immune function of central nervous system under immunosuppres⁃sive state.Furthermore,LW-AFC could significantly up-regulate the proliferation of splenic lymphocyte stimulated by LPS and ConA,up-regulate the proportion of CD3+CD8+cells,reduce the proportion of CD4+/CD8+cells,decrease the secretion of inflammatory factors IL-6 and MCP-1 in plasma,and increase the level of anti-inflammatory factor IL-10 in plasma of mice induced by chronic corticosteroneinjection.While LW-AFC could promote the inflammatory factors TNF-α and IL-6in plasma,inhibit the secretion of anti-inflammatory factor IL-10 and inflammatory cytokine MCP-1 in hippocampus of corticosterone-induced mice with Cy intervention.CONCLUSION LW-AFC can improve anxiety-likebehavior induced by chronic stress,the Cy intervention affects the alleviation of anxiety-like behavior by LW-AFC as well as the regulation of immune function.The regulation of immune function might be the main way for LW-AFC to improve the function of central nervous system.
基金supported by the National Key R&D Program of China(grant number 2021YFC2701100 and 2021YFC2701102)China-U.S.Program for Biomedical Collaborative Research(NSFCNIH)(grant number 81961128022)+1 种基金the National Natural Science Foundation of China(grant number 81903351)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Pyridaben(PY)is a widely used organochlorine acaricide,which can be detected in the peripheral blood of pregnant women.Available evidence suggests that PY has reproductive toxicity.However,it remains uncertain whether prenatal PY exposure impacts neurobehavioral development in offspring.Here,we administered PY to pregnant mice at a dose of 0.5 and 5 mg kg^(-1)day^(-1)via gavage and observed anxietylike behaviors in PY offspring aged five weeks.We then integrated the metabolome and transcriptome of the offspring's brain to explore the underlying mechanism.Metabolome data indicated that the vitamin B6 metabolism pathway was significantly affected,and the pyridoxal 50-phosphate(PLP)concentration and the active form of vitamin B6 was significantly reduced.Moreover,the transcriptome data showed that both PLP generation-related Pdxk and anxiety-related Gad1 were significantly down-regulated.Meanwhile,there was a decreasing trend in the concentration of GABA in the hippocampal DG region.Next,we supplemented PLP at a dose of 20 mg kg^(-1)day^(-1)to the PY offspring via intraperitoneal injection at three weeks.We found up-regulated expression of Pdxk and Gad1 and restored anxiety-like behaviors.This study suggests that prenatal exposure to PY can disrupt vitamin B6 metabolism,reduce the concentration of PLP,down-regulate the expression levels of Pdxk and Gad1,inhibit the production of GABA,and ultimately lead to anxiety-like behaviors in offspring.
基金supported by the National Research Foundation (NRF)of Korea Grant funded by the Korean Government (NRF-2022R1A2C100402212RS-2023-00219517)。
文摘Structural plasticity is critical for the functional diversity of neurons in the brain.Experimental autoimmune encephalomyelitis(EAE)is the most commonly used model for multiple sclerosis(MS),successfully mimicking its key pathological features(inflammation,demyelination,axonal loss,and gliosis)and clinical symptoms(motor and non-motordysfunctions).Recentstudieshave demonstrated the importance of synaptic plasticity in EAE pathogenesis.In the present study,we investigated the features of behavioral alteration and hippocampal structural plasticity in EAE-affected mice in the early phase(11 days post-immunization,DPI)and chronic phase(28DPI).EAE-affected mice exhibited hippocampus-related behavioral dysfunction in the open field test during both early and chronic phases.Dendritic complexity was largely affected in the cornu ammonis 1(CA1)and CA3 apical and dentate gyrus(DG)subregions of the hippocampus during the chronic phase,while this effect was only noted in the CA1 apical subregion in the early phase.Moreover,dendritic spine density was reduced in the hippocampal CA1 and CA3 apical/basal and DG subregions in the early phase of EAE,but only reduced in the DG subregion during the chronic phase.Furthermore,mRNA levels of proinflammatory cytokines(Il1β,Tnfα,and Ifnγ)and glial cell markers(Gfap and Cd68)were significantly increased,whereas the expression of activity-regulated cytoskeletonassociated protein(ARC)was reduced during the chronic phase.Similarly,exposure to the aforementioned cytokines in primary cultures of hippocampal neurons reduced dendritic complexity and ARC expression.Primary cultures of hippocampal neurons also showed significantly reduced extracellular signal-regulated kinase(ERK)phosphorylation upon treatment with proinflammatory cytokines.Collectively,these results suggest that autoimmune neuroinflammation alters structural plasticity in the hippocampus,possibly through the ERK-ARC pathway,indicating that this alteration may be associated with hippocampal dysfunctions in EAE.
基金United States Department of Veterans Affairs,VA Merit Grant,No.BX002695United States National Institute of Health,No.R01AG055359,No.R01GM126181 and No.R01NS39041-15.
文摘BACKGROUND Acute pancreatitis(AP)and recurring AP are serious health care problems causing excruciating pain and potentially lethal outcomes due to sepsis.The validated caerulein-(CAE)induced mouse model of acute/recurring AP produces secondary persistent hypersensitivity and anxiety-like behavioral changes for study.AIM To determine efficacy of acetyl-L-carnitine(ALC)to reduce pain-related behaviors and brain microglial activation along the pain circuitry in CAE-pancreatitis.METHODS Pancreatitis was induced with 6 hly intraperitoneal(i.p.)injections of CAE(50μg/kg),3 d a week for 6 wk in male C57BL/6J mice.Starting in week 4,mice received either vehicle or ALC until experiment’s end.Mechanical hypersensitivity was assessed with von Frey filaments.Heat hypersensitivity was determined with the hotplate test.Anxiety-like behavior was tested in week 6 using elevated plus maze and open field tests.Microglial activation in brain was quantified histologically by immunostaining for ionized calcium-binding adaptor molecule 1(Iba1).RESULTS Mice with CAE-induced pancreatitis had significantly reduced mechanical withdrawal thresholds and heat response latencies,indicating ongoing pain.Treatment with ALC attenuated inflammation-induced hypersensitivity,but hypersensitivity due to abdominal wall injury caused by repeated intraperitoneal injections persisted.Animals with pancreatitis displayed spontaneous anxiety-like behavior in the elevated plus maze compared to controls.Treatment with ALC resulted in increased numbers of rearing activity events,but time spent in“safety”was not changed.After all the abdominal injections,pancreata were translucent if excised at experiment’s end and opaque if excised on the subsequent day,indicative of spontaneous healing.Post mortem histopathological analysis performed on pancreas sections stained with Sirius Red and Fast Green identified wide-spread fibrosis and acinar cell atrophy in sections from mice with CAE-induced pancreatitis that was not rescued by treatment with ALC.Microglial Iba1 immunostaining was significantly increased in hippocampus,thalamus(intralaminar nuclei),hypothalamus,and amygdala of mice with CAE-induced pancreatitis compared to naïve controls but unchanged in the primary somatosensory cortex compared to naïves.CONCLUSION CAE-induced pancreatitis caused increased pain-related behaviors,pancreatic fibrosis,and brain microglial changes.ALC alleviated CAE-induced mechanical and heat hypersensitivity but not abdominal wall injury-induced hypersensitivity caused by the repeated injections.
基金Supported by National Natural Science Foundation of China:81873384。
文摘Objective: Electroacupuncture (EA) in the treating principle of “soothing the liver and regulating the kidney” was applied to intervion the rats with post-traumatic stress disorder (PTSD), and its effect on anxiety-like behavior, spatial learning and memory ability, and expressions of synaptophysin (SYN) and postsynaptic dense 95 (PSD95) in hippocampus of rats were observed to explore the underlying mechanism.Methods: Twenty-four male SD rats were randomly divided into control group, model group, and EA group, with 8 rats in each group. There was no intervention in the control group. The rest 16 rats were prepared for modeling. The single-prolonged stress & shock (SPS&S) method was used to establish the PTSD models. There was no intervention in the model group after modeling. In the EA group, “Bǎihuì (百会GV20)”“ Shéntíng (神庭GV24)”“Gānshū (肝俞BL18)”“Shènshū (肾俞BL23)” were manipulated with EA stimulation, intensity 1 mA, frequency 2/100 Hz, disperse-dense wave, and treatment was performed once a day, 20 min each time, for a total of 21 days. Open field test, elevated plus maze and Morris water maze tests were used to observe the behavioral differences of rats in each group. Immunohistochemical method was used to observe the differences of positive expressions of proteins SYN and PSD95 in hippocampus.Results: In the open field test, compared with the control group, the total traveling distance, the percentage of the time spent in the central cell and the numbers of the central cells crossing in the model group were all decreased (all P < 0.05). Compared with the model group, these indicators in the EA group were significantly all increased (all P < 0.05). In the elevated plus maze test, compared with the control group, the percentages of open arm staying time and entering times in the model group were both decreased (both P < 0.05). Compared with the model group, these indicators in the EA group were both significantly increased (both P < 0.05). The results of Morris water maze test showed that compared with the control group, the escape latency time and travelled distance of rats in the model group were all increased from day1 to day 4 (all P < 0.05), and the percentage of staying time in the target quadrant was decreased (P < 0.05). Compared with the model group, the escape latency time and travelled distance of EA group were both significantly shortened (both P < 0.05), and the percentage of staying time in the target quadrant was significantly increased (P < 0.05). The immunohistochemical results showed that, compared with the control group, the positive expressions of SYN and PSD95 in the hippocampus of the model group were significantly down-regulated (both P < 0.05). Compared with the model group, the positive expressions of SYN and PSD95 in the hippocampus of the EA group were significantly up-regulated (both P < 0.05).Conclusions: EA in the treating principle of “soothing the liver and regulating the kidney” can effectively relieve anxiety-like behavior and improve spatial learning and memory ability of rats with PTSD, and the mechanism is related to the up-regulation of the expressions of SYN and PSD95 in the hippocampus.
基金Natural Science Foundation of Shanghai:No.17ZR1428100TCM Science and Technology Innovation Project of Shanghai Health and Family Planning Commission:No.ZYKC20161016+1 种基金Special Project for Clinical ResearchShanghai Municipal Health Commission:No.20174Y0009。
文摘Background:The effectiveness of acupuncture for insomnia and insomnia-related anxiety and depression has been widely investigated in clinical trials.However,whether higher dosage(more frequent)acupuncture can bring greater responses(a greater size of effect)is less understood.Objective:This study is designed to investigate whether a five-times weekly(5 Ts/w)electroacupuncture(EA)treatment is better than a three-times weekly(3 Ts/w)EA in alleviating sleep deprivation,and sleep disturbance-induced cognitive dysfunctions and negative emotions in rats through four various behavioral te sts.Methods:Forty-six male Sprague-Dawley rats were randomly divided into control group(n=10),model group(n=12),EA-3 Ts/w group(n=12),and EA-5 Ts/w group(n=12).Except for the control group,the other three groups were established as chronic sleep deprivation models via the modified multi-platform water environment methodology.Then,rats in both EA-3 Ts/w group and EA-5 Ts/w group received corresponding dosage of EA therapy,respectively.After modeling and interventions,all four groups received four behavioral tests as follows:(1)sleep behavioral monitoring and evaluation was achieved by Comprehensive Lab Animal Monitoring System(CLAMS).(2)Cognitive functions were assessed by Novel Object Recognition(NOR)test.(3)Depressive-like behaviors was evaluated by Open-Field(OF)test.(4)Anxietylike behaviors was appraised by Elevated Plus-Maze(EPM)test.After finishing the behavioral tests,the hippocampus of each rat was removed and its synaptic structure changes were observed under electron microscope.Results:(1)CLAMS:two EA groups derived more sleep time within 24 h than the model group(both P<0.05),and no statistical differences was found between these two EA groups(P>0.05).(2)NOR test:NOR ratio in the EA-3 Ts/w group was higher than that of the model group(P<0.05)but lower than that of either the control group(P<0.05)or the EA-5 Ts/w group(P<0.05).(3)OF test:the difference of horizontal movements between the EA-3 Ts/w group and the EA-5 Ts/w group was not significant(P>0.05),although both of them were lower than that of the control group(both P<0.05)but higher than that of the model group(P<0.05).(4)EPM test:no significant decline of open-arm total time(OT)was found in EA-3 Ts/w group(P>0.05)but was found in both the model group(P<0.05)and the EA-5 Ts/w group(P<0.05)compared to the control group.Conclusion:(1)Five-week EA treatment can partially mitigate cognitive dysfunctions,anxiety-like behaviors,and depressive behaviors in rats with sleep deprivation,and this effect might be associated with the repairs on mitochondrial damage in hippocampal neurons.(2)There is insufficient evidence supporting 3 Ts/w EA treatment is less effective than 5 Ts/w EA treatment in mitigating sleep deprivation symptoms and depressive behaviors induced by sleep deprivation among rats.(3)5 Ts/w EA treatment might be more effective than 3 Ts/w EA treatment in attenuating sleep deprivation-induced cognitive impairments while it might further increase rat’s anxiety-like behaviors at the same time.
