AIM:To investigate the activity of vesicular glutamate transporter-3(VGLUT3) in a visceral hyperalgesia rat model of irritable bowel syndrome,and the role of mast cells(MCs).METHODS:Transient intestinal infection was ...AIM:To investigate the activity of vesicular glutamate transporter-3(VGLUT3) in a visceral hyperalgesia rat model of irritable bowel syndrome,and the role of mast cells(MCs).METHODS:Transient intestinal infection was inducedby oral administration of Trichinella spiralis larvae in rats.On the 100th day post-infection(PI),the rats were divided into an acute cold restraint stress(ACRS)group and a non-stressed group.Age-matched untreated rats served as controls.The abdominal withdrawal reflex was used to measure the visceromotor response to colorectal distension(CRD).The expression levels of VGLUT3 in peripheral and central neurons were analyzed by immunofluorescence and western blotting.RESULTS:VGLUT3 expression in the L6S1 dorsal root ganglion cells was significantly higher in the PI group than in the control group(0.32±0.009 vs0.22±0.008,P<0.01),and there was no significant difference in the expression of VGLUT3 between MCdeficient rats and their normal wild-type littermates.Immunofluorescence showed that the expression levels of VGLUT3 in PI+ACRS rats were enhanced in the prefrontal cortex of the brain compared with the control group.CONCLUSION:VGLUT3 is involved in the pathogenesis of visceral hyperalgesia.Coexpression of c-fos,5-hydroxytryptamine and VGLUT3 after CRD was observed in associated neuronal pathways.Increased VGLUT3 induced by transient intestinal infection was found in peripheral nerves,and was independent of MCs.Moreover,the expression of VGLUT3 was enhanced in the prefrontal cortex in rats with induced infection and stress.展开更多
Activation of inflammatory responses regulates the transmission of pain pathways through an integrated network in the peripheral and central nervous systems.The immunopotentiator thymosin alpha-1(Tal)has recently been...Activation of inflammatory responses regulates the transmission of pain pathways through an integrated network in the peripheral and central nervous systems.The immunopotentiator thymosin alpha-1(Tal)has recently been reported to have anti-inflammatory and neuroprotective functions in rodents.However,how Tα1 affects inflammatory pain remains unclear.In the present study,intraperitoneal injection of Tal attenuated complete Freund's adjuvant(CFA)-induced pain hypersensitivity,and decreased the up-regulation of pro-inflammatory cytokines(TNF-α,IL-1β,and IL-6)in inflamed skin and the spinal cord.We found that CFA-induced peripheral inflammation evoked strong microglial activation,but the effect was reversed by Tα1.Notably,Tα1 reversed the CFA-induced up-regulation of vesicular glutamate transporter(VGLUT)and down-regulated the vesicular γ-aminobutyric acid transporter(VGAT)in the spinal cord.Taken together,these results suggest that Tα1 plays a therapeutic role in inflammatory pain and in the modulation of microgliainduced pro-inflammatory cytokine production in addition to mediation of VGLUT and VGAT expression in the spinal cord.展开更多
Background:Depression affects approximately 5% of elderly people and its etiology might be related to chronic stress exposure during neurodevelopmental periods.In this study,we examined the effects of adolescent chron...Background:Depression affects approximately 5% of elderly people and its etiology might be related to chronic stress exposure during neurodevelopmental periods.In this study,we examined the effects of adolescent chronic social stress in aged mice on depressive behaviors and the excitatory-inhibitory (E/I) balance in stress-sensitive regions of the brain.Methods:Sixty-four adolescent,male C57BL/6 mice were randomly assigned to either the 7-week (from post-natal days 29 to 77) social instability stress (stress group,n =32) or normal housing conditions (control group,n =32).At 15 months of age,16 mice were randomly selected from each group for a series of behavioral tests,including two depression-related tasks (the sucrose preference test and the tail suspension test).Three days following the last behavioral test,eight mice were randomly selected from each group for immunohistochemical analyses to measure the cell density of parvalbumin (PV+)-and calretinin (CR+)-positive gamma-aminobutyric-acid (GABA)ergic inhibitory inter-neurons,and the expression levels of vesicular transporters of glutamate-1 (VGIuT1) and vesicular GABA transporter (VGAT) in three stress-sensitive regions of the brain (the medial pre-frontal cortex [mPFC],hippocampus,and amygdala).Results:Behaviorally,compared with the control group,adolescent chronic stress increased depression-like behaviors as shown in decreased sucrose preference (54.96 ± 1.97% vs.43.11 ± 2.85%,t(22)=3.417,P =0.003) and reduced latency to immobility in the tail suspension test (92.77 ± 25.08 s vs.33.14 ± 5.95 s,t(25)=2.394,P =0.025),but did not affect anxiety-like behaviors and pre-pulse inhibition.At the neurobiologic level,adolescent stress down-regulated PV+,not CR+,inter-neuron density in the mPFC (F(1,39)=19.30,P < 0.001),and hippocampus (F(1,42)=5.823,P =0.020) and altered the CR+,not PV+,inter-neuron density in the amygdala (F(1,28)=23.16,P < 0.001).The VGluT1/VGAT ratio was decreased in all three regions (all F > 10.09,all P < 0.004),which suggests stress-induced hypoexcitability in these regions.Conclusions:Chronic stress during adolescence increased depression-like behaviors in aged mice,which may be associated with the F/I imbalance in stress-sensitive brain regions.展开更多
基金Supported by National Natural Science Foundation of China,No.30940033the Doctoral Program of Higher Education of China
文摘AIM:To investigate the activity of vesicular glutamate transporter-3(VGLUT3) in a visceral hyperalgesia rat model of irritable bowel syndrome,and the role of mast cells(MCs).METHODS:Transient intestinal infection was inducedby oral administration of Trichinella spiralis larvae in rats.On the 100th day post-infection(PI),the rats were divided into an acute cold restraint stress(ACRS)group and a non-stressed group.Age-matched untreated rats served as controls.The abdominal withdrawal reflex was used to measure the visceromotor response to colorectal distension(CRD).The expression levels of VGLUT3 in peripheral and central neurons were analyzed by immunofluorescence and western blotting.RESULTS:VGLUT3 expression in the L6S1 dorsal root ganglion cells was significantly higher in the PI group than in the control group(0.32±0.009 vs0.22±0.008,P<0.01),and there was no significant difference in the expression of VGLUT3 between MCdeficient rats and their normal wild-type littermates.Immunofluorescence showed that the expression levels of VGLUT3 in PI+ACRS rats were enhanced in the prefrontal cortex of the brain compared with the control group.CONCLUSION:VGLUT3 is involved in the pathogenesis of visceral hyperalgesia.Coexpression of c-fos,5-hydroxytryptamine and VGLUT3 after CRD was observed in associated neuronal pathways.Increased VGLUT3 induced by transient intestinal infection was found in peripheral nerves,and was independent of MCs.Moreover,the expression of VGLUT3 was enhanced in the prefrontal cortex in rats with induced infection and stress.
基金supported by the Foundation for Distinguished Young Talents in Higher Education of Guangdong Province, China (2016KQNCX019 and 2016KQNCX027)the National Natural Science Foundation of China (31571041)+1 种基金the Guangdong Provincial Department of Education Innovating Strong National Engineering Major Project (2014GKXM031)Guangdong Provincial Universities and Colleges Pearl River Scholar Funded Scheme (2016)
文摘Activation of inflammatory responses regulates the transmission of pain pathways through an integrated network in the peripheral and central nervous systems.The immunopotentiator thymosin alpha-1(Tal)has recently been reported to have anti-inflammatory and neuroprotective functions in rodents.However,how Tα1 affects inflammatory pain remains unclear.In the present study,intraperitoneal injection of Tal attenuated complete Freund's adjuvant(CFA)-induced pain hypersensitivity,and decreased the up-regulation of pro-inflammatory cytokines(TNF-α,IL-1β,and IL-6)in inflamed skin and the spinal cord.We found that CFA-induced peripheral inflammation evoked strong microglial activation,but the effect was reversed by Tα1.Notably,Tα1 reversed the CFA-induced up-regulation of vesicular glutamate transporter(VGLUT)and down-regulated the vesicular γ-aminobutyric acid transporter(VGAT)in the spinal cord.Taken together,these results suggest that Tα1 plays a therapeutic role in inflammatory pain and in the modulation of microgliainduced pro-inflammatory cytokine production in addition to mediation of VGLUT and VGAT expression in the spinal cord.
基金grants from the National Natural Science Foundation of China (Nos. 81630031, 81401129, 81571321, and 81571312)the Beijing Brain Project (No.Z171100000117016), the National Key Basic Research Program of China (973 program+1 种基金No. 2015CB856401)the Peking University Medicine Seed Fund for Interdisciplinary Research (No. BMU2017MX021).
文摘Background:Depression affects approximately 5% of elderly people and its etiology might be related to chronic stress exposure during neurodevelopmental periods.In this study,we examined the effects of adolescent chronic social stress in aged mice on depressive behaviors and the excitatory-inhibitory (E/I) balance in stress-sensitive regions of the brain.Methods:Sixty-four adolescent,male C57BL/6 mice were randomly assigned to either the 7-week (from post-natal days 29 to 77) social instability stress (stress group,n =32) or normal housing conditions (control group,n =32).At 15 months of age,16 mice were randomly selected from each group for a series of behavioral tests,including two depression-related tasks (the sucrose preference test and the tail suspension test).Three days following the last behavioral test,eight mice were randomly selected from each group for immunohistochemical analyses to measure the cell density of parvalbumin (PV+)-and calretinin (CR+)-positive gamma-aminobutyric-acid (GABA)ergic inhibitory inter-neurons,and the expression levels of vesicular transporters of glutamate-1 (VGIuT1) and vesicular GABA transporter (VGAT) in three stress-sensitive regions of the brain (the medial pre-frontal cortex [mPFC],hippocampus,and amygdala).Results:Behaviorally,compared with the control group,adolescent chronic stress increased depression-like behaviors as shown in decreased sucrose preference (54.96 ± 1.97% vs.43.11 ± 2.85%,t(22)=3.417,P =0.003) and reduced latency to immobility in the tail suspension test (92.77 ± 25.08 s vs.33.14 ± 5.95 s,t(25)=2.394,P =0.025),but did not affect anxiety-like behaviors and pre-pulse inhibition.At the neurobiologic level,adolescent stress down-regulated PV+,not CR+,inter-neuron density in the mPFC (F(1,39)=19.30,P < 0.001),and hippocampus (F(1,42)=5.823,P =0.020) and altered the CR+,not PV+,inter-neuron density in the amygdala (F(1,28)=23.16,P < 0.001).The VGluT1/VGAT ratio was decreased in all three regions (all F > 10.09,all P < 0.004),which suggests stress-induced hypoexcitability in these regions.Conclusions:Chronic stress during adolescence increased depression-like behaviors in aged mice,which may be associated with the F/I imbalance in stress-sensitive brain regions.
