OBJECTIVE There is growing evidence that uridine may act as an endogenous neuromodulator with a potential signaling role in the central nervous system in addition to its function in pyrimidine metabolism.We previously...OBJECTIVE There is growing evidence that uridine may act as an endogenous neuromodulator with a potential signaling role in the central nervous system in addition to its function in pyrimidine metabolism.We previously found that acute morphine treatment significantly increased uridine release in the dorsal striatum of mice,while the mechanism involved in morphine-induced uridine release and the role of uridine in morphine-induced neurobehavioral changes have not been understood.METHODS Uridine release in the dorsal striatum of mice was assessed by in vivo microdialysis coupled with high performance liquid chromatography(HPLC) after morphine treatment.Western blotting and immunofluorescence were used to evaluate the expression of uridine-related proteins.Morphine-induced neurobehavioral changes were assessed by locomotor activity,behavioral sensitization and conditioned place preference(CPP)test.The expression of NT5E,an extracellular enzyme involved in formation of nucleosides,including uridine,was specifically knocked down in the dorsal striatum of mice using adeno-associated virus(AAV)-mediated short hairpin RNA(shRNA).RESULTS Both acute and chronic morphine administration significantly increased uridine release in the dorsal striatum,and this was associated with upregulation of NT5E but not other uridine-related proteins.Inhibition of NT5E with APCP or shRNA markedly inhibited morphine-induced uridine release in the dorsal striatum and related neurobehavioral changes,including hyperlocomotor activity,behavioral sensitization and CPP.CONCLUSION The present study increases our understanding of the contribution of NT5E in regulating morphine-induced neurobehavioral changes,at least as related to uridine,and suggests that NT5E may be a novel therapeutic target to manage morphine abuse.展开更多
Objective:To investigate the effect of Nigella sativa oil on cardiomyopathy and neurobehavioral changes induced by doxorubicin in mice.Methods:Swiss strain of albino female mice were divided into 6 groups of 5 animals...Objective:To investigate the effect of Nigella sativa oil on cardiomyopathy and neurobehavioral changes induced by doxorubicin in mice.Methods:Swiss strain of albino female mice were divided into 6 groups of 5 animals in each:GroupⅠ(control group),groupⅡ(doxorubicin,10 mg/kg,i.v.),groupⅢ,Ⅳ,andⅤ(Nigella sativa oil;1.5,3,and 6 mL/kg,respectively),groupⅥ(Nigella sativa oil per se;6 mL/kg,p.o.).The duration of treatment was 15 d(10 days’pre-treatment and 5 days’post-treatment)and doxorubicin was administered on day 11th of the treatment schedule.Following Nigella sativa oil treatment,neurobehavioral tests,cardiac hypertrophy tests,and biochemical tests in serum and tissues were performed.Neurological tests included assessment of anxiety-like behavior in the elevated plus maze,spontaneous alternation behavior in the cross maze,and depression-like behavior in modified forced swim tests.Biochemical tests included serum lactate dehydrogenase and creatinine kinase-MB,malondialdehyde and reduced glutathione in tissues.Lastly,molecular docking was used to estimate the affinity of the phytoconstituents of Nigella sativa oil with histone deacetylases.Results:Nigella sativa oil treatment significantly(P<0.001)restored doxorubicin-induced neurobehavioral changes,decreased lactate dehydrogenase and creatinine kinase-MB in the plasma,malondialdehyde contents in tissues,and increased reduced glutathione level.Besides,no significant alteration was observed in Nigella sativa oil per se group as compared to the control.Molecular docking showed that Nigella sativa oil components had appreciable binding affinitiy with the protein cavities of HDAC1 and HDAC6.Conclusions:The result shows that Nigella sativa oil exerts anxiolytic,antidepressant,and memory-enhancing effects in addition to cardioprotective effect against doxorubicin-induced cardiomyopathy in mice.The modulatory effect of Nigella sativa oil on oxidative stress could contribute to the cardioprotective effect and associated neurobehavioral changes in mice.展开更多
Objective:Moderate traumatic brain injury(TBI)can lead to a lifetime of physical,cognitive,emotional,and behavioral changes.Moreover,the secondary brain injury(SBI)during subacute and chronic phase after TBI could be ...Objective:Moderate traumatic brain injury(TBI)can lead to a lifetime of physical,cognitive,emotional,and behavioral changes.Moreover,the secondary brain injury(SBI)during subacute and chronic phase after TBI could be blamed for these deficits.Exercise is widely recognized as promoting health and improving bad moods,but the mechanisms by which exercise affects SBI are still unclear.Methods:Lateral fluid percussion(LFP)method was used to fabricate moderate TBI in motor and somatosensory cortex of the C57 BL/6 J mice.A 4-weeks voluntary running wheel exercise with 6-day training per week was modified based on the previous protocols.Neurological status,sensorimotor function,spatial memory,electrophysiological,post-traumatic stress disorder(PTSD)associated anxiety and depression,cortical pathohistological changes were assessed to evaluate effects TBI and exercise intervention.Results:After moderate LFP injury,the TBI mice showed severe motor deficits at the early stage in acute phase but gradually recovered.During acute and subacute phase after TBI,novel object recognition(NOR)ability and spatial memory functions were consistently impaired in TBI mice;hippocampal firing frequency and burst probability were hampered.Analysis of the altered burst firing shows a clear hippocampal theta rhythm drop.These electrophysiological impacts were associated with substantially lowered NOR preference as compared with the sham group during adulthood.4-weeks voluntary wheel running performed prior to induction of a moderate TBI,combined with 2 weeks voluntary motor skill training after TBI was found to inhibit plasma TNF-α,improve locomotor activity levels,alleviate anxiety and depression and promote spatial working memory recovery in rodents.At the meantime,histopathological deterioration was eased in the hippocampus in exercised mice.Conclusion:moderate TBI could induce neurological and neurobehavior impairments in mice.Aerobic exercise rehabilitation alleviated above mentioned deficits and may be an effective supplemental invention treatment for TBI patients.展开更多
Blood-brain barrier(BBB)disruption underlies the vasogenic edema and neuronal cell death induced by acute ischemic stroke.Reducing this disruption has therapeutic potential.Transcranial focused ultrasound stimulation ...Blood-brain barrier(BBB)disruption underlies the vasogenic edema and neuronal cell death induced by acute ischemic stroke.Reducing this disruption has therapeutic potential.Transcranial focused ultrasound stimulation has shown neuromodulatory and neuroprotective effects in various brain diseases including ischemic stroke.Ultrasound stimulation can reduce inflammation and promote angiogenesis and neural circuit remodeling.However,its effect on the BBB in the acute phase of ischemic stroke is unknown.In this study of mice subjected to middle cerebral artery occlusion for 90 minutes,low-intensity low-frequency(0.5 MHz)transcranial focused ultrasound stimulation was applied 2,4,and 8 hours after occlusion.Ultrasound stimulation reduced edema volume,improved neurobehavioral outcomes,improved BBB integrity(enhanced tight junction protein ZO-1 expression and reduced IgG leakage),and reduced secretion of the inflammatory factors tumor necrosis factor-αand activation of matrix metalloproteinase-9 in the ischemic brain.Our results show that low-intensity ultrasound stimulation attenuated BBB disruption and edema formation,which suggests it may have therapeutic use in ischemic brain disease as a protector of BBB integrity.展开更多
A cross sectional epidemiological study of 93 arc welders in a shipyard was conducted to observe the adverse effect of exposure to manganese welding fumes. Among them, 37 workers with paired controls were given the ne...A cross sectional epidemiological study of 93 arc welders in a shipyard was conducted to observe the adverse effect of exposure to manganese welding fumes. Among them, 37 workers with paired controls were given the neurobehavioral tests. Air concentration of manganese in working place, hair manganese and platelet 5 hydroxytryptamine in both exposed workers and controls was also measured. The higher percentage of respiratory symptoms including sour throat and dyspnea in the welders were observed as compared with the controls. The results of neurobehavioral tests showed that the welders exhibited poorer performance in simple reaction time and Santa Ana dexterity tests than that in the controls. The hair manganese concentration was higher and the blood platelet 5 HT level decreased in the welders. In conclusion, symptoms in the welders might be related to the exposure of manganese. Long term exposure to manganese welding fume could cause the change in simple reaction time and Santa Ana dexterity tests. The hair manganese concentration could be used as a biological monitoring index of exposure to manganese.展开更多
The study treated 72 s,rague-Dawley rats that were divided into 4 groups, one controlgroup and low, middle and higa dose groups, through drinking lead acetate solutions for threemonths. On the basis of founding subcli...The study treated 72 s,rague-Dawley rats that were divided into 4 groups, one controlgroup and low, middle and higa dose groups, through drinking lead acetate solutions for threemonths. On the basis of founding subclinical lead poisoning model, behavioral toxicological testwhich consisted of neurobehavioral functions, neuroelectrophysiology and neurobiochemistry wascarried out. The results indicabo that low lvel lead exposure could result in the obvious changes orneurobehavioral function, neuroelectrophyslology and ueurobiochemistry, and the changes of neurobeltavioral runctiou had close correlatiom with P6B, Zap, NCV and DA, and they also had promlnant dose-response relatiouskips. The results suggested that the indexes of neurobehavioral functionmight be cousldered as early, semitive indexes for subolinical’lead poisoning. The combination ofneurobehavioral function with neuroectrophysiology could be used to evaluate the early neurotic toxicity of lead. The results also suggested that the change of dopamine metabolism of the central nervous system (CNS) might be one of the biological foundation of lead neurotic toxicity which changedthe neurobehavioral function of laboratory rats.展开更多
Acute and sub chronic effects of oral dexamethasone on anxiety and memory in mice were evaluated using the elevated plus maze, Y maze and radial arm maze. Adult male Swiss albino mice assigned to five groups were give...Acute and sub chronic effects of oral dexamethasone on anxiety and memory in mice were evaluated using the elevated plus maze, Y maze and radial arm maze. Adult male Swiss albino mice assigned to five groups were given vehicle (normal saline), a standard drug (Diazepam or Scopolamine) or one of three selected doses of dexamethasone (0.5, 1.0 and 1.5 mg/kg) daily for a period of 14 days. Behavioral tests were carried out on days 1 and 14 after administration. Results were analysed using a one-way ANOVA followed by a posthoc test (Student-Newman-Keul) and expressed as mean ± S.E.M. Elevated plus maze test showed a significant reduction in the time spent in the open arm and in the number of open arm entries compared to control. Results of radial arm and Y maze tasks showed an improvement in spatial memory following dexamethasone administration. Y maze locomotor activity was significantly increased, although radial arm maze exploration did not increase significantly. The study concluded that oral dexamethasone given either acutely or sub chronically has both anxiogenic and memory enhancing effects.展开更多
Effects of amodiaquine, artesunate and artesunate amodiaquine combination on open field novelty-induced behaviors and spatial memory in healthy mice were studied. Forty mice were used in the open field and fifty each ...Effects of amodiaquine, artesunate and artesunate amodiaquine combination on open field novelty-induced behaviors and spatial memory in healthy mice were studied. Forty mice were used in the open field and fifty each in the radial arm maze and Y maze;mice were assigned into four or five groups of ten each, Group A served as control (distilled water), Groups B, C and D received artesunate (4 mg/kg), amodiaquine (10 mg/kg) and artesunate-amodiaquine combination (4 mg/kg and10 mg/kg) respectively, while Group E animals (for the cognition tests) were given scopolamine (2 mg/kg). Drugs and vehicle were administered orally for three days. Results were analysed by one way analysis of variance followed by a posthoc test. Results showed that artesunate and amodiaquine either in combination or administered singly caused a significant increase in open field novelty-induced horizontal locomotion and rearing. Grooming in the open field showed increments in the artesunate alone and artesunate amodiaquine groups while significant reductions in spatial memory were also seen in the cognition models used.展开更多
Developmental exposure to organophosphate insecticide is well known to induce neurobehavioral impairments, at late period. The present study aims to investigate the effects of subchronic exposure to Dimethoate, on loc...Developmental exposure to organophosphate insecticide is well known to induce neurobehavioral impairments, at late period. The present study aims to investigate the effects of subchronic exposure to Dimethoate, on locomotors skills and anxiety like behavior among wistar rat. Two groups of female’s rats are used. The intoxicated group receives daily, during five weeks, by intragastric gavage, a dose of Dimethoate dissolved in corn oil (100 mg/kg body weight). The control group receives only the corn oil. Spontaneous locomotors activity is evaluated using the Open Field test (OF) and anxiety-like behavior is measured using Elevated Plus-Maze (EPM). Dimethoate induced significant impairment of spontaneous locomotors activities, which is reflected by high decrease of number of squares crossed (SC) in OF. Females exposed to Dimethoate develop further anxiety-like response, expressed by significant reductions of the time spent in open arm of Elevated Plus-Maze.展开更多
Developmental exposure to organophosphate insecticide is well known to induce neurobeha-vioral impairments, at late period. The present study aims to investigate the effects of chronic exposure to Malathion, from in u...Developmental exposure to organophosphate insecticide is well known to induce neurobeha-vioral impairments, at late period. The present study aims to investigate the effects of chronic exposure to Malathion, from in utero to young adult stage, on locomotor skills and anxiety like- behavior among wistar rat. Four groups of female rats, bred with one non-pesticide exposed male, are used. On gestational day 6, three groups receive daily, by intragastric gavage, 3 different doses of Malathion dissolved in corn oil (100, 200 and 300 mg/kg body weight). The control group receives the corn oil only. On postnatal day 21, weaned offsprings are submitted to the similar treatment until adult age. Spontaneous locomotor activity is evaluated using the Open-Field test (OF) and anxiety-like behavior is measured using both Open-Field (OF) test and Elevate Plus-Maze (EPM). Malathion at 300 mg/kg is toxic to pregnant dams, and pups are stillborns. In males, Malathionlevelat 100 and 200 mg/kg induced significant impairment of spontaneous locomotor activities, which is reflected by high decrease of number of squares crossed in OF. In contrast, no discernible changes are observed within females Malathion-treated-group. However, females exposed to both malathion levels develop further anxiety-like response, expressed by significant reductions of exploratory activities in OF and time spent in open arm of EPM. Neurochemistry assay shows that cerebellum and neocortex acetylcholinesterase (AChE) activity inhibition are significantly increased with neurobehavioral deficits in males, relative to females. Overall, neurobehavioral outcomes of current study reveal that developmental exposure to Malathion induces sex-selective effects with greater changes in females.展开更多
Abnormal postoperative neurobehavioral performance(APNP)is a common phenomenon in the early postoperative period.The disturbed homeostatic status of metabolites in the brain after anesthesia and surgery might make a s...Abnormal postoperative neurobehavioral performance(APNP)is a common phenomenon in the early postoperative period.The disturbed homeostatic status of metabolites in the brain after anesthesia and surgery might make a significant contribution to APNP.The dynamic changes of metabolites in different brain regions after anesthesia and surgery,as well as their potential association with APNP are still not well understood.Here,we used a battery of behavioral tests to assess the effects of laparotomy under isoflurane anesthesia in aged mice,and investigated the metabolites in 12 different sub-regions of the brain at different time points using proton nuclear magnetic resonance('H-NMR)spectroscopy.The abnormal neurobehavioral performance occurred at 6 h and/or 9 h,and recovered at 24 h after anesthesia/surgery.Compared with the control group,the altered metabolite of the model group at 6 h was aspartate(Asp),and the difference was mainly displayed in the cortex;while significant changes at 9 h occurred predominantly in the cortex and hippocampus,and the corresponding metabolites were Asp and glutamate(Glu).All changes returned to baseline at 24 h.The altered metabolic changes could have occurred as a result of the acute APNP,and the metabolites Asp and Glu in the cortex and hippocampus could provide preliminary evidence for understanding the APNP process.展开更多
An association between assisted reproductive technology (ART) and neurobehavioral imprinting disorders has been reported in many studies,and it seems that ART may interfere with imprint reprogramming.However,it has ne...An association between assisted reproductive technology (ART) and neurobehavioral imprinting disorders has been reported in many studies,and it seems that ART may interfere with imprint reprogramming.However,it has never been explored whether epigenetic errors or imprinting disease susceptibility induced by ART can be inherited transgenerationally.Hence,the aim of this study was to determine the effect of in vitro fertilization and embryo transfer (IVF-ET) on transgenerational inheritance in an inbred mouse model.Mice derived from IVF-ET were outcrossed to wild-type C57BL/6J to obtain their female and male line F2 and F3 generations.Their behavior,morphology,histology,and DNA methylation status at several important differentially methylated regions (DMRs) were analyzed by Morris water maze,hematoxylin and eosin (H&E) staining,and bisulfite genomic sequencing.No significant differences in spatial learning or phenotypic abnormality were found in adults derived from IVF (F1) and female and male line F2 and F3 generations.A borderline trend of hypomethylation was found in H19 DMR CpG island 3 in the female line-derived F3 generation (0.40±0.118,P=0.086).Methylation status in H19/Igf2 DMR island 1,Igf2 DMR,KvDMR,and Snrpn DMR displayed normal patterns.Methylation percentage did not differ significantly from that of adults conceived naturally,and the expression of the genes they regulated was not disturbed.Transgenerational integrity,such as behavior,morphology,histology,and DNA methylation status,was maintained in these generations,which indicates that exposure of female germ cells to hormonal stimulation and gamete manipulation might not affect the individuals and their descendents.展开更多
The article reviewed the research progress of ligustilide in recent years and elaborated its pharmacological functions and mechanisms in detail, especially in ischemic brain injury. Its mechanism includes reducing cer...The article reviewed the research progress of ligustilide in recent years and elaborated its pharmacological functions and mechanisms in detail, especially in ischemic brain injury. Its mechanism includes reducing cerebral infarct volumes and improving neurobehavioral deficits, anti-oxidant and anti-apoptosis, antithrombotic activity, calcium channel blockers function, and effect on erythropoietin. Other pharmacological effects of ligustilide including inhibiting vascular smooth muscle cell proliferation, anti-inflammatory and analgesic effects, effects on LPS-induced endotoxic shock, inhibiting constriction effect, suppression of the central nervous system, and ameliorating the memory impairment induced by scopolamine and so on, are also introduced. Ligustilide has potential pharmacological value, which provides a reference for its further research and development.展开更多
Memory impairment in children is an ongoing issue worldwide related to a learning disability. This neurobiological condition has been suggested to associate with bisphenol A (BPA) exposure during pregnancy. BPA is an ...Memory impairment in children is an ongoing issue worldwide related to a learning disability. This neurobiological condition has been suggested to associate with bisphenol A (BPA) exposure during pregnancy. BPA is an inorganic compound used to produce polycarbonate plastics and epoxy resins. We conduct this study to investigate the effects of prenatal BPA exposure on the level of the N-methyl-D-aspartate (NMDA) receptor subunits, synaptic markers of the hippocampus and neurobehavioral outcomes in rats. The pregnant rats were given a daily dose of 5 mg/kg and 50 mg/kg of BPA with 0.5% Tween 80 orally from gestation day 2 until 21 (GD21). The level of GluN2A, GluN2B, PSD-95 and synapsin I in the hippocampus and its neurobehaviour outcomes were quantified and evaluated in the male foetus and adolescent rat. Prenatal BPA exposure reduced GluN2A, GluN2B, synapsin I and PSD-95 (Postsynaptic Density-95) in the male foetus and adolescent rat hippocampus compared to the control group. The prenatal BPA exposed rats demonstrated anxiety-related behaviour and impairment in aversive and spatial memory. The findings suggested that the impairment in neurobehavioral performance may inhibit the signalling pathway in the NMDA receptor subunits in the male foetus rat hippocampus leading to learning and memory deficits when reaching adolescence.展开更多
基金National Natural Science Foundation of China(81373383).
文摘OBJECTIVE There is growing evidence that uridine may act as an endogenous neuromodulator with a potential signaling role in the central nervous system in addition to its function in pyrimidine metabolism.We previously found that acute morphine treatment significantly increased uridine release in the dorsal striatum of mice,while the mechanism involved in morphine-induced uridine release and the role of uridine in morphine-induced neurobehavioral changes have not been understood.METHODS Uridine release in the dorsal striatum of mice was assessed by in vivo microdialysis coupled with high performance liquid chromatography(HPLC) after morphine treatment.Western blotting and immunofluorescence were used to evaluate the expression of uridine-related proteins.Morphine-induced neurobehavioral changes were assessed by locomotor activity,behavioral sensitization and conditioned place preference(CPP)test.The expression of NT5E,an extracellular enzyme involved in formation of nucleosides,including uridine,was specifically knocked down in the dorsal striatum of mice using adeno-associated virus(AAV)-mediated short hairpin RNA(shRNA).RESULTS Both acute and chronic morphine administration significantly increased uridine release in the dorsal striatum,and this was associated with upregulation of NT5E but not other uridine-related proteins.Inhibition of NT5E with APCP or shRNA markedly inhibited morphine-induced uridine release in the dorsal striatum and related neurobehavioral changes,including hyperlocomotor activity,behavioral sensitization and CPP.CONCLUSION The present study increases our understanding of the contribution of NT5E in regulating morphine-induced neurobehavioral changes,at least as related to uridine,and suggests that NT5E may be a novel therapeutic target to manage morphine abuse.
文摘Objective:To investigate the effect of Nigella sativa oil on cardiomyopathy and neurobehavioral changes induced by doxorubicin in mice.Methods:Swiss strain of albino female mice were divided into 6 groups of 5 animals in each:GroupⅠ(control group),groupⅡ(doxorubicin,10 mg/kg,i.v.),groupⅢ,Ⅳ,andⅤ(Nigella sativa oil;1.5,3,and 6 mL/kg,respectively),groupⅥ(Nigella sativa oil per se;6 mL/kg,p.o.).The duration of treatment was 15 d(10 days’pre-treatment and 5 days’post-treatment)and doxorubicin was administered on day 11th of the treatment schedule.Following Nigella sativa oil treatment,neurobehavioral tests,cardiac hypertrophy tests,and biochemical tests in serum and tissues were performed.Neurological tests included assessment of anxiety-like behavior in the elevated plus maze,spontaneous alternation behavior in the cross maze,and depression-like behavior in modified forced swim tests.Biochemical tests included serum lactate dehydrogenase and creatinine kinase-MB,malondialdehyde and reduced glutathione in tissues.Lastly,molecular docking was used to estimate the affinity of the phytoconstituents of Nigella sativa oil with histone deacetylases.Results:Nigella sativa oil treatment significantly(P<0.001)restored doxorubicin-induced neurobehavioral changes,decreased lactate dehydrogenase and creatinine kinase-MB in the plasma,malondialdehyde contents in tissues,and increased reduced glutathione level.Besides,no significant alteration was observed in Nigella sativa oil per se group as compared to the control.Molecular docking showed that Nigella sativa oil components had appreciable binding affinitiy with the protein cavities of HDAC1 and HDAC6.Conclusions:The result shows that Nigella sativa oil exerts anxiolytic,antidepressant,and memory-enhancing effects in addition to cardioprotective effect against doxorubicin-induced cardiomyopathy in mice.The modulatory effect of Nigella sativa oil on oxidative stress could contribute to the cardioprotective effect and associated neurobehavioral changes in mice.
文摘Objective:Moderate traumatic brain injury(TBI)can lead to a lifetime of physical,cognitive,emotional,and behavioral changes.Moreover,the secondary brain injury(SBI)during subacute and chronic phase after TBI could be blamed for these deficits.Exercise is widely recognized as promoting health and improving bad moods,but the mechanisms by which exercise affects SBI are still unclear.Methods:Lateral fluid percussion(LFP)method was used to fabricate moderate TBI in motor and somatosensory cortex of the C57 BL/6 J mice.A 4-weeks voluntary running wheel exercise with 6-day training per week was modified based on the previous protocols.Neurological status,sensorimotor function,spatial memory,electrophysiological,post-traumatic stress disorder(PTSD)associated anxiety and depression,cortical pathohistological changes were assessed to evaluate effects TBI and exercise intervention.Results:After moderate LFP injury,the TBI mice showed severe motor deficits at the early stage in acute phase but gradually recovered.During acute and subacute phase after TBI,novel object recognition(NOR)ability and spatial memory functions were consistently impaired in TBI mice;hippocampal firing frequency and burst probability were hampered.Analysis of the altered burst firing shows a clear hippocampal theta rhythm drop.These electrophysiological impacts were associated with substantially lowered NOR preference as compared with the sham group during adulthood.4-weeks voluntary wheel running performed prior to induction of a moderate TBI,combined with 2 weeks voluntary motor skill training after TBI was found to inhibit plasma TNF-α,improve locomotor activity levels,alleviate anxiety and depression and promote spatial working memory recovery in rodents.At the meantime,histopathological deterioration was eased in the hippocampus in exercised mice.Conclusion:moderate TBI could induce neurological and neurobehavior impairments in mice.Aerobic exercise rehabilitation alleviated above mentioned deficits and may be an effective supplemental invention treatment for TBI patients.
基金supported by the National Natural Science Foundation of China,Nos.81802232(to JXW),81801170(to YHT),82071284(to YHT),2019YFA0112000(to YHT)the Scientific Research and Innovation Program of Shanghai Education Commission,No.2019-01-07-00-02-E00064(to GYY)+1 种基金Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission,No.20JC1411900(to GYY)Science and Technology Commission of Shanghai,No.19441907900(to JFS).
文摘Blood-brain barrier(BBB)disruption underlies the vasogenic edema and neuronal cell death induced by acute ischemic stroke.Reducing this disruption has therapeutic potential.Transcranial focused ultrasound stimulation has shown neuromodulatory and neuroprotective effects in various brain diseases including ischemic stroke.Ultrasound stimulation can reduce inflammation and promote angiogenesis and neural circuit remodeling.However,its effect on the BBB in the acute phase of ischemic stroke is unknown.In this study of mice subjected to middle cerebral artery occlusion for 90 minutes,low-intensity low-frequency(0.5 MHz)transcranial focused ultrasound stimulation was applied 2,4,and 8 hours after occlusion.Ultrasound stimulation reduced edema volume,improved neurobehavioral outcomes,improved BBB integrity(enhanced tight junction protein ZO-1 expression and reduced IgG leakage),and reduced secretion of the inflammatory factors tumor necrosis factor-αand activation of matrix metalloproteinase-9 in the ischemic brain.Our results show that low-intensity ultrasound stimulation attenuated BBB disruption and edema formation,which suggests it may have therapeutic use in ischemic brain disease as a protector of BBB integrity.
文摘A cross sectional epidemiological study of 93 arc welders in a shipyard was conducted to observe the adverse effect of exposure to manganese welding fumes. Among them, 37 workers with paired controls were given the neurobehavioral tests. Air concentration of manganese in working place, hair manganese and platelet 5 hydroxytryptamine in both exposed workers and controls was also measured. The higher percentage of respiratory symptoms including sour throat and dyspnea in the welders were observed as compared with the controls. The results of neurobehavioral tests showed that the welders exhibited poorer performance in simple reaction time and Santa Ana dexterity tests than that in the controls. The hair manganese concentration was higher and the blood platelet 5 HT level decreased in the welders. In conclusion, symptoms in the welders might be related to the exposure of manganese. Long term exposure to manganese welding fume could cause the change in simple reaction time and Santa Ana dexterity tests. The hair manganese concentration could be used as a biological monitoring index of exposure to manganese.
文摘The study treated 72 s,rague-Dawley rats that were divided into 4 groups, one controlgroup and low, middle and higa dose groups, through drinking lead acetate solutions for threemonths. On the basis of founding subclinical lead poisoning model, behavioral toxicological testwhich consisted of neurobehavioral functions, neuroelectrophysiology and neurobiochemistry wascarried out. The results indicabo that low lvel lead exposure could result in the obvious changes orneurobehavioral function, neuroelectrophyslology and ueurobiochemistry, and the changes of neurobeltavioral runctiou had close correlatiom with P6B, Zap, NCV and DA, and they also had promlnant dose-response relatiouskips. The results suggested that the indexes of neurobehavioral functionmight be cousldered as early, semitive indexes for subolinical’lead poisoning. The combination ofneurobehavioral function with neuroectrophysiology could be used to evaluate the early neurotic toxicity of lead. The results also suggested that the change of dopamine metabolism of the central nervous system (CNS) might be one of the biological foundation of lead neurotic toxicity which changedthe neurobehavioral function of laboratory rats.
文摘Acute and sub chronic effects of oral dexamethasone on anxiety and memory in mice were evaluated using the elevated plus maze, Y maze and radial arm maze. Adult male Swiss albino mice assigned to five groups were given vehicle (normal saline), a standard drug (Diazepam or Scopolamine) or one of three selected doses of dexamethasone (0.5, 1.0 and 1.5 mg/kg) daily for a period of 14 days. Behavioral tests were carried out on days 1 and 14 after administration. Results were analysed using a one-way ANOVA followed by a posthoc test (Student-Newman-Keul) and expressed as mean ± S.E.M. Elevated plus maze test showed a significant reduction in the time spent in the open arm and in the number of open arm entries compared to control. Results of radial arm and Y maze tasks showed an improvement in spatial memory following dexamethasone administration. Y maze locomotor activity was significantly increased, although radial arm maze exploration did not increase significantly. The study concluded that oral dexamethasone given either acutely or sub chronically has both anxiogenic and memory enhancing effects.
文摘Effects of amodiaquine, artesunate and artesunate amodiaquine combination on open field novelty-induced behaviors and spatial memory in healthy mice were studied. Forty mice were used in the open field and fifty each in the radial arm maze and Y maze;mice were assigned into four or five groups of ten each, Group A served as control (distilled water), Groups B, C and D received artesunate (4 mg/kg), amodiaquine (10 mg/kg) and artesunate-amodiaquine combination (4 mg/kg and10 mg/kg) respectively, while Group E animals (for the cognition tests) were given scopolamine (2 mg/kg). Drugs and vehicle were administered orally for three days. Results were analysed by one way analysis of variance followed by a posthoc test. Results showed that artesunate and amodiaquine either in combination or administered singly caused a significant increase in open field novelty-induced horizontal locomotion and rearing. Grooming in the open field showed increments in the artesunate alone and artesunate amodiaquine groups while significant reductions in spatial memory were also seen in the cognition models used.
文摘Developmental exposure to organophosphate insecticide is well known to induce neurobehavioral impairments, at late period. The present study aims to investigate the effects of subchronic exposure to Dimethoate, on locomotors skills and anxiety like behavior among wistar rat. Two groups of female’s rats are used. The intoxicated group receives daily, during five weeks, by intragastric gavage, a dose of Dimethoate dissolved in corn oil (100 mg/kg body weight). The control group receives only the corn oil. Spontaneous locomotors activity is evaluated using the Open Field test (OF) and anxiety-like behavior is measured using Elevated Plus-Maze (EPM). Dimethoate induced significant impairment of spontaneous locomotors activities, which is reflected by high decrease of number of squares crossed (SC) in OF. Females exposed to Dimethoate develop further anxiety-like response, expressed by significant reductions of the time spent in open arm of Elevated Plus-Maze.
文摘Developmental exposure to organophosphate insecticide is well known to induce neurobeha-vioral impairments, at late period. The present study aims to investigate the effects of chronic exposure to Malathion, from in utero to young adult stage, on locomotor skills and anxiety like- behavior among wistar rat. Four groups of female rats, bred with one non-pesticide exposed male, are used. On gestational day 6, three groups receive daily, by intragastric gavage, 3 different doses of Malathion dissolved in corn oil (100, 200 and 300 mg/kg body weight). The control group receives the corn oil only. On postnatal day 21, weaned offsprings are submitted to the similar treatment until adult age. Spontaneous locomotor activity is evaluated using the Open-Field test (OF) and anxiety-like behavior is measured using both Open-Field (OF) test and Elevate Plus-Maze (EPM). Malathion at 300 mg/kg is toxic to pregnant dams, and pups are stillborns. In males, Malathionlevelat 100 and 200 mg/kg induced significant impairment of spontaneous locomotor activities, which is reflected by high decrease of number of squares crossed in OF. In contrast, no discernible changes are observed within females Malathion-treated-group. However, females exposed to both malathion levels develop further anxiety-like response, expressed by significant reductions of exploratory activities in OF and time spent in open arm of EPM. Neurochemistry assay shows that cerebellum and neocortex acetylcholinesterase (AChE) activity inhibition are significantly increased with neurobehavioral deficits in males, relative to females. Overall, neurobehavioral outcomes of current study reveal that developmental exposure to Malathion induces sex-selective effects with greater changes in females.
基金We would like to express our gratitude to Mrs.Pingping An(Wuhan Institute of Physics and Mathematics,Chinese Academy of Sciences)for her help in housing the animals.This work was supported by grants from the National Natural Science Foundation of China(8187051484,8157050329,81600933)the Interdisciplinary Medicine Seed Fund of Peking University(BMU2017MC006)the Youth Innovation Promotion Association of the Chinese Academy of Sciences,China(Y6Y0021004).
文摘Abnormal postoperative neurobehavioral performance(APNP)is a common phenomenon in the early postoperative period.The disturbed homeostatic status of metabolites in the brain after anesthesia and surgery might make a significant contribution to APNP.The dynamic changes of metabolites in different brain regions after anesthesia and surgery,as well as their potential association with APNP are still not well understood.Here,we used a battery of behavioral tests to assess the effects of laparotomy under isoflurane anesthesia in aged mice,and investigated the metabolites in 12 different sub-regions of the brain at different time points using proton nuclear magnetic resonance('H-NMR)spectroscopy.The abnormal neurobehavioral performance occurred at 6 h and/or 9 h,and recovered at 24 h after anesthesia/surgery.Compared with the control group,the altered metabolite of the model group at 6 h was aspartate(Asp),and the difference was mainly displayed in the cortex;while significant changes at 9 h occurred predominantly in the cortex and hippocampus,and the corresponding metabolites were Asp and glutamate(Glu).All changes returned to baseline at 24 h.The altered metabolic changes could have occurred as a result of the acute APNP,and the metabolites Asp and Glu in the cortex and hippocampus could provide preliminary evidence for understanding the APNP process.
基金supported by the National Basic Research Program (973) of China (No. 2007CB948104)the National Natural Science Foundation of China (No. 81070532)the Zhejiang Provincial Natural Science Foundation of China (No. Z207021)
文摘An association between assisted reproductive technology (ART) and neurobehavioral imprinting disorders has been reported in many studies,and it seems that ART may interfere with imprint reprogramming.However,it has never been explored whether epigenetic errors or imprinting disease susceptibility induced by ART can be inherited transgenerationally.Hence,the aim of this study was to determine the effect of in vitro fertilization and embryo transfer (IVF-ET) on transgenerational inheritance in an inbred mouse model.Mice derived from IVF-ET were outcrossed to wild-type C57BL/6J to obtain their female and male line F2 and F3 generations.Their behavior,morphology,histology,and DNA methylation status at several important differentially methylated regions (DMRs) were analyzed by Morris water maze,hematoxylin and eosin (H&E) staining,and bisulfite genomic sequencing.No significant differences in spatial learning or phenotypic abnormality were found in adults derived from IVF (F1) and female and male line F2 and F3 generations.A borderline trend of hypomethylation was found in H19 DMR CpG island 3 in the female line-derived F3 generation (0.40±0.118,P=0.086).Methylation status in H19/Igf2 DMR island 1,Igf2 DMR,KvDMR,and Snrpn DMR displayed normal patterns.Methylation percentage did not differ significantly from that of adults conceived naturally,and the expression of the genes they regulated was not disturbed.Transgenerational integrity,such as behavior,morphology,histology,and DNA methylation status,was maintained in these generations,which indicates that exposure of female germ cells to hormonal stimulation and gamete manipulation might not affect the individuals and their descendents.
基金National Key Technology Research and Decelopment Program (2007BAI37B06)
文摘The article reviewed the research progress of ligustilide in recent years and elaborated its pharmacological functions and mechanisms in detail, especially in ischemic brain injury. Its mechanism includes reducing cerebral infarct volumes and improving neurobehavioral deficits, anti-oxidant and anti-apoptosis, antithrombotic activity, calcium channel blockers function, and effect on erythropoietin. Other pharmacological effects of ligustilide including inhibiting vascular smooth muscle cell proliferation, anti-inflammatory and analgesic effects, effects on LPS-induced endotoxic shock, inhibiting constriction effect, suppression of the central nervous system, and ameliorating the memory impairment induced by scopolamine and so on, are also introduced. Ligustilide has potential pharmacological value, which provides a reference for its further research and development.
基金funded by the Fundamental Research Grant SchemeMinistry of Higher Education+2 种基金Malaysia (Grant No. FRGS/1/2018/SKK08/UITM/02/9)Geran Penyelidikan KhasUniversiti Teknologi MARA [Grant No. 600-RMC/GPK 5/3 (191/2020)]
文摘Memory impairment in children is an ongoing issue worldwide related to a learning disability. This neurobiological condition has been suggested to associate with bisphenol A (BPA) exposure during pregnancy. BPA is an inorganic compound used to produce polycarbonate plastics and epoxy resins. We conduct this study to investigate the effects of prenatal BPA exposure on the level of the N-methyl-D-aspartate (NMDA) receptor subunits, synaptic markers of the hippocampus and neurobehavioral outcomes in rats. The pregnant rats were given a daily dose of 5 mg/kg and 50 mg/kg of BPA with 0.5% Tween 80 orally from gestation day 2 until 21 (GD21). The level of GluN2A, GluN2B, PSD-95 and synapsin I in the hippocampus and its neurobehaviour outcomes were quantified and evaluated in the male foetus and adolescent rat. Prenatal BPA exposure reduced GluN2A, GluN2B, synapsin I and PSD-95 (Postsynaptic Density-95) in the male foetus and adolescent rat hippocampus compared to the control group. The prenatal BPA exposed rats demonstrated anxiety-related behaviour and impairment in aversive and spatial memory. The findings suggested that the impairment in neurobehavioral performance may inhibit the signalling pathway in the NMDA receptor subunits in the male foetus rat hippocampus leading to learning and memory deficits when reaching adolescence.
