Background:Besides seizures,a myriad of overlapping neuropsychiatric and cognitive comorbidities occur in patients with epilepsy,which further debilitates their quality of life.This study provides an in-depth characte...Background:Besides seizures,a myriad of overlapping neuropsychiatric and cognitive comorbidities occur in patients with epilepsy,which further debilitates their quality of life.This study provides an in-depth characterization of the impact of brivaracetam and rufinamide individually and in combination at 10 and 20 mg/kg doses,respec-tively,on corneal kindling-induced generalized seizures and behavioral alterations.Furthermore,observed convulsive frequency and behavioral changes were corre-lated to post-kindling-induced changes in the activity of markers of oxidative stress.Methods:Adult C57BL/6 mice were kindled via twice-daily transcorneal 50-Hz elec-trical stimulations(3 mA)for 3 s for 12 days until animals reached a fully kindled state.After the kindling procedure,animals were tested using a set of behavioral tests,and neurochemical alterations were assessed.Results:Corneal-kindled animals exhibited intense generalized convulsions,altered behavioral phenotypes typified by positive symptoms(hyperlocomotion),negative symptoms(anxiety and anhedonia),and deficits in semantic and working memory.BRV 10+RFM 20 dual regime increased convulsive threshold and propensity toward the start of stage 4–5 seizures and improved phenotypical deficits,that is,anxiety,depression,and memory impairments.Moreover,this combination therapy mitigated kindling-induced redox impairments as evidenced by reduced malondialdehyde and acetylcholinesterase levels and increased glutathione antioxidant activity in the brain of animals subjected to repetitive brain insult.Conclusion:Based on our outcomes,this dual therapy provides supporting evidence in alleviating epilepsy-induced neurobehavioral comorbidities and changes in redox homeostasis.展开更多
Tetramethylammonium hydroxide(TMAH)is an important compound that utilized and released by the rapidly expanding semiconductor industry,which could hardly be removed by the conventional wastewater treatment techniques....Tetramethylammonium hydroxide(TMAH)is an important compound that utilized and released by the rapidly expanding semiconductor industry,which could hardly be removed by the conventional wastewater treatment techniques.As a cholinergic agonist,the tetramethylammonium ion(TMA^(+))has been reported to induce toxicity to muscular and respiratory systems of mammals and human,however the toxicity on aquatic biota remains poorly known.We investigated the neurotoxic effects of TMA^(+)exposure on zebrafish,based on neurobehavior tests and a series of biomarkers.Significant inhibitions on the swimming distance of zebrafish larvae were observed when the exposure level exceeded 50 mg/L,and significant alterations on swimming path angles(straight and deflective movements)occurred even at 10 mg/L.The tested neurobehavioral endpoints of zebrafish larvae were significantly positively correlated with reactive oxygen species(ROS)and malondialdehyde(MDA),significantly negatively related with the activities of antioxidant enzymes,but not significantly correlated with the level of acetylcholinesterase(AChE).Such relationship indicates that the observed neurotoxic effects on swimming behavior of zebrafish larvae is mainly driven by oxidative stress,rather than the alterations of neurotransmitter.At the highest exposure concentration(200 mg/L),TMA^(+)evoked more severe toxicity on zebrafish juveniles,showing significantly stronger elevation on the MDA activity,and greater inhibitions on the activities of antioxidant enzymes and ACh E,suggesting juveniles were more susceptible to TMA^(+)exposure than larval zebrafish.展开更多
Tetrabromobisphenol A(TBBPA)is a widely used brominated flame retardant.There is evidence showing that TBBPA can exert thyroid disrupting effects in mammals,but different results were also reported,along with inconsis...Tetrabromobisphenol A(TBBPA)is a widely used brominated flame retardant.There is evidence showing that TBBPA can exert thyroid disrupting effects in mammals,but different results were also reported,along with inconsistent reports regarding its neurotoxicity.Here,we investigated thyroid disrupting effects and neurotoxicity of TBBPA(5,50,500μg/(kg·day))to male mice following maternal and direct exposure through drinking water,with the antithyroid drug propylthiouracil(PTU)as the positive control.On postnatal day(PND)15,we expectedly observed severe thyroid compensatory hyperplasia and cerebellar developmental retardation in PTU-treated pups.The highest dose of TBBPA also caused thyroid histological alteration but had no effects on cerebellar development in terms of Purkinje cell morphology and the thickness of the internal granular layer and the molecular layer of the cerebellum.During puberty and adulthood,the thyroid morphological alterations became more pronounced in the TBBPA-treated animals,accompanied by decreased serum thyroid hormone levels.Furthermore,the 50 and 500μg/(kg·day)TBBPA groups showed a significant decrease in the serum level of serotonin,a neurotransmitter associated with anxiety behaviors.Correspondingly,the highest dose group displayed anxiety-like behaviors in the elevated plus-maze test on PND 35,but this neurobehavioral alteration disappeared on PND 56.Moreover,no changes in neurobehavioral parameters tested were found in TBBPAtreated animals at puberty and adulthood.Altogether,all observations show that TBBPA can exert thyroid disrupting effects but has little overt impact on brain development and neurobehaviors in mice,suggesting that thyroid disruption does not necessarily cause overtly adverse neurodevelopmental outcomes.展开更多
Fetuses and neonates are known to be high-risk groups for Methylmercury（MeHg）exposure.MeHg can be transferred to the fetus through the placenta and to newborn offspring through breast milk.The aim of the present stu...Fetuses and neonates are known to be high-risk groups for Methylmercury（MeHg）exposure.MeHg can be transferred to the fetus through the placenta and to newborn offspring through breast milk.The aim of the present study was to investigate the neurotoxic effects of low doses of MeHg（1 and 5 μg/m L in drinking water） administration,from gestational day 1 to postnatal day（PND） 21,on the neurobehavioral development of rats.The results showed that the no-observed-effect level of MeHg is somewhere in the range of 1-4 μg/mL.Neurobehavioral development analysis revealed a delayed appearance of cliff drop and negative geotaxis reflexes in the 5 μg/mL MeHg exposure group.Developmental exposure to MeHg affected locomotor activity functions for the females,but not for the males,implying that the female pups were more vulnerable than the male pups.All pups exposed to 5 μg/mL of MeHg showed a significant deficit in motor coordination in the rotarod test compared with controls,and the highest accumulated concentrations of Hg were found in the cerebellum,followed by the hippocampus and cerebral cortex,indicating that the cerebellum is a possible target for MeHg toxicity.We demonstrated adverse effects of developmental exposure to MeHg associated with tissue concentrations very close to the current human body burden of this persistent and bioaccumulative compound.展开更多
Objective The aim of this study was to assess the effects of yttrium nitrate on neurobehaviora development in Sprague-Dawley rats. Methods Dams were orally exposed to 0, 5, 15, or 45 mg/kg daily of yttrium nitrate fro...Objective The aim of this study was to assess the effects of yttrium nitrate on neurobehaviora development in Sprague-Dawley rats. Methods Dams were orally exposed to 0, 5, 15, or 45 mg/kg daily of yttrium nitrate from gestation day （GD） 6 to postnatal day （PND） 21. Body weight and food consumption were monitored weekly. Neurobehavior was assessed by developmental landmarks and reflexes, motor activity, hot plate, Rota-rod and cognitive tests. Additionally, brain weights were measured on PND 21 and 70. Results No significant difference was noted among all groups for maternal body weight and food consumption. All yttrium-exposed offspring showed an increase in body weight on PND 21; however, no significant difference in body weight for exposed pups versus controls was observed 2 weeks or more after the yttrium solution was discontinued. The groups given 5 mg/kg daily decreased significantly in the duration of female forelime grip strength and ambulation on PND 13. There was no significant difference between yttrium-exposed offspring and controls with respect to other behavioral ontogeny parameters and postnatal behavioral test results. Conclusion Exposure of rats to yttrium nitrate in concentrations up to 45 mg/kg daily had no adverse effects on their neurobehavioral development.展开更多
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
Neurobehavioral and neurochemical effects of occupational lead exposure were invstigated by WHO Ncurobehavioral Core Test Battery (NCTB) testing and a serics of monoamine neurotransmitters and their metabolites analyz...Neurobehavioral and neurochemical effects of occupational lead exposure were invstigated by WHO Ncurobehavioral Core Test Battery (NCTB) testing and a serics of monoamine neurotransmitters and their metabolites analyzing in workers from lead smeltery and storage-battery manufacturing factory and matched controls. Indicators of lead exposure, the blood lead (PbB) and zinc protophorphyrin (ZPP) levels were found significantly higher in the expeed group compared with that of the controls (70.55μg/dL vs 3.6μg/dL; and 294.92 μg/dL vs 38.32μg/dL, respectively). Furthermore, elevated urinary homovanillic acid (HVA) and impairment of certain neurobehavioral performances were also found in the lead exposed wokers; the latter included attention/response speed, manual dexterity, perceptual-motor speed, visual perception/memory, and motor speed/steadiness. Positive or negative correlations were observed between certain parameters. Thus, homovanillic acid (HVA) is peitively correlated With PbB and ZPP; dopamine (DA) negatively correlated with Benton visual retention (BVR); and HVA negatively correlated with digit symbol (DSy), BVR, and pursuit aiming (PA). It is suggested that the alterations of dopamine and its metabolites HVA in urine associated with impairment of neurobehavioral function might be served as biomarkers of lead-induced neurotoxicity.展开更多
BACKGROUND： Recently, it has been reported that blood lead level lower than 24 μ mol/L can lead to learning and cognitive deficits. OBJECTIVE： To investigate the relationship of lead level in foremilk and early neu...BACKGROUND： Recently, it has been reported that blood lead level lower than 24 μ mol/L can lead to learning and cognitive deficits. OBJECTIVE： To investigate the relationship of lead level in foremilk and early neurobehavioral development of neonates taking lead level in foremilk as lead exposure index. DESIGN： A controlled observation. SETTING： Maternal and Child Health Center, Shanxi Children＇s Hospital. PARTICIPANTS： Totally 128 neonates of full-term normal delivery, 76 male and 52 female, from Shanxi Provincial Maternal and Child Health Center and Jiexiu Maternal and Child Health Center were involved in this study. All the involved neonates had no peripartal ischemic/hypoxic history. The corresponding puerperants were aged （27 ±5 ）years. They had no various acute and chronic diseases during pregnancy, and family history of neurological disease as well as occupational lead exposure. Informed consents of detected items were obtained from the puerperants. METHODS： ①Determination of lead level in foremilk- Altogether 128 foremilk samples, 1 mL each, were collected between January and February 2005. The same amount of violet acid was added to each sample. After foremilk was fully dissolved, 0.2 mL solution was taken for determining lead level with atomic absorption spectrometer in graphite stove. The determined process strictly followed the internal quantity control of laboratory and was involved in the blind quality control of Institute of Environmental Health of Chinese Academy. ②Participants grouping： Totally 128 neonates were involved, and the normal reference value of lead level of foremilk was 0.06 - 0.48 μ mol/L. The involved neonates were assigned into high-level lead group （≥ 0.24 μ mol/L, n =60） and low-level lead group （〈 0.24 μ mol/L, n =68）. ③Assessment of neurobehavioral development of neonates： Neurobehavioral development level of neonates who was born 24 to 72 hours was assessed with 20-item neonatal neurobehavioral determination method, which involved behavioral ability （6 items）, passive muscular tension （4 items）, active muscular tension （4 items）, primitive reflection （3 items） and general evaluation （3 items）. Each above-mentioned scoring had 3 scales （0,1 and 2 points）. The full mark of 20 items was 40 points. Neurological behaviors of neonates might be unabnormal when scoring was 〈 35 points. OUTCOME MEASURES： Assessment results of neurobehavioral development of neonates in high- and low-level lead neonates. RESULTS： After lead-level determination, the involved neonates in two groups participated in the final analysis. Neurobehavioral total scores of neonates of high-level lead group were lower than those in the low-level lead group [ （35.9±1.3 ） points vs. （37.7 ±1.4） points, P 〈 0.01 ]. The scores of neonatal erection in high-level lead group were lower than those in low-level lead group [ （ 1.4±0.4） points vs. （ 1.8 ±0.5 ） points, P 〈0.01], and time for head erection of neonates in the high-level lead group was shortened as compared with that in the low-level lead group [ （1.8±1.7） minutesvs. （3.3±2.2） minutes, P〈0.01]. CONCLUSION： 0.24 μ mol/L lead level in foremilk has certain relationship with neurobehavioral development. The main influenced manifestations are shortened duration of neonatal head erection and actively contracted extensor, i.e. cervical curved ability is weakened.展开更多
Because of the importance of central nervous system (CNS) functions to productive capacity and quality of life, biomarkers of these functions will play a key role in evaluating the success of interventions targeting a...Because of the importance of central nervous system (CNS) functions to productive capacity and quality of life, biomarkers of these functions will play a key role in evaluating the success of interventions targeting aging processes. The CNS biomarkers may also be useful for predicting aging in other systems and in the organism as a whole. Age-related behavioral changes, the products of CNS aging, have content and predictive validity with respect to human functional capacities and may, therefore, represent important 'neurobehavioral' markers of functional aging. This article presents a discussion of some behavioral paradigms which are currently being considered as neurobehavioral biomarkers of aging in mice and the experimental approaches being employed in the assessment of their validity. Studies conducted in the authors' laboratory using dietary restriction and genetic comparisons to evaluate the validity of neurobehavioral biomarkers have revealed several methodological concerns, and hypothetical and empirical examples of these pitfalls are described and discussed. In spite of those concerns, it is concluded that approaches to validity using genetic comparisons and dietary restriction can be successfully implemented and should ultimately lead to identification of valid and useful neurobehavioral biomarkers of aging.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
目的:研究不同全身麻醉维持药物对婴幼儿唇腭裂手术后短期神经行为发育的影响。方法:纳入2岁以下在全身麻醉下行唇腭裂手术的患儿79例,按照麻醉维持期间用药方式不同分为吸入麻醉组(IA组)和静吸复合麻醉组(CIIA组)。记录术前基线(T0)、...目的:研究不同全身麻醉维持药物对婴幼儿唇腭裂手术后短期神经行为发育的影响。方法:纳入2岁以下在全身麻醉下行唇腭裂手术的患儿79例,按照麻醉维持期间用药方式不同分为吸入麻醉组(IA组)和静吸复合麻醉组(CIIA组)。记录术前基线(T0)、术后6个月(M6)及术后12个月(M12)时的盖泽尔发育诊断量表(Gesell Development Diagnosis Scale,GDDS)评分,结果包括适应性、精细运动、粗运动、语言和社交技能5个能区,比较组间GDDS各能区评分在术后各随访点的差异,并进行矫正回归分析。采用R 4.0.5软件包对数据进行统计学处理。结果:术前两组患儿基本特征及基线GDDS评分各能区组间无统计学差异,麻醉诱导用药及全麻维持的吸入用七氟烷浓度两组之间也无统计学差异。在矫正月龄、身体质量指数、性别、母亲教育程度、家庭收入、麻醉时间等影响因素后,M12时间点CIIA组精细动作能力显著低于IA组(P<0.05)。结论:在全身麻醉维持阶段,相比全凭吸入麻醉,在此基础上复合静脉麻醉对唇腭裂患儿全麻术后短期的精细动作能力可能造成轻度影响。展开更多
基金The authors extend their appreciation to the Distinguished Scientist Fellowship program at King Saud University,Riyadh,Saudi Arabia,for funding this work through Research Supporting Project Number RSP2024R131.
文摘Background:Besides seizures,a myriad of overlapping neuropsychiatric and cognitive comorbidities occur in patients with epilepsy,which further debilitates their quality of life.This study provides an in-depth characterization of the impact of brivaracetam and rufinamide individually and in combination at 10 and 20 mg/kg doses,respec-tively,on corneal kindling-induced generalized seizures and behavioral alterations.Furthermore,observed convulsive frequency and behavioral changes were corre-lated to post-kindling-induced changes in the activity of markers of oxidative stress.Methods:Adult C57BL/6 mice were kindled via twice-daily transcorneal 50-Hz elec-trical stimulations(3 mA)for 3 s for 12 days until animals reached a fully kindled state.After the kindling procedure,animals were tested using a set of behavioral tests,and neurochemical alterations were assessed.Results:Corneal-kindled animals exhibited intense generalized convulsions,altered behavioral phenotypes typified by positive symptoms(hyperlocomotion),negative symptoms(anxiety and anhedonia),and deficits in semantic and working memory.BRV 10+RFM 20 dual regime increased convulsive threshold and propensity toward the start of stage 4–5 seizures and improved phenotypical deficits,that is,anxiety,depression,and memory impairments.Moreover,this combination therapy mitigated kindling-induced redox impairments as evidenced by reduced malondialdehyde and acetylcholinesterase levels and increased glutathione antioxidant activity in the brain of animals subjected to repetitive brain insult.Conclusion:Based on our outcomes,this dual therapy provides supporting evidence in alleviating epilepsy-induced neurobehavioral comorbidities and changes in redox homeostasis.
基金supported by the National Key Research and Development Program of China(No.2019YFC0408203)。
文摘Tetramethylammonium hydroxide(TMAH)is an important compound that utilized and released by the rapidly expanding semiconductor industry,which could hardly be removed by the conventional wastewater treatment techniques.As a cholinergic agonist,the tetramethylammonium ion(TMA^(+))has been reported to induce toxicity to muscular and respiratory systems of mammals and human,however the toxicity on aquatic biota remains poorly known.We investigated the neurotoxic effects of TMA^(+)exposure on zebrafish,based on neurobehavior tests and a series of biomarkers.Significant inhibitions on the swimming distance of zebrafish larvae were observed when the exposure level exceeded 50 mg/L,and significant alterations on swimming path angles(straight and deflective movements)occurred even at 10 mg/L.The tested neurobehavioral endpoints of zebrafish larvae were significantly positively correlated with reactive oxygen species(ROS)and malondialdehyde(MDA),significantly negatively related with the activities of antioxidant enzymes,but not significantly correlated with the level of acetylcholinesterase(AChE).Such relationship indicates that the observed neurotoxic effects on swimming behavior of zebrafish larvae is mainly driven by oxidative stress,rather than the alterations of neurotransmitter.At the highest exposure concentration(200 mg/L),TMA^(+)evoked more severe toxicity on zebrafish juveniles,showing significantly stronger elevation on the MDA activity,and greater inhibitions on the activities of antioxidant enzymes and ACh E,suggesting juveniles were more susceptible to TMA^(+)exposure than larval zebrafish.
基金supported by the National Key Research and Development Program of China(No.2018YFA0901103)the National Natural Science Foundation of China(No.21876196)。
文摘Tetrabromobisphenol A(TBBPA)is a widely used brominated flame retardant.There is evidence showing that TBBPA can exert thyroid disrupting effects in mammals,but different results were also reported,along with inconsistent reports regarding its neurotoxicity.Here,we investigated thyroid disrupting effects and neurotoxicity of TBBPA(5,50,500μg/(kg·day))to male mice following maternal and direct exposure through drinking water,with the antithyroid drug propylthiouracil(PTU)as the positive control.On postnatal day(PND)15,we expectedly observed severe thyroid compensatory hyperplasia and cerebellar developmental retardation in PTU-treated pups.The highest dose of TBBPA also caused thyroid histological alteration but had no effects on cerebellar development in terms of Purkinje cell morphology and the thickness of the internal granular layer and the molecular layer of the cerebellum.During puberty and adulthood,the thyroid morphological alterations became more pronounced in the TBBPA-treated animals,accompanied by decreased serum thyroid hormone levels.Furthermore,the 50 and 500μg/(kg·day)TBBPA groups showed a significant decrease in the serum level of serotonin,a neurotransmitter associated with anxiety behaviors.Correspondingly,the highest dose group displayed anxiety-like behaviors in the elevated plus-maze test on PND 35,but this neurobehavioral alteration disappeared on PND 56.Moreover,no changes in neurobehavioral parameters tested were found in TBBPAtreated animals at puberty and adulthood.Altogether,all observations show that TBBPA can exert thyroid disrupting effects but has little overt impact on brain development and neurobehaviors in mice,suggesting that thyroid disruption does not necessarily cause overtly adverse neurodevelopmental outcomes.
基金financially supported by the National Natural Science Foundation of China (No.21177087)the National Program on Key Basic Research Project of China (973 Program) (No.2013CB430005)
文摘Fetuses and neonates are known to be high-risk groups for Methylmercury（MeHg）exposure.MeHg can be transferred to the fetus through the placenta and to newborn offspring through breast milk.The aim of the present study was to investigate the neurotoxic effects of low doses of MeHg（1 and 5 μg/m L in drinking water） administration,from gestational day 1 to postnatal day（PND） 21,on the neurobehavioral development of rats.The results showed that the no-observed-effect level of MeHg is somewhere in the range of 1-4 μg/mL.Neurobehavioral development analysis revealed a delayed appearance of cliff drop and negative geotaxis reflexes in the 5 μg/mL MeHg exposure group.Developmental exposure to MeHg affected locomotor activity functions for the females,but not for the males,implying that the female pups were more vulnerable than the male pups.All pups exposed to 5 μg/mL of MeHg showed a significant deficit in motor coordination in the rotarod test compared with controls,and the highest accumulated concentrations of Hg were found in the cerebellum,followed by the hippocampus and cerebral cortex,indicating that the cerebellum is a possible target for MeHg toxicity.We demonstrated adverse effects of developmental exposure to MeHg associated with tissue concentrations very close to the current human body burden of this persistent and bioaccumulative compound.
基金financially supported by the National Science and Technology Support Program(2012BAK01B00)
文摘Objective The aim of this study was to assess the effects of yttrium nitrate on neurobehaviora development in Sprague-Dawley rats. Methods Dams were orally exposed to 0, 5, 15, or 45 mg/kg daily of yttrium nitrate from gestation day （GD） 6 to postnatal day （PND） 21. Body weight and food consumption were monitored weekly. Neurobehavior was assessed by developmental landmarks and reflexes, motor activity, hot plate, Rota-rod and cognitive tests. Additionally, brain weights were measured on PND 21 and 70. Results No significant difference was noted among all groups for maternal body weight and food consumption. All yttrium-exposed offspring showed an increase in body weight on PND 21; however, no significant difference in body weight for exposed pups versus controls was observed 2 weeks or more after the yttrium solution was discontinued. The groups given 5 mg/kg daily decreased significantly in the duration of female forelime grip strength and ambulation on PND 13. There was no significant difference between yttrium-exposed offspring and controls with respect to other behavioral ontogeny parameters and postnatal behavioral test results. Conclusion Exposure of rats to yttrium nitrate in concentrations up to 45 mg/kg daily had no adverse effects on their neurobehavioral development.
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Neurobehavioral and neurochemical effects of occupational lead exposure were invstigated by WHO Ncurobehavioral Core Test Battery (NCTB) testing and a serics of monoamine neurotransmitters and their metabolites analyzing in workers from lead smeltery and storage-battery manufacturing factory and matched controls. Indicators of lead exposure, the blood lead (PbB) and zinc protophorphyrin (ZPP) levels were found significantly higher in the expeed group compared with that of the controls (70.55μg/dL vs 3.6μg/dL; and 294.92 μg/dL vs 38.32μg/dL, respectively). Furthermore, elevated urinary homovanillic acid (HVA) and impairment of certain neurobehavioral performances were also found in the lead exposed wokers; the latter included attention/response speed, manual dexterity, perceptual-motor speed, visual perception/memory, and motor speed/steadiness. Positive or negative correlations were observed between certain parameters. Thus, homovanillic acid (HVA) is peitively correlated With PbB and ZPP; dopamine (DA) negatively correlated with Benton visual retention (BVR); and HVA negatively correlated with digit symbol (DSy), BVR, and pursuit aiming (PA). It is suggested that the alterations of dopamine and its metabolites HVA in urine associated with impairment of neurobehavioral function might be served as biomarkers of lead-induced neurotoxicity.
基金Key Technologies Research and Development Program of Shanxi Province, No. 041074
文摘BACKGROUND： Recently, it has been reported that blood lead level lower than 24 μ mol/L can lead to learning and cognitive deficits. OBJECTIVE： To investigate the relationship of lead level in foremilk and early neurobehavioral development of neonates taking lead level in foremilk as lead exposure index. DESIGN： A controlled observation. SETTING： Maternal and Child Health Center, Shanxi Children＇s Hospital. PARTICIPANTS： Totally 128 neonates of full-term normal delivery, 76 male and 52 female, from Shanxi Provincial Maternal and Child Health Center and Jiexiu Maternal and Child Health Center were involved in this study. All the involved neonates had no peripartal ischemic/hypoxic history. The corresponding puerperants were aged （27 ±5 ）years. They had no various acute and chronic diseases during pregnancy, and family history of neurological disease as well as occupational lead exposure. Informed consents of detected items were obtained from the puerperants. METHODS： ①Determination of lead level in foremilk- Altogether 128 foremilk samples, 1 mL each, were collected between January and February 2005. The same amount of violet acid was added to each sample. After foremilk was fully dissolved, 0.2 mL solution was taken for determining lead level with atomic absorption spectrometer in graphite stove. The determined process strictly followed the internal quantity control of laboratory and was involved in the blind quality control of Institute of Environmental Health of Chinese Academy. ②Participants grouping： Totally 128 neonates were involved, and the normal reference value of lead level of foremilk was 0.06 - 0.48 μ mol/L. The involved neonates were assigned into high-level lead group （≥ 0.24 μ mol/L, n =60） and low-level lead group （〈 0.24 μ mol/L, n =68）. ③Assessment of neurobehavioral development of neonates： Neurobehavioral development level of neonates who was born 24 to 72 hours was assessed with 20-item neonatal neurobehavioral determination method, which involved behavioral ability （6 items）, passive muscular tension （4 items）, active muscular tension （4 items）, primitive reflection （3 items） and general evaluation （3 items）. Each above-mentioned scoring had 3 scales （0,1 and 2 points）. The full mark of 20 items was 40 points. Neurological behaviors of neonates might be unabnormal when scoring was 〈 35 points. OUTCOME MEASURES： Assessment results of neurobehavioral development of neonates in high- and low-level lead neonates. RESULTS： After lead-level determination, the involved neonates in two groups participated in the final analysis. Neurobehavioral total scores of neonates of high-level lead group were lower than those in the low-level lead group [ （35.9±1.3 ） points vs. （37.7 ±1.4） points, P 〈 0.01 ]. The scores of neonatal erection in high-level lead group were lower than those in low-level lead group [ （ 1.4±0.4） points vs. （ 1.8 ±0.5 ） points, P 〈0.01], and time for head erection of neonates in the high-level lead group was shortened as compared with that in the low-level lead group [ （1.8±1.7） minutesvs. （3.3±2.2） minutes, P〈0.01]. CONCLUSION： 0.24 μ mol/L lead level in foremilk has certain relationship with neurobehavioral development. The main influenced manifestations are shortened duration of neonatal head erection and actively contracted extensor, i.e. cervical curved ability is weakened.
文摘Because of the importance of central nervous system (CNS) functions to productive capacity and quality of life, biomarkers of these functions will play a key role in evaluating the success of interventions targeting aging processes. The CNS biomarkers may also be useful for predicting aging in other systems and in the organism as a whole. Age-related behavioral changes, the products of CNS aging, have content and predictive validity with respect to human functional capacities and may, therefore, represent important 'neurobehavioral' markers of functional aging. This article presents a discussion of some behavioral paradigms which are currently being considered as neurobehavioral biomarkers of aging in mice and the experimental approaches being employed in the assessment of their validity. Studies conducted in the authors' laboratory using dietary restriction and genetic comparisons to evaluate the validity of neurobehavioral biomarkers have revealed several methodological concerns, and hypothetical and empirical examples of these pitfalls are described and discussed. In spite of those concerns, it is concluded that approaches to validity using genetic comparisons and dietary restriction can be successfully implemented and should ultimately lead to identification of valid and useful neurobehavioral biomarkers of aging.
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.
文摘目的:研究不同全身麻醉维持药物对婴幼儿唇腭裂手术后短期神经行为发育的影响。方法:纳入2岁以下在全身麻醉下行唇腭裂手术的患儿79例,按照麻醉维持期间用药方式不同分为吸入麻醉组(IA组)和静吸复合麻醉组(CIIA组)。记录术前基线(T0)、术后6个月(M6)及术后12个月(M12)时的盖泽尔发育诊断量表(Gesell Development Diagnosis Scale,GDDS)评分,结果包括适应性、精细运动、粗运动、语言和社交技能5个能区,比较组间GDDS各能区评分在术后各随访点的差异,并进行矫正回归分析。采用R 4.0.5软件包对数据进行统计学处理。结果:术前两组患儿基本特征及基线GDDS评分各能区组间无统计学差异,麻醉诱导用药及全麻维持的吸入用七氟烷浓度两组之间也无统计学差异。在矫正月龄、身体质量指数、性别、母亲教育程度、家庭收入、麻醉时间等影响因素后,M12时间点CIIA组精细动作能力显著低于IA组(P<0.05)。结论:在全身麻醉维持阶段,相比全凭吸入麻醉,在此基础上复合静脉麻醉对唇腭裂患儿全麻术后短期的精细动作能力可能造成轻度影响。
