Potential role of ecto-5'-nucleotidase in morphine-induced uridine release and neurobehavioral changes

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.

Alterations of Monoamine Metabolites and Neurobehavioral Function in Lead-Exposed Workers

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.

Nigella sativa oil alleviates doxorubicin-induced cardiomyopathy and neurobehavioral changes in mice:In vivo and in-silico study

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.

Lead level in foremilk and neurobehavioral development of neonates

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.

Neurobehavioral Biomarkers of Aging: Influence of Genotype and Dietary Restriction

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.

Neurobehavioral Assessment of Rats Exposed to Yttrium Nitrate during Development

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.

NP-8 Moderate Brain Injury Causes Neurobehavioral Deficits and Effects of Aerobic Exercise

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.

Assessing pre/post-weaning neurobehavioral development for perinatal exposure to low doses of methylmercury

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.

Changes in mean cerebral blood flow velocity during cognitive task-induced cerebral fatigue in high performance fighter pilots

BACKGROUND： Several studies have demonstrated that sustained cognitive tasks can induce cognitive fatigue and that the mean cerebral blood flow velocity changes in some cerebral regions during cerebral fatigue. OBJECTIVE： To dynamically monitor the changes in mean cerebral blood flow velocity in different brain regions of high performance fighter pilots during mental arithmetic tasks and consecutive performance tasks. DESIGN, TIME AND SETTING： The present neurophysiological trial, based on controlled observation, was performed at the Laboratory of Neurophysiology, Institute of Aviation Medicine, Air Force of China between January 2003 and December 2005. PARTICIPANTS： Forty-five males, high performance fighter pilots, averaging （27.6±2.5） years, were recruited for this study. METHODS： The mean cerebral blood flow velocity in the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery of subjects was dynamically tested using transcranial Doppler during 5- hour mental arithmetic tasks and during 5- hour consecutive performance tasks. The neurobehavioral ability index was analyzed throughout each trial according to the number of correct responses, false responses, and lost responses. Simultaneously, cerebral cognitive fatigue-induced lethargy was assessed by the Stanford Sleepiness Scale. MAIN OUTCOME MEASURES： Changes in mean cerebral blood flow velocity in the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery; neurobehavioral ability index of mental arithmetic and consecutive performance tasks; Stanford Sleepiness Scale scores. RESULTS： During mental arithmetic tasks, the mean cerebral blood flow velocity in the anterior cerebral artery increased during hour 2 and decreased after hour 4. There was no significant change in mean cerebral blood flow velocity in the middle cerebral artery and posterior cerebral artery. During hour 4, cerebral cognitive fatigue was observed and, simultaneously, Stanford Sleepiness Scale scores demonstrated the presence of fatigue. During such a stage, the neurobehavioral ability index decreased, indicating a decline in performance ability. During consecutive performance tasks, the mean cerebral blood flow velocity declined earlier in the posterior cerebral artery compared to the middle cerebral artery. CONCLUSION： Five- hour mental arithmetic tasks have few effects on cerebral functions and do not lead to a significant change in mean cerebral blood flow velocity. Five-hour consecutive performance tasks can induce cerebral cognitive fatigue, and a marked decline in mean cerebral blood flow velocity.

Transcranial focused ultrasound stimulation reduces vasogenic edema after middle cerebral artery occlusion in mice

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.

Neuroprotective effect of high-dose hyperbaric oxygenation on rats with acute cerebral infarction in super-early stage:Curative comparison between 9-hour and 18-hour therapeutic protocols

BACKGROUND： Previously, only single short-time low-dose hyperbaric oxygenation （HBO） protocol was administrated to treat acute ischemic stroke in early stage and the conflicting results were obtained. There are few studies to report the outcome of administering long-time （can cover all the natural pathologic progression period） high-dose HBO to treat the disease. OBJECTIVE： To evaluate the therapeutic effect between two kinds of high-dose hyperbaric oxygenation on super-early stage of acute permanent middle cerebral artery occlusion （MCAO） in rats. DESIGN： A randomized controlled experimental study. SETTING： Beijing Tiantan Hospital, Capital Medical University; Beijing Research Institute of Neurosurgery. MATERIALS： Seventy-four male SD rats, aged 2.5 months old, weighing （ 280 ＋ 20） g, were provided by the Animal Institute, Chinese Academy of Medical Sciences. Hyperbaric oxygenation device was hyperbaric air cabin in which there was a self-made pure oxygen animal experimental cabin （made in China）. METHODS： This experiment was carried out in the municipal laboratory of Beijing Tiantan Hospital affiliated to Capital Medical University and Beijing Research Institute of Neurosurgery. ① Experimental intervention： All the rats were developed into models of permanent MCAO by suture embolism. Then, they were randomly divided into two HBO groups （9 hours and 18 hours） and control group, with 24 rats in each as well as 3-hour ultrastructure control group, with 2 rats. After being modeled for 3 hours, rats in the two HBO groups stayed in the hyperbaric cabin for 9 hours and 18 hours, separately. Rats in the 9-hour HBO group inhaled pure oxygen at hours 1, 3, 5, 7 and 9, and hyperbaric air at hours 2, 4, 6 and 8. Rats in the 18-hour HBO group inhaled pure oxygen at hours l, 3, 5, 7, 9, 11, 13, 15 and 17, and hyperbaric air at hours 2, 4, 6, 8, l0 12, 14, 16 and 18. After being created into models, rats in the control group and 3-hour ultrastructure control group breathed room air. ② Experimental evaluation： Neurologic functions of rat models in the 9-hour and 18-hour HBO groups as well as control group were scored by Bederson and Garica two neurological grading systems at hours 14 and 28 and on day 5; Infarct volume of rat models in the two HBO groups and control group was measured at hour 24 and on day 5 with NIH image processing software Image J; The pathological changes of brain tissue in the brain infarct region and its opposite region of rat models in the two HBO groups and 3-hour ultrastructure control group were observed with a Philips EM 208S transmission electron microscope. MAIN OUTCOME MEASURES： ① Neurobehavioral outcome. ② Rat brain infarct volume. ③ Ultrastructure of brain tissue in the ischemic penumbra of infarct models at the different time points RESULTS： ① Neurobehavioral outcome： After treatment, Garica score in the 9-hour and 18-hour HBO groups was significantly higher than that in the control group （P 〈 0.01）. Bederson score on day 5 after modeling in the 9-hour and 18-hour HBO groups was significantly lower than that in the control group （P 〈 0.01）. ② Cerebral infarct volume： Cerebral infarct volume in the 9-hour and 18-hour HBO groups was significantly smaller than that in the control group at hour 24 and on day 5 after modeling （P 〈 0.01）. In the 18-hour HBO group, infarct volume on day 5 after modeling was significantly larger than that at hour 24 after modeling （P 〈 0.05）. ③In the 3-hour ultrastructure control group, astrocyte edema and neuron damage around the capillary in the infarct cerebral tissue significantly relieved in the rats which were subjected to HBO. CONCLUSION： High dose of HBO is highly efficient in reducing infarct volume and improving neurobehavioral outcome of rats with acute cerebral infarction, and also has an important role in inhibiting the pathological progression of ischemic brain tissue after cerebral infarction.

Early Detection of Neurotoxic Effect of Manganese Exposure

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.

Compound Formula Rehmannia alleviates levodopainduced dyskinesia in Parkinson's disease

Compound Formula Rehmannia has been shown to be clinically effective in treating Parkinson＇s disease and levodopa-induced dyskinesia; however, the mechanisms remain unclear. In this study, we established a model of Parkinson＇s disease dyskinesia in rats, and treated these animals with Compound Formula Rehmannia. Compound Formula Rehmannia inhibited the increase in mRNA expression of N-methyl-D-aspartate receptor subunits 1 and 2 and excitatory amino acid neurotransmitter genes, and it inhibited the reduction in expression of γ-aminobutyric acid receptor B1, an inhibitory amino acid neurotransmitter gene, in the corpus striatum. In addition, Compound Formula Rehmannia alleviated dyskinesia symptoms in the Parkinson＇s disease rats. These experimental findings indicate that Compound Formula Rehmannia alleviates levodopa-induced dyskinesia in Parkinson＇s disease by modulating neurotransmitter signaling in the corpus striatum.

Ultrasound measurement of the corpus callosum and neural development of premature infants

Length and thickness of 152 corpus callosa Using ultrasonic diagnostic equipment with a were measured in neonates within 24 hours ot b^rtn. neonatal brain-specific probe, corpus callosum length and thickness of the genu, body, and splenium were measured on the standard mid-sagittal plane, and the anteroposterior diameter of the genu was measured in the coronal plane. Results showed that corpus callosum length as well as thickness of the genu and splenium increased with gesta- tional age and birth weight, while other measures did not. These three factors on the standard mid-sagittal plane are therefore likely to be suitable for real-time evaluation of corpus callosum de- velopment in premature infants using cranial ultrasound. Further analysis revealed that thickness of the body and splenium and the anteroposterior diameter of the genu were greater in male infants than in female infants, suggesting that there are sex differences in corpus callosum size during the neonatal period. A second set of measurements were taken from 40 premature infants whose ges- tational age was 34 weeks or less. Corpus callosum measurements were corrected to a gestational age of 40 weeks, and infants were grouped for analysis depending on the outcome of a neonatal behavioral neurological assessment. Compared with infants with a normal neurological assessment, corpus callosum length and genu and splenium thicknesses were less in those with abnormalities, indicating that corpus callosum growth in premature infants is associated with neurobehavioral development during the early extrauterine stage.

STUDY OF BEHAVIORAL TOXICOLOGY IN LEAD EXPOSED RATS

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.

Dexamethasone Regimens Alter Spatial Memory and Anxiety Levels in Mice

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.

Oral Amodiaquine, Artesunate and Artesunate Amodiaquine Combination Affects Open Field Behaviors and Spatial Memory in Healthy Swiss Mice

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.

Effects of Dimethoate Exposure on Locomotor Activity and Anxiety-Like Behavior in Female Wistar Rat

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.

Developmental effects of Malathion exposure on locomotor activity and anxiety-like behavior in Wistar rat

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.

Tetrabromobisphenol A exerts thyroid disrupting effects but has little overt impact on postnatal brain development and neurobehaviors in mice

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.