Effects of maternal exposure to arsenic on social behavior and related gene expression in F2 male mice

BACKGROUND@#Arsenic is a developmental neurotoxicant. It means that its neurotoxic effect could occur in offspring by maternal arsenic exposure. Our previous study showed that developmental arsenic exposure impaired social behavior and serotonergic system in C3H adult male mice. These effects might affect the next generation with no direct exposure to arsenic. This study aimed to detect the social behavior and related gene expression changes in F2 male mice born to gestationally arsenite-exposed F1 mice.@*METHODS@#Pregnant C3H/HeN mice (F0) were given free access to tap water (control mice) or tap water containing 85 ppm sodium arsenite from days 8 to 18 of gestation. Arsenite was not given to F1 or F2 mice. The F2 mice were generated by mating among control F1 males and females, and arsenite-F1 males and females at the age of 10 weeks. At 41 weeks and 74 weeks of age respectively, F2 males were used for the assessment of social behavior by a three-chamber social behavior apparatus. Histological features of the prefrontal cortex were studied by ordinary light microscope. Social behavior-related gene expressions were determined in the prefrontal cortex by real time RT-PCR method.@*RESULTS@#The arsenite-F2 male mice showed significantly poor sociability and social novelty preference in both 41-week-old group and 74-week-old group. There was no significant histological difference between the control mice and the arsenite-F2 mice. Regarding gene expression, serotonin receptor 5B (5-HT 5B) mRNA expression was significantly decreased (p < 0.05) in the arsenite-F2 male mice compared to the control F2 male mice in both groups. Brain-derived neurotrophic factor (BDNF) and dopamine receptor D1a (Drd1a) gene expressions were significantly decreased (p < 0.05) only in the arsenite-F2 male mice of the 74-week-old group. Heme oxygenase-1 (HO-1) gene expression was significantly increased (p < 0.001) in the arsenite-F2 male mice of both groups, but plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) and cyclooxygenase-2 (COX-2) gene expression were not significantly different. Interleukin-1β (IL-1β) mRNA expression was significantly increased only in 41-week-old arsenite-F2 mice.@*CONCLUSIONS@#These findings suggest that maternal arsenic exposure affects social behavior in F2 male mice via serotonergic system in the prefrontal cortex. In this study, COX-2 were not increased although oxidative stress marker (HO-1) was increased significantly in arsnite-F2 male mice.

Intranasal mucoadhesivemicroemulsion for neuroprotective effect of curcuminin mptp induced Parkinson model

ABSTRACT This study was to investigate the neuroprotective effect of curcumin against inflammation-mediated dopaminergic neurodegeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice model of Parkinson's disease (PD). Curcumin loaded sodium hyaluronate based mucoadhesive microemulsion (CMME) was developed by using Box Behnken design of Response surface method (RSM) and was characterized. Male C57BL/6 mice were first treated with four intraperitoneal injections of MPTP (20 mg/kg of body weight) at 2 h intervals followed CMME intranasal administration for 14 days at 2.86 mg of curcumin/kg of body weight per once a day. Optimal CMME containing 3% Capmul MCM as oil phase, 37 % of Accenon CC and Transcutol HP at 2.5:1 ratio and 0.5% sodium hyaluronate was stable, non-ciliotoxic with 57.66 nm±3.46 as average globule size. PdI value (0.190 ± 0.19) and TEM result depicted the narrow size distribution of CMME.All three independent variables had a significant effect (p<0.05) on the responses and the designed model was significant for all taken responses. In-vivo results revealed significant reduction of MPTP-mediated dopamine depletion after nasal administration of CMME. MPTP intoxication significantly decreased striatal DA content to 21.29 % which was then elevated to 55.37% after intranasal curcumin treatment. Significant improvement in motor performance as well as gross behavioural activity of mice was observed from rota-rod and open field test findings. Findings of the investigation revealed the symptomatic neuroprotection of curcumin against MPTP-induced neurodegradation in the striatum and hence could be considered as a promising approach to treat PD.

Reproductive toxicity of 2,4-D butylate to male mice / 中国比较医学杂志

Objective To explore the reproductive toxicity of 2,4-D butylate to the testis in male mice.Methods Forty-eight ICR male mice were randomly divided into four groups : the control group, and three 2,4-D butylate experimental groups (10, 20, 40 mg/kg), 12 mice in each group.2,4-D butylate was intragastrically administered once a day and six days per week for five weeks .At the end of the exposure, the activities of total antioxidant capacity (T-AOC), Na+ K+-ATPase, Ca+ + Mg+ +-ATPase, lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) in testis homogenate were measured by spectrophotometry .Results The activity of T-AOC was gradually decreased with the increase of doses, with a significant difference between the high dose group and other groups .The activities of LDH in the moderate and high dose groups were significantly lower than those of the low dose group and control group , and there was a significant difference between the high dose group and moderate dose group .The activities of SDH in the testis was gradually decreased with the increase of the 2,4-D butylate dose, showing significant differences between the high dose group and the moderate dose and control groups , and between the high and moderate dose groups and the low dose group . The activities of Na +K +-ATPase in the moderate and high dose groups were significantly lower than that of the control and low dose group.The activities of Ca++Mg++-ATPase was significantly lower in the experimental groups than that in the control group.Conclusion Exposure to 2,4-D butylate has certain toxic effect on the testicular tissue in male mice .

Toxic effects of artemisia aqueous extract on general reproduction in male mice / 重庆医科大学学报

Objective:To observe the toxic effects of artemisia aqueous extract on the ability of reproduction in male mice.Methods:Mice were randomly divided into 0,20,100 and 500 mg/kg dose groups and administered intraperitoneally for 60 days then mated and exeduted. The coefficient of testicle and epididymis,fertility index,sperm,the percentage of motile sperm,deformity of sperm and histopathological changes of testicle were detected.Results:The concentrations of artemisia aqueous extract used in this study have no significant influence on the aforementioned parameters.Conclusion:Reproductive functions of male mice does not obviously impaired by artemisia aqueous extract.

Effect of Hordeum vulgare on Sex Hormone Level in Male Mice / 中国药房

OBJECTIVE:To study the effect of Hordeum vulgare on hormone level in male mice.METHODS:Male mature mice(5～6 months) were treated with Hordeum vulgare decoction 1 mL(equivalent to 0.5 g?mL-1 crude drug) bid for 14 consecutive days.Follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2) and testosterone(T) in blood were monitored.RESULTS:In Hordeum vulgare group compared normal control,serum E2 increased significantly,serum level of testosterone decreased significantly,while FSH and LH levels remained stable.CONCLUSION:Hordeum vulgare can influence the hormone level in male mice by influencing the gonad axis of the mice.

The effect of different swimming loads on change of bone metabolism in the aged male mice / 中华物理医学与康复杂志

Objective To investigate the effect of different loads of swimming on change of bone metabolism of the aged male mice. Methods Forty Kunming strain male mice aged twelve months were randomly divided into five groups: thirty minute group, sixty minute group, sixty minute plus load group, experimental control group and sedentary control group. Eight male mice of two months old were recruited and served as the young sedentary controls. At the end of the 8 week, training period, all mice were sacrificed, the femur and thoracic vertebra were sampled for determining content of hydroxyproline, and serum testosterone, estradiol, osteocalcin, alkaline phosphatase and calcium were tested. Results After 8 weeks of swimming training, serum testosterone and estradiol levels and the content of hydroxyproline in the femur were significantly increased ( P

The Toxic Effect of 2-Methyl-4-chlorophenoxyacetic Acid in Male Mice / 环境与健康杂志

Objective To observe the toxic effects of2-methyl-4-chlorophenoxyacetic acid(MCPA)in male mice.Meth-ods The Kunming male mice were divided into4groups,10male mice per group.The control group were purfused into stom-ach by distilled water,the other three groups were perfused into stomach by20,100and200mg /kg MCPA,once a day,6times per week,continuously for17days.The body weight ,T 4 ,TSH,cholesterol,the ratio of spleen and testis to body weight and the specific activity of LDH,SDH in the testis were analyzed.Results The body weight of mice in MCPA-exposure groups in-creased more slowly than that in the control group.The contents of TSH in serum and ratio of spleen to body weight in200mg/kg group were significantly lower than those in control group.The contents of cholesterol in serum increased with the increases of MCPA-exposure doses.The contents of T 4 in serum were significantly higher in20mg /kg group and lower in200mg /kg group compared with that in control group.The ratio of the testis to body weight reduced with increase of the MCPA-exposure doses,and the specific activity of LDH in the testis of MCPA-exposure groups increased significantly,but the specific activity of SDH in the testis of MCPA-exposure groups revealed no significant variations compared with that of control group.Conclusion MC-PA inhibited the growth of male mice,resulted in endocrine disorder,the atrophy of spleen,and presented the toxicity of repro-ductive system.