To assess the neurotoxic effects and redoxresponses of Aroclor 1254 (A1254) on perinatallyexposed rat offspring, A1254 was administered bygavage from gestational day (GD) 6 to postnatal day(PND) 21. Neurobehavio...To assess the neurotoxic effects and redoxresponses of Aroclor 1254 (A1254) on perinatallyexposed rat offspring, A1254 was administered bygavage from gestational day (GD) 6 to postnatal day(PND) 21. Neurobehavioral development,antioxidant enzyme activities, lipid peroxidation(LPO), nitric oxide (NO), and NO synthase (NOS)levels were analyzed in the offspring.Neurobehavioral development analysis revealeddelayed appearance of the righting reflex, negativegeotaxis, and cliff drop test responses in A1254exposed group. Developmental A1254 exposurealso caused oxidative stress in the brain of PND 22offspring via reductions in the activity of SOD andGSH-Px, and by promoting a rise in the levels of NOand NOS.展开更多
Thirty-two Wistar rats were divided randomly into four groups of eight with six females and two males in each group. The rats were exposed to high fluoride drinking water (45 mg F-L^-1 from 100 mg NaF L-1), low diet...Thirty-two Wistar rats were divided randomly into four groups of eight with six females and two males in each group. The rats were exposed to high fluoride drinking water (45 mg F-L^-1 from 100 mg NaF L-1), low dietary iodine (0.0855 mg kg-1), or both together in order to assess the effects of these three regimens on the thyroid function of the offspring rats. After the animal model was established, the offspring rats were bred and 10-, 20-, 30-, 60-, and 90-d-old rats were used for the experiment. The treatments for the offspring rats were the same as those of their parents. In comparison with control rats, the relative thyroid glands were changed by three regimens, but the mean values of thyroid weight in the experimental groups saw no marked difference. Serum TT3 levels were increased in all stages in the low iodine (LI) group. In the high fluoride (HiF) group, increase in TT3 levels was observed except in 20-d-old rats. Decrease in TT3 at 20- and 90-d and increase in TT3 at 30- and 60-d were found in HiF+LI group. Serum TT4 levels first saw an increase, and then dropped in the LI and HiF+LI group. However, an increase in TT4 was found in the HiF group. The levels of TSH in serum rocketed at d 20, and then dropped in the next stages in experimental groups. The results suggested that thyroid disorder could be induced by high flroride in drinking water, low iodine diet, or both of them. Exposure time to fluoride or low iodine diet was one of the important factors that fluoride can induce the development of thyroid dyfunction.展开更多
Daily separation of rat pups from their mothers while the preweaning period has an impact on behavior and stress response of pups. We hypothesized that maternal separation may create a depression-like state in mother ...Daily separation of rat pups from their mothers while the preweaning period has an impact on behavior and stress response of pups. We hypothesized that maternal separation may create a depression-like state in mother rats from which we separate the rat pups and decrease their reproductive function and fertility. Also, we aimed to evaluate the transmission degree of depression and anxiety across generations. Females aged 3 months were divided in two groups of 10 rats each. After a first mating and a first parturition, we conducted maternal separation 3 h during 22 days for the experienced group while the control group mothers kept their pups. At 4 months of age, females underwent behavioral tests and a second mating. Second generation’s pups were also subjected to behavioral tests. Behavioral tests showed that mothers which experienced separation were more depressive and anxious than control ones, also they had a lower litter size. Rats pups of the second generation whose mothers experienced maternal separation also revealed behavior changes akin to depression and anxiety. Thus, maternal separation causes depressive and anxious-likestates on mother rats which experienced separation and has an impact on their litter size. Also, consequences of maternal separation seem to last throughout generations.展开更多
Rats were exposed to1 or 10 μg/mL bisphenol A (BPA) in water during pregnancy and lactation. Offspring rats were given normal water and a standard diet from weaning to postnatal day (PND) 50. Perinatal exposure t...Rats were exposed to1 or 10 μg/mL bisphenol A (BPA) in water during pregnancy and lactation. Offspring rats were given normal water and a standard diet from weaning to postnatal day (PND) 50. Perinatal exposure to BPA resulted in significantly increased body weight, visceral adipose tissue, abnormal serum lipids, and lower adiponectin (ADP) levels in both female and male offspring rats. Liver adipose triglyceride lipase (Atgl) mRNA levels and ADP protein in visceral adipose tissue were significantly decreased in BPA-exposed offspring rats. In both female or male offspring rats, obesity and dyslipidemia induced by perinatal exposure to BPA were associated with down regulation of Atgl mRNA in liver and ADP protein in visceral adipose tissue.展开更多
Background The well-known ‘pyrotherapy’ of Julius Wagner-Jauregg might be the beginning of the study on the immunological concepts of schizophrenia. As the primary immune effector cells in the brain, microglia play...Background The well-known ‘pyrotherapy’ of Julius Wagner-Jauregg might be the beginning of the study on the immunological concepts of schizophrenia. As the primary immune effector cells in the brain, microglia play a pivotal role in neuroinfammatory processes. Maternal viral infection during pregnancy is associated with an increased risk for psychiatric disorders with presumed neurodevelopmental origin, including autism spectrum disorders and schizophrenia. The present study was to quantify microglia activation in vivo in the mature offspring of rats exposed to polyriboinosinic–polyribocytidilicacid (Poly I:C) during pregnancy using ^11C-PK11195 positron emission tomography (PET) and immunohistochemistry.Objective The study aimed to quantify microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly I:C exposed rats.Methods Offspring of Poly I:C-treated dams were the model group, offspring of saline-treated dams were the control group. Behavioural test for two groups was taken by spontaneous activity, prepulse inhibition (PPI) and latent inhibition (LI) test (including active avoidance conditioning task and passive avoidance conditioning task). Randomly selected successful model rats were assessed by behavioural test in the model group and control group rats. 11C-PK11195 micro-PET/CT and immunohistochemistry were performed on the selected rats to measure microglia activation.Results The treatment group showed hyperlocomotion and defcits in PPI and LI compared with the control group. The treatment group also showed an increased 11C-PK11195 uptake ratio in the prefrontal cortex (t=-3.990, p=0.003) and hippocampus (t=-4.462, p=0.001). The number of activated microglia cells was signifcantly higher in the treatment group than in the control group (hippocampus: t=8.204, p〈0.001; prefrontal: t=6.995, p〈0.001). Within the treatment group, there were signifcant correlations between the behavioural parameters and the activation of microglia as measured by PET and immunohistochemistry.Conclusions The present study demonstrated microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly I:C exposed rats. This study suggests that microglia activation may play a possible or potential role in the pathogenesis of schizophrenia.展开更多
Objective:To investigate the effects of developmental damage of hippocampal neurons in offspring rats induced by sevoflurane inhalation anesthesia during pregnancy and its related mechanisms.Methods:Eighteen pregnant ...Objective:To investigate the effects of developmental damage of hippocampal neurons in offspring rats induced by sevoflurane inhalation anesthesia during pregnancy and its related mechanisms.Methods:Eighteen pregnant female Sprague-Dawley(SD)rats were randomly divided into three experimental groups:the control group(intraperitoneal injection of 0.9%sodium chloride solution 100 mL),the sevoflurane inhalation anesthesia group(inhalation of 1 MAC sevoflurane for 6 h and intraperitoneal injection of 0.9%sodium chloride solution 100 mL),and the dexmedetomidine combined with sevoflurane inhalation anesthesia group(inhalation of 1 MAC sevoflurane for 6 h and intraperitoneal injection of dexmedetomidine 100 mL),with 6 rats in each group.On the day of birth,the offspring rats of each experimental group were randomly selected.And blood gas analysis was performed with left ventricular artery blood of each offspring.The expression of cleaved-caspase-3 in hippocampal neurons was measured by Western blot.The mRNA expressions of growth-associated protein-43(GAP-43)and neuronal nitric oxide synthase(nNOS)in hippocampus of offspring rats were detected by real-time RT-PCR.The protein expressions of GAP-43 and nNOS were tested by immunohistochemistry and Western blot.Results:Compared with the control group,cleaved-caspase-3 expression in hippocampal neurons of offspring rats in sevoflurane inhalation anesthesia group increased significantly.Cleaved-caspase-3 in hippocampal neurons of offspring after dexmedetomidine combined with sevoflurane inhalation anesthesia was dramatically lower than that in sevoflurane inhalation anesthesia group.Compared with the sevoflurane inhalation anesthesia group,dexmedetomidine combined with sevoflurane inhalation anesthesia could markedly up-regulate the mRNA and protein expressions of GAP-43 and nNOS.Conclusion:Dexmedetomidine can protect hippocampal neurons from developmental damage induced by sevoflurane inhalation anesthesia during pregnancy,which may be related to the up-regulation of the mRNA and protein expressions GAP-43 and nNOS.展开更多
BACKGROUND: Prenatal stress has been shown to inhibit cell proliferation in the dentate gyrus and hippocampus, reduce hippocampal volume, and cause neuronal loss and oxidative damage in the hippocampus of offspring r...BACKGROUND: Prenatal stress has been shown to inhibit cell proliferation in the dentate gyrus and hippocampus, reduce hippocampal volume, and cause neuronal loss and oxidative damage in the hippocampus of offspring rats, but the sexual difference of the effects on offsprings is seldom referred to. OBJECTIVE: To observe the effect of prenatal stress to adult pregnant rats on expression of extracellular signal-regulated kinases (ERK) in hippocampus of the offspring rats of different genders. DESIGN : A randomized and control animal experiment.SETTING: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University. MATERIALS : The experiments were carried out in the Key Laboratory of Environment and Gene Related Diseases (Xi'an Jiaotong University), Ministry of Education between October 2005 and March 2006. Fifteen female and five male adult Sprague-Dawley rats were adopted. Female rats weighing 230-250 g and male rats weighing 280-350 g were used. METHODS: The virgin female rats were placed overnight with adult male rats (3:1) for mating. A total of twelve pregnant rats were randomly assigned to prenatal stress group (PNS group, n=6) and control group (n=6). The pregnant rats of the PNS group were exposed to restraint stress on days 14-20 of pregnancy three times a day, 45 minutes for each time . The restraint device was a transparent plastic tube (6.8 cm in diameter) with air holes for breathing and closed end. The length could be adjusted to accommodate the size of the animals. To prevent habituation of animals to the daily procedure, restraint periods were randomly shifted within certain time periods (8:00-11:00, 11:00-14:00, and 16:00-19:00). After birth, offsprings of all groups were culled to 8-10 litters in each group and housed in the same animal room, and kept together with their biologic mothers. The pregnant rats of the control group were left undisturbed. On day 21, after all the offspring were weaned, male and female pups were separated and housed four in each cage respectively until test at 30 days of age. At the end of postnatal day 30, one male and female offspring rats from the same dam were selected with a random choice and a total of 24 animals from 12 different dams were used. The experimental rats were sacrificed by decapitation under anesthesia. Bilateral hippocampal tissues were isolated and homogenized in cold condition. Alkaline carbonate buffer (BCA) method was used to detect the concentration of extracellular signal-regulated kinases (ERK), then mixed with loading buffer, the constant voltage was 100 V. Finally, BCIP/NBT staining and electrDphoresis were performed, the absorbance (A) value for the bands was detected with the Bandscan analytical software, and the expression of ERK in hippocampus of offspring rats of different genders in each group was quantitatively analyzed. MAIN OUTCOME MEASURES: The level of ERK expression in hippocampus of offspring rats of different genders in each group was observed.RESULTS: All the 24 offspring rats were involved in the analysis of results. ① The staining results of ERP activity in the extract of brain tissue detected with Western blotting technique and specific antibody analysis showed that the ERP in hippocampus of offspring rats had two subtypes of ERK-1 and ERK-2, and the latter was the main type.② Standardized by the average A value in the control group, the quantitative data of the general A value of total ERK showed that the expression of ERK-2 in hippocampus of female offspring rats was obviously higher in the PNS group than in the control group (A value: 126±6.76,100±4.89,P〈 0.01). ③The expression of ERK-2 had no obvious difference between the female and male offspring rats in the control group.④ The expression of ERK-2 in hippocampus of male offspring rats was a little higher in the PNS group than in the control group (A value: 104±6.27,102±5.48,P 〉 0.05). CONCLUSION : PNS significantly affects the increase of ERK expression in hippocampus of female offspring rats, but has no obvious influence on that of male ones.展开更多
Free Fatty acid is an end-product of hepatic metabolism of fructose. Most of past studies have demonstrated significant relationship between gestational high fat diet and metabolic and physiology outcomes in offspring...Free Fatty acid is an end-product of hepatic metabolism of fructose. Most of past studies have demonstrated significant relationship between gestational high fat diet and metabolic and physiology outcomes in offspring. However, there is a scarce of data extended to the effects of high fructose diet-fed dams on juveniles’ progeny. Therefore, the present experiment was designed to examine the later effects of maternal high fructose diet intake during pregnancy and lactation on juvenile offspring rats emotional behaviors and memory abilities. We tested whether methyl donors supplemented to that high fructose diet could reverse the adverse effects. We found at two months of age, anxiety-like behavior and depression-like behavior were elevated in off springs of mother fed to high fructose diet and a sex difference effect with males were more affected than females. In addition, behavioral outcomes indicated that the high fructose diet also impaired spatial working and recognition memories in the Y-maze and object recognition test respectively. Blood glucose intolerance increased significantly in juvenile males rats of dams fed with high fructose diet when compared to females. However, a supplementation of the maternal diet with methyl donors attenuated all these changes. Our study suggested a controlled fructose diet supplemented to methyl donors during critical period of brain developing (in utero and pre-weaning stage), otherwise that could induced irreversible detrimental effects on offspring behavior and cognitive health.展开更多
Folic acid participates in the metabolism of homocysteine and lowers plasma homocysteine levels directly or indirectly. To establish a hyperhomocysteinemic pregnant rat model, 2 mL of DL-homocysteine was administered ...Folic acid participates in the metabolism of homocysteine and lowers plasma homocysteine levels directly or indirectly. To establish a hyperhomocysteinemic pregnant rat model, 2 mL of DL-homocysteine was administered daily by intraperitoneal injection at a dose of 200 mg/kg from day 10 to day 19 of gestation. Folic acid was administered by intragastric administration at a dose of 20 mg/kg during the period of preeclampsia induction. Results showed that systolic blood pressure, proteinuria/creatinine ratio, and plasma homocysteine levels in the hyperhomocysteinemic pregnant rats increased significantly, and that body weight and brain weight of rat pups significantly decreased. Folic acid supplementation markedly reversed the above-mentioned abnormal changes of hyperhomocysteinemic pregnant rats and rat pups. These findings suggest that folic acid can alleviate the symptoms of hyperhomocysteinemia- induced preeclampsia in pregnant rats without influencing brain development of rat pups.展开更多
[目的]探讨甲醛对大鼠子代早期神经行为发育的影响。[方法]进行两代一窝繁殖试验,选用体重110-130 g Wistar大鼠120只,随机分为4组,染毒浓度分别为,高浓度组:(119.6±15.4)mg/m3、中浓度组:(25.2±4.6)mg/m3、低浓度组:(4.8...[目的]探讨甲醛对大鼠子代早期神经行为发育的影响。[方法]进行两代一窝繁殖试验,选用体重110-130 g Wistar大鼠120只,随机分为4组,染毒浓度分别为,高浓度组:(119.6±15.4)mg/m3、中浓度组:(25.2±4.6)mg/m3、低浓度组:(4.8±1.3)mg/m3、对照组:室内空气。采用静式吸入法,每天染毒1 h,雄鼠连续染毒至交配后,雌鼠连续染毒至子代断乳,用一组行为毒理学方法检测雌、雄大鼠暴露于甲醛后子代生理及神经行为发育的情况。[结果]随着染毒浓度的增加,F1、F2代大鼠张耳、门齿萌出和开眼3项反映早期生理发育指标和平面翻正反射和悬崖回避试验阳性率呈逐渐降低趋势(P<0.05),学习、记忆达标训练次数和达标时间明显增多和延长(P<0.05),高浓度组学习达标时间、记忆达标时间分别高达(307.0±49.5)s、(279.7±42.35)s,持续游泳时间及耐缺氧时间均逐渐缩短,分别为(31.63±7.50)min、(43.40±4.94)min,P<0.05。[结论]甲醛对子代大鼠的神经系统有明显的损害作用。展开更多
基金supported by the National Natural Science Foundation of China(No.21177087)
文摘To assess the neurotoxic effects and redoxresponses of Aroclor 1254 (A1254) on perinatallyexposed rat offspring, A1254 was administered bygavage from gestational day (GD) 6 to postnatal day(PND) 21. Neurobehavioral development,antioxidant enzyme activities, lipid peroxidation(LPO), nitric oxide (NO), and NO synthase (NOS)levels were analyzed in the offspring.Neurobehavioral development analysis revealeddelayed appearance of the righting reflex, negativegeotaxis, and cliff drop test responses in A1254exposed group. Developmental A1254 exposurealso caused oxidative stress in the brain of PND 22offspring via reductions in the activity of SOD andGSH-Px, and by promoting a rise in the levels of NOand NOS.
基金sponsored by the National Natural Science Foundation of China (30170681)the Foundation of Henan Institute of Science and Technology, China(6007)
文摘Thirty-two Wistar rats were divided randomly into four groups of eight with six females and two males in each group. The rats were exposed to high fluoride drinking water (45 mg F-L^-1 from 100 mg NaF L-1), low dietary iodine (0.0855 mg kg-1), or both together in order to assess the effects of these three regimens on the thyroid function of the offspring rats. After the animal model was established, the offspring rats were bred and 10-, 20-, 30-, 60-, and 90-d-old rats were used for the experiment. The treatments for the offspring rats were the same as those of their parents. In comparison with control rats, the relative thyroid glands were changed by three regimens, but the mean values of thyroid weight in the experimental groups saw no marked difference. Serum TT3 levels were increased in all stages in the low iodine (LI) group. In the high fluoride (HiF) group, increase in TT3 levels was observed except in 20-d-old rats. Decrease in TT3 at 20- and 90-d and increase in TT3 at 30- and 60-d were found in HiF+LI group. Serum TT4 levels first saw an increase, and then dropped in the LI and HiF+LI group. However, an increase in TT4 was found in the HiF group. The levels of TSH in serum rocketed at d 20, and then dropped in the next stages in experimental groups. The results suggested that thyroid disorder could be induced by high flroride in drinking water, low iodine diet, or both of them. Exposure time to fluoride or low iodine diet was one of the important factors that fluoride can induce the development of thyroid dyfunction.
文摘Daily separation of rat pups from their mothers while the preweaning period has an impact on behavior and stress response of pups. We hypothesized that maternal separation may create a depression-like state in mother rats from which we separate the rat pups and decrease their reproductive function and fertility. Also, we aimed to evaluate the transmission degree of depression and anxiety across generations. Females aged 3 months were divided in two groups of 10 rats each. After a first mating and a first parturition, we conducted maternal separation 3 h during 22 days for the experienced group while the control group mothers kept their pups. At 4 months of age, females underwent behavioral tests and a second mating. Second generation’s pups were also subjected to behavioral tests. Behavioral tests showed that mothers which experienced separation were more depressive and anxious than control ones, also they had a lower litter size. Rats pups of the second generation whose mothers experienced maternal separation also revealed behavior changes akin to depression and anxiety. Thus, maternal separation causes depressive and anxious-likestates on mother rats which experienced separation and has an impact on their litter size. Also, consequences of maternal separation seem to last throughout generations.
基金supported by Liaoning Nature Science Foundation of China(project number 2015020466)the National Natural Science Foundation of China(project number 81072311)
文摘Rats were exposed to1 or 10 μg/mL bisphenol A (BPA) in water during pregnancy and lactation. Offspring rats were given normal water and a standard diet from weaning to postnatal day (PND) 50. Perinatal exposure to BPA resulted in significantly increased body weight, visceral adipose tissue, abnormal serum lipids, and lower adiponectin (ADP) levels in both female and male offspring rats. Liver adipose triglyceride lipase (Atgl) mRNA levels and ADP protein in visceral adipose tissue were significantly decreased in BPA-exposed offspring rats. In both female or male offspring rats, obesity and dyslipidemia induced by perinatal exposure to BPA were associated with down regulation of Atgl mRNA in liver and ADP protein in visceral adipose tissue.
基金provided by the National Natural Science Foundation of China(No 81571318 to XQSNo 81371472 to LXL+5 种基金No 81401110 to XL)the Science and Technology Planning Project of Health and Family Planning Commission(No 201501015 to XQS)the International Science and Technology Cooperation Program of Henan(No 162102410061 to XQS)the Henan Province Union Fund Project(162300410275)the Zhengzhou University doctor team projectthe Youth Fund of the First Affiliated Hospital of Zhengzhou University(to XL and LJP)
文摘Background The well-known ‘pyrotherapy’ of Julius Wagner-Jauregg might be the beginning of the study on the immunological concepts of schizophrenia. As the primary immune effector cells in the brain, microglia play a pivotal role in neuroinfammatory processes. Maternal viral infection during pregnancy is associated with an increased risk for psychiatric disorders with presumed neurodevelopmental origin, including autism spectrum disorders and schizophrenia. The present study was to quantify microglia activation in vivo in the mature offspring of rats exposed to polyriboinosinic–polyribocytidilicacid (Poly I:C) during pregnancy using ^11C-PK11195 positron emission tomography (PET) and immunohistochemistry.Objective The study aimed to quantify microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly I:C exposed rats.Methods Offspring of Poly I:C-treated dams were the model group, offspring of saline-treated dams were the control group. Behavioural test for two groups was taken by spontaneous activity, prepulse inhibition (PPI) and latent inhibition (LI) test (including active avoidance conditioning task and passive avoidance conditioning task). Randomly selected successful model rats were assessed by behavioural test in the model group and control group rats. 11C-PK11195 micro-PET/CT and immunohistochemistry were performed on the selected rats to measure microglia activation.Results The treatment group showed hyperlocomotion and defcits in PPI and LI compared with the control group. The treatment group also showed an increased 11C-PK11195 uptake ratio in the prefrontal cortex (t=-3.990, p=0.003) and hippocampus (t=-4.462, p=0.001). The number of activated microglia cells was signifcantly higher in the treatment group than in the control group (hippocampus: t=8.204, p〈0.001; prefrontal: t=6.995, p〈0.001). Within the treatment group, there were signifcant correlations between the behavioural parameters and the activation of microglia as measured by PET and immunohistochemistry.Conclusions The present study demonstrated microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly I:C exposed rats. This study suggests that microglia activation may play a possible or potential role in the pathogenesis of schizophrenia.
基金This study was supported by the Shenyang Science and Technology Project in 2018(Grant No.18-014-4-32).
文摘Objective:To investigate the effects of developmental damage of hippocampal neurons in offspring rats induced by sevoflurane inhalation anesthesia during pregnancy and its related mechanisms.Methods:Eighteen pregnant female Sprague-Dawley(SD)rats were randomly divided into three experimental groups:the control group(intraperitoneal injection of 0.9%sodium chloride solution 100 mL),the sevoflurane inhalation anesthesia group(inhalation of 1 MAC sevoflurane for 6 h and intraperitoneal injection of 0.9%sodium chloride solution 100 mL),and the dexmedetomidine combined with sevoflurane inhalation anesthesia group(inhalation of 1 MAC sevoflurane for 6 h and intraperitoneal injection of dexmedetomidine 100 mL),with 6 rats in each group.On the day of birth,the offspring rats of each experimental group were randomly selected.And blood gas analysis was performed with left ventricular artery blood of each offspring.The expression of cleaved-caspase-3 in hippocampal neurons was measured by Western blot.The mRNA expressions of growth-associated protein-43(GAP-43)and neuronal nitric oxide synthase(nNOS)in hippocampus of offspring rats were detected by real-time RT-PCR.The protein expressions of GAP-43 and nNOS were tested by immunohistochemistry and Western blot.Results:Compared with the control group,cleaved-caspase-3 expression in hippocampal neurons of offspring rats in sevoflurane inhalation anesthesia group increased significantly.Cleaved-caspase-3 in hippocampal neurons of offspring after dexmedetomidine combined with sevoflurane inhalation anesthesia was dramatically lower than that in sevoflurane inhalation anesthesia group.Compared with the sevoflurane inhalation anesthesia group,dexmedetomidine combined with sevoflurane inhalation anesthesia could markedly up-regulate the mRNA and protein expressions of GAP-43 and nNOS.Conclusion:Dexmedetomidine can protect hippocampal neurons from developmental damage induced by sevoflurane inhalation anesthesia during pregnancy,which may be related to the up-regulation of the mRNA and protein expressions GAP-43 and nNOS.
基金the National Natural Science Foundation of China, No. 30270445
文摘BACKGROUND: Prenatal stress has been shown to inhibit cell proliferation in the dentate gyrus and hippocampus, reduce hippocampal volume, and cause neuronal loss and oxidative damage in the hippocampus of offspring rats, but the sexual difference of the effects on offsprings is seldom referred to. OBJECTIVE: To observe the effect of prenatal stress to adult pregnant rats on expression of extracellular signal-regulated kinases (ERK) in hippocampus of the offspring rats of different genders. DESIGN : A randomized and control animal experiment.SETTING: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University. MATERIALS : The experiments were carried out in the Key Laboratory of Environment and Gene Related Diseases (Xi'an Jiaotong University), Ministry of Education between October 2005 and March 2006. Fifteen female and five male adult Sprague-Dawley rats were adopted. Female rats weighing 230-250 g and male rats weighing 280-350 g were used. METHODS: The virgin female rats were placed overnight with adult male rats (3:1) for mating. A total of twelve pregnant rats were randomly assigned to prenatal stress group (PNS group, n=6) and control group (n=6). The pregnant rats of the PNS group were exposed to restraint stress on days 14-20 of pregnancy three times a day, 45 minutes for each time . The restraint device was a transparent plastic tube (6.8 cm in diameter) with air holes for breathing and closed end. The length could be adjusted to accommodate the size of the animals. To prevent habituation of animals to the daily procedure, restraint periods were randomly shifted within certain time periods (8:00-11:00, 11:00-14:00, and 16:00-19:00). After birth, offsprings of all groups were culled to 8-10 litters in each group and housed in the same animal room, and kept together with their biologic mothers. The pregnant rats of the control group were left undisturbed. On day 21, after all the offspring were weaned, male and female pups were separated and housed four in each cage respectively until test at 30 days of age. At the end of postnatal day 30, one male and female offspring rats from the same dam were selected with a random choice and a total of 24 animals from 12 different dams were used. The experimental rats were sacrificed by decapitation under anesthesia. Bilateral hippocampal tissues were isolated and homogenized in cold condition. Alkaline carbonate buffer (BCA) method was used to detect the concentration of extracellular signal-regulated kinases (ERK), then mixed with loading buffer, the constant voltage was 100 V. Finally, BCIP/NBT staining and electrDphoresis were performed, the absorbance (A) value for the bands was detected with the Bandscan analytical software, and the expression of ERK in hippocampus of offspring rats of different genders in each group was quantitatively analyzed. MAIN OUTCOME MEASURES: The level of ERK expression in hippocampus of offspring rats of different genders in each group was observed.RESULTS: All the 24 offspring rats were involved in the analysis of results. ① The staining results of ERP activity in the extract of brain tissue detected with Western blotting technique and specific antibody analysis showed that the ERP in hippocampus of offspring rats had two subtypes of ERK-1 and ERK-2, and the latter was the main type.② Standardized by the average A value in the control group, the quantitative data of the general A value of total ERK showed that the expression of ERK-2 in hippocampus of female offspring rats was obviously higher in the PNS group than in the control group (A value: 126±6.76,100±4.89,P〈 0.01). ③The expression of ERK-2 had no obvious difference between the female and male offspring rats in the control group.④ The expression of ERK-2 in hippocampus of male offspring rats was a little higher in the PNS group than in the control group (A value: 104±6.27,102±5.48,P 〉 0.05). CONCLUSION : PNS significantly affects the increase of ERK expression in hippocampus of female offspring rats, but has no obvious influence on that of male ones.
文摘Free Fatty acid is an end-product of hepatic metabolism of fructose. Most of past studies have demonstrated significant relationship between gestational high fat diet and metabolic and physiology outcomes in offspring. However, there is a scarce of data extended to the effects of high fructose diet-fed dams on juveniles’ progeny. Therefore, the present experiment was designed to examine the later effects of maternal high fructose diet intake during pregnancy and lactation on juvenile offspring rats emotional behaviors and memory abilities. We tested whether methyl donors supplemented to that high fructose diet could reverse the adverse effects. We found at two months of age, anxiety-like behavior and depression-like behavior were elevated in off springs of mother fed to high fructose diet and a sex difference effect with males were more affected than females. In addition, behavioral outcomes indicated that the high fructose diet also impaired spatial working and recognition memories in the Y-maze and object recognition test respectively. Blood glucose intolerance increased significantly in juvenile males rats of dams fed with high fructose diet when compared to females. However, a supplementation of the maternal diet with methyl donors attenuated all these changes. Our study suggested a controlled fructose diet supplemented to methyl donors during critical period of brain developing (in utero and pre-weaning stage), otherwise that could induced irreversible detrimental effects on offspring behavior and cognitive health.
基金The Medical Science and Technology Foundation of Chinese PLA during Twelfth "Five-year" Development Period(General Program),No. CWS11J003
文摘Folic acid participates in the metabolism of homocysteine and lowers plasma homocysteine levels directly or indirectly. To establish a hyperhomocysteinemic pregnant rat model, 2 mL of DL-homocysteine was administered daily by intraperitoneal injection at a dose of 200 mg/kg from day 10 to day 19 of gestation. Folic acid was administered by intragastric administration at a dose of 20 mg/kg during the period of preeclampsia induction. Results showed that systolic blood pressure, proteinuria/creatinine ratio, and plasma homocysteine levels in the hyperhomocysteinemic pregnant rats increased significantly, and that body weight and brain weight of rat pups significantly decreased. Folic acid supplementation markedly reversed the above-mentioned abnormal changes of hyperhomocysteinemic pregnant rats and rat pups. These findings suggest that folic acid can alleviate the symptoms of hyperhomocysteinemia- induced preeclampsia in pregnant rats without influencing brain development of rat pups.
文摘[目的]探讨甲醛对大鼠子代早期神经行为发育的影响。[方法]进行两代一窝繁殖试验,选用体重110-130 g Wistar大鼠120只,随机分为4组,染毒浓度分别为,高浓度组:(119.6±15.4)mg/m3、中浓度组:(25.2±4.6)mg/m3、低浓度组:(4.8±1.3)mg/m3、对照组:室内空气。采用静式吸入法,每天染毒1 h,雄鼠连续染毒至交配后,雌鼠连续染毒至子代断乳,用一组行为毒理学方法检测雌、雄大鼠暴露于甲醛后子代生理及神经行为发育的情况。[结果]随着染毒浓度的增加,F1、F2代大鼠张耳、门齿萌出和开眼3项反映早期生理发育指标和平面翻正反射和悬崖回避试验阳性率呈逐渐降低趋势(P<0.05),学习、记忆达标训练次数和达标时间明显增多和延长(P<0.05),高浓度组学习达标时间、记忆达标时间分别高达(307.0±49.5)s、(279.7±42.35)s,持续游泳时间及耐缺氧时间均逐渐缩短,分别为(31.63±7.50)min、(43.40±4.94)min,P<0.05。[结论]甲醛对子代大鼠的神经系统有明显的损害作用。