Effects of High Fluoride and Low Iodine on Thyroid Function in Offspring Rats

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.

Effect of Perinatal Bisphenol A Exposure on Serum Lipids and Lipid Enzymes in Offspring Rats of Different Sex

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.

Sexual differences of the effects of prenatal stress on the expression of extracellular signal-regulated kinaseas in the hippocampus of offspring rats

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.

Microglia activation in the offspring of prenatal Poly I:C exposed rats:a PET imaging and immunohistochemistry study

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 neuroinflammatory 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 l:C) during pregnancy using 11 C'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 l:C exposed rats.Methods Offspring of Poly l: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.11 C-PK11195 micro-PET/CT and immunohistochemistry were performed on the selected rats to measure microglia activation.Results The treatment group showed hyperlocomotion and deficits in PPI and LI compared with the control group. The treatment group also showed an increased11 C-PK11195 uptake ratio in the prefrontal cortex(f=-3.990, p=0.003) and hippocampus(f=-4.462,p=0.001). The number of activated microglia cells was significantly higher in the treatment group than in the control gro叩(hippocampus: f=8.204, p<0.001; prefrontal:f=6.995, p<0.001). Within the treatment group, there were significant 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 l:C exposed rats.This study suggests that microglia activation may play a possible or potential role in the pathogenesis of schizophrenia.

Assessing Adverse Effects of Aroclor 1254 on Perinatally Exposed Rat Offspring

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.

Methyl Donors Supplementation Attenuates the Adverse Effects of Maternal High Fructose Diet of Offspring Emotional and Cognitive Behaviors

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.