Brief communication: prenatal and early postnatal stress exposure influences long bone length in adult rat offspring.

Stress during the prenatal and early postnatal periods (perinatal stress, PS) is known to impact offspring cognitive, behavioral, and physical development, but effects on skeletal growth are not clear. Our objective was to analyze effects of variable, mild, daily PS exposure on adult offspring long bone length. Twelve pregnant rat dams were randomly assigned to receive variable stress from gestational days 14-21 (Prenatal group), postpartum days 2-9 (Postnatal), both periods (Pre-Post), or no stress (Control). Differences in adult offspring tibia and femur length were analyzed among treatment groups. Mean tibia length differed among groups for males (P = 0.016) and females (P = 0.009), and differences for femur length approached significance for males (P = 0.051). Long bone length was shorter among PS-exposed offspring, especially those exposed to postnatal stress (Postnatal and Pre-Post groups). Results persisted when controlling for nose-tail length. These differences might reflect early stunting that is maintained in adulthood, or delayed growth among PS-exposed offspring. This study suggests that PS results in shorter long bones in adulthood, independently of effects on overall body size. Stunting and growth retardation are major global health burdens. Our study adds to a growing body of evidence suggesting that PS is a risk factor for poor linear growth.

The Effect of Left-Behind Experience and Self-Esteem on Aggressive Behavior in Young Adults in China : A Cross-Sectional Study.

There is little investigation on the independent effects of left-behind experience (LBE) on self-esteem and aggressive behavior in Chinese young adult populations, or the interaction effects of LBE and self-esteem on aggressive behavior. Thus, a school-based health survey was conducted in Anhui province in China in 2017. A total of 4,154 college students completed standard questionnaires which contain details of left-behind-related characters, self-esteem, aggressive behavior, and sociodemographic profile. Of included students, 55.3% were those with LBE (LBEs). Compared to students without left-behind experiences (NLBEs), LBEs had significantly increased scores of aggressive behavior and decreased score of self-esteem. The increased aggression in LBEs was highly related to longer left-behind duration, younger age of left-behind for the first time, and decreased self-esteem. On the other side, the aggressive behavior was demonstrated negatively correlated with self-esteem in both LBEs and NLBEs. There was an interaction effect of left-behind duration and self-esteem on physical aggression and of frequency of contacting with parents and self-esteem on verbal aggression. Besides, the interaction of primary caregiver and self-esteem on hostility and aggression toward self were also observed, respectively. Our results indicated LBEs and low self-esteem are associated with increased risk of aggressive behavior in Chinese young adults. The increased aggressive behavior in LBEs were highly related to longer left-behind duration, younger age of left-behind for the first time and decreased self-esteem. In those LBEs with some certain left-behind-related characters, aggressive behavior decreased more prominently with the increase of self-esteem. Strategies to improve self-esteem, particularly among young adults who have certain characters of LBE, should be a significant component of prevention and interventions of aggressive behavior.

Respiratory syncytial virus infection of microglia exacerbates SH-SY5Y neuronal cell injury by inducing the secretion of inflammatory cytokines: A Transwell in vitro study.

OBJECTIVES: To elucidate the mechanism of Respiratory Syncytial Virus (RSV) infection and central neuronal disease and to understand the role of microglia in neuronal injuries during RSV infection. MATERIALS AND METHODS: The effects of RSV and the cytokines produced by RSV-infected CHME-5 microglial cells on SY5Y neuronal cells were evaluated based on an in vitro Transwell coculture system. Five treatment groups were established in this study, including the normal control SY5Y group, RSV+SY5Y infection group, (cytokine+CHME-5)+SY5Y Transwell group, (RSV+CHME-5)+SY5Y Transwell group, and (RSV+cytokine+CHME-5)+SY5Y Transwell group. The morphological and physical alterations in SY5Y cells and their synapses were analyzed by confocal microscopy. The mRNA and protein expression levels of TLR3/RIG-I, as well as the expression of Hv1, in microglia were measured by qRT-PCR and Western blot assays. In addition, the apoptosis ratio of neuronal cells was determined by flow cytometry. RESULTS: RSV infection activated the protein expression of Hv1 protein in microglia in vitro (P<0.05), induced morphological changes in SY5Y cells, lengthened synapses (73.36±0.12 µm vs 38.10±0.11 µm), simultaneously activated TLR3 and RIG-I protein expression (P<0.05), upregulated the secretion of the inflammatory cytokines TNF-α, IL-6, and IL-8 (P<0.01), and increased the apoptosis rate of SY5Y cells (P<0.01). CONCLUSION: The results demonstrate that RSV infection of microglia can induce SY5Y neuronal cell injury and stimulate apoptosis through inflammatory cytokine release.

Inhibitory effect of melatonin on lung oxidative stress induced by respiratory syncytial virus infection in mice.

Previous research has shown that antioxidant (butylated hydroxyanisole) treatment ameliorates respiratory syncytial virus (RSV)-induced disease and lung inflammation. Melatonin has been reported to exhibit a wide varieties of biological effects, including antioxidant and anti-inflammation, and has no evident toxicity and side effect. But it is not known whether melatonin would modify RSV-induced lung disease and oxidative stress. The present study was to establish the involvement of oxidative stress in the pathogenesis of RSV-induced lung inflammation, and to investigate the protective effect of administration of melatonin in mice with RSV-induced oxidative pulmonary injury for 4 days. Malondialdehyde (MDA), an end product of lipid peroxidation, and glutathione (GSH) and superoxide dismutase (SOD) and nitric oxide (NO) levels were evaluated in lung tissue homogenates by spectrophotometry. Hydroxyl radical (.-OH), one of the indicators of free radical formation, was also detected in lung homogenates by Fenton reaction. Tumor necrosis factor-a (TNF-a) concentrations in mouse serum were measured with ELISA assay. The results demonstrated that the mice intranasally inoculated with RSV resulted in oxidative stress changes by increasing NO, MDA and .-OH levels, and decreasing GSH and SOD activities, whereas administration of melatonin significantly reversed all these effects. Furthermore, melatonin inhibited production of proinflammatory cytokines such as TNF-a in serum of RSV-infected mice. These results suggest that melatonin ameliorates RSV-induced lung inflammatory injury in mice via inhibition of oxidative stress and proinflammatory cytokine production and may be as a novel therapeutic agent in virus-induced pulmonary infection.

Protective effects of omega-3 fish oil on lead-induced impairment of long-term potentiation in rat dentate gyrus in vivo.

In order to evaluate the effect of omega-3 fish oil supplement by gavage (0.4 mL/100 g body weight) on the chronic lead-induced (0.2% lead acetate) impairments of long-term potentiation (LTP) in rat dentate gyrus (DG) in vivo, we designed the experiments which were carried out in four groups of newborn Wistar rats (the control, the lead-exposed, the control with fish oil treatment and the lead-exposed with fish oil treatment, respectively). The excitatory postsynaptic potential (EPSP) and population spike (PS) amplitude were measured in the DG of rats with above different treatments at the age of 80-90 d in response to stimulation applied to the lateral perforant path. The results showed (1) postnatal chronic lead-exposure impaired LTP measured on both EPSP slope and PS amplitude in DG area of the hippocampus; (2) in the control rats, omega-3 fish oil had no effect on LTP while in the lead-exposed rats, omega-3 fish oil had a protective effect on LTP. These results suggest that omega-3 fish oil supplement could protect rats from the lead-induced impairment of LTP. Omega-3 fish oil might be a preventive substance in reducing LTP deficits induced by lead.

The impacts of maternal separation experience and its pattern on depression and dysfunctional attitude in middle school students in rural China.

BACKGROUND: In China, because of the growth of economically driven rural-to-urban migration, there are lots of children in rural area who are separating or have separation experience with their parents. Until now, few studies focused on solely maternal separation and no research studied whether its pattern will affect children's later psychological status. AIM: The aim of this study was to determine whether early or late maternal separation affects depression and dysfunctional attitude in middle school students and what is the role of cumulative duration and meeting frequency. METHODS: Maternal separation experience was obtained by using questionnaires. We got early maternal separation group first. Then, late maternal separation and control group were obtained with the same number by matching grade, sex and family socioeconomic status. All the students in the three groups completed the scales of Children's Depression Inventory (CDI) and Dysfunctional Attitude Scale (DAS). RESULTS: Both CDI and DAS scores of early separation group are higher than the other two groups. When we split the data by sex, only females presented the same results. When cumulative duration is short, there is significant difference in both scores of CDI and DAS among the three groups, which showed the scores of early separation group are higher than the other two groups. When the cumulative duration is long, there is no significant difference among the three groups. When meeting frequency is high, there is no significant difference among the three groups. When it is low, there is significant difference among the three groups, which showed the CDI and DAS scores of early separation group are higher than the other two groups. Furthermore, the same results are also found in females. CONCLUSION: Early maternal separation may exert negative influence on student's depression and dysfunctional attitude. The sex, cumulative duration and meeting frequency may also play important roles in the effect.

Effects of chronic administration of melatonin on spatial learning ability and long-term potentiation in lead-exposed and control rats.

OBJECTIVE: To explore the changes in spatial learning performance and long-term potentiation (LTP) which is recognized as a component of the cellular basis of learning and memory in normal and lead-exposed rats after administration of melatonin (MT) for two months. METHODS: Experiment was performed in adult male Wistar rats (12 controls, 12 exposed to melatonin treatment, 10 exposed to lead and 10 exposed to lead and melatonin treatment). The lead-exposed rats received 0.2% lead acetate solution from their birth day while the control rats drank tap water. Melatonin (3 mg/kg) or vehicle was administered to the control and lead-exposed rats from the time of their weaning by gastric gavage each day for 60 days, depending on their groups. At the age of 81-90 days, all the animals were subjected to Morris water maze test and then used for extracellular recording of LTP in the dentate gyrus (DG) area of the hippocampus in vivo. RESULTS: Low dose of melatonin given from weaning for two months impaired LTP in the DG area of hippocampus and induced learning and memory deficit in the control rats. When melatonin was administered over a prolonged period to the lead-exposed rats, it exacerbated LTP impairment, learning and memory deficit induced by lead. CONCLUSION: Melatonin is not suitable for normal and lead-exposed children.

S-adenosyl-L-methionine improves impaired hippocampal long-term potentiation and water maze performance induced by developmental lead exposure in rats.

Lead (Pb(2+)) exposure in children can induce long-lasting deficits in cognitive function and has been modeled in experimental animals. Based on previous studies which demonstrated that S-adenosyl-l-methionine (SAM) is beneficial in the treatment of lead intoxication, here, we asked the question if SAM treatment could rescue the impaired cognition and synaptic plasticity induced by lead. Rats drank 1500 ppm lead acetate (PbAc) solution or distilled water throughout gestation and lactation. After weaning at postnatal day 22, one half of the control and lead-exposed male offspring were intraperitoneally injected 20 mg SAM/kg daily over a period of 20-22 days. Electrophysiological and Morris water maze test were performed at 44-54 days of age. The result showed that the impaired learning ability induced by lead could be improved significantly by SAM. Furthermore, our results revealed that long-term potentiation (LTP) of excitatory postsynaptic potential and population spike impairments induced by lead were also ameliorated by SAM treatment.

Melatonin decreases TLR3-mediated inflammatory factor expression via inhibition of NF-kappa B activation in respiratory syncytial virus-infected RAW264.7 macrophages.

Double-stranded (ds) RNA has been identified as a ligand for Toll-like receptor 3 (TLR3). Respiratory syncytial virus (RSV), a single-stranded RNA virus and a major respiratory pathogen and pneumovirus in human infants pathogenesis of which relies on early inflammatory and immune events of the host in response to RSV, could be recognized by TLR3 sensing viral dsRNA produced during replication. The downstream signaling pathway from TLR3 leads to activation of IFN regulatory factor (IRF)-3 and/or NF-kappaB and subsequent expression of numerous proinflammatory factors. Melatonin (MT) is an effective regulator of the immune system. To determine the molecular mechanisms responsible for the suppressive effect of MT on RSV infection, we analyzed signaling molecules involved in the TLR3-mediated activation of inflammatory factors in macrophages infected with RSV and the modulatory role of MT on these mediators. We report that RSV infection of RAW264.7 macrophages time-dependently stimulate the rapid activation of TLR3 and NF-kappaB, as well as subsequent NF-kappaB-dependent gene expression such as those encoding TNF-alpha and inducible nitric oxide synthase. Moreover, we demonstrate that MT decreased TLR3-mediated downstream gene expression in RSV-infected macrophages in a dose- and time-dependent manner, and that MT inhibition of NF-kappaB activity seemed to be the key event required to explain the reduction in inflammatory gene expression caused by MT. But MT did not influence TLR3 at either the protein or mRNA level or MyD88 transcription. These results could be related to the beneficial immunoregulatory role of MT in RSV-infected macrophages and address the possible therapeutic potential of this indoleamine in human RSV diseases.

[Protection effects of S-adenosyl-L-methionine on lead-exposed rats during development and its mechanism of long-term potentiation].

OBJECTIVE: To explore the effects of S-adenosyl-L-methionine (SAM) on blood lead concentration and oxidative stress of tissue in prenatal and postnatal lead-exposed rats, and evaluate the potential reparation exerted by SAM on paired-pulse facilitation (PPF) and long-term potentiation (LTP) in lead-exposed rat. METHODS: Pregnant Wistar rats were randomly divided into three groups: control, lead-exposed and lead-exposed with SAM treatment groups. Lead-exposed rats drank 1.5 g/L lead acetate solution through pregnancy until weaning and then the pups received 20 mg/kg SAM or saline daily intraperitoneally depending on their group. Control group rats drank tap water throughout the experiment. At the postnatal 44-60 days, all the pup rats were given an extracellular recording measured in dentate gyrus (DG) area of hippocampus. The blood lead concentration and oxidative stress in liver, brain and hippocampus were also detected. RESULTS: The blood lead concentration in lead-exposed group was higher (159. 3 +/- 10. 9 microg/L) in comparing with those of control group (27.5 +/-3.8 microg/L) and lead +SAM group (33.1 +/-9.5 microg/L) (F=213.5, P<0.01). A significant recovery of liver, brain glutathione (GSH) and malondialdehyde (MDA) level was clearly produced in lead-exposed rats after SAM treatment (P <0.05). Chronic lead exposure during development impaired LTP measured on field excitatory postsynaptic potential (EPSP) [(112 +/-2.1)%] compared with control rats [(131+/-4.5)%] and the impaired LTP could be significantly increased by SAM treatment [(120 +/- 2.6)%] (F = 26. 1, P <0. 05). CONCLUSION: SAM might be beneficial for treatment of lead intoxication, especially in the rescue of learning and memory impairment induced by lead and should deserve more detailed research.