Administration of Histidine to Female Rats Induces Changes in Oxidative Status in Cortex and Hippocampus of the Offspring

Histidinemia is an inherited metabolic disorder biochemically characterized by high concentrations of histidine in biological fluids. Usually affected patients are asymptomatic although some individuals have mental retardation and speech disorders. Considering the high prevalence of histidinemia and the scarce information on the effects of maternal histidinemia on their progeny, we investigated various parameters of oxidative stress in brain cortex and hippocampus of the offspring from female rats that received histidine (0.5 mg/g of body weight) in the course of pregnancy and lactation. At 21 days of age we found a significant increase of thiobarbituric acid reactive substances (TBARS), 2′,7′-dihydrodichlorofluorescein oxidation, superoxide dismutase (SOD) activity, catalase (CAT) activity, total sulfhydryls and glutathione (GSH) content in cerebral cortex and hippocampus. We also verified that at 60 days of age, GSH, SOD and total sulfhydryls returned to normal levels in brain cortex, while the other parameters decreased in the same structure. In the hippocampus, at 60 days of age GSH returned to normal levels, CAT persisted elevated and the other parameters decreased. These results indicate that histidine administration to female rats can induce oxidative stress in the brain from the offspring, which partially recovers 40 days after breastfeeding stopped.     

Neonatal Exposure to Bacterial Lipopolysaccharide Affects Behavior and Expression of Ionotropic Glutamate Receptors in the Hippocampus of Adult Rats after Psychogenic Trauma

Biochemistry (Moscow) - According to the two-hit hypothesis of psychoneuropathology formation, infectious diseases and other pathological conditions occurring during the critical periods of early...     

饲喂雌鼠大豆异黄酮对后代雌性生殖性状的影响

目的研究雌性小鼠饲喂异黄酮后对其后代雌鼠生殖性状的影响。方法分别在雌鼠从断奶到妊娠前和妊娠期间两个不同阶段的日粮中添加不同剂量的大豆异黄酮（0、50、400 mg/kg）。记录F1代的出生窝产仔数、出生窝重、雌鼠的阴道最早开张时间和最早见栓时间,以及后代雌鼠性成熟期和体成熟期生殖器官重量、血清雌激素的含量。结果雌鼠妊娠期饲喂含50、400 mg/kg大豆异黄酮的饲料后F1代的窝产仔数显著高于对照组（P〈0.05）;雌鼠妊娠期采食400 mg/kg大豆异黄酮饲料,其后代雌鼠初次配种时间明显延迟（P〈0.05）;45、65日龄体重显著低于对照组,65日龄子宫重显著低于对照组,卵巢重显著高于对照组;血清中雌激素含量显著低于对照组（P〈0.05）,妊娠期间采食50 mg/kg大豆异黄酮饲料,其F1代雌鼠仅窝产仔数和45日龄时血清中雌激素含量受到影响;而雌鼠从断奶到怀孕期间饲喂含大豆异黄酮饲料的F1代在各项指标与对照组均差异无显著性。结论雌鼠妊娠期间饲喂含400 mg/kg大豆异黄酮的饲料会显著影响其雌性后代的初情期、生殖器官发育、血清雌激素含量等生殖生理性状,而在非妊娠期饲喂含大豆异黄酮饲料对F1代无显著影响。     

Neuritin在大鼠脑外伤合并骨折过程中的作用研究

目的:研究脑外伤合并股骨骨折的骨痂中Neuritin的表达及血清中变化,探讨中枢神经系统损伤加速对骨折愈合的作用,为临床难治性骨创伤提供新的理论依据。方法:取96只雄性SD大鼠随机分成:A组正常组8只、B组单纯骨折组40只、C组单纯脑外伤组8只及D组骨折合并脑外伤组40只,做股骨骨折和采用脑损伤液压装置建脑损伤模型,术后3、7、14、21、28天取血离心,ELISA法测血清中的Neuritin值。分时间处死B组和D组,取骨痂做切片,行免疫组织化学染色,观测各时间点骨痂中Neuritin的变化和骨折愈合情况。结果:①免疫组织化学染色:骨折愈合过程中血管内皮细胞、软骨细胞及成骨细胞的胞浆中有阳性表达,并显色强。D组1w至3w时的Neuritin阳性细胞百分数均高于B组有显著性统计意义(P<0.05),但4周时(P>0.05)。②血清浓度值:A组值(81.37±1.37),B组、C组、D组3天(94.94±3.77 107.28±3.46 118.35±1.43)逐渐升高,2周达到高峰(110.18±1.48131.89±3.26 161.48±1.46),然后下降,3d至3w时各组有显著性统计意义(P<0.05),4周下降为略高于正常(P>0.05)结论:血清和骨痂中Neuritin的表达显著升高,提示Neuritin可能是大鼠股骨骨折合并脑损伤时促进骨折修复的重要因素一     

Neuritin在大鼠脑外伤合并骨折过程中的作用研究

目的：研究脑外伤合并股骨骨折的骨痂中Neuritin的表达及血清中变化,探讨中枢神经系统损伤加速对骨折愈合的作用,为临床难治性骨创伤提供新的理论依据。方法：取96只雄性SD大鼠随机分成：A组正常组8只、B组单纯骨折组40只、C组单纯脑外伤组8只及D组骨折合并脑外伤组40只,做股骨骨折和采用脑损伤液压装置建脑损伤模型,术后3、7、14、21、28天取血离心,ELISA法测血清中的Neuritin值。分时间处死B组和D组,取骨痂做切片,行免疫组织化学染色,观测各时间点骨痂中Neuritin的变化和骨折愈合情况。结果：①免疫组织化学染色：骨折愈合过程中血管内皮细胞、软骨细胞及成骨细胞的胞浆中有阳性表达,并显色强。D组1w至3w时的Neuritin阳性细胞百分数均高于B组有显著性统计意义（P〈0．05）,但4周时（P〉0．05）。②血清浓度值：A组值（81．37±1．37）,B组、C组、D组3天（94．94±3．77107．28±3．46118．35±1．43）逐渐升高,2周达到高峰（110．18±1．48131．89±3．26161．48±1．46）,然后下降,3d至3w时各组有显著性统计意义（P〈0．05）,4周下降为略高于正常（P〉0．05）。结论：血清和骨痂中Neuritin的表达显著升高,提示Neuritin可能是大鼠股骨骨折合并脑损伤时促进骨折修复的重要因素一。     

Mitochondrial DNA Deletion in Offspring of Female Mice Exposed to X-Rays

Biophysics - Abstract—The effects of X-ray exposure on the mitochondrial genome were studied in the offspring of female mice exposed in the preconception period at doses of 0.5 and 2 Gy....     

Social Experience During Development and Female Offspring Aggression in Peromyscus Mice

Cross‐fostering between the highly aggressive, biparental California mouse (Peromyscus californicus) and the less aggressive, less parental white‐footed mouse (P. leucopus) influences female offspring attack latency in California mice, but not in white‐footed mice. Adult female California mice raised by white‐footed mice expressed longer attack latencies in a neutral‐arena test but not in a resident‐intruder test. One social cue that may be used by offspring to develop environmentally appropriate levels of aggression is the type of parental care during development. In California mice, a composite score of maternal behavior was positively associated with neutral‐arena aggression as indicated by decreased attack latency. In both species, paternal nest‐building was positively associated with neutral‐arena aggression and higher maternal retrieval behavior predicted higher offspring resident‐intruder aggression as indicated by decreased attack latency. Together, these results indicate that parental behavior has the potential to shape the development of attack latency in female offspring.     

Lipopolysaccharide Exposure during Pregnancy Leads to Aortic Dysfunction in Offspring Rats

Background

Prenatal exposure to Lipopolysaccharide (LPS) produces hypertension in adult offspring rats. The present study was to explore the effects of prenatal inflammation on morphological and functional changes in the aorta from offspring rats and to further assess its susceptibility to cardiovascular diseases.

Methods and Results

Pregnant rats were treated intraperitoneally on gestation Days 8, 10 and 12 with saline, LPS (0.79 mg/kg), or pyrrolidine dithiocarbamate (PDTC, 100 mg/kg)+LPS, respectively. Aortic ring reactivity and histopathological alteration were analyzed in offspring at the age of 12 weeks. The detections of connexin (Cx) 37, Cx40, Cx43, and Cx45, including immunofluorescent patterns, protein levels and mRNA expression in the aorta, were performed as well. Furthermore, the expressions of Nuclear factor (NF)-κB (p65), IκBα, phospho-IκBα and IκBβ were determined. The results showed that prenatal LPS exposure leads to morphological abnormalities and impaired aortic reactivity in offspring. Prenatal LPS exposure also decreased the protein and mRNA expression of Cx37 in the aorta from offspring rats. NF-κB and phospho-IκBα levels were both increased, IκBα level, however, was decreased in the aorta of offspring from the maternal LPS exposure compared to the controls. Simultaneously, PDTC treatment markedly reversed the action of LPS.

Conclusions

Decreased expression of Cx37 contributed to the aortic dysfunction of prenatal LPS exposure offspring, which should be associated with NF-κB activation.     

Female Control of Offspring Sex Ratios Based on Male Attractiveness in the Guppy

The sex allocation hypothesis predicts that females manipulate the offspring sex ratios according to mate attractiveness. Although there is increasing evidence to support this prediction, it is possible that paternal effects may often obscure the relationship between female control of offspring sex ratios and male attractiveness. In the present study, we examined whether females played a primary role in the manipulation their offspring sex ratios based on male attractiveness, in the guppy Poecilia reticulata, a live‐bearing fish. We excluded the paternal effects by controlling the relative sexual attractiveness of the male by presenting them to the females along with a more attractive or less attractive stimulus male. The test male was perceived to be relatively more attractive by females when it was presented along with a less attractive stimulus male, or vice versa. Subsequently, test male was mated in two different roles (relatively more and less attractive) with two females. If females were responsible for offspring sex ratio manipulation, the sex ratio of the brood would be altered on the basis of the relative attractiveness of the test male. On the other hand, if males play a primary role in offspring sex ratio manipulation, the sex ratios would not differ with the relative attractiveness of the test male. We found that females gave birth to more male‐biased broods when they mated with test males in the attractive role than when they mated with males in the less attractive role. This finding suggests that females are responsible for the manipulation of offspring sex ratios based on the attractiveness of their mates.     

Immune Effects of Nonylphenol on Offspring of Rats Exposed During Pregnancy

Effects of nonylphenol on immune system of male rats were examined. Dams were treated orally with nonylphenol at doses of 0, 20, 40, 80, or 200 mg/kg, respectively, from pregnant days 14 to 19. The offspring rats were investigated at postnatal day 60. Compared with the control groups, the doses of 80 and 200 mg nonylphenol/kg induced an obvious decrease in the absolute and relative weight of spleen and thymus. In the 200 mg/kg nonylphenol-treated group, the proliferative responses of murine spleen lymphocytes cultured in vitro were suppressed, Cytokine productions of interferon-gamma and interleukin-6 in serum were markedly lower than those in the control group. Histologically, the boundary between splenic red pulp and white pulp was unclear, expansion and congestion appeared in splenic sinus, lymphocytes in spleen and thymus dramatically reduced, and lots of focal necrosis cells were present. The results of this study show that nonylphenol can cross the placenta barrier, and that in utero exposure to 200 mg/kg/day nonylphenol can inhibit immune function in male offspring rats.     

Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood

Naltrexone is not recommended during pregnancy. However, sustained-release naltrexone implant use in humans has resulted in cases of inadvertent foetal exposure. Here, we used clinically relevant dosing to examine the effects of maternally administered sustained-release naltrexone on the rat brain by examining offspring at birth and in adulthood. Maternal treatment (naltrexone or placebo implant) started before conception and ceased during gestation, birth or weaning. Morphometry was assessed in offspring at birth and adulthood. Adult offspring were evaluated for differences in locomotor behaviour (basal and morphine-induced, 10 mg/kg, s.c.) and opioid neurochemistry, propensity to self-administer morphine and cue-induced drug-seeking after abstinence. Blood analysis confirmed offspring exposure to naltrexone during gestation, birth and weaning. Naltrexone exposure increased litter size and reduced offspring birth-weight but did not alter brain morphometry. Compared to placebo, basal motor activity of naltrexone-exposed adult offspring was lower, yet they showed enhanced development of psychomotor sensitization to morphine. Developmental naltrexone exposure was associated with resistance to morphine-induced down-regulation of striatal preproenkephalin mRNA expression in adulthood. Adult offspring also exhibited greater operant responding for morphine and, in addition, cue-induced drug-seeking was enhanced. Collectively, these data show pronounced effects of developmental naltrexone exposure, some of which persist into adulthood, highlighting the need for follow up of humans that were exposed to naltrexone in utero.     

Prenatal Stress Causes Oxidative Damage to Mitochondrial DNA in Hippocampus of Offspring Rats

Mitochondrion, the primary source of reactive oxygen species (ROS), is also the target of ROS. 8-Hydroxy-2′-deoxyguanosine (8-OH-dG) is the major end-product of damaged DNA caused by ROS. In our previous studies, we showed that prenatal stress (PNS) preferentially caused cognitive dysfunction and increased ROS in the hippocampus of female offspring rats. The present study aimed to determine 8-OH-dG level of mitochondria in order to elucidate the mechanism of hippocampal pyramidal neuronal damage and cognitive dysfunction induced by PNS. Pregnant rats were divided into two groups: control group (undisturbed) and PNS group (exposed to a restraint stress for 7 days at the late stage of gestation). Offspring rats were divided into four groups: female-control group, male-control group, female-stress group, male-stress group and used at 30-day-old after their birth. The content of 8-OH-dG was determined by high performance liquid chromatography-electrochemical detection (HPLC-ECD). The results showed that the contents of 8-OH-dG in female and male prenatal stressed offspring were significantly higher than that in their respective controls (P < 0.001). 8-OH-dG level was significantly higher in the female-stress group than in the male-stress group (P < 0.05), whereas there was no any gender-dependent difference in the control groups. These results suggest that accumulation of oxidative mitochondrial DNA damage may play an important role in PNS-induced cognitive dysfunction in female offspring rats. Special issue article in honor of Dr. Akitane Mori.     

Folic Acid Affects Iron Status in Female Rats with Deficiency of These Micronutrients

Biological Trace Element Research - Although simultaneous supplementation with iron and folic acid is justified, the potential interactions between these micronutrients are unknown. The aim of this...     

Neuroprotective Effects of N-acetylcysteine on Experimental Closed Head Trauma in Rats

N-acetylcysteine (NAC) is a precursor of glutathione, a potent antioxidant, and a free radical scavenger. The beneficial effect of NAC on nervous system ischemia and ischemia/reperfusion models has been well documented. However, the effect of NAC on nervous system trauma remains less understood. Therefore, we aimed to investigate the therapeutic efficacy of NAC with an experimental closed head trauma model in rats. Thirty-six adult male Sprague–Dawley rats were randomly divided into three groups of 12 rats each: Group I (control), Group II (trauma-alone), and Group III (trauma+NAC treatment). In Groups II and III, a cranial impact was delivered to the skull from a height of 7 cm at a point just in front of the coronal suture and over the right hemisphere. Rats were sacrificed at 2 h (Subgroups I-A, II-A, and III-A) and 12 h (Subgroups I-B, II-B, and III-B) after the onset of injury. Brain tissues were removed for biochemical and histopathological investigation. The closed head trauma significantly increased tissue malondialdehyde (MDA) levels (P<0.05), and significantly decreased tissue superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities (P<0.05), but not tissue catalase (CAT) activity, when compared with controls. The administration of a single dose of NAC (150 mg/kg) 15 min after the trauma has shown protective effect via decreasing significantly the elevated MDA levels (P<0.05) and also significantly (P<0.05) increasing the reduced antioxidant enzyme (SOD and GPx) activities, except CAT activity. In the trauma-alone group, the neurons became extensively dark and degenerated into picnotic nuclei. The morphology of neurons in the NAC treatment group was well protected. The number of neurons in the trauma-alone group was significantly less than that of both the control and trauma+NAC treatment groups. In conclusion, the NAC treatment might be beneficial in preventing trauma-induced oxidative brain tissue damage, thus showing potential for clinical implications.     

Advanced Parental Age Impaired Fear Conditioning and Hippocampal LTD in Adult Female Rat Offspring

Advanced maternal or paternal age is associated with increased risks of cognitive and emotional disorders. Chronic stress is also a common experience in human life that causes psychiatric diseases. However, the synergistic effects of these two factors on offspring are rarely studied. In the present study, the offspring of both young (3–4 months) and old (12–14 months) rat parents were given CUMS for 21 days at the age of 4 weeks. The effects of advanced parental age and chronic unpredictable mild stress (CUMS) on emotional and cognitive behaviors and the related cellular mechanisms were investigated by using behavioral and electrophysiological techniques. We found that CUMS decreased sucrose consumption, increased anxiety, and impaired learning and memory in offspring from both old and young breeders. However, advanced parental age impaired fear memory and spatial memory mainly in female offspring. The serum corticosterone of female offspring was lower than males, but advanced parental age significantly elevated serum corticosterone in female offspring in response to electrical foot shocks. In addition, hippocampal LTD was severely impaired in female offspring from older parents. Our results indicated that female offspring from older breeders might be more sensitive to stress, and the hippocampal function was more vulnerable. These results might provide experimental basis for the prevention and treatment of advanced parental age related psychiatric disorders in future.     

Time-Dependent Effects of Trichloroethylene on Motor Activity in Rats

Circadian variations in acute and subacute neurobehavioural effects of trichloroethylene (TRI: 1.2 g/kg i.p.) were investigated in the rat under a light: dark = 12:12 hr cycle. An acute effect of TRI evaluated by decreased muscle tone was maximal during the early dark phase (21:00). A subacute effect of TRI was evaluated by a continuous recording of spontaneous locomotor activity in the rat. The circadian rhythm in spontaneous locomotor activity was extensively impaired by the injection of TRI for three consecutive days. Spectral analysis of spontaneous locomotor activity showed that ultradian periods became more dominant than the circadian period, and the 1//fluctuation of the spectrum disappeared after the injection of TRI. The effect of TRI on the circadian rhythm in spontaneous locomotor activity was circadian-phase dependent, and the treatment of TRI at 09:00 provoked greater circadian rhythm impairment than that at 21:00. The mechanisms of the time-dependent effect of TRI on neurobehaviour are the subject of further investigation.     

Wistar大鼠运动皮层代表区的微刺激测定

在１５例氯胺酮麻醉的Ｗｉｓｔａｒ大鼠利用皮层内微刺激技术测定了躯体的运动皮层代表区。电刺激为３５０Ｈｚ的阴极串脉冲,电流最大值限为８０μＡ。结果表明大多数皮层点诱发对侧肌肉反应。虽然代表区的大小有很大个体差异,分区的相对位置是恒定的。但在分区内部未见分域排列。部分大鼠存在前部前肢区,但无一例发现前部后肢区。比较文献结果提示Ｗｉｓｔａｒ大鼠的运动皮层的分化程度比Ｌｏｎｇ－Ｅｖａｎｓ黑顶鼠低。