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Sample records for 2-knockout mice exposed

  1. Arginase inhibition in airways from normal and nitric oxide synthase 2-knockout mice exposed to ovalbumin

    International Nuclear Information System (INIS)

    Arginase1 and nitric oxide synthase2 (NOS2) utilize L-arginine as a substrate, with both enzymes expressed at high levels in the asthmatic lung. Inhibition of arginase in ovalbumin-exposed C57BL/6 mice with the transition state inhibitor Nω-hydroxy-nor-L-arginine (nor-NOHA) significantly increased total L-arginine content in the airway compartment. We hypothesized that such an increase in L-arginine content would increase the amount of nitric oxide (NO) being produced in the airways and thereby decrease airway hyperreactivity and eosinophilic influx. We further hypothesized that despite arginase inhibition, NOS2 knockout (NOS2-/-) mice would be unable to up-regulate NO production in response to allergen exposure and would demonstrate higher amounts of airway hyperreactivity and eosinophilia under conditions of arginase inhibition than C57BL/6 animals. We found that administration of nor-NOHA significantly decreased airway hyperreactivity and eosinophilic airway inflammation in ovalbumin-exposed C57BL/6 mice, but these parameters were unchanged in ovalbumin-exposed NOS2-/- mice. Arginase1 protein content was increased in mice exposed to ovalbumin, an effect that was reversed upon nor-NOHA treatment in C57BL/6 mice. Arginase1 protein content in the airway compartment directly correlated with the degree of airway hyperreactivity in all treatment groups. NOS2-/- mice had significantly greater arginase1 and arginase2 concentrations compared to their respective C57BL/6 groups, indicating that inhibition of arginase may be dependent upon NOS2 expression. Arginase1 and 2 content were not affected by nor-NOHA administration in the NOS2-/- mice. We conclude that L-arginine metabolism plays an important role in the development of airway hyperreactivity and eosinophilic airway inflammation. Inhibition of arginase early in the allergic inflammatory response decreases the severity of the chronic inflammatory phenotype. These effects appear to be attributable to NOS2, which is a

  2. Sleep in Kcna2 knockout mice

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    Messing Albee

    2007-10-01

    Full Text Available Abstract Background Shaker codes for a Drosophila voltage-dependent potassium channel. Flies carrying Shaker null or hypomorphic mutations sleep 3–4 h/day instead of 8–14 h/day as their wild-type siblings do. Shaker-like channels are conserved across species but it is unknown whether they affect sleep in mammals. To address this issue, we studied sleep in Kcna2 knockout (KO mice. Kcna2 codes for Kv1.2, the alpha subunit of a Shaker-like voltage-dependent potassium channel with high expression in the mammalian thalamocortical system. Results Continuous (24 h electroencephalograph (EEG, electromyogram (EMG, and video recordings were used to measure sleep and waking in Kcna2 KO, heterozygous (HZ and wild-type (WT pups (P17 and HZ and WT adult mice (P67. Sleep stages were scored visually based on 4-s epochs. EEG power spectra (0–20 Hz were calculated on consecutive 4-s epochs. KO pups die by P28 due to generalized seizures. At P17 seizures are either absent or very rare in KO pups ( Conclusion Kv1.2, a mammalian homologue of Shaker, regulates neuronal excitability and affects NREM sleep.

  3. Subchronic exposure to ethyl tertiary butyl ether resulting in genetic damage in Aldh2 knockout mice.

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    Weng, Zuquan; Suda, Megumi; Ohtani, Katsumi; Mei, Nan; Kawamoto, Toshihiro; Nakajima, Tamie; Wang, Rui-Sheng

    2013-09-15

    Ethyl tertiary butyl ether (ETBE) is biofuel additive recently used in Japan and some other countries. Limited evidence shows that ETBE has low toxicity. Acetaldehyde (AA), however, as one primary metabolite of ETBE, is clearly genotoxic and has been considered to be a potential carcinogen. The aim of this study was to evaluate the effects of ALDH2 gene on ETBE-induced genotoxicity and metabolism of its metabolites after inhalation exposure to ETBE. A group of wild-type (WT) and Aldh2 knockout (KO) C57BL/6 mice were exposed to 500ppm ETBE for 1-6h, and the blood concentrations of ETBE metabolites, including AA, tert-butyl alcohol and 2-methyl-1,2-propanediol, were measured. Another group of mice of WT and KO were exposed to 0, 500, 1750, or 5000ppm ETBE for 6h/day with 5 days per weeks for 13 weeks. Genotoxic effects of ETBE in these mice were measured by the alkaline comet assay, 8-hydroxyguanine DNA-glycosylase modified comet assay and micronucleus test. With short-term exposure to ETBE, the blood concentrations of all the three metabolites in KO mice were significantly higher than the corresponding concentrations of those in WT mice of both sexes. After subchronic exposure to ETBE, there was significant increase in DNA damage in a dose-dependent manner in KO male mice, while only 5000ppm exposure significantly increased DNA damage in male WT mice. Overall, there was a significant sex difference in genetic damage in both genetic types of mice. These results showed that ALDH2 is involved in the detoxification of ETBE and lack of enzyme activity may greatly increase the sensitivity to the genotoxic effects of ETBE, and male mice were more sensitive than females. PMID:23810710

  4. Expression of PPARα modifies fatty acid effects on insulin secretion in uncoupling protein-2 knockout mice

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    Chan Catherine B

    2007-03-01

    Full Text Available Abstract Aims/hypothesis In uncoupling protein-2 (UCP2 knockout (KO mice, protection of beta cells from fatty acid exposure is dependent upon transcriptional events mediated by peroxisome proliferator-activated receptor-α (PPARα. Methods PPARα expression was reduced in isolated islets from UCP2KO and wild-type (WT mice with siRNA for PPARα (siPPARα overnight. Some islets were also cultured with oleic or palmitic acid, then glucose stimulated insulin secretion (GSIS was measured. Expression of genes was examined by quantitative RT-PCR or immunoblotting. PPARα activation was assessed by oligonucleotide consensus sequence binding. Results siPPARα treatment reduced PPARα protein expression in KO and WT islets by >85%. In siPPARα-treated UCP2KO islets, PA but not OA treatment significantly decreased the insulin response to 16.5 mM glucose. In WT islets, siPPARα treatment did not modify GSIS in PA and OA exposed groups. In WT islets, PA treatment significantly increased UCP2 mRNA and protein expression. Both PA and OA treatment significantly increased PPARα expression in UCP2KO and WT islets but OA treatment augmented PPARα protein expression only in UCP2KO islets (p Conclusion These data show that the negative effect of saturated fatty acid on GSIS is mediated by PPARα/UCP2. Knockout of UCP2 protects beta-cells from PA exposure. However, in the absence of both UCP2 and PPARα even a short exposure (24 h to PA significantly impairs GSIS.

  5. Lack of stress responses to long-term effects of corticosterone in Caps2 knockout mice

    OpenAIRE

    MISHIMA, Yuriko; Shinoda, Yo; Sadakata, Tetsushi; Kojima, Masami; Wakana, Shigeharu; Furuichi, Teiichi

    2015-01-01

    Chronic stress is associated with anxiety and depressive disorders, and can cause weight gain. Ca2+-dependent activator protein for secretion 2 (CAPS2) is involved in insulin release. Caps2 knockout (KO) mice exhibit decreased body weight, reduced glucose-induced insulin release, and abnormal psychiatric behaviors. We chronically administered the stress hormone corticosterone (CORT), which induces anxiety/depressive-like behavior and normally increases plasma insulin levels, via the drinking ...

  6. Gliosis after traumatic brain injury in conditional ephrinB2-knockout mice

    Institute of Scientific and Technical Information of China (English)

    LIU Ling; CHEN Xiao-lin; YANG Jian-kai; REN Ze-guang; WANG Shuo

    2012-01-01

    Background In response to the injury of the central nervous system (CNS),the astrocytes upregulate the expression of glial fibrillary acidic protein (GFAP),which largely contributes to the reactive gliosis after brain injury.The regulatory mechanism of this process is still not clear.In this study,we aimed to compare the ephrin-B2 deficient mice with the wild type ones with regard to gliosis after traumatic brain injury.Methods We generated ephrin-B2 knockout mice specifically in CNS astrocytes.Twelve mice from this gene-knockout strain were randomly selected along with twelve mice from the wild type littermates.In both groups,a modified controlled cortical impact injury model was applied to create a closed traumatic brain injury.Twenty-eight days after the injury,Nissl staining and GFAP immunofluorescence staining were used to compare the brain atrophy and GFAP immunoreactivity between the two groups.All the data were analyzed by t-test for between-group comparison.Results We successfully set up the conditional ephrin-B2 knockout mice strain,which was confirmed by genotyping and ephrin-B2/GFAP double staining.These mice developed normally without apparent abnormality in general appearance.Twenty-eight days following brain injury,histopathology revealed by immunohistochemistry showed different degrees of cerebral injuries in both groups.Compared with wild-type group,the ephrin-B2 knockout group exhibited less brain atrophy ratio for the injured hemispheres (P=0.005) and hippocampus (P=0.027).Also the wild-type group demonstrated greater GFAP immunoreactivity increment within hippocampal regions (P=0.008).Conclusions The establishment of conditional ephrin-B2 knockout mice provides us with a new way to explore the role of ephrin-B2 in astrocytes.Our findings revealed less atrophy and GFAP immunoreactivity in the knockout mice strain after traumatic brain injury,which implied ephrin-B2 could be one of the promoters to upregulate gliosis following brain injury.

  7. CXCR2 knockout mice are protected against DSS-colitis-induced acute kidney injury and inflammation.

    Science.gov (United States)

    Ranganathan, Punithavathi; Jayakumar, Calpurnia; Manicassamy, Santhakumar; Ramesh, Ganesan

    2013-11-15

    Organ cross talk exists in many diseases of the human and animal models of human diseases. A recent study demonstrated that inflammatory mediators can cause acute kidney injury and neutrophil infiltration in a mouse model of dextran sodium sulfate (DSS)-colitis. However, the chemokines and their receptors that may mediate distant organ effects in colitis are unknown. We hypothesized that keratinocyte chemoattractant (KC)/IL-8 receptor chemokine (C-X-C motif) ligand 2 (CXCL2) mediates DSS-colitis-induced acute kidney injury. Consistent with our hypothesis, wild-type (WT) mice developed severe colitis with DSS treatment, which was associated with inflammatory cytokine and chemokine expression and neutrophil infiltration in the colon. DSS-colitis in WT was accompanied by acute kidney injury and enhanced expression of inflammatory cytokines in the kidney. However, CXCR2 knockout mice were protected against DSS-colitis as well as acute kidney injury. Moreover, the expression of cytokines and chemokines and neutrophil infiltration was blunted in CXCR2 knockout mice in the colon and kidney. Administration of recombinant KC exacerbated DSS-colitis-induced acute kidney injury. Our results suggest that KC/IL-8 and its receptor CXCR2 are critical and major mediators of organ cross talk in DSS colitis and neutralization of CXCR2 will help to reduce the incidence of acute kidney injury due to ulcerative colitis and Crohn's disease in humans.

  8. Alleviation of high-fat diet-induced fatty liver damage in group IVA phospholipase A2-knockout mice.

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    Ii, Hiromi; Yokoyama, Naoki; Yoshida, Shintaro; Tsutsumi, Kae; Hatakeyama, Shinji; Sato, Takashi; Ishihara, Keiichi; Akiba, Satoshi

    2009-12-01

    Hepatic fat deposition with hepatocellular damage, a feature of non-alcoholic fatty liver disease, is mediated by several putative factors including prostaglandins. In the present study, we examined whether group IVA phospholipase A(2) (IVA-PLA(2)), which catalyzes the first step in prostanoid biosynthesis, is involved in the development of fatty liver, using IVA-PLA(2)-knockout mice. Male wild-type mice on high-fat diets (20% fat and 1.25% cholesterol) developed hepatocellular vacuolation and liver hypertrophy with an increase in the serum levels of liver damage marker aminotransferases when compared with wild-type mice fed normal diets. These high-fat diet-induced alterations were markedly decreased in IVA-PLA(2)-knockout mice. Hepatic triacylglycerol content was lower in IVA-PLA(2)-knockout mice than in wild-type mice under normal dietary conditions. Although high-fat diets increased hepatic triacylglycerol content in both genotypes, the degree was lower in IVA-PLA(2)-knockout mice than in wild-type mice. Under the high-fat dietary conditions, IVA-PLA(2)-knockout mice had lower epididymal fat pad weight and smaller adipocytes than wild-type mice. The serum level of prostaglandin E(2), which has a fat storage effect, was lower in IVA-PLA(2)-knockout mice than in wild-type mice, irrespective of the kind of diet. In both genotypes, high-fat diets increased serum leptin levels equally between the two groups, but did not affect the serum levels of adiponectin, resistin, free fatty acid, triacylglycerol, glucose, or insulin. Our findings suggest that a deficiency of IVA-PLA(2) alleviates fatty liver damage caused by high-fat diets, probably because of the lower generation of IVA-PLA(2) metabolites, such as prostaglandin E(2). IVA-PLA(2) could be a promising therapeutic target for obesity-related diseases including non-alcoholic fatty liver disease.

  9. Serotonin abnormalities in Engrailed-2 knockout mice: New insight relevant for a model of Autism Spectrum Disorder.

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    Viaggi, Cristina; Gerace, Claudio; Pardini, Carla; Corsini, Giovanni U; Vaglini, Francesca

    2015-08-01

    Autism spectrum disorder (ASD) is a congenital neurodevelopmental behavioral disorder that appears in early childhood. Recent human genetic studies identified the homeobox transcription factor, Engrailed 2 (EN2), as a possible ASD susceptibility gene. En2 knockout mice (En2-/-) display subtle cerebellar neuropathological changes and reduced levels of tyrosine hydroxylase, noradrenaline and serotonin in the hippocampus and cerebral cortex similar to those ones which have been observed in the ASD brain. Furthermore other similarities link En2 knockout mice to ASD patients. Several lines of evidence suggest that serotonin may play an important role in the pathophysiology of the disease. In the present study we measured, by using an HPLC, the 5-HT levels in different brain areas and at different ages in En2-/- mice. In the frontal and occipital cortex, the content of 5HT was reduced in En2-/- 1 and 3 months old mice; in 6 month old mice, the difference was still present, but it was not statistically significant. The 5-HT content of cerebellar cortex was significantly reduced at 1 month old but significantly high when the KO mice reached 3 months of age. The increase was present even at 6 months of age. A similar trend was highlighted by SERT immunolabeling in En2-/- mice compared to control in the same areas and age analyzed. Our findings, in agreement with the current knowledge on the 5-HT system alterations in ASD, confirm the early neurotransmitter deficit with a late compensatory recovery in En2 KO-mice further suggesting that this experimental animal may be considered a good predictive model for the human disease. PMID:26002543

  10. Salivary Gland Hypofunction in tyrosylprotein sulfotransferase-2 Knockout Mice Is Due to Primary Hypothyroidism

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    Westmuckett, Andrew D.; Joseph C Siefert; Tesiram, Yasvir A; Pinson, David M.; Moore, Kevin L.

    2013-01-01

    Background Protein-tyrosine sulfation is a post-translational modification of an unknown number of secreted and membrane proteins mediated by two known Golgi tyrosylprotein sulfotransferases (TPST-1 and TPST-2). We reported that Tpst2-/- mice have mild-moderate primary hypothyroidism, whereas Tpst1-/- mice are euthyroid. While using magnetic resonance imaging (MRI) to look at the thyroid gland we noticed that the salivary glands in Tpst2-/- mice appeared smaller than in wild type mice. This p...

  11. Aggressive mammary carcinoma progression in Nrf2 knockout mice treated with 7,12-dimethylbenz[a]anthracene

    International Nuclear Information System (INIS)

    Activation of nuclear factor erythroid 2-related factor (Nrf2), which belongs to the basic leucine zipper transcription factor family, is a strategy for cancer chemopreventive phytochemicals. It is an important regulator of genes induced by oxidative stress, such as glutathione S-transferases, heme oxygenase-1 and peroxiredoxin 1, by activating the antioxidant response element (ARE). We hypothesized that (1) the citrus coumarin auraptene may suppress premalignant mammary lesions via activation of Nrf2/ARE, and (2) that Nrf2 knockout (KO) mice would be more susceptible to mammary carcinogenesis. Premalignant lesions and mammary carcinomas were induced by medroxyprogesterone acetate and 7,12-dimethylbenz[a]anthracene treatment. The 10-week pre-malignant study was performed in which 8 groups of 10 each female wild-type (WT) and KO mice were fed either control diet or diets containing auraptene (500 ppm). A carcinogenesis study was also conducted in KO vs. WT mice (n = 30-34). Comparisons between groups were evaluated using ANOVA and Kaplan-Meier Survival statistics, and the Mann-Whitney U-test. All mice treated with carcinogen exhibited premalignant lesions but there were no differences by genotype or diet. In the KO mice, there was a dramatic increase in mammary carcinoma growth rate, size, and weight. Although there was no difference in overall survival, the KO mice had significantly lower mammary tumor-free survival. Also, in the KO mammary carcinomas, the active forms of NF-κB and β-catenin were increased ~2-fold whereas no differences in oxidized proteins were observed. Many other tumors were observed, including lymphomas. Interestingly, the incidences of lung adenomas in the KO mice were significantly higher than in the WT mice. We report, for the first time, that there was no apparent difference in the formation of premalignant lesions, but rather, the KO mice exhibited rapid, aggressive mammary carcinoma progression

  12. Aggressive mammary carcinoma progression in Nrf2 knockout mice treated with 7,12-dimethylbenz[a]anthracene

    Directory of Open Access Journals (Sweden)

    Yamamoto Masayuki

    2010-10-01

    Full Text Available Abstract Background Activation of nuclear factor erythroid 2-related factor (Nrf2, which belongs to the basic leucine zipper transcription factor family, is a strategy for cancer chemopreventive phytochemicals. It is an important regulator of genes induced by oxidative stress, such as glutathione S-transferases, heme oxygenase-1 and peroxiredoxin 1, by activating the antioxidant response element (ARE. We hypothesized that (1 the citrus coumarin auraptene may suppress premalignant mammary lesions via activation of Nrf2/ARE, and (2 that Nrf2 knockout (KO mice would be more susceptible to mammary carcinogenesis. Methods Premalignant lesions and mammary carcinomas were induced by medroxyprogesterone acetate and 7,12-dimethylbenz[a]anthracene treatment. The 10-week pre-malignant study was performed in which 8 groups of 10 each female wild-type (WT and KO mice were fed either control diet or diets containing auraptene (500 ppm. A carcinogenesis study was also conducted in KO vs. WT mice (n = 30-34. Comparisons between groups were evaluated using ANOVA and Kaplan-Meier Survival statistics, and the Mann-Whitney U-test. Results All mice treated with carcinogen exhibited premalignant lesions but there were no differences by genotype or diet. In the KO mice, there was a dramatic increase in mammary carcinoma growth rate, size, and weight. Although there was no difference in overall survival, the KO mice had significantly lower mammary tumor-free survival. Also, in the KO mammary carcinomas, the active forms of NF-κB and β-catenin were increased ~2-fold whereas no differences in oxidized proteins were observed. Many other tumors were observed, including lymphomas. Interestingly, the incidences of lung adenomas in the KO mice were significantly higher than in the WT mice. Conclusions We report, for the first time, that there was no apparent difference in the formation of premalignant lesions, but rather, the KO mice exhibited rapid, aggressive mammary

  13. Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development

    NARCIS (Netherlands)

    Baardman, Maria E.; Zwier, Mathijs V.; Wisse, Lambertus J.; Gittenberger-de Groot, Adriana C.; Kerstjens-Frederikse, Wilhelmina S.; Hofstra, Robert M. W.; Jurdzinski, Angelika; Hierck, Beerend P.; Jongbloed, Monique R. M.; Berger, Rolf M. F.; Plosch, Torsten; DeRuiter, Marco C.

    2016-01-01

    Lipoprotein-related receptor protein 2 (LRP2) is important for development of the embryonic neural crest and brain in both mice and humans. Although a role in cardiovascular development can be expected, the hearts of Lrp2 knockout (KO) mice have not yet been investigated. We studied the cardiovascul

  14. Salivary gland hypofunction in tyrosylprotein sulfotransferase-2 knockout mice is due to primary hypothyroidism.

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    Andrew D Westmuckett

    Full Text Available BACKGROUND: Protein-tyrosine sulfation is a post-translational modification of an unknown number of secreted and membrane proteins mediated by two known Golgi tyrosylprotein sulfotransferases (TPST-1 and TPST-2. We reported that Tpst2-/- mice have mild-moderate primary hypothyroidism, whereas Tpst1-/- mice are euthyroid. While using magnetic resonance imaging (MRI to look at the thyroid gland we noticed that the salivary glands in Tpst2-/- mice appeared smaller than in wild type mice. This prompted a detailed analysis to compare salivary gland structure and function in wild type, Tpst1-/-, and Tpst2 -/- mice. METHODOLOGY/PRINCIPAL FINDINGS: Quantitative MRI imaging documented that salivary glands in Tpst2-/- females were (≈ 30% smaller than wild type or Tpst1-/- mice and that the granular convoluted tubules in Tpst2-/- submandibular glands were less prominent and were almost completely devoid of exocrine secretory granules compared to glands from wild type or Tpst1-/- mice. In addition, pilocarpine-induced salivary flow and salivary α-amylase activity in Tpst2-/- mice of both sexes was substantially lower than in wild type and Tpst1-/- mice. Anti-sulfotyrosine Western blots of salivary gland extracts and saliva showed no differences between wild type, Tpst1-/-, and Tpst2-/- mice, suggesting that the salivary gland hypofunction is due to factor(s extrinsic to the salivary glands. Finally, we found that all indicators of hypothyroidism (serum T4, body weight and salivary gland hypofunction (salivary flow, salivary α-amylase activity, histological changes were restored to normal or near normal by thyroid hormone supplementation. CONCLUSIONS/SIGNIFICANCE: Our findings conclusively demonstrate that low body weight and salivary gland hypofunction in Tpst2-/- mice is due solely to primary hypothyroidism.

  15. Ethanol and Acetaldehyde After Intraperitoneal Administration to Aldh2-Knockout Mice-Reflection in Blood and Brain Levels.

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    Jamal, Mostofa; Ameno, Kiyoshi; Tanaka, Naoko; Ito, Asuka; Takakura, Ayaka; Kumihashi, Mitsuru; Kinoshita, Hiroshi

    2016-05-01

    This paper reports, for the first time, on the analysis of ethanol (EtOH) and acetaldehyde (AcH) concentrations in the blood and brains of Aldh2-knockout (Aldh2-KO) and C57B6/6J (WT) mice. Animals were administrated EtOH (1.0, 2.0 or 4.0 g/kg) or 4-methylpyrazole (4-MP, 82 mg/kg) plus AcH (50, 100 or 200 mg/kg) intraperitoneally. During the blood tests, samples from the orbital sinus of the eye were collected. During the brain tests, dialysates were collected every 5 min (equal to a 15 µl sample) from the striatum using in vivo brain microdialysis. Samples were collected at 5, 10, 15, 20, 25, 30 and 60 min intervals post-EtOH and -AcH injection, and then analyzed by head-space GC. In the EtOH groups, high AcH levels were found in the blood and brains of Aldh2-KO mice, while only small traces of AcH were seen in the blood and brains of WT mice. No significant differences in EtOH levels were observed between the WT and the Aldh2-KO mice for either the EtOH dose. EtOH concentrations in the brain were comparable to the EtOH concentrations in the blood, but the AcH concentrations in the brain were four to five times lower compared to the AcH concentrations in the blood. In the AcH groups, high AcH levels were found in both WT and Aldh2-KO mice. Levels reached a sharp peak at 5 min and then quickly declined for 60 min. Brain AcH concentrations were almost equal to the concentrations found in the blood, where the AcH concentrations were approximately two times higher in the Aldh2-KO mice than in the WT mice, both in the blood and the brain. Our results suggest that systemic EtOH and AcH administration can cause a greater increase in AcH accumulation in the blood and brains of Aldh2-KO mice, where EtOH concentrations in the Aldh2-KO mice were comparable to the EtOH concentrations in the WT mice. Furthermore, detection of EtOH and AcH in the blood and brain was found to be dose-dependent in both genotypes. PMID:26646001

  16. Autism-relevant social abnormalities and cognitive deficits in engrailed-2 knockout mice.

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    Jennifer Brielmaier

    Full Text Available ENGRAILED 2 (En2, a homeobox transcription factor, functions as a patterning gene in the early development and connectivity of rodent hindbrain and cerebellum, and regulates neurogenesis and development of monoaminergic pathways. To further understand the neurobiological functions of En2, we conducted neuroanatomical expression profiling of En2 wildtype mice. RTQPCR assays demonstrated that En2 is expressed in adult brain structures including the somatosensory cortex, hippocampus, striatum, thalamus, hypothalamus and brainstem. Human genetic studies indicate that EN2 is associated with autism. To determine the consequences of En2 mutations on mouse behaviors, including outcomes potentially relevant to autism, we conducted comprehensive phenotyping of social, communication, repetitive, and cognitive behaviors. En2 null mutants exhibited robust deficits in reciprocal social interactions as juveniles and adults, and absence of sociability in adults, replicated in two independent cohorts. Fear conditioning and water maze learning were impaired in En2 null mutants. High immobility in the forced swim test, reduced prepulse inhibition, mild motor coordination impairments and reduced grip strength were detected in En2 null mutants. No genotype differences were found on measures of ultrasonic vocalizations in social contexts, and no stereotyped or repetitive behaviors were observed. Developmental milestones, general health, olfactory abilities, exploratory locomotor activity, anxiety-like behaviors and pain responses did not differ across genotypes, indicating that the behavioral abnormalities detected in En2 null mutants were not attributable to physical or procedural confounds. Our findings provide new insight into the role of En2 in complex behaviors and suggest that disturbances in En2 signaling may contribute to neuropsychiatric disorders marked by social and cognitive deficits, including autism spectrum disorders.

  17. PDH activation during in vitro muscle contractions in PDH kinase 2 knockout mice: effect of PDH kinase 1 compensation.

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    Dunford, Emily C; Herbst, Eric A; Jeoung, Nam Ho; Gittings, William; Inglis, J Greig; Vandenboom, Rene; LeBlanc, Paul J; Harris, Robert A; Peters, Sandra J

    2011-06-01

    Pyruvate dehydrogenase (PDH) plays an important role in regulating carbohydrate oxidation in skeletal muscle. PDH is deactivated by a set of PDH kinases (PDK1, PDK2, PDK3, PDK4), with PDK2 and PDK4 being the most predominant isoforms in skeletal muscle. Although PDK2 is the most abundant isoform, few studies have examined its physiological role. The role of PDK2 on PDH activation (PDHa) at rest and during muscle stimulation at 10 and 40 Hz (eliciting low- and moderate-intensity muscle contractions, respectively) in isolated extensor digitorum longus muscles was studied in PDK2 knockout (PDK2KO) and wild-type (WT) mice (n = 5 per group). PDHa activity was unexpectedly 35 and 77% lower in PDK2KO than WT muscle (P = 0.043), while total PDK activity was nearly fourfold lower in PDK2KO muscle (P = 0.006). During 40-Hz contractions, initial force was lower in PDK2KO than WT muscle (P PDK2 and was 1.8-fold higher in PDK2KO than WT muscle (P = 0.019). This likely contributed to ensuring that resting PDHa activity was similar between the groups and accounts for the lower PDH activation during muscle contraction, as PDK1 is a very potent inhibitor of the PDH complex. Increased PDK1 expression appears to be regulated by hypoxia inducible factor-1α, which was 3.5-fold higher in PDK2KO muscle. It is clear that PDK2 activity is essential, even at rest, in regulation of carbohydrate oxidation and production of reducing equivalents for the electron transport chain. In addition, these results underscore the importance of the overall kinetics of the PDK isoform population, rather than total PDK activity, in determining transformation of the PDH complex and PDHa activity during muscle contraction. PMID:21411764

  18. Apo A1 Mimetic Rescues the Diabetic Phenotype of HO-2 Knockout Mice via an Increase in HO-1 Adiponectin and LKBI Signaling Pathway

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    Jian Cao

    2012-01-01

    Full Text Available Insulin resistance, with adipose tissue dysfunction, is one of the hallmarks of metabolic syndrome. We have reported a metabolic syndrome-like phenotype in heme oxygenase (HO-2 knockout mice, which presented with concurrent HO-1 deficiency and were amenable to rescue by an EET analog. Apo A-I mimetic peptides, such as L-4F, have been shown to induce HO-1 expression and decrease oxidative stress and adiposity. In this study we aimed to characterize alleviatory effects of HO-1 induction (if any on metabolic imbalance observed in HO-2 KO mice. In this regard, HO-2(−/− mice were injected with 2 mg/kg/day L-4F, or vehicle, i.p., for 6 weeks. As before, compared to WT animals, the HO-2 null mice were obese, displayed insulin resistance, and had elevated blood pressure. These changes were accompanied by enhanced tissue (hepatic oxidative stress along with attenuation of HO-1 expression and activity and reduced adiponectin, pAMPK, and LKB1 expression. Treatment with L-4F restored HO-1 expression and activity and increased adiponectin, LKB1, and pAMPK in the HO-2(−/− mice. These alterations resulted in a decrease in blood pressure, insulin resistance, blood glucose, and adiposity. Taken together, our results show that a deficient HO-1 response, in a state with reduced HO-2 basal levels, is accompanied by disruption of metabolic homeostasis which is successfully restored by an HO-1 inducer.

  19. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice.

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    Nicolas, G; Bennoun, M; Devaux, I; Beaumont, C; Grandchamp, B; Kahn, A; Vaulont, S

    2001-07-17

    We previously reported the disruption of the murine gene encoding the transcription factor USF2 and its consequences on glucose-dependent gene regulation in the liver. We report here a peculiar phenotype of Usf2(-/-) mice that progressively develop multivisceral iron overload; plasma iron overcomes transferrin binding capacity, and nontransferrin-bound iron accumulates in various tissues including pancreas and heart. In contrast, the splenic iron content is strikingly lower in knockout animals than in controls. To identify genes that may account for the abnormalities of iron homeostasis in Usf2(-/-) mice, we used suppressive subtractive hybridization between livers from Usf2(-/-) and wild-type mice. We isolated a cDNA encoding a peptide, hepcidin (also referred to as LEAP-1, for liver-expressed antimicrobial peptide), that was very recently purified from human blood ultrafiltrate and from urine as a disulfide-bonded peptide exhibiting antimicrobial activity. Accumulation of iron in the liver has been recently reported to up-regulate hepcidin expression, whereas our data clearly show that a complete defect in hepcidin expression is responsible for progressive tissue iron overload. The striking similarity of the alterations in iron metabolism between HFE knockout mice, a murine model of hereditary hemochromatosis, and the Usf2(-/-) hepcidin-deficient mice suggests that hepcidin may function in the same regulatory pathway as HFE. We propose that hepcidin acts as a signaling molecule that is required in conjunction with HFE to regulate both intestinal iron absorption and iron storage in macrophages. PMID:11447267

  20. Increased oxidative stress and apoptosis in the hypothalamus of diabetic male mice in the insulin receptor substrate-2 knockout model

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    Eva Baquedano

    2016-05-01

    Full Text Available Insulin receptor substrate-2-deficient (IRS2−/− mice are considered a good model to study the development of diabetes because IRS proteins mediate the pleiotropic effects of insulin-like growth factor-I (IGF-I and insulin on metabolism, mitogenesis and cell survival. The hypothalamus might play a key role in the early onset of diabetes, owing to its involvement in the control of glucose homeostasis and energy balance. Because some inflammatory markers are elevated in the hypothalamus of diabetic IRS2−/− mice, our aim was to analyze whether the diabetes associated with the absence of IRS2 results in hypothalamic injury and to analyze the intracellular mechanisms involved. Only diabetic IRS2−/− mice showed increased cell death and activation of caspase-8 and -3 in the hypothalamus. Regulators of apoptosis such as FADD, Bcl-2, Bcl-xL and p53 were also increased, whereas p-IκB and c-FLIPL were decreased. This was accompanied by increased levels of Nox-4 and catalase, enzymes involved in oxidative stress. In summary, the hypothalamus of diabetic IRS2−/− mice showed an increase in oxidative stress and inflammatory markers that finally resulted in cell death via substantial activation of the extrinsic apoptotic pathway. Conversely, non-diabetic IRS2−/− mice did not show cell death in the hypothalamus, possibly owing to an increase in the levels of circulating IGF-I and in the enhanced hypothalamic IGF-IR phosphorylation that would lead to the stimulation of survival pathways. In conclusion, diabetes in IRS2-deficient male mice is associated with increased oxidative stress and apoptosis in the hypothalamus.

  1. Increased oxidative stress and apoptosis in the hypothalamus of diabetic male mice in the insulin receptor substrate-2 knockout model.

    Science.gov (United States)

    Baquedano, Eva; Burgos-Ramos, Emma; Canelles, Sandra; González-Rodríguez, Agueda; Chowen, Julie A; Argente, Jesús; Barrios, Vicente; Valverde, Angela M; Frago, Laura M

    2016-05-01

    Insulin receptor substrate-2-deficient (IRS2(-/-)) mice are considered a good model to study the development of diabetes because IRS proteins mediate the pleiotropic effects of insulin-like growth factor-I (IGF-I) and insulin on metabolism, mitogenesis and cell survival. The hypothalamus might play a key role in the early onset of diabetes, owing to its involvement in the control of glucose homeostasis and energy balance. Because some inflammatory markers are elevated in the hypothalamus of diabetic IRS2(-/-) mice, our aim was to analyze whether the diabetes associated with the absence of IRS2 results in hypothalamic injury and to analyze the intracellular mechanisms involved. Only diabetic IRS2(-/-) mice showed increased cell death and activation of caspase-8 and -3 in the hypothalamus. Regulators of apoptosis such as FADD, Bcl-2, Bcl-xL and p53 were also increased, whereas p-IκB and c-FLIPL were decreased. This was accompanied by increased levels of Nox-4 and catalase, enzymes involved in oxidative stress. In summary, the hypothalamus of diabetic IRS2(-/-) mice showed an increase in oxidative stress and inflammatory markers that finally resulted in cell death via substantial activation of the extrinsic apoptotic pathway. Conversely, non-diabetic IRS2(-/-) mice did not show cell death in the hypothalamus, possibly owing to an increase in the levels of circulating IGF-I and in the enhanced hypothalamic IGF-IR phosphorylation that would lead to the stimulation of survival pathways. In conclusion, diabetes in IRS2-deficient male mice is associated with increased oxidative stress and apoptosis in the hypothalamus. PMID:27013528

  2. Increased oxidative stress and apoptosis in the hypothalamus of diabetic male mice in the insulin receptor substrate-2 knockout model

    Science.gov (United States)

    Canelles, Sandra; Argente, Jesús; Barrios, Vicente

    2016-01-01

    ABSTRACT Insulin receptor substrate-2-deficient (IRS2−/−) mice are considered a good model to study the development of diabetes because IRS proteins mediate the pleiotropic effects of insulin-like growth factor-I (IGF-I) and insulin on metabolism, mitogenesis and cell survival. The hypothalamus might play a key role in the early onset of diabetes, owing to its involvement in the control of glucose homeostasis and energy balance. Because some inflammatory markers are elevated in the hypothalamus of diabetic IRS2−/− mice, our aim was to analyze whether the diabetes associated with the absence of IRS2 results in hypothalamic injury and to analyze the intracellular mechanisms involved. Only diabetic IRS2−/− mice showed increased cell death and activation of caspase-8 and -3 in the hypothalamus. Regulators of apoptosis such as FADD, Bcl-2, Bcl-xL and p53 were also increased, whereas p-IκB and c-FLIPL were decreased. This was accompanied by increased levels of Nox-4 and catalase, enzymes involved in oxidative stress. In summary, the hypothalamus of diabetic IRS2−/− mice showed an increase in oxidative stress and inflammatory markers that finally resulted in cell death via substantial activation of the extrinsic apoptotic pathway. Conversely, non-diabetic IRS2−/− mice did not show cell death in the hypothalamus, possibly owing to an increase in the levels of circulating IGF-I and in the enhanced hypothalamic IGF-IR phosphorylation that would lead to the stimulation of survival pathways. In conclusion, diabetes in IRS2-deficient male mice is associated with increased oxidative stress and apoptosis in the hypothalamus. PMID:27013528

  3. Reduced intestinal lipid absorption and body weight-independent improvements in insulin sensitivity in high-fat diet-fed Park2 knockout mice.

    Science.gov (United States)

    Costa, Diana K; Huckestein, Brydie R; Edmunds, Lia R; Petersen, Max C; Nasiri, Ali; Butrico, Gina M; Abulizi, Abudukadier; Harmon, Daniel B; Lu, Canying; Mantell, Benjamin S; Hartman, Douglas J; Camporez, João-Paulo G; O'Doherty, Robert M; Cline, Gary W; Shulman, Gerald I; Jurczak, Michael J

    2016-07-01

    Mitochondrial dysfunction is associated with many human diseases and results from mismatch of damage and repair over the life of the organelle. PARK2 is a ubiquitin E3 ligase that regulates mitophagy, a repair mechanism that selectively degrades damaged mitochondria. Deletion of PARK2 in multiple in vivo models results in susceptibility to stress-induced mitochondrial and cellular dysfunction. Surprisingly, Park2 knockout (KO) mice are protected from nutritional stress and do not develop obesity, hepatic steatosis or insulin resistance when fed a high-fat diet (HFD). However, these phenomena are casually related and the physiological basis for this phenotype is unknown. We therefore undertook a series of acute HFD studies to more completely understand the physiology of Park2 KO during nutritional stress. We find that intestinal lipid absorption is impaired in Park2 KO mice as evidenced by increased fecal lipids and reduced plasma triglycerides after intragastric fat challenge. Park2 KO mice developed hepatic steatosis in response to intravenous lipid infusion as well as during incubation of primary hepatocytes with fatty acids, suggesting that hepatic protection from nutritional stress was secondary to changes in energy balance due to altered intestinal triglyceride absorption. Park2 KO mice showed reduced adiposity after 1-wk HFD, as well as improved hepatic and peripheral insulin sensitivity. These studies suggest that changes in intestinal lipid absorption may play a primary role in protection from nutritional stress in Park2 KO mice by preventing HFD-induced weight gain and highlight the need for tissue-specific models to address the role of PARK2 during metabolic stress. PMID:27166280

  4. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice.

    OpenAIRE

    Nicolas, Gaël; Bennoun, Myriam; Devaux, Isabelle; Beaumont, Carole; Grandchamp, Bernard; Kahn, Axel; Vaulont, Sophie

    2001-01-01

    We previously reported the disruption of the murine gene encoding the transcription factor USF2 and its consequences on glucose-dependent gene regulation in the liver. We report here a peculiar phenotype of Usf2(-/-) mice that progressively develop multivisceral iron overload; plasma iron overcomes transferrin binding capacity, and nontransferrin-bound iron accumulates in various tissues including pancreas and heart. In contrast, the splenic iron content is strikingly lower in knockout animal...

  5. Colonic mucosal DNA methylation, immune response, and microbiome patterns in Toll-like receptor 2-knockout mice

    OpenAIRE

    Kellermayer, Richard; Dowd, Scot E.; Harris, R. Alan; Balasa, Alfred; Schaible, Tiffany D.; Wolcott, Randy D; Tatevian, Nina; Szigeti, Reka; Li, Zhijie; Versalovic, James; Smith, C. Wayne

    2011-01-01

    The connection between intestinal microbiota and host physiology is increasingly becoming recognized. The details of this dynamic interaction, however, remain to be explored. Toll-like receptor 2 (Tlr2) is important for its role in bacterial recognition, intestinal inflammation, and obesity-related metabolic changes. Therefore, we sought to determine the epigenomic and metagenomic consequences of Tlr2 deficiency in the colonic mucosa of mice to gain insights into biological pathways that shap...

  6. A selective histone deacetylase-6 inhibitor improves BDNF trafficking in hippocampal neurons from Mecp2 knockout mice:implications for Rett syndrome

    Directory of Open Access Journals (Sweden)

    Xin eXu

    2014-03-01

    Full Text Available Rett syndrome (RTT is a neurodevelopmental disorder caused by loss-of-function mutations in the transcriptional modulator methyl-CpG-binding protein 2 (MECP2. One of the most prominent gene targets of MeCP2 is brain-derived neurotrophic factor (Bdnf, a potent modulator of activity-dependent synaptic development, function and plasticity. Dysfunctional BDNF signaling has been demonstrated in several pathophysiological mechanisms of RTT disease progression. To evaluate whether the dynamics of BDNF trafficking is affected by Mecp2 deletion, we analyzed movements of BDNF tagged with yellow fluorescent protein (YFP in cultured hippocampal neurons by time-lapse fluorescence imaging. We found that both anterograde and retrograde vesicular trafficking of BDNF-YFP are significantly impaired in Mecp2 knockout hippocampal neurons. Selective inhibitors of histone deacetylase 6 (HDAC6 show neuroprotective effects in neurodegenerative diseases and stimulate microtubule-dependent vesicular trafficking of BDNF-containing dense core vesicles. Here, we show that the selective HDAC6 inhibitor Tubastatin-A increased the velocity of BDNF-YFP vesicles in Mecp2 knockout neurons in both directions by increasing αtubulin acetylation. Tubastatin-A also restored activity-dependent BDNF release from Mecp2 knockout neurons to levels comparable to those shown by wildtype neurons. These findings demonstrate that a selective HDAC6 inhibitor is a potential pharmacological strategy to reverse cellular and synaptic impairments in RTT resulting from impaired BDNF signaling.

  7. Ultrastructural characterization of the mesostriatal dopamine innervation in mice, including two mouse lines of conditional VGLUT2 knockout in dopamine neurons.

    Science.gov (United States)

    Bérubé-Carrière, Noémie; Guay, Ginette; Fortin, Guillaume M; Kullander, Klas; Olson, Lars; Wallén-Mackenzie, Åsa; Trudeau, Louis-Eric; Descarries, Laurent

    2012-02-01

    Despite the increasing use of genetically modified mice to investigate the dopamine (DA) system, little is known about the ultrastructural features of the striatal DA innervation in the mouse. This issue is particularly relevant in view of recent evidence for expression of the vesicular glutamate transporter 2 (VGLUT2) by a subset of mesencephalic DA neurons in mouse as well as rat. We used immuno-electron microscopy to characterize tyrosine hydroxylase (TH)-labeled terminals in the core and shell of nucleus accumbens and the neostriatum of two mouse lines in which the Vglut2 gene was selectively disrupted in DA neurons (cKO), their control littermates, and C57BL/6/J wild-type mice, aged P15 or adult. The three regions were also examined in cKO mice and their controls of both ages after dual TH-VGLUT2 immunolabeling. Irrespective of the region, age and genotype, the TH-immunoreactive varicosities appeared similar in size, vesicular content, percentage with mitochondria, and exceedingly low frequency of synaptic membrane specialization. No dually labeled axon terminals were found at either age in control or in cKO mice. Unless TH and VGLUT2 are segregated in different axon terminals of the same neurons, these results favor the view that the glutamatergic cophenotype of mesencephalic DA neurons is more important during the early development of these neurons than for the establishment of their scarce synaptic connectivity. They also suggest that, in mouse even more than rat, the mesostriatal DA system operates mainly through non-targeted release of DA, diffuse transmission and the maintenance of an ambient DA level.

  8. A new mutant transcript generated in Znf230 exon 2 knockout mice reveals a potential exon structure in the targeting vector sequence

    Institute of Scientific and Technical Information of China (English)

    Yunqiang Liu; Dachang Tao; Sunkai Ma; Ying Kuang; Dan Su; Hao Zhang; Yuan Yang

    2013-01-01

    Testis gene Znf230 may play a role in mammalian spermatogenesis according to previous reports.Deleting 5' important exons to block the formation of protein was a routine way in gene-knockout experiments.To investigate the physiological function of Znf230 gene,the mutant mice with disrupted exon 2 of Znf230 were generated in this study.Results showed that,mutant Znf230 mice were fertile and showed normal body,genitourinary organs,testes weights,and spermatid number but the litter size of the offspring reduced with unclear reasons.Hematoxylin and eosin staining showed that the testicular tissue of mutant mice was intact.Reverse transcriptase polymerase chain reaction analysis showed that two novel mutant transcripts appeared in the mutant mice:the short one including exon-1 and exon-3 to-6,the long one unexpectedly containing a partial sequence from the pPNT vector acting as a new exon 2.Bioinformatic analysis of the long transcript revealed that it might code a 24-kDa N-terminal mutant protein with the same 182 amino acids as that of the wild-type Znf230 in the C-terminus,indicating that the potential functional region of C3HC4-type RING finger was intact in mutant protein.Western blot and immunohistochemistry analyses also implied that this N-terminal mutation of Znf230 might not disrupt the possible role that wild-type Znf230 played in spermatogenesis.In summary,a potential exon structure in the targeting vector sequence involved in the expression of targeting Znf230 gene and disturbed the strategy of this gene-targeting experiment.

  9. REPRODUCTIVE DEVELOPMENT IN MALE DEER MICE EXPOSED TO AGGRESSIVE BEHAVIOR

    Science.gov (United States)

    Male deer mice (Peromyscus maniculatus bairdii) were reared in a long photoperiod and housed individually from 3 weeks of age until they were killed 2, 4, or 6 weeks later. Males that were exposed to aggressive females for 2 min, three times per week, were of normal body weight a...

  10. Short-Chain Fatty Acid Propionate Alleviates Akt2 Knockout-Induced Myocardial Contractile Dysfunction

    Directory of Open Access Journals (Sweden)

    Linlin Li

    2012-01-01

    Full Text Available Background and Aims. Dysregulation of Akt has been implicated in diseases such as cancer and diabetes, although little is known about the role of Akt deficiency on cardiomyocyte contractile function. This study was designed to examine the effect of Akt2 knockout-induced cardiomyocyte contractile response and the effect of dietary supplementation of short-chain fatty acid propionate on Akt2 knockout-induced cardiac dysfunction, if any. Methods and Results. Adult male wild-type (WT and Akt2 knockout mice were treated with propionate (0.3 g/kg, p.o. or vehicle for 7 days. Oral glucose tolerance test (OGTT was performed. Cardiomyocyte contractile function and mitochondrial membrane potential were assessed. Expression of insulin-signaling molecules Akt, PTEN, GSK3β, and eNOS receptors for short-chain fatty acids GPR41, and GPR43 as well as protein phosphatase PP2AA, PP2AB, PP2C were evaluated using Western blot analysis. Our results revealed that Akt2 knockout led to overt glucose intolerance, compromised cardiomyocyte contractile function (reduced peak shortening and maximal velocity of shortening/relengthening as well as prolonged relengthening, loss of mitochondrial membrane potential, decreased GPR41 and elevated GPR43 expression, all of which, with the exception of glucose intolerance and elevated GPR43 level, were significantly attenuated by propionate. Neither Akt2 knockout nor propionate affected the expression of protein phosphatases, eNOS, pan, and phosphorylated PTEN and GSK3β. Conclusions. Taken together, these data depicted that Akt2 knockout may elicit cardiomyocyte contractile and mitochondrial defects and a beneficial role of propionate or short-chain fatty acids against Akt2 deficiency-induced cardiac anomalies.

  11. Genetic Analysis of Mice Skin Exposed by Hyper-Gravity

    Science.gov (United States)

    Takahashi, Rika; Terada, Masahiro; Seki, Masaya; Higashibata, Akira; Majima, Hideyuki J.; Ohira, Yoshinobu; Mukai, Chiaki; Ishioka, Noriaki

    2013-02-01

    In the space environment, physiological alterations, such as low bone density, muscle weakness and decreased immunity, are caused by microgravity and cosmic radiation. On the other hand, it is known that the leg muscles are hypertrophy by 2G-gravity. An understanding of the effects on human body from microgravity to hyper-gravity is very important. Recently, the Japan Aerospace Exploration Agency (JAXA) has started a project to detect the changes on gene expression and mineral metabolism caused by microgravity by analyzing the hair of astronauts who stay in the international Space Station (ISS) for a long time. From these results of human hair’s research, the genetic effects of human hair roots by microgravity will become clear. However, it is unclear how the gene expression of hair roots was effected by hypergravity. Therefore, in this experiment, we analyzed the effect on mice skin contained hair roots by comparing microgravity or hypergravity exposed mice. The purpose of this experiment is to evaluate the genetic effects on mice skin by microgravity or 2G-gravity. The samples were taken from mice exposed to space flight (FL) or hypergravity environment (2G) for 3-months, respectively. The extracted and amplified RNA from these mice skin was used to DNA microarray analysis. in this experiment, we analyzed the effect of gravity by using mice skin contained hair roots, which exposed space (FL) and hyper-gravity (2G) for 3 months and each control. By DNA microarray analysis, we found the common 98 genes changed in both FL and 2G. Among these 98 genes, the functions and pathways were identified by Gene Ontology (GO) analysis and Ingenuity Pathways Analysis (IPA) software. Next, we focused the one of the identified pathways and compared the effects on each molecules in this pathways by the different environments, such as FL and 2G. As the results, we could detect some interesting molecules, which might be depended on the gravity levels. In addition, to investigate

  12. Memory deficit in Swiss mice exposed to tannery effluent.

    Science.gov (United States)

    Rabelo, Letícia Martins; Costa E Silva, Bianca; de Almeida, Sabrina Ferreira; da Silva, Wellington Alves Mizael; de Oliveira Mendes, Bruna; Guimarães, Abraão Tiago Batista; da Silva, Anderson Rodrigo; da Silva Castro, André Luis; de Lima Rodrigues, Aline Sueli; Malafaia, Guilherme

    2016-01-01

    Although it is known that tannery effluents constitute highly toxic pollutants whose effects in humans represent public health problems in several countries, studies involving experimental mammalian models are rare. In this context, the objective of the present study was to assess the effect of the exposure to tannery effluent on the memory of male and female Swiss mice. Animals of each sex were distributed into two experimental groups: the control group, in which the animals received only drinking water and the effluent group, in which the mice received 1% of gross tannery effluent diluted in water. The animals were exposed to the effluent by gavage, oral dosing, for 15days, ensuring the administration of 0.1mL of liquid (water or effluent)/10g of body weight/day. On the 14th and 15th experimental days the animals were submitted to the object recognition test. It was observed that the new object recognition indices calculated for the animals exposed to the effluent (males and females) were significantly lower than those obtained with the control group. The exposure to tannery effluent caused memory deficit in Swiss mice in a similar way for both sexes, reinforcing previous findings that these pollutants affect the central nervous system. It contributes to the knowledge in the area by attesting harmful effects to the cognition of such animals. PMID:27063058

  13. Melatonin protects uterus and oviduct exposed to nicotine in mice

    Directory of Open Access Journals (Sweden)

    Seyed Saadat Seyedeh Nazanin

    2014-03-01

    Full Text Available Smoking is associated with higher infertility risk. The aim of this study was to evaluate protective effects of melatonin on the uterus and oviduct in mice exposed to nicotine. Adult female mice (n=32 were divided into four groups. Group A: control animals received normal saline, Group B: injected with nicotine 40 μg/kg, Group C: injected with melatonin 10 μg, Group D: injected with nicotine 40 μg/kg and melatonin 10 μg. All animals were treated over 15 days intraperitoneally. On the 16th day, animals in the estrus phase were dissected and their uterus and oviducts were removed. Immunohistochemistry was recruited for studying apoptosis and for detection of estrogen receptor (ER alpha in luminal epithelium of the uterus and oviduct. Enzyme-linked immunosorbent assay was used for serum estradiol level determination. Nicotine in group B decreased estradiol level and ERalpha numbers both in the uterus and oviduct (p<0.05. Co-administration of melatonin-nicotine in Group D ameliorated the histology of the uterus and oviduct, increased ERalpha numbers and reduced apoptosis in the uterus and oviduct compared with the nicotine Group B (p<0.05. This study indicates that nicotine impairs the histology of the uterus and oviduct and co-administration of melatonin-nicotine ameliorates these findings, partly through alteration in ERalpha numbers and reduction of apoptosis

  14. Yangjing Capsule Ameliorates Spermatogenesis in Male Mice Exposed to Cyclophosphamide

    Directory of Open Access Journals (Sweden)

    Hongle Zhao

    2015-01-01

    Full Text Available Yangjing capsule (YC, a traditional Chinese compound herbal preparation, has been proven as an effective drug to improve spermatogenesis in clinical practice. However, its pharmacological mechanisms were not fully clarified. This study was designed to investigate the protective effects of YC on spermatogenesis in the mouse model of spermatogenesis dysfunction induced by cyclophosphamide (CP. The administration of YC significantly increased the epididymal index, sperm count, and sperm motility of model mice. Histopathological changes demonstrated that CP caused obvious structural damage to testis, which were reversed by the administration of YC. Results from TUNEL assay showed that treatment with YC dramatically decreased the apoptosis of spermatogenic cell induced by CP. Moreover, YC treatment could inhibit the mRNA and protein expression of Bax to Bcl-2 and also raised expression of AR at both mRNA and protein levels. These data suggest that YC might ameliorate spermatogenesis in male mice exposed to CP through inhibiting the apoptosis of spermatogenic cell and enhancing the actions of testosterone in spermatogenesis.

  15. Inducibility of aryl hydrocarbon hydroxylase in BALB/c/ki mice exposed to urban air pollution.

    Science.gov (United States)

    Mostardi, R A; Ely, D L; Liebelt, A; Grossman, S; Fu, M M

    1981-05-01

    In two separate experiments BALB/c/ki mice were exposed to urban air pollution. Mice exposed to clean air served as controls. In both experiments there were no obvious quantitative or qualitative differences in lung or liver tissue examined by light microscopy. In both experiments higher aryl hydrocarbon hydroxylase activities and higher trace metal concentrations were observed in the mice exposed to polluted urban air. These data are interpreted in terms of health hazards of urban air pollutants. PMID:7265310

  16. Inducibility of aryl hydrocarbon hydroxylase in BALB/c/Ki mice exposed to urban air pollution

    Energy Technology Data Exchange (ETDEWEB)

    Mostardi, R.A. (Univ. of Akron, OH); Ely, D.L.; Liebelt, A.; Grossman, S.; Fu, M.M.

    1981-05-01

    In two separate experiments BALB/c/Kl mice were exposed to urban air pollution. Mice exposed to clean air served as controls. In both experiments there were no obvious quantitative or qualitative differences in lung or liver tissue examined by light microscopy. In both experiments higher aryl hydrocarbon hydroxylase activities and higher trace metal concentrations were observed in the mice exposed to polluted urban air. These data are interpreted in terms of health hazards of urban air pollutants.

  17. Levels of Mercury in the Organs of Normal and Acatalasemic Mice Exposed to Metallic Mercury Vapor

    OpenAIRE

    "愛甲, 博美"; "アイコウ, ヒロミ"; Hiromi", "Aikoh

    1993-01-01

    "The levels of mercury in the organs of normal and acatalasemic mice exposed to metallic mercury vapor after administration of ethanol or aminotriazole was inves tigated. Levels of mercuric ion in the liver of normal and acatalasemic mice immediately and after 6 hours following exposure to metallic mercury vapor increased in order to mice pretreated with ethanol (ET), pretreated with aminotriazole (AT) and control mice, respectively. Levels of mercuric ion in the lungs of both mice after 6 ho...

  18. The effects of electric fields on the immune system of exposed mice

    International Nuclear Information System (INIS)

    Swiss-Webster male mice were exposed for 30 and 60 days in a 60-Hz, 100 kV/meter electric field to determine the effect of exposure on humoral and cellular components of the immune system. Quantitation of serum lgG and lgM with a double-antibody radioimmune assay revealed no significant difference in the levels of these immunoglobulins between exposed and sham-exposed mice for the two time periods. In conjunction with the serum studies, the relative concentrations of T and B lymphocytes in the peripheral blood were measured using the spontaneous rosette assay and the binding of fluorescent-labeled goat anti-mouse immunoglobulins. No significant difference was observed in the distribution of these lymphocyte populations in exposed and sham-exposed mice. (author)

  19. Curcumin improves liver damage in male mice exposed to nicotine

    OpenAIRE

    Salahshoor, Mohammadreza; Mohamadian, Sabah; Kakabaraei, Seyran; Roshankhah, Shiva; Jalili, Cyrus

    2015-01-01

    The color of turmeric (薑黃 jiāng huáng) is because of a substance called curcumin. It has different pharmacological effects, such as antioxidant and anti-inflammatory properties. Nicotine is a major pharmacologically active substance in cigarette smoke. It is mainly metabolized in the liver and causes devastating effects. This study was designed to evaluate the protective role of curcumin against nicotine on the liver in mice. Forty-eight mice were equally divided into eight groups; control (n...

  20. Adaptive response in mice exposed to 900 MHz radiofrequency fields: primary DNA damage.

    Directory of Open Access Journals (Sweden)

    Bingcheng Jiang

    Full Text Available The phenomenon of adaptive response (AR in animal and human cells exposed to ionizing radiation is well documented in scientific literature. We have examined whether such AR could be induced in mice exposed to non-ionizing radiofrequency fields (RF used for wireless communications. Mice were pre-exposed to 900 MHz RF at 120 µW/cm(2 power density for 4 hours/day for 1, 3, 5, 7 and 14 days and then subjected to an acute dose of 3 Gy γ-radiation. The primary DNA damage in the form of alkali labile base damage and single strand breaks in the DNA of peripheral blood leukocytes was determined using the alkaline comet assay. The results indicated that the extent of damage in mice which were pre-exposed to RF for 1 day and then subjected to γ-radiation was similar and not significantly different from those exposed to γ-radiation alone. However, mice which were pre-exposed to RF for 3, 5, 7 and 14 days showed progressively decreased damage and was significantly different from those exposed to γ-radiation alone. Thus, the data indicated that RF pre-exposure is capable of inducing AR and suggested that the pre-exposure for more than 4 hours for 1 day is necessary to elicit such AR.

  1. Combination of valproate and paroxetine in mice exposed to picrotoxin

    Directory of Open Access Journals (Sweden)

    Kamal SM

    2012-05-01

    Full Text Available Sahar M KamalDepartment of Pharmacology, Faculty of Medicine, University of Ain-Shams, Cairo, EgyptAbstract: The frequent coexistence of depression in epileptic patients raises the issue of simultaneous use of antidepressants along with antiepileptic drugs in the management of such cases. However, it is necessary to evaluate the safety of these antiepileptic/antidepressant drug combinations. The present study investigates the effect of the antidepressant paroxetine (a selective serotonin reuptake inhibitor administered alone or in combination with the antiepileptic drug sodium valproate on chemoconvulsions induced by picrotoxin (PTX. Seizure score was recorded in vivo, and the levels of thiobarbituric acid-reactive substances and gamma aminobutyric acid (GABA were measured in the nucleus accumbens of the tested groups of mice. The results show enhancement of seizure severity with significant reduction in GABA levels upon PTX treatment that were reversed by its combination with sodium valproate. On the other hand, paroxetine administered in combination with sodium valproate provided significant protection against PTX-induced convulsions as well as a significant increase in GABA levels in selected brain areas. These results favor their application in management of epilepsy-depression comorbidities.Keywords: valproate, paroxetine, GABA, nucleus accumbens, albino mice

  2. Behavioral changes in female Swiss mice exposed to tannery effluents

    Directory of Open Access Journals (Sweden)

    Sabrina Ferreira de Almeida

    2016-06-01

    Full Text Available Among the anthropic activities generating potentially toxic residues are those involved with bovine hide processing (tannery industries. However, knowledge is scant regarding the damage caused to the health of various organisms by tannery waste and studies are rare, especially in mammalian experimental models. This study therefore aimed to evaluate the physical and behavioral effects of the exposure of female Swiss mice to tannery effluent. To accomplish this, for a period of 15 days the animals were fed tannery effluent diluted with water in the following concentrations: 0% (control group, received only potable water, 5% and 10%. The body mass of the animals was evaluated at the beginning and end of the experiment, as well as the daily consumption of water and food. After 15 days of exposure to the effluent, the animals were submitted to the elevated plus maze (predictive of anxiety and the forced swim test (predictive of depression. The treatments did not affect the animals' body mass, either in eating behavior or in consumption of water. However, it was found that the animals that ingested tannery effluent concentrations of 5% and 10% exhibited an anxiolytic (lower level of anxiety, greater percentage of time in the open arms, longer time and frequency in the diving behavior, less time of lurks and less frequency of freezing and an antidepressant effect (more time in climbing behavior and less time of immobility when compared to the control group. It was concluded that the exposure of female Swiss mice to tannery effluents (5% and 10% diluted with water causes behavioral changes, possibly related to the neurotoxicity of this waste, without causing physical changes in the animals.

  3. Exacerbation of Soft Tissue Lesions in Lead Exposed Virus Infected Mice

    Institute of Scientific and Technical Information of China (English)

    PRATIBHA GUPTA; M. M. HUSAIN; RAVI SHANKER; R. K. S. DOGRA; P. K. SETH; R. K. MAHESHWARI

    2003-01-01

    Objective To investigate the effect of Lead (Pb) acetate exposure on Semliki forest virus (SFV)pathogenesis in mice. Methods Different doses (62.5, 125, 250 and 500 mg/Kg body weight) of Pb dissolved in normal saline were given to mice by oral intubation in a sub-acute (28 days) and sub-chronic (90 days) regimen followed by SFV infection. Morbidity, mortality, clinical symptoms,mean survival time (MST), changes in body and organ weight, accumulation of lead in soft tissues,virus titre in brain and histopathological alterations were compared between lead exposed and infected groups. Results Early appearance of virus symptoms, increased mortality, decreased MST, enhanced SFV titre and greater tissue damage were observed in lead exposed-SFV-infected mice. Conclusion Pre-exposure to lead increases the susceptibility of mice towards SFV infection. Further studies are suggested in view of the persistence of lead in the environment and the possibility of infection bymicrobial pathogens.

  4. Gene expression profile in bone marrow and hematopoietic stem cells in mice exposed to inhaled benzene

    Energy Technology Data Exchange (ETDEWEB)

    Faiola, Brenda; Fuller, Elizabeth S.; Wong, Victoria A.; Recio, Leslie

    2004-05-18

    Acute myeloid leukemia and chronic lymphocytic leukemia are associated with benzene exposure. In mice, benzene induces chromosomal breaks as a primary mode of genotoxicity in the bone marrow (BM). Benzene-induced DNA lesions can lead to changes in hematopoietic stem cells (HSC) that give rise to leukemic clones. To gain insight into the mechanism of benzene-induced leukemia, we investigated the DNA damage repair and response pathways in total bone marrow and bone marrow fractions enriched for HSC from male 129/SvJ mice exposed to benzene by inhalation. Mice exposed to 100 ppm benzene for 6 h per day, 5 days per week for 2 week showed significant hematotoxicity and genotoxicity compared to air-exposed control mice. Benzene exposure did not alter the level of apoptosis in BM or the percentage of HSC in BM. RNA isolated from total BM cells and the enriched HSC fractions from benzene-exposed and air-exposed mice was used for microarray analysis and quantitative real-time RT-PCR. Interestingly, mRNA levels of DNA repair genes representing distinct repair pathways were largely unaffected by benzene exposure, whereas altered mRNA expression of various apoptosis, cell cycle, and growth control genes was observed in samples from benzene-exposed mice. Differences in gene expression profiles were observed between total BM and HSC. Notably, p21 mRNA was highly induced in BM but was not altered in HSC following benzene exposure. The gene expression pattern suggests that HSC isolated immediately following a 2 weeks exposure to 100 ppm benzene were not actively proliferating. Understanding the toxicogenomic profile of the specific target cell population involved in the development of benzene-associated diseases may lead to a better understanding of the mechanism of benzene-induced leukemia and may identify important interindividual and tissue susceptibility factors.

  5. The protective effect of amifostine on ultraviolet B-exposed xeroderma pigmentosum mice

    OpenAIRE

    Henry, SL; Christiansen, D; Kazmier, FR; Besch-Williford, CL; Concannon, MJ

    2010-01-01

    Background: Amifostine is a pharmaceutical agent that is used clinically to counteract the side-effects of chemotherapy and radiotherapy. It acts as a free radical scavenger that protects against harmful DNA cross-linking. The purpose of this study was to determine the effect of amifostine on the development of skin cancer in xeroderma pigmentosum (XP) mice exposed to ultraviolet B radiation (UVB). Methods: Twenty-five XP mice were equally divided into five groups. Group 1 (control) received ...

  6. Spatial Cognition in Adult and Aged Mice Exposed to High-Fat Diet.

    Science.gov (United States)

    Kesby, James P; Kim, Jane J; Scadeng, Miriam; Woods, Gina; Kado, Deborah M; Olefsky, Jerrold M; Jeste, Dilip V; Achim, Cristian L; Semenova, Svetlana

    2015-01-01

    Aging is associated with a decline in multiple aspects of cognitive function, with spatial cognition being particularly sensitive to age-related decline. Environmental stressors, such as high-fat diet (HFD) exposure, that produce a diabetic phenotype and metabolic dysfunction may indirectly lead to exacerbated brain aging and promote the development of cognitive deficits. The present work investigated whether exposure to HFD exacerbates age-related cognitive deficits in adult versus aged mice. Adult (5 months old) and aged (15 months old) mice were exposed to control diet or HFD for three months prior to, and throughout, behavioral testing. Anxiety-like behavior in the light-dark box test, discrimination learning and memory in the novel object/place recognition tests, and spatial learning and memory in the Barnes maze test were assessed. HFD resulted in significant gains in body weight and fat mass content with adult mice gaining significantly more weight and adipose tissue due to HFD than aged mice. Weight gain was attributed to food calories sourced from fat, but not total calorie intake. HFD increased fasting insulin levels in all mice, but adult mice showed a greater increase relative to aged mice. Behaviorally, HFD increased anxiety-like behavior in adult but not aged mice without significantly affecting spatial cognition. In contrast, aged mice fed either control or HFD diet displayed deficits in novel place discrimination and spatial learning. Our results suggest that adult mice are more susceptible to the physiological and anxiety-like effects of HFD consumption than aged mice, while aged mice displayed deficits in spatial cognition regardless of dietary influence. We conclude that although HFD induces systemic metabolic dysfunction in both adult and aged mice, overall cognitive function was not adversely affected under the current experimental conditions.

  7. Spatial Cognition in Adult and Aged Mice Exposed to High-Fat Diet.

    Directory of Open Access Journals (Sweden)

    James P Kesby

    Full Text Available Aging is associated with a decline in multiple aspects of cognitive function, with spatial cognition being particularly sensitive to age-related decline. Environmental stressors, such as high-fat diet (HFD exposure, that produce a diabetic phenotype and metabolic dysfunction may indirectly lead to exacerbated brain aging and promote the development of cognitive deficits. The present work investigated whether exposure to HFD exacerbates age-related cognitive deficits in adult versus aged mice. Adult (5 months old and aged (15 months old mice were exposed to control diet or HFD for three months prior to, and throughout, behavioral testing. Anxiety-like behavior in the light-dark box test, discrimination learning and memory in the novel object/place recognition tests, and spatial learning and memory in the Barnes maze test were assessed. HFD resulted in significant gains in body weight and fat mass content with adult mice gaining significantly more weight and adipose tissue due to HFD than aged mice. Weight gain was attributed to food calories sourced from fat, but not total calorie intake. HFD increased fasting insulin levels in all mice, but adult mice showed a greater increase relative to aged mice. Behaviorally, HFD increased anxiety-like behavior in adult but not aged mice without significantly affecting spatial cognition. In contrast, aged mice fed either control or HFD diet displayed deficits in novel place discrimination and spatial learning. Our results suggest that adult mice are more susceptible to the physiological and anxiety-like effects of HFD consumption than aged mice, while aged mice displayed deficits in spatial cognition regardless of dietary influence. We conclude that although HFD induces systemic metabolic dysfunction in both adult and aged mice, overall cognitive function was not adversely affected under the current experimental conditions.

  8. The growth and development of Schistosoma mansoni in mice exposed to sublethal doses of radiation

    Energy Technology Data Exchange (ETDEWEB)

    Aitken, R.; Wilson, R.A. (Univ. of York, Heslington (England))

    1989-12-01

    The maturation of Schistosoma mansoni was studied in mice exposed to various sublethal doses of radiation. Although the treatment of mice with 500 rads of radiation prior to infection did not alter parasite maturation, doses in excess of 500 rads led to a reduction in worm burden. This could not be attributed to a delay in the arrival of parasites in the hepatic portal system. Worms developing in mice treated with 800 rads commenced egg-laying about 1 wk later than worms in intact mice, and the rate of egg deposition appeared to be lower in irradiated hosts. The data demonstrate that exposure of C57BL/6 mice to doses of radiation in excess of 500 rads impairs their ability to carry infections of S. mansoni. The findings do not support the hypothesis that primary worm burdens in the mouse are controlled by a host immune response.

  9. Tiotropium Attenuates Virus-Induced Pulmonary Inflammation in Cigarette Smoke-Exposed Mice.

    Science.gov (United States)

    Bucher, Hannes; Duechs, Matthias J; Tilp, Cornelia; Jung, Birgit; Erb, Klaus J

    2016-06-01

    Viral infections trigger exacerbations in chronic obstructive pulmonary disease (COPD), and tiotropium, a M3 receptor antagonist, reduces exacerbations in patients by unknown mechanisms. In this report, we investigated whether tiotropium has anti-inflammatory effects in mice exposed to cigarette smoke (CS) and infected with influenza virus A/PR/8/34 (H1N1) or respiratory syncytial virus (RSV) and compared these effects with those of steroid fluticasone and PDE4-inhibitor roflumilast. Mice were exposed to CS; infected with H1N1 or RSV; and treated with tiotropium, fluticasone, or roflumilast. The amount of cells and cytokine levels in the airways, lung function, and viral load was determined. NCI-H292 cells were infected with H1N1 or RSV and treated with the drugs. In CS/H1N1-exposed mice, tiotropium reduced neutrophil and macrophage numbers and levels of interleukin-6 (IL-6) and interferon-γ (IFN-γ) in the airways and improved lung function. In contrast, fluticasone increased the loss of body weight; failed to reduce neutrophil or macrophage numbers; increased IL-6, KC, and tumor necrosis factor-α (TNF-α) in the lungs; and worsened lung function. Treatment with roflumilast reduced macrophage numbers, IL-6, and KC in the lungs but had no effect on neutrophil numbers or lung function. In CS/RSV-exposed mice, treatment with tiotropium, but not fluticasone or roflumilast, reduced neutrophil numbers and IL-6 and TNF-α levels in the lungs. Viral load of H1N1 and RSV was significantly elevated in CS/virus-exposed mice and NCI-H292 cells after fluticasone treatment, whereas tiotropium and roflumilast had no effect. In conclusion, tiotropium has anti-inflammatory effects on CS/virus-induced inflammation in mice that are superior to the effects of roflumilast and fluticasone. This finding might help to explain the observed reduction of exacerbation rates in COPD patients. PMID:27016458

  10. Tularemia among free-ranging mice without infection of exposed humans, Switzerland, 2012.

    Science.gov (United States)

    Origgi, Francesco C; König, Barbara; Lindholm, Anna K; Mayor, Désirée; Pilo, Paola

    2015-01-01

    The animals primarily infected by Francisella tularensis are rapidly consumed by scavengers, hindering ecologic investigation of the bacterium. We describe a 2012 natural tularemia epizootic among house mice in Switzerland and the assessment of infection of exposed humans. The humans were not infected, but the epizootic coincided with increased reports of human cases in the area.

  11. Postexposure aerosolized heparin reduces lung injury in chlorine-exposed mice.

    Science.gov (United States)

    Zarogiannis, Sotirios G; Wagener, Brant M; Basappa, Susanna; Doran, Stephen; Rodriguez, Cilina A; Jurkuvenaite, Asta; Pittet, Jean Francois; Matalon, Sadis

    2014-09-01

    Chlorine (Cl2) is a highly reactive oxidant gas that, when inhaled, may cause acute lung injury culminating in death from respiratory failure. In this study, we tested the hypothesis that exposure of mice to Cl2 causes intra-alveolar and systemic activation of the coagulation cascade that plays an important role in development of lung injury. C57Bl/6 mice were exposed to Cl2 (400 for 30 min or 600 ppm for 45 min) in environmental chambers and then returned to room air for 1 or 6 h. Native coagulation (NATEM) parameters such as blood clotting time and clot formation time were measured in whole blood by the viscoelastic technique. D-dimers and thrombin-anti-thrombin complexes were measured in both plasma and bronchoalveolar lavage fluid (BALF) by ELISA. Our results indicate that mice exposed to Cl2 gas had significantly increased clotting time, clot formation time, and D-dimers compared with controls. The thrombin-anti-thrombin complexes were also increased in the BALF of Cl2 exposed animals. To test whether increased coagulation contributed to the development of acute lung injury, mice exposed to Cl2 and returned to room air were treated with aerosolized heparin or vehicle for 20 min. Aerosolized heparin significantly reduced protein levels and the number of inflammatory cells in the BALF at 6 h postexposure. These findings highlight the importance of coagulation abnormities in the development of Cl2-induced lung injury. PMID:25038191

  12. Anti-apoptotic role of retinoic acid in the inner ear of noise-exposed mice

    International Nuclear Information System (INIS)

    Exposure to loud noise can induce temporary or permanent hearing loss, and acoustic trauma is the major cause of hearing impairment in industrial nations. However, the mechanisms underlying the death of hair cells after acoustic trauma remain unclear. In addition to its involvement in cellular stress and apoptosis, the c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase family, is involved in cell survival, transformation, embryonic morphogenesis, and differentiation. JNK is primarily activated by various environmental stresses including noise, and the phenotypic result appears be to cell death. All-trans retinoic acid (ATRA) is an active metabolite of vitamin A that regulates a wide range of biological processes, including cell proliferation, differentiation, and morphogenesis. We evaluated the role of ATRA in preserving hearing in mice exposed to noise that can induce permanent hearing loss. Mice fed with ATRA before and during 3 consecutive days of noise exposure had a more preserved hearing threshold than mice fed sesame oil or saline. Histological and TUNEL staining of the cochlea showed significantly enhanced preservation of the organ of Corti, including outer hair cells and relatively low apoptotic nuclei, in mice-fed ATRA than in mice-fed sesame oil or saline. Phospho-JNK immunohistochemistry showed that ATRA inhibited the activation of JNK. These results suggest that ATRA has an anti-apoptotic effect on cochleae exposed to noise

  13. Postexposure aerosolized heparin reduces lung injury in chlorine-exposed mice

    OpenAIRE

    Zarogiannis, Sotirios G.; Wagener, Brant M.; Basappa, Susanna; Doran, Stephen; Rodriguez, Cilina A.; Jurkuvenaite, Asta; Pittet, Jean Francois; Matalon, Sadis

    2014-01-01

    Chlorine (Cl2) is a highly reactive oxidant gas that, when inhaled, may cause acute lung injury culminating in death from respiratory failure. In this study, we tested the hypothesis that exposure of mice to Cl2 causes intra-alveolar and systemic activation of the coagulation cascade that plays an important role in development of lung injury. C57Bl/6 mice were exposed to Cl2 (400 for 30 min or 600 ppm for 45 min) in environmental chambers and then returned to room air for 1 or 6 h. Native coa...

  14. TNF-α and temporal changes in sleep architecture in mice exposed to sleep fragmentation.

    Directory of Open Access Journals (Sweden)

    Navita Kaushal

    Full Text Available TNF-α plays critical roles in host-defense, sleep-wake regulation, and the pathogenesis of various disorders. Increases in the concentration of circulating TNF-α after either sleep deprivation or sleep fragmentation (SF appear to underlie excessive daytime sleepiness in patients with sleep apnea (OSA. Following baseline recordings, mice were subjected to 15 days of SF (daily for 12 h/day from 07.00 h to 19.00 h, and sleep parameters were recorded on days1, 7 and 15. Sleep architecture and sleep propensity were assessed in both C57BL/6J and in TNF-α double receptor KO mice (TNFR KO. To further confirm the role of TNF-α, we also assessed the effect of treatment with a TNF- α neutralizing antibody in C57BL/6J mice. SF was not associated with major changes in global sleep architecture in C57BL/6J and TNFR KO mice. TNFR KO mice showed higher baseline SWS delta power. Further, following 15 days of SF, mice injected with TNF-α neutralizing antibody and TNFR KO mice showed increased EEG SWS activity. However, SWS latency, indicative of increased propensity to sleep, was only decreased in C57BL/6J, and was unaffected in TNFR KO mice as well as in C57BL/6J mice exposed to SF but treated with TNF-α neutralizing antibody. Taken together, our findings show that the excessive sleepiness incurred by recurrent arousals during sleep may be due to activation of TNF-alpha-dependent inflammatory pathways, despite the presence of preserved sleep duration and global sleep architecture.

  15. Histopathological assessment of C57Bl/J mice organs exposed to tannery effluents

    OpenAIRE

    Joyce Moreira de Souza; Abraão Tiago Batista Guimarães; Wellington Alves Mizael da Silva; Bruna de Oliveira Mendes; Dieferson da Costa Estrela; Aline Sueli de Lima Rodrigues; Adriana da Silva Santos; Guilherme Malafaia

    2016-01-01

    The effluent produced in tanneries can cause environmental damage and public health problems when disposed of improperly. However, few toxicological studies have evaluated the effects of the intake of tannery wastewater by mammals. The objective of this study is the histological assessment of organs of C57Bl/J mice exposed to the intake of different concentrations of raw tannery effluents, beginning with the hypothesis that these effluents can cause damage to the histological structure of the...

  16. Circulating microRNA signatures in mice exposed to lipoteichoic acid

    Directory of Open Access Journals (Sweden)

    Hsieh Ching-Hua

    2013-01-01

    Full Text Available Abstract Background Previously, we had identified a specific whole blood–derived microRNAs (miRNAs signature in mice following in vivo injection of lipopolysaccharide (LPS originated from Gram-negative bacteria. This study was designed to profile the circulating miRNAs expression in mice exposed to lipoteichoic acid (LTA which is a major component of the wall of Gram-positive bacteria. Results C57BL/6 mice received intraperitoneal injections of 100 μg of LTA originated from Bacillus subtilis, Streptococcus faecalis, and Staphylococcus aureus were killed 6 h and the whole blood samples were obtained for miRNA expression analysis using a miRNA array (Phalanx miRNA OneArray® 1.0. Up-regulated expression of miRNA targets in the whole blood, serum and white blood cells (WBCs of C57BL/6 and Tlr2−/− mice upon LTA treatment in 10, 100, or 1000 ug concentrations was quantified at indicated time (2, 6, 24, and 72 h using real-time RT-PCR and compared with that in the serum of C57BL/6 mice injected with 100 ug of LPS. A significant increase of 4 miRNAs (miR-451, miR-668, miR-1902, and miR-1904 was observed in the whole blood and the serum in a dose- and time-dependent fashion following LTA injection. Induction of miRNA occurred in the serum after 2 h and persisted for at least 6 h. No increased expression of these 4 miRNAs was found in the WBCs. Higher but not significant expression level of these 4 miRNAs were observed following LTA treatment in the serum of Tlr2−/−against that of C57BL6 mice. In contrast, LPS exposure induced moderate expression of miR-451 but not of the other 3 miRNA targets. Conclusions We identified a specific circulating miRNA signature in mice exposed to LTA. That expression profile is different from those of mice exposed to LPS. Those circulating miRNAs induced by LTA or LPS treatment may serve as promising biomarkers for the differentiation between exposures to Gram-positive or Gram-negative bacteria.

  17. Inflammation but no DNA (deoxyribonucleic acid) damage in mice exposed to airborne dust from a biofuel plant

    DEFF Research Database (Denmark)

    Madsen, Anne Mette; Saber, Anne Thoustrup; Nordly, Pernille;

    2008-01-01

    Objectives Particles in ambient air are associated with such health effects as lung diseases and cancer of the lung. Exposure to bioaerosols has been found to be associated with respiratory symptoms. The toxic properties of exposure to combustion and bioaerosol particles from biofuel plants have...... not been studied in detail. This study investigated whether exposure to dust from biofuel plants induces DNA (deoxyribonucleic acid) damage and inflammation in exposed mice. Methods DNA damage and inflammation were evaluated in mice exposed through the intratracheal installation of airborne dust collected...... at a biofuel plant at the straw storage hall and in the boiler room. The mice were given either a single dose of dust (18 or 54 mu g) or four doses of 54 mu g on each of four consecutive days. Control mice were exposed to a 0.9% sodium chloride solution. Results In the mice exposed to 4 x 54 mu g of dust...

  18. Effect of adiponectin deficiency on intestinal damage and hematopoietic responses of mice exposed to gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ponemone, Venkatesh; Fayad, Raja; Gove, Melissa E.; Pini, Maria [Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL 60612 (United States); Fantuzzi, Giamila, E-mail: giamila@uic.edu [Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL 60612 (United States)

    2010-08-07

    Adiponectin (APN) is an adipose tissue-derived cytokine that regulates insulin sensitivity and inflammation. It is also involved in modulation of cell proliferation by binding to various growth factors. Based on its known effects in modulating cell proliferation and oxidative stress, APN may potentially be involved in regulating tissue damage and repair following irradiation. Adiponectin KO mice and their WT littermates were exposed to a single whole-body dose of 3 or 6 Gy gamma radiation. Radiation-induced alterations were studied in jejunum, blood, bone marrow and thymus at days 1 and 5 post-irradiation and compared with sham-irradiated groups. In WT mice, irradiation did not significantly alter serum APN levels while inducing a significant decrease in serum leptin. Irradiation caused a significant reduction in thymocyte cellularity, with concomitant decrease in CD4{sup +}, CD8{sup +} and CD4{sup +}CD8{sup +} T cell populations, with no significant differences between WT and APN KO mice. Irradiation resulted in a significantly higher increase in the frequency of micronucleated reticulocytes in the blood of APN KO compared with WT mice, whereas frequency of micronucleated normochromatic erythrocytes in the bone marrow at day 5 was significantly higher in WT compared with APN KO mice. Finally, irradiation induced similar alterations in villus height and crypt cell proliferation in the jejunum of WT and APN KO mice. Jejunum explants from sham-irradiated APN KO mice produced higher levels of IL-6 compared with tissue from WT animals, but the difference was no longer apparent following irradiation. Our data indicate that APN deficiency does not play a significant role in modulating radiation-induced gastrointestinal injury in mice, while it may participate in regulation of damage to the hematopoietic system.

  19. Methionine stimulates motor impairment and cerebellar mercury deposition in methylmercury-exposed mice.

    Science.gov (United States)

    Zimmermann, Luciana T; dos Santos, Danúbia B; Colle, Dirleise; dos Santos, Alessandra A; Hort, Mariana A; Garcia, Solange C; Bressan, Lucas Paines; Bohrer, Denise; Farina, Marcelo

    2014-01-01

    Methylmercury (MeHg) is a highly toxic environmental contaminant that produces neurological and developmental impairments in animals and humans. Although its neurotoxic properties have been widely reported, the molecular mechanisms by which MeHg enters the cells and exerts toxicity are not yet completely understood. Taking into account that MeHg is found mostly bound to sulfhydryl-containing molecules such as cysteine in the environment and based on the fact that the MeHg-cysteine complex (MeHg-S-Cys) can be transported via the L-type neutral amino acid carrier transport (LAT) system, the potential beneficial effects of L-methionine (L-Met, a well known LAT substrate) against MeHg (administrated as MeHg-S-Cys)-induced neurotoxicity in mice were investigated. Mice were exposed to MeHg (daily subcutaneous injections of MeHg-S-Cys, 10 mg Hg/kg) and/or L-Met (daily intraperitoneal injections, 250 mg/kg) for 10 consecutive days. After treatments, the measured hallmarks of toxicity were mostly based on behavioral parameters related to motor performance, as well as biochemical parameters related to the cerebellar antioxidant glutathione (GSH) system. MeHg significantly decreased motor activity (open-field test) and impaired motor performance (rota-rod task) compared with controls, as well as producing disturbances in the cerebellar antioxidant GSH system. Interestingly, L-Met administration did not protect against MeHg-induced behavioral and cerebellar changes, but rather increased motor impairments in animals exposed to MeHg. In agreement with this observation, cerebellar levels of mercury (Hg) were higher in animals exposed to MeHg plus L-Met compared to those only exposed to MeHg. However, this event was not observed in kidney and liver. These results are the first to demonstrate that L-Met enhances cerebellar deposition of Hg in mice exposed to MeHg and that this higher deposition may be responsible for the greater motor impairment observed in mice simultaneously

  20. Exacerbation of allergic inflammation in mice exposed to diesel exhaust particles prior to viral infection

    Directory of Open Access Journals (Sweden)

    Chason Kelly D

    2009-08-01

    Full Text Available Abstract Background Viral infections and exposure to oxidant air pollutants are two of the most important inducers of asthma exacerbation. Our previous studies have demonstrated that exposure to diesel exhaust increases the susceptibility to influenza virus infections both in epithelial cells in vitro and in mice in vivo. Therefore, we examined whether in the setting of allergic asthma, exposure to oxidant air pollutants enhances the susceptibility to respiratory virus infections, which in turn leads to increased virus-induced exacerbation of asthma. Ovalbumin-sensitized (OVA male C57BL/6 mice were instilled with diesel exhaust particles (DEP or saline and 24 hours later infected with influenza A/PR/8. Animals were sacrificed 24 hours post-infection and analyzed for markers of lung injury, allergic inflammation, and pro-inflammatory cytokine production. Results Exposure to DEP or infection with influenza alone had no significant effects on markers of injury or allergic inflammation. However, OVA-sensitized mice that were exposed to DEP and subsequently infected with influenza showed increased levels of eosinophils in lung lavage and tissue. In addition Th2-type cytokines, such as IL-4 and IL-13, and markers of eosinophil chemotaxis, such as CCL11 and CCR3, were increased in OVA-sensitized mice exposed to DEP prior to infection with influenza. These mice also showed increased levels of IL-1α, but not IL-10, RANTES, and MCP-1 in lung homogenates. Conclusion These data suggest that in the setting of allergic asthma, exposure to diesel exhaust could enhance virus-induced exacerbation of allergic inflammation.

  1. Cytogenetic damage in adult and newborn mice exposed to Elf magnetic fields

    Energy Technology Data Exchange (ETDEWEB)

    Ieradi, L.A. [Istituto per lo Studio degli Ecosistemi, CNR, Rome (Italy); Udroiu, I.; Chiuchiarelli, G.; Migliorini, D.; Cristaldi, M. [Universite La Sapienza, Dipt. di Biologia Animale e dell' Uomo, Rome (Italy); Tanzarella, C. [Roma Univ., Dipt. di Biologia (Italy)

    2006-07-01

    Data obtained in newborn mice show that the chronic exposure during intra-uterine life to a 50 Hz, 650 {mu}T E.L.F. magnetic field induce a genetic damage. Nevertheless, the increase of DNA strand break in brain and in micronuclei frequency in peripheral blood and liver disagree with the data obtained by Abramsson-Zetterberg and Grawe (13) which did not find any genetic alterations in mice exposed to extremely low frequency (E.L.F.) magnetic field. In any case, along with other dissimilarities in the experimental design, the intensity of the field (14 {mu}T) and the time of sampling (35 days) were different. It is important to underline the four-fold increase in C.R.E.S.T.+ micronuclei frequency in circulating erythrocytes in the exposed group in comparison with the control group. Even though this value is quite low, it could indicate that E.L.F. magnetic fields may have different properties to damage the genome integrity. This stresses the need for further investigation on the possible link between electromagnetic fields and aneuploidy in order to elucidate the relationship with carcinogenesis. Preliminary data obtained with sperm abnormality assay show a significant increase of sperm abnormalities in mice exposed to E.L.F. magnetic fields and suggest a possible alteration to the spermatogenic process after exposure. This data agrees with data obtained by Tablado et al. (1998), in mice exposed continually for 35 days to a field of 1 T. Regarding the palatal ridges alterations assay, the results obtained show that the development of the secondary palate is not affected by E.L.F. magnetic field (50 Hz, 0,65 T). Nevertheless further studies at different frequency and intensity should be carried out to detect the possible epigenetic damage induced by E.L.F. exposure (Migliorini, 2005). With regard to the mechanism of action, it is generally believed that the damage induced by the magnetic field is an oxidative damage and that free radicals are involved. Some authors

  2. Polyphenolic metabolites in the blood and bone marrow of mice exposed to low levels of benzene

    Energy Technology Data Exchange (ETDEWEB)

    Bechtold, W.E.; Strunk, M.R.; Thornton-Manning, J.R.; Henderson, R. [Inhalation Toxicology Research Inst., Albuquerque, NM (United States)

    1996-12-31

    Exposure to benzene can cause an increased incidence of leukemia in humans, possibly through the formation of polyphenolic metabolites. To define exposure-dose relationships, male B6C3F1 mice were exposed by inhalation for 6 hr to benzene at 60 ppm or {sup 13}C-benzene at 8 ppm. Levels of phenol, catechol, and hydroquinone were measured in blood and bone marrow by gas chromatography/mass spectrometry, and compared with unexposed controls. Levels of all three metabolites, after background correction, were significantly increased in both the blood and bone marrow of the mice exposed to 60 ppm relative to those exposed to 8 ppm. However, levels of the {sup 13}C metabolites in blood and bone marrow were consistently lower than background levels of the equivalent {sup 12}C polyphenolics in unexposed controls. These results demonstrate that single exposures of benzene of less than 10 ppm add little to the blood and bone marrow burdens of polyphenolic metabolites.

  3. Reduced inflammatory response in cigarette smoke exposed Mrp1/Mdr1a/1b deficient mice

    Directory of Open Access Journals (Sweden)

    Postma Dirkje S

    2007-07-01

    Full Text Available Abstract Background Tobacco smoke is the principal risk factor for chronic obstructive pulmonary disease (COPD, though the mechanisms of its toxicity are still unclear. The ABC transporters multidrug resistance-associated protein 1 (MRP1 and P-glycoprotein (P-gp/MDR1 extrude a wide variety of toxic substances across cellular membranes and are highly expressed in bronchial epithelium. Their impaired function may contribute to COPD development by diminished detoxification of noxious compounds in cigarette smoke. Methods We examined whether triple knock-out (TKO mice lacking the genes for Mrp1 and Mdr1a/1b are more susceptible to develop COPD features than their wild-type (WT littermates. TKO and WT mice (six per group were exposed to 2 cigarettes twice daily by nose-only exposure or room air for 6 months. Inflammatory infiltrates were analyzed in lung sections, cytokines and chemokines in whole lung homogenates, emphysema by mean linear intercept. Multiple linear regression analysis with an interaction term was used to establish the statistical significances of differences. Results TKO mice had lower levels of interleukin (IL-7, KC (mouse IL-8, IL-12p70, IL-17, TNF-alpha, G-CSF, GM-CSF and MIP-1-alpha than WT mice independent of smoke exposure (P P P Conclusion Mrp1/Mdr1a/1b knock-out mice have a reduced inflammatory response to cigarette smoke. In addition, the expression levels of several cytokines and chemokines were also lower in lungs of Mrp1/Mdr1a/1b knock-out mice independent of smoke exposure. Further studies are required to determine whether dysfunction of MRP1 and/or P-gp contribute to the pathogenesis of COPD.

  4. Behavioral differentiation of mice exposed to a water tank social interaction test.

    Science.gov (United States)

    Nejdi, A; Guastavino, J M; Lalonde, R; Desor, D; Krafft, B

    1996-02-01

    Male or female C57BL/6J mice were exposed to a water tank in which food could be obtained only by wading in the water towards a feeder. Behavioral differentiation occurred in that three distinct categories could be distinguished: major carriers (transporting over 80% of the food pellets), sporadic carriers (transporting less than 20% of the food pellets) and non-carriers. In the elevated + -maze, major carriers were more willing to explore open spaces than non-carriers. Sporadic carriers showed some evidence of the same tendency of decreased anxiety, but in a minor way. The willingness of mice to become carriers is associated with their willingness to explore novel areas. This test may be useful for the assessment of anxiolytic compounds in a social situation.

  5. Adult Behavior in Male Mice Exposed to E-Cigarette Nicotine Vapors during Late Prenatal and Early Postnatal Life.

    Directory of Open Access Journals (Sweden)

    Dani Smith

    Full Text Available Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG or 0% nicotine /PG once a day from gestational day 15 until delivery. After delivery, offspring and mothers were exposed to E-cigarette vapors for an additional 14 days from postnatal day 2 through 16. Following their last exposure serum cotinine levels were measured in female juvenile mice. Male mice underwent behavioral testing at 14 weeks of age to assess sensorimotor, affective, and cognitive functional domains.Adult male mice exposed to 2.4% nicotine/PG E-cigarette vapors had significantly more head dips in the zero maze test and higher levels of rearing activity in the open field test compared to 0% nicotine/PG exposed mice and untreated controls. In the water maze test after reversal training, the 2.4% nicotine/PG mice spent more than 25% of time in the new location whereas the other groups did not.Adult male mice exhibited increased levels of activity in the zero maze and open field tests when exposed to E-cigarette vapor containing nicotine during late prenatal and early postnatal life. These findings indicate that nicotine exposure from E-cigarettes may cause persistent behavioral changes when exposure occurs during a period of rapid brain growth.

  6. Dehydrogenase activity of liver parenchyma in mice exposed to arsenic in drinking water

    Energy Technology Data Exchange (ETDEWEB)

    Bencko, V.; Rossner, P.; Mokry, M.

    1975-01-01

    The objective was to detect changes in dehydrogenase activity (DHA) of liver parenchyma in mice exposed to arsenic in drinking water (for 2, 4, 8, 16, 32 and 64 days). The concentrations used guaranteed threshold, above-threshold and toxic doses of arsenic. A concentration of 5 mg/l produced no significant difference (in comparison with control), a concentration of 250 mg/l caused a deep decline in DHA activity. A concentration of 50 mg/l reduced DHA solely in the first exposure interval. It was found that DHA activity was substantially less altered by arsenic than the metabolic consumption of oxygen under identical conditions.

  7. Ozone increases airway hyperreactivity and mucus hyperproduction in mice previously exposed to allergen

    DEFF Research Database (Denmark)

    Larsen, Søren T; Matsubara, Shigeki; McConville, Glen;

    2010-01-01

    Acute exacerbations of asthma represent a common clinical problem with major economic impact. Air pollutants including ozone have been shown to contribute to asthma exacerbation, but the mechanisms underlying ozone-induced asthma exacerbation are only partially understood. The present study aimed...... with goblet-cell metaplasia. Even the lowest concentration of ozone tested, 100 ppb, which may be exceeded in urban environments and in the workplace, resulted in a significant increase in AHR, most prominent 24 h after exposure in the OVA-exposed mice....

  8. Histopathological assessment of C57Bl/J mice organs exposed to tannery effluents

    Directory of Open Access Journals (Sweden)

    Joyce Moreira de Souza

    2016-03-01

    Full Text Available The effluent produced in tanneries can cause environmental damage and public health problems when disposed of improperly. However, few toxicological studies have evaluated the effects of the intake of tannery wastewater by mammals. The objective of this study is the histological assessment of organs of C57Bl/J mice exposed to the intake of different concentrations of raw tannery effluents, beginning with the hypothesis that these effluents can cause damage to the histological structure of the organs. The animals were divided into the following groups: control (0% effluent and exposed to 0.1%, 1%, and 5% raw tannery effluent diluted in water, for a period of 120 days. For the histopathological evaluations, samples of the liver, kidney, spleen, heart, and lung were collected, fixed, and stained by the hematoxylin and eosin staining techniques. No anomalies were observed in kidney, spleen, heart, and lung fragments. Alterations were observed only in liver fragments. Moderate hydropic degeneration was detected in animals exposed to tannery effluents, mainly in the periportal space. A large number of necrotic hepatocytes (p<0.05 were detected, especially in animals exposed to higher tannery effluent concentrations. Further, the largest number of hepatocytes with karyomegaly (p<0.05 was observed in animals exposed to the highest effluent concentrations. Our study suggests that the observed alterations are related to the intake of tannery effluents and that these effluents cause changes that lead to an increase of free radical production and direct aggressions to hepatocyte membranes as well as to the appearance of hepatocellular karyomegaly.

  9. Alteration of cytokine profiles in mice exposed to chronic low-dose ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Suk Chul [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of); Lee, Kyung-Mi [Global Research Lab, BAERI Institute, Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 136-705 (Korea, Republic of); Kang, Yu Mi [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of); Kim, Kwanghee [Global Research Lab, BAERI Institute, Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 136-705 (Korea, Republic of); Kim, Cha Soon; Yang, Kwang Hee; Jin, Young-Woo [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of); Kim, Chong Soon [Department of Nuclear Medicine, Haeundae Paik Hospital, Inje University, Busan 612-030 (Korea, Republic of); Kim, Hee Sun, E-mail: hskimdvm@khnp.co.kr [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of)

    2010-07-09

    While a high-dose of ionizing radiation is generally harmful and causes damage to living organisms, a low-dose of radiation has been shown to be beneficial in a variety of animal models. To understand the basis for the effect of low-dose radiation in vivo, we examined the cellular and immunological changes evoked in mice exposed to low-dose radiation at very low (0.7 mGy/h) and low (3.95 mGy/h) dose rate for the total dose of 0.2 and 2 Gy, respectively. Mice exposed to low-dose radiation, either at very low- or low-dose rate, demonstrated normal range of body weight and complete blood counts. Likewise, the number and percentage of peripheral lymphocyte populations, CD4{sup +} T, CD8{sup +} T, B, or NK cells, stayed unchanged following irradiation. Nonetheless, the sera from these mice exhibited elevated levels of IL-3, IL-4, leptin, MCP-1, MCP-5, MIP-1{alpha}, thrombopoietin, and VEGF along with slight reduction of IL-12p70, IL-13, IL-17, and IFN-{gamma}. This pattern of cytokine release suggests the stimulation of innate immunity facilitating myeloid differentiation and activation while suppressing pro-inflammatory responses and promoting differentiation of naive T cells into T-helper 2, not T-helper 1, types. Collectively, our data highlight the subtle changes of cytokine milieu by chronic low-dose {gamma}-radiation, which may be associated with the functional benefits observed in various experimental models.

  10. Alteration of cytokine profiles in mice exposed to chronic low-dose ionizing radiation

    International Nuclear Information System (INIS)

    While a high-dose of ionizing radiation is generally harmful and causes damage to living organisms, a low-dose of radiation has been shown to be beneficial in a variety of animal models. To understand the basis for the effect of low-dose radiation in vivo, we examined the cellular and immunological changes evoked in mice exposed to low-dose radiation at very low (0.7 mGy/h) and low (3.95 mGy/h) dose rate for the total dose of 0.2 and 2 Gy, respectively. Mice exposed to low-dose radiation, either at very low- or low-dose rate, demonstrated normal range of body weight and complete blood counts. Likewise, the number and percentage of peripheral lymphocyte populations, CD4+ T, CD8+ T, B, or NK cells, stayed unchanged following irradiation. Nonetheless, the sera from these mice exhibited elevated levels of IL-3, IL-4, leptin, MCP-1, MCP-5, MIP-1α, thrombopoietin, and VEGF along with slight reduction of IL-12p70, IL-13, IL-17, and IFN-γ. This pattern of cytokine release suggests the stimulation of innate immunity facilitating myeloid differentiation and activation while suppressing pro-inflammatory responses and promoting differentiation of naive T cells into T-helper 2, not T-helper 1, types. Collectively, our data highlight the subtle changes of cytokine milieu by chronic low-dose γ-radiation, which may be associated with the functional benefits observed in various experimental models.

  11. Cytokine expression in mice exposed to diesel exhaust particles by inhalation. Role of tumor necrosis factor

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    Loft Steffen

    2006-02-01

    Full Text Available Abstract Background Particulate air pollution has been associated with lung and cardiovascular disease, for which lung inflammation may be a driving mechanism. The pro-inflammatory cytokine, tumor necrosis factor (TNF has been suggested to have a key-role in particle-induced inflammation. We studied the time course of gene expression of inflammatory markers in the lungs of wild type mice and Tnf-/- mice after exposure to diesel exhaust particles (DEPs. Mice were exposed to either a single or multiple doses of DEP by inhalation. We measured the mRNA level of the cytokines Tnf and interleukin-6 (Il-6 and the chemokines, monocyte chemoattractant protein (Mcp-1, macrophage inflammatory protein-2 (Mip-2 and keratinocyte derived chemokine (Kc in the lung tissue at different time points after exposure. Results Tnf mRNA expression levels increased late after DEP-inhalation, whereas the expression levels of Il-6, Mcp-1 and Kc increased early. The expression of Mip-2 was independent of TNF if the dose was above a certain level. The expression levels of the cytokines Kc, Mcp-1 and Il-6, were increased in the absence of TNF. Conclusion Our data demonstrate that Tnf is not important in early DEP induced inflammation and rather exerts negative influence on Mcp-1 and Kc mRNA levels. This suggests that other signalling pathways are important, a candidate being one involving Mcp-1.

  12. Ethanol and acetaldehyde differentially alter extracellular dopamine and serotonin in Aldh2-knockout mouse dorsal striatum: A reverse microdialysis study.

    Science.gov (United States)

    Jamal, Mostofa; Ameno, Kiyoshi; Miki, Takanori; Tanaka, Naoko; Ito, Asuka; Ono, Junichiro; Takakura, Ayaka; Kumihashi, Mitsuru; Kinoshita, Hiroshi

    2016-01-01

    Dopamine (DA) and serotonin (5-HT) seem to be involved in several of the effects of ethanol (EtOH). Acetaldehyde (AcH), especially in the brain, induces effects that mimic those of EtOH. The purpose of this study was to investigate the effects of local perfusion of EtOH and AcH on extracellular DA and 5-HT in the dorsal striatum of Aldh2-knockout (Aldh2-KO) and wild-type (WT) mice. Aldh2-KO mice were used as a model of aldehyde dehydrogenase 2 deficiency in humans to examine the effects of AcH. Mice were perfused with Ringer's solution (control), EtOH (100, 200, or 500mM) and AcH (100, 200, or 500μM) into the dorsal striatum. Dialysate samples were collected every 5min, and then analyzed with HPLC coupled to an ECD. We found that local perfusion with 500mM EtOH increased extracellular levels of DA (p<0.05) in both Aldh2-KO and WT mice, while 5-HT levels remain unchanged. EtOH at a dose of 200mM also increased DA in WT mice, but this was limited to a 30-40-min time-point. In contrast, perfusion with 200 and 500μM AcH decreased both DA and 5-HT (p<0.05) in Aldh2-KO mice, but this decrease was not found in WT mice at any AcH dose, indicating an effect of AcH on DA and 5-HT levels. There were no genotype effects on the basal levels of DA and 5-HT. These results indicate that high EtOH can stimulate DA, whereas high AcH can depress both DA and 5-HT in the dorsal striatum of mice. PMID:26711020

  13. Effect of intestinal microflora on the survival time of mice exposed to lethal whole-body γ irradiation

    International Nuclear Information System (INIS)

    The effect of intestinal microflora on the survival time of mice exposed to 2-kR whole-body γ irradiation was studied using germfree, monoassociated, and conventionalized ICR mice. The germfree mice were monoassociated with 1 of 11 bacterial strains, which were isolated from the fresh feces of conventional mice, 2 weeks prior to irradiation. All mice died within 3 weeks after irradiation. Monoassociation with Fusobacterium sp., Streptococcus faecalis, Escherichia coli, or Pseudomonas sp. significantly reduced the mean survival time compared to that of germfree mice. In contrast, monoassociation with Clostridium sp., Bifidobacterium pseudolongum, or Lactobacillus acidophilus significantly prolonged the mean survival time compared to that of germfree mice. This suggests that the latter organisms may perform some activity to protect the mice from radiation injury. In this histopathological autopsy examination, the main lesions were hypocellularity in hematopoietic organs and hemorrhage in various organs. Neither karyorrhexis nor desquamation of intestinal mucosal cells was observed in any mice. From these observations, it is suggested that the death of these mice was related to hematopoietic damage. Bacterial invasion into various organs was observed in conventionalized and Pseudomonas-, E. coli-, or S. faecalis-monoassociated mice but not in Clostridium-, B. pseudolongum-, L. acidophilus-, or Fusobacterium-monoassociated mice

  14. Whole blood-derived microRNA signatures in mice exposed to lipopolysaccharides

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    Hsieh Ching-Hua

    2012-07-01

    RNA targets. Conclusions We identified a specific whole blood–derived miRNA signature in mice exposed to LPS, but not to LTA, from different gram-negative bacteria. These whole blood-derived miRNAs are promising as biomarkers for LPS exposure.

  15. Statins do not alter the incidence of mesothelioma in asbestos exposed mice or humans.

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    Cleo Robinson

    Full Text Available Mesothelioma is principally caused by asbestos and may be preventable because there is a long latent period between exposure and disease development. The most at-risk are a relatively well-defined population who were exposed as a consequence of their occupations. Although preventative agents investigated so far have not been promising, discovery of such an agent would have a significant benefit world-wide on healthcare costs and personal suffering. Statins are widely used for management of hypercholesterolemia and cardiovascular risk; they can induce apoptosis in mesothelioma cells and epidemiological data has linked their use to a lower incidence of cancer. We hypothesised that statins would inhibit the development of asbestos-induced mesothelioma in mice and humans. An autochthonous murine model of asbestos-induced mesothelioma was used to test this by providing atorvastatin daily in the feed at 100 mg/kg, 200 mg/kg and 400 mg/kg. Continuous administration of atorvastatin did not alter the rate of disease development nor increase the length of time that mice survived. Latency to first symptoms of disease and disease progression were also unaffected. In a parallel study, the relationship between the use of statins and development of mesothelioma was investigated in asbestos-exposed humans. In a cohort of 1,738 asbestos exposed people living or working at a crocidolite mine site in Wittenoom, Western Australia, individuals who reported use of statins did not have a lower incidence of mesothelioma (HR = 1.01; 95% CI = 0.44-2.29, p = 0.99. Some individuals reported use of both statins and non-steroidal anti-inflammatory drugs or COX-2 inhibitors, and these people also did not have an altered risk of mesothelioma development (HR = 1.01; 95% CI = 0.61-1.67, p = 0.97. We conclude that statins do not moderate the rate of development of mesothelioma in either a mouse model or a human cohort exposed to asbestos.

  16. Repair and biochemical protection in life shortening of mice exposed to fractionated X-irradiation

    International Nuclear Information System (INIS)

    Male mice of the BALB/c+ strain were exposed to X-rays at fractionation intervals of 7, 15, 30, and 60 days. One group received a mixture of radioprotectors, another only AET (only 30 days fractionation), a third one served as control. The doses ranged, dependent on the treatment, from 300-1,500 R. When survival was corrected for acute death, the control and AET treated animals died after an accumulated dose of about 2,000 R whereas those treated with a mixture of radioprotectors died after about 4,000 R. Bone marrow failure and lung damage is the main cause of death within the initial 200 days after start of the exposure. At later times, fibrotic changes and in particular glomerulosclerosis are observed. (orig.)

  17. Studies on Some Biophysical Properties of the Serum Protein of Mice blood exposed to an electric field

    International Nuclear Information System (INIS)

    As an indication of the effect of the electric field on each of the dielectric properties and the molecular structure of the serum protein of the mice blood, an electric field of a 6 kv/m strength and 50 Hz frequency was directed to three groups of mice for exposure periods 30, 45 and 60 days respectively, and investigated directly. Another group was exposed to also 60 days, but investigated after 30 days from switching off the electric field for delayed effect studies. The molecular structure of the serum protein was studied by measuring each of the dielectric relaxation and the electric conductivity in the frequency range 0.15 MHz at 4 ± 0.5 degree C and the dielectric increment (Δ), relaxation time (τ) and average molecular radii (τ) were calculated for all groups. The absorption spectra of the extracted protein were also measured in the wavelength range 200 600 nm. Moreover, electrophoresis of enzymes B-esterase, lactate and Malate dehydrogenase extracted from the blood serum of exposed mice were taken by using the gel electrophoresis technique. The results indicated that exposure of the animals to 50 H, 6 kv/m electric field resulted in the decrease of serum protein permittivity values and increase its conductivity a fact that indicates pronounced changes in the molecular structure of total serum protein the exposed mice. In addition, the intensity of the absorption spectral bands of serum protein of exposed mice were found to decrease relative to unexposed mice. Also the enzymes B-esterase and lactate dehydrogenase were slightly affected by exposing to the electric field whereas their number of bands and their intensities changed relative to the unexposed mice but the malate dehydrogenase was not affected

  18. Cardiovascular changes in atherosclerotic ApoE-deficient mice exposed to Co60 (γ radiation.

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    Prem Kumarathasan

    Full Text Available BACKGROUND: There is evidence for a role of ionizing radiation in cardiovascular diseases. The goal of this work was to identify changes in oxidative and nitrative stress pathways and the status of the endothelinergic system during progression of atherosclerosis in ApoE-deficient mice after single and repeated exposure to ionizing radiation. METHODS AND RESULTS: B6.129P2-ApoE tmlUnc mice on a low-fat diet were acutely exposed (whole body to Co60 (γ (single dose 0, 0.5, and 2 Gy at a dose rate of 36.32 cGy/min, or repeatedly (cumulative dose 0 and 2 Gy at a dose-rate of 0.1 cGy/min for 5 d/wk, over a period of 4 weeks. Biological endpoints were investigated after 3-6 months of recovery post-radiation. The nitrative stress marker 3-nitrotyrosine and the vasoregulator peptides endothelin-1 and endothelin-3 in plasma were increased (p<0.05 in a dose-dependent manner 3-6 months after acute or chronic exposure to radiation. The oxidative stress marker 8-isoprostane was not affected by radiation, while plasma 8-hydroxydeoxyguanosine and L-3,4-dihydroxyphenylalanine decreased (p<0.05 after treatment. At 2Gy radiation dose, serum cholesterol was increased (p = 0.008 relative to controls. Percent lesion area increased (p = 0.005 with age of animal, but not with radiation treatment. CONCLUSIONS: Our observations are consistent with persistent nitrative stress and activation of the endothelinergic system in ApoE-/- mice after low-level ionizing radiation exposures. These mechanisms are known factors in the progression of atherosclerosis and other cardiovascular diseases.

  19. Erythropoiesis in mice exposed to continuous whole body irradiation of gamma-rays

    Energy Technology Data Exchange (ETDEWEB)

    Joshima, Hisamasa; Fukutsu, Kumiko; Matsushita, Satoru; Kashima, Masatoshi

    1988-09-01

    The erythropoietic effects of continuous ..gamma..-irradiation with a daily regime of 0.029, 0.083 and 0.374 Gy were studied in mice. Irradiation was performed with /sup 137/Cs ..gamma..-rays for 22 hr/day. The length of irradiation time varied from 3 to 112 days. Erythropoiesis was investigated on the basis of clearance of /sup 59/Fe from the circulation and of incorporation of /sup 59/Fe into circulating erythrocytes and erythropoietic tissue. A chemical method for the separation of heme and nonheme iron-containing fractions was employed to examine the uptake of /sup 59/Fe into both the heme and nonheme iron fractions. Daily exposure to 0.029 and 0.083 Gy caused no significant changes in erythropoiesis. Daily exposure to 0.374 Gy caused some significant changes in erythropoiesis. On day 7 of continuous irradiation, the amount of /sup 59/Fe incorporated into erythrocytes decreased, but the values returned to normal on day 14 and 28 of continuous irradiation, indicating recovery within erythropoietic tissues at earlier time. On day 56, depressed incorporation of /sup 59/Fe into erythrocytes with normal rate of disappearance of /sup 59/Fe from the circulation and increased heme level of /sup 59/Fe in the femoral marrow were observed. Results observed on day 56 may suggest the possibility of ineffective erythropoiesis during the continuous irradiation. On day 112, some mice showed almost the same changes in erythropoiesis as those mice exposed to acute X-rays radiation.

  20. ALTERATIONS IN THE ACETYLCHOLINESTERASE ACTIVITY IN THE BRAIN OF ALBINO MICE EXPOSED TO ACEPHATE

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    M. SIVA PRASAD

    2013-01-01

    Full Text Available Acephate (AP, a widely available organophosphorus (OP insecticide, has low mammalian toxicity and isconsidered non-phytotoxic on many crop plants and therefore it is preferred in agricultural crops. In plants andinsects, AP is metabolized extensively to methamidophos (MP, a more potent OP insecticide. The limitedmammalian metabolism of AP to MP has been studied in laboratory rat models and suggests that initial formationof MP from AP may inhibit further formation. Hence in the present investigation we have studied the effect of anAP in cholinergic mechanisms in the different regions of brain. For the present study the male mice were exposedto 1/10th LD50 of AP via oral gavage (i.e. 40.5mg/kg body weight. Our results indicate a steady decline of AChEactivity in all the regions of the brain of Acephate exposed animals. As expected an increase in ACh activity wasnoticed in all the regions of the AP exposed animals. We suggest that cholinergic system is seriously affected bythe intoxication of Acephate and the effect was more effective in 30 days when compared to 10 days

  1. Frontal Cortex Transcriptome Analysis of Mice Exposed to Electronic Cigarettes During Early Life Stages

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    Dana E. Lauterstein

    2016-04-01

    Full Text Available Electronic cigarettes (e-cigarettes, battery-powered devices containing nicotine, glycerin, propylene glycol, flavorings, and other substances, are increasing in popularity. They pose a potential threat to the developing brain, as nicotine is a known neurotoxicant. We hypothesized that exposure to e-cigarettes during early life stages induce changes in central nervous system (CNS transcriptome associated with adverse neurobiological outcomes and long-term disease states. To test the hypothesis, pregnant C57BL/6 mice were exposed daily (via whole body inhalation throughout gestation (3 h/day; 5 days/week to aerosols produced from e-cigarettes either with nicotine (13–16 mg/mL or without nicotine; following birth, pups and dams were exposed together to e-cigarette aerosols throughout lactation beginning at postnatal day (PND 4–6 and using the same exposure conditions employed during gestational exposure. Following exposure, frontal cortex recovered from ~one-month-old male and female offspring were excised and analyzed for gene expression by RNA Sequencing (RNA-Seq. Comparisons between the treatment groups revealed that e-cigarette constituents other than nicotine might be partly responsible for the observed biological effects. Transcriptome alterations in both offspring sexes and treatment groups were all significantly associated with downstream adverse neurobiological outcomes. Results from this study demonstrate that e-cigarette exposure during early life alters CNS development potentially leading to chronic neuropathology.

  2. Frontal Cortex Transcriptome Analysis of Mice Exposed to Electronic Cigarettes During Early Life Stages.

    Science.gov (United States)

    Lauterstein, Dana E; Tijerina, Pamella B; Corbett, Kevin; Akgol Oksuz, Betul; Shen, Steven S; Gordon, Terry; Klein, Catherine B; Zelikoff, Judith T

    2016-04-12

    Electronic cigarettes (e-cigarettes), battery-powered devices containing nicotine, glycerin, propylene glycol, flavorings, and other substances, are increasing in popularity. They pose a potential threat to the developing brain, as nicotine is a known neurotoxicant. We hypothesized that exposure to e-cigarettes during early life stages induce changes in central nervous system (CNS) transcriptome associated with adverse neurobiological outcomes and long-term disease states. To test the hypothesis, pregnant C57BL/6 mice were exposed daily (via whole body inhalation) throughout gestation (3 h/day; 5 days/week) to aerosols produced from e-cigarettes either with nicotine (13-16 mg/mL) or without nicotine; following birth, pups and dams were exposed together to e-cigarette aerosols throughout lactation beginning at postnatal day (PND) 4-6 and using the same exposure conditions employed during gestational exposure. Following exposure, frontal cortex recovered from ~one-month-old male and female offspring were excised and analyzed for gene expression by RNA Sequencing (RNA-Seq). Comparisons between the treatment groups revealed that e-cigarette constituents other than nicotine might be partly responsible for the observed biological effects. Transcriptome alterations in both offspring sexes and treatment groups were all significantly associated with downstream adverse neurobiological outcomes. Results from this study demonstrate that e-cigarette exposure during early life alters CNS development potentially leading to chronic neuropathology.

  3. Metabolic changes and DNA hypomethylation in cerebellum are associated with behavioral alterations in mice exposed to trichloroethylene postnatally

    International Nuclear Information System (INIS)

    Previous studies demonstrated that low-level postnatal and early life exposure to the environmental contaminant, trichloroethylene (TCE), in the drinking water of MRL +/+ mice altered glutathione redox homeostasis and increased biomarkers of oxidative stress indicating a more oxidized state. Plasma metabolites along the interrelated transmethylation pathway were also altered indicating impaired methylation capacity. Here we extend these findings to further characterize the impact of TCE exposure in mice exposed to water only or two doses of TCE in the drinking water (0, 2, and 28 mg/kg/day) postnatally from birth until 6 weeks of age on redox homeostasis and biomarkers of oxidative stress in the cerebellum. In addition, pathway intermediates involved in methyl metabolism and global DNA methylation patterns were examined in cerebellar tissue. Because the cerebellum is functionally important for coordinating motor activity, including exploratory and social approach behaviors, these parameters were evaluated in the present study. Mice exposed to 28 mg/kg/day TCE exhibited increased locomotor activity over time as compared with control mice. In the novel object exploration test, these mice were more likely to enter the zone with the novel object as compared to control mice. Similar results were obtained in a second test when an unfamiliar mouse was introduced into the testing arena. The results show for the first time that postnatal exposure to TCE causes key metabolic changes in the cerebellum that may contribute to global DNA methylation deficits and behavioral alterations in TCE-exposed mice. - Highlights: • We exposed male mice to low-level trichloroethylene from postnatal days 1 through 42. • This exposure altered redox potential and increased oxidative stress in cerebellum. • This exposure altered metabolites important in cellular methylation in cerebellum. • This exposure promoted DNA hypomethylation in cerebellum. • This exposure enhanced locomotor

  4. Sex- and Tissue-Specific Methylome Changes in Brains of Mice Perinatally Exposed to Lead

    Science.gov (United States)

    Sánchez-Martín, Francisco Javier; Lindquist, Diana M.; Landero-Figueroa, Julio; Zhang, Xiang; Chen, Jing; Cecil, Kim M.; Medvedovic, Mario; Puga, Alvaro

    2014-01-01

    Changes in DNA methylation and subsequent changes in gene expression regulation are the hallmarks of age- and tissue-dependent epigenetic drift and plasticity resulting from the combinatorial integration of genetic determinants and environmental cues. To determine whether perinatal lead exposure caused persistent DNA methylation changes in target tissues, we exposed mouse dams to 0, 3 or 30 ppm of lead acetate in drinking water for a period extending from 2 months prior to mating, through gestation, until weaning of pups at postnatal day-21, and analyzed whole-genome DNA methylation in brain cortex and hippocampus of 2-month old exposed and unexposed progeny. Lead exposure resulted in hypermethylation of three differentially methylated regions in the hippocampus of females, but not males. These regions mapped to Rn4.5s, Sfi1, and Rn45s loci in mouse chromosomes 2, 11 and 17, respectively. At a conservative fdr<0.001, 1,623 additional CpG sites were differentially methylated in female hippocampus, corresponding to 117 unique genes. Sixty of these genes were tested for mRNA expression and showed a trend towards negative correlation between mRNA expression and methylation in exposed females but not males. No statistically significant methylome changes were detected in male hippocampus or in cortex of either sex. We conclude that exposure to lead during embryonic life, a time when the organism is most sensitive to environmental cues, appears to have a sex- and tissue-specific effect on DNA methylation that may produce pathological or physiological deviations from the epigenetic plasticity operative in unexposed mice. PMID:25530354

  5. Gastric dilatation syndrome associated with chronic nephropathy, hypergastrinemia, and gastritis in mice exposed to high levels of environmental antigens.

    Science.gov (United States)

    García, A; Erdman, S; Sheppard, B J; Murphy, J C; Fox, J G

    2001-06-01

    Gastric dilatation (GD) has been observed in Tac:(SW)fBR surveillance mice, with mean age of 10 months, that are exposed to high levels of environmental antigens during routine exposure to dirty bedding. The aim of the study reported here was to determine whether GD was associated with other systemic conditions affecting mice. Three groups of nine animals including-surveillance mice not exposed to dirty bedding (control), surveillance mice with out GD (NGD), and surveillance mice with GD (group GD)-had mean stomach weight with ingesta of 0.5 +/- 0.02 g, 1.09 +/- 0.07 g (P < 0.0001), and 2.54 +/- 0.4 g (P < 0.0001), respectively. Mean serum creatinine concentration was significantly higher in GD (1.6 +/- 0.25 mg/dl), compared with NGD (0.17 +/- 0.22 mg/dl, P < 0.0001) and control (0.2 +/- 0.16 mg/ dl, P < 0.0001) mice. In addition, lesions consistent with severe chronic nephropathy and mild gastritis were common in GD, compared with NGD and control mice. Finally, serum amidated gastrin concentration was significantly high in GD (179.37 +/- 53.86 pM, P < 0.03) and NGD (264.89 +/- 115.89 pM, P < 0.009), compared with control (60.77 +/- 8.39 pM) mice. Gastric dilatation syndrome is associated with chronic nephropathy, hypergastrinemia, and gastritis in surveillance mice exposed to high levels of environmental antigens. PMID:11924783

  6. B cells play key roles in th2-type airway immune responses in mice exposed to natural airborne allergens.

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    Li Yin Drake

    Full Text Available Humans are frequently exposed to various airborne allergens. In addition to producing antibodies, B cells participate in immune responses via various mechanisms. The roles of B cells in allergic airway inflammation and asthma have been controversial. We examined the functional importance of B cells in a mouse model of asthma, in which mice were exposed repeatedly to common airborne allergens. Naïve wild-type BALB/c mice or B cell-deficient JH-/- mice were exposed intranasally to a cocktail of allergen extracts, including Alternaria, Aspergillus, and house dust mite, every other day for two weeks. Ovalbumin was included in the cocktail to monitor the T cell immune response. Airway inflammation, lung pathology, and airway reactivity were analyzed. The airway exposure of naïve wild type mice to airborne allergens induced robust eosinophilic airway inflammation, increased the levels of Th2 cytokines and chemokines in the lung, and increased the reactivity to inhaled methacholine. These pathological changes and immune responses were attenuated in B cell-deficient JH-/- mice. The allergen-induced expansion of CD4+ T cells was impaired in the lungs and draining lymph nodes of JH-/- mice. Furthermore, lymphocytes from JH-/- mice failed to produce Th2 cytokines in response to ovalbumin re-stimulation in vitro. Our results suggest that B cells are required for the optimal development of Th2-type immune responses and airway inflammation when exposed to common airborne allergens. The therapeutic targeting of B cells may be beneficial to treat asthma in certain patients.

  7. Response, thermal regulatory threshold and thermal breakdown threshold of restrained RF-exposed mice at 905 MHz

    Energy Technology Data Exchange (ETDEWEB)

    Ebert, S [Swiss Federal Institute of Technology (ETH), Zurich, 8092 Zurich (Switzerland); Eom, S J [Swiss Federal Institute of Technology (ETH), Zurich, 8092 Zurich (Switzerland); Schuderer, J [Foundation for Research on Information Technologies in Society (IT' IS), Zeughausstrasse 43, 8004 Zurich (Switzerland); Apostel, U [Fraunhofer Institute for Toxicology and Experimental Medicine, Nicolai-Fuchs-Strasse 1, 30625 Hannover (Germany); Tillmann, T [Fraunhofer Institute for Toxicology and Experimental Medicine, Nicolai-Fuchs-Strasse 1, 30625 Hannover (Germany); Dasenbrock, C [Fraunhofer Institute for Toxicology and Experimental Medicine, Nicolai-Fuchs-Strasse 1, 30625 Hannover (Germany); Kuster, N [Swiss Federal Institute of Technology (ETH), Zurich, 8092 Zurich (Switzerland)

    2005-11-07

    The objective of this study was the determination of the thermal regulatory and the thermal breakdown thresholds for in-tube restrained B6C3F1 and NMRI mice exposed to radiofrequency electromagnetic fields at 905 MHz. Different levels of the whole-body averaged specific absorption rate (SAR 0, 2, 5, 7.2, 10, 12.6 and 20 W kg{sup -1}) have been applied to the mice inside the 'Ferris Wheel' exposure setup at 22 {+-} 2 {sup 0}C and 30-70% humidity. The thermal responses were assessed by measurement of the rectal temperature prior, during and after the 2 h exposure session. For B6C3F1 mice, the thermal response was examined for three different weight groups (20 g, 24 g, 29 g), both genders and for pregnant mice. Additionally, NMRI mice with a weight of 36 g were investigated for an interstrain comparison. The thermal regulatory threshold of in-tube restrained mice was found at SAR levels between 2 W kg{sup -1} and 5 W kg{sup -1}, whereas the breakdown of regulation was determined at 10.1 {+-} 4.0 W kg{sup -1}(K = 2) for B6C3F1 mice and 7.7 {+-} 1.6 W kg{sup -1}(K = 2) for NMRI mice. Based on a simplified power balance equation, the thresholds show a clear dependence upon the metabolic rate and weight. NMRI mice were more sensitive to thermal stress and respond at lower SAR values with regulation and breakdown. The presented data suggest that the thermal breakdown for in-tube restrained mice, whole-body exposed to radiofrequency fields, may occur at SAR levels of 6 W kg{sup -1}(K = 2) at laboratory conditions.

  8. Modulation of pulmonary inflammatory responses and antimicrobial defenses in mice exposed to diesel exhaust.

    Science.gov (United States)

    Gowdy, Kymberly; Krantz, Quentin T; Daniels, Mary; Linak, William P; Jaspers, Ilona; Gilmour, M Ian

    2008-06-15

    Diesel exhaust (DE) is a major component of urban air pollution and has been shown to increase the severity of infectious and allergic lung disease. The purpose of this study was to evaluate the effects of DE exposure on pulmonary inflammation, mediator production and antimicrobial defenses in an exposure model that had previously been shown to increase susceptibility to influenza. BALB/c mice were exposed to filtered air, or to DE diluted to yield 0.5 or 2 mg/m(3) of diesel exhaust particles (DEP) for 4 h per day for 1 or 5 days. Immediately and 18 h after one or five diesel exposures mice were euthanized to assess both immediate and delayed effects. DE exposure for 5 days at either concentration caused higher neutrophil numbers and lesion scoring compared to air controls. Intracellular adhesion molecule-1 (ICAM-1), which recruits inflammatory cells and is an entry site for rhinoviruses was increased immediately after 1 or 5 days of DE exposure. Several inflammatory and immune cytokines (TNF-alpha, MIP-2, IL-6, IFN-gamma, and IL-13) were also upregulated at various time points and concentrations. In contrast, clara cell secretory protein (CCSP), surfactant protein A (SP-A), and surfactant protein D (SP-D) which are important host defense molecules, were significantly decreased at both the message and protein level with DE exposure. We conclude that exposure to moderate and high occupational levels of DE caused an increase in lung injury and inflammation, and a decrease in host defense molecules, which could result in increased susceptibility to respiratory pathogens. PMID:18343473

  9. Modulation of pulmonary inflammatory responses and antimicrobial defenses in mice exposed to diesel exhaust

    International Nuclear Information System (INIS)

    Diesel exhaust (DE) is a major component of urban air pollution and has been shown to increase the severity of infectious and allergic lung disease. The purpose of this study was to evaluate the effects of DE exposure on pulmonary inflammation, mediator production and antimicrobial defenses in an exposure model that had previously been shown to increase susceptibility to influenza. BALB/c mice were exposed to filtered air, or to DE diluted to yield 0.5 or 2 mg/m3 of diesel exhaust particles (DEP) for 4 h per day for 1 or 5 days. Immediately and 18 h after one or five diesel exposures mice were euthanized to assess both immediate and delayed effects. DE exposure for 5 days at either concentration caused higher neutrophil numbers and lesion scoring compared to air controls. Intracellular adhesion molecule-1 (ICAM-1), which recruits inflammatory cells and is an entry site for rhinoviruses was increased immediately after 1 or 5 days of DE exposure. Several inflammatory and immune cytokines (TNF-α, MIP-2, IL-6, IFN-γ, and IL-13) were also upregulated at various time points and concentrations. In contrast, clara cell secretory protein (CCSP), surfactant protein A (SP-A), and surfactant protein D (SP-D) which are important host defense molecules, were significantly decreased at both the message and protein level with DE exposure. We conclude that exposure to moderate and high occupational levels of DE caused an increase in lung injury and inflammation, and a decrease in host defense molecules, which could result in increased susceptibility to respiratory pathogens

  10. Menthol attenuates respiratory irritation and elevates blood cotinine in cigarette smoke exposed mice.

    Directory of Open Access Journals (Sweden)

    Michael A Ha

    Full Text Available Addition of menthol to cigarettes may be associated with increased initiation of smoking. The potential mechanisms underlying this association are not known. Menthol, likely due to its effects on cold-sensing peripheral sensory neurons, is known to inhibit the sensation of irritation elicited by respiratory irritants. However, it remains unclear whether menthol modulates cigarette smoke irritancy and nicotine absorption during initial exposures to cigarettes, thereby facilitating smoking initiation. Using plethysmography in a C57Bl/6J mouse model, we examined the effects of L-menthol, the menthol isomer added to cigarettes, on the respiratory sensory irritation response to primary smoke irritants (acrolein and cyclohexanone and smoke of Kentucky reference 2R4 cigarettes. We also studied L-menthol's effect on blood levels of the nicotine metabolite, cotinine, immediately after exposure to cigarette smoke. L-menthol suppressed the irritation response to acrolein with an apparent IC₅₀ of 4 ppm. Suppression was observed even at acrolein levels well above those necessary to produce a maximal response. Cigarette smoke, at exposure levels of 10 mg/m³ or higher, caused an immediate and marked sensory irritation response in mice. This response was significantly suppressed by L-menthol even at smoke concentrations as high as 300 mg/m³. Counterirritation by L-menthol was abolished by treatment with a selective inhibitor of Transient Receptor Potential Melastatin 8 (TRPM8, the neuronal cold/menthol receptor. Inclusion of menthol in the cigarette smoke resulted in roughly a 1.5-fold increase in plasma cotinine levels over those observed in mice exposed to smoke without added menthol. These findings document that, L-menthol, through TRPM8, is a strong suppressor of respiratory irritation responses, even during highly noxious exposures to cigarette smoke or smoke irritants, and increases blood cotinine. Therefore, L-menthol, as a cigarette additive, may

  11. Menthol attenuates respiratory irritation and elevates blood cotinine in cigarette smoke exposed mice.

    Science.gov (United States)

    Ha, Michael A; Smith, Gregory J; Cichocki, Joseph A; Fan, Lu; Liu, Yi-Shiuan; Caceres, Ana I; Jordt, Sven Eric; Morris, John B

    2015-01-01

    Addition of menthol to cigarettes may be associated with increased initiation of smoking. The potential mechanisms underlying this association are not known. Menthol, likely due to its effects on cold-sensing peripheral sensory neurons, is known to inhibit the sensation of irritation elicited by respiratory irritants. However, it remains unclear whether menthol modulates cigarette smoke irritancy and nicotine absorption during initial exposures to cigarettes, thereby facilitating smoking initiation. Using plethysmography in a C57Bl/6J mouse model, we examined the effects of L-menthol, the menthol isomer added to cigarettes, on the respiratory sensory irritation response to primary smoke irritants (acrolein and cyclohexanone) and smoke of Kentucky reference 2R4 cigarettes. We also studied L-menthol's effect on blood levels of the nicotine metabolite, cotinine, immediately after exposure to cigarette smoke. L-menthol suppressed the irritation response to acrolein with an apparent IC₅₀ of 4 ppm. Suppression was observed even at acrolein levels well above those necessary to produce a maximal response. Cigarette smoke, at exposure levels of 10 mg/m³ or higher, caused an immediate and marked sensory irritation response in mice. This response was significantly suppressed by L-menthol even at smoke concentrations as high as 300 mg/m³. Counterirritation by L-menthol was abolished by treatment with a selective inhibitor of Transient Receptor Potential Melastatin 8 (TRPM8), the neuronal cold/menthol receptor. Inclusion of menthol in the cigarette smoke resulted in roughly a 1.5-fold increase in plasma cotinine levels over those observed in mice exposed to smoke without added menthol. These findings document that, L-menthol, through TRPM8, is a strong suppressor of respiratory irritation responses, even during highly noxious exposures to cigarette smoke or smoke irritants, and increases blood cotinine. Therefore, L-menthol, as a cigarette additive, may promote smoking

  12. Protective Effect of Porcine Cerebral Hydrolysate Peptides on Learning and Memory Deficits and Oxidative Stress in Lead-Exposed Mice.

    Science.gov (United States)

    Zou, Ye; Feng, Weiwei; Wang, Wei; Chen, Yao; Zhou, Zhaoxiang; Li, Qian; Zhao, Ting; Mao, Guanghua; Wu, Xiangyang; Yang, Liuqing

    2015-12-01

    In this study, lead acetate solution and porcine cerebral hydrolysate peptides (PCHPs) were administered to developing mice. Porcine cerebral protein pretreated by ultrasound was hydrolyzed with alcalase, and 11 peptide fragments were obtained by Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis of PCHPs. Our data showed that PCHPs significantly decreased Pb2+-induced spontaneous locomotor activity, latencies to reach the platform, and the time in target quadrant. It also decreased the accumulation of lead in the blood and brain of Pb2+-exposed developing mice. Co-administration of PCHPs and dimercaptosuccinic acid (DMSA) did not only reduce the accumulation of lead in blood but also increased the absorption of zinc and iron in Pb2+-exposed mice. Administration of PCHPs individually significantly enhanced hematopoietic parameters compared with the Pb2+-exposed group. PCHPs significantly reduced the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) but increased glutathione (GSH) content and anti-oxidant enzymes and nitric oxide synthase (NOS) activities in Pb2+-exposed brain. Our findings suggest that PCHPs have the ability to protect against Pb2+-exposed learning and memory deficits and oxidative damage. PMID:25956150

  13. Direct assessment of cumulative aryl hydrocarbon receptor agonist activity in sera from experimentally exposed mice and environmentally exposed humans

    DEFF Research Database (Denmark)

    Schlezinger, Jennifer J; Bernard, Pamela L; Haas, Amelia;

    2010-01-01

    readouts to provide a broader context for estimating human risk than that obtained with serum extraction and gas chromatography/mass spectroscopy (GC/MS)-based assays alone. METHODS: AhR agonist activity was quantified in sera from dioxin-treated mice, commercial human sources, and polychlorinated biphenyl......BACKGROUND: Aryl hydrocarbon receptor (AhR) ligands adversely affect many biological processes. However, assessment of the significance of human exposures is hampered by an incomplete understanding of how complex mixtures affect AhR activation/inactivation. OBJECTIVES: These studies used biological...

  14. Antigenotoxic potential of rutin and quercetin in Swiss mice exposed to gamma radiation

    Directory of Open Access Journals (Sweden)

    Shrikant L Patil

    2014-10-01

    Full Text Available Background: Ionizing radiation induces a variety of genetic damages through the formation free radicals such as reactive oxygen species (ROS. Appropriate antioxidant intervention may inhibit or reduce free radical toxicity and thus offer protection against radiation. Rutin (RUT and quercetin (QRT are flavonoids known to be potent dietary antioxidants. Methods: The present study tested the antigenotoxic effect of RUT and QRT in vivo against radiation- induced chromosomal damage. Swiss albino mice were administered orally with RUT and QRT (10 and 20 mg/kg b.wt. once daily for five consecutive days. One hour after the last administration of RUT and QRT on the fifth day, the animals were whole body exposed to 3 Gy gamma radiation. The anti-genotoxic potential was assessed in terms of chromosomal aberrations, micronucleus test, and alkaline comet assay. Results: Significant decline in dicentric formation was observed in RUT and QRT treated group. Further, the antigenotoxic potential of RUT and QRT caused a significant (p < 0.001 reduction in micronucleated polychromatic, normochromatic erythrocytes; increased PCE/NCE ratio was observed in the RUT and QRT treated group. Administration of RUT and QRT before irradiation resulted in a significant (p < 0.01 decrease in the DNA damage at the post-irradiation time when compared with irradiation alone group. Conclusions: Present findings demonstrate the potential of RUT and QRT in mitigating radiation-induced mortality and cytogenetic damage, which may be attributed to scavenging of radiation-induced free radicals.

  15. Inflammation and emphysema in cigarette smoke-exposed mice when instilled with poly (I:C) or infected with influenza A or respiratory syncytial viruses

    OpenAIRE

    Mebratu, Yohannes A.; Smith, Kevin R.; Agga, Getahun E.; Tesfaigzi, Yohannes

    2016-01-01

    Background The length of time for cigarette smoke (CS) exposure to cause emphysema in mice is drastically reduced when CS exposure is combined with viral infection. However, the extent of inflammatory responses and lung pathologies of mice exposed to CS and infected with influenza A virus (IAV), respiratory syncytial virus (RSV), or treated with the viral derivative dsRNA (polyinosine-polycytidylic acid [poly (I:C)] have not been compared. Methods Mice were exposed to CS or filtered air for 4...

  16. Life-span studies on mice exposed to heavy charged particles or photons

    International Nuclear Information System (INIS)

    The carcinogenic risk associated with heavy charged (HZE) particles is currently undefined. Precise relationships have been established for relative biological effectiveness (RBE) and linear energy transfer (LET) for the killing of cells in vitro and for other short-term (acute) biological responses to charged particles, but comparable information is lacking on carcinogenic response. Experiments are in progress to study induction/promotion of Harderian gland tumors, and the present life-span studies should provide complementary information because it is inferred that over the dose range explored in the present experiments, most of the life shortening is attributable to induction/promotion of neoplastic diseases. The information sought is important both for understanding fundamental mechanisms of radiation carcinogenesis and for assessing the risk of the space radiation environment and of radiation therapy or other medical applications of heavy charged particles in young patients whose life expectancy could permit expression of a tumor. The hypothesis tested in the core experiment, designated SKYHOOK, is that LET dependence for life shortening and excess mortality rates observed after mice are exposed to heavy charged particles (HZE) will conform to existing theory and observations based on other endpoints; namely, a peak RBE at a dose-averaged LET value of approximately 100 keV/μm, with RBE diminishing at lesser and greater values of LET. Because results on cell killing show different RBE values, at the same approximate LET, for different charged particles, the possibility exists that LET by itself is not a fully adequate descriptor for biological response, and physical characteristics such as mass, charge, or velocity may also be of great importance

  17. Expression profiling reveals novel hypoxic biomarkers in peripheral blood of adult mice exposed to chronic hypoxia.

    Directory of Open Access Journals (Sweden)

    Matias Mosqueira

    Full Text Available Hypoxia induces a myriad of changes including an increase in hematocrit due to erythropoietin (EPO mediated erythropoiesis. While hypoxia is of importance physiologically and clinically, lacunae exist in our knowledge of the systemic and temporal changes in gene expression occurring in blood during the exposure and recovery from hypoxia. To identify these changes expression profiling was conducted on blood obtained from cohorts of C57Bl-10 wild type mice that were maintained at normoxia (NX, exposed for two weeks to normobaric chronic hypoxia (CH or two weeks of CH followed by two weeks of normoxic recovery (REC. Using stringent bioinformatic cut-offs (0% FDR, 2 fold change cut-off, 230 genes were identified and separated into four distinct temporal categories. Class I contained 1 transcript up-regulated in both CH and REC; Class II contained 202 transcripts up-regulated in CH but down-regulated after REC; Class III contained 9 transcripts down-regulated both in CH and REC; Class IV contained 18 transcripts down-regulated after CH exposure but up-regulated after REC. Profiling was independently validated and extended by analyzing expression levels of selected genes as novel biomarkers from our profile (e.g. spectrin alpha-1, ubiquitin domain family-1 and pyrroline-5-carboxylate reductase-1 by performing qPCR at 7 different time points during CH and REC. Our identification and characterization of these genes define transcriptome level changes occurring during chronic hypoxia and normoxic recovery as well as novel blood biomarkers that may be useful in monitoring a variety of physiological and pathological conditions associated with hypoxia.

  18. Effects of pentoxifylline on Wnt/β-catenin signaling in mice chronically exposed to cigarette smoke

    Institute of Scientific and Technical Information of China (English)

    WANG Zheng; ZHANG Jin-nong; HU Xiao-fei; CHEN Xue-lin; WANG Xiao-rong; ZHAO Ting-ting; PENG Mei-jun; ZOU Ping

    2010-01-01

    Background Previous discovery that long-term administration of pentoxifylline (PTX) to mice chronically exposed to smoke led to the development of pulmonary fibrosis rather than emphysema initiated our curiosity on whether the Wnt/β-catenin pathway, a set of signaling proteins essential to organ development and lung morphogenesis in particular were activated in the pathogenesis of pulmonary fibrosis.Methods Male BALB/c mice were randomized into four study groups: Group Sm, smoke exposure and taken regular forage; Group PTX, no smoke but taken PTX-rich forage; Group Sm+PTX, smoke exposure and taken PTX-rich forage;Group control: shamed smoke exposure and taken regular forage. Animals were sacrificed at day 120. Morphometry of the lung sections and the expressions of TGF-β, hydroxyproline, β-catenin, cyclin D1, T cell factor 1 (Tcf-1) and lymphoid enhancer factor 1 (Lef-1) mRNA, etc, in the lung homogenate or in situ were qualitatively or quantitatively analyzed.Results As expected, smoke exposure along with PTX administration for 120 days, lungs of the mice progressed to be a fibrosis-like phenotype, with elevated fibrosis score (3.9±1.1 vs. 1.7±-0.6 in Group Sm, P <0.05). TGF-β (pg/g)(1452.4±465.7 vs. 818.9±202.8 in Group Sm, P <0.05) and hydroxyproline (mg/g) (5.6±0.6, vs. 2.4±0.1 in Group Sm, P<0.05) were also consistently increased. The upregulation of β-catenin measured either by counting the cell with positive staining in microscopic field (17.4±7.9 vs. 9.9±2.9 in Group Sm, P <0.05) or by estimation of the proportion of blue-stained area by Masson's trichrome (11.8±5.6 vs. 4.7±2.4 in Group Sm) in Group SM+PTX was much more noticeable as than those in Group Sm. The expression of β-catenin measured by positive cell counts was correlated to TGF-β1 concentration in lung tissue (r=0.758, P <0.001). PTX per se caused neither fibrosis nor emphysema though expression of β-catenin and downstream gene cyclin D1 may also be altered by this

  19. NanoTIO2 (UV-Titan) does not induce ESTR mutations in the germline of prenatally exposed female mice

    DEFF Research Database (Denmark)

    Boisen, Anne Mette Zenner; Shipley, Thomas; Hougaard, Karin Sørig;

    2012-01-01

    Particulate air pollution has been linked to an increased risk of cardiovascular disease and cancer. Animal studies have shown that inhalation of air particulates induces mutations in the male germline. Expanded simple tandem repeat (ESTR) loci in mice are sensitive markers of mutagenic effects...... on male germ cells resulting from environmental exposures; however, female germ cells have received little attention. Oocytes may be vulnerable during stages of active cell division (e.g., during fetal development). Accordingly, an increase in germline ESTR mutations in female mice prenatally exposed...... exposed by whole-body inhalation to the nanoTiO2 UV-Titan L181 (~42.4 mg UV-Titan/m3) or filtered clean air on gestation days (GD) 8–18. Female C57BL/6 F1 offspring were raised to maturity and mated with unexposed CBA males. The F2 descendents were collected and ESTR germline mutation rates...

  20. Effect on fertility of aging female mice exposed to different doses of X-rays

    International Nuclear Information System (INIS)

    The reproductive performance of aging female mice of CFW/pzh strain was observed after irradiation with doses from 8 to 256 cGy. The reproductive capacity decreased statistically after irradiation of 26 weeks old mice with doses higher than 8 cGy. For mice irradiated at 40 weeks of age the same effect was observed only after irradiation with doses from 32 to 128 cGy. Comparison of these results with the effects of neonatal irradiation indicates that in the case of reproduction the sensitivity of the ovaries of 26 and 40 weeks old mice is higher than in that of newborns. 7 refs., 1 fig., 2 tabs. (author)

  1. Association of EGF Receptor and NLRs signaling with Cardiac Inflammation and Fibrosis in Mice Exposed to Fine Particulate Matter.

    Science.gov (United States)

    Jin, Yuefei; Wu, Zhaoke; Wang, Na; Duan, Shuyin; Wu, Yongjun; Wang, Jing; Wu, Weidong; Feng, Feifei

    2016-09-01

    ЄAmbient fine particulate matter (PM2.5 ) could induce cardiovascular diseases (CVD), but the mechanism remains unknown. To investigate the roles of epidermal growth factor receptor (EGFR) and NOD-like receptors (NLRs) in PM2.5 -induced cardiac injury, we set up a BALB/c mice model of PM2.5 -induced cardiac inflammation and fibrosis with intratracheal instillation of PM2.5 suspension (4.0 mg/kg b.w.) for 5 consecutive days (once per day). After exposure, we found that mRNA levels of CXCL1, interleukin (IL)-6, and IL-18 were elevated, but interestingly, mRNA level of NLRP12 was significant decreased in heart tissue from PM2.5 -induced mice compared with those of saline-treated mice using real-time PCR. Protein levels of phospho-EGFR (Tyr1068), phospho-Akt (Thr308), NLRP3, NF-κB-p52/p100, and NF-κB-p65 in heart tissue of PM2.5 -exposed mice were all significantly increased using immunohistochemistry or Western blotting. Therefore, PM2.5 exposure could induce cardiac inflammatory injury in mice, which may be involved with EGFR/Akt signaling, NLRP3, and NLRP12.

  2. Effects of exogenous glutathione on arsenic burden and NO metabolism in brain of mice exposed to arsenite through drinking water

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yan [China Medical University, Department of Environmental and Occupational Health, School of Public Health, Heping District, Shenyang, Liaoning (China); Liaoning University of Traditional Chinese Medicine, Department of Public Health Management, School of Professional Technology, Shenyang, Liaoning (China); Zhao, Fenghong; Jin, Yaping; Zhong, Yuan; Yu, Xiaoyun; Li, Gexin; Lv, Xiuqiang; Sun, Guifan [China Medical University, Department of Environmental and Occupational Health, School of Public Health, Heping District, Shenyang, Liaoning (China)

    2011-03-15

    Chronic exposure to inorganic arsenic (iAs) is associated with neurotoxicity. Studies to date have disclosed that methylation of ingested iAs is the main metabolic pathway, and it is a process relying on reduced glutathione (GSH). The aim of this study was to explore the effects of exogenous GSH on arsenic burden and metabolism of nitric oxide (NO) in the brain of mice exposed to arsenite via drinking water. Mice were exposed to sodium arsenite through drinking water contaminated with 50 mg/L arsenic for 4 weeks and treated intraperitoneally with saline solution, 200 mg/kg body weight (b.w), 400 mg/kg b.w, or 800 mg/kg b.w GSH, respectively, at the 4th week. Levels of iAs, monomethylarsenic acid, and dimethylarsenic acid (DMAs) in the liver, blood, and brain were determined by method of hydride generation coupled with atomic absorption spectrophotometry. Activities of nitric oxide synthase (NOS) and contents of NO in the brain were determined by colorimetric method. Compared with mice exposed to arsenite alone, administration of GSH increased dose-dependently the primary and secondary methylation ratio in the liver, which caused the decrease in percent iAs and increase in percent DMAs in the liver, as a consequence, resulted in significant decrease in iAs levels in the blood and total arsenic levels in both blood and brain. NOS activities and NO levels in the brain of mice in iAs group were significantly lower than those in control; however, administration of GSH could increase significantly activities of NOS and contents of NO. Findings from this study suggested that exogenous GSH could promote both primary and secondary arsenic methylation capacity in the liver, which might facilitate excretion of arsenicals, and consequently reduce arsenic burden in both blood and brain and furthermore ameliorate the effects of arsenicals on NO metabolism in the brain. (orig.)

  3. Expression of c-fos and c-jun protooncogenes in the uteri of immature mice neonatally exposed to diethylstilbestrol.

    Science.gov (United States)

    Yamashita, S; Takayanagi, A; Shimizu, N

    2003-01-01

    We studied the cell-type-specific and temporal expression of c-fos and c-jun protooncogenes after 17beta-estradiol (E2) stimulation in the uteri of immature 3-week-old mice neonatally exposed to diethylstilbestrol (DES), DES-mice, and the ontogenic expression of these genes in the uteri of DES-mice using immunohistochemistry and in situ hybridization. A single E2 injection induced the transient and rapid expression of c-fos mRNA and c-Fos protein in the endometrial epithelium and endothelial cells of the blood vessels in both 3-week-old vehicle-treated controls and DES-mice; a peak of mRNA expression was 2 hours after E2 injection and that of protein expression was 2 to 3 hours after the injection. The expression of c-fos mRNA and protein after E2 stimulation was lower in the DES-mice than in the control animals. There were no significant differences in the c-jun expression patterns in both experimental groups before and after the E2 injection. The E2 injection transiently down-regulated the c-jun expression in the epithelium and up-regulated it in the stroma and myometrium. The uterine epithelium of DES-mice showed much stronger c-Jun immunostaining on days 4 and 10, compared with those of controls. Neonatal DES treatment reduced c-Jun immunoreactivity in the uterine epithelium on days 4 and 10, and increased the reaction in the stroma on day 4. These results suggested that the neonatal DES treatment induces permanent changes in the c-fos expression pattern independent of the postpuberal secretion of ovarian steroids. The changes in the expression of c-fos and c-jun protooncogenes, particularly during postnatal development, are likely to play important roles in the production of uterine abnormalities in the DES-mice.

  4. Lack of acute phase response in the livers of mice exposed to diesel exhaust particles or carbon black by inhalation

    Directory of Open Access Journals (Sweden)

    Williams Andrew

    2009-04-01

    Full Text Available Abstract Background Epidemiologic and animal studies have shown that particulate air pollution is associated with increased risk of lung and cardiovascular diseases. Although the exact mechanisms by which particles induce cardiovascular diseases are not known, studies suggest involvement of systemic acute phase responses, including C-reactive protein (CRP and serum amyloid A (SAA in humans. In this study we test the hypothesis that diesel exhaust particles (DEP – or carbon black (CB-induced lung inflammation initiates an acute phase response in the liver. Results Mice were exposed to filtered air, 20 mg/m3 DEP or CB by inhalation for 90 minutes/day for four consecutive days; we have previously shown that these mice exhibit pulmonary inflammation (Saber AT, Bornholdt J, Dybdahl M, Sharma AK, Loft S, Vogel U, Wallin H. Tumor necrosis factor is not required for particle-induced genotoxicity and pulmonary inflammation., Arch. Toxicol. 79 (2005 177–182. As a positive control for the induction of an acute phase response, mice were exposed to 12.5 mg/kg of lipopolysaccharide (LPS intraperitoneally. Quantitative real time RT-PCR was used to examine the hepatic mRNA expression of acute phase proteins, serum amyloid P (Sap (the murine homologue of Crp and Saa1 and Saa3. While significant increases in the hepatic expression of Sap, Saa1 and Saa3 were observed in response to LPS, their levels did not change in response to DEP or CB. In a comprehensive search for markers of an acute phase response, we analyzed liver tissue from these mice using high density DNA microarrays. Globally, 28 genes were found to be significantly differentially expressed in response to DEP or CB. The mRNA expression of three of the genes (serine (or cysteine proteinase inhibitor, clade A, member 3C, apolipoprotein E and transmembrane emp24 domain containing 3 responded to both exposures. However, these changes were very subtle and were not confirmed by real time RT

  5. Abnormal Behaviors and Microstructural Changes in White Matter of Juvenile Mice Repeatedly Exposed to Amphetamine

    Directory of Open Access Journals (Sweden)

    Hong-Ju Yang

    2011-01-01

    Full Text Available Amphetamine (AMP is an addictive CNS stimulant and has been commonly abused by adolescents and young adults, during which period brain white matter is still developing. This study was to examine the effect of a nonneurotoxic AMP on the white matter of juvenile mice. d-AMP (1.0 mg/kg was given to young male C57BL/6 mice once a day for 21 days. The spatial working memory and locomotion of mice were measured at the end. Then, mice were sacrificed and their brains were processed for morphological analyses to examine the white matter structure and for Western blot analysis to measure three main proteins expressed in mature oligodendrocytes. AMP-treated mice displayed higher locomotion and spatial working memory impairment and showed lower levels of Nogo-A and GST-pi proteins in frontal cortex and lower MBP protein in the frontal cortex and hippocampus. They also had fewer mature oligodendrocytes and weak MBP immunofluorescent staining in the same two brain regions. But the striatum was spared. These results suggest that the late-developing white matter is vulnerable to AMP treatment which is able to increase striatal and cortical dopamine. Both the compromised white matter and increased dopamine may contribute to the observed behavioral changes in AMP-treated mice.

  6. Influence of seed extract of Syzygium Cumini (Jamun) on mice exposed to different doses of gamma-radiation.

    Science.gov (United States)

    Jagetia, Ganesh Chandra; Baliga, Manjeshwar Shrinath; Venkatesh, Ponemone

    2005-03-01

    The radioprotective activity of the hydroalcoholic extract of jamun seeds (SCE) was studied in mice exposed to different doses of gamma radiation. The mice were injected with 0, 5, 10, 20, 40, 60, 80, 100, 120, 140 or 160 mg/kg body weight of SCE, before exposure to 10 Gy of gamma radiation, to select the optimum dose of radiation protection. The 80 mg/kg SCE was found to offer highest protection, therefore, further studies were carried out using this dose. The drug was more effective when administered through the intraperitoneal route at equimolar doses than the oral route. Since higher survival was observed for the i.p. route (50%), than the oral route (29.2%), all other studies were carried out by injecting SCE intraperitoneally. The mice treated with 80 mg/kg body weight SCE intraperitoneally before exposure to 6, 7, 8, 9, 10 and 11 Gy of gamma radiation showed reduction in the symptoms of radiation sickness and mortality at all exposure doses and caused a significant increase in the animal survival when compared with the concurrent double distilled water (DDW) + irradiation group. The SCE treatment protected mice against the gastrointestinal as well as bone marrow deaths and the DRF was found to be 1.24. PMID:15802860

  7. Sequence analysis of laci mutations obtained from lung cells of radon-exposed big blue{trademark} transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Layton, A.D.; Cross, F.T.; Steigler, G.L.; Stillwell, L.S.; Jostes, R.F. [Pacific Northwest Laboratory, Richland, WA (United States); Lutze, L.H. [Univ. of California, San Francisco, CA (United States)

    1994-12-31

    We have exposed Big Blue{trademark} transgenic mice by inhalation to 320, 640 and 960 Working Level Months (WLM) of radon progeny. Mice were sacrificed after 3, 6 and 9 days; the time periods required to obtain the exposures. Control mice were also sacrificed at each time interval. In each case all tissues were excised, flash frozen in liquid nitrogen, and stored at -80{degrees}C for further analysis. Twelve lacI mutations have been isolated from the lung tissue of a mouse from the 960-WLM exposure group; the lacI genes from these mutants have been sequenced. Sequence data indicate that three of the mutants have a C;G deletion at BP 978 and are possibly clonal in origin. Two mutants have multiple events within the gene: one has a an A:T to C:G transversion and a C:G insertion separated by 291 BPs; the second has a G:C to A:T transition as well as an A:T deletion followed by 6 base pairs downstream by a T:A insertion. Other mutations include a single G:C to A:T transition, a two base pair deletion, and a C:G to T:A transition. Mutant plaques are being evaluated from individual mice at other dose levels. Time course experiments are also planned. These studies will help define the molecular fine structure of mutations induced by high-LET radiation exposure.

  8. Sequence analysis of laci mutations obtained from lung cells of radon-exposed big blue trademark transgenic mice

    International Nuclear Information System (INIS)

    We have exposed Big Blue trademark transgenic mice by inhalation to 320, 640 and 960 Working Level Months (WLM) of radon progeny. Mice were sacrificed after 3, 6 and 9 days; the time periods required to obtain the exposures. Control mice were also sacrificed at each time interval. In each case all tissues were excised, flash frozen in liquid nitrogen, and stored at -80 degrees C for further analysis. Twelve lacI mutations have been isolated from the lung tissue of a mouse from the 960-WLM exposure group; the lacI genes from these mutants have been sequenced. Sequence data indicate that three of the mutants have a C;G deletion at BP 978 and are possibly clonal in origin. Two mutants have multiple events within the gene: one has a an A:T to C:G transversion and a C:G insertion separated by 291 BPs; the second has a G:C to A:T transition as well as an A:T deletion followed by 6 base pairs downstream by a T:A insertion. Other mutations include a single G:C to A:T transition, a two base pair deletion, and a C:G to T:A transition. Mutant plaques are being evaluated from individual mice at other dose levels. Time course experiments are also planned. These studies will help define the molecular fine structure of mutations induced by high-LET radiation exposure

  9. Lack of acute phase response in the livers of mice exposed to diesel exhaust particles or carbon black by inhalation

    DEFF Research Database (Denmark)

    Saber, Anne T; Halappanavar, Sabina; Folkmann, Janne K;

    2009-01-01

    BACKGROUND: Epidemiologic and animal studies have shown that particulate air pollution is associated with increased risk of lung and cardiovascular diseases. Although the exact mechanisms by which particles induce cardiovascular diseases are not known, studies suggest involvement of systemic acute...... phase responses, including C-reactive protein (CRP) and serum amyloid A (SAA) in humans. In this study we test the hypothesis that diesel exhaust particles (DEP) - or carbon black (CB)-induced lung inflammation initiates an acute phase response in the liver. RESULTS: Mice were exposed to filtered air......, 20 mg/m3 DEP or CB by inhalation for 90 minutes/day for four consecutive days; we have previously shown that these mice exhibit pulmonary inflammation (Saber AT, Bornholdt J, Dybdahl M, Sharma AK, Loft S, Vogel U, Wallin H. Tumor necrosis factor is not required for particle-induced genotoxicity and...

  10. Metabolomic Profiling of Urine Samples from Mice Exposed to Protons Reveals Radiation Quality and Dose Specific Differences

    OpenAIRE

    Laiakis, Evagelia C.; Trani, Daniela; Moon, Bo-Hyun; Strawn, Steven J.; Fornace, Albert J.

    2015-01-01

    As space travel is expanding to include private tourism and travel beyond low-Earth orbit, so is the risk of exposure to space radiation. Galactic cosmic rays and solar particle events have the potential to expose space travelers to significant doses of radiation that can lead to increased cancer risk and other adverse health consequences. Metabolomics has the potential to assess an individual’s risk by exploring the metabolic perturbations in a biofluid or tissue. In this study, C57BL/6 mice...

  11. Histopathological Studies on Some Vital Organs of Mice Exposed To Extremely Low Frequency Magnetic Field

    Directory of Open Access Journals (Sweden)

    Aida Abd El-Karim Salama, (2 Neveen Hussein Mahmoud,

    2006-03-01

    Full Text Available Twenty five male Swiss albino mice were used in this study to detect the effect of extremely low frequency magnetic field (ELFMF 2 milli Tesla-50 Hertz (2 mT,50 Hz 8 hours/day at different time intervals. Mice were divided into five groups, control group and 4 treated groups, two groups represented the direct effect of (ELFMF and the other two represented the late effect. The direct effect groups were sacrificed direcly after the end of exposure to (ELFMF, while the late effect groups were sacrificed after certain duration period of the exposure away from (ELFMF. In the present work, histopathological studies revealed severe degeneration changes in kidney, spleen and testes of all groups of mice direct and late effect groups and no sign of complete recovery could be detected in the late effect groups. Glomerular volume, number of glomeruli, relative glomerular blood volume (RGBV of the kidney; and the mean number cells of spermatogenesis cells of the testes were calculated in control and treated groups. The histopathological changes observed in the kidney, spleen and testes of treated mice were less in direct effect groups than that observed in late effect groups.

  12. [Redistribution of immune defence in male mice exposed by female scent].

    Science.gov (United States)

    Litvinova, E A; Garms, A I; Zaĭdman, A M; Korel', A V; Gerlinskaia, L A; Moshkin, M P

    2009-01-01

    Since scent marks of mice are harbored by parasites, their sniffing during olfactory search of the mating partner leads to increase of the infection risk. A hypothesis that sexual signals can induce, along with the reproductive behavior, non-specific immune defense against respiratory infections is tested in the present paper. It was found in the experiments on outbred ICR mice that the scent of soiled bedding from cages with mature females stimulated leukocyte intervention to the upper air-ways. Migration of the white blood cells to lung tissue was accompanied with a more prominent immune and endocrine responeses to intranasal application of the bacterial lipopolysacharide (LPS). In particular, LPS administration to male mice treated by female scent was resulted in much greater amount of leukocyte aggregations in the peribronchial areas than that was found in the males kept isolated from the female signals. The female scent also enhanced adrenocortical response to LPS administration, which was coincided with statistically significant increase of IL-1beta concentration in hypothalamus. So, chemical signals of the mature female induce travel of white blood cells to the upper air-waya in the scent treated male mice. It can increase resistance to respiratory infections, on the one hand, and aggravates stress response to inhalation of the bacterial compounds, on the other hand. PMID:19326854

  13. Exposing to cadmium stress cause profound toxic effect on microbiota of the mice intestinal tract.

    Directory of Open Access Journals (Sweden)

    Yehao Liu

    Full Text Available Cadmium (Cd, one of the heavy metals, is an important environmental pollutant and a potent toxicant to organism. It poses a severe threat to the growth of the organism, and also has been recognized as a human carcinogen. However, the toxicity of cadmium and its influences on microbiota in mammal's intestine are still unclear. In our experiment, the changes of intestinal microbiota in two groups of mice were investigated, which were supplied with 20 and 100 mg kg(-1 cadmium chloride respectively for 3 weeks. The control group was treated with water free from cadmium chloride only. This study demonstrated that Cd accumulated in some tissues of mice after Cd administration and the gut barrier was impaired. Cd exposure also significantly elevated the colonic level of TNF-α. On the other hand, Cd-treatment could slow down the growth of gut microbiota and reduced the abundance of total intestinal bacteria of the mice. Among them, the growth of Bacteroidetes was significantly suppressed while Firmicutes growth was not. The probiotics including Lactobacillus and Bifidobacterium were notably inhibited. We also observed that the copies of key genes involved in the metabolism of carbohydrates to short-chain fatty acids (SCFAs were lower in Cd-treated groups than control. As a result, the levels of short-chain fatty acids in colonic decreased significantly. In summary, this study provides valuable insight into the effects of Cd intake on mice gut microbiota.

  14. Onset of behavioral effects in mice exposed to 10-Gy 60Co radiation

    Energy Technology Data Exchange (ETDEWEB)

    Maier, D.M.; Landauer, M.R.

    1990-10-01

    The effects of 10 Gray (Gy)60Co radiation on social behavior, locomotor activity, and body weight were assessed in individually housed male Swiss-Webster mice. In Experiment 1, aggressive behavior was evaluated prior to irradiation and for 7 d postirradiation by placing an untreated intruder in the irradiated or sham-irradiated resident's home cage for 5 min. Offensive aggressive behavior was not affected significantly by radiation until day 7 postirradiation, when attack latency increased, the frequency and duration of fighting decreased, and the frequency of bites, lunges, and chases decreased. Untreated intruder mice paired with irradiated resident mice showed a decrease in the duration of defensive upright postures, squeaks, and escapes on day 7 postirradiation. In Experiment 2, locomotor activity and body weight were monitored for 7 d postirradiation. Body weight was decreased in irradiated mice beginning 4 d postirradiation. Locomotor activity was suppressed in irradiated animals 90 min after irradiation and remained depressed throughout the 7-d testing period.

  15. Onset of behavioral effects in mice exposed to 10 Gy Co-60 radiation

    Energy Technology Data Exchange (ETDEWEB)

    Maier, D.M.; Landauer, M.R. (Armed Forces Radiobiology Research Institute, Bethesda, MD (USA))

    1990-10-01

    The effects of 10 Gray (Gy) Co-60 radiation on social behavior, locomotor activity, and body weight were assessed in individually housed male Swiss-Webster mice. In experiment 1, aggressive behavior was evaluated prior to irradiation and for 7 d postirradiation by placing an untreated intruder in the irradiated or sham-irradiated resident's home cage for 5 min. Offensive aggressive behavior was not affected significantly by radiation until day 7 postirradiation, when attack latency increased, the frequency and duration of fighting decreased, and the frequency of bites, lunges, and chases decreased. Untreated intruder mice paired with irradiated resident mice showed a decrease in the duration of defensive upright postures and a decrease in the frequency of defensive upright postures, squeaks, and escapes on day 7 postirradiation. In experiment 2, locomotor activity and body weight were monitored for 7 d postirradiation. Body weight was decreased in irradiated mice beginning 4 d postirradiation. Locomotor activity was suppressed in irradiated animals 90 min after irradiation and remained depressed throughout the 7-d testing period. 25 refs.

  16. An enhanced postnatal autoimmune profile in 24 week-old C57BL/6 mice developmentally exposed to TCDD

    International Nuclear Information System (INIS)

    Developmental exposure of mice to the environmental contaminant and AhR agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), causes persistent postnatal suppression of T cell-mediated immune responses. The extent to which prenatal TCDD may induce or exacerbate postnatal autoimmune disease remains unknown. In the present study, time-pregnant high affinity AhR C57BL/6 mice received a single oral administration of 0, 2.5, or 5 μg/kg TCDD on gestation day (gd) 12. Offspring of these mice (n = 5/gender/treatment) were evaluated at 24 weeks-of-age and showed considerable immune dysregulation that was often gender-specific. Decreased thymic weight and percentages of CD4+CD8+ thymocytes, and increased CD4+CD8- thymocytes, were present in the female but not male offspring. Males but not females showed decreased CD4-CD8+ T cells, and increased Vβ3+ and Vβ17a+ T cells, in the spleen. Males but not females also showed increased percentages of bone marrow CD24-B220+ B cell progenitors. Antibody titers to dsDNA, ssDNA and cardiolipin displayed increasing trends in both male and female mice, reaching significance for anti-dsDNA in both genders and for ssDNA in males at 5 μg/kg TCDD. Immunofluorescent staining of IgG and C3 deposition in kidney glomeruli increased in both genders of prenatal TCDD-exposed mice, suggestive of early stages of autoimmune glomerulonephritis. Collectively, these results show that exposure to TCDD during immune system development causes persistent humoral immune dysregulation as well as altered cell-mediated responses, and induces an adult profile of changes suggestive of increased risk for autoimmune disease

  17. Proteomic identification of carbonylated proteins in the kidney of trichloroethene-exposed MRL+/+ mice

    OpenAIRE

    Fan, Xiuzhen; WANG, GANGDUO; English, Robert D.; Khan, M. Firoze

    2013-01-01

    Trichloroethene (TCE), a common environmental and occupational pollutant, is associated with multi-organ toxicity. Kidney is one of major target organs affected as a result of TCE exposure. Our previous studies have shown that exposure to TCE causes increased protein oxidation (protein carbonylation) in the kidneys of autoimmune-prone MRL +/+ mice, and suggested a potential role of protein oxidation in TCE-mediated nephrotoxicity. To assess the impact of chronic TCE exposure on protein oxidat...

  18. Exaggerated phosphorylation of brain tau protein in CRH KO mice exposed to repeated immobilization stress.

    Science.gov (United States)

    Kvetnansky, Richard; Novak, Petr; Vargovic, Peter; Lejavova, Katarina; Horvathova, Lubica; Ondicova, Katarina; Manz, George; Filipcik, Peter; Novak, Michal; Mravec, Boris

    2016-07-01

    Neuroendocrine and behavioral stress responses are orchestrated by corticotropin-releasing hormone (CRH) and norepinephrine (NE) synthesizing neurons. Recent findings indicate that stress may promote development of neurofibrillary pathology in Alzheimer's disease. Therefore, we investigated relationships among stress, tau protein phosphorylation, and brain NE using wild-type (WT) and CRH-knockout (CRH KO) mice. We assessed expression of phosphorylated tau (p-tau) at the PHF-1 epitope and NE concentrations in the locus coeruleus (LC), A1/C1 and A2/C2 catecholaminergic cell groups, hippocampus, amygdala, nucleus basalis magnocellularis, and frontal cortex of unstressed, singly stressed or repeatedly stressed mice. Moreover, gene expression and protein levels of tyrosine hydroxylase (TH) and CRH receptor mRNA were determined in the LC. Plasma corticosterone levels were also measured. Exposure to a single stress increases tau phosphorylation throughout the brain in WT mice when compared to singly stressed CRH KO animals. In contrast, repeatedly stressed CRH KO mice showed exaggerated tau phosphorylation relative to WT controls. We also observed differences in extent of tau phosphorylation between investigated structures, e.g. the LC and hippocampus. Moreover, CRH deficiency leads to different responses to stress in gene expression of TH, NE concentrations, CRH receptor mRNA, and plasma corticosterone levels. Our data indicate that CRH effects on tau phosphorylation are dependent on whether stress is single or repeated, and differs between brain regions. Our findings indicate that CRH attenuates mechanisms responsible for development of stress-induced tau neuropathology, particularly in conditions of chronic stress. However, the involvement of central catecholaminergic neurons in these mechanisms remains unclear and is in need of further investigation.

  19. Effect of tannins from Dioscoreae Cirrhosae and Galla chinensis on gamma ray exposed mice

    International Nuclear Information System (INIS)

    Objective: To explore the protective effect of tannins from Dioscoreae Cirrhosae and Galla chinensis on radiation injury. Methods: Forty male Chinese Kunming mice were randomly divided into non-radiation group, radiation group without drugs,radiation group with tea polyphenols, radiation group with tannins from Dioscoreae Cirrhosae and radiation group with tannins from Galla chinensis. The radiation groups were irradiated with a single exposure of 8.0 Gy γ rays from 60Co. The mice were intragastric ally administered 2 h before radiation and were done 18 h after radiation. The 30-day survival rate, the mean survival time and the protective coefficients were confirmed. Results: All the mice of radiation group without drugs died in 16 d after exposure,and their mean survival time was (12.0±2.45) d, while the radiation groups with tannins from Dioscoreae Cirrhosae, with tannins from Galla chinensis and with tea polyphenols were (26.25±7.13) d, (21.88±8.89) d and (23.25±9.33) d respectively. There was significant difference in comparison with radiation group without drugs (P60Co and could present a significant protection effect on radiation injuries. (authors)

  20. Longevity and tumour incidence in mice exposed to fast neutrons at different ages

    International Nuclear Information System (INIS)

    Experiments are under way in the authors' laboratory to observe both neoplastic and non-neoplastic late effects in mice irradiated with fission neutrons and X-rays at three different ages. Analysis of data from over 2800 animals is in progress and a preliminary evaluation can be made on the survival and the pathology at spontaneous death of mice irradiated in utero and at 3 months of age. Single doses of 250kV X-rays or of attenuated fission neutrons obtained in the biological channel of the experimental fast reactor RSV TAPIRO of the Casaccia Centre were given to male BC3F1 mice of 3 months of age and to pregnant females on day 17.5 post coitum. Both male and female offspring of the latter group were followed to spontaneous death, along with appropriate untreated controls. As for the 3 month old irradiated animals their mean survival time was decreased by X-rays, the dose-effect relationship being compatible with a linear fitting. Fission neutrons proved to be more efficient than X-rays in the induction of life shortening, but the shape of the dose-effect relationship did not fit a linear model because efficiency is higher at low than at high neutron doses. Reticulum cell sarcoma (RCS) was decreased by increasing X-ray and neutron doses, the latter being more efficient. The final incidences of all other neoplasms, regardless of tumour type and site, indicate that neutrons are more efficient than X-rays in tumour induction at low and intermediate doses. As for prenatally irradiated mice, no detectable effect on mean lifespan was observed for either type of radiation. A low final frequency of RCS was seen after irradiation at all dose levels of both types of radiation. The incidence of all other tumours was practically unchanged in male mice irradiated as foetuses with X-rays, but a significant excess was found after neutron irradiation, showing a frequency peak in the range of 0.27-0.45Gy. Similar results were obtained after irradiation of foetal females. (author)

  1. Severe iron deficiency anemia in transgenic mice expressing liver hepcidin

    OpenAIRE

    Nicolas, Gaël; Bennoun, Myriam; Porteu, Arlette; Mativet, Sandrine; Beaumont, Carole; Grandchamp, Bernard; Sirito, Mario; Sawadogo, Michèle; Kahn, Axel; Vaulont, Sophie

    2002-01-01

    We recently reported the hemochromatosis-like phenotype observed in our Usf2 knockout mice. In these mice, as in murine models of hemochromatosis and patients with hereditary hemochromatosis, iron accumulates in parenchymal cells (in particular, liver and pancreas), whereas the reticuloendothelial system is spared from this iron loading. We suggested that this phenotypic trait could be attributed to the absence, in the Usf2 knockout mice, of a secreted liver-specific peptide, hepcidin. We con...

  2. SPONTANEOUS TUMORS IN MICE EXPOSED TO CIGARETTE SECOND-HAND SMOKE

    OpenAIRE

    Tume, L.F.

    2014-01-01

    Cigarette smoke inhaled second-hand is common with different types of cigarettes and can lead to an increased risk of developing tumors if the frequency is constant. In this experiment a group of four individuals (Mus musculus) were exposed to second-handcigarettesmoke three times a week for four months; later the occurrence of spontaneous tumors was observed in contrast to the control group. This study provides further evidence that second-hand cigarette smoke has components t...

  3. Modulation by metformin of molecular and histopathological alterations in the lung of cigarette smoke-exposed mice.

    Science.gov (United States)

    Izzotti, Alberto; Balansky, Roumen; D'Agostini, Francesco; Longobardi, Mariagrazia; Cartiglia, Cristina; Micale, Rosanna T; La Maestra, Sebastiano; Camoirano, Anna; Ganchev, Gancho; Iltcheva, Marietta; Steele, Vernon E; De Flora, Silvio

    2014-06-01

    The anti-diabetic drug metformin is endowed with anti-cancer properties. Epidemiological and experimental studies, however, did not provide univocal results regarding its role in pulmonary carcinogenesis. We used Swiss H mice of both genders in order to detect early molecular alterations and tumors induced by mainstream cigarette smoke. Based on a subchronic toxicity study, oral metformin was used at a dose of 800 mg/kg diet, which is 3.2 times higher than the therapeutic dose in humans. Exposure of mice to smoke for 4 months, starting at birth, induced a systemic clastogenic damage, formation of DNA adducts, oxidative DNA damage, and extensive downregulation of microRNAs in lung after 10 weeks. Preneoplastic lesions were detectable after 7.5 months in both lung and urinary tract along with lung tumors, both benign and malignant. Modulation by metformin of 42 of 1281 pulmonary microRNAs in smoke-free mice highlighted a variety of mechanisms, including modulation of AMPK, stress response, inflammation, NFκB, Tlr9, Tgf, p53, cell cycle, apoptosis, antioxidant pathways, Ras, Myc, Dicer, angiogenesis, stem cell recruitment, and angiogenesis. In smoke-exposed mice, metformin considerably decreased DNA adduct levels and oxidative DNA damage, and normalized the expression of several microRNAs. It did not prevent smoke-induced lung tumors but inhibited preneoplastic lesions in both lung and kidney. In conclusion, metformin was able to protect the mouse lung from smoke-induced DNA and microRNA alterations and to inhibit preneoplastic lesions in lung and kidney but failed to prevent lung adenomas and malignant tumors induced by this complex mixture. PMID:24683044

  4. Modulation by metformin of molecular and histopathological alterations in the lung of cigarette smoke-exposed mice

    International Nuclear Information System (INIS)

    The anti-diabetic drug metformin is endowed with anti-cancer properties. Epidemiological and experimental studies, however, did not provide univocal results regarding its role in pulmonary carcinogenesis. We used Swiss H mice of both genders in order to detect early molecular alterations and tumors induced by mainstream cigarette smoke. Based on a subchronic toxicity study, oral metformin was used at a dose of 800 mg/kg diet, which is 3.2 times higher than the therapeutic dose in humans. Exposure of mice to smoke for 4 months, starting at birth, induced a systemic clastogenic damage, formation of DNA adducts, oxidative DNA damage, and extensive downregulation of microRNAs in lung after 10 weeks. Preneoplastic lesions were detectable after 7.5 months in both lung and urinary tract along with lung tumors, both benign and malignant. Modulation by metformin of 42 of 1281 pulmonary microRNAs in smoke-free mice highlighted a variety of mechanisms, including modulation of AMPK, stress response, inflammation, NFκB, Tlr9, Tgf, p53, cell cycle, apoptosis, antioxidant pathways, Ras, Myc, Dicer, angiogenesis, stem cell recruitment, and angiogenesis. In smoke-exposed mice, metformin considerably decreased DNA adduct levels and oxidative DNA damage, and normalized the expression of several microRNAs. It did not prevent smoke-induced lung tumors but inhibited preneoplastic lesions in both lung and kidney. In conclusion, metformin was able to protect the mouse lung from smoke-induced DNA and microRNA alterations and to inhibit preneoplastic lesions in lung and kidney but failed to prevent lung adenomas and malignant tumors induced by this complex mixture

  5. Histopathology related to cadmium and lead bioaccumulation in chronically exposed wood mice, Apodemus sylvaticus, around a former smelter.

    Science.gov (United States)

    Tête, Nicolas; Durfort, Mercè; Rieffel, Dominique; Scheifler, Renaud; Sánchez-Chardi, Alejandro

    2014-05-15

    The ceasing of industrial activities often reduces the emission of pollutants but also often leaves disturbed areas without remediation and with persistent pollutants that can still be transferred along the food chain. This study examines the potential relationships between non-essential trace metals and histopathology in target tissues of wood mice (Apodemus sylvaticus) collected along a gradient of contamination around the former smelter, Metaleurop Nord (northern France). Cadmium and lead concentrations were measured, and histological alterations attributable to chronic trace metal exposure were assessed in the liver and the kidneys of 78 individuals. Metal concentrations quantified in the present study were among the highest observed for this species. Some histological alterations significantly increased with Cd or Pb concentrations in the soil and in the organs. Sixteen mice from polluted sites were considered at risk for metal-induced stress because their Cd and/or Pb tissue concentrations exceeded the LOAELs for single exposure to these elements. These mice also exhibited a higher severity of histological alterations in their organs than individuals with lower metal burdens. These results indicate that the Metaleurop smelter, despite its closure in 2003, still represents a threat to the local ecosystem because of the high levels and high bioavailability of Cd and Pb in the soil. However, among the mice not considered at risk for metal-induced stress based on the metal levels in their tissues, a large percentage of individuals still exhibited histological alterations. Thus, the present study suggests that the evaluation of toxic effects based only on the LOAELs for single metal exposure may result in the underestimation of the real risks when specimens are exposed to multiple stressors.

  6. [Cytogenetic investigations of bone marrow cells from mice exposed onboard biosatellite "Bion-M1"].

    Science.gov (United States)

    Dorozhkina, O V; Ivanov, A A

    2015-01-01

    The results of studying the mitotic activities and chromosomal aberrations in bone marrow cells from C57/BL6N mice with the help of the anaphase technique in 12 hours after completion of the 30-day "Bion-M1" mission and ground-based experiment using flight equipment are presented. A statistically reliable decline of the mitotic activity (0.74%) was found in cells taken from the space flown animals. In the ground-based experiment, a statistically reliable downward trend in proliferative activity (1.37%) was revealed after the comparison with groups of vivarium control (1.46-1.53%). In both experiments mice increased the number of initial mitotic phases (prophase + metaphase) relative to the sum of anaphases and telophases. The number of aberrant mitoses grew reliably in the group of flight animals by 29.7%, whereas in the ground-based experiment an upward trend was insignificant as their number increased up to 2.3% only. In the vivarium controls aberrant mitoses constituted 1.75-1.8%. An increase in chromosomal aberrations was largely due to such abnormalities as fragments. These findings seem to have been a result of summation of the effects of radiation and other stressful factors in space flight.

  7. Radioprotective effect of calcium channel blocker, diltiazem on survival in gamma rays exposed mice

    International Nuclear Information System (INIS)

    Diltiazem, a calcium channel blocker, used widely in cardio-vascular therapy, protected mice against death and weight loss due to ionising radiation. Administration of such compound 30 minutes prior to 8.0 Gy gamma irradiation enhanced the 30 days survival of animals to 37.5 and 82.5 percent at the dose of 50 and 100 mg/kg b. wt., respectively. On the contrary, 100 per cent death was noted at the dose of 25 mg and 82.5 percent at 200 mg/kg b.wt. Pre-treatment with a dose of 100 mg/kg b.wt. enhanced 30 day survival after lethal irradiation and also inhibited the radiation induced life span shortening. Prior treatment of diltiazem accelerated the recovery of radiation induced weight loss also. Data on dose response demonstrate that higher dose of diltiazem (up to 100 mg/kg b.wt.) is more effective against lethal gamma radiation dose. However, doses above 100 mg/kg b. wt. was found to be quite ineffective in preventing mice against deleterious effects of radiation. (author)

  8. [Cytogenetic investigations of bone marrow cells from mice exposed onboard biosatellite "Bion-M1"].

    Science.gov (United States)

    Dorozhkina, O V; Ivanov, A A

    2015-01-01

    The results of studying the mitotic activities and chromosomal aberrations in bone marrow cells from C57/BL6N mice with the help of the anaphase technique in 12 hours after completion of the 30-day "Bion-M1" mission and ground-based experiment using flight equipment are presented. A statistically reliable decline of the mitotic activity (0.74%) was found in cells taken from the space flown animals. In the ground-based experiment, a statistically reliable downward trend in proliferative activity (1.37%) was revealed after the comparison with groups of vivarium control (1.46-1.53%). In both experiments mice increased the number of initial mitotic phases (prophase + metaphase) relative to the sum of anaphases and telophases. The number of aberrant mitoses grew reliably in the group of flight animals by 29.7%, whereas in the ground-based experiment an upward trend was insignificant as their number increased up to 2.3% only. In the vivarium controls aberrant mitoses constituted 1.75-1.8%. An increase in chromosomal aberrations was largely due to such abnormalities as fragments. These findings seem to have been a result of summation of the effects of radiation and other stressful factors in space flight. PMID:25958465

  9. Increased hippocampal Disrupted-In-Schizophrenia 1 expression in mice exposed prenatally to lead

    Institute of Scientific and Technical Information of China (English)

    Yuanyuan You; Liguang Sun; Bo Peng; Yan Li; Songbin Ben; Shuang Gao

    2012-01-01

    Disrupted-In-Schizophrenia 1 is a susceptibility gene for schizophrenia and other psychiatric disorders.Developmental lead exposure can cause neurological disorders similar to hyperactivity disorder,dyslexia and schizophrenia. In the present study, we examined the impact of developmental lead exposure, administered in vitro and in vivo, on hippocampal Disrupted-In- Schizophrenia 1 expression. Our results show that in cultured hippocampal neurons, in vitro exposure to 0.1-10 μM lead, inhibited neurite growth and increased Disrupted-In-Schizophrenia 1 mRNA and protein expression dose-dependently. In addition, blood lead levels in mice were increased with increasing mouse maternal lead (0.01-1 mM) exposure. Hippocampal neurons from these mice showed a concomitant increase in Disrupted-In-Schizophrenia 1 mRNA and protein expression. Overall our findings suggest that in vivo and in vitro lead exposure increases Disrupted-In-Schizophrenia 1 expression in hippocampal neurons dose-dependently, and consequently may influence synapse formation in newborn neurons.

  10. Toxicity of Lunar Dust in Lungs Assessed by Examining Biomarkers in Exposed Mice

    Science.gov (United States)

    Lam, C.-W.; James, J. T.; Zeidler-Erdely, P. C.; Castranova, V.; Young, S. H.; Quan, C. L.; Khan-Mayberry, N.; Taylor, L. A.

    2010-01-01

    NASA is contemplating to build an outpost on the Moon for prolonged human habitation and research. The lunar surface is covered by a layer of soil, of which the finest portion is highly reactive dust. Dust samples of respirable sizes were aerodynamically isolated from two lunar soil samples of different maturities (cosmic exposure ages) collected during the Apollo 16 mission. The lunar dust samples, TiO2, or quartz, suspended in normal saline were given to groups of 5 C57 male mice by intrapharyngeal aspiration at 0. 1, 0.3, or 1.0 mg/mouse. Because lunar dust aggregates rapidly in aqueous media, some tests were conducted with dusts suspended in Survanta/saline (1:1). The mice were euthanized 7 or 30 days later, and their lungs were lavaged to assess the presence of toxicity biomarkers in bronchioalveolar lavage fluids. The overall results showed that the two lunar dust samples were similar in toxicity, they were more toxic than T102 , but less toxic than quartz. This preliminary study is a part of the large study to obtain data for setting exposure limits for astronauts living on the Moon

  11. Western diet enhances hepatic inflammation in mice exposed to cecal ligation and puncture

    Directory of Open Access Journals (Sweden)

    Houghton Jeff

    2010-10-01

    Full Text Available Abstract Background Obese patients display an exaggerated morbidity during sepsis. Since consumption of a western-style diet (WD is a major factor for obesity in the United States, the purpose of the present study was to examine the influence of chronic WD consumption on hepatic inflammation in mice made septic via cecal ligation and puncture (CLP. Feeding mice diets high in fat has been shown to enhance evidence of TLR signaling and this pathway also mediates the hepatic response to invading bacteria. Therefore, we hypothesized that the combined effects of sepsis and feeding WD on TRL-4 signaling would exacerbate hepatic inflammation. Male C57BL/6 mice were fed purified control diet (CD or WD that was enriched in butter fat (34.4% of calories for 3 weeks prior to CLP. Intravital microscopy was used to evaluate leukocyte adhesion in the hepatic microcirculation. To demonstrate the direct effect of saturated fatty acid on hepatocytes, C3A human hepatocytes were cultured in medium containing 100 μM palmitic acid (PA. Quantitative real-time PCR was used to assess mRNA expression of tumor necrosis factor-alpha (TNF-α, monocyte chemotactic protein-1 (MCP-1, intercellular adhesion molecule-1 (ICAM-1, toll-like receptor-4 (TLR-4 and interleukin-8 (IL-8. Results Feeding WD increased firm adhesion of leukocytes in the sinusoids and terminal hepatic venules by 8-fold six hours after CLP; the increase in platelet adhesion was similar to the response observed with leukocytes. Adhesion was accompanied by enhanced expression of TNF-α, MCP-1 and ICAM-1. Messenger RNA expression of TLR-4 was also exacerbated in the WD+CLP group. Exposure of C3A cells to PA up-regulated IL-8 and TLR-4 expression. In addition, PA stimulated the static adhesion of U937 monocytes to C3A cells, a phenomenon blocked by inclusion of an anti-TLR-4/MD2 antibody in the culture medium. Conclusions These findings indicate a link between obesity-enhanced susceptibility to sepsis and

  12. Altered immunological response in mice subjected to stress and exposed to fungal spores

    Science.gov (United States)

    Kurup, Viswanath P.; Choi, Hongyung; Kumar, Anoopa; Murali, Pazhayannur S.; Mishra, S. K.; Pierson, Duane L.

    1992-01-01

    Space flight and related factors such as stress appear to have an adverse effect on astronauts' immune systems. The presence of potentially pathogenic microbes including several genera of fungi reported from spacecraft environment may be a cause of concern in such situations. In order to study the role of such organisms in causing opportunistic or allergic diseases in crewmembers, we have tried to develop an animal model. BALB/c mice were suspended upside down for varying periods of time to induce stress, and their lymphocyte functions were evaluated. These studies indicate that the stress resulted in lowered mitogen induced lymphocyte stimulation as represented by 3H-thymidine uptake. We have also studied the ability of these animals to respond to Aspergillus fumigatus spores. The results of the study clearly demonstrate a definite down-regulation in T-cell proliferation and a higher incidence of infection with A. fumigatus.

  13. Differential proteome and gene expression for testis of mice exposed to carbon ion radiation

    Science.gov (United States)

    Zhang, Hong; Li, Hongyan

    Objective To investigate the effect and mechanism of high linear energy transfer (LET) carbon ion irradiation (CIR) on reproduction in the testis of male Swiss Webster mice, and assess the risk associated with space environment. Methods Male mice underwent whole-body irradiation with CIR (0.5, 1 and 4Gy), and matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF) analysis was used to determine the alteration in protein expression in 2-DE (two-dimensional gel electrophoresis) gels of testes caused by irradiation after 7, 14 days. Results 15 differentially expressed proteins, such as glucose-regulated protein(GRP78), aconitate hydratase-mitochondrial precursor (ACO), pyruvate kinase isozymes M1/M2 (PKM1/M2), glutathione-S-transferaseA3 (GSTA3), glutathione S-transferase Pi 1 (GSTP1), Cu/Zn super-oxide dismutase (SOD1), Peptidyl-prolyl cis-trans isomerase (Pin1) and Heat shock 70 kDa protein 4L (HSPa4L), were identified and these proteins were mainly involved in energy supply, the endoplasmic reticulum, cell proliferation, cell cycle, antioxidant capacity and mitochondrial respiration, which play important roles in the inhibition of testicular function in response to CIR. Furthermore, we confirmed the relationship between transcription of mRNA and the abundance of proteins. Conclusion The findings of the present study demonstrated that these proteins may lead to new insights into the molecular mechanism of CIR toxicity, and suggested that the gene expression response to CIR involves diverse regulatory mechanisms from transcription of mRNA to the formation of functional proteins. These data also may provide a scientific basis for protecting astronauts and space traveler’s health and safety.

  14. Suppression of NMDA receptor function in mice prenatally exposed to valproic acid improves social deficits and repetitive behaviors

    Directory of Open Access Journals (Sweden)

    Jaeseung eKang

    2015-05-01

    Full Text Available Animals prenatally exposed to valproic acid (VPA, an antiepileptic agent, have been used as a model for autism spectrum disorders (ASDs. Previous studies have identified enhanced NMDA receptor (NMDAR function in the brain of VPA rats, and demonstrated that pharmacological suppression of NMDAR function normalizes social deficits in these animals. However, whether repetitive behavior, another key feature of ASDs, can be rescued by NMDAR inhibition remains unknown. We report here that memantine, an NMDAR antagonist, administered to VPA mice rescues both social deficits and repetitive behaviors such as self-grooming and jumping. These results suggest that suppression of elevated NMDAR function in VPA animals normalizes repetitive behaviors in addition to social deficits.

  15. Modest effect on plaque progression and vasodilatory function in atherosclerosis-prone mice exposed to nanosized TiO2

    DEFF Research Database (Denmark)

    Mikkelsen, Lone; Sheykhzade, Majid; Jensen, Keld A;

    2011-01-01

    of atherosclerotic plaques in aorta was assessed in mice exposed to nanosized TiO2 (0.5 mg/kg bodyweight) once a week for 4 weeks. We measured mRNA levels of Mcp-1, Mip-2, Vcam-1, Icam-1 and Vegf in lung tissue to assess pulmonary inflammation and vascular function. TiO2-induced alterations in nitric oxide (NO......) production were assessed in human umbilical vein endothelial cells (HUVECs). RESULTS: The exposure to nTiO2 was associated with a modest increase in plaque progression in aorta, whereas there were unaltered vasodilatory function and expression levels of Mcp-1, Mip-2, Vcam-1, Icam-1 and Vegf in lung tissue...

  16. Morphofunctional evaluation of human skin preserved in glycerol and exposed to gamma radiation: a study in athymic mice

    International Nuclear Information System (INIS)

    Extensive skin lesions expose the body to damaging agents, which makes spontaneous regeneration difficult and, in many cases, leads patient to death. In such cases, if there are no donating areas for autograft, allografts can be used. In this type of graft, tissue is processed in tissue banks, where it can be subjected to radiosterilization. According to in vitro studies, gamma radiation, in doses higher than 25 kGy, induces alterations in skin preserved in glycerol at 85%, reducing the tensile strength of irradiated tissue. Clinical observation also suggests faster integration of such graft with the receptors tissue. In order to assess if the alterations observed in vitro, would compromise in vivo use, transplants of human tissue, irradiated or not, were performed in Nude mice. The skin of the mice was subjected to macroscopic analysis, optical coherence tomography imaging, histological and biomechanical assays. It was possible to conclude that grafts irradiated with 25 kGy promoted greater initial contraction, without alteration of the final dimensions of the repair area, also displaying a faster closing of the wound. Moreover, the use of irradiated grafts (25 and 50 kGy) enabled the formation of a more organized healing process without significant effects on biomechanical properties. (author)

  17. Incorporation and disappearance of oxygen-18 in lung from mice exposed to 1 ppm (18)O sub 3 (1)

    Energy Technology Data Exchange (ETDEWEB)

    Santrock, J.; Hatch, G.E.; Slade, R.; Hayes, J.M.

    1989-01-01

    In the study, (18)O(3) was used as a tracer for inhaled ozone in mice. The amount of ozone-derived oxygen (ODO) in the lungs was determined by measuring the amount of oxygen-18 in excess of the natural abundance level which remained covalently bound to organic constituents of lung tissue following exposure to 1 ppm (18)O(3). The rate of disappearance of ODO from the lungs was determined by quantifying the rate of decrease of oxygen-18 in excess of the natural abundance level in lung tissue from mice exposed to 1 ppm (18)O(3) for 45 min. With exposure to 1 ppm (18)O(3), ozone-derived oxygen accumulated in lung tissue at a rate of 4.38 pmoles of ODO/mg/min. ODO had a half-life in lung tissue of approximately 6 h. It was impossible to determine accurately the dose of ozone to tissue from these data. However, it was estimated that in each animal a minimum of 44 pmoles of O(3) reacted with molecular constituents of lung tissue every minute of exposure to 1 ppm O(3).

  18. Incorporation and disappearance of oxygen-18 in lung from mice exposed to 1 ppm 18O3.

    Science.gov (United States)

    Santrock, J; Hatch, G E; Slade, R; Hayes, J M

    1989-03-15

    In this study, 18O3 was used as a tracer for inhaled ozone in mice. The amount of ozone-derived oxygen (ODO) in the lungs was determined by measuring the amount of oxygen-18 in excess of the natural abundance level which remained covalently bound to organic constituents of lung following exposure to 1 ppm 18O3 for less than or equal to 60 min. The rate of disappearance of ODO from the lungs was determined by quantifying the rate of decrease of oxygen-18 in excess of the natural abundance level in lung from mice exposed to 1 ppm 18O3 for 45 min. With exposure to 1 ppm 18O3. ODO accumulated in lung at a rate of 4.38 pmol/mg dry weight/min. Ozone-derived oxygen had a half-life in lung of approximately 6 hr. We estimate that a minimum of 44 pmol of O3 reacted with lung every minute of exposure to 1 ppm O3. PMID:2929022

  19. Incorporation and disappearance of oxygen-18 in lung from mice exposed to 1 ppm /sup 18/O/sub 3/

    Energy Technology Data Exchange (ETDEWEB)

    Santrock, J.; Hatch, G.E.; Slade, R.; Hayes, J.M.

    1989-03-15

    In this study, /sup 18/O/sub 3/ was used as a tracer for inhaled ozone in mice. The amount of ozone-derived oxygen (ODO) in the lungs was determined by measuring the amount of oxygen-18 in excess of the natural abundance level which remained covalently bound to organic constituents of lung following exposure to 1 ppm /sup 18/O/sub 3/ for less than or equal to 60 min. The rate of disappearance of ODO from the lungs was determined by quantifying the rate of decrease of oxygen-18 in excess of the natural abundance level in lung from mice exposed to 1 ppm /sup 18/O/sub 3/ for 45 min. With exposure to 1 ppm /sup 18/O/sub 3/. ODO accumulated in lung at a rate of 4.38 pmol/mg dry weight/min. Ozone-derived oxygen had a half-life in lung of approximately 6 hr. We estimate that a minimum of 44 pmol of O3 reacted with lung every minute of exposure to 1 ppm O3.

  20. Effect of Green Tea Extract on T cell Mediated Hypersensitivity Reaction in BALB/c Mice Exposed to Gamma Irradiation

    International Nuclear Information System (INIS)

    Gamma radiation is widely used in the treatment of malignant neoplasms. However, it deprives the host immune function which may retard tumor rejection by the immune response. The main purpose of the present study is to test the ability of green tea dry extract to restore the T cell hypersensitivity reaction in gamma irradiated BALB/c mice. It aims also to elucidate the possible mechanism of action of ionizing radiation and green tea dry extract in the immune function. Four groups of BALB/c mice, each of ten, have been used in each experiment. The first group served as a control, the second group received green tea dry extract and the third group was exposed to 2 Gy gamma irradiation, while the fourth group received green tea dry extract before and after gamma irradiation. The following parameters were determined, the contact sensitivity reaction by the mouse ear swelling response, local dendritic cell migration, local lymph node weight, lymphocyte proliferation, spleen and thymus weight with their lymphocyte count. The effect of gamma irradiation and green tea dry extract on the elicitation phase of contact sensitivity was also determined. Data from the present study showed that gamma irradiation caused a significant decrease of the mouse ear swelling response and retarded dendritic cell migration. They also showed a significant decline in the lymphocytes proliferation in lymph node draining the contact sensitizer application. Total body exposure to 2 Gy gamma irradiation induced marked decline of thymus weight and thymocyte count, while it reduced spleen weight and spleenocyte count to a lesser extent. Exposure to gamma irradiation enhanced the elicitation phase of contact sensitivity. Administration of green tea dry extract partially preserved the contact sensitivity response to oxazolone in gamma irradiated BALB/c mice. It markedly minimized the enhancement of the elicitation phase of ear swelling. In conclusion, the present study heralds a beneficial role of

  1. Commentary to Krishna et al. (2014): brain deposition and neurotoxicity of manganese in adult mice exposed via the drinking water.

    Science.gov (United States)

    Kumasaka, Mayuko Y; Yajima, Ichiro; Ohgami, Nobutaka; Naito, Hisao; Omata, Yasuhiro; Kato, Masashi

    2014-05-01

    Krishna et al. (Arch Toxicol 88(1):47-64, 2014) recently published the results of a study in which adult C57BL/6 mice were subchronically exposed to 400,000 μg/L manganese (Mn) using manganese chloride via drinking water for 8 weeks and examined the neurotoxic effects. After 5 weeks of Mn exposure, significant deposition of Mn in all of the brain regions examined by magnetic resonance imaging was detected. After 6 weeks of Mn exposure, neurobehavioral deficits in an open field test, a grip strength test, and a forced swim test were observed. Eight weeks of Mn exposure increased striatal 5-hydroxyindoleacetic acid (a serotonin metabolite) levels, but did not alter the levels of striatal dopamine, its metabolites and serotonin. Krishna et al. also reported significant increases in mRNA levels of GFAP (an astrocyte activation marker), HO-1 (an oxidative stress marker) and NOS2 (a nitrosative stress marker), and in protein expression level of GFAP in the substantia nigra pars reticulata after 8 weeks of Mn exposure. These results suggest that 400,000 μg/L Mn exposure via drinking water in mice induces neurobehavioral deficits, serotonergic imbalance, and glial activation accompanied by an increase in brain Mn deposition. The report by Krishna et al. is interesting because the studies on the neurobehavioral effect of Mn exposure by drinking water in mice are very limited. However, Mn concentrations previously reported in well drinking water (Agusa et al. in Vietnam Environ Pollut 139(1):95-106, 2006; Buschmann et al. in Environ Int 34(6):756-764, 2008; Hafeman et al. in Environ Health Perspect 115(7):1107-1112, 2007; Wasserman et al. in Bangladesh Environ Health Perspect 114(1):124-129, 2006) were lower than 400,000 μg/L.

  2. Autoantibodies from mice exposed to Libby amphibole asbestos bind SSA/Ro52-enriched apoptotic blebs of murine macrophages

    International Nuclear Information System (INIS)

    Asbestos exposure is associated with increased autoimmune responses in humans. For example, in Libby, MT where significant asbestos exposure has occurred due to an asbestos-contaminated vermiculite mine near the community, residents have developed increased autoimmune responses compared to an unexposed population. However, the exact mechanism by which Libby amphibole asbestos generates autoimmune responses is unclear. A murine model of amphibole asbestos-induced autoimmunity was recently established, and one of the targets of the autoantibodies (AAs) was the SSA/Ro52 autoantigen. The purpose of this study was to determine whether the SSA/Ro52 autoantigen is exposed at the surface of cells as a result of asbestos exposure as a possible mechanism leading to antigenicity. Our results indicate that Libby asbestos induces apoptosis in murine macrophages as determined by phosphatidylserine exposure, cleavage of poly(ADP-ribose) polymerase and morphological changes such as nuclear condensation. Moreover, asbestos-induced apoptosis results in the formation of apoptotic cell surface blebs enriched in SSA/Ro52 as determined by confocal microscopy. Most importantly, apoptotic cell surface blebs are recognized by AAs from mice exposed to amphibole asbestos suggesting that these cell surface structures may be antigenic when presented in a pro-inflammatory context. This study supports the hypothesis that the induction of apoptosis plays a key role in environmentally induced autoimmunity through cell surface exposure of a known autoantigen

  3. Differential Transcriptional Changes in Mice Exposed to Chemically Distinct Diesel Samples

    Science.gov (United States)

    Stevens, Tina; Hester, Susan; Gilmour, M. Ian

    2010-01-01

    Epidemiological studies have linked exposure to ambient particulate matter (PM) with increased asthmatic symptoms. Diesel exhaust particles (DEP) are a predominant source of vehicle derived ambient PM, and experimental studies have demonstrated that they may have adjuvant potential when given with an antigen. We previously compared 3 DEP samples: N-DEP, A-DEP, and C-DEP in a murine ovalbumin (OVA) mucosal sensitization model and reported the adjuvant activity to be: C-DEP ≈ A-DEP > N-DEP. The present study analyzed gene expression changes from the lungs of these mice. Transcription profiling demonstrated that all the DEP samples altered cytokine and toll-like receptor pathways regardless of type, with or without antigen sensitization. Further analysis of DEP exposure with OVA showed that all DEP treatments altered networks involved in immune and inflammatory responses. The A- and C-DEP/OVA treatments induced differential expression of apoptosis pathways in association with stronger adjuvant responses, while expression of cell cycle control and DNA damage pathways were also altered in the C-DEP/OVA treatment. This comprehensive approach using gene expression analysis to examine changes at a pathway level provides detailed information on events occurring in the lung after DEP exposure, and confirms that the most bioactive sample induced many more individual genes and changes in immunoregulatory and homeostatic pathways.

  4. Gallic acid regulates skin photoaging in UVB-exposed fibroblast and hairless mice.

    Science.gov (United States)

    Hwang, Eunson; Park, Sang-Yong; Lee, Hyun Ji; Lee, Tae Youp; Sun, Zheng-Wang; Yi, Tae Hoo

    2014-12-01

    Ultraviolet (UV) radiation is the primary factor in skin photoaging, which is characterized by wrinkle formation, dryness, and thickening. The mechanisms underlying skin photoaging are closely associated with degradation of collagen via upregulation of matrix metalloproteinase (MMP) activity, which is induced by reactive oxygen species (ROS) production. Gallic acid (GA), a phenolic compound, possesses a variety of biological activities including antioxidant and antiinflammatory activities. We investigated the protective effects of GA against photoaging caused by UVB irradiation using normal human dermal fibroblasts (NHDFs) in vitro and hairless mice in vivo. The production levels of ROS, interlukin-6, and MMP-1 were significantly suppressed, and type I procollagen expression was stimulated in UVB-irradiated and GA-treated NHDFs. GA treatment inhibited the activity of transcription factor activation protein 1. The effects of GA following topical application and dietary administration were examined by measuring wrinkle formation, histological modification, protein expression, and physiological changes such as stratum corneum hydration, transepidermal water loss, and erythema index. We found that GA decreased dryness, skin thickness, and wrinkle formation via negative modulation of MMP-1 secretion and positive regulation of elastin, type I procollagen, and transforming growth factor-β1. Our data indicate that GA is a potential candidate for the prevention of UVB-induced premature skin aging.

  5. Toxicogenomic analysis of placenta samples from mice exposed to different doses of BPA.

    Science.gov (United States)

    Tait, Sabrina; Tassinari, Roberta; Maranghi, Francesca; Mantovani, Alberto

    2015-06-01

    Bisphenol A (BPA), a widespread Endocrine Disrupter mainly used in food contact plastics, may induce adverse effects especially on susceptible lifestages, first of all pregnancy. The present study considered placental development as a potential target of BPA and investigated potential differences in the modes of action of two doses of BPA by a toxicogenomic approach. Pregnant CD-1 mice were administered with vehicle, 0.5 (BPA05) or 50 mg/kg (BPA50) body weight (bw)/die of BPA, from gestational day (GD) 1 to GD11. At GD12 dams were sacrificed and transcriptomic analysis was performed on placenta samples. Histological, histomorphometrical and immunohistochemical analyses were also performed to phenotypically anchor transcriptional changes associated with BPA exposure. The interpretation and description of the overall data are included in a manuscript under revision [1]. Here we describe the experimental design and the analysis performed on the gene expression data which are publicly available through the Gene Expression Omnibus (GEO) database with accession number GSE63852. PMID:26484192

  6. Radiomodification by Aloe vera leaf extract on skin of Swiss albino mice exposed to gamma radiation

    International Nuclear Information System (INIS)

    The development of effective radioprotectors and radiorecovery drugs is of great importance in view of their potential application during both planned (e.g. radiotherapy) and unplanned (e.g. in nuclear industry, natural background radiation emanating from the earth or other sources) radiation exposure. Over the past 50 years, research in the development of radioprotectors has focused on screening a plethora of chemical and biological compounds. Several synthetic chemical compounds have been tested for protection against radiation. But they have limited use due to inherent toxicity. Herbal medicine is still the mainstay of about 75-80 percent of the world population mainly in the developing nations for primary health care because of better cultural acceptability, better compatibility with the human body and lesser side effects. Thus, natural products offer an alternative to their synthetic counterparts due to low toxicity with no side effects. The present investigation has been an attempt to asses the radioprotective efficacy of Aloe vera leaf extract on biochemical alterations in skin of Swiss albino mice

  7. Toxicogenomic analysis of placenta samples from mice exposed to different doses of BPA

    Directory of Open Access Journals (Sweden)

    Sabrina Tait

    2015-06-01

    Full Text Available Bisphenol A (BPA, a widespread Endocrine Disrupter mainly used in food contact plastics, may induce adverse effects especially on susceptible lifestages, first of all pregnancy. The present study considered placental development as a potential target of BPA and investigated potential differences in the modes of action of two doses of BPA by a toxicogenomic approach. Pregnant CD-1 mice were administered with vehicle, 0.5 (BPA05 or 50 mg/kg (BPA50 body weight (bw/die of BPA, from gestational day (GD 1 to GD11. At GD12 dams were sacrificed and transcriptomic analysis was performed on placenta samples. Histological, histomorphometrical and immunohistochemical analyses were also performed to phenotypically anchor transcriptional changes associated with BPA exposure. The interpretation and description of the overall data are included in a manuscript under revision [1]. Here we describe the experimental design and the analysis performed on the gene expression data which are publicly available through the Gene Expression Omnibus (GEO database with accession number GSE63852.

  8. Persistence of chromosome aberrations in mice acutely exposed to 56Fe+26 ions.

    Science.gov (United States)

    Tucker, James D; Marples, Brian; Ramsey, Marilyn J; Lutze-Mann, Louise H

    2004-06-01

    Space exploration has the potential to yield exciting and significant discoveries, but it also brings with it many risks for flight crews. Among the less well studied of these are health effects from space radiation, which includes the highly charged, energetic particles of elements with high atomic numbers that constitute the galactic cosmic rays. In this study, we demonstrated that 1 Gy iron ions acutely administered to mice in vivo resulted in highly complex chromosome damage. We found that all types of aberrations, including dicentrics as well as translocations, insertions and acentric fragments, disappear rapidly with time after exposure, probably as a result of the death of heavily damaged cells, i.e. cells with multiple and/or complex aberrations. In addition, numerous cells have apparently simple exchanges as their only aberrations, and these cells appear to survive longer than heavily damaged cells. Eight weeks after exposure, the frequency of cells showing cytogenetic damage was reduced to less than 20% of the levels evident at 1 week, with little further decline apparent over an additional 8 weeks. These results indicate that exposure to 1 Gy iron ions produces heavily damaged cells, a small fraction of which appear to be capable of surviving for relatively long periods. The health effects of exposure to high-LET radiation in humans on prolonged space flights should remain a matter of concern. PMID:15161355

  9. The effect of oxidative stress in myocardial cell injury in mice exposed to chronic intermittent hypoxia

    Institute of Scientific and Technical Information of China (English)

    LIU Jian-nan; ZHANG Jie-xin; LIU gan; QIU Yan; YANG Di; YIN Guo-yong; ZHANG Xi-long

    2010-01-01

    Background Obstructive sleep apnea syndrome (OSAS) is an important risk factor for cardiovascular diseases. Chronic intermittent hypoxia (CIH) is considered to be one of the most important causes of cardiovascular diseases in OSA patients. This repeated hypoxia and reoxygenation cycle is similar to hypoxia-reperfusion injury, which initiates oxidative stress. In this study, we observed cardiocytes injury induced by CIH and the effect of N-acetylcysteine (NAC). Methods Thirty ICR mice were randomly assigned to 3 groups: control, CIH and NAC (CIH+NAC) groups. Malondialdehyde (MDA) and superoxide dismutase (SOD) of cardiocyte homogenates were measured. Serum lipids were measured by an instrument method. Serum cardiac troponin I (cTnl) was detected by enzyme-linked immunosorbent assays (ELISA). Myocardium pathological sections were observed.Results (1) The SOD activity and MDA concentration of cardiocyte homogenates in the CIH group were significantly higher than in other groups (P <0.005). The MDA concentration of the NAC group was lower than that of the control group (P <0.01). (2) The serum cTnl concentration of the CIH and NAC groups was significantly higher than that of the control group (P<0.01). (3) Serum triglyceride levels in the NAC group were lower than in the other groups (P<0.01), while there were no significant differences in low density lipoprotein and high density lipoprotein among the three groups. (4) The degeneration of myocardium, transverse striation blurred, and fabric effusion were observed in tissue sections in the CIH and NAC groups. However, normal tissue was found in the control group.Conclusion The oxidative stress induced by CIH can injure cardiocytes and the injury effect can be partially inhibited by NAC.

  10. Pulmonary gene and microRNA expression changes in mice exposed to benzo(a)pyrene by oral gavage

    International Nuclear Information System (INIS)

    Highlights: → The study examines pulmonary response in mice exposed to BaP by oral gavage. → We examined pulmonary gene and miRNA expression changes and measured DNA adducts. → We compare the mechanisms of action that operate in lungs relative to the liver. → We show differences in biological pathways activated in lungs versus the liver. → We suggest that liver miRNAs are less sensitive to perturbations than lung miRNAs. -- Abstract: Exposure to the environmental mutagen benzo(a)pyrene (BaP) alters the expression of AHR-responsive genes as well as genes involved in other pathways. We recently reported that exposure of adult mice to BaP resulted in a robust transcriptome response in the liver, but this was accompanied by a complete lack of change in microRNA (miRNA) expression. Since BaP exposure does not result in hepatocarcinogenicity, but does cause lung cancer, in the present study we examine the pulmonary mRNA and miRNA responses to BaP in the same mice. Adult male B6C3F1 mice were exposed to 150 and 300 mg/kg BaP by oral gavage for three consecutive days and sacrificed 4 h after the last exposure. Serum clinical chemistry was performed for both the doses to assess the general toxicity of BaP; a modest decrease in serum inorganic phosphorous was observed at both the doses. A small decrease in serum glucose following 150 mg/kg and alkaline phosphatase following 300 mg/kg BaP was observed. BaP-DNA adduct levels in whole lung and liver tissues were assessed by 32P postlabelling and similar dose dependent increases were observed for lung and liver. Using DNA microarrays, pulmonary mRNA and miRNA expressions were analysed. Over 1000 genes were statistically differentially expressed (p < 0.05). The perturbed pathways included oxidative stress, xenobiotic metabolism, cell proliferation, cell cycle, B and T-cell receptor signalling and primary immunodeficiency signalling pathways. Analysis of miRNA profiles revealed downregulation of miR-150, miR-142-5p, mi

  11. DNA damage and apoptosis of endometrial cells cause loss of the early embryo in mice exposed to carbon disulfide

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Bingzhen [Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan (China); Shen, Chunzi [Centers for Disease Control and Prevention, Zibo (China); Yang, Liu; Li, Chunhui; Yi, Anji [Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan (China); Wang, Zhiping, E-mail: zhipingw@sdu.edu.cn [Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan (China)

    2013-12-01

    Carbon disulfide (CS{sub 2}) may lead to spontaneous abortion and very early pregnancy loss in women exposed in the workplace, but the mechanism remains unclear. We designed an animal model in which gestating Kunming strain mice were exposed to CS{sub 2} via i.p. on gestational day 4 (GD4). We found that the number of implanted blastocysts on GD8 was significantly reduced by each dose of 0.1 LD{sub 50} (157.85 mg/kg), 0.2 LD{sub 50} (315.7 mg/kg) and 0.4 LD{sub 50} (631.4 mg/kg). In addition, both the level of DNA damage and apoptosis rates of endometrial cells on GD4.5 were increased, showed definite dose–response relationships, and inversely related to the number of implanted blastocysts. The expressions of mRNA and protein for the Bax and caspase-3 genes in the uterine tissues on GD4.5 were up-regulated, while the expressions of mRNA and protein for the Bcl-2 gene were dose-dependently down-regulated. Our results indicated that DNA damage and apoptosis of endometrial cells were important reasons for the loss of implanted blastocysts induced by CS{sub 2}. - Highlights: • We built an animal model of CS2 exposure during blastocyst implantation. • Endometrial cells were used in the comet assay to detect DNA damage. • CS2 exposure caused DNA damage and endometrial cell apoptosis. • DNA damage and endometrial cell apoptosis were responsible for embryo loss.

  12. Metabolomic profiling of urine samples from mice exposed to protons reveals radiation quality and dose specific differences.

    Science.gov (United States)

    Laiakis, Evagelia C; Trani, Daniela; Moon, Bo-Hyun; Strawn, Steven J; Fornace, Albert J

    2015-04-01

    As space travel is expanding to include private tourism and travel beyond low-Earth orbit, so is the risk of exposure to space radiation. Galactic cosmic rays and solar particle events have the potential to expose space travelers to significant doses of radiation that can lead to increased cancer risk and other adverse health consequences. Metabolomics has the potential to assess an individual's risk by exploring the metabolic perturbations in a biofluid or tissue. In this study, C57BL/6 mice were exposed to 0.5 and 2 Gy of 1 GeV/nucleon of protons and the levels of metabolites were evaluated in urine at 4 h after radiation exposure through liquid chromatography coupled to time-of-flight mass spectrometry. Significant differences were identified in metabolites that map to the tricarboxylic acid (TCA) cycle and fatty acid metabolism, suggesting that energy metabolism is severely impacted after exposure to protons. Additionally, various pathways of amino acid metabolism (tryptophan, tyrosine, arginine and proline and phenylalanine) were affected with potential implications for DNA damage repair and cognitive impairment. Finally, presence of products of purine and pyrimidine metabolism points to direct DNA damage or increased apoptosis. Comparison of these metabolomic data to previously published data from our laboratory with gamma radiation strongly suggests a more pronounced effect on metabolism with protons. This is the first metabolomics study with space radiation in an easily accessible biofluid such as urine that further investigates and exemplifies the biological differences at early time points after exposure to different radiation qualities. PMID:25768838

  13. Radio-protective effect of vitamin E on spermatogenesis in mice exposed to γ-irradiation: a flow cytometric study

    Institute of Scientific and Technical Information of China (English)

    C.Songthaveesin; J.Saikhun; Y.Kitiyanant; K.Pavasuthipaisit

    2004-01-01

    Aim: To investigate the effect of vitamin E on the radioprotection of spermatogenesis and chromatin condensation of spermatozoa during passage through the epididymis in mice exposed to irradiation. Methods: Adult outbred male ICR mice were orally administered natural vitamin E (VE,D-a-tocopheryl acetate) at 400 IU/kg for 7 days before exposure to 1 Gy of y-irradiation. The animals were sacrificed at day 1,7,14,21, 28, 35 and 70 post-irradiation (IR) and the percentage of testicular germ cells and epididymal sperm chromatin condensation was analyzed using flow cytometry. Results: Serum D-a-tocopheryl acetate levels were 47.4±3.2μg/dL in the treatedgroup, yet it could not be detected in the control group. The testicular weight of irradiated mice pretreated with VE+IR was significantly (P<0.05) higher than that of those without VE treatment (IR) at day 14 and 21 post-irradiation. The percentage of primary spermatocytes (4C) in the VE+IR group was comparable to the controls but significantly (P<0.05) higher than those in the IR group from day 7 to 35 post-irradiation. The percentage of round spermatids (1C) in the VE+IR group was also significantly (P<0.05) higher than those in the IR group at day 28 postirradiation. The primary spermatocytes:spermatogonia ratio in the IR group was significantly (P<0.05) declined at day 7 to 35 post-irradiation when compared to the VE+IR and control groups. The round spermatid:spermatogonia ratio in the VE+IR group was significantly (P<0.05) higher than that of the IR group at day 14 and 28 post-irradiation.The chromatin condensation of epididymal spermatozoa measured by propidium iodide uptake was not affected by 1 Gy of γ-irradiation. Conclusion: The administration of VE prior to irradiation protects spermatogenic cells fromradiation. (Asian J Androl 2004 Dec; 6: 331-336)

  14. Augmented atherogenesis in ApoE-null mice co-exposed to polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin

    International Nuclear Information System (INIS)

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) are persistent organic pollutants found as complex mixtures in the environment throughout the world. Therefore, humans are ubiquitously and simultaneously exposed to TCDD and PCBs. TCDD and PCBs alone have been linked to atherosclerosis. However, the effects of interactions or synergism between TCDD and PCBs on atherogenesis are unknown. We investigated the possible enhanced atherogenesis by co-exposure to TCDD and PCBs and the potential mechanism(s) involved in this enhancement. Male ApoE−/− mice were exposed to TCDD (15 μg/kg) and Aroclor1254 (55 mg/kg, a representative mixture of PCBs) alone or in combination by intraperitoneal injection four times over six weeks of duration. Our results showed that mice exposed to TCDD alone, but not Aroclor1254 alone, developed atherosclerotic lesions. Moreover, we found that atherosclerotic disease was exacerbated to the greatest extent in mice co-exposed to TCDD and Aroclor1254. The enhanced lesions correlated with several pro-atherogenic changes, including a marked increase in the accumulation of the platelet-derived chemokine PF4, and the expression of the proinflammatory cytokine MCP-1 and the critical immunity gene-RIG-I. Our data demonstrated that co-exposure to TCDD and Aroclor1254 markedly enhanced atherogenesis in ApoE−/− mice. Significantly, our observations suggest that combined exposure to TCDD and PCBs may be a greater cardiovascular health risk than previously anticipated from individual studies. - Highlights: • Augmented atherogenesis was found in ApoE−/− mice co-exposed to Aroclor1254 and TCDD. • Enhanced expression of PF4, MCP-1 and RIG-I correlated with augmented lesions. • POPs combination may be a greater cardiovascular health risk than individual POPs

  15. Augmented atherogenesis in ApoE-null mice co-exposed to polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin

    Energy Technology Data Exchange (ETDEWEB)

    Shan, Qiuli [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Wang, Jing, E-mail: avaecn@gmail.com [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Huang, Fengchen [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Lv, Xiaowen [Feed Safety Reference Laboratory of Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Zhongguancun South Street 12, Beijing 100081 (China); Ma, Min [Laboratory of Biotechnology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Du, Yuguo [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China)

    2014-04-15

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) are persistent organic pollutants found as complex mixtures in the environment throughout the world. Therefore, humans are ubiquitously and simultaneously exposed to TCDD and PCBs. TCDD and PCBs alone have been linked to atherosclerosis. However, the effects of interactions or synergism between TCDD and PCBs on atherogenesis are unknown. We investigated the possible enhanced atherogenesis by co-exposure to TCDD and PCBs and the potential mechanism(s) involved in this enhancement. Male ApoE{sup −/−} mice were exposed to TCDD (15 μg/kg) and Aroclor1254 (55 mg/kg, a representative mixture of PCBs) alone or in combination by intraperitoneal injection four times over six weeks of duration. Our results showed that mice exposed to TCDD alone, but not Aroclor1254 alone, developed atherosclerotic lesions. Moreover, we found that atherosclerotic disease was exacerbated to the greatest extent in mice co-exposed to TCDD and Aroclor1254. The enhanced lesions correlated with several pro-atherogenic changes, including a marked increase in the accumulation of the platelet-derived chemokine PF4, and the expression of the proinflammatory cytokine MCP-1 and the critical immunity gene-RIG-I. Our data demonstrated that co-exposure to TCDD and Aroclor1254 markedly enhanced atherogenesis in ApoE{sup −/−} mice. Significantly, our observations suggest that combined exposure to TCDD and PCBs may be a greater cardiovascular health risk than previously anticipated from individual studies. - Highlights: • Augmented atherogenesis was found in ApoE{sup −/−} mice co-exposed to Aroclor1254 and TCDD. • Enhanced expression of PF4, MCP-1 and RIG-I correlated with augmented lesions. • POPs combination may be a greater cardiovascular health risk than individual POPs.

  16. Bone marrow transplantation controlling hormonal and structural changes in radiation exposed pregnant mice and their developing embryos

    International Nuclear Information System (INIS)

    Ascending doses of whole body gamma irradiation delivered at different gestational stages of mouse exposed to 1 and 2 Gy gamma rays fractionated at 1 Gy installments and possible curative role of bone marrow transplantation has been studied. The results confirmed the impairment of the levels of the two maternal hormones 17 estradiol and progesterone besides histopathological changes in the skin, heart and skeleton at different embryonic stages. 17 Beta estradiol level was not changed significantly in mice treated with 1 Gy and fractionated 2 Gy. Bone marrow treatment remarkably restored its level. Animals subjected to the dose level 1 Gy exhibited a slight decrease in the progesterone level while a significant drop in the hormone level was noticed upon irradiation at 2 Gy. Bone marrow transplantation provided little repair for the hormone. Treatment with bone marrow transplantation, was effective in alleviating the histopathological changes due to the lower dose (One Gy), yet it had less pronounced recovery of defects produced by the higher irradiation dose

  17. 39. Ultrastructural Changes of Neurons Located at Anterior Horn of Lumbar Spinal cord in Ethylene Oxide Exposed Mice

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Mice inhaled ethylene oxide at concentration of 360 mg/m3 for two hours a day, six days a week for 14 weeks. At the end of second and third month, the neurons located at anterior horn of lumbar spinal cord were observed under transmission electron microscope and scanning electron microscope with freeze etching. The results showed that the morphological changes in neuron cells became more obvious as the inhalation period prolonged. Following changes were observed : The distribution of integrating proteins in neuron membrane changed from normal stochastic into clustered one, the endoplasmic reticulum reduced in number and appeared as small vesicles, the ribosomes attached to the surface of rough endoplasmic reticulum were also decreased in number, arranged irregularly, disintegrated or even degranulated. The numher of mitochondria was also decreased. Observed aiso were the swelling of the axons of myelinated nerve fibers and loss of stratification of their myelin sheaths. The above results indicated that the ethylene oxide can induce structural changes in neuron cells, and this inevitably may cause functional abnormality of nervous system and manifestation of neurotoxic symptoms in ethylene oxide exposed individuals.

  18. Synchrotron X-ray microscopy reveals early calcium and iron interaction with crocidolite fibers in the lung of exposed mice.

    Science.gov (United States)

    Pascolo, Lorella; Zabucchi, Giuliano; Gianoncelli, Alessandra; Kourousias, George; Trevisan, Elisa; Pascotto, Ernesto; Casarsa, Claudia; Ryan, Chris; Lucattelli, Monica; Lungarella, Giuseppe; Cavarra, Eleonora; Bartalesi, Barbara; Zweyer, Marina; Cammisuli, Francesca; Melato, Mauro; Borelli, Violetta

    2016-01-22

    Human exposure to asbestos can cause a wide variety of lung diseases that are still a current major health concern, even if asbestos has been banned in many countries. It has been shown in many studies that asbestos fibers, ingested by alveolar macrophages, disrupt lung iron homeostasis by sequestering iron. Calcium can also be deposited on the fibers. The pathways along which iron and above all calcium interact with fibers are still unknown. Our aim was that of investigating if the iron accumulation induced by the inhaled asbestos fibers also involves calcium ions accumulation. Lung sections of asbestos-exposed mice were analyzed using an extremely sensitive procedure available at the synchrotron facilities, that provides morphological and chemical information based on X-ray fluorescence microspectroscopy (μ-XRF). In this study we show that (1) where conventional histochemical procedures revealed only weak deposits of iron and calcium, μ-XRF analysis is able to detect significant deposits of both iron and calcium on the inhaled asbestos fibers; (2) the extent of the deposition of these ions is proportionally directly related and (3) iron and calcium deposition on inhaled asbestos fibers is concomitant with the appearance of inflammatory and hyperplastic reactions. PMID:26602167

  19. Hepatic and Nephric NRF2 Pathway Up-Regulation, an Early Antioxidant Response, in Acute Arsenic-Exposed Mice

    Directory of Open Access Journals (Sweden)

    Jinlong Li

    2015-10-01

    Full Text Available Inorganic arsenic (iAs, a proven human carcinogen, damages biological systems through multiple mechanisms, one of them being reactive oxygen species (ROS production. NRF2 is a redox-sensitive transcription factor that positively regulates the genes of encoding antioxidant and detoxification enzymes to neutralize ROS. Although NRF2 pathway activation by iAs has been reported in various cell types, however, the experimental data in vivo are very limited and not fully elucidated in humans. The present investigation aimed to explore the hepatic and nephric NRF2 pathway upregulation in acute arsenic-exposed mice in vivo. Our results showed 10 mg/kg NaAsO2 elevated the NRF2 protein and increased the transcription of Nrf2 mRNA, as well as up-regulated NRF2 downstream targets HO-1, GST and GCLC time- and dose-dependently both in the liver and kidney. Acute NaAsO2 exposure also resulted in obvious imbalance of oxidative redox status represented by the increase of GSH and MDA, and the decrease of T-AOC. The present investigation reveals that hepatic and nephric NRF2 pathway expression is an early antioxidant defensive response upon iAs exposure. A better knowledge about the NRF2 pathway involvment in the cellular response against arsenic could help improve the strategies for reducing the cellular toxicity related to this metalloid.

  20. Spatial learning and memory deficits in young adult mice exposed to a brief intense noise at postnatal age

    Institute of Scientific and Technical Information of China (English)

    Shan Tao; Lijie Liu; Lijuan Shi; Xiaowei Li; Pei Shen; Qingying Xun; Xiaojing Guo; Zhiping Yu; Jian Wang

    2015-01-01

    Noise pollution is a major hazardous factor to human health and is likely harmful for vulnerable groups such as pre-term infants under life-support system in an intensive care unit. Previous studies have suggested that noise exposure impairs children's learning ability and cognitive performance and cognitive functions in animal models in which the effect is mainly attributed to the oxidant stress of noise on the cognitive brain. The potential role of noise induced hearing loss (NIHL), rather than the oxidant stress, has also been indicated by a depression of neurogenesis in the hippocampus long after a brief noise exposure, which produces only a tentative oxidant stress. It is not clear if noise exposure and NIHL during early development exerts a long term impact on cognitive function and neurogenesis towards adulthood. In the present study, a brief noise exposure at high sound level was performed in neonatal C57BL/6J mice (15 days after birth) to produce a significant amount of permanent hearing loss as proved 2 months after the noise. At this age, the noise-exposed animals showed deteriorated spatial learning and memory abilities and a reduction of hippocampal neurogenesis as compared with the control. The averaged hearing threshold was found to be strongly correlated with the scores for spatial learning and memory. We consider the effects observed are largely due to the loss of hearing sensitivity, rather than the oxidant stress, due to the long interval between noise exposure and the observations.

  1. Inhibition of radiation-induced DNA damage by jamun, Syzygium cumini, in the cultured splenocytes of mice exposed to different doses of γ-radiation.

    Science.gov (United States)

    Jagetia, Ganesh Chandra; Shetty, Prakash Chandra; Vidyasagar, Mamidipudi Srinivasa

    2012-06-01

    The radioprotective property of 50 mg/kg body weight jamun (Syzygium cumini) extract was studied in the cultured splenocytes of mice exposed to 0, 0.5, 1, 2, 3, or 4 Gy of γ-radiation. The spleens of irradiated mice were removed aseptically and the splenocytes were extracted from the individual spleens and cultured. The micronuclei were prepared 72 hours after irradiation in binucleate splenocytes by blocking cytokinesis with cytochalasin-B. Irradiation of mice resulted in a dose-dependent elevation in the micronucleated splenocytes. The exposure of mice not only elevated splenocytes bearing one micronucleus but also cells bearing 2 and multiple (>2) micronuclei indicating induction of complex DNA damage after irradiation. Oral treatment of mice with 50 mg/kg body weight of jamun leaf extract protected against the radiation-induced micronuclei formation. Jamun extract also protected against the formation of 2 and multiple micronuclei indicating repair or inhibition of complex DNA damage. The assessment of lipid peroxidation in mice brain homogenate has indicated a concentration dependent inhibition of lipid peroxidation by jamun extract. Studies in a cell free system revealed that jamun extract inhibited the formation of OH, O(2)-, DPPH, and ABTS(+) free radicals in a concentration dependent manner. Our study demonstrates that jamun extract protected mice against the radiation-induced DNA damage and inhibition of radiation-induced free radical formation may be one of the mechanisms of radioprotection. PMID:21733986

  2. Ultrastructural findings in the brain of fruit flies (Drosophila melanogaster) and mice exposed to high-energy particle radiation

    Energy Technology Data Exchange (ETDEWEB)

    D' Amelio, F.; Kraft, L.M.; D' Antoni-D' Amelio, E.; Benton, E.V.; Miquel, J.

    1984-01-01

    Effects of high energy, heavy particle (HZE) radiation were studied in the brain of the fruit fly (Drosophila melanogaster) exposed to argon (40Ar) or krypton (84Kr) ions. In the flies exposed to argon the fluence ranged from 6 X 10(4) to 8 X 10(7) particles/cm2. The insects were killed 35 days after exposure. Extensive tissue fragmentation was observed at the higher fluence employed. At fluences ranging from 5 X 10(6) (one hit/two cell bodies) to 9 X 10(4) (one hit/90 cell bodies) particles/cm2, swelling of the neuronal cytoplasm and focally fragmented membranes was observed. Marked increase of glial lamellae around nerve cell processes was seen at fluences ranging from one hit/six to one hit/135 cell bodies. In the flies irradiated with krypton, the fluences employed were 5.8 X 10(3) and 2.2 X 10(6) particles/cm2. Acute and late effects were evaluated. In the flies killed 36 hours after exposure (acute effects) to either fluence, glycogen particles were found in the neuroglial compartment. The granules were no longer present in flies killed 35 days later (late effects). From these studies it appears that the Drosophila brain is a useful model to investigate radiation damage to mature neurons, neuroglia, and therefore, to the glio-neuronal metabolic unit. In a separate study, the synaptic profiles of the neuropil in layers II-III of the frontal cerebral cortex of anesthesized adult LAFl mice were quantitatively appraised after exposure to argon (40Ar) particles. The absorbed dose ranged from 0.05 to 5 gray (Gy) plateau. It was determined that the sodium pentobarbital anesthesia per se results in a significant decrease in synaptic profile length one day after anesthetization, with return to normal values after 2-28 days. Irradiation with 0.05-5 Gy argon particles significantly inhibited the synaptic shortening effect of anesthesia at one day after exposure.

  3. Effect of Ocimum sanctum, ascorbic acid, and verapamil on macrophage function and oxidative stress in mice exposed to cocaine

    Directory of Open Access Journals (Sweden)

    Bhattacharya S

    2009-01-01

    Full Text Available Objective: To investigate the effect of Ocimum sanctum, ascorbic acid, and verapamil on macrophage function and oxidative stress in experimental animals exposed to cocaine. Materials and Methods: Mice were used in this study and were divided randomly into different groups of six animals each. They were either treated with intraperitoneal injection of saline or cocaine hydrochloride or an oral feeding of oil of Ocimum sanctum, ascorbic acid or verapamil, or both (ascorbic acid and verapamil, and were evaluated for a respiratory burst of macrophages, superoxide and nitric oxide (NO production, estimation of TNF-a in the serum and supernatant of cultured macrophages, estimation of lipid peroxidation (malondialdehyde- MDA in the serum, and superoxide dismutase activity in the erythrocytes. Results: Unstimulated respiratory burst as well as superoxide production was enhanced on treatment with cocaine and all the three drugs were found to attenuate this enhancement. The bactericidal capacity of macrophages decreased significantly on chronic cocaine exposure, as it was associated with decreased respiratory burst and superoxide production. There was a significant decrease in NO production by macrophages on chronic cocaine exposure and all the test drugs were found to restore nitrite formation to a normal level. There was an increase in the malonylodialdehyde (MDA level and decrease in the superoxide dismutase level on chronic cocaine exposure, and all the three drugs effectively decreased the MDA level and increased superoxide dismutase level. There was an increase in serum TNF-α on chronic cocaine exposure, which was decreased significantly by ascorbic acid and verapamil. Conclusion: O. sanctum, ascorbic acid, and verapamil were equally effective in improving the macrophage function and reducing oxidative stress. These findings suggested that O. sanctum, ascorbic acid, and verapamil attenuated acute and chronic cocaine-mediated effects.

  4. Genomics-based screening of differentially expressed genes in the brains of mice exposed to silver nanoparticles via inhalation

    International Nuclear Information System (INIS)

    Silver nanoparticles (AgNP) are among the fastest growing product categories in the nanotechnology industry. Despite the importance of AgNP in consumer products and clinical applications, relatively little is known regarding AgNP toxicity and its associated risks. We investigated the effects of AgNP on gene expression in the mouse brain using Affymetrix Mouse Genome Arrays. C57BL/6 mice were exposed to AgNP (geometric mean diameter, 22.18 ± 1.72 nm; 1.91 x 107 particles/cm3) for 6 h/day, 5 days/week using the nose-only exposure system for 2 weeks. Total RNA isolated from the cerebrum and cerebellum was subjected to hybridization. From over 39,000 probe sets, 468 genes in the cerebrum and 952 genes in the cerebellum were identified as AgNP-responsive (one-way analysis of variance; p < 0.05). The largest groups of gene products affected by AgNP exposure included 73 genes in the cerebrum and 144 genes in the cerebellum. AgNP exposure modulated the expression of several genes associated with motor neuron disorders, neurodegenerative disease, and immune cell function, indicating potential neurotoxicity and immunotoxicity associated with AgNP exposure. Real-time PCR data for five genes analyzed from whole blood showed good correlation with the observed changes in the brain. Following rigorous validation and substantiation, these genes may assist in the development of surrogate markers for AgNP exposure and/or toxicity.

  5. “Skittish” Abca2 Knockout Mice Display Tremor, Hyperactivity, and Abnormal Myelin Ultrastructure in the Central Nervous System▿ †

    OpenAIRE

    Mack, Jody T.; Beljanski, Vladimir; Soulika, Athena M; Townsend, Danyelle M.; Brown, Carol B.; Davis, Warren; Tew, Kenneth D.

    2006-01-01

    The ATP-binding cassette transporter 2 (ABCA2) is an endolysosomal protein most highly expressed in the central and peripheral nervous system tissues and macrophages. Previous studies indicated its role in cholesterol/steroid (estramustine, estradiol, and progesterone) trafficking/sequestration, oxidative stress response, and Alzheimer's disease. Developmental studies have shown its expression during macrophage and oligodendrocyte differentiation, processes requiring membrane growth. To deter...

  6. Mice Exposed to Chronic Intermittent Hypoxia Simulate Clinical Features of Deficiency of both Qi and Yin Syndrome in Traditional Chinese Medicine

    OpenAIRE

    Chengzhi Chai; Junping Kou; Danni Zhu; Yongqing Yan; Boyang Yu

    2011-01-01

    Deficiency of both Qi and Yin Syndrome (DQYS) is one of the common syndromes in traditional Chinese medicine (TCM), mainly characterized by tiredness, emaciation, anorexia, fidget, palpitation and rapid pulse, and so forth. Currently, there is no available animal model which can reflect the clinical features of this syndrome. In the present paper, we observed the time-course changes of whole behavior, body weight, food intake, locomotive activity and electrocardiogram in mice exposed to chron...

  7. Executive function deficits and social-behavioral abnormality in mice exposed to a low dose of dioxin in utero and via lactation.

    Directory of Open Access Journals (Sweden)

    Toshihiro Endo

    Full Text Available An increasing prevalence of mental health problems has been partly ascribed to abnormal brain development that is induced upon exposure to environmental chemicals. However, it has been extremely difficult to detect and assess such causality particularly at low exposure levels. To address this question, we here investigated higher brain function in mice exposed to dioxin in utero and via lactation by using our recently developed automated behavioral flexibility test and immunohistochemistry of neuronal activation markers Arc, at the 14 brain areas. Pregnant C57BL/6 mice were given orally a low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD at a dose of either 0, 0.6 or 3.0 µg/kg on gestation day 12.5. When the pups reached adulthood, they were group-housed in IntelliCage to assess their behavior. As a result, the offspring born to dams exposed to 0.6 µg TCDD/kg were shown to have behavioral inflexibility, compulsive repetitive behavior, and dramatically lowered competitive dominance. In these mice, immunohistochemistry of Arc exhibited the signs of hypoactivation of the medial prefrontal cortex (mPFC and hyperactivation of the amygdala. Intriguingly, mice exposed to 3.0 µg/kg were hardly affected in both the behavioral and neuronal activation indices, indicating that the robust, non-monotonic dose-response relationship. In conclusion, this study showed for the first time that perinatal exposure to a low dose of TCDD in mice develops executive function deficits and social behavioral abnormality accompanied with the signs of imbalanced mPFC-amygdala activation.

  8. U19/Eaf2 knockout causes lung adenocarcinoma, B-cell lymphoma, hepatocellular carcinoma and prostatic intraepithelial neoplasia

    OpenAIRE

    Xiao, W; Zhang, Q; Habermacher, G; Yang, X.; Zhang, A-y; Cai, X.; Hahn, J.; Liu, J; Pins, M; Doglio, L; Dhir, R; Gingrich, J; Wang, Z.(Institute of High Energy Physics, Beijing, China)

    2007-01-01

    Upregulated gene 19 (U19)/ELL-associated factor 2 (Eaf2) is a potential human tumor suppressor that exhibits frequent allelic loss and downregulation in high-grade prostate cancer. U19/Eaf2, along with its homolog Eaf1, has been reported to regulate transcriptional elongation via interaction with the eleven-nineteen lysine-rich leukemia (ELL) family of proteins. To further explore the tumor-suppressive effects of U19/Eaf2, we constructed and characterized a murine U19/Eaf2-knockout model. Hom...

  9. The Lack of Cytotoxic Effect and Radioadaptive Response in Splenocytes of Mice Exposed to Low Level Internal β-Particle Irradiation through Tritiated Drinking Water in Vivo

    Directory of Open Access Journals (Sweden)

    Matthew Flegal

    2013-12-01

    Full Text Available Health effects of tritium, a β-emitter and a by-product of the nuclear industry, is a subject of significant controversy. This mouse in vivo study was undertaken to monitor biological effects of low level tritium exposure. Mice were exposed to tritiated drinking water (HTO at 10 KBq/L, 1 MBq/L and 20 MBq/L concentrations for one month. The treatment did not result in a significant increase of apoptosis in splenocytes. To examine if this low level tritium exposure alters radiosensitivity, the extracted splenocytes were challenged in vitro with 2 Gy γ-radiation, and apoptotic responses at 1 and 24 h were measured. No alterations in the radiosensitivity were detected in cells from mice exposed to tritium compared to sham-treated mice. In contrast, low dose γ-irradiation at 20 or 100 mGy, resulted in a significant increase in resistance to apoptotic cell death after 2 Gy irradiation; an indication of the radioadaptive response. Overall, our data suggest that low concentrations of tritium given to mice as HTO in drinking water do not exert cytotoxic effect in splenocytes, nor do they change cellular sensitivity to additional high dose γ-radiation. The latter may be considered as the lack of a radioadaptive response, typically observed after low dose γ-irradiation.

  10. Comparison of local and systemic immunity after intratracheal, intraperitoneal and intravenous immunization of mice exposed to either aerosolized or ingested lead

    Energy Technology Data Exchange (ETDEWEB)

    Hillam, R.P.; Ozkan, A.N.

    1986-04-01

    The humoral immunity of newborn mice exposed for 28 days to 2.5 mg/m/sup 3/ aerosolized Pb(NO/sub 3/)/sub 2/ (Pb/sub 28-aero/) or of 2-week-old mice similarly exposed for 14 days (Pb/sub 14-aero/) was compared with that of both 2-week-old mice given 125 ..mu..g Pb(NO/sub 3/)/sub 2//day by gastric intubation for 14 days (Pb/sub 14-aero/) and of 4-week-old nonexposed controls. Mice from each group were immunized with 10/sup 8/ sheep red blood cells by intravenous (iv), intraperitoneal (ip), or intratracheal (it) routes of immunization. Immunity was assessed by both hemagglutination and the enumeration of antibody-forming cells from the spleen and thoracic lymph nodes. All treatment groups had decreased thymus/body weight and spleen/body weight ratios whereas only Pb/sub aero/ groups had enlarged livers. The most significant immunosuppression occurred in the ip-immunized Pb/sub 28-aero/ group. A significant suppression of humoral immunity was also observed in thoracic lymph node samples from Pb/sub aero/ groups immunized it or iv. There was no apparent immunosuppression in any treatment group after iv immunization. These results indicate that aerosolized lead is more immunosuppressive than equivalent amounts of ingested lead. This is most likely due to the greater absorption of inhaled lead and the subsequent cytotoxicity of lead for cells in the draining lymph nodes.

  11. Pronounced susceptibility to infection by Salmonella enterica serovar Typhimurium in mice chronically exposed to lead correlates with a shift to Th2-type immune responses

    International Nuclear Information System (INIS)

    Persistent exposure to inorganic lead (Pb) is known to adversely affect the immune system. In the present study, we assessed the effect of chronic Pb exposure on susceptibility to infection by the facultative intracellular pathogen Salmonella enterica serovar Typhimurium. Mice were exposed to 10 mM Pb-acetate in drinking water for ∼ 16 weeks, resulting in a significant level of Pb in the blood (106.2 ± 8.9 μg/dl). Pb exposure rendered mice susceptible to Salmonella infection, manifested by increased bacterial burden in target organs and heightened mortality. Flow cytometric analysis of the splenic cellular composition in normal and Pb-exposed mice revealed no gross alteration in the ratios of B and T lymphocytes or myeloid cells. Similarly, the capacity of B and T cells to upregulate the expression of activation antigens in response to mitogenic or inflammatory stimuli was not hindered by Pb exposure. Analysis of the ability of ex vivo-cultured splenocytes to secrete cytokines demonstrated a marked reduction in IFN-γ and IL-12p40 production associated with Pb exposure. In contrast, secretion of IL-4 by splenocytes of Pb-treated mice was 3- to 3.6-fold higher than in normal mice. The increased capacity to produce IL-4 correlated with a shift in the in vivo anti-Salmonella antibody response from the protective IgG2a isotype to the Th2-induced IgG1 isotype. We conclude that chronic exposure to high levels of Pb results in a state of immunodeficiency which is not due to an overt cytotoxic or immunosuppressive mechanism, but rather is largely caused by a shift in immune responsiveness to Th2-type reactions

  12. Mice Exposed to Chronic Intermittent Hypoxia Simulate Clinical Features of Deficiency of both Qi and Yin Syndrome in Traditional Chinese Medicine

    Directory of Open Access Journals (Sweden)

    Chengzhi Chai

    2011-01-01

    Full Text Available Deficiency of both Qi and Yin Syndrome (DQYS is one of the common syndromes in traditional Chinese medicine (TCM, mainly characterized by tiredness, emaciation, anorexia, fidget, palpitation and rapid pulse, and so forth. Currently, there is no available animal model which can reflect the clinical features of this syndrome. In the present paper, we observed the time-course changes of whole behavior, body weight, food intake, locomotive activity and electrocardiogram in mice exposed to chronic intermittent hypoxia for 6 weeks, and measured bleeding time at last according to the clinical features of DQYS and one key pathological factor. The results showed that the mice exposed to intermittent hypoxia for certain time presented lackluster hair, dull looking hair, resistance, attacking, body weight loss, food intake decline, locomotive activity decrease, heart rate quickening and T wave elevating, which were similar to the major clinical features of DQYS. Meanwhile, bleeding time shortening was also found, which was consistent with the clinical fact that DQYS often accompanied with blood stasis. The possible explanation was also outlined according to the available literature. Such findings suggested chronic intermittent hypoxia could induce similar symptoms and signs in mice accorded with the clinical features of DQYS, which provided a suitable animal model for evaluation of drugs for the treatment of this syndrome and further exploration of pathological process or correlation of the syndrome and related diseases.

  13. Mice Exposed to Chronic Intermittent Hypoxia Simulate Clinical Features of Deficiency of both Qi and Yin Syndrome in Traditional Chinese Medicine.

    Science.gov (United States)

    Chai, Chengzhi; Kou, Junping; Zhu, Danni; Yan, Yongqing; Yu, Boyang

    2011-01-01

    Deficiency of both Qi and Yin Syndrome (DQYS) is one of the common syndromes in traditional Chinese medicine (TCM), mainly characterized by tiredness, emaciation, anorexia, fidget, palpitation and rapid pulse, and so forth. Currently, there is no available animal model which can reflect the clinical features of this syndrome. In the present paper, we observed the time-course changes of whole behavior, body weight, food intake, locomotive activity and electrocardiogram in mice exposed to chronic intermittent hypoxia for 6 weeks, and measured bleeding time at last according to the clinical features of DQYS and one key pathological factor. The results showed that the mice exposed to intermittent hypoxia for certain time presented lackluster hair, dull looking hair, resistance, attacking, body weight loss, food intake decline, locomotive activity decrease, heart rate quickening and T wave elevating, which were similar to the major clinical features of DQYS. Meanwhile, bleeding time shortening was also found, which was consistent with the clinical fact that DQYS often accompanied with blood stasis. The possible explanation was also outlined according to the available literature. Such findings suggested chronic intermittent hypoxia could induce similar symptoms and signs in mice accorded with the clinical features of DQYS, which provided a suitable animal model for evaluation of drugs for the treatment of this syndrome and further exploration of pathological process or correlation of the syndrome and related diseases.

  14. Modulation by aspirin and naproxen of nucleotide alterations and tumors in the lung of mice exposed to environmental cigarette smoke since birth.

    Science.gov (United States)

    La Maestra, Sebastiano; D'Agostini, Francesco; Izzotti, Alberto; Micale, Rosanna T; Mastracci, Luca; Camoirano, Anna; Balansky, Roumen; Trosko, James E; Steele, Vernon E; De Flora, Silvio

    2015-12-01

    Chemoprevention provides an important strategy for cancer control in passive smokers. Due to the crucial role played by smoke-related chronic inflammation in lung carcinogenesis, of special interest are extensively used pharmacological agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs). We evaluated the ability of aspirin and naproxen, inhibitors of both cyclooxygenase-1 and cyclooxygenase -2, to modulate environmental cigarette smoke (ECS)-induced lung carcinogenesis in A/J mice of both genders. Based on a subchronic toxicity study in 180 postweaning mice, we used 1600 mg/kg diet aspirin and 320 mg/kg diet naproxen. In the tumor chemoprevention study, using 320 mice, exposure to ECS started soon after birth and administration of NSAIDs started after weaning. At 10 weeks of life, the NSAIDs did not affect the presence of occult blood in feces. As assessed in a subset of 40 mice, bulky DNA adducts and 8-hydroxy-2'-deoxyguanosine levels were considerably increased in ECS-exposed mice and, irrespective of gender, both NSAIDs remarkably inhibited these nucleotide alterations. After exposure for 4 months followed by 5 months in filtered air, ECS induced a significant increase in the yield of surface lung tumors, the 43.7% of which were adenomas and the 56.3% were adenocarcinomas. Oct-4 (octamer-binding transcription factor 4), a marker of cell stemness, was detected in some adenocarcinoma cells. The NAIDs attenuated the yield of lung tumors, but prevention of ECS-induced lung adenomas was statistically significant only in female mice treated with aspirin, which supports a role for estrogens in ECS-related lung carcinogenesis and highlights the antiestrogenic properties of NSAIDs.

  15. Modulation by aspirin and naproxen of nucleotide alterations and tumors in the lung of mice exposed to environmental cigarette smoke since birth.

    Science.gov (United States)

    La Maestra, Sebastiano; D'Agostini, Francesco; Izzotti, Alberto; Micale, Rosanna T; Mastracci, Luca; Camoirano, Anna; Balansky, Roumen; Trosko, James E; Steele, Vernon E; De Flora, Silvio

    2015-12-01

    Chemoprevention provides an important strategy for cancer control in passive smokers. Due to the crucial role played by smoke-related chronic inflammation in lung carcinogenesis, of special interest are extensively used pharmacological agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs). We evaluated the ability of aspirin and naproxen, inhibitors of both cyclooxygenase-1 and cyclooxygenase -2, to modulate environmental cigarette smoke (ECS)-induced lung carcinogenesis in A/J mice of both genders. Based on a subchronic toxicity study in 180 postweaning mice, we used 1600 mg/kg diet aspirin and 320 mg/kg diet naproxen. In the tumor chemoprevention study, using 320 mice, exposure to ECS started soon after birth and administration of NSAIDs started after weaning. At 10 weeks of life, the NSAIDs did not affect the presence of occult blood in feces. As assessed in a subset of 40 mice, bulky DNA adducts and 8-hydroxy-2'-deoxyguanosine levels were considerably increased in ECS-exposed mice and, irrespective of gender, both NSAIDs remarkably inhibited these nucleotide alterations. After exposure for 4 months followed by 5 months in filtered air, ECS induced a significant increase in the yield of surface lung tumors, the 43.7% of which were adenomas and the 56.3% were adenocarcinomas. Oct-4 (octamer-binding transcription factor 4), a marker of cell stemness, was detected in some adenocarcinoma cells. The NAIDs attenuated the yield of lung tumors, but prevention of ECS-induced lung adenomas was statistically significant only in female mice treated with aspirin, which supports a role for estrogens in ECS-related lung carcinogenesis and highlights the antiestrogenic properties of NSAIDs. PMID:26464196

  16. Biomedical Analyses of Mice Body Hair Exposed to Long-term Space Flight as a Compliment of Human Research

    Science.gov (United States)

    Mukai, Chiaki

    Introduction: To understand the effect of space environment characterized by microgravity and radiation on protein and mineral metabolisms is important for developing the countermeasures to the adverse effects happening on the astronauts who stay long-term in space. Thus JAXA has started a human research to study the effects of long-term exposure in space flight on gene expression and mineral metabolism by analyzing astronaut's hair grown in space since December 2009 (Experiment nicknamed "HAIR"). Ten human subjects who are the crew of the International Space Station (ISS) will be expected to complete this experiment. Thanks to the tissue sharing program of space-flown mice which is presented and organized by AGI(Italian Space Agency), we can also have an opportunity to analyze rodents samples which will greatly compliment human hair experiment by enable us to conduct more detailed analysis with the expansion of skin analysis which is not include in human experiment. The purpose of this flown-mice experiment is to study the effects of long-term exposure to space environment such as microgravity and space radiation on mineral and protein metabolism, the biological responses to the stress levels, and the initial process of skin carcinogenesis by analyzing hair shaft, its root cells, and skin. Approach and Method In this experiment, we analyzed hair shaft, hair root and skin. Hair samples with skin were taken from 3-month space-flown mice and ground-control mice in the AGI's tissue sharing program in 2009. The sample numbers of space-flown mice and control-mice were three and six, respectively. And they were at the Mice Drawer System (MDS) in ISS and in the laboratory of Geneva University. For the hair shaft, the mineral balance is investi-gated by energy dispersive X-ray spectroscopy (SEM-EDX). For hair root, the extracted RNA undergoes DNA microarray analysis, and will be further examined particular interests of gene-expression by real time Reverse Transcription

  17. Strain Specific Induction of Pyometra and Differences in Immune Responsiveness in Mice Exposed to 17α-Ethinyl Estradiol or the Endocrine Disrupting Chemical Bisphenol A

    OpenAIRE

    Jessica A. Kendziorski; Kendig, Eric L.; Gear, Robin L.; Belcher, Scott M.

    2012-01-01

    Pyometra is an inflammatory disease of the uterus that can be caused by chronic exposure to estrogens. It is unknown whether weakly estrogenic endocrine disruptors can cause pyometra. We investigated whether dietary exposures to the estrogenic endocrine disruptor bisphenol A (BPA) induced pyometra. Pyometra did not occur in CD1 mice exposed to different dietary doses of BPA ranging from 4.1 to >4000 µg/kg/day or 17α-ethinyl estradiol (EE; 1.2 to >150 µg/kg/day). In the C57BL/6 strain, pyometr...

  18. Quantification of DNA adducts formed in liver, lungs, and isolated lung cells of rats and mice exposed to (14)C-styrene by nose-only inhalation.

    Science.gov (United States)

    Boogaard, P J; de Kloe, K P; Wong, B A; Sumner, S C; Watson, W P; van Sittert, N J

    2000-10-01

    Bronchiolo-alveolar tumors were observed in mice exposed chronically to 160 ppm styrene, whereas no tumors were seen in rats up to concentrations of 1000 ppm. Clara cells, which are predominant in the bronchiolo-alveolar region in mouse lungs but less numerous in rat and human lung, contain various cytochrome P450s, which may oxidize styrene to the rodent carcinogen styrene-7,8-oxide (SO) and other reactive metabolites. Reactive metabolites may form specific DNA adducts and induce the tumors observed in mice. To determine DNA adducts in specific tissues and cell types, rats and mice were exposed to 160 ppm [ring-U-(14)C]styrene by nose-only inhalation for 6 h in a recirculating exposure system. Liver and lungs were isolated 0 and 42 h after exposure. Fractions enriched in Type II cells and Clara cells were isolated from rat and mouse lung, respectively. DNA adduct profiles differed quantitatively and qualitatively in liver, total lung, and enriched lung cell fractions. At 0 and 42 h after exposure, the two isomeric N:7-guanine adducts of SO (measured together, HPEG) were present in liver at 3.0 +/- 0.2 and 1.9 +/- 0.3 (rat) and 1.2 +/- 0.2 and 3.2 +/- 0.5 (mouse) per 10(8) bases. Several other, unidentified adducts were present at two to three times higher concentrations in mouse, but not in rat liver. In both rat and mouse lung, HPEG was the major adduct at approximately 1 per 10(8) bases at 0 h, and these levels halved at 42 h. In both rat Type II and non-Type II cells, HPEG was the major adduct and was about three times higher in Type II cells than in total lung. For mice, DNA adduct levels in Clara cells and non-Clara cells were similar to total lung. The hepatic covalent binding index (CBI) at 0 and 42 h was 0.19 +/- 0.06 and 0.14 +/- 0.03 (rat) and 0. 25 +/- 0.11 and 0.44 +/- 0.23 (mouse), respectively. The pulmonary CBIs, based on tissues combined for 0 and 42 h, were 0.17 +/- 0.04 (rat) and 0.24 +/- 0.04 (mouse). Compared with CBIs for other genotoxicants

  19. DOES RESPONSE EVALUATION OF GENE EXPRESSION PROFILES IN THE SKIN OF K6/ODC MICE EXPOSED TO SODIUM ARSENITE

    Science.gov (United States)

    Abstract - Chronic drinking water exposure to inorganic arsenic and its metabolites increases tumor frequency in the skin of K6/ODC transgenic mice. To identify potential biomarkers and modes of action for this skin tumorigenicity, gene expression profiles were characterized fro...

  20. Lack of acute phase response in the livers of mice exposed to diesel exhaust particles or carbon black by inhalation

    DEFF Research Database (Denmark)

    Saber, Anne T; Halappanavar, Sabina; Folkmann, Janne K;

    2009-01-01

    analyzed liver tissue from these mice using high density DNA microarrays. Globally, 28 genes were found to be significantly differentially expressed in response to DEP or CB. The mRNA expression of three of the genes (serine (or cysteine) proteinase inhibitor, clade A, member 3C, apolipoprotein E...

  1. Protective role of diet supplements Spirulina and Tamarind fruit pulp on kidney in sodium fluoride exposed Swiss albino mice: Histological and biochemical indices.

    Science.gov (United States)

    Yadav, N; Sharma, Shweta; Sharma, K p; Pandey, A; Pareek, P; Sharma, Subhasini

    2016-01-01

    Fluoride toxicity through potable water, particularly ground water, is not uncommon in countries such as India, China, Iran, Iraq, Turkey, parts of Africa and Afghanistan. Kidney being the main organ involved in fluoride removal, it accumulates considerable amount of fluoride. Here, we report toxic effects of oral exposure of Swiss albino mice to fluoride (sub-acute: 190 mg/kg body wt. for 7 days; and sub-chronic: 94 mg/kg body wt. for 90 days) and recovery of sub-chronic fluoride exposed mice after 90 days of sodium fluoride (NaF) withdrawal. The role of diet supplements (Spirulina and tamarind fruit pulp @ 230 mg/kg body wt. independently as well as in combination) in amelioration of fluoride toxicity has also been screened. Compared with controls, feed intake decreased from 3-43%, body wt. 4-18%, and kidney wt. 5-12% in treated mice (except diet supplement groups of sub-chronic exposure) while their water intake increased from 4-43%. Histopathological changes in the cortical region of kidney in fluoride treated mice were as follows: dilation of bowman's capsule and thickening of its parietal and visceral layer; alterations in glomeruli size and their sclerotization; increase in bowman's space; proliferation of mesangial cells; reduction in podocyte counts; and dilation of proximal and distal tubules. Fluoride exposure altered tissue biochemistry (protein, acid phosphatase and alkaline phosphatase content) and increased urea (23-58%) and creatinine content (14-127%) in the serum. Sub-acute exposure was found more toxic. The diet modulation not only reduced fluoride toxicity but also led to better recovery of treated mice after withdrawal, especially in combination. PMID:26891552

  2. Allogeneic compact bone-derived mesenchymal stem cell transplantation increases survival of mice exposed to lethal total body irradiation: a potential immunological mechanism

    Institute of Scientific and Technical Information of China (English)

    Qiao Shukai; Ren Hanyun; Shi Yongjin; Liu Wei

    2014-01-01

    Background Radiation-induced injury after accidental or therapeutic total body exposure to ionizing radiation has serious pathophysiological consequences,and currently no effective therapy exists.This study was designed to investigate whether transplantation of allogeneic murine compact bone derived-mesenchymal stem cells (CB-MSCs) could improve the survival of mice exposed to lethal dosage total body irradiation (TBI),and to explore the potential immunoprotective role of MSCs.Methods BALB/c mice were treated with 8 Gy TBI,and then some were administered CB-MSCs isolated from C57BL/6 mice.Survival rates and body weight were analyzed for 14 days post-irradiation.At three days post-irradiation,we evaluated IFN-Y and IL-4 concentrations; CD4+CD25+Foxp3+ regulatory T cell (Treg) percentage; CXCR3,CCR5,and CCR7 expressions on CD3+T cells; and splenocyte T-bet and GATA-3 mRNA levels.CB-MSC effects on bone marrow hemopoiesis were assessed via colony-forming unit granulocyte/macrophage (CFU-GM) assay.Results After lethal TBI,compared to non-transplanted mice,CB-MSC-transplanted mice exhibited significantly increased survival,body weight,and CFU-GM counts of bone marrow cells (P<0.05),as well as higher Treg percentages,reduced IFN-Y,CXCR3 and CCR5 down-regulation,and CCR7 up-regulation.CB-MSC transplantation suppressed Th1 immunity.Irradiated splenocytes directly suppressed CFU-GM formation from bone marrow cells,and CB-MSC co-culture reversed this inhibition.Conclusion Allogeneic CB-MSC transplantation attenuated radiation-induced hematopoietic toxicity,and provided immunoprotection by alleviating lymphocyte-mediated CFU-GM inhibition,expanding Tregs,regulating T cell chemokine receptor expressions,and skewing the Th1/Th2 balance toward anti-inflammatory Th2 polarization.

  3. Protective role of diet supplements Spirulina and Tamarind fruit pulp on kidney in sodium fluoride exposed Swiss albino mice: Histological and biochemical indices.

    Science.gov (United States)

    Yadav, N; Sharma, Shweta; Sharma, K p; Pandey, A; Pareek, P; Sharma, Subhasini

    2016-01-01

    Fluoride toxicity through potable water, particularly ground water, is not uncommon in countries such as India, China, Iran, Iraq, Turkey, parts of Africa and Afghanistan. Kidney being the main organ involved in fluoride removal, it accumulates considerable amount of fluoride. Here, we report toxic effects of oral exposure of Swiss albino mice to fluoride (sub-acute: 190 mg/kg body wt. for 7 days; and sub-chronic: 94 mg/kg body wt. for 90 days) and recovery of sub-chronic fluoride exposed mice after 90 days of sodium fluoride (NaF) withdrawal. The role of diet supplements (Spirulina and tamarind fruit pulp @ 230 mg/kg body wt. independently as well as in combination) in amelioration of fluoride toxicity has also been screened. Compared with controls, feed intake decreased from 3-43%, body wt. 4-18%, and kidney wt. 5-12% in treated mice (except diet supplement groups of sub-chronic exposure) while their water intake increased from 4-43%. Histopathological changes in the cortical region of kidney in fluoride treated mice were as follows: dilation of bowman's capsule and thickening of its parietal and visceral layer; alterations in glomeruli size and their sclerotization; increase in bowman's space; proliferation of mesangial cells; reduction in podocyte counts; and dilation of proximal and distal tubules. Fluoride exposure altered tissue biochemistry (protein, acid phosphatase and alkaline phosphatase content) and increased urea (23-58%) and creatinine content (14-127%) in the serum. Sub-acute exposure was found more toxic. The diet modulation not only reduced fluoride toxicity but also led to better recovery of treated mice after withdrawal, especially in combination.

  4. The use of the mouse chimera assay to detect early embryonic damage from male mice exposed to low-dose radiation

    International Nuclear Information System (INIS)

    Mouse chimeras are in vitro aggregations of two 4-cell embryos and are used to detect subtle, nonlethal changes, which are expressed as a proliferative disadvantage in exposed embryos. One of the embryos is labeled with a viable dye (FITC) in order to determine the relative cellular contribution of each embryo when the chimera is dissociated 40 hours later. This proliferative disadvantage has been seen at doses which do not produce an effect on cell number when the embryos are cultured singly. Previously, the assay has detected a decrease in cellular proliferation in embryos from male mice exposed to a single dose of x-radiation as low as 0.05 Gy. In the current study, male mice were irradiated with a single dose of 0, 0.001, 0.01, or 0.05 Gy, and then serially mated for the next 8 weeks to unexposed females. Chimeras were constructed from control and treated embryos. Embryos from males treated with 0.05 Gy exhibited a significant decrease in cellular proliferation during weeks 6 and 7 post-irradiation. A similar decrease was seen in the males treated with 0.01 Gy. No reductions were observed from embryos cultured singly in any of the treatment groups

  5. Topical AC-11 abates actinic keratoses and early squamous cell cancers in hairless mice exposed to Ultraviolet A (UVA) radiation.

    Science.gov (United States)

    Mentor, Julian M; Etemadi, Amir; Patta, Abrienne M; Scheinfeld, Noah

    2015-04-16

    AC-11 is an aqueous extract of the botanical, Uncaria tomentosa, which has a variety of effects that enhance DNA repair and down regulate inflammation. AC-11 is essentially free of oxindole alkaloids (AC-11 at 0.5%, 1.5%, and 3.0% in a non-irritating, dye-free, perfume-free, and fragrance-free vanishing cream vehicle. Ten mice used vehicle only and 10 were untreated. Each concentration of AC-11 and was applied daily to the backs of the mice prior to exposure to a 1,600-watt solar simulator used in this work (Solar Light Co. Philadelphia, PA) emitting (mainly Ultraviolet A (UVA) and B (UVB) radiation) duration of the experimental period with UVB wavelengths was filtered out with a 1.0 cm Schott WG 345 filter. AC-11 with a peak absorption at 200nm does act as a sun block. We tested for and focused on clinical appearance of mice and histological appearance of tumors in mice rather than metrics of radiation generated inflammation. Tumor progression scores were assigned as follows: 4+ = extensive tumor development; 3+ = early malignancies (raised palpable plaques)(early squamous cell cancers) 2+ = firm scaling, palpable keratosis (actinic keratoses); 1+ = light scaling with erythema. Following a total cumulative dose of 738 J/cm2, 85.7% all of the irradiated control animals, which did not receive AC-11 had precancerous actinic keratosis (AK)-type lesions (2+) (64.3% versus 42.9%) or early squamous cell carcinoma (SCC) (3+) (21.4% vs. 4.8%), in comparison with 47.7 % of AC-11-treated animals. There were no significant differences between the AC-11 groups. Three months after cessation of exposure to UVA radiation, the lesions in all but three of the 14 animals which were treated with AC-11 that were still evaluable irradiated with UVA radiation progressed to papillomas and frank squamous cell carcinomas (+4 responses). AC-11 retarded, but did not stop, carcinogenesis progression. It is possible that if AC-11 was continuously applied tumors would not have in mice treated

  6. Des-Aspartate-Angiotensin I Attenuates Mortality of Mice Exposed to Gamma Radiation via a Novel Mechanism of Action.

    Directory of Open Access Journals (Sweden)

    Hong Wang

    Full Text Available ACE inhibitors and ARBs (angiotensin receptor blockers have been shown to attenuate radiation injuries in animal models of lethal gamma irradiation. These two classes of drug act by curtailing the actions of angiotensin II-linked inflammatory pathways that are up-regulated during gamma radiation in organ systems such as the brain, lung, kidney, and bone marrow. ACE inhibitors inhibit ACE and attenuate the formation of angiotensin II from angiotensin I; ARBs block the angiotensin AT1 receptor and attenuate the actions of angiotensin II that are elicited through the receptor. DAA-I (des-aspartate-angiotensin I, an orally active angiotensin peptide, also attenuates the deleterious actions of angiotensin II. It acts as an agonist on the angiotensin AT1 receptor and elicits responses that oppose those of angiotensn II. Thus, DAA-I was investigated for its anticipated radioprotection in gamma irradiated mice. DAA-I administered orally at 800 nmole/kg/day for 30 days post exposure (6.4 Gy attenuated the death of mice during the 30-day period. The attenuation was blocked by losartan (50 nmole/kg/day, i.p. that was administered sequential to DAA-I administration. This shows that the radioprotection was mediated via the angiotensin AT1 receptor. Furthermore, the radioprotection correlated to an increase in circulating PGE2 of surviving animals, and this suggests that PGE2 is involved in the radioprotection in DAA-I-treated mice. At the hematopoietic level, DAA-I significantly improved two syndromes of myelosuppression (leucopenia and lymphocytopenia, and mice pre-treated with DAA-I prior to gamma irradiation showed significant improvement in the four myelodysplastic syndromes that were investigated, namely leucopenia, lymphocytopenia, monocytopenia and thrombocytopenia. Based on the known ability of PGE2 to attenuate the loss of functional hematopoietic stem and progenitor cells in radiation injury, we hypothesize that PGE2 mediated the action of DAA

  7. Behavioral Outputs of Fragile-X Autistic Mice Exposed to Open-Field, Randomized, Short-Term Visual Stimuli

    OpenAIRE

    DiCola, Nicholas M; Chubykin, Alexander A.

    2015-01-01

    Animal models of different neurological disorders are required for studying the pathophysiology of these diseases, and for potential development of pharmacological and behavioral treatments. The scientific community often uses mouse models for behavior studies due to their powerful genetic tools and low cost. However, subjective measurement techniques are often used when analyzing mice for behavioral traits which often results in discrepancies in results. An automated tracking software would ...

  8. Pharmacological reduction of adult hippocampal neurogenesis modifies functional brain circuits in mice exposed to a cocaine conditioned place preference paradigm.

    Science.gov (United States)

    Castilla-Ortega, Estela; Blanco, Eduardo; Serrano, Antonia; Ladrón de Guevara-Miranda, David; Pedraz, María; Estivill-Torrús, Guillermo; Pavón, Francisco Javier; Rodríguez de Fonseca, Fernando; Santín, Luis J

    2016-05-01

    We investigated the role of adult hippocampal neurogenesis in cocaine-induced conditioned place preference (CPP) behaviour and the functional brain circuitry involved. Adult hippocampal neurogenesis was pharmacologically reduced with temozolomide (TMZ), and mice were tested for cocaine-induced CPP to study c-Fos expression in the hippocampus and in extrahippocampal addiction-related areas. Correlational and multivariate analysis revealed that, under normal conditions, the hippocampus showed widespread functional connectivity with other brain areas and strongly contributed to the functional brain module associated with CPP expression. However, the neurogenesis-reduced mice showed normal CPP acquisition but engaged an alternate brain circuit where the functional connectivity of the dentate gyrus was notably reduced and other areas (the medial prefrontal cortex, accumbens and paraventricular hypothalamic nucleus) were recruited instead of the hippocampus. A second experiment unveiled that mice acquiring the cocaine-induced CPP under neurogenesis-reduced conditions were delayed in extinguishing their drug-seeking behaviour. But if the inhibited neurons were generated after CPP acquisition, extinction was not affected but an enhanced long-term CPP retention was found, suggesting that some roles of the adult-born neurons may differ depending on whether they are generated before or after drug-contextual associations are established. Importantly, cocaine-induced reinstatement of CPP behaviour was increased in the TMZ mice, regardless of the time of neurogenesis inhibition. The results show that adult hippocampal neurogenesis sculpts the addiction-related functional brain circuits, and reduction of the adult-born hippocampal neurons increases cocaine seeking in the CPP model. PMID:25870909

  9. Lung tumorigenic response of strain A mice exposed to hypoxic cell sensitizers alone and in combination with gamma-radiation

    Energy Technology Data Exchange (ETDEWEB)

    Mian, T.A.; Theiss, J.C.; Grdina, D.J.

    1983-01-01

    The influence of metronidazole, misonidazole, and desmethylmisonidazole on the induction of lung adenomas in the strain A mouse was examined. Two dose levels of the hypoxic cell sensitizers, 0.2 and 0.6 mg/g, were used either alone or in combination with 900 rads of gamma-radiation in a fractionated dose schedule of twice a week for 3 weeks. In the groups of mice which received hypoxic cell sensitizers only, the prevalence and the mean number of lung tumors per mouse were somewhat increased (p less than 0.10) in the group receiving the higher dose (0.6 mg/g) of misonidazole but was not significantly different from results for the control animals in the other two sensitizer groups. The combination of hypoxic cell sensitizer and radiation did not show any significant enhancement of lung tumor response when compared with the group which received radiation only. The dose of radiation used in this study significantly enhanced lung tumor formation in mice when compared with that in the control group. Thus, under the experimental exposure conditions used in this investigation, which were somewhat similar to the exposure conditions occurring in clinical treatment, each of the hypoxic cell sensitizers tested failed to sensitize significantly the mice to the carcinogenic effects of gamma-radiation.

  10. Lung tumorigenic response of strain A mice exposed to hypoxic cell sensitizers alone and in combination with gamma-radiation.

    Science.gov (United States)

    Mian, T A; Theiss, J C; Grdina, D J

    1983-01-01

    The influence of metronidazole, misonidazole, and desmethylmisonidazole on the induction of lung adenomas in the strain A mouse was examined. Two dose levels of the hypoxic cell sensitizers, 0.2 and 0.6 mg/g, were used either alone or in combination with 900 rads of gamma-radiation in a fractionated dose schedule of twice a week for 3 weeks. In the groups of mice which received hypoxic cell sensitizers only, the prevalence and the mean number of lung tumors per mouse were somewhat increased (p less than 0.10) in the group receiving the higher dose (0.6 mg/g) of misonidazole but was not significantly different from results for the control animals in the other two sensitizer groups. The combination of hypoxic cell sensitizer and radiation did not show any significant enhancement of lung tumor response when compared with the group which received radiation only. The dose of radiation used in this study significantly enhanced lung tumor formation in mice when compared with that in the control group. Thus, under the experimental exposure conditions used in this investigation, which were somewhat similar to the exposure conditions occurring in clinical treatment, each of the hypoxic cell sensitizers tested failed to sensitize significantly the mice to the carcinogenic effects of gamma-radiation.

  11. Modification of an exposed loop in the C1 domain reduces immune responses to factor VIII in hemophilia A mice.

    Science.gov (United States)

    Wroblewska, Aleksandra; van Haren, Simon D; Herczenik, Eszter; Kaijen, Paul; Ruminska, Aleksandra; Jin, Sheng-Yu; Zheng, X Long; van den Biggelaar, Maartje; ten Brinke, Anja; Meijer, Alexander B; Voorberg, Jan

    2012-05-31

    Development of neutralizing Abs to blood coagulation factor VIII (FVIII) provides a major complication in hemophilia care. In this study we explored whether modulation of the uptake of FVIII by APCs can reduce its intrinsic immunogenicity. Endocytosis of FVIII by professional APCs is significantly blocked by mAb KM33, directed toward the C1 domain of FVIII. We created a C1 domain variant (FVIII-R2090A/K2092A/F2093A), which showed only minimal binding to KM33 and retained its activity as measured by chromogenic assay. FVIII-R2090A/K2092A/F2093A displayed a strongly reduced internalization by human monocyte-derived dendritic cells and macrophages, as well as murine BM-derived dendritic cells. We subsequently investigated the ability of this variant to induce an immune response in FVIII-deficient mice. We show that mice treated with FVIII-R2090A/K2092A/F2093A have significantly lower anti-FVIII Ab titers and FVIII-specific CD4(+) T-cell responses compared with mice treated with wild-type FVIII. These data show that alanine substitutions at positions 2090, 2092, and 2093 reduce the immunogenicity of FVIII. According to our findings we hypothesize that FVIII variants displaying a reduced uptake by APCs provide a novel therapeutic approach to reduce inhibitor development in hemophilia A. PMID:22498747

  12. Artificial daylight photodynamic therapy with "non-inflammatory" doses of hexyl aminolevulinate only marginally delays SCC development in UV-exposed hairless mice.

    Science.gov (United States)

    Togsverd-Bo, Katrine; Lerche, Catharina M; Philipsen, Peter A; Hædersdal, Merete; Wulf, Hans Christian

    2013-12-01

    Photodynamic therapy (PDT) is effective for actinic keratoses, but is associated with pain and post-treatment inflammation. Daylight-mediated PDT and PpIX-precursors at low concentrations reduce pain and inflammation intensity. The objective was to evaluate the effect of repeated low-concentration PDT combined with artificial daylight on SCC development. Mice (n = 265) were exposed to simulated solar UV-irradiation (UVR) 3 times weekly mimicking "summer-dose"-exposure (3 SED). Selected groups of mice received a "winter-dose"-exposure (0.6 SED) for the first 90 days. PDT was delivered with 0.1%, 0.05% and 0.02% hexyl aminolevulinate (HAL) cream and artificial daylight for 2.5 hours (6 J cm(-2)) in different treatment regimes (1-3 times weekly, 45-days intervals, days 1-180 and from day 180 onwards). The primary end-point was the time to first SCC (1 mm diameter). 0.1% HAL-PDT given 3 times weekly slightly delayed SCC development and induced minimal inflammation. In winter- and summer UVR-treatment regimes, 0.1% HAL PDT delayed the time to first SCC compared to control UVR and placebo-PDT when mice were PDT-treated on days 1-180 (median 213 vs. 199 days, p = 0.011) and from day 180 onwards (median 218 vs. 199 days, p = 0.006). PDT with 0.05% and 0.02% HAL did not influence SCC development (medians 206 days, p = ns). In summer UVR-exposed mice, 0.1% HAL-PDT marginally postponed the time to first SCC compared to control UVR (median 160 days) when treatments were given 3 times weekly for 180 days (median 166, p = 0.01), but not for 90 days (median 161, p = 0.112). In conclusion, repeated low-concentration HAL-PDT combined with artificial daylight is well-tolerated, but only marginally delays SCC development in mice. PMID:24064675

  13. Evaluation of the radioprotective effect of the leaf extract of Syzygium cumini (Jamun) in mice exposed to a lethal dose of gamma-irradiation.

    Science.gov (United States)

    Jagetia, Ganesh Chandra; Baliga, Manjeshwar Shrinath

    2003-06-01

    The effects of various concentrations (5, 10, 20, 30, 40, 50, 60, and 80 mg/kg body weight (b.wt.) of the leaf extracts of Syzygium cumini Linn. and Eugenia cumini (SCE, black plum, Jamun, family Myrtaceae) on the radiation-induced sickness and mortality in mice exposed to 10 Gy gamma-irradiation were studied. The treatment of mice with different doses of SCE, consecutively for five days before irradation, delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the nondrug-treated irradiated controls. All doses of SCE provied protection against the gastrointestinal death increasing the survival by 66.66% after treatment with 20, 30, and 40 mg/kg SCE versus a 12% survival in the irradiated control group (oil + irradiation). Similarly, SCE provided protection against the radiation-induced bone marrow death in mice treated with 10-60 mg/kg b.wt. of SCE. However, the best protection was obtained for 30 mg/kg b.wt. SCE, where the number of, survivors after 30 days post-irradiation was highest (41.66%) when compared with the other doses of SCE. PMID:12866620

  14. Topical AC-11 abates actinic keratoses and early squamous cell cancers in hairless mice exposed to Ultraviolet A (UVA) radiation.

    Science.gov (United States)

    Mentor, Julian M; Etemadi, Amir; Patta, Abrienne M; Scheinfeld, Noah

    2015-04-01

    AC-11 is an aqueous extract of the botanical, Uncaria tomentosa, which has a variety of effects that enhance DNA repair and down regulate inflammation. AC-11 is essentially free of oxindole alkaloids (< 0.05%, w/w) but contains more than 8% carboxy alkyl esters (CAEs) as their active ingredients. Three groups of 10 outbred SK-1 hairless or SK-II hairless strains of mice each were treated with AC-11 at 0.5%, 1.5%, and 3.0% in a non-irritating, dye-free, perfume-free, and fragrance-free vanishing cream vehicle. Ten mice used vehicle only and 10 were untreated. Each concentration of AC-11 and was applied daily to the backs of the mice prior to exposure to a 1,600-watt solar simulator used in this work (Solar Light Co. Philadelphia, PA) emitting (mainly Ultraviolet A (UVA) and B (UVB) radiation) duration of the experimental period with UVB wavelengths was filtered out with a 1.0 cm Schott WG 345 filter. AC-11 with a peak absorption at 200nm does act as a sun block. We tested for and focused on clinical appearance of mice and histological appearance of tumors in mice rather than metrics of radiation generated inflammation. Tumor progression scores were assigned as follows: 4+ = extensive tumor development; 3+ = early malignancies (raised palpable plaques)(early squamous cell cancers) 2+ = firm scaling, palpable keratosis (actinic keratoses); 1+ = light scaling with erythema. Following a total cumulative dose of 738 J/cm2, 85.7% all of the irradiated control animals, which did not receive AC-11 had precancerous actinic keratosis (AK)-type lesions (2+) (64.3% versus 42.9%) or early squamous cell carcinoma (SCC) (3+) (21.4% vs. 4.8%), in comparison with 47.7 % of AC-11-treated animals. There were no significant differences between the AC-11 groups. Three months after cessation of exposure to UVA radiation, the lesions in all but three of the 14 animals which were treated with AC-11 that were still evaluable irradiated with UVA radiation progressed to papillomas and frank

  15. Suppression of NMDA receptor function in mice prenatally exposed to valproic acid improves social deficits and repetitive behaviors

    OpenAIRE

    Jaeseung eKang; Eunjoon eKim

    2015-01-01

    Animals prenatally exposed to valproic acid (VPA), an antiepileptic agent, have been used as a model for autism spectrum disorders (ASDs). Previous studies have identified enhanced NMDA receptor (NMDAR) function in the brain of VPA rats, and demonstrated that pharmacological suppression of NMDAR function normalizes social deficits in these animals. However, whether repetitive behavior, another key feature of ASDs, can be rescued by NMDAR inhibition remains unknown. We report here that memanti...

  16. Defensive effect of lansoprazole in dementia of AD type in mice exposed to streptozotocin and cholesterol enriched diet.

    Directory of Open Access Journals (Sweden)

    Rupinder K Sodhi

    Full Text Available The present study investigates the potential of lansoprazole (a proton pump inhibitor and agonist of liver x receptors in experimental dementia of AD type. Streptozotocin [STZ, 3 mg/kg, injected intracerebroventricular (i.c.v, and high fat diet (HFD, administered for 90 days] were used to induce dementia in separate groups of Swiss mice. Morris water maze (MWM test was performed to assess learning and memory of the animals. A battery of biochemical and histopathological studies were also performed. Extent of oxidative stress was measured by estimating the levels of brain reduced glutathione (GSH and thiobarbituric acid reactive species (TBARS. Brain acetylcholinestrase (AChE activity and serum cholesterol levels were also estimated. The brain level of myeloperoxidase (MPO was measured as a marker of inflammation. STZ and HFD produced a marked decline in MWM performance of the animals, reflecting impairment of learning and memory. STZ/HFD treated mice exhibited a marked accentuation of AChE activity, TBARS and MPO levels along with a fall in GSH levels. Further, the stained micrographs of STZ/HFD treated mice indicated pathological changes, severe neutrophilic infiltration and amyloid deposition. Lansoprazole treatment significantly attenuated STZ and HFD -induced memory deficits, biochemical and histopathological alterations. It also prevented HFD-induced rise in the cholesterol level. Therefore, the findings demonstrate potential of lansoprazole in memory dysfunctions which may probably be attributed to its anti-cholinesterase, anti-oxidative and anti-inflammatory effects. Moreover, both cholesterol-dependent as well as cholesterol-independent effects of lansoprazole appear to play a role. In addition study indicates the role of liver x receptors in dementia.

  17. Topical AC-11 abates actinic keratoses and early squamous cell cancers in hairless mice exposed to Ultraviolet A (UVA) radiation

    OpenAIRE

    Mentor, Julian M; Etemadi, Amir; Patta, Abrienne M; Scheinfeld, Noah

    2015-01-01

    AC-11 is an aqueous extract of the botanical, Uncaria tomentosa, which has a variety of effects that enhance DNA repair and down regulate inflammation. AC-11 is essentially free of oxindole alkaloids (< 0.05%, w/w) but contains more than 8% carboxy alkyl esters (CAEs) as their active ingredients. Three groups of 10 outbred SK-1 hairless or SK-II hairless strains of mice each were treated with AC-11 at 0.5%, 1.5%, and 3.0% in a non-irritating, dye-free, perfume-free, and fragrance-free vanishi...

  18. Modulation by metformin of molecular and histopathological alterations in the lung of cigarette smoke-exposed mice

    OpenAIRE

    Izzotti, Alberto; Balansky, Roumen; D'Agostini, Francesco; Longobardi, Mariagrazia; Cartiglia, Cristina; Rosanna T Micale; La Maestra, Sebastiano; Camoirano, Anna; Ganchev, Gancho; Iltcheva, Marietta; Steele, Vernon E; De Flora, Silvio

    2014-01-01

    The anti-diabetic drug metformin is endowed with anti-cancer properties. Epidemiological and experimental studies, however, did not provide univocal results regarding its role in pulmonary carcinogenesis. We used Swiss H mice of both genders in order to detect early molecular alterations and tumors induced by mainstream cigarette smoke. Based on a subchronic toxicity study, oral metformin was used at a dose of 800 mg/kg diet, which is 3.2 times higher than the therapeutic dose in humans. Expo...

  19. CDRI-08 Attenuates REST/NRSF-Mediated Expression of NMDAR1 Gene in PBDE-209-Exposed Mice Brain.

    Science.gov (United States)

    Verma, Priya; Gupta, Rajaneesh K; Gandhi, Behrose S; Singh, Poonam

    2015-01-01

    CDRI-08 is a standardized bacoside enriched ethanolic extract of Bacopa monnieri, a nootropic plant. We reported that CDRI-08 attenuated oxidative stress and memory impairment in mice, induced by a flame retardant, PBDE-209. In order to explore the mechanism, present study was designed to examine the role of CDRI-08 on the expression of NMDAR1 (NR1) and the binding of REST/NRSF to NR1 promoter against postnatal exposure of PBDE-209. Male mice pups were orally supplemented with CDRI-08 at the doses of 40, 80, or 120 mg/kg along with PBDE-209 (20 mg/kg) during PND 3-10 and frontal cortex and hippocampus were collected at PND 11 and 60 to study the expression and regulation of NR1 by RT-PCR and electrophoretic mobility shift assay, respectively. The findings showed upregulated expression of NR1 and decreased binding of REST/NRSF to NR1 promoter after postnatal exposure of PBDE-209. Interestingly, supplementation with CDRI-08 significantly restored the expression of NR1 and binding of REST/NRSF to NR1 promoter near to the control value at the dose of 120 mg/kg. In conclusion, the results suggest that CDRI-08 possibly acts on glutamatergic system through expression and regulation of NR1 and may restore memory, impaired by PBDE-209 as reported in our previous study.

  20. CDRI-08 Attenuates REST/NRSF-Mediated Expression of NMDAR1 Gene in PBDE-209-Exposed Mice Brain

    Directory of Open Access Journals (Sweden)

    Priya Verma

    2015-01-01

    Full Text Available CDRI-08 is a standardized bacoside enriched ethanolic extract of Bacopa monnieri, a nootropic plant. We reported that CDRI-08 attenuated oxidative stress and memory impairment in mice, induced by a flame retardant, PBDE-209. In order to explore the mechanism, present study was designed to examine the role of CDRI-08 on the expression of NMDAR1 (NR1 and the binding of REST/NRSF to NR1 promoter against postnatal exposure of PBDE-209. Male mice pups were orally supplemented with CDRI-08 at the doses of 40, 80, or 120 mg/kg along with PBDE-209 (20 mg/kg during PND 3–10 and frontal cortex and hippocampus were collected at PND 11 and 60 to study the expression and regulation of NR1 by RT-PCR and electrophoretic mobility shift assay, respectively. The findings showed upregulated expression of NR1 and decreased binding of REST/NRSF to NR1 promoter after postnatal exposure of PBDE-209. Interestingly, supplementation with CDRI-08 significantly restored the expression of NR1 and binding of REST/NRSF to NR1 promoter near to the control value at the dose of 120 mg/kg. In conclusion, the results suggest that CDRI-08 possibly acts on glutamatergic system through expression and regulation of NR1 and may restore memory, impaired by PBDE-209 as reported in our previous study.

  1. The neuropsychopharmacological effects of Catha edulis in mice offspring born to mothers exposed during pregnancy and lactation.

    Science.gov (United States)

    Bedada, Worku; Engidawork, Ephrem

    2010-02-01

    Chewing fresh leaves of the khat plant (Catha edulis Forsk) is a deep rooted and widespread habit in East Africa and the Middle East. Although a body of knowledge exists about the adverse effects of khat during pregnancy, data are sparse with regard to the consequences of long-term exposure during pregnancy and lactation. The present work, therefore, was initiated to evaluate the neuropsychopharmacological effects of Catha edulis exposure during pregnancy and lactation in mice at postnatal day 28. To this effect, a lyophilized extract of khat (100 mg/kg, K100 and 200 mg/kg, K200), amphetamine (1 mg/kg, positive control, AMP), and a similar volume of 2% v/v Tween-80 in distilled water (negative control, CONT) were administered daily to pregnant mice from gestational day 6 until weaning. Neuropsychopharmacological measurements were done by making use of a battery of neurobehavioural and cognitive tests. Moreover, toxicity to liver and kidney was also evaluated by determining biochemical markers for possible tissue damage. K200 produced significant motor in-coordination and emotional instability; as revealed by impairment in both cliff avoidance (p effect only on grip strength where a decrement was noted (p effects during pregnancy and lactation which might pose a serious impediment to the physical and mental development of the offspring. PMID:19585482

  2. Induction of Chronic Inflammation and Altered Levels of DNA Hydroxymethylation in Somatic and Germinal Tissues of CBA/CaJ Mice Exposed to (48)Ti Ions.

    Science.gov (United States)

    Rithidech, Kanokporn Noy; Jangiam, Witawat; Tungjai, Montree; Gordon, Chris; Honikel, Louise; Whorton, Elbert B

    2016-01-01

    Although the lung is one of the target organs at risk for cancer induction from exposure to heavy ions found in space, information is insufficient on cellular/molecular responses linked to increased cancer risk. Knowledge of such events may aid in the development of new preventive measures. Furthermore, although it is known that germinal cells are sensitive to X- or γ-rays, there is little information on the effects of heavy ions on germinal cells. Our goal was to investigate in vivo effects of 1 GeV/n (48)Ti ions (one of the important heavy ions found in the space environment) on somatic (lung) and germinal (testis) tissues collected at various times after a whole body irradiation of CBA/CaJ mice (0, 0.1, 0.25, or 0.5 Gy, delivered at 1 cGy/min). We hypothesized that (48)Ti-ion-exposure induced damage in both tissues. Lung tissue was collected from each mouse from each treatment group at 1 week, 1 month, and 6 months postirradiation. For the testis, we collected samples at 6 months postirradiation. Hence, only late-occurring effects of (48)Ti ions in the testis were studied. There were five mice per treatment group at each harvest time. We investigated inflammatory responses after exposure to (48)Ti ions by measuring the levels of activated nuclear factor kappa B and selected pro-inflammatory cytokines in both tissues of the same mouse. These measurements were coupled with the quantitation of the levels of global 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). Our data clearly showed the induction of chronic inflammation in both tissues of exposed mice. A dose-dependent reduction in global 5hmC was found in the lung at all time-points and in testes collected at 6 months postirradiation. In contrast, significant increases in global 5mC were found only in lung and testes collected at 6 months postirradiation from mice exposed to 0.5 Gy of 1 GeV/n (48)Ti ions. Overall, our data showed that (48)Ti ions may create health risks in both

  3. Absolute quantification of superoxide dismutase in cytosol and mitochondria of mice hepatic cells exposed to mercury by a novel metallomic approach

    International Nuclear Information System (INIS)

    Highlights: • Identification and quantification of Cu,Zn-superoxide dismutase in mice hepatic cells. • IDA-ICP-MSis applied to obtain a high degree of accuracy, precision and sensibility. • This methodology reduces the time of analysis and avoids clean-up procedures. • The application of this method to Hg-exposed mice reveals perturbations in Cu,Zn-SOD. - Abstract: In the last years, the development of new methods for analyzing accurate and precise individual metalloproteins is of increasing importance, since numerous metalloproteins are excellent biomarkers of oxidative stress and diseases. In that way, methods based on the use of post column isotopic dilution analysis (IDA) or enriched protein standards are required to obtain a sufficient degree of accuracy, precision and high limits of detection. This paper reports the identification and absolute quantification of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) in cytosol and mitochondria from mice hepatic cells using a innovative column switching analytical approach. The method consisted of orthogonal chromatographic systems coupled to inductively coupling plasma-mass spectrometry equipped with a octopole reaction systems (ICP-ORS-MS) and UV detectors: size exclusion fractionation (SEC) of the cytosolic and mitochondrial extracts followed by online anion exchange chromatographic (AEC) separation of Cu/Zn containing species. After purification, Cu,Zn-SOD was identified after tryptic digestion by molecular mass spectrometry (MS). The MS/MS spectrum of a doubly charged peptide was used to obtain the sequence of the protein using the MASCOT searching engine. This optimized methodology reduces the time of analysis and avoids the use of sample preconcentration and clean-up procedures, such as cut-off centrifuged filters, solid phase extraction (SPE), precipitation procedures, off-line fractions insolates, etc. In this sense, the method is robust, reliable and fast with typical chromatographic run time less than 20 min

  4. Absolute quantification of superoxide dismutase in cytosol and mitochondria of mice hepatic cells exposed to mercury by a novel metallomic approach

    Energy Technology Data Exchange (ETDEWEB)

    García-Sevillano, M.A.; García-Barrera, T. [Department of Chemistry and Materials Science, Faculty of Experimental Sciences, University of Huelva, Campus de El Carmen, Huelva 21007 (Spain); Research Center on Health and Environment (CYSMA), University of Huelva (Spain); International Campus of Excellence on Agrofood (ceiA3), University of Huelva (Spain); Navarro, F. [International Campus of Excellence on Agrofood (ceiA3), University of Huelva (Spain); Department of Environmental Biology and Public Health, Cell Biology, Faculty of Experimental Sciences, University of Huelva, Campus El Carmen, Huelva 21007 (Spain); Gómez-Ariza, J.L., E-mail: ariza@uhu.es [Department of Chemistry and Materials Science, Faculty of Experimental Sciences, University of Huelva, Campus de El Carmen, Huelva 21007 (Spain); Research Center on Health and Environment (CYSMA), University of Huelva (Spain); International Campus of Excellence on Agrofood (ceiA3), University of Huelva (Spain)

    2014-09-09

    Highlights: • Identification and quantification of Cu,Zn-superoxide dismutase in mice hepatic cells. • IDA-ICP-MSis applied to obtain a high degree of accuracy, precision and sensibility. • This methodology reduces the time of analysis and avoids clean-up procedures. • The application of this method to Hg-exposed mice reveals perturbations in Cu,Zn-SOD. - Abstract: In the last years, the development of new methods for analyzing accurate and precise individual metalloproteins is of increasing importance, since numerous metalloproteins are excellent biomarkers of oxidative stress and diseases. In that way, methods based on the use of post column isotopic dilution analysis (IDA) or enriched protein standards are required to obtain a sufficient degree of accuracy, precision and high limits of detection. This paper reports the identification and absolute quantification of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) in cytosol and mitochondria from mice hepatic cells using a innovative column switching analytical approach. The method consisted of orthogonal chromatographic systems coupled to inductively coupling plasma-mass spectrometry equipped with a octopole reaction systems (ICP-ORS-MS) and UV detectors: size exclusion fractionation (SEC) of the cytosolic and mitochondrial extracts followed by online anion exchange chromatographic (AEC) separation of Cu/Zn containing species. After purification, Cu,Zn-SOD was identified after tryptic digestion by molecular mass spectrometry (MS). The MS/MS spectrum of a doubly charged peptide was used to obtain the sequence of the protein using the MASCOT searching engine. This optimized methodology reduces the time of analysis and avoids the use of sample preconcentration and clean-up procedures, such as cut-off centrifuged filters, solid phase extraction (SPE), precipitation procedures, off-line fractions insolates, etc. In this sense, the method is robust, reliable and fast with typical chromatographic run time less than 20 min

  5. Dose response relationship for unstable-type chromosome aberration rate of spleen cells from mice continuously exposed to low-dose-rate gamma-rays

    International Nuclear Information System (INIS)

    It has been reported that people who are chronically exposed to radiation such as nuclear facility workers and medical radiologists have slightly higher incidences of chromosome aberrations than non-exposed people. However, chronological changes of chromosome aberration rates related to accumulated doses and dose-rates for low dose-rate radiation exposures have not been well studied. Precise analyses of human populations are quite limited because confounding factors influence the results. For this reason, animal experiments are important for analyses. Mice were continuously exposed to gamma-rays at 400 mGy/22 hr/day for 10 days, 20 mGy/22 hr/day for about 400 days, and 1 mGy/22 hr/day for about 615 days under SPF conditions. Chronological changes of unstable-type chromosome aberration rates of spleen cells were observed along with accumulated doses at the middle dose rate and the two low-dose rates by conventional Giemsa-staining method. Aberrations such as dicentric chromosome, ring chromosome and fragment increased in a two-phase manner within 0-1.2 Gy and 2-8 Gy at 20 mGy/22 hr/day. They slightly increased up to 0.5 Gy at 1 mGy/22 hr/day. Aberration rates for 1, 2, 8 Gy at the 20 mGy/22 hr/day and for 0.5 Gy at 1 mGy/22 hr/day were 5.1, 9.6, 13.9 and 2.2 times higher than those of age-matched, non-irradiated control mice, respectively. Chromosome aberration rates at 400 mGy/22 hr/day were 2.7 times higher than that of 20 mGy/22 hr/day for the same total dose of 1.2 Gy. The results that unstable-type chromosome aberrations increased with accumulated dose of the low-dose rate radiation will be important to establish biological dosimetry for people who are chronically exposed to radiation. (author)

  6. Slight respiratory irritation but not inflammation in mice exposed to (1→3-β-D-glucan aerosols

    Directory of Open Access Journals (Sweden)

    A. Korpi

    2003-01-01

    Full Text Available Airway irritation effects after single and repeated inhalation exposures to aerosols of β-glucan (grifolan were investigated in mice. In addition, the effects on serum total immunoglobulin E (IgE production and histopathological inflammation in the respiratory tract were studied. The β-glucan aerosols provoked slight sensory irritation in the airways, but the response was not concentration dependent at the levels studied. Slight pulmonary irritation was observed after repeated exposures. No effect was found on the serum total IgE levels, and no signs of inflammation were seen in the airways 6 h after the final exposure. The results suggest that, irrespective of previous fungal sensitization of the animals, inhaled β-glucan may cause symptoms of respiratory tract irritation but without apparent inflammation. Respiratory tract irritation reported after inhalation of fungi may not be entirely attributed to β-glucan.

  7. Hematologycal disorders in mice of C57BL family exposed to full body radiation by Radioactive Cobalt

    International Nuclear Information System (INIS)

    Seven groups of 5C57B1 mice were submitted to full body radiation ina a single dose of 1.000 r (258m C/Kg). Each group was sacrified respectively on the 5th, 7th, 8th, and 10th day after exposition to radiation. Another group (8th) of 5 animals was used as control group, and was to submitted to radiation. Before sacrificing the animals, peripheral blood was collected to prepare extensions which were stained by Leishman. Then the left femur was removed in order to prepare sections of the bone marrow. We observed accentuated reduction of blood corpuscles, parallel to a similar medullar depression that occurred progressively until the 10th day, when aplasia was almost total. At that time the bone marrow showed almost exclusively lymphocytes, plasmocytes, fibroblasts and endothelial cells, with arare megacaryocytes. However, blood platelets remained normal in the peripheral blood. (author)

  8. Detection of differential DNA methylation in repetitive DNA of mice and humans perinatally exposed to bisphenol A

    Science.gov (United States)

    Faulk, Christopher; Kim, Jung H.; Anderson, Olivia S.; Nahar, Muna S.; Jones, Tamara R.; Sartor, Maureen A.; Dolinoy, Dana C.

    2016-01-01

    ABSTRACT Developmental exposure to bisphenol A (BPA) has been shown to induce changes in DNA methylation in both mouse and human genic regions; however, the response in repetitive elements and transposons has not been explored. Here we present novel methodology to combine genomic DNA enrichment with RepeatMasker analysis on next-generation sequencing data to determine the effect of perinatal BPA exposure on repetitive DNA at the class, family, subfamily, and individual insertion level in both mouse and human samples. Mice were treated during gestation and lactation to BPA in chow at 0, 50, or 50,000 ng/g levels and total BPA was measured in stratified human fetal liver tissue samples as low (non-detect to 0.83 ng/g), medium (3.5 to 5.79 ng/g), or high (35.44 to 96.76 ng/g). Transposon methylation changes were evident in human classes, families, and subfamilies, with the medium group exhibiting hypomethylation compared to both high and low BPA groups. Mouse repeat classes, families, and subfamilies did not respond to BPA with significantly detectable differential DNA methylation. In human samples, 1251 individual transposon loci were detected as differentially methylated by BPA exposure, but only 19 were detected in mice. Of note, this approach recapitulated the discovery of a previously known mouse environmentally labile metastable epiallele, CabpIAP. Thus, by querying repetitive DNA in both mouse and humans, we report the first known transposons in humans that respond to perinatal BPA exposure. PMID:27267941

  9. Chronic radiation injury with mice and dogs exposed to external whole-body irradiation at the Argonne National Laboratory

    International Nuclear Information System (INIS)

    This document describes studies on chronic radiation injury in experimental animals and the extrapolation of derived injury parameters to man. Most of the large studies have used mice given single, weekly, or continuous exposure to cobalt-60 gamma rays, or, more recently, single or weekly exposure to fission neutrons from the JANUS reactor. Primary measures of injury have been life shortening and the associated major pathological changes, particularly neoplastic diseases. Recent and ongoing studies compare the effects of extremely low neutron exposures with gamma irradiations delivered as a single dose or in 60 equal weekly increments. Total neutron doses range from 1 to 40 rads; gamma-ray doses range from 22.5 to 600 rads. Selected genetic studies are performed concurrently to provide a nearly complete matrix of somatic and genetic effects of these low exposures. Studies with the beagle have complemented those with mice and have shown a strong parallelism in the responses of the two species. Present exposures are at 0.3, 0.75, and 1.88 rads per day of continuous gamma irradiation to test a model for the prediction of life shortening in man which has evolved from Argonne's long-term studies. The dog offers the opportunity for longitudinal clinical evaluations that are not possible in the mouse, to develop a broader view of the neoplastic disease spectrum, and to study the mechanisms of radiation induction of leukemia. Diverse statistical approaches have been used to measure excess risk, dose-response functions, and rates of injury and repair. Actuarial statistical methods have been favored since they permit a more direct means of extrapolation to man. 50 refs., 4 figs

  10. Influence of the leaf extract of mentha arvensis linn. (Mint) on the survival of mice exposed to different doses of gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Jagetia, G.C.; Baliga, M.S. [Kasturba Medical Coll., Manipal (India). Dept. of Radiobiology

    2002-02-01

    Background: The aim of the present study was to evaluate the radioprotective effect of Mentha arvensis (mint) on the survival of mice exposed to various doses of whole-body gamma radiation. Material and Methods: The radioprotective effect of various doses (0, 2.5, 5, 10, 20, 40 and 80 mg/kg body weight) of chloroform extract of mint (Mentha arvensis Linn.) was studied in mice exposed to 10 Gy gamma radiation. Results: The 10 mg/kg of mint extract was found to afford best protection as evidenced by the highest number of survivors in this group at 30 days post-irradiation, and further experiments were carried out using this dose of mint extract. The mice treated with 10 mg/kg body weight mint extract or oil were exposed to 6, 7, 8, 9 and 10 Gy of gamma radiation and observed for the induction of radiation-sickness and mortality up to 30 days post-irradiation. The mint extract pretreatment was found to reduce the severity of symptoms of radiation sickness and mortality at all exposure doses and a significant increase in the animal survival was observed when compared with the oil + irradiation group. All of the animals that were treated with 10 mg/kg mint extract and then exposed to 7 Gy irradiation were protected against the radiation-induced mortality when compared with the concurrent oil + irradiation group, in which 20% animals died by 30 days post-irradiation. The mint extract treatment protected the mice against the gastrointestinal death as well as bone marrow deaths. The DRF was found to be 1.2. The drug was non-toxic up to a dose of 1 000 mg/kg body weight, the highest drug dose that could be tested for acute toxicity. Conclusion: From our study it is clear that mint extract provides protection against the radiation-induced sickness and mortality and the optimum protective dose of 10 mg/kg is safe from the point of drug-induced toxicity. (orig.) [German] Hintergrund: Ziel der vorliegenden Studie war es, den radioprotektiven Effekt von Mentha arvensis (Minze

  11. Delayed radiation injury of gut-exposed and gut-shielded mice. I. The decrement in resistance to continuous gamma-ray stress

    Energy Technology Data Exchange (ETDEWEB)

    Spalding, J.F.; Archuleta, R.F.; London, J.E.; Prine, J.R.

    1977-02-01

    Two mouse strains (RF/J and C57B1/6J) were exposed to x-ray doses totaling 400, 800, or 1200 rad. Total doses were given in 200-rad fractions at 7-day intervals to the whole body, gut only, or gut shielded. Animals treated as above (conditioned) were divided into 2 groups to form a two-part investigation. X-ray-conditioned and control mice were subjected to a continuous gamma-ray stress (challenge exposure) 28 days after the last x-ray dose. Delayed injury was measured as a reduction in mean after-survival (MAS) time and was observed in whole-body, gut-conditioned, and gut-shielded groups. The cause of death was attributed to hemopoietic hypoplasia in all groups. MAS reduction in all conditioned groups in both strains was linear with dose within the dose range used. Delayed injury per volume dose (measured as a reduction in MAS) was independent of the tissue initially conditioned with an acute dose of x rays. Thus, delayed injury per unit weight of gut tissue exposed was equal to that of either whole-body or gut-shielded radiation injury. Comparative weight loss observations during the continuous gamma-ray challenge exposure revealed a decrement in metabolic processes associated with body weight maintenance. This decrement was seen in all x-ray-conditioned groups.

  12. Biological and pathological studies of new synthetic copper complex in mice inoculated with tumours and exposed to gamma irradiation

    International Nuclear Information System (INIS)

    New derivatives of neutral copper complexes, particularly copper salicylate complexes having the formula Cu [ C6H4(OH) CO O]2 ROH in which ROH represent an alkanol, were prepared and characterized through IR spectroscopy and mass spectroscopy. The compounds have the same surface active properties. Cu(II) bis (salicylate) octanol (Cu-Bisod) and Cu(II) bis (salicylate) dodecanol (Cu-BISOD) were chosen in this study to evaluate their effects as antitumour agents. The compounds were administered i.p in mice bearing solid tumour of ehrlich carcinoma with four successive doses, 25 mg/kg for each dose alone or 20 min before a fractionated dose of gamma-irradiation (1.5 Gy x 4). The effects of these copper complexes were examined on solid ehrlich cells tumour growing in vivo as well in vitro systems.The study was also extended to show the effect of treatment on the histopathology of the tumour cells beside some liver histological studies. This investigation represents a preliminary study which might clarify the role of copper complexes compounds as an antitumour agents

  13. Induction of the interleukin 6/ signal transducer and activator of transcription pathway in the lungs of mice sub-chronically exposed to mainstream tobacco smoke

    Directory of Open Access Journals (Sweden)

    Williams Andrew

    2009-08-01

    Full Text Available Abstract Background Tobacco smoking is associated with lung cancer and other respiratory diseases. However, little is known about the global molecular changes that precede the appearance of clinically detectable symptoms. In this study, the effects of mainstream tobacco smoke (MTS on global transcription in the mouse lung were investigated. Methods Male C57B1/CBA mice were exposed to MTS from two cigarettes daily, 5 days/week for 6 or 12 weeks. Mice were sacrificed immediately, or 6 weeks following the last cigarette. High density DNA microarrays were used to characterize global gene expression changes in whole lung. Microarray results were validated by Quantitative real-time RT-PCR. Further analysis of protein synthesis and function was carried out for a select set of genes by ELISA and Western blotting. Results Globally, seventy nine genes were significantly differentially expressed following the exposure to MTS. These genes were associated with a number of biological processes including xenobiotic metabolism, redox balance, oxidative stress and inflammation. There was no differential gene expression in mice exposed to smoke and sampled 6 weeks following the last cigarette. Moreover, cluster analysis demonstrated that these samples clustered alongside their respective controls. We observed simultaneous up-regulation of interleukin 6 (IL-6 and its antagonist, suppressor of cytokine signalling (SOCS3 mRNA following 12 weeks of MTS exposure. Analysis by ELISA and Western blotting revealed a concomitant increase in total IL-6 antigen levels and its downstream targets, including phosphorylated signal transducer and activator of transcription 3 (Stat3, basal cell-lymphoma extra large (BCL-XL and myeloid cell leukemia 1 (MCL-1 protein, in total lung tissue extracts. However, in contrast to gene expression, a subtle decrease in total SOCS3 protein was observed after 12 weeks of MTS exposure. Conclusion Global transcriptional analysis identified a set

  14. CXCL12 expression in hematopoietic tissues of mice exposed to sublethal dose of ionizing radiation in the presence od iNOS inhibitor

    International Nuclear Information System (INIS)

    Full text of publication follows: We study the production of CXCL12, a stem cell homing chemokine, in spleen and bone marrow of mice exposed at LD50% of γ-radiation, w/wo a iNOS blocker, aminoguanidine, to test if inflammatory nitric oxide is involved in necrotic processes of stem cell death after ionizing radiation exposure. Groups of 10 male 6-week old C57Bl/6j mice were killed at specific time points after a 8Gy dose irradiation (60Co source; 4,22kGy/h dose rate) and spleen and bone marrow samples were immersed and stored in TriZOL for total mRNA extraction. RT-PCR assays were performed to determine the production of CXCL12 as compared to murine β-actin at days 2nd, 5th, 7th, 9th and 15th days after radiation in a semiquantitative way. PCR was performed after cDNA synthesis using Oligo-dT primers and specific primers for CXCL12 and β-actin. Artificial optical density was determined in silver-stained PAGE resolved specific amplification products of CXCL12, using amplification of murine β-actin as standard, and measurements obtained by the Image J freeware. CXCL12 production in spleen samples reached its maximum at 5th day after radiation exposure in animals not treated with aminoguanidine, but this peak was extended to at 7th day in treated animals. Non treated animals presented a decrease of CXCL12 expression up to 15th day of experiment, and aminoguanidine treated animals showed sustained increase of expression levels between 9th and 15th days. In bone marrow samples, the main difference among the two different experimental groups was a maintenance of CXCL12 mRNA expression between 7th and 9th days, persisting until the end of the experiment. Our data demonstrates that the effect of aminoguanidine appears to sustain the CXCL12 mRNA synthesis in hematopoietic tissues of irradiated mice, providing some evidences that the axis iNOS -NO - inflammation must be involved in stem cell death, aside to the direct radiation effect, suggesting their use associated to

  15. Lead induces similar gene expression changes in brains of gestationally exposed adult mice and in neurons differentiated from mouse embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Francisco Javier Sánchez-Martín

    Full Text Available Exposure to environmental toxicants during embryonic life causes changes in the expression of developmental genes that may last for a lifetime and adversely affect the exposed individual. Developmental exposure to lead (Pb, an ubiquitous environmental contaminant, causes deficits in cognitive functions and IQ, behavioral effects, and attention deficit hyperactivity disorder (ADHD. Long-term effects observed after early life exposure to Pb include reduction of gray matter, alteration of myelin structure, and increment of criminal behavior in adults. Despite growing research interest, the molecular mechanisms responsible for the effects of lead in the central nervous system are still largely unknown. To study the molecular changes due to Pb exposure during neurodevelopment, we exposed mice to Pb in utero and examined the expression of neural markers, neurotrophins, transcription factors and glutamate-related genes in hippocampus, cortex, and thalamus at postnatal day 60. We found that hippocampus was the area where gene expression changes due to Pb exposure were more pronounced. To recapitulate gestational Pb exposure in vitro, we differentiated mouse embryonic stem cells (ESC into neurons and treated ESC-derived neurons with Pb for the length of the differentiation process. These neurons expressed the characteristic neuronal markers Tubb3, Syp, Gap43, Hud, Ngn1, Vglut1 (a marker of glutamatergic neurons, and all the glutamate receptor subunits, but not the glial marker Gafp. Importantly, several of the changes observed in Pb-exposed mouse brains in vivo were also observed in Pb-treated ESC-derived neurons, including those affecting expression of Ngn1, Bdnf exon IV, Grin1, Grin2D, Grik5, Gria4, and Grm6. We conclude that our ESC-derived model of toxicant exposure during neural differentiation promises to be a useful model to analyze mechanisms of neurotoxicity induced by Pb and other environmental agents.

  16. Increased nitration and carbonylation of proteins in MRL +/+ mice exposed to trichloroethene: Potential role of protein oxidation in autoimmunity

    International Nuclear Information System (INIS)

    Even though reactive oxygen and nitrogen species (RONS) are implicated as mediators of autoimmune diseases (ADs), little is known about contribution of protein oxidation (carbonylation and nitration) in the pathogenesis of such diseases. The focus of this study was, therefore, to establish a link between protein oxidation and induction and/or exacerbation of autoimmunity. To achieve this, female MRL +/+ mice were treated with trichloroethene (TCE), an environmental contaminant known to induce autoimmune response, for 6 or 12 weeks (10 mmol/kg, i.p., every 4th day). TCE treatment resulted in significantly increased formation of nitrotyrosine (NT) and induction of iNOS in the serum at both 6 and 12 weeks of treatment, but the response was greater at 12 weeks. Likewise, TCE treatment led to greater NT formation, and iNOS protein and mRNA expression in the livers and kidneys. Moreover, TCE treatment also caused significant increases (∼3 fold) in serum protein carbonyls (a marker of protein oxidation) at both 6 and 12 weeks. Significantly increased protein carbonyls were also observed in the livers and kidneys (2.1 and 1.3 fold, respectively) at 6 weeks, and to a greater extent at 12 weeks (3.5 and 2.1 fold, respectively) following TCE treatment. The increases in TCE-induced protein oxidation (carbonylation and nitration) were associated with significant increases in Th1 specific cytokine (IL-2, IFN-γ) release into splenocyte cultures. These results suggest an association between protein oxidation and induction/exacerbation of autoimmune response. The results present a potential mechanism by which oxidatively modified proteins could contribute to TCE-induced autoimmune response and necessitates further investigations for clearly establishing the role of protein oxidation in the pathogenesis of ADs.

  17. Evaluation of gene, protein and neurotrophin expression in the brain of mice exposed to space environment for 91 days.

    Directory of Open Access Journals (Sweden)

    Daniela Santucci

    Full Text Available Effects of 3-month exposure to microgravity environment on the expression of genes and proteins in mouse brain were studied. Moreover, responses of neurobiological parameters, nerve growth factor (NGF and brain derived neurotrophic factor (BDNF, were also evaluated in the cerebellum, hippocampus, cortex, and adrenal glands. Spaceflight-related changes in gene and protein expression were observed. Biological processes of the up-regulated genes were related to the immune response, metabolic process, and/or inflammatory response. Changes of cellular components involving in microsome and vesicular fraction were also noted. Molecular function categories were related to various enzyme activities. The biological processes in the down-regulated genes were related to various metabolic and catabolic processes. Cellular components were related to cytoplasm and mitochondrion. The down-regulated molecular functions were related to catalytic and oxidoreductase activities. Up-regulation of 28 proteins was seen following spaceflight vs. those in ground control. These proteins were related to mitochondrial metabolism, synthesis and hydrolysis of ATP, calcium/calmodulin metabolism, nervous system, and transport of proteins and/or amino acids. Down-regulated proteins were related to mitochondrial metabolism. Expression of NGF in hippocampus, cortex, and adrenal gland of wild type animal tended to decrease following spaceflight. As for pleiotrophin transgenic mice, spaceflight-related reduction of NGF occurred only in adrenal gland. Consistent trends between various portions of brain and adrenal gland were not observed in the responses of BDNF to spaceflight. Although exposure to real microgravity influenced the expression of a number of genes and proteins in the brain that have been shown to be involved in a wide spectrum of biological function, it is still unclear how the functional properties of brain were influenced by 3-month exposure to microgravity.

  18. Microglia are less pro-inflammatory than myeloid infiltrates in the hippocampus of mice exposed to status epilepticus.

    Science.gov (United States)

    Vinet, Jonathan; Vainchtein, Ilia D; Spano, Carlotta; Giordano, Carmela; Bordini, Domenico; Curia, Giulia; Dominici, Massimo; Boddeke, Hendrikus W G M; Eggen, Bart J L; Biagini, Giuseppe

    2016-08-01

    Activated microglia, astrogliosis, expression of pro-inflammatory cytokines, blood brain barrier (BBB) leakage and peripheral immune cell infiltration are features of mesial temporal lobe epilepsy. Numerous studies correlated the expression of pro-inflammatory cytokines with the activated morphology of microglia, attributing them a pro-epileptogenic role. However, microglia and myeloid cells such as macrophages have always been difficult to distinguish due to an overlap in expressed cell surface molecules. Thus, the detrimental role in epilepsy that is attributed to microglia might be shared with myeloid infiltrates. Here, we used a FACS-based approach to discriminate between microglia and myeloid infiltrates isolated from the hippocampus 24 h and 96 h after status epilepticus (SE) in pilocarpine-treated CD1 mice. We observed that microglia do not express MHCII whereas myeloid infiltrates express high levels of MHCII and CD40 96 h after SE. This antigen-presenting cell phenotype correlated with the presence of CD4(pos) T cells. Moreover, microglia only expressed TNFα 24 h after SE while myeloid infiltrates expressed high levels of IL-1β and TNFα. Immunofluorescence showed that astrocytes but not microglia expressed IL-1β. Myeloid infiltrates also expressed matrix metalloproteinase (MMP)-9 and 12 while microglia only expressed MMP-12, suggesting the involvement of both cell types in the BBB leakage that follows SE. Finally, both cell types expressed the phagocytosis receptor Axl, pointing to phagocytosis of apoptotic cells as one of the main functions of microglia. Our data suggests that, during early epileptogenesis, microglia from the hippocampus remain rather immune supressed whereas myeloid infiltrates display a strong inflammatory profile. GLIA 2016 GLIA 2016;64:1350-1362. PMID:27246930

  19. ESR evidence for in vivo formation of free radicals in tissue of mice exposed to single-walled carbon nanotubes.

    Science.gov (United States)

    Shvedova, A A; Kisin, E R; Murray, A R; Mouithys-Mickalad, A; Stadler, K; Mason, R P; Kadiiska, M

    2014-08-01

    Nanomaterials are being utilized in an increasing variety of manufactured goods. Because of their unique physicochemical, electrical, mechanical, and thermal properties, single-walled carbon nanotubes (SWCNTs) have found numerous applications in the electronics, aerospace, chemical, polymer, and pharmaceutical industries. Previously, we have reported that pharyngeal exposure of C57BL/6 mice to SWCNTs caused dose-dependent formation of granulomatous bronchial interstitial pneumonia, fibrosis, oxidative stress, acute inflammatory/cytokine responses, and a decrease in pulmonary function. In the current study, we used electron spin resonance (ESR) to directly assess whether exposure to respirable SWCNTs caused formation of free radicals in the lungs and in two distant organs, the heart and liver. Here we report that exposure to partially purified SWCNTs (HiPco technique, Carbon Nanotechnologies, Inc., Houston, TX, USA) resulted in the augmentation of oxidative stress as evidenced by ESR detection of α-(4-pyridyl-1-oxide)-N-tert-butylnitrone spin-trapped carbon-centered lipid-derived radicals recorded shortly after the treatment. This was accompanied by a significant depletion of antioxidants and elevated biomarkers of inflammation presented by recruitment of inflammatory cells and an increase in proinflammatory cytokines in the lungs, as well as development of multifocal granulomatous pneumonia, interstitial fibrosis, and suppressed pulmonary function. Moreover, pulmonary exposure to SWCNTs also caused the formation of carbon-centered lipid-derived radicals in the heart and liver at later time points (day 7 postexposure). Additionally, SWCNTs induced a significant accumulation of oxidatively modified proteins, increase in lipid peroxidation products, depletion of antioxidants, and inflammatory response in both the heart and the liver. Furthermore, the iron chelator deferoxamine noticeably reduced lung inflammation and oxidative stress, indicating an important role for

  20. Hepatic immunophenotyping for streptozotocin-induced hyperglycemia in mice

    Science.gov (United States)

    Lee, Young-Sun; Eun, Hyuk Soo; Kim, So Yeon; Jeong, Jong-Min; Seo, Wonhyo; Byun, Jin-Seok; Jeong, Won-Il; Yi, Hyon-Seung

    2016-01-01

    Emerging evidence revealed that diabetes induces abnormal immune responses that result in serious complications in organs. However, the effect of hyperglycemia on hepatic immunity remains obscure. We evaluated the population and function of hepatic immune cells in streptozotocin (STZ)-induced hyperglycemic mice. CC chemokine receptor 2 (CCR2)-knockout mice and mice with a depletion of regulatory T cells (DEREG) were used to investigate the migration and role of regulatory T cells (Tregs) in hyperglycemic mice. The inflammatory cytokines and hepatic transaminase levels were significantly increased in the hyperglycemic mice. The population and number of infiltrating monocytes, granulocytes, and Tregs were enhanced in the livers of the hyperglycemic mice. Hepatic monocytes other than macrophages showed the increased expression of inflammatory cytokines and chemokines in the hyperglycemic mice. The CCR2 knockout and DEREG chimeric mice exhibited increased populations of activated T cells and neutrophils compared to the WT chimeric mice, which promoted hepatic inflammation in the hyperglycemic mice. The migration of CCR2 knockout Tregs into the liver was significantly reduced compared to the WT Tregs. We demonstrated that hyperglycemia contributes to increase in infiltrating monocytes and Tregs, which are associated with hepatic immune dysfunction in mice. CCR2-mediated migration of Tregs regulates hyperglycemia-induced hepatic inflammation. PMID:27464894

  1. Toxicological responses in SW mice exposed to inhaled pyrolysates of polymer/tobacco mixtures and blended tobacco.

    Science.gov (United States)

    Werley, Michael S; Lee, K Monika; Lemus-Olalde, Ranulfo

    2009-12-01

    Modern cigarette manufacturing is highly automated and produces millions of cigarettes per day. The potential for small inclusions of non-cigarette materials such as wood, cardboard packaging, plastic, and other materials exists as a result of bulk handling and high-speed processing of tobacco. Many non-tobacco inclusions such as wood, paper, and cardboard would be expected to yield similar pyrolysis products as a burning cigarette. The aircraft industry has developed an extensive literature on the pyrolysis products of plastics, however, that have been reported to yield toxic by-products upon burning, by-products that have been lethal in animals and humans upon acute exposure under some exposure conditions. Some of these smoke constituents have also been reported in cigarette smoke. Five synthetic polymers, nylon 6, acrylonitrile-butadiene-styrene (ABS), nylon 12, nylon 6,6, and acrylonitrile-butadiene (AB), and the natural polymer wool were evaluated by adding them to tobacco at a 3, 10, and 30% inclusion level and then pyrolyzing the mixture. The validated smoke generation and exposure system have been described previously. We used the DIN 53-436 tube furnace and nose-only exposure chamber in combination to conduct exposures in Swiss-Webster mice. Potentially useful biological endpoints for predicting hazards in humans included sensory irritation and pulmonary irritation, respiratory function, clinical signs, body weights, bronchoalveolar lavage (BAL) fluid analysis, carboxyhemoglogin, blood cyanide concentrations, and histopathology of the respiratory tract. Chemical analysis of selected smoke constituents in the test atmosphere was also performed in order to compare the toxicological responses with exposure to the test atmospheres. Under the conditions of these studies, biological responses considered relevant and useful for prediction of effects in humans were found for sensory irritation, body weights, BAL fluid analysis, and histopathology of the nose

  2. Claudin-2 knockout by TALEN-mediated gene targeting in MDCK cells: claudin-2 independently determines the leaky property of tight junctions in MDCK cells.

    Directory of Open Access Journals (Sweden)

    Shinsaku Tokuda

    Full Text Available Tight junctions (TJs regulate the movements of substances through the paracellular pathway, and claudins are major determinants of TJ permeability. Claudin-2 forms high conductive cation pores in TJs. The suppression of claudin-2 expression by RNA interference in Madin-Darby canine kidney (MDCK II cells (a low-resistance strain of MDCK cells was shown to induce a three-fold increase in transepithelial electrical resistance (TER, which, however, was still lower than in high-resistance strains of MDCK cells. Because RNA interference-mediated knockdown is not complete and only reduces gene function, we considered the possibility that the remaining claudin-2 expression in the knockdown study caused the lower TER in claudin-2 knockdown cells. Therefore, we investigated the effects of claudin-2 knockout in MDCK II cells by establishing claudin-2 knockout clones using transcription activator-like effector nucleases (TALENs, a recently developed genome editing method for gene knockout. Surprisingly, claudin-2 knockout increased TER by more than 50-fold in MDCK II cells, and TER values in these cells (3000-4000 Ω·cm2 were comparable to those in the high-resistance strains of MDCK cells. Claudin-2 re-expression restored the TER of claudin-2 knockout cells dependent upon claudin-2 protein levels. In addition, we investigated the localization of claudin-1, -2, -3, -4, and -7 at TJs between control MDCK cells and their respective knockout cells using their TALENs. Claudin-2 and -7 were less efficiently localized at TJs between control and their knockout cells. Our results indicate that claudin-2 independently determines the 'leaky' property of TJs in MDCK II cells and suggest the importance of knockout analysis in cultured cells.

  3. On the effect of minocycline on the depressive-like behavior of mice repeatedly exposed to malathion: interaction between nitric oxide and cholinergic system.

    Science.gov (United States)

    Saeedi Saravi, Seyed Soheil; Amirkhanloo, Roya; Arefidoust, Alireza; Yaftian, Rahele; Saeedi Saravi, Seyed Sobhan; Shokrzadeh, Mohammad; Dehpour, Ahmad Reza

    2016-06-01

    This study was performed to investigate the antidepressant-like effect of minocycline in mice exposed to organophosphate pesticide malathion and possible involvement of nitric oxide/cGMP pathway in this paradigm. Mice were administered specific doses of malathion once daily for 7 consecutive days. After induction of depression, different doses of minocycline were daily injected alone or combined with non-specific NOS inhibitor, L-NAME, specific inducible NOS inhibitor, AG, NO precursor, L-arginine, and PDE5I, sildenafil. After locomotion assessment in open-field test, immobility times were recorded in the FST and TST. Moreover, hippocampal nitrite concentrations and acetylcholinesterase activity were measured. The results showed that repeated exposure to malathion induces depressive-like behavior at dose of 250 mg/kg. Minocycline (160 mg/kg) significantly reduced immobility times in FST and TST (P < 0.001). Combination of sub-effective doses of minocycline (80 mg/kg) with either L-NAME (3 mg/kg) or AG (25 mg/kg) significantly exerted a robust antidepressant-like effect in FST and TST (P < 0.001). Furthermore, minocycline at the same dose which has antidepressant-like effect, significantly reduced hippocampal nitrite concentration. The investigation indicates the essential role for NO/cGMP pathway in malathion-induced depressive-like behavior and antidepressant-like effect of minocycline. Moreover, the interaction between nitrergic and cholinergic systems are suggested to be involved in malathion-induced depression. PMID:26581675

  4. Urine arsenic methylated metabolism in mice exposed to acute arsenic%急性砷暴露小鼠尿砷甲基化代谢的研究

    Institute of Scientific and Technical Information of China (English)

    董丹丹; 王欣; 赵朔; 段晓旭; 李炜; 李冰

    2013-01-01

    Objective To investigate the level of urine arsenic excretion and methylated metabolism pattern in mice exposed to acute arsenic. Methods Healthy female Kunming mice were exposed to sodium arsenite ( NaAsO2) by intragastric infusion at doses of 2.5 mg/kg, 5.0 mg/kg, 10.0 mg/kg and 20.0 mg/kg, the exposure time for each group were 12 hours, 24 hours, 48 hours and 72 hours. The mice were placed in metabolic cages and urine samples of 24 - hour group were collected (urine samples of 12 hours were collect from 12 - hour group) before the end of exposure day. The level of inorganic arsenic (iAs) , monomethy-lated arsenic [ MMA) and dimethylated arsenic ( DMA) in urine were determined by cold trap hydride generation atomic absorption spectrophotometer respectively, the level of T-As, iAs% , MMA% , DMA% , primary methylation index (PMI) and secondary methylation index ( SMI) were calculated. Results Urine T - As level, iAs% and MMA in the mice exposed to acute arsenic increased significantly with the increase of arsenic concentration, but DMA% and SMI decreased with stable PMI. With the increase of time after exposure, urine T - As level, iAs% and MMA% gradually decreased, while DMA% , PMI and SMI increased significantly. The most urine arsenic were excreted within 24 hours, and its percentage content and methylation index were at same level, the level of urine arsenic excretion was very low in 48 - hour and 72 hour groups and their percentage content and methylation index were at same level. Conclusion Urine arsenic excretion in mice exposed to acute arsenic has obvious dose deffect relation and time - effect relation; High concentration of arsenic exposure may effectively inhibit methylated metabolism , and urine arsenic content within 24 hours could be used as an indicator to determine the arsenic burden of an acute arsenic poisoned body.%目的 探讨急性砷暴露小鼠尿砷排泄及其甲基化代谢模式.方法 健康雌性昆明种小鼠一次性灌

  5. Resveratrol Suppresses Cytokine Production Linked to FcεRI-MAPK Activation in IgE-Antigen Complex-Exposed Basophilic Mast Cells and Mice.

    Science.gov (United States)

    Han, Seon-Young; Choi, Yean-Jung; Kang, Min-Kyung; Park, Jung Han Yoon; Kang, Young-Hee

    2015-01-01

    A complicated interplay between resident mast cells and other recruited inflammatory cells contributes to the development and progression of allergic inflammation entailing the promotion of T helper 2 (Th2) cytokine responses. The current study examined whether resveratrol suppressed the production of inflammatory Th2 cytokines in cultured rat basophilic leukemia RBL-2H3 cells. Cells pre-treated with resveratrol nontoxic at 1–25 μM were sensitized with anti-dinitrophenyl (anti-DNP), and subsequently stimulated by dinitrophenyl-human serum albumin (DNP–HSA) antigen. Resveratrol dose-dependently diminished the secretion of interleukin (IL)-3, IL-4, IL-13 as well as tumor necrosis factor (TNF)-α by the antigen stimulation from sensitized cells. It was found that resveratrol mitigated the phosphorylation of p38 MAPK, ERK, and JNK elevated in mast cells exposed to Fc epsilon receptor I (FcεRI)-mediated immunoglobulin E (IgE)-antigen complex. The FcεRI aggregation was highly enhanced on the surface of mast cells following the HSA stimulation, which was retarded by treatment with 1–25 μM resveratrol. The IgE-receptor engagement rapidly induced tyrosine phosphorylation of c-Src-related focal adhesion protein paxillin involved in the cytoskeleton rearrangement. The FcεRI-mediated rapid activation of c-Src and paxillin was attenuated in a dose-dependent manner. In addition, the paxillin activation entailed p38 MAPK and ERK-responsive signaling, but the JNK activation was less involved. Consistently, oral administration of resveratrol reduced the tissue level of phosphorylated paxillin in the dorsal skin of DNP–HSA-challenged mice. The other tyrosine kinase Tyk2-STAT1 signaling was activated in the dorsal epidermis of antigen-exposed mice, which was associated with allergic inflammation. These results showed that resveratrol inhibited Th2 cytokines- and paxillin-linked allergic responses dependent upon MAPK signaling. Therefore, resveratrol may possess the

  6. Methylation changes in muscle and liver tissues of male and female mice exposed to acute and chronic low-dose X-ray-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kovalchuk, Olga; Burke, Paula; Besplug, Jill; Slovack, Mark; Filkowski, Jody; Pogribny, Igor

    2004-04-14

    The biological and genetic effects of chronic low-dose radiation (LDR) exposure and its relationship to carcinogenesis have received a lot of attention in the recent years. For example, radiation-induced genome instability, which is thought to be a precursor of tumorogenesis, was shown to have a transgenerational nature. This indicates a possible involvement of epigenetic mechanisms in LDR-induced genome instability. Genomic DNA methylation is one of the most important epigenetic mechanisms. Existing data on radiation effects on DNA methylation patterns is limited, and no one has specifically studied the effects of the LDR. We report the first study of the effects of whole-body LDR exposure on global genome methylation in muscle and liver tissues of male and female mice. In parallel, we evaluated changes in promoter methylation and expression of the tumor suppressor gene p16{sup INKa} and DNA repair gene O{sup 6}-methylguanine-DNA methyltransferase (MGMT). We observed different patterns of radiation-induced global genome DNA methylation in the liver and muscle of exposed males and females. We also found sex and tissue-specific differences in p16{sup INKa} promoter methylation upon LDR exposure. In male liver tissue, p16{sup INKa} promoter methylation was more pronounced than in female tissue. In contrast, no significant radiation-induced changes in p16{sup INKa} promoter methylation were noted in the muscle tissue of exposed males and females. Radiation also did not significantly affect methylation status of MGMT promoter. We also observed substantial sex differences in acute and chronic radiation-induced expression of p16{sup INKa} and MGMT genes. Another important outcome of our study was the fact that chronic low-dose radiation exposure proved to be a more potent inducer of epigenetic effects than the acute exposure. This supports previous findings that chronic exposure leads to greater genome destabilization than acute exposure.

  7. Changes in the level of DNA-protein cross-links in spleen lymphocytes of mice exposed to low-intensity γ-radiation at low doses

    International Nuclear Information System (INIS)

    Levels of DNA-protein cross-links (DPC) and DNA single-strand breaks (SSB) in spleen lymphocytes were studied in mice exposed to low-intensity γ-radiation at low doses (1.7 mGy/day) for 1, 4, 10, 20, and 30 days. Spleen mass and count of lymphocytes isolated from this organ also has been investigated. Statistically true increase in the DPC level as compared to the control occurred on the 10-th and 30-th days of irradiation at doses of 1.7 and 5.1 cGy, accordingly. Number of spleen lymphocytes normalized to organ mass significantly decreased on the 4-th and 30-th days of the experiment. No increase was found in levels of alkali-labile sites and SSB. In contrast , the increase in the amount of duplex form DNA was recorded on the 4-th and 10-th days of the experiment. Result obtained permit to suppose that DPC formation under irradiation at low doses represents some form of cellular response to the damaging agent

  8. Dose-rate effects and chronological changes of chromosome aberration rates in spleen cells from mice that are chronically exposed to gamma-ray at low dose rates

    International Nuclear Information System (INIS)

    Dose-rate effects have not been examined in the low dose-rate regions of less than 60-600 mGy/h. Mice were chronically exposed to gamma-ray at 20 mGy/day (approximately 1 mGy/h) up to 700 days and at 1 mGy/day (approximately 0.05 mGy/h) for 500 days under SPF conditions. Chronological changes of chromosome aberration rates in spleen cells were observed along with accumulated doses at both low dose-rates. Unstable aberrations increased in a biphasic manner within 0-2 Gy and 4-14 Gy in 20 mGy/day irradiation. They slightly increased up to 0.5 Gy in 1 mGy/day irradiation. Chromosome aberration rates at 20 mGy/day and 1 mGy/day were compared at the same total doses of 0.5 Gy and 0.25 Gy. They were 2.0 vs. 0.53, and 1.0 vs. 0.47 respectively. Thus, dose-rate effects were observed in these low dose-rate regions. (author)

  9. Observation of acute radiation damage on mice exposed to X-rays%X射线致小鼠急性损伤的观察

    Institute of Scientific and Technical Information of China (English)

    何火聪; 吴君心; 苏颖; 潘剑茹; 郑光进; 刘树滔

    2012-01-01

    本研究用6GyX射线对小鼠进行全身一次性照射,分别在照射后l、3和7d经颈椎脱臼处死,测定小鼠外周血红、白细胞数量,胸腺指数和脾脏指数,骨髓嗜多染红细胞微核形成率以及肝脏抗氧化水平.结果表明:照射24 h后,小鼠外周血白细胞数量急剧降低,胸腺指数和脾脏指数下降,骨髓嗜多染红细胞微核形成率增加,肝脏脂质过氧化水平上升.放射7d后,胸腺指数稍有回升,骨髓红细胞微核形成率和肝脏脂质过氧化水平略为降低,其它指标随时间变化损伤程度持续增加.%Mice were whole-body exposed to X-rays with absorbed dose of 6 Gy and sacrificed on the 1st, 3rd and 7th day by cervical dislocation after irradiation, respectively. The number of red blood cells and white blood cells in peripheral blood, the index of thymus and spleen, the micronucleus rate of bone marrow polychromatic erythro-blasts (PCE) and the level of antioxidant of liver were determined. It was observed that white blood cells decreased, the index of thymus and spleen also decreased meanwhile both of the micronucleus rate of bone marrow PCE and level of lipid peroxidation of liver increased at 24 h after irradiation. However, the index of thymus was up slightly on the 7th day after irradiation, while the PCE and the level of lipid peroxidation of liver got down slightly. The other index of injured mice increased continually with time.

  10. 砷致小鼠肝纤维化模型的建立%Model establishment of liver fibrosis in oral arsenic solution exposed mice

    Institute of Scientific and Technical Information of China (English)

    吴君; 程明亮; 李玲; 李诚秀; 蒋玲; 张韵; 欧兵

    2009-01-01

    Objective To discuss and compare the model estabhshment of liver fibrosis in oral arsenic solution exposed mice and mice with high-fat feedstuff. Methods A total of 240 mice were divided randomly into 6 groups: control group, sodium arsenite group, sodium arsenate group, high-fat feedstuff group, sodium arsenite group with high-fat feedstuff and sodium arsenate group with high-fat feedstuff with 40 mice esch. Control group and high-fat feedstuff group (drinking tap water), sodium arsenite group and sodium arsenite group with high-fat feedstuff (drinking 300 mg/L iAs3+ water), sodium arsenate group and sodium arsenate group with high-fat feedstuff (drinking 300 mg/L iAs5+ water). The mice were sacrificed after 3, 6, 10 months' arsenic-exposure and examined for liver function. HE dyeing and Masson dyeing were also employed to observe the pathological changes in hepatic tissue in each group. Results After 3 months' modeling, ALT and AST in control group, sodium arsenite group, sodium arsenate group, sodium arsenite group with high-fat feedstuff and sodium arsenate group with high-fat feedstuff were (36.7±5.7 ) U/L and (110±22) U/L, (55.6±4.6) U/L and (249±41) U/L, (52.6±8.8) U/L and (161±15) U/L, (311.3±19.7)U/L and (484±15)U/L and (515.0±60.8)U/L and (671±24)U/L. They were higher in all the arsenic groups than in control group (P<0.05); all the HE dyeing samples in arsenic groups showed liver injury in varying degrees such as hydropic degeneration, fatty degeneration, spotty necrosis, fecal necrosis and inflammatory cell infiltration. There were liver cell regeneration and fibroplasias in varying degrees. The liver injury of the mice in all arsenic groups aggravated as exposure time prolonged. Masson dyeing after 10 months' modeling showed hyperplasia in portal areas and central venous areas; the mean area of fibrosis in control group, sodium arsenite group, sodium arsenate group, sodium arsenite group with high-fat feedstuff and sodium arsenate group with

  11. Effects of acamprosate on attentional set-shifting and cellular function in the prefrontal cortex of chronic alcohol-exposed mice

    Science.gov (United States)

    Hu, Wei

    Background: The medial prefrontal cortex (mPFC) inhibits impulsive and compulsive behaviors that characterize drug abuse and dependence. Acamprosate is the leading medication approved for the maintenance of abstinence, shown to reduce craving and relapse in animal models and human alcoholics. Whether acamprosate can modulate executive functions that are impaired by chronic ethanol exposure is unknown. Here we explored the effects of acamprosate on an attentional set-shifting task, and tested whether these behavioral effects are correlated with modulation of glutamatergic synaptic transmission and intrinsic excitability of mPFC neurons. Methods: We induced alcohol dependence in mice via chronic intermittent ethanol (CIE) exposure in vapor chambers and measured changes in alcohol consumption in a limited access 2-bottle choice paradigm. Impairments of executive function were assessed in an attentional set-shifting task. Acamprosate was applied subchronically for 2 days during withdrawal before the final behavioral test. Alcohol-induced changes in cellular function of layer 5/6 pyramidal neurons, and the potential modulation of these changes by acamprosate, were measured using patch clamp recordings in brain slices. Results: Chronic ethanol exposure impaired cognitive flexibility in the attentional set-shifting task. Acamprosate improved overall performance and reduced perseveration. Recordings of mPFC neurons showed that chronic ethanol exposure increased use-dependent presynaptic transmitter release and enhanced postsynaptic N-methyl-D-aspartate receptor (NMDAR) function. Moreover, CIE-treatment lowered input resistance, and decreased the threshold and the afterhyperpolarization (AHP) of action potentials, suggesting chronic ethanol exposure also impacted membrane excitability of mPFC neurons. However, acamprosate treatment did not reverse these ethanol-induced changes cellular function. Conclusion: Acamprosate improved attentional control of ethanol exposed animals

  12. SOCS2 deletion protects against hepatic steatosis but worsens insulin resistance in high-fat-diet-fed mice

    DEFF Research Database (Denmark)

    Zadjali, Fahad; Santana-Farre, Ruyman; Vesterlund, Mattias;

    2012-01-01

    in the development of diet-induced hepatic steatosis and insulin resistance. SOCS2-knockout (SOCS2(-/-)) mice and wild-type littermates were fed for 4 mo with control or high-fat diet, followed by assessment of insulin sensitivity, hepatic lipid content, and expression of inflammatory cytokines. SOCS2(-/-) mice...

  13. New Hippocampal Neurons Are Not Obligatory for Memory Formation; Cyclin D2 Knockout Mice with No Adult Brain Neurogenesis Show Learning

    Science.gov (United States)

    Jaholkowski, Piotr; Kiryk, Anna; Jedynak, Paulina; Abdallah, Nada M. Ben; Knapska, Ewelina; Kowalczyk, Anna; Piechal, Agnieszka; Blecharz-Klin, Kamilla; Figiel, Izabela; Lioudyno, Victoria; Widy-Tyszkiewicz, Ewa; Wilczynski, Grzegorz M.; Lipp, Hans-Peter; Kaczmarek, Leszek; Filipkowski, Robert K.

    2009-01-01

    The role of adult brain neurogenesis (generating new neurons) in learning and memory appears to be quite firmly established in spite of some criticism and lack of understanding of what the new neurons serve the brain for. Also, the few experiments showing that blocking adult neurogenesis causes learning deficits used irradiation and various drugs…

  14. Curcumin-Induced Heme Oxygenase-1 Expression Prevents H2O2-Induced Cell Death in Wild Type and Heme Oxygenase-2 Knockout Adipose-Derived Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Niels A. J. Cremers

    2014-10-01

    Full Text Available Mesenchymal stem cell (MSC administration is a promising adjuvant therapy to treat tissue injury. However, MSC survival after administration is often hampered by oxidative stress at the site of injury. Heme oxygenase (HO generates the cytoprotective effector molecules biliverdin/bilirubin, carbon monoxide (CO and iron/ferritin by breaking down heme. Since HO-activity mediates anti-apoptotic, anti-inflammatory, and anti-oxidative effects, we hypothesized that modulation of the HO-system affects MSC survival. Adipose-derived MSCs (ASCs from wild type (WT and HO-2 knockout (KO mice were isolated and characterized with respect to ASC marker expression. In order to analyze potential modulatory effects of the HO-system on ASC survival, WT and HO-2 KO ASCs were pre-treated with HO-activity modulators, or downstream effector molecules biliverdin, bilirubin, and CO before co-exposure of ASCs to a toxic dose of H2O2. Surprisingly, sensitivity to H2O2-mediated cell death was similar in WT and HO-2 KO ASCs. However, pre-induction of HO-1 expression using curcumin increased ASC survival after H2O2 exposure in both WT and HO-2 KO ASCs. Simultaneous inhibition of HO-activity resulted in loss of curcumin-mediated protection. Co-treatment with glutathione precursor N-Acetylcysteine promoted ASC survival. However, co-incubation with HO-effector molecules bilirubin and biliverdin did not rescue from H2O2-mediated cell death, whereas co-exposure to CO-releasing molecules-2 (CORM-2 significantly increased cell survival, independently from HO-2 expression. Summarizing, our results show that curcumin protects via an HO-1 dependent mechanism against H2O2-mediated apoptosis, and likely through the generation of CO. HO-1 pre-induction or administration of CORMs may thus form an attractive strategy to improve MSC therapy.

  15. The Detrimental Role Played by Lipocalin-2 in Alcoholic Fatty Liver in Mice.

    Science.gov (United States)

    Cai, Yan; Jogasuria, Alvin; Yin, Huquan; Xu, Ming-Jiang; Hu, Xudong; Wang, Jiayou; Kim, Chunki; Wu, Jiashin; Lee, Kwangwon; Gao, Bin; You, Min

    2016-09-01

    We have previously shown that the ethanol-mediated elevation of lipocaline-2 (LCN2) is closely associated with the development of alcoholic fatty liver disease (AFLD) in mice. Herein, we aimed to understand the functional significance of LCN2 induction by ethanol and to explore its underlying mechanisms. We evaluated the effects of LCN2 in an in vitro cellular alcoholic steatosis model and in an animal study using wild-type and LCN2 knockout mice fed for 4 weeks with an ethanol-supplemented Lieber-DeCarli diet. In the cellular model of alcoholic steatosis, recombinant LCN2 or overexpression of LCN2 exacerbated ethanol-induced fat accumulation, whereas knocking down LCN2 prevented steatosis in hepatocytes exposed to ethanol. Consistently, removal of LCN2 partially but significantly alleviated alcoholic fatty liver injury in mice. Mechanistically, LCN2 mediates detrimental effects of ethanol in the liver via disrupted multiple signaling pathways, including aberrant nicotinamide phosphoribosyltransferase-sirtuin 1 axis, perturbed endocrine metabolic regulatory fibroblast growth factor 15/19 signaling, and impaired chaperone-mediated autophagy. Finally, compared with healthy human livers, liver samples from patients with AFLD had lower gene expression of several LCN2-regualted molecules. Our study demonstrated a pivotal and causal role of LCN2 in the development of AFLD and suggested that targeting the LCN2 could be of great value for the treatment of human AFLD. PMID:27427417

  16. Regulation of Gene Expression of Catecholamine Biosynthetic Enzymes in Dopamine-β-Hydroxylase- and CRH-Knockout Mice Exposed to Stress

    OpenAIRE

    Richard, Kvetnansky; Olga, Krizanova; Andrej, Tillinger; Sabban Esther, L.; Thomas Steven, A; Lucia, Kubovcakova

    2008-01-01

    Norepinephrine-deficient mice harbor a disruption of the gene for dopamine-β-hydroxylase (DBH-KO). Corticotropin-releasing hormone knockout mice (CRH-KO) have markedly reduced HPA activity. The aim of the present work was to study how deficiency of DBH and CRH would affect tyrosine hydroxylase (TH), DBH, and phenylethanolamine N-methyltransferase (PNMT) gene expression and protein levels in the adrenal medulla (AM) and stellate ganglia (SG) of control and stressed mice. Both in AM and SG, sin...

  17. Research on suppression function of compound prescription powder made from rana japonica oil on hydroxy free radical in serum of big mice exposed to X ray

    International Nuclear Information System (INIS)

    The models of Wistar big mice under X ray irradiation were copied and intervened by the compound prescription powder made from rana japonica oil, for the purpose to examines the ability of suppression on the hydroxy free radicals in the serum taken from each group of big mice which was being examined. Results show that the ability of prevention group of suppression hydroxy free radical is obviously higher than blank control group and tailored radiation group (p<0.05). Ability of treatment group suppress hydroxy free radically is obviously higher than tailored radiation group (p<0.05). There is not the remarkable difference between blank control group and tailored radiation group. The above results demonstrates that compound prescription powder mainly made from the rana japonica oil might assist to strengthen the suppression of serum taken from the big mice under X ray irradiation on the hydroxy free radical. (authors)

  18. Effect of sex and age on the frequency of tumors arising in non-linear mice exposed to total gamma irradiation

    International Nuclear Information System (INIS)

    The effect of sex and age of nonlinear mice on the frequency of tumours was studied. Nonlinear mice of the SHK colony of both sexes were gamma-irradiated with 137Cs. The histological material, frequency and time of tumour appearance were investigated in dependence on age. Single exposure accelerated the appearance of tumours of the hemopoietic tissue in females and lung and liver tumours in males. The irradiation increased the frequency of tumour appearance in females. The frequency of mammary gland tumours increased under irradiation of females of older age. Ovary tumours developed irrespective of mouse age by the time of irradiation. Average longevity reduced only in young females

  19. Sm29, but not Sm22.6 retains its ability to induce a protective immune response in mice previously exposed to a Schistosoma mansoni infection.

    Directory of Open Access Journals (Sweden)

    Clarice Carvalho Alves

    2015-02-01

    Full Text Available BACKGROUND: A vaccine against schistosomiasis would have a great impact in disease elimination. Sm29 and Sm22.6 are two parasite tegument proteins which represent promising antigens to compose a vaccine. These antigens have been associated with resistance to infection and reinfection in individuals living in endemic area for the disease and induced partial protection when evaluated in immunization trials using naïve mice. METHODOLOGY/PRINCIPALS FINDINGS: In this study we evaluated rSm29 and rSm22.6 ability to induce protection in Balb/c mice that had been previously infected with S. mansoni and further treated with Praziquantel. Our results demonstrate that three doses of the vaccine containing rSm29 were necessary to elicit significant protection (26%-48%. Immunization of mice with rSm29 induced a significant production of IL-2, IFN-γ, IL-17, IL-4; significant production of specific antibodies; increased percentage of CD4+ central memory cells in comparison with infected and treated saline group and increased percentage of CD4+ effector memory cells in comparison with naïve Balb/c mice immunized with rSm29. On the other hand, although immunization with Sm22.6 induced a robust immune response, it failed to induce protection. CONCLUSION/SIGNIFICANCE: Our results demonstrate that rSm29 retains its ability to induce protection in previously infected animals, reinforcing its potential as a vaccine candidate.

  20. Attenuation of γ-aminobutyric acid (GABA) transaminase activity contributes to GABA increase in the cerebral cortex of mice exposed to β-cypermethrin.

    Science.gov (United States)

    Han, Y; Cao, D; Li, X; Zhang, R; Yu, F; Ren, Y; An, L

    2014-03-01

    The current study investigated the γ-aminobutyric acid (GABA) levels and GABA metabolic enzymes (GABA transaminase (GABA(T)) and glutamate decarboxylase (GAD)) activities at 2 and 4 h after treatment, using a high-performance liquid chromatography with ultraviolet detectors and colorimetric assay, in the cerebral cortex of mice treated with 20, 40 or 80 mg/kg β-cypermethrin by a single oral gavage, with corn oil as vehicle control. In addition, GABA protein (4 h after treatment), GABA(T) protein (2 h after treatment) and GABA receptors messenger RNA (mRNA) expression were detected by immunohistochemistry, Western blot and real-time quantitative reverse transcriptase polymerase chain reaction, respectively. β-Cypermethrin (80 mg/kg) significantly increased GABA levels in the cerebral cortex of mice, at both 2 and 4 h after treatment, compared with the control. Also, GABA immunohistochemistry results suggested that the number of positive granules was increased in the cerebral cortex of mice 4 h after exposure to 80 mg/kg β-cypermethrin when compared with the control. Furthermore, the results also showed that GABA(T) activity detected was significantly decreased in the cerebral cortex of mice 2 h after β-cypermethrin administration (40 or 80 mg/kg). No significant changes were found in GAD activity, or the expression of GABA(T) protein and GABAB receptors mRNA, in the cerebral cortex of mice, except that 80 mg/kg β-cypermethrin caused a significant decrease, compared with the vehicle control, in GABAA receptors mRNA expression 4 h after administration. These results suggested that attenuated GABA(T) activity induced by β-cypermethrin contributed to increased GABA levels in the mouse brain. The downregulated GABAA receptors mRNA expression is most likely a downstream event.

  1. The influence of sex on life shortening and tumor induction in CBA/Cne mice exposed to x rays or fission neutrons

    International Nuclear Information System (INIS)

    An experimental study of male and female CBA/Cne mice was set up at Casaccia primarily to investigate the influence of sex on long-term survival and tumor induction after exposure to high- and low-LET radiation. Mice were whole-body-irradiated at 3 months of age with fission-neutron doses of 0.1, 0.2, 0.4, 0.8, 1.2 and 1.8 Gy at the RSV-TAPIRO reactor (mean neutron energy 0.4 MeV, in terms of kerma, yD = 51.5 KeV/μm), or with 250 KVp X-ray doses of 1, 3, 5 and 7 Gy. Control and irradiated animals were then followed for their entire life span. As a general finding, male CBA/Cne mice appear more susceptible to tumori-genesis than females. In particular, the incidences of induced acute myeloid leukemia and malignant lymphomas are significant only in male mice. Benign and malignant solid tumors of many types are observed in mice of both sexes, the most frequent being in the lung, liver and ovary. However, evidence for a radiation response is limited to the case of Harderian gland neoplasms. In addition, a comparison of the observed frequency of all irradiated compared to unirradiated animals bearing solid tumors shows that the total tumor occurrence is not altered markedly by radiation exposure. A decrease in survival time is observed for both sexes and radiation types and correlates well with increasing dose. Moreover, both sex and radiation quality appear to influence the life shortening. A similar dose dependence of survival time is found when tumor-free animals alone are considered, suggesting a non-specific component of life-shortening. 18 refs., 3 figs., 5 tabs

  2. Palmoplantar keratoderma in Slurp2-deficient mice

    Science.gov (United States)

    Allan, Christopher M.; Procaccia, Shiri; Tran, Deanna; Tu, Yiping; Barnes, Richard H.; Larsson, Mikael; Allan, Bernard B.; Young, Lorraine C.; Hong, Cynthia; Tontonoz, Peter; Fong, Loren G.; Young, Stephen G.; Beigneux, Anne P.

    2015-01-01

    SLURP1, a member of the Ly6 protein family, is secreted by suprabasal keratinocytes. Mutations in SLURP1 cause a palmoplantar keratoderma (PPK) known as mal de Meleda. Another secreted Ly6 protein, SLURP2, is encoded by a gene located ~20 kb downstream from SLURP1. SLURP2 is produced by suprabasal keratinocytes. To investigate the importance of SLURP2, we first examined Slurp2 knockout mice in which exon 2–3 sequences had been replaced with lacZ and neo cassettes. Slurp2−/− mice exhibited hyperkeratosis on the volar surface of the paws (i.e., PPK), increased keratinocyte proliferation, and an accumulation of lipid droplets in the stratum corneum. They also exhibited reduced body weight and hind limb clasping. These phenotypes are very similar to those of Slurp1−/− mice. To solidify a link between Slurp2 deficiency and PPK and to be confident that the disease phenotypes in Slurp2−/− mice were not secondary to the effects of the lacZ and neo cassettes on Slurp1 expression, we created a new line of Slurp2 knockout mice (Slurp2X−/−) in which Slurp2 was inactivated with a simple nonsense mutation. Slurp2X−/− mice exhibited the same disease phenotypes. Thus, Slurp2 deficiency and Slurp1 deficiencies cause the same disease phenotypes. PMID:26967477

  3. Effects of Duloxetine Treatment on Cognitive Flexibility and BDNF Expression in the mPFC of Adult Male Mice Exposed to Social Stress during Adolescence

    Science.gov (United States)

    Xu, Hang; Zhang, Yu; Zhang, Fan; Yuan, San-na; Shao, Feng; Wang, Weiwen

    2016-01-01

    Early stress is a significant risk factor for the onset of mood disorders such as depression during adulthood. Impairments in cognitive flexibility mediated by prefrontal cortex (PFC) dysfunction are increasingly recognized as important etiological and pathological factors in the development of depression. Our previous study demonstrated that social defeat stress during early adolescence produced delayed deficits in cognitive flexibility in adult mice. The potential molecular mechanisms underlying these long-term consequences remain unclear. One candidate molecule is brain-derived neurotrophic factor (BDNF), which plays a vital role in neural development and synaptic plasticity. In this study, we initially examined the effects of adolescent social stress on cognitive flexibility and PFC BDNF expression within a week after the last stress exposure and 6 weeks later during adulthood. Adolescent (PND 28) male mice were subjected to stress or control manipulation for 10 days. The attentional set-shifting task (AST) was used to assess cognitive flexibility. Levels of BDNF mRNA and protein in the PFC were examined after behavioral testing. The results demonstrated that previously stressed mice exhibited delayed extra-dimensional set-shifting deficits in AST when tested as adults but not when tested as adolescents. Consistent with the cognitive alterations, adolescent stress induced dynamic alterations in BDNF expression in the medial PFC (mPFC), with a transient increase observed shortly after the stress, followed by a decrease 6 weeks later during adulthood. Next, we further determined the effects of chronic treatment with the antidepressant duloxetine during early adulthood on cognitive and molecular alterations induced by adolescent stress. Compared with the controls, duloxetine treatment reversed the cognitive deficits and increased the BDNF protein expression in the mPFC during adulthood in previously stressed mice. These findings demonstrated that BDNF expression

  4. Investigation of the neuroprotective action of saffron (Crocus sativus L.) in aluminum-exposed adult mice through behavioral and neurobiochemical assessment.

    Science.gov (United States)

    Linardaki, Zacharoula I; Orkoula, Malvina G; Kokkosis, Alexandros G; Lamari, Fotini N; Margarity, Marigoula

    2013-02-01

    In the present study, the possible reversal effects of saffron against established aluminum (Al)-toxicity in adult mice, were investigated. Control, Al-treated (50 mg AlCl(3)/kg/day diluted in the drinking water for 5 weeks) and Al+saffron (Al-treatment as previously plus 60 mg saffron extract/kg/day intraperitoneally for the last 6 days), groups of male Balb-c mice were used. We assessed learning/memory, the activity of acetylcholinesterase [AChE, salt-(SS)/detergent-soluble(DS) isoforms], butyrylcholinesterase (BuChE, SS/DS isoforms), monoamine oxidase (MAO-A, MAO-B), the levels of lipid peroxidation (MDA) and reduced glutathione (GSH), in whole brain and cerebellum. Brain Al was determined by atomic absorption spectrometry, while, for the first time, crocetin, the main active metabolite of saffron, was determined in brain after intraperitoneal saffron administration by HPLC. Al intake caused memory impairment, significant decrease of AChE and BuChE activity, activation of brain MAO isoforms but inhibition of cerebellar MAO-B, significant elevation of brain MDA and significant reduction of GSH content. Although saffron extract co-administration had no effect on cognitive performance of mice, it reversed significantly the Al-induced changes in MAO activity and the levels of MDA and GSH. AChE activity was further significantly decreased in cerebral tissues of Al+saffron group. The biochemical changes support the neuroprotective potential of saffron under toxicity.

  5. [Induction of DNA damage in blood leucocytes and of cytogenetic injuries in bone marrow polychromatic erythrocytes in mice exposed to low-LET and high-LET radiation and in their progeny].

    Science.gov (United States)

    Kuznetsova, E A; Zaichkina, S I; Sirota, N P; Abdullaev, S A; Rozanova, O M; Aptikaeva, G F; Sorokina, S S; Romanchenko, S P; Smirnova, E N

    2014-01-01

    The present work was aimed at studying the molecular and cellular levels of the response of the hematopoietic system in mice and their progeny to the action of low-LET and high-LET radiation at different times after exposure. The damage to the genome at the molecular level was assessed by the comet assay in peripheral blood leucocytes, whereas at the cellular level it was estimated by means of the micronuclear test in the marrow cells, after exposure of mice to X-radiation of 1, 3 and 5 Gy and to a high-LET low-intensity radiation at thedoses of 0.14 and 0.35 Gy, as well as to a combined effect of these types of radiation. When accessing the level of the DNA damage to individual cells by the comet assay, we also used, apart from a commonly accepted parameter %TDNA, additional characteristics: the proportions of leucocytes with an intact and highly fragmented DNA. Using these parameters, we detected the changes characterizing the dynamics of the leukocyte population in mouse blood at different times after the action of X-ray and high-LET radiation. It was found that: (1) the DNA damage increases with the dose of high-LET radiation; (2) the level of damage in the progeny of the animals exposed to high-LET radiation does not differ from that in unirradiated animals both at the molecular and cytogenetic levels; and (3) a decrease in the radiosensitivity of the progeny of the mice exposed to high-LET radiation at a dose of 0.35 Gy makes itself evident only at the molecular level, which may point to the possible transgeneration transmission of genomic lesions. PMID:25775822

  6. 次声导致小鼠脑损伤的生化指标研究%The Change of GFAP in the brains of mice exposed to infrasound

    Institute of Scientific and Technical Information of China (English)

    牟翔; 陈景藻; 李玲; 邱建勇; 贾克勇

    2001-01-01

    Objective To explore the change of GFAP in the brains of mice exposed to infrasound. Methods mice were exposed to infrasound of 16Hz with intensity of 90dB for 1,7, 14, 21 and 28 days .Immunohistochemical technique was exployed to detect the expression of GFAP. Results GFAP immunoreactive cells presented mainly hippocampus, cortex and hypothalamus et al after exposed for certain times. The number of the GFAP immunoreactive cells grew as increasing the time of infrasound action.Conclusion These regions are sensitive to infrasound and effects of infrasound can increase expression of the GFAP.%目的研究次声影响小鼠脑组织的生化指标。方法BALB/C小鼠暴露于16Hz、声压90dB次声,2h/d,分别作用1、7、14、21和28d后,采用免疫组织化学方法观察小鼠脑中胶质原纤维酸性蛋白(GFAP)的表达。结果次声作用一定时间后,GFAP阳性星形细胞主要分布在海马、皮质、下丘脑等脑区,且随次声作用天数增加,GFAP阳性星形细胞数目增多。结论GFAF阳性细胞的增加可以证实次声对以上这些脑区有不同程度的损伤。

  7. Voluntary wheel-running attenuates insulin and weight gain and affects anxiety-like behaviors in C57BL6/J mice exposed to a high-fat diet.

    Science.gov (United States)

    Hicks, Jasmin A; Hatzidis, Aikaterini; Arruda, Nicole L; Gelineau, Rachel R; De Pina, Isabella Monteiro; Adams, Kenneth W; Seggio, Joseph A

    2016-09-01

    It is widely accepted that lifestyle plays a crucial role on the quality of life in individuals, particularly in western societies where poor diet is correlated to alterations in behavior and the increased possibility of developing type-2 diabetes. While exercising is known to produce improvements to overall health, there is conflicting evidence on how much of an effect exercise has staving off the development of type-2 diabetes or counteracting the effects of diet on anxiety. Thus, this study investigated the effects of voluntary wheel-running access on the progression of diabetes-like symptoms and open field and light-dark box behaviors in C57BL/6J mice fed a high-fat diet. C57BL/6J mice were placed into either running-wheel cages or cages without a running-wheel, given either regular chow or a high-fat diet, and their body mass, food consumption, glucose tolerance, insulin and c-peptide levels were measured. Mice were also exposed to the open field and light-dark box tests for anxiety-like behaviors. Access to a running-wheel partially attenuated the obesity and hyperinsulinemia associated with high-fat diet consumption in these mice, but did not affect glucose tolerance or c-peptide levels. Wheel-running strongly increased anxiety-like and decreased explorative-like behaviors in the open field and light-dark box, while high-fat diet consumption produced smaller increases in anxiety. These results suggest that voluntary wheel-running can assuage some, but not all, of the physiological problems associated with high-fat diet consumption, and can modify anxiety-like behaviors regardless of diet consumed. PMID:27154535

  8. Increased accumulation of neutrophils and decreased fibrosis in the lung of NADPH oxidase-deficient C57BL/6 mice exposed to carbon nanotubes

    International Nuclear Information System (INIS)

    Single-walled carbon nanotubes (SWCNT) have been introduced into a large number of new technologies and consumer products. The combination of their exceptional features with very broad applications raised concerns regarding their potential health effects. The prime target for SWCNT toxicity is believed to be the lung where exposure may occur through inhalation, particularly in occupational settings. Our previous work has demonstrated that SWCNT cause robust inflammatory responses in rodents with very early termination of the acute phase and rapid onset of chronic fibrosis. Timely elimination of polymorphonuclear neutrophils (PMNs) through apoptosis and their subsequent clearance by macrophages is a necessary stage in the resolution of pulmonary inflammation whereby NADPH oxidase contributes to control of apoptotic cell death and clearance of PMNs. Thus, we hypothesized that NADPH oxidase may be an important regulator of the transition from the acute inflammation to the chronic fibrotic stage in response to SWCNT. To experimentally address the hypothesis, we employed NADPH oxidase-deficient mice which lack the gp91phox subunit of the enzymatic complex. We found that NADPH oxidase null mice responded to SWCNT exposure with a marked accumulation of PMNs and elevated levels of apoptotic cells in the lungs, production of pro-inflammatory cytokines, decreased production of the anti-inflammatory and pro-fibrotic cytokine, TGF-β, and significantly lower levels of collagen deposition, as compared to C57BL/6 control mice. These results demonstrate a role for NADPH oxidase-derived reactive oxygen species in determining course of pulmonary response to SWCNT

  9. Recovery of behavioral changes and compromised white matter in C57BL/6 mice exposed to cuprizone: Effects of antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Haiyun eXu

    2011-07-01

    Full Text Available Recent animal and human studies have suggested that the cuprizone (CPZ, a copper chelator-feeding C57BL/6 mouse may be used as an animal model of schizophrenia. The goals of this study were to see the recovery processes of CPZ-induced behavioral changes and damaged white matter and to examine possible effects of antipsychotic drugs on the recovery processes. Mice were fed a CPZ-containing diet for five weeks then returned to normal food for three weeks, during which period mice were treated with different antipsychotic drugs. Various behaviors were measured at the end of CPZ-feeding phase as well as on the 14th and 21st days after CPZ-withdrawal. The damage to and recovery status of white matter in the brains of mice were examined. Dietary CPZ resulted in white matter damage and behavioral abnormalities in the elevated plus-maze, social interaction and Y-maze test. Elevated plus-maze performance recovered to normal range within two weeks after CPZ withdrawal. But, alterations in social interaction showed no recovery. Antipsychotics did not alter animals’ behavior in either of these tests during the recovery period. Altered performance in the Y-maze showed some recovery in the vehicle group; atypical antipsychotics, but not haloperidol, significantly promoted this recovery process. The recovery of damaged white matter was incomplete during the recovery period. None of the drugs significantly promoted the recovery of damaged white matter. These results suggest that CPZ-induced white matter damage and social interaction deficit may be resistant to the antipsychotic treatment employed in this study. They are in good accordance with the clinical observations that positive symptoms in schizophrenic patients respond well to antipsychotic drugs while social dysfunction is usually intractable.

  10. Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD: implication for COPD-associated neuropathogenesis.

    Directory of Open Access Journals (Sweden)

    Isaac K Sundar

    Full Text Available The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d, sub-chronic (10 d or chronic (6 mo CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD.

  11. Antidepressant-Like Behavioral, Anatomical, and Biochemical Effects of Petroleum Ether Extract from Maca (Lepidium meyenii) in Mice Exposed to Chronic Unpredictable Mild Stress

    OpenAIRE

    Ai, Zhong; Cheng, Ai-Fang; Yu, Yuan-Tao; Yu, Long-Jiang; Jin, Wenwen

    2014-01-01

    Maca has been consumed as a medical food in Peru for thousands of years, and exerts anxiolytic and antidepressant effects. Our present study aimed to evaluate the behavior and anatomical and biochemical effects of petroleum ether extract from maca (ME) in the chronic unpredictable mild stress (CUMS) model of depression in mice. Three different doses of maca extract (125, 250, and 500 mg/kg) were orally administrated in the six-week CUMS procedure. Fluoxetine (10 mg/kg) was used as a positive ...

  12. HIPPOCAMPAL SPINE-ASSOCIATED Rap-SPECIFIC GTPase-ACTIVATING PROTEIN INDUCES ENHANCEMENT OF LEARNING AND MEMORY IN POSTNATALLY HYPOXIA-EXPOSED MICE

    OpenAIRE

    Lu, X.-J.; Chen, X. -Q; Weng, J.; Zhang, H.-Y.; PAK, D. T.; LUO, J.-H.; DU, J.-Z.

    2009-01-01

    Spine-associated Rap-specific GTPase-activating protein (SPAR) is a postsynaptic protein that forms a complex with postsynaptic density (PSD)-95 and N-methyl-D-aspartate receptors (NMDARs), and morphologically regulates dendritic spines. Mild intermittent hypoxia (IH, 16.0% O2, 4 h/day for 4 weeks) is known to markedly enhance spatial learning and memory in postnatal developing mice. Here, we report that this effect is correlated with persistent increases in SPAR expression as well as long-te...

  13. Different behavioral effect dose–response profiles in mice exposed to two-carbon chlorinated hydrocarbons: Influence of structural and physical properties

    Energy Technology Data Exchange (ETDEWEB)

    Umezu, Toyoshi, E-mail: umechan2@nies.go.jp; Shibata, Yasuyuki, E-mail: yshibata@nies.go.jp

    2014-09-01

    The present study aimed to clarify whether dose–response profiles of acute behavioral effects of 1,2-dichloroethane (DCE), 1,1,1-trichloroethane (TCE), trichloroethylene (TRIC), and tetrachloroethylene (PERC) differ. A test battery involving 6 behavioral endpoints was applied to evaluate the effects of DCE, TCE, TRIC, and PERC in male ICR strain mice under the same experimental conditions. The behavioral effect dose–response profiles of these compounds differed. Regression analysis was used to evaluate the relationship between the dose–response profiles and structural and physical properties of the compounds. Dose–response profile differences correlated significantly with differences in specific structural and physical properties. These results suggest that differences in specific structural and physical properties of DCE, TCE, TRIC, and PERC are responsible for differences in behavioral effects that lead to a variety of dose–response profiles. - Highlights: • We examine effects of 4 chlorinated hydrocarbons on 6 behavioral endpoints in mice. • The behavioral effect dose–response profiles for the 4 compounds are different. • We utilize regression analysis to clarify probable causes of the different profiles. • The compound's physicochemical properties probably produce the different profiles.

  14. Antidepressant-like effects of sodium butyrate and its possible mechanisms of action in mice exposed to chronic unpredictable mild stress.

    Science.gov (United States)

    Sun, Jing; Wang, Fangyan; Hong, Guangliang; Pang, Mengqi; Xu, Hailing; Li, Haixiao; Tian, Feng; Fang, Renchi; Yao, Ye; Liu, Jiaming

    2016-04-01

    Sodium butyrate (NaB) has exhibited neuroprotective activity. This study aimed to explore that NaB exerts beneficial effects on chronic unpredictable mild stress (CUMS)-induced depression-like behaviors and its possible mechanisms. The behavioral tests including sucrose preference test (SPT), open field test (OFT), tail suspension test (TST) and forced swimming test (FST) were to evaluate the antidepressant effects of NaB. Then changes of Nissl's body in the hippocampus, brain serotonin (5-HT) concentration, brain-derived neurotrophic factor (BDNF) and tight junctions (TJs) proteins level were assessed to explore the antidepressant mechanisms. Our results showed that CUMS caused significant depression-like behaviors, neuropathological changes, and decreased brain 5-HT concentration, TJs protein levels and BDNF expression in the hippocampus. However, NaB treatment significantly ameliorated behavioral deficits of the CUMS-induced mice, increased 5-HT concentration, increased BDNF expression, and up-regulated Occludin and zonula occludens-1(ZO-1) protein levels in the hippocampus, which demonstrated that NaB could partially restore CUMS-induced blood-brain barrier (BBB) impairments. Besides, the pathologic changes were alleviated. In conclusion, these results demonstrated that NaB significantly improved depression-like behaviors in CUMS-induced mice and its antidepressant actions might be related with, at least in part, the increasing brain 5-HT concentration and BDNF expression and restoring BBB impairments. PMID:26957230

  15. Investigation into Variation of Endogenous Metabolites in Bone Marrow Cells and Plasma in C3H/He Mice Exposed to Benzene

    Directory of Open Access Journals (Sweden)

    Rongli Sun

    2014-03-01

    Full Text Available Benzene is identified as a carcinogen. Continued exposure of benzene may eventually lead to damage to the bone marrow, accompanied by pancytopenia, aplastic anemia or leukemia. This paper explores the variations of endogenous metabolites to provide possible clues for the molecular mechanism of benzene-induced hematotoxicity. Liquid chromatography coupled with time of flight-mass spectrometry (LC-TOF-MS and principal component analysis (PCA was applied to investigate the variation of endogenous metabolites in bone marrow cells and plasma of male C3H/He mice. The mice were injected subcutaneously with benzene (0, 300, 600 mg/day once daily for seven days. The body weights, relative organ weights, blood parameters and bone marrow smears were also analyzed. The results indicated that benzene caused disturbances in the metabolism of oxidation of fatty acids and essential amino acids (lysine, phenylalanine and tyrosine in bone marrow cells. Moreover, fatty acid oxidation was also disturbed in plasma and thus might be a common disturbed metabolic pathway induced by benzene in multiple organs. This study aims to investigate the underlying molecular mechanisms involved in benzene hematotoxicity, especially in bone marrow cells.

  16. Remarkable induction of UV-signature mutations at the 3'-cytosine of dipyrimidine sites except at 5'-TCG-3' in the UVB-exposed skin epidermis of xeroderma pigmentosum variant model mice.

    Science.gov (United States)

    Ikehata, Hironobu; Chang, Yumin; Yokoi, Masayuki; Yamamoto, Masayuki; Hanaoka, Fumio

    2014-10-01

    The human POLH gene is responsible for the variant form of xeroderma pigmentosum (XP-V), a genetic disease highly susceptible to cancer on sun-exposed skin areas, and encodes DNA polymerase η (polη), which is specialized for translesion DNA synthesis (TLS) of UV-induced DNA photolesions. We constructed polη-deficient mice transgenic with lacZ mutational reporter genes to study the effect of Polh null mutation (Polh(-/-)) on mutagenesis in the skin after UVB irradiation. UVB induced lacZ mutations with remarkably higher frequency in the Polh(-/-) epidermis and dermis than in the wild-type (Polh(+/+)) and heterozygote. DNA sequences of a hundred lacZ mutants isolated from the epidermis of four UVB-exposed Polh(-/-) mice were determined and compared with mutant sequences from irradiated Polh(+)(/)(+) mice. The spectra of the mutations in the two genotypes were both highly UV-specific and dominated by C→T transitions at dipyrimidines, namely UV-signature mutations. However, sequence preferences of the occurrence of UV-signature mutations were quite different between the two genotypes: the mutations occurred at a higher frequency preferentially at the 5'-TCG-3' sequence context than at the other dipyrimidine contexts in the Polh(+/+) epidermis, whereas the mutations were induced remarkably and exclusively at the 3'-cytosine of almost all dipyrimidine contexts with no preference for 5'-TCG-3' in the Polh(-/-) epidermis. In addition, in Polh(-/-) mice, a small but remarkable fraction of G→T transversions was also observed exclusively at the 3'-cytosine of dipyrimidine sites, strongly suggesting that these transversions resulted not from oxidative damage but from UV photolesions. These results would reflect the characteristics of the error-prone TLS functioning in the bypass of UV photolesions in the absence of polη, which would be mediated by mechanisms based on the two-step model of TLS. On the other hand, the deamination model would explain well the mutation

  17. Remarkable induction of UV-signature mutations at the 3'-cytosine of dipyrimidine sites except at 5'-TCG-3' in the UVB-exposed skin epidermis of xeroderma pigmentosum variant model mice.

    Science.gov (United States)

    Ikehata, Hironobu; Chang, Yumin; Yokoi, Masayuki; Yamamoto, Masayuki; Hanaoka, Fumio

    2014-10-01

    The human POLH gene is responsible for the variant form of xeroderma pigmentosum (XP-V), a genetic disease highly susceptible to cancer on sun-exposed skin areas, and encodes DNA polymerase η (polη), which is specialized for translesion DNA synthesis (TLS) of UV-induced DNA photolesions. We constructed polη-deficient mice transgenic with lacZ mutational reporter genes to study the effect of Polh null mutation (Polh(-/-)) on mutagenesis in the skin after UVB irradiation. UVB induced lacZ mutations with remarkably higher frequency in the Polh(-/-) epidermis and dermis than in the wild-type (Polh(+/+)) and heterozygote. DNA sequences of a hundred lacZ mutants isolated from the epidermis of four UVB-exposed Polh(-/-) mice were determined and compared with mutant sequences from irradiated Polh(+)(/)(+) mice. The spectra of the mutations in the two genotypes were both highly UV-specific and dominated by C→T transitions at dipyrimidines, namely UV-signature mutations. However, sequence preferences of the occurrence of UV-signature mutations were quite different between the two genotypes: the mutations occurred at a higher frequency preferentially at the 5'-TCG-3' sequence context than at the other dipyrimidine contexts in the Polh(+/+) epidermis, whereas the mutations were induced remarkably and exclusively at the 3'-cytosine of almost all dipyrimidine contexts with no preference for 5'-TCG-3' in the Polh(-/-) epidermis. In addition, in Polh(-/-) mice, a small but remarkable fraction of G→T transversions was also observed exclusively at the 3'-cytosine of dipyrimidine sites, strongly suggesting that these transversions resulted not from oxidative damage but from UV photolesions. These results would reflect the characteristics of the error-prone TLS functioning in the bypass of UV photolesions in the absence of polη, which would be mediated by mechanisms based on the two-step model of TLS. On the other hand, the deamination model would explain well the mutation

  18. L-histidine provokes a state-dependent memory retrieval deficit in mice re-exposed to the elevated plus-maze

    Directory of Open Access Journals (Sweden)

    K.R. Serafim

    2010-01-01

    Full Text Available The effects of L-histidine (LH on anxiety and memory retrieval were investigated in adult male Swiss Albino mice (weight 30-35 g using the elevated plus-maze. The test was performed on two consecutive days: trial 1 (T1 and trial 2 (T2. In T1, mice received an intraperitoneal injection of saline (SAL or LH before the test and were then injected again and retested 24 h later. LH had no effect on anxiety at the dose of 200 mg/kg since there was no difference between the SAL-SAL and LH-LH groups at T1 regarding open-arm entries (OAE and open-arm time (OAT (mean ± SEM; OAE: 4.0 ± 0.71, 4.80 ± 1.05; OAT: 40.55 ± 9.90, 51.55 ± 12.10, respectively; P > 0.05, Kruskal-Wallis test, or at the dose of 500 mg/kg (OAE: 5.27 ± 0.73, 4.87 ± 0.66; OAT: 63.93 ± 11.72, 63.58 ± 10.22; P > 0.05, Fisher LSD test. At T2, LH-LH animals did not reduce open-arm activity (OAE and OAT at the dose of 200 mg/kg (T1: 4.87 ± 0.66, T2: 5.47 ± 1.05; T1: 63.58 ± 10.22; T2: 49.01 ± 8.43 for OAE and OAT, respectively; P > 0.05, Wilcoxon test or at the dose of 500 mg/kg (T1: 4.80 ± 1.60, T2: 4.70 ± 1.04; T1: 51.55 ± 12.10, T2: 43.88 ± 10.64 for OAE and OAT, respectively; P > 0.05, Fisher LSD test, showing an inability to evoke memory 24 h later. These data suggest that LH does not act on anxiety but does induce a state-dependent memory retrieval deficit in mice.

  19. L-histidine provokes a state-dependent memory retrieval deficit in mice re-exposed to the elevated plus-maze.

    Science.gov (United States)

    Serafim, K R; Kishi, M; Canto-de-Souza, A; Mattioli, R

    2010-01-01

    The effects of L-histidine (LH) on anxiety and memory retrieval were investigated in adult male Swiss Albino mice (weight 30-35 g) using the elevated plus-maze. The test was performed on two consecutive days: trial 1 (T1) and trial 2 (T2). In T1, mice received an intraperitoneal injection of saline (SAL) or LH before the test and were then injected again and retested 24 h later. LH had no effect on anxiety at the dose of 200 mg/kg since there was no difference between the SAL-SAL and LH-LH groups at T1 regarding open-arm entries (OAE) and open-arm time (OAT) (mean +/- SEM; OAE: 4.0 +/- 0.71, 4.80 +/- 1.05; OAT: 40.55 +/- 9.90, 51.55 +/- 12.10, respectively; P > 0.05, Kruskal-Wallis test), or at the dose of 500 mg/kg (OAE: 5.27 +/- 0.73, 4.87 +/- 0.66; OAT: 63.93 +/- 11.72, 63.58 +/- 10.22; P > 0.05, Fisher LSD test). At T2, LH-LH animals did not reduce open-arm activity (OAE and OAT) at the dose of 200 mg/kg (T1: 4.87 +/- 0.66, T2: 5.47 +/- 1.05; T1: 63.58 +/- 10.22; T2: 49.01 +/- 8.43 for OAE and OAT, respectively; P > 0.05, Wilcoxon test) or at the dose of 500 mg/kg (T1: 4.80 +/- 1.60, T2: 4.70 +/- 1.04; T1: 51.55 +/- 12.10, T2: 43.88 +/- 10.64 for OAE and OAT, respectively; P > 0.05, Fisher LSD test), showing an inability to evoke memory 24 h later. These data suggest that LH does not act on anxiety but does induce a state-dependent memory retrieval deficit in mice.

  20. Effects of ginsenoside Rb1 on behaviors and memory of lead-exposed mice%人参皂苷Rb1对染铅小鼠行为记忆的影响

    Institute of Scientific and Technical Information of China (English)

    刘微; 王艳春; 范红艳; 沈楠; 任旷

    2009-01-01

    AIM: To explore the effects of ginsenoside Rb1 on the blood lead levels and behaviors of lesd-exposed mice. METHODS: Lead-exposed models of mice were established with lead acetate drinking water, and different doses of ginsenoside Rb1 (100, 50, 25 mg/kg) were fed. Morris water maze test was employed to evaluate the effects of ginsenoside Rb1 on the learning and memory functions of the lead-exposed mice. The blood lead content and the activity of superoxide dismutase(SOD) and nitric oxide synthase ( NOS ) were detected. RESULTS : Morris water maze test showed that the searching distance and the latent periods were extended in lead-exposure mice. The activity of SOD decreased while the activity of NOS increased compared with those in control group (P<0.05 or P<0.01). Ginsenoside Rb1 markedly shortened the searching distance and latent periods, decreased the blood lead content, promoted the activity of SOD, and lowered the activity of NOS (P<0.05 or P<0.01). CONCLUSION: The results suggest that ginsenoside Rb1 reduces the blood lead concentration and alleviates the learning and memory obstacles of lead-expesed mice by restoring the vitality of the antioxidant system.%目的:研究人参皂苷Rb1对染铅小鼠血铅水平及行为记忆的影响.方法:以醋酸铅饮水制备染铅小鼠模型,灌胃给予100,50,25 mg/kg不同剂量的人参皂苷Rb1,采用Mor-ris水迷宫实验评价人参皂苷Rb1对小鼠学习记忆的影响,并测定小鼠血中铅含量、脑组织中超氧化物歧化酶(SOD)活性和一氧化氮合酶(NOS)活性.结果:染铅可导致小鼠水迷宫实验搜索路程及潜伏期延长;SOD活性降低及NOS活性升高,与空白对照组相比较差异显著(P<0.05或P<0.01).给予人参皂苷Rb1后,染铅小鼠水迷宫实验搜索路程及潜伏期缩短;血铅含量降低;SOD活性升高;NOS活性降低,与染铅模型组相比较差异显著(P<0.05或P<0.01).结论:人参皂苷Rb1能明显降低血铅浓度;通过提高染铅小鼠体内

  1. Morphofunctional evaluation of human skin preserved in glycerol and exposed to gamma radiation: a study in athymic mice; Avaliacao morfofuncional de pele humana conservada em glicerol e submetida a radiacao gama: estudo em camundongos atimicos

    Energy Technology Data Exchange (ETDEWEB)

    Bringel, Fabiana de Andrade

    2011-07-01

    Extensive skin lesions expose the body to damaging agents, which makes spontaneous regeneration difficult and, in many cases, leads patient to death. In such cases, if there are no donating areas for autograft, allografts can be used. In this type of graft, tissue is processed in tissue banks, where it can be subjected to radiosterilization. According to in vitro studies, gamma radiation, in doses higher than 25 kGy, induces alterations in skin preserved in glycerol at 85%, reducing the tensile strength of irradiated tissue. Clinical observation also suggests faster integration of such graft with the receptors tissue. In order to assess if the alterations observed in vitro, would compromise in vivo use, transplants of human tissue, irradiated or not, were performed in Nude mice. The skin of the mice was subjected to macroscopic analysis, optical coherence tomography imaging, histological and biomechanical assays. It was possible to conclude that grafts irradiated with 25 kGy promoted greater initial contraction, without alteration of the final dimensions of the repair area, also displaying a faster closing of the wound. Moreover, the use of irradiated grafts (25 and 50 kGy) enabled the formation of a more organized healing process without significant effects on biomechanical properties. (author)

  2. Gene expression profiling in brain of mice exposed to the marine neurotoxin ciguatoxin reveals an acute anti-inflammatory, neuroprotective response

    Directory of Open Access Journals (Sweden)

    Ryan James C

    2010-08-01

    Full Text Available Abstract Background Ciguatoxins (CTXs are polyether marine neurotoxins and potent activators of voltage-gated sodium channels. This toxin is carried by multiple reef-fish species and human consumption of ciguatoxins can result in an explosive gastrointestinal/neurologic illness. This study characterizes the global transcriptional response in mouse brain to a symptomatic dose of the highly toxic Pacific ciguatoxin P-CTX-1 and additionally compares this data to transcriptional profiles from liver and whole blood examined previously. Adult male C57/BL6 mice were injected with 0.26 ng/g P-CTX-1 while controls received only vehicle. Animals were sacrificed at 1, 4 and 24 hrs and transcriptional profiling was performed on brain RNA with Agilent whole genome microarrays. RT-PCR was used to independently validate gene expression and the web tool DAVID was used to analyze gene ontology (GO and molecular pathway enrichment of the gene expression data. Results A pronounced 4°C hypothermic response was recorded in these mice, reaching a minimum at 1 hr and lasting for 8 hrs post toxin exposure. Ratio expression data were filtered by intensity, fold change and p-value, with the resulting data used for time course analysis, K-means clustering, ontology classification and KEGG pathway enrichment. Top GO hits for this gene set included acute phase response and mono-oxygenase activity. Molecular pathway analysis showed enrichment for complement/coagulation cascades and metabolism of xenobiotics. Many immediate early genes such as Fos, Jun and Early Growth Response isoforms were down-regulated although others associated with stress such as glucocorticoid responsive genes were up-regulated. Real time PCR confirmation was performed on 22 differentially expressed genes with a correlation of 0.9 (Spearman's Rho, p Conclusions Many of the genes differentially expressed in this study, in parallel with the hypothermia, figure prominently in protection against

  3. Induction of p53-mediated apoptosis in splenocytes and thymocytes of C57BL/6 mice exposed to perfluorooctane sulfonate (PFOS)

    International Nuclear Information System (INIS)

    Perfluorooctane sulfonate (PFOS) is a persistent environmental contaminant found in human and wildlife tissues. It has been reported that PFOS can cause atrophy of the immune organs and apoptosis of immunocytes in rodents. However, the mechanism behind such cause is still unclear. To understand the model of cell death and its mechanism on lymphoid cells in vivo, we conducted a dose/response experiment in which 4 groups of male adult C57BL/6 mice (12 mice per group) were dosed daily by oral gavage with PFOS at 0, 0.0167, 0.0833, or 0.8333 mg/kg/day, yielding targeted Total Administered Dose (TAD) of 0, 1, 5, or 50 mg PFOS/kg, respectively, over 60 days. The results showed that spleen and thymus weight were significantly reduced in the highest PFOS-dose-group (TAD 50 mg PFOS/kg) compared to the control group, whereas liver weight was significantly increased. We analyzed the cell death via apoptosis with an annexin-V/propidium iodide assay by flow cytometry, and observed that both the percentage of apoptosis and the expression of the pro-apoptotic proteins p53 in splenocytes and thymocytes increased in a dose-related manner after PFOS treatment. We also observed that PFOS induced p53-dependent apoptosis through the cooperation between the Bcl-xl down regulation without changing the Bcl-2 and Bax expression. The down regulation of Bcl-xl was strongly indicating mitochondrial involvement in apoptosis. It is confirmed by the release of cytochrome c and activation of caspase-3. All of these findings establish an important role of p53 and mitochondrial function in PFOS induced toxic environment in the host. -- Highlights: ► PFOS immunotoxicity is caused by induction of apoptosis via the p53 activation. ► PFOS exposure can induce down regulation of Bcl-xl. ► Mitochondria are involved in PFOS-induced apoptosis. ► PFOS exposure can cause the release of cytochrome c and activation of caspase-3.

  4. Induction of p53-mediated apoptosis in splenocytes and thymocytes of C57BL/6 mice exposed to perfluorooctane sulfonate (PFOS)

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Guang-Hui, E-mail: ghdong@mail.cmu.edu.cn [School of Public Health, China Medical University, Shenyang 110001 (China); Wang, Jing [Department of Biostatistics, School of Public Health, Saint Louis University, Saint Louis, MO 63104 (United States); Zhang, Ying-Hua; Liu, Miao-Miao; Wang, Da [School of Public Health, China Medical University, Shenyang 110001 (China); Zheng, Li [Department of Immunology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Jin, Yi-He [School of Public Health, China Medical University, Shenyang 110001 (China); School of Environmental Science and Technology, Dalian University of Technology, Key Laboratory of Industrial Ecology and Environmental Engineering, Ministry of Education, Dalian 116024 (China)

    2012-10-15

    Perfluorooctane sulfonate (PFOS) is a persistent environmental contaminant found in human and wildlife tissues. It has been reported that PFOS can cause atrophy of the immune organs and apoptosis of immunocytes in rodents. However, the mechanism behind such cause is still unclear. To understand the model of cell death and its mechanism on lymphoid cells in vivo, we conducted a dose/response experiment in which 4 groups of male adult C57BL/6 mice (12 mice per group) were dosed daily by oral gavage with PFOS at 0, 0.0167, 0.0833, or 0.8333 mg/kg/day, yielding targeted Total Administered Dose (TAD) of 0, 1, 5, or 50 mg PFOS/kg, respectively, over 60 days. The results showed that spleen and thymus weight were significantly reduced in the highest PFOS-dose-group (TAD 50 mg PFOS/kg) compared to the control group, whereas liver weight was significantly increased. We analyzed the cell death via apoptosis with an annexin-V/propidium iodide assay by flow cytometry, and observed that both the percentage of apoptosis and the expression of the pro-apoptotic proteins p53 in splenocytes and thymocytes increased in a dose-related manner after PFOS treatment. We also observed that PFOS induced p53-dependent apoptosis through the cooperation between the Bcl-xl down regulation without changing the Bcl-2 and Bax expression. The down regulation of Bcl-xl was strongly indicating mitochondrial involvement in apoptosis. It is confirmed by the release of cytochrome c and activation of caspase-3. All of these findings establish an important role of p53 and mitochondrial function in PFOS induced toxic environment in the host. -- Highlights: ► PFOS immunotoxicity is caused by induction of apoptosis via the p53 activation. ► PFOS exposure can induce down regulation of Bcl-xl. ► Mitochondria are involved in PFOS-induced apoptosis. ► PFOS exposure can cause the release of cytochrome c and activation of caspase-3.

  5. Antidepressant-like behavioral, anatomical, and biochemical effects of petroleum ether extract from maca (Lepidium meyenii) in mice exposed to chronic unpredictable mild stress.

    Science.gov (United States)

    Ai, Zhong; Cheng, Ai-Fang; Yu, Yuan-Tao; Yu, Long-Jiang; Jin, Wenwen

    2014-05-01

    Maca has been consumed as a medical food in Peru for thousands of years, and exerts anxiolytic and antidepressant effects. Our present study aimed to evaluate the behavior and anatomical and biochemical effects of petroleum ether extract from maca (ME) in the chronic unpredictable mild stress (CUMS) model of depression in mice. Three different doses of maca extract (125, 250, and 500 mg/kg) were orally administrated in the six-week CUMS procedure. Fluoxetine (10 mg/kg) was used as a positive control drug. Maca extract (250 and 500 mg/kg) significantly decreased the duration of immobility time in the tail suspension test. After treatment with maca extract (250 and 500 mg/kg), the granule cell layer in the dentate gyrus appeared thicker. Maca extract (250 and 500 mg/kg) also induced a significant reduction in corticosterone levels in mouse serum. In mouse brain tissue, after six weeks of treatment, noradrenaline and dopamine levels were increased by maca extract, and the activity of reactive oxygen species was significantly inhibited. Serotonin levels were not significantly altered. These results demonstrated that maca extract (250 and 500 mg/kg) showed antidepressant-like effects and was related to the activation of both noradrenergic and dopaminergic systems, as well as attenuation of oxidative stress in mouse brain. PMID:24730393

  6. Long-term effects of environmentally relevant doses of 2,2',4,4',5,5' hexachlorobiphenyl (PCB153 on neurobehavioural development, health and spontaneous behaviour in maternally exposed mice

    Directory of Open Access Journals (Sweden)

    Heegaard Einar

    2011-01-01

    Full Text Available Abstract Background Polychlorinated biphenyls (PCBs are widespread in the environment, human food and breast milk. Seafood is known to contain nutrients beneficial for the normal development and function of the brain, but also contaminants such as PCBs which are neurotoxic. Exposure to non-coplanar PCBs during brain development can disrupt spontaneous behaviour in mice and lead to hyperactive behaviour. Humans are chronically exposed to the highest relative levels of organochlorines in early childhood during brain development, though usually at doses which do not give clinical symptoms of toxicity. This study aimed to elucidate the developmental and behavioural effects of 2,2',4,4',5,5' hexachlorobiphenyl (PCB153 in mice, mimicking human exposure during gestation and lactation. Methods Environmentally relevant doses of PCB153 were added to the experimental diets. Feed concentrations were approximately 0.5, 6.5, and 1500 μg PCB153/kg feed, representing a realistic and a worst case scenario of frequent consumption of contaminated fish. The study also investigated the effects of maternal nutrition, i.e. a standard rodent diet versus a high inclusion of salmon. Mice pups were examined for physical- and reflex development, sensorimotor function and spontaneous behaviour from five days after birth until weaning. A selection of pups were followed until 16 weeks of age and tested for open field behaviour and the acoustic startle response (ASR with prepulse inhibition (PPI. Blood thyroid hormones and liver enzymes, blood lipids and PCB153 content in fat were examined at 16 weeks. Statistical analyses modelled the three way interactions of diet, PCB exposure and litter size on behaviour, using generalized linear models (GLM and linear mixed effect models (LME. The litter was used as a random variable. Non-parametric tests were used for pair wise comparisons of biochemical analyses. Results Litter size consistently influenced pup development and behaviour

  7. Severe iron deficiency anemia in transgenic mice expressing liver hepcidin.

    Science.gov (United States)

    Nicolas, Gaël; Bennoun, Myriam; Porteu, Arlette; Mativet, Sandrine; Beaumont, Carole; Grandchamp, Bernard; Sirito, Mario; Sawadogo, Michèle; Kahn, Axel; Vaulont, Sophie

    2002-04-01

    We recently reported the hemochromatosis-like phenotype observed in our Usf2 knockout mice. In these mice, as in murine models of hemochromatosis and patients with hereditary hemochromatosis, iron accumulates in parenchymal cells (in particular, liver and pancreas), whereas the reticuloendothelial system is spared from this iron loading. We suggested that this phenotypic trait could be attributed to the absence, in the Usf2 knockout mice, of a secreted liver-specific peptide, hepcidin. We conjectured that the reverse situation, namely overexpression of hepcidin, might result in phenotypic traits of iron deficiency. This question was addressed by generating transgenic mice expressing hepcidin under the control of the liver-specific transthyretin promoter. We found that the majority of the transgenic mice were born with a pale skin and died within a few hours after birth. These transgenic animals had decreased body iron levels and presented severe microcytic hypochromic anemia. So far, three mosaic transgenic animals have survived. They were unequivocally identified by physical features, including reduced body size, pallor, hairless and crumpled skin. These pleiotropic effects were found to be associated with erythrocyte abnormalities, with marked anisocytosis, poikylocytosis and hypochromia, which are features characteristic of iron-deficiency anemia. These results strongly support the proposed role of hepcidin as a putative iron-regulatory hormone. The animal models devoid of hepcidin (the Usf2 knockout mice) or overexpressing the peptide (the transgenic mice presented in this paper) represent valuable tools for investigating iron homeostasis in vivo and for deciphering the molecular mechanisms of hepcidin action. PMID:11930010

  8. 碧萝芷对辐射所致小鼠各脏器中自由基的清除作用%Scavenging Effect of Pycnogenol on Free Radicals in Radiation Exposed Mice Organs

    Institute of Scientific and Technical Information of China (English)

    丁翔; 强亦忠; 王利利; 程跃进; 江家贵; 崔凤梅

    2011-01-01

    目的 观察碧萝芷对60Coγ射线整体照射所致小鼠主要脏器中超氧化物歧化酶( superoxide dismutase,SOD)活力、丙二醛(malondialdehyde,MDA)含量、抗超氧阴离子自由基能力和抑制羟自由基能力的影响.方法 小鼠随机分成3组:正常对照组,辐照对照组及碧萝芷实验组.辐照对照组及碧萝芷实验组各接受1次γ射线照射,同时碧萝芷实验组用碧萝芷灌胃,连续7d.处死后取肝、脾、肾和睾丸组织,测定SOD活力、MDA含量、抑制羟自由基能力和抗超氧阴离子自由基能力.结果 碧萝芷对受照小鼠脏器中SOD活力影响不大,可降低脏器中MDA含量;能增加肝脏、肾脏和睾丸组织中抗超氧阴离子自由基能力和抑制羟自由基能力,增加脾脏抑制羟自由基能力.结论 碧萝芷具有一定的抗辐射损伤作用,其通过直接中和超氧阴离子自由基和羟自由基而发挥抗氧化功能,并不增加组织中的抗氧化酶含量.%Objective To observe the effects of pycnogenol on contents of SOD and MDA, and the inhibition of superoxide anion and hydroxyl radical in '"Co y-ray exposed mice organs. Methods The mice were randomly divided into 3 groups I. E. The normal control, irradiation control and pycnogenol experiment groups. The irradiation control and pycnogenol experiment groups were exposed to 60Co y- ray, and the mice of pycnogenol experiment group were given pycnogenol for 7 days after radiation. The tissues were obtained after being sacrificed, in which the vitality of SOD, the content of MDA and the inhibition of superoxide anion and hydroxyl radical were detected. Results Results showed that after the mice were irradiated pycnogenol had no effect on SOD; however, the content of MDA could be reduced in organs. Pycnogenol could increase the inhibition of superoxide anion and hydroxyl radical in kidney, liver and testicular and could increase the inhibition of hydroxyl radical in spleen. Conclusions Pycnogenol shows

  9. Estudo imunohistoquímico do remodelamento pulmonar em camundongos expostos à fumaça de cigarro Immunohistochemical study of lung remodeling in mice exposed to cigarette smoke

    Directory of Open Access Journals (Sweden)

    Samuel Santos Valença

    2008-10-01

    metalloproteinases is associated with cytokines, and evidence suggests that the matrix metalloproteinase-12 (MMP-12 plays an important role. Our objective was to investigate tissue inhibitor of metalloproteinase-2 (TIMP-2, tumor necrosis factor-alpha (TNF-α and interleukin-6 (IL-6 detection by immunohistochemical methods in mouse lung. METHODS: Male C57BL/6 mice were exposed 3 times a day to smoke of 3 cigarettes over a period of 10, 20, 30 or 60 days in an inhalation chamber (groups CS10, CS20, CS30 and CS60, respectively. Controls were exposed to the same conditions in room air. RESULTS: A progressive increase in the number of alveolar macrophages was observed in the bronchoalveolar lavage fluid of the exposed mice. The mean linear intercept, an indicator of alveolar destruction, was greater in all exposed groups when compared to control group. In the CS10, CS20 and CS30 mice, the immunohistochemical index (II for MMP-12 increased in parallel with a decrease in II for TIMP-2 in the CS10, CS20 and CS30 mice. The II for the cytokines TNF-α and IL-6 was greater in all exposed groups than in the control group. Emphysema, with changes in volume density of collagen and elastic fibers, was observed in the CS60 group. CONCLUSIONS: These findings suggest that cigarette smoke induces emphysema with major participation of TNF-α and IL-6 without participation of neutrophils.

  10. Specific-locus experiments show that female mice exposed near the time of birth to low-LET ionizing radiation exhibit both a low mutational response and a dose-rate effect

    International Nuclear Information System (INIS)

    Female mice were exposed to 300 R of 73-93 R/min X-radiation either as fetuses at 18.5d post conception (p.c.) or within 9h after birth. Combining the similar results from these 2 groups yielded a specific-locus mutation frequency of 9.4x10-8 mutation/locus/R, which is statistically significantly higher than the historical-control mutation frequency, but much lower than the rate obtained by irradiating mature and maturing oocytes in adults. Other females, exposed at 18.5 days p.c. to 300 R of 0.79 R/min γ-radiation, yielded a mutation frequency that was statistically significantly lower than the frequency at high dose rates. The low-dose-rate group also had markedly higher fertility. It appears that the doe-rate effect for mutations induced near the time of birth may be more pronounced than that reported for mature and maturing oocytes of adults. A hypothesis sometimes advanced to explain low mutation frequencies recovered from cell populations that experience considerable radiation-induced cell killing is that there is selection against mutant cells. The reason for the relatively low mutational response following acute irradiation in the experiments is unknown; however, the finding of a dose-rate effect in these oocytes in the presence of only minor radiation-induced cell killing (as judged from fertility) makes it seem unlikely that selection was responsible for the low mutational response following acute exposure. Had selection been an important factor, the mutation frequency should have increased when oocyte killing was markedly reduced. (author). 32 refs.; 5 figs.; 5 tabs

  11. Anxiety-like behaviors in mice lacking GIT2

    OpenAIRE

    Schmalzigaug, Robert; Rodriguiz, Ramona M.; Phillips, Lindsey E.; Davidson, Collin E.; Wetsel, William C.; Premont, Richard T.

    2008-01-01

    G protein-coupled receptor kinase-interactor 2 (GIT2) is a signaling scaffold protein that also functions as GTPase-activating protein (GAPs) for ADP-ribosylation factor (Arf) small GTP-binding proteins. GIT2 has been implicated in the regulation of G protein-coupled receptor trafficking and cell adhesion and migration. To evaluate possible neurobehavioral functions of GIT2 in vivo, we evaluated GIT2-knockout (KO) mice for abnormalities in emotionality and mood. Male and female GIT2-KO mice p...

  12. Window contamination on Expose-R

    Science.gov (United States)

    Demets, R.; Bertrand, M.; Bolkhovitinov, A.; Bryson, K.; Colas, C.; Cottin, H.; Dettmann, J.; Ehrenfreund, P.; Elsaesser, A.; Jaramillo, E.; Lebert, M.; van Papendrecht, G.; Pereira, C.; Rohr, T.; Saiagh, K.

    2015-01-01

    Expose is a multi-user instrument for astrobiological and astrochemical experiments in space. Installed at the outer surface of the International Space Station, it enables investigators to study the impact of the open space environment on biological and biochemical test samples. Two Expose missions have been completed so far, designated as Expose-E (Rabbow et al. 2012) and Expose-R (Rabbow et al. this issue). One of the space-unique environmental factors offered by Expose is full-spectrum, ultraviolet (UV)-rich electromagnetic radiation from the Sun. This paper describes and analyses how on Expose-R, access of the test samples to Solar radiation degraded during space exposure in an unpredicted way. Several windows in front of the Sun-exposed test samples acquired a brown shade, resulting in a reduced transparency in visible light, UV and vacuum UV (VUV). Post-flight investigations revealed the discolouration to be caused by a homogenous film of cross-linked organic polymers at the inside of the windows. The chemical signature varied per sample carrier. No such films were found on windows from sealed, pressurized compartments, or on windows that had been kept out of the Sun. This suggests that volatile compounds originating from the interior of the Expose facility were cross-linked and photo-fixed by Solar irradiation at the rear side of the windows. The origin of the volatiles was not fully identified; most probably there was a variety of sources involved including the biological test samples, adhesives, plastics and printed circuit boards. The outer surface of the windows (pointing into space) was chemically impacted as well, with a probable effect on the transparency in VUV. The reported analysis of the window contamination on Expose-R is expected to help the interpretation of the scientific results and offers possibilities to mitigate this problem on future missions - in particular Expose-R2, the direct successor of Expose-R.

  13. THC Prevents MDMA Neurotoxicity in Mice.

    Directory of Open Access Journals (Sweden)

    Clara Touriño

    Full Text Available The majority of MDMA (ecstasy recreational users also consume cannabis. Despite the rewarding effects that both drugs have, they induce several opposite pharmacological responses. MDMA causes hyperthermia, oxidative stress and neuronal damage, especially at warm ambient temperature. However, THC, the main psychoactive compound of cannabis, produces hypothermic, anti-inflammatory and antioxidant effects. Therefore, THC may have a neuroprotective effect against MDMA-induced neurotoxicity. Mice receiving a neurotoxic regimen of MDMA (20 mg/kg x 4 were pretreated with THC (3 mg/kg x 4 at room (21 degrees C and at warm (26 degrees C temperature, and body temperature, striatal glial activation and DA terminal loss were assessed. To find out the mechanisms by which THC may prevent MDMA hyperthermia and neurotoxicity, the same procedure was carried out in animals pretreated with the CB(1 receptor antagonist AM251 and the CB(2 receptor antagonist AM630, as well as in CB(1, CB(2 and CB(1/CB(2 deficient mice. THC prevented MDMA-induced-hyperthermia and glial activation in animals housed at both room and warm temperature. Surprisingly, MDMA-induced DA terminal loss was only observed in animals housed at warm but not at room temperature, and this neurotoxic effect was reversed by THC administration. However, THC did not prevent MDMA-induced hyperthermia, glial activation, and DA terminal loss in animals treated with the CB(1 receptor antagonist AM251, neither in CB(1 and CB(1/CB(2 knockout mice. On the other hand, THC prevented MDMA-induced hyperthermia and DA terminal loss, but only partially suppressed glial activation in animals treated with the CB(2 cannabinoid antagonist and in CB(2 knockout animals. Our results indicate that THC protects against MDMA neurotoxicity, and suggest that these neuroprotective actions are primarily mediated by the reduction of hyperthermia through the activation of CB(1 receptor, although CB(2 receptors may also contribute to

  14. The study of susceptibility to carbon tetrachloride and benzene in offspring of expanded simple tandem repeats mutation mice exposed to formaldehyde%甲醛致扩张性简单串联重复序列突变小鼠子代对四氯化碳和苯暴露易感性研究

    Institute of Scientific and Technical Information of China (English)

    王超; 刘云儒; 周印; 李爱萍; 周建伟

    2011-01-01

    为5.88‰±4.55‰,F10代为8.25‰±2.06‰;C组1000 mg/kg苯染毒组:F5代为7.50‰±6.99‰,F10代为10.67‰±1.16‰;H组500 mg/kg苯染毒组:F5代为7.88‰±3.09‰,F10代为9.20‰±1.30‰;H组1000 mg/kg苯染毒组:F5代为9.63‰±4.34‰,F10代为13.33‰±2.08‰)随苯剂量的增加而增加,与溶剂对照组(C组F5代为1.13‰±0.35‰,F10代为1.20‰±0.82‰;H组F5代为1.25‰±0.46‰,F10代为1.33‰±1.03‰)的差异均有统计学意义(P<0.05,P<0.01).结论 甲醛暴露引起的基因组ESTR突变可改变子代小鼠对CCl4和苯的易感性.ESTR突变可能是影响机体对化学物易感性的生物学标志,其分子机制有待进一步阐明.%Objective To investigate the susceptibility to carbon tetrachloride and benzene in offspring of expanded simple tandem repeats (ESTR) mutation mice exposed to formaldehyde (FA). Methods F5 and F10 offspring (200 mg/m3 ×2 hours) served as H group and ICR mice were used as control group(group C). The F5 and F10 offspring were exposed to 10 ml/kg carbon tetrachloride at the doses of 0.05%, 0.50% or 5.00% for 24 hours, respectively or 500 or 1000 mg/kg benzene for 24 hours, respectively by intraperitoneal injection. Serum alanine transaminase (ALT), aspartate transaminase (AST) and the hepatic superoxide dismutase (SOD) or malondialdehyde (MDA) were detected; also the hepatic pathological changes were observed under light microscope; the micronucleus in sternum bone marrow cells as the biomarker of benzene blood toxicity were measured. Results ALT and AST activities in group C of F5 mice exposed to 0.50% and 5.00% CCl4, ALT in groups C and H of F10 mice exposed to 0.05%, 0.50%, 5.00% CCl4, AST in groups C and H of F10 mice exposed to 0.50% and 5.00% CCl4 were significantly higher than those in controls, respectively (P<0.05); as compared to the control, hepatic SOD activities in group C of F5 and F10 mice exposed to 0.50% and 5.00% CCl4, in group H of F5 mice exposed to 0.50% and 5.00% CCl4, and

  15. PI3K-AKT Signaling via Nrf2 Protects against Hyperoxia-Induced Acute Lung Injury, but Promotes Inflammation Post-Injury Independent of Nrf2 in Mice.

    Directory of Open Access Journals (Sweden)

    Narsa M Reddy

    Full Text Available Lung epithelial and endothelial cell death accompanied by inflammation contributes to hyperoxia-induced acute lung injury (ALI. Impaired resolution of ALI can promote and/or perpetuate lung pathogenesis, including fibrosis. Previously, we have shown that the transcription factor Nrf2 induces cytoprotective gene expression and confers protection against hyperoxic lung injury, and that Nrf2-mediated signaling is also crucial for the restoration of lung homeostasis post-injury. Although we have reported that PI3K/AKT signaling is required for Nrf2 activation in lung epithelial cells, significance of the PI3K/AKT-Nrf2 crosstalk during hyperoxic lung injury and repair remains unclear. Thus, we evaluated this aspect using Nrf2 knockout (Nrf2(-/- and wild-type (Nrf2(+/+ mouse models. Here, we show that pharmacologic inhibition of PI3K/AKT signaling increased lung inflammation and alveolar permeability in Nrf2(+/+ mice, accompanied by decreased expression of Nrf2-target genes such as Nqo1 and Hmox1. PI3K/AKT inhibition dampened hyperoxia-stimulated Nqo1 and Hmox1 expression in lung epithelial cells and alveolar macrophages. Contrasting with its protective effects, PI3K/AKT inhibition suppressed lung inflammation in Nrf2(+/+ mice during post-injury. In Nrf2(-/- mice exposed to room-air, PI3K/AKT inhibition caused lung injury and inflammation, but it did not exaggerate hyperoxia-induced ALI. During post-injury, PI3K/AKT inhibition did not augment, but rather attenuated, lung inflammation in Nrf2(-/- mice. These results suggest that PI3K/AKT-Nrf2 signaling is required to dampen hyperoxia-induced lung injury and inflammation. Paradoxically, the PI3K/AKT pathway promotes lung inflammation, independent of Nrf2, during post-injury.

  16. Time- and age-dependent effects of serotonin on gasping and autoresuscitation in neonatal mice.

    Science.gov (United States)

    Chen, Jianping; Magnusson, Jennifer; Karsenty, Gerard; Cummings, Kevin J

    2013-06-15

    The role of brain stem serotonin (5-hydroxytryptamine, 5-HT) in autoresuscitation in neonatal life is unclear. We hypothesized that a specific loss of 5-HT would compromise gasping and autoresuscitation mainly in the second postnatal week and that acute restoration of 5-HT would reverse the defects. We exposed postnatal day (P)4-5, P8-9, and P11-12 tryptophan-hydroxylase-2 knockout (TPH2(-/-)) and wild-type littermates (WT) to 10 episodes of anoxia (97% N2, 3% CO2), measuring survival, gasp latency, gasp frequency (fB), and the time required to restore eupnea and heart rate. We also tested P8-9 TPH2(-/-) mice after restoring 5-HT with a single injection of 5-hydroxytryptophan (5-HTP) 1-2 h before testing or with multiple injections beginning 24 h before testing. At P4-5 and P8-9, but not at P11-12, gasp latency and the recovery of eupnea were delayed ~2- to 3-fold in TPH2(-/-) pups compared with WT (P pups displayed reduced gasp fB (~20-30%; P rate recovery (~60%; P = 0.002) compared with WT littermates. TPH2(-/-) survival was reduced compared with WT (P pups, improved cardiorespiratory recovery and survival required 24 h of treatment. Our data suggest that 5-HT operates over a long time span (24 h) to improve survival during episodic severe hypoxia. Early in development (P4-9), 5-HT is critical for both respiratory and cardiovascular components of autoresuscitation; later (P11-12), it is critical mainly for cardiovascular components. Nevertheless, the effect of 5-HT deficiency on survival is most striking from P8 to P12. PMID:23558391

  17. Minimal impact of age and housing temperature on the metabolic phenotype of Acc2-/- mice.

    Science.gov (United States)

    Brandon, Amanda E; Stuart, Ella; Leslie, Simon J; Hoehn, Kyle L; James, David E; Kraegen, Edward W; Turner, Nigel; Cooney, Gregory J

    2016-03-01

    An important regulator of fatty acid oxidation (FAO) is the allosteric inhibition of CPT-1 by malonyl-CoA produced by the enzyme acetyl-CoA carboxylase 2 (ACC2). Initial studies suggested that deletion of Acc2 (Acacb) increased fat oxidation and reduced adipose tissue mass but in an independently generated strain of Acc2 knockout mice we observed increased whole-body and skeletal muscle FAO and a compensatory increase in muscle glycogen stores without changes in glucose tolerance, energy expenditure or fat mass in young mice (12-16 weeks). The aim of the present study was to determine whether there was any effect of age or housing at thermoneutrality (29 °C; which reduces total energy expenditure) on the phenotype of Acc2 knockout mice. At 42-54 weeks of age, male WT and Acc2(-/-) mice had similar body weight, fat mass, muscle triglyceride content and glucose tolerance. Consistent with younger Acc2(-/-) mice, aged Acc2(-/-) mice showed increased whole-body FAO (24 h average respiratory exchange ratio=0.95±0.02 and 0.92±0.02 for WT and Acc2(-/-) mice respectively, Pmuscle glycogen content (+60%, P<0.05) without any detectable change in whole-body energy expenditure. Hyperinsulinaemic-euglycaemic clamp studies revealed no difference in insulin action between groups with similar glucose infusion rates and tissue glucose uptake. Housing Acc2(-/-) mice at 29 °C did not alter body composition, glucose tolerance or the effects of fat feeding compared with WT mice. These results confirm that manipulation of Acc2 may alter FAO in mice, but this has little impact on body composition or insulin action.

  18. Rapid doubling of Alzheimer’s amyloid-β40 and 42 levels in brains of mice exposed to a nickel nanoparticle model of air pollution [v1; ref status: indexed, http://f1000r.es/T5Rxeo

    Directory of Open Access Journals (Sweden)

    Soong Ho Kim

    2012-12-01

    Full Text Available Background: Over 20 genetic risk factors have been confirmed to associate with elevated risk for Alzheimer’s disease (AD, but the identification of environmental and/or acquired risk factors has been more elusive. At present, recognized acquired risks for AD include traumatic brain injury, hypercholesterolemia, obesity, hypertension, and type 2 diabetes. Methods: Based on reports associating various inhalants with AD pathology, we investigated the possibility that air pollution might contribute to AD risk by exposing wild-type mice to a standard air pollution modeling system employing nickel nanoparticle-enriched atmosphere for 3 hr. Results: Mice exposed to air pollution showed 72-129% increases in brain levels of both amyloid-β peptides Aβ40 and Aβ42, as well as Aβ42/40 (p <0.01. Conclusions: These effects on elevation of brain Aβ exceed those associated with trisomy 21, a known risk for early onset AD pathology, raising the possibility that clinical importance might be attached. Further work is required to establish the molecular and physiological basis for these phenomena. The rapid, dramatic effect, if verified, would suggest that inhalant exposures should be evaluated for their possible roles in contributing to the environmental risk for common forms of AD.

  19. The Nicotinamide Adenine Dinucleotide Phosphate Oxidase Homologues NOX1 and NOX2/gp91phox Mediate Hepatic Fibrosis in Mice

    OpenAIRE

    Paik, Yong-Han; Iwaisako, Keiko; Seki, Ekihiro; Inokuchi, Sayaka; Schnabl, Bernd; Österreicher, Christoph H.; Kisseleva, Tatiana; Brenner, David A

    2011-01-01

    NADPH oxidase (NOX) is a multicomponent enzyme that mediates electron transfer from NADPH to molecular oxygen, which leads to the production of superoxide. NOX2/gp91phox is a catalytic subunit of NOX expressed in phagocytic cells. Several homologues of NOX2, including NOX1, have been identified in non-phagocytic cells. We investigated the contributory role of NOX1 and NOX2 in hepatic fibrosis. Hepatic fibrosis was induced in wild-type (WT) mice, NOX1-knockout (NOX1KO) mice, and NOX2-knockout ...

  20. Determination of arsenic in liver and kidney of mice exposed in realgar by HG-FAAS%HG-FAAS 法测定雄黄染毒小鼠肝及肾脏中的砷含量

    Institute of Scientific and Technical Information of China (English)

    苑洁; 霍韬光; 王艳蕾; 郭婧潭; 焦雪鑫; 张颖花; 袁媛; 高岚岳; 姜泓

    2015-01-01

    A novel hydride generation‐flame atomic absorption spectrometry (HG‐FAAS ) method was established for the determination of arsenic in liver and kidney of mice after realgar exposure .The results showed that the method was accurate ,sensitive ,reliable and low detec‐tion limit .The distribution levels of arsenic in liver ,kidney of realgar infected mice were fairly with the liver and kidney content .Meanwhile hydride generation conditions were optimized .%建立了氢化物发生‐火焰原子吸收法(HG‐FAAS)测定雄黄染毒小鼠肝及肾脏中砷含量的方法。结果表明,该方法准确、灵敏、可靠、检出限低。雄黄染毒小鼠肝、肾脏中砷的分布水平相当。同时对氢化物发生条件进行了优化。

  1. Hematotoxicity and genotoxicity evaluations in Swiss mice intraperitoneally exposed to Bacillus thuringiensis (var kurstaki) spore crystals genetically modified to express individually Cry1Aa, Cry1Ab, Cry1Ac, or Cry2Aa.

    Science.gov (United States)

    Mezzomo, Bélin Poletto; Miranda-Vilela, Ana Luisa; Barbosa, Lilian Carla Pereira; Albernaz, Vanessa Lima; Grisolia, Cesar Koppe

    2016-08-01

    Bacillus thuringiensis (Bt) has been widely used in foliar sprays as part of integrated pest management strategies against insect pests of agricultural crops. Since the advent of genetically modified plants expressing Bt δ-endotoxins, the bioavailability of Cry proteins has increased, and therefore for biosafety reasons their adverse effects should be studied, mainly for nontarget organisms. We evaluated, in Swiss mice, the hematotoxicity and genotoxicity of the genetically modified strains of Bt spore crystals Cry1Aa, 1Ab, 1Ac, or 2Aa at 27 mg/kg, and Cry1Aa, 1Ab and 2Aa also at 136 and 270 mg/kg, administered with a single intraperitoneal injection 24 h before euthanasia. Controls received filtered water or cyclophosphamide. Blood samples collected by cardiac puncture were used to perform hemogram, and bone marrow was extracted for the micronucleus test. Bt spore crystals presented toxicity for lymphocytes when in higher doses, which varied according to the type of spore crystal studied, besides promoting cytotoxic and genotoxic effects for the erythroid lineage of bone marrow, mainly at highest doses. Although the profile of such adverse side effects can be related to their high level of exposure, which is not commonly found in the environment, results indicated that these Bt spore crystals were not harmless to mice. This suggests that a more specific approach should be taken to increase knowledge about their toxicological properties and to establish the toxicological risks to nontarget organisms. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 970-978, 2016.

  2. 不同声压级次声作用小鼠后脑胶质纤维酸性蛋白的含量和意义%Change and significance of gfap in the brain of mice exposed to infrasound

    Institute of Scientific and Technical Information of China (English)

    牟翔; 陈景藻; 李玲; 贾克勇; 刘静

    2001-01-01

    目的 究不同声压级次声作用小鼠后脑中胶质纤维酸性蛋白(GFAP)的改变和意义。方法BALB/C小鼠暴露于16Hz,声压90dB和130dB次声。每天作用2h,分别作用1、7、14、21和28d后,采用免疫组织化学方法观察小鼠脑中GFAP的改变。结果 现90dB和130dB次声作用后,GFAP的表达主要在海马、皮质和下丘脑等区域明显增多;130dB次声作用较90dB次声作用强;在相同强度的次声作用下,作用次数的多少与脑内GFAP的改变程度呈正相关。结论 马、皮质和下丘脑等区域对次声敏感,次声的作用效应与声压级和作用时间有关;次声可以通过脑内GFAP的改变造成脑损伤,这是次声导致脑损害的重要因素之一。%Objective To study the change and significance of GFAP in the brain of the mice exposed to infrasound of different sound pressure level .Method The BALB/C mice were exposed to infrasound of 16Hz with intensity of 90dB and 130dB for 1,7,14,21and 28 days. It was for 2h every day. Then immunohistochemical technique was exployed to detect the change of GFAP in the brain of the mice. Results The expression of GFAP increased mainly in the hippocampus,cortex and hypothamus regions after infrasound of 90dB and 130dB exposed .The effect at 130dB infrasound was more than 90dB.Conclusion The extent of GFAP change is closely related to the action times under infrasound of same sound pressure level. Infrasound bring about brain injury through the change of GFAP in the brain, which is one of the important factors that infrasound cause brain injury.

  3. 不同声压级次声作用小鼠后脑胶质纤维酸性蛋白的含量和意义%Change and significance of gfap in the brain of mice exposed to infrasound

    Institute of Scientific and Technical Information of China (English)

    牟翔; 陈景藻; 李玲; 贾克勇; 刘静

    2001-01-01

    Objective To study the change and significance of GFAP in thebrain of the mice exposed to infrasound of different sound pressure level .Method The BALB/C mice were exposed to infrasound of 16Hz with intensity of 90dB and 130dB for 1,7,14,21and 28 days. It was for 2h every day. Then immunohistochemical technique was exployed to detect the change of GFAP in the brain of the mice. Results The expression of GFAP increased mainly in the hippocampus,cortex and hypothamus regions after infrasound of 90dB and 130dB exposed .The effect at 130dB infrasound was more than 90dB.Conclusion The extent of GFAP change is closely related to the action times under infrasound of same sound pressure level. Infrasound bring about brain injury through the change of GFAP in the brain, which is one of the important factors that infrasound cause brain injury.%目的 研究不同声压级次声作用小鼠后脑中胶质纤维酸性蛋白(GFAP)的改变和意义。方法BALB/C小鼠暴露于16Hz,声压90dB和130dB次声。每天作用2h,分别作用1、7、14、21和28d后,采用免疫组织化学方法观察小鼠脑中GFAP的改变。结果 现90dB和130dB次声作用后,GFAP的表达主要在海马、皮质和下丘脑等区域明显增多;130dB次声作用较90dB次声作用强;在相同强度的次声作用下,作用次数的多少与脑内GFAP的改变程度呈正相关。结论 马、皮质和下丘脑等区域对次声敏感,次声的作用效应与声压级和作用时间有关;次声可以通过脑内GFAP的改变造成脑损伤,这是次声导致脑损害的重要因素之一。

  4. Hematotoxicity and genotoxicity evaluations in Swiss mice intraperitoneally exposed to Bacillus thuringiensis (var kurstaki) spore crystals genetically modified to express individually Cry1Aa, Cry1Ab, Cry1Ac, or Cry2Aa.

    Science.gov (United States)

    Mezzomo, Bélin Poletto; Miranda-Vilela, Ana Luisa; Barbosa, Lilian Carla Pereira; Albernaz, Vanessa Lima; Grisolia, Cesar Koppe

    2016-08-01

    Bacillus thuringiensis (Bt) has been widely used in foliar sprays as part of integrated pest management strategies against insect pests of agricultural crops. Since the advent of genetically modified plants expressing Bt δ-endotoxins, the bioavailability of Cry proteins has increased, and therefore for biosafety reasons their adverse effects should be studied, mainly for nontarget organisms. We evaluated, in Swiss mice, the hematotoxicity and genotoxicity of the genetically modified strains of Bt spore crystals Cry1Aa, 1Ab, 1Ac, or 2Aa at 27 mg/kg, and Cry1Aa, 1Ab and 2Aa also at 136 and 270 mg/kg, administered with a single intraperitoneal injection 24 h before euthanasia. Controls received filtered water or cyclophosphamide. Blood samples collected by cardiac puncture were used to perform hemogram, and bone marrow was extracted for the micronucleus test. Bt spore crystals presented toxicity for lymphocytes when in higher doses, which varied according to the type of spore crystal studied, besides promoting cytotoxic and genotoxic effects for the erythroid lineage of bone marrow, mainly at highest doses. Although the profile of such adverse side effects can be related to their high level of exposure, which is not commonly found in the environment, results indicated that these Bt spore crystals were not harmless to mice. This suggests that a more specific approach should be taken to increase knowledge about their toxicological properties and to establish the toxicological risks to nontarget organisms. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 970-978, 2016. PMID:25899034

  5. Maternal Microchimerism Leads to the Presence of Interleukin-2 in Interleukin-2 Knock Out Mice: Implications for the Role of Interleukin-2 in Thymic Function

    OpenAIRE

    Wrenshall, Lucile E.; Stevens, Elliot T.; Smith, Deandra R.; Miller, John D.

    2007-01-01

    The role of interleukin-2 (IL-2) in thymic development is uncertain. Not surprisingly, IL-2 knockout (KO) mice have been used to address this question. However, as we report here, such mice are chimeric, containing both IL-2 KO cells and IL-2-expressing cells transferred in utero from their heterozygous mothers. These cells produce IL-2 in amounts detectable by conventional means, and their presence in lymphoid tissues confounds efforts to define the true IL-2 KO phenotype. To minimize the am...

  6. Mutations in Mll2, an H3K4 methyltransferase, result in insulin resistance and impaired glucose tolerance in mice.

    Directory of Open Access Journals (Sweden)

    Michelle Goldsworthy

    Full Text Available We employed a random mutagenesis approach to identify novel monogenic determinants of type 2 diabetes. Here we show that haplo-insufficiency of the histone methyltransferase myeloid-lineage leukemia (Mll2/Wbp7 gene causes type 2 diabetes in the mouse. We have shown that mice heterozygous for two separate mutations in the SET domain of Mll2 or heterozygous Mll2 knockout mice were hyperglycaemic, hyperinsulinaemic and developed non-alcoholic fatty liver disease. Consistent with previous Mll2 knockout studies, mice homozygous for either ENU mutation (or compound heterozygotes died during embryonic development at 9.5-14.5 days post coitum. Heterozygous deletion of Mll2 induced in the adult mouse results in a normal phenotype suggesting that changes in chromatin methylation during development result in the adult phenotype. Mll2 has been shown to regulate a small subset of genes, a number of which Neurod1, Enpp1, Slc27a2, and Plcxd1 are downregulated in adult mutant mice. Our results demonstrate that histone H3K4 methyltransferase Mll2 is a component of the genetic regulation necessary for glucose homeostasis, resulting in a specific disease pattern linking chromatin modification with causes and progression of type 2 diabetes, providing a basis for its further understanding at the molecular level.

  7. Nrf2-mediated haeme oxygenase-1 up-regulation induced by cobalt protoporphyrin has antinociceptive effects against inflammatory pain in the formalin test in mice.

    Science.gov (United States)

    Rosa, Angelo O; Egea, Javier; Lorrio, Silvia; Rojo, Ana I; Cuadrado, Antonio; López, Manuela G

    2008-07-15

    This study investigated the effect of haeme oxygenase-1 (HO-1) in nociception induced by formalin injection in the mice hind paw. Intraperitoneal (i.p.) administration of cobalt protoporphyrin (CoPP, an HO-1 inducer, 5mg/kg) 24h before the test, inhibited the nociceptive response during the second phase, but not during the first phase of the formalin test. The effect of CoPP was prevented by treatment with tin protoporphyrin (SnPP, an inhibitor of HO-1 activity) administered either by i.p. (25mg/kg, 30 min before the test) or intraplantar (400 nmol/paw, 5 min before the test) routes. Human embryonic kidney (HEK) 293T cells treated with 10 microM CoPP expressed 20-fold higher HO-1 levels when compared to controls; this effect was suppressed by transfection with the dominant negative for the nuclear factor-erythroid 2-related factor 2 (Nrf2). Western blot analysis also revealed that CoPP treatment induced a similar 20-fold increase in HO-1 expression in the paw; this effect was attenuated in knockout mice for Nrf2. CoPP treatment of wild-type, but not in Nrf2 knockout mice, resulted in a striking increase of HO-1 stained cells surrounding the muscular tissues of the hind limbs. HO-1 positive cells were scarce in wild-type and in Nrf2 knockout untreated mice. CoPP-induced HO-1 expression in Nrf2 knockout mice was lost and correlated with the loss of antinociceptive effects. In conclusion, Nrf2-mediated HO-1 expression induced an antinociceptive effect at peripheral sites. These results suggest that HO-1 modulates the inflammatory pain pathways. Hence, the development of drugs that could raise peripheral HO-1 could be relevant in inflammatory pain treatment.

  8. Fire exposed aluminium structures

    NARCIS (Netherlands)

    Maljaars, J.; Fellinger, J.H.H.; Soetens, F.

    2006-01-01

    Material properties and mechanical response models for fire design of steel structures are based on extensive research and experience. Contrarily, the behaviour of aluminium load bearing structures exposed to fire is relatively unexplored. This article gives an overview of physical and mechanical pr

  9. 米邦塔仙人掌果胶对慢性不可预知温和应激小鼠绝望症状的改善作用%Study on the improvement of milpa alta cactus pectin on desperate symptoms in mice exposed to chronic unpreditc able mild stress

    Institute of Scientific and Technical Information of China (English)

    肖同楚; 黄朝明; 杨兴娥; 湛进进; 郭莲军

    2015-01-01

    目的:研究米邦塔仙人掌果胶( MCP)对慢性不可预知温和应激( CUMS)小鼠绝望症状的改善作用。方法雄性昆明种小鼠随机分为空白对照组、模型组、MCP低剂量组(50 mg/kg)、MCP中剂量组(100 mg/kg)、MCP高剂量组(200 mg/kg)。除空白对照组不进行任何应激处理外,其余组均进行CUMS,各MCP组均在进行CUMS期间每天灌胃相应剂量MCP。造模结束24 h后进行悬尾实验,48 h后进行强迫游泳实验。结果模型组悬尾实验潜伏期显著短于空白对照组(P<0.01),累计不动时间显著长于空白对照组(P<0.01);MCP高剂量组潜伏期显著长于模型组(P<0.05),MCP中、高剂量组累计不动时间显著短于模型组(P均<0.01)。模型组强迫游泳实验潜伏期显著短于空白对照组(P<0.01),累计不动时间显著长于空白对照组(P<0.01);MCP各给药组潜伏期与空白对照组比较差异均无统计学意义(P均>0.05),而MCP高剂量组累计不动时间显著短于模型组(P<0.05)。结论 MCP能较好地缓解CMS小鼠的行为绝望症状。%Objetc ive It is to investigate the effect of milpa alta cactus pectin ( MCP) on desperate symptoms in mice ex-posed to chronic unpredictable mild stress ( CUMS) .Methods The male Kunming mice were randomly divided into 5 groups such as control group, CUMS+Vehicle group, CUMS+MCP 50 mg/kg group, CUMS+MCP 100 mg/kg group, and CUMS+MCP 200 mg/kg group.Except the control group, the other groups were exposed to CUMS for 6 weeks.And during this peri-od, the animals were treated with corresponding drug by intragastric administration.While the ends of the model, the tail sus-pension test ( TST) was carried out after 24 hours, and the forced swimming test ( FST) were conducted after 48 hours.Re-sults In TST, the latency of the CUMS+Vehicle group was significantly shorter (P0.05), and the immobility time of the

  10. Peripheral activation of corticotropin-releasing factor receptor 2 inhibits food intake and alters meal structures in mice

    OpenAIRE

    Wang, Lixin; Stengel, Andreas; Goebel, Miriam; Martinez, Vicente; Gourcerol, Guillaume; Rivier, Jean; Taché, Yvette

    2010-01-01

    The orexigenic effect of urocortins (Ucn 1, Ucn 2 and Ucn 3) through activation of corticotropin-releasing factor (CRF) receptors, has been well characterized after injection into the brain but not in the periphery. We examined the role of CRF receptor subtype 2 (CRF2) in the regulation of food intake using intraperitoneal (ip) injection of Ucns, the selective CRF2 antagonist, astressin2-B, and CRF2 knockout (−/−) mice. Meal structures were monitored using an automated episodic solid food int...

  11. Determination and evaluation of arsenic speciation and glutathione level in lever and blood of mice subchronically exposed to inorganic arsenic%亚慢性砷暴露小鼠血和肝中砷形态及谷胱甘肽水平检测分析

    Institute of Scientific and Technical Information of China (English)

    牛玉红; 曲春清; 钟媛; 于霄云; 李革新; 吕秀强; 孙贵范; 金亚平

    2008-01-01

    Objective To explore the distribution of arsenic speciafion and to estimate the effect of arsenic on glutathione(GSH)levels in the blood and liver of mice exposed to different concentrations of inorganic AsⅢ through drinking water.Methods Mice drank water containing arsenite at concentrations of iAsⅢ of 0(contr01),25,50,100 ms/L for 6 weeks.Blood and liver were sampled to asses$the levels of inorganic arsenic(iAs),monomethylarsenic acid(MMA),dimethylarsenic acid(DMA)by the method of hydride generation trapping and ultra-hypothermia coupled with atomic absorption spectrometry,and the level of GSH by the method of 5,5'-Dithio-bis (2-Nitrobenzoic acid).Results Leveh of iAs.MMA and DMA in blood and in liver increased along with the increase of iAs concentrations in drinking water.Primary methylated index(PMI)and secondary methylation index (SMI)of liver and blood were significantly higher in exposed groups than those in control group(P<0.05).SMI of liver in 50 mg/L exposed group[(50.45±2.94)%]was significantly higher than those in 25 mg/L and 100 mg/Lgroups[(41.68±7.09)%and(41.19±8.87)%,respectively],the difference being statistically significant(P<0.05).The ratio of iAs.MMA and DMA in blood and liver in exposed group were 2:3:5 and 4:3:3,the percentage of level of organic arsenic(MMA+DMA)were 80%and 60%.GSH in blood and liver in exposed group decreased along with iAs concentrations in drinking water and had significant differences compared with those in control group (P<0.05).However,levels of GSH in liver and blood did not differ significantly between exposed groups and control group(P>0.05).Conclusions Membolism of iAs in liver is maximized when the iAs concentrations in drinking water increases to a certain level.However,the percentage of arsenic speciation in blood is different from that in liver,suggesting that other organs and tissues may be capable of methylation of inorganic arsenic.The level of GSH in liver and blood in mice is a good mark t

  12. Effect of glutathione and sodium selenite on the metabolism of arsenic in mice exposed to arsenic through drinking water%谷胱甘肽与亚硒酸钠对饮水砷暴露小鼠体内砷代谢的影响

    Institute of Scientific and Technical Information of China (English)

    于霄云; 钟媛; 牛玉红; 曲春清; 李革新; 吕秀强; 孙贵范; 金亚平

    2008-01-01

    Objective To explore the effect of glutathione(GSH)and sodium selenite on the metabolism of arsenic in the liver,kidney and blood of mice exposed to iAsⅢ through drinking water.Methods The mice were randomly divided into control,arsenic,GSH and sodium selenite group,respectively.And each group had eight mice and the mice were exposed to 50 mg/L arsenite by drinking water for 4 weeks.Mice were intraperitoneally injected with GSH(600 mg/kg)and sodium selenite (1 mg/kg)for seven days from the beginning of the fourth week.At the end of the fourth week,liver,kidney and blood were samplod to assess the concentrations of inorganic arsenic(iAs),monomethylarsenic acid(MMA),dimethylarsenic acid(DMA)by hydride generation trapping by ultra-hypothermia coupled with atomic absorption spectrometry.Results The liver DMA(233.76±60.63 ng/g)concentration in GSH group was significantly higher than the arsenic group(218.36±42.71 ng/g).The concentration of DMA (88.52±30.86 ng/g)and total arenic(Tas)(162.32±49.45 ng/g)in blood of GSH group was significantly higher than those[(45.32±12.19 ng/g),(108.51±18.00 ng/g),respectively]of arsenic groups(q values were 3.06,6.40,10.72 respectively,P<0.05).The primary methylated index(PMI)(0.65±0.050)and secondary methyhted index(SMI)(0.55±0.050)in liver sample of GSH group were significantly higher than those(0.58±0.056,0.44±0.093)in arsenic group.In blood samples,the PMI (0.85±0.066)in GSH group was significantly higher than that(0.54±0.113)in arsenic group(q values were 3.75,5.26,4.21 respectively,P<0.05).However,no significant difference was identified between sodium selenite and arsenic groups in liver,kidney or blood samples.And no significant difference was detected in kidney samples among all arsenic exposing groups.Conclusion Exogenous GSH could promote the methylated metabolism of iAsⅢ,but sodium selenite showed no significant effects.%目的 探讨给予外源性谷胱甘肽(GSH)和亚硒酸钠(sodium selenite)对饮

  13. 胚胎植入期二硫化碳暴露对孕鼠脾脏淋巴细胞DNA损伤的影响%DNA damage of splenic lymphocytes in pregnant mice exposed to carbon disulfide in implantation phase

    Institute of Scientific and Technical Information of China (English)

    胡程霞; 张炳珍; 李春辉; 吴艳玲; 杨柳; 王志萍

    2013-01-01

    目的 研究胚胎植入期二硫化碳(CS2)暴露对孕鼠脾脏淋巴细胞DNA损伤的影响,从免疫损伤角度探讨CS2致胚胎植入障碍的机制.方法 分别建立不同暴露剂量和不同暴露时间2个动物模型:模型1为不同CS2暴露剂量,即在小鼠受孕第4天(GD4),分别给予4组小鼠一次性腹腔注射低(0.1LD50,157.8 mg/kg)、中(0.2LD50,315.7 mg/kg)、高(0.4LD50,631.4 mg/kg)剂量的CS2和橄榄油对照组;模型2为不同CS2暴露时间,即4组小鼠分别在GD3、GD4、GD5和GD6一次性腹腔注射CS2(0.4LD50,631.4 mg/kg),各组设平行对照.两模型对照组均注射等体积橄榄油.实验终点,制备胚胎植入期小鼠脾脏淋巴细胞单细胞悬液,用台盼蓝法检测细胞活性,并进行碱性单细胞凝胶电泳(SCGE)试验,检测孕鼠脾脏淋巴细胞DNA损伤状况.结果 (1)中、高剂量组的DNA损伤程度与对照组相比差异均有统计学意义(P<0.01);反映DNA损伤程度的各指标与暴露剂量之间均存在回归关系,且差异有统计学意义(P<0.01).(2)GD3、GD4、GD5和GD6暴露组的DNA损伤程度与对照组比较,差异均有统计学意义(P<0.01),且GD4暴露组DNA损伤程度最明显.结论 胚胎植入期CS2暴露可导致孕鼠脾脏淋巴细胞的DNA损伤,并且呈明显的剂量反应关系;GD4可能是CS2暴露致孕鼠脾脏淋巴细胞DNA损伤的敏感时间点.%Objective To investigate the DNA damage of splenic lymphocytes in pregnant mice exposed to carbon disulfide (CS2) in the implantation phase and to explore the mechanism of abnormal implantation induced by CS2 from the perspective of immune injury.Methods Mice were exposed to CS2 at different doses or at different time points in the implantation phase to establish model 1 and model 2.For model 1,mice were assigned to four groups to receive a single intraperitoneal injection of low-dose CS2 (0.1 LD50,157.8mg/kg),middle-dose CS2 (0.2 LD50,315.7 mg/kg),and high-dose CS2 (0.4 LD50,631.4 mg

  14. Increased sensitivity to kindling in mice lacking TSP1.

    Science.gov (United States)

    Mendus, D; Rankin-Gee, E K; Mustapha, M; Porter, B E

    2015-10-01

    The development of a hyperexcitable neuronal network is thought to be a critical event in epilepsy. Thrombospondins (TSPs) regulate synaptogenesis by binding the neuronal α2δ subunit of the voltage-gated calcium channel. TSPs regulate synapse formation during development and in the mature brain following injury. It is unclear if TSPs are involved in hyperexcitability that contributes to the development of epilepsy. Here we explore the development of epilepsy using a pentylenetetrazole (PTZ) kindling model in mice lacking TSP1 and TSP2. Unexpectedly, we found increased sensitivity to PTZ kindling in mice lacking TSP1, while mice lacking TSP2 kindled similar to wild-type. We found that the increased seizure susceptibility in the TSP1 knockout (KO) mice was not due to a compensatory increase in TSP2 mRNA as TSP1/2 KO mice were sensitive to PTZ, similar to the TSP1 KO mice. Furthermore, there were similar levels of TGF-B signal activation during kindling in the TSP1 KO mice compared to wild-type. We observed decreased expression of voltage-dependent calcium channel subunit CACNA2D1 mRNA in TSP1, TSP2, and TSP1/2 KO mice. Decreased CACNA2D2 mRNA was only detected in mice that lacked TSP1 and α2δ-1/2 protein levels in the cortex were lower in the TSP 1/2 KO mice. CACNA2D2 knockout mice have spontaneous seizures and increased PTZ seizure susceptibility. Here we report similar findings, TSP1, and TSP1/2 KO mice have low levels of CACNA2D2 mRNA expression and α2δ-1/2 receptor level in the cortex, and are more susceptible to seizures. CACNA2D2 mutations in mice and humans can cause epilepsy. Our data suggest TSP1 in particular may control CACNA2D2 levels and could be a modifier of seizure susceptibility.

  15. Combination of valproate and paroxetine in mice exposed to picrotoxin

    OpenAIRE

    Kamal SM

    2012-01-01

    Sahar M KamalDepartment of Pharmacology, Faculty of Medicine, University of Ain-Shams, Cairo, EgyptAbstract: The frequent coexistence of depression in epileptic patients raises the issue of simultaneous use of antidepressants along with antiepileptic drugs in the management of such cases. However, it is necessary to evaluate the safety of these antiepileptic/antidepressant drug combinations. The present study investigates the effect of the antidepressant paroxetine (a selective serotonin reup...

  16. Anaplerotic triheptanoin diet enhances mitochondrial substrate use to remodel the metabolome and improve lifespan, motor function, and sociability in MeCP2-null mice.

    Directory of Open Access Journals (Sweden)

    Min Jung Park

    Full Text Available Rett syndrome (RTT is an autism spectrum disorder (ASD caused by mutations in the X-linked MECP2 gene that encodes methyl-CpG binding protein 2 (MeCP2. Symptoms range in severity and include psychomotor disabilities, seizures, ataxia, and intellectual disability. Symptom onset is between 6-18 months of age, a critical period of brain development that is highly energy-dependent. Notably, patients with RTT have evidence of mitochondrial dysfunction, as well as abnormal levels of the adipokines leptin and adiponectin, suggesting overall metabolic imbalance. We hypothesized that one contributor to RTT symptoms is energy deficiency due to defective nutrient substrate utilization by the TCA cycle. This energy deficit would lead to a metabolic imbalance, but would be treatable by providing anaplerotic substrates to the TCA cycle to enhance energy production. We show that dietary therapy with triheptanoin significantly increased longevity and improved motor function and social interaction in male mice hemizygous for Mecp2 knockout. Anaplerotic therapy in Mecp2 knockout mice also improved indicators of impaired substrate utilization, decreased adiposity, increased glucose tolerance and insulin sensitivity, decreased serum leptin and insulin, and improved mitochondrial morphology in skeletal muscle. Untargeted metabolomics of liver and skeletal muscle revealed increases in levels of TCA cycle intermediates with triheptanoin diet, as well as normalizations of glucose and fatty acid biochemical pathways consistent with the improved metabolic phenotype in Mecp2 knockout mice on triheptanoin. These results suggest that an approach using dietary supplementation with anaplerotic substrate is effective in improving symptoms and metabolic health in RTT.

  17. Cyclooxygenase-2 suppresses the anabolic response to PTH infusion in mice.

    Directory of Open Access Journals (Sweden)

    Shilpa Choudhary

    Full Text Available We previously reported that the ability of continuously elevated PTH to stimulate osteoblastic differentiation in bone marrow stromal cell cultures was abrogated by an osteoclastic factor secreted in response to cyclooxygenase-2 (Cox2-produced prostaglandin E2. We now examine the impact of Cox2 (Ptgs2 knockout (KO on the anabolic response to continuously elevated PTH in vivo. PTH (40 μg/kg/d or vehicle was infused for 12 or 21 days in 3-mo-old male wild type (WT and KO mice in the outbred CD-1 background. Changes in bone phenotype were assessed by bone mineral density (BMD, μCT and histomorphometry. PTH infusion for both 12 and 21 days increased femoral BMD in Cox2 KO mice and decreased BMD in WT mice. Femoral and vertebral trabecular bone volume fractions were increased in KO mice, but not in WT mice, by PTH infusion. In the femoral diaphysis, PTH infusion increased cortical area in Cox2 KO, but not WT, femurs. PTH infusion markedly increased trabecular bone formation rate in the femur, serum markers of bone formation, and expression of bone formation-related genes, growth factors, and Wnt target genes in KO mice relative to WT mice, and decreased gene expression of Wnt antagonists only in KO mice. In contrast to the differential effects of PTH on anabolic factors in WT and KO mice, PTH infusion increased serum markers of resorption, expression of resorption-related genes, and the percent bone surface covered by osteoclasts similarly in both WT and KO mice. We conclude that Cox2 inhibits the anabolic, but not the catabolic, effects of continuous PTH. These data suggest that the bone loss with continuously infused PTH in mice is due largely to suppression of bone formation and that this suppression is mediated by Cox2.

  18. Comparative Proteomic Study of Mouse Liver Exposed to Differing Gravitational Environments

    OpenAIRE

    Phinney, Brett S.; Weber, Darren M.; Fuller, Charles A.; Salemi, Michelle

    2013-01-01

    It has been shown that long term exposure to altered gravitational environments leads to altered intermediary metabolism with a concomitant reduction in body adiposity. This effect on liver protein expression has been poorly examined. Using gel/c MS/MS on extracted liver proteins we will compare protein profiles from mice flown in space compared to control mice maintained at earth's gravity on the ground. Livers were obtained from mice that were exposed for 90 days to three different living c...

  19. Cartilage-specific deletion of ephrin-B2 in mice results in early developmental defects and an osteoarthritis-like phenotype during aging in vivo

    OpenAIRE

    Valverde-Franco, Gladys; Lussier, Bertrand; Hum, David; Wu, Jiangping; Hamadjida, Adjia; Dancause, Numa; Fahmi, Hassan; Kapoor, Mohit; Pelletier, Jean-Pierre; Martel-Pelletier, Johanne

    2016-01-01

    Background Ephrins and their related receptors have been implicated in some developmental events. We have demonstrated that ephrin-B2 (EFNB2) could play a role in knee joint pathology associated with osteoarthritis (OA). Here, we delineate the in vivo role of EFNB2 in musculoskeletal growth, development, and in OA using a cartilage-specific EFNB2 knockout (EFNB2Col2KO) mouse model. Methods EFNB2Col2KO was generated with Col2a1-Cre transgenic mice. The skeletal development was evaluated using ...

  20. Differential Fmo3 gene expression in various liver injury models involving hepatic oxidative stress in mice

    International Nuclear Information System (INIS)

    Flavin-containing monooxygenase-3 (FMO3) catalyzes metabolic reactions similar to cytochrome P450 monooxygenase, however, most metabolites of FMO3 are considered non-toxic. Recent findings in our laboratory demonstrated Fmo3 gene induction following toxic acetaminophen (APAP) treatment in mice. The goal of this study was to evaluate Fmo3 gene expression in other diverse mouse models of hepatic oxidative stress and injury. Fmo3 gene regulation by Nrf2 was also investigated using Nrf2 knockout (Nrf2 KO) mice. In our studies, male C57BL/6J mice were treated with toxic doses of hepatotoxicants or underwent bile duct ligation (BDL, 10 days). Hepatotoxicants included APAP (400 mg/kg, 24–72 h), alpha-naphthyl isothiocyanate (ANIT; 50 mg/kg, 2–48 h), carbon tetrachloride (CCl4; 10 or 30 μL/kg, 24 and 48 h) and allyl alcohol (AlOH; 30 or 60 mg/kg, 6 and 24 h). Because oxidative stress activates nuclear factor (erythroid-derived 2)-like 2 (Nrf2), additional studies investigated Fmo3 gene regulation by Nrf2 using Nrf2 knockout (Nrf2 KO) mice. At appropriate time-points, blood and liver samples were collected for assessment of plasma alanine aminotransferase (ALT) activity, plasma and hepatic bile acid levels, as well as liver Fmo3 mRNA and protein expression. Fmo3 mRNA expression increased significantly by 43-fold at 12 h after ANIT treatment, and this increase translates to a 4-fold change in protein levels. BDL also increased Fmo3 mRNA expression by 1899-fold, but with no change in protein levels. Treatment of mice with CCl4 decreased liver Fmo3 gene expression, while no change in expression was detected with AlOH treatment. Nrf2 KO mice are more susceptible to APAP (400 mg/kg, 72 h) treatment compared to their wild-type (WT) counterparts, which is evidenced by greater plasma ALT activity. The Fmo3 mRNA and protein expression increased in Nrf2 KO mice after APAP treatment. Collectively, not all hepatotoxicants that produce oxidative stress alter Fmo3 gene expression

  1. Effect of aging and radiation in mice of different genotypes

    International Nuclear Information System (INIS)

    Data are presented on the life span of nine inbred strains and five hybrid strains of mice based on 400 mice of each sex for inbred and 200 mice of each sex for hybrid. Some of these mice were exposed when 120 days old to 250 R or 450 R of x radiation delivered at a dose rate of 60 R/min. Data on strain, sample size, and mean survival times are presented in tables

  2. Toxicity and teratogenicity evaluation of fenproporex in mice fetuses descending from parents that were exposed to this drug during intrauterine life Avaliação da toxicidade e da teratogenicidade do femproporex em fetos de camundongos provenientes de pais expostos à droga durante a vida intra-uterina

    Directory of Open Access Journals (Sweden)

    Camila Queiroz Moreira

    2007-10-01

    Full Text Available Fenproporex is an anorectic drug that is transformed into amphetamine in the organism. The use of amphetaminic compounds during pregnancy increases the risk of exencephaly, cleft palate and cardiac malformations. The aim of this study was to evaluate embryo-fetal development, embryotoxicity and possible teratogenic effects in mice fetuses descending from parents that were exposed to fenproporex duringintra-uterine development. Pregnant females were treated daily, by gavage, with 15 mg/kg of fenproporex during all the gestation. When the off springs reached the adult age, they were mated with integral mice, obtaining the2nd generation. On the 18th gestational day, female mice were killed. It was observed that fenproporex did not alter significantly placent weight, fetuses length, rate of postimplantation loss, visceral and skeletal analysis. This may have occurred due to the decrease of the amphetamine effects on the 2nd generation. However, there was statistically significant difference in relation to the fetuses weight. The reduction of fetal weight is used as parameter to evidence toxic effects of asubstance. Therefore, the results suggest that fenproporex presented fetaltoxicity in the tested experimental conditions. Femproporex é um anorexígeno que se transforma em anfetamina no organismo. O uso de compostos anfetamínicos durante a gravidez aumenta o risco de exencefalia, de fenda palatina e de malformações cardíacas. O objetivo deste estudo foi avaliar o desenvolvimento embriofetal, a embriotoxicidade e possíveis efeitos teratogênicos em fetos de camundongos provenientes de pais que foram expostos ao femproporex durante o desenvolvimento intra-uterino. As fêmeas prenhes foram tratadas diariamente, via gavage, com 15 mg/kg de femproporex, durante toda a gestação. Quando as progênies atingiram a idade adulta, foram acasaladas com camundongos íntegros, obtendo-se a 2ª geração. No 18º dia de prenhez, as fêmeas foram mortas

  3. Akt2 Deficiency is Associated with Anxiety and Depressive Behavior in Mice

    Directory of Open Access Journals (Sweden)

    Christina Leibrock

    2013-09-01

    Full Text Available Background: The economic burden associated with major depressive disorder and anxiety disorders render both disorders the most common and debilitating psychiatric illnesses. To date, the exact cellular and molecular mechanisms underlying the pathophysiology, successful treatment and prevention of these highly associated disorders have not been identified. Akt2 is a key protein in the phosphatidylinositide-3 (PI3K / glycogen synthase 3 kinase (GSK3 signaling pathway, which in turn is involved in brain-derived neurotrophic factor (BDNF effects on fear memory, mood stabilisation and action of several antidepressant drugs. The present study thus explored the impact of Akt2 on behaviour of mice. Methods: Behavioural studies (Open-Field, Light-Dark box, O-Maze, Forced Swimming Test, Emergence Test, Object Exploration Test, Morris Water Maze, Radial Maze have been performed with Akt2 knockout mice (akt-/- and corresponding wild type mice (akt+/+. Results: Anxiety and depressive behavior was significantly higher in akt-/- than in akt+/+ mice. The akt-/- mice were cognitively unimpaired but displayed increased anxiety in several behavioral tests (O-Maze test, Light-Dark box, Open Field test. Moreover, akt-/- mice spent more time floating in the Forced Swimming test, which is a classical feature of experimental depression. Conclusion: Akt2 might be a key factor in the pathophysiology of depression and anxiety.

  4. Behavioral and neurobiological changes in C57BL/6 mouse exposed to cuprizone: effects of antipsychotics

    Directory of Open Access Journals (Sweden)

    Haiyun Xu

    2010-03-01

    Full Text Available Recent human studies suggest a role for altered oligodendrocytes in the pathophysiology of schizophrenia. Our recent animal study has reported some schizophrenia-like behaviors in mice exposed to cuprizone (Xu et al., 2009, a copper chelator that has been shown to selectively damage the white matter. This study was to explore mechanisms underlying the behavioral changes in cuprizone-exposed mice and to examine effects of the antipsychotics haloperidol, clozapine and quetiapine on the changes in the mice. Mice given cuprizone for 14 days showed a deficit in the prepulse inhibition of acoustic startle response and higher dopamine in the prefrontal cortex (PFC, which changes were not seen in mice given cuprizone plus antipsychotics. Mice given cuprizone for 21 days showed lower spontaneous alternations in Y-maze, which was not seen in mice treated with the antipsychotics. Mice given cuprizone for 28 days displayed less social interactions, which was not seen in mice given cuprizone plus clozapine/quetiapine, but was seen in mice given cuprizone plus haloperidol. Mice given cuprizone for 42 days showed myelin sheath loss and lower myelin basic protein in PFC, caudate putamen, and hippocampus. The white matter damage in PFC was attenuated in mice given cuprizone plus clozapine/haloperidol. But the white matter damage in caudate putamen and hippocampus was only attenuated by clozapine and quetiapine, not by haloperidol. These results help us to understand the behavioral changes and provide experimental evidence for the protective effects of antipsychotics on white matter damage in cuprizone-exposed mice.

  5. 补充维生素B2对急性低氧暴露小鼠血浆代谢组的影响%Effect of vitamin B2 supplementation on plasma metabonome in the mice exposed to acute hypoxia

    Institute of Scientific and Technical Information of China (English)

    王宇平; 郭长江; 杨继军; 韦京豫; 吴健全; 高蔚娜

    2010-01-01

    目的 观察补充维生素B2对急性低氧暴露小鼠外周血代谢组的影响.方法 采用随机数字表法将35只雄性昆明小鼠随机分为:正常对照组,低氧对照组,2倍、4倍及8倍维生素B2补充组,每组7只.以相应饲料(维生素B2含量分别为6 mg/kg、12 mg/kg、24 mg/kg和48 mg/kg)喂养2周后,除正常对照组外,其它各组均在模拟6000 m高度停留8 h,采集血浆,以核磁共振的方法分析其代谢组变化.结果 急性低氧暴露后,各组动物血浆代谢组在得分图中呈聚类型分布,且有先分离后同归的代谢模式变化轨迹,显示出补充不同剂量维生素B2后小鼠血浆代谢组逐渐恢复的趋势.代谢模式产生差别的原因是脂类、乳酸、丙氨酸、N-乙酰糖蛋白、谷氨酸、胆碱、牛磺酸、糖、肉碱、甘氨酸和肌酐等物质的水平发生了变化,表明相关的代谢途径发生了变化.结论 补充维生素B2使急性低氧暴露机体碳水化合物、脂肪、蛋白质代谢发生改变,而维生素B2可以改善碳水化合物代谢,并可能通过肉碱间接调节了脂肪代谢;同时还发现一些氨基酸代谢发生显著变化.%Objective To observe the effects of vitamin B2 supplementation on plasma metabonome of the mice which exposed to acute hypoxia. Methods Thirty-five male Kunming mice were randomly and averagely divided into 5 groups, among which the control and hypoxia control groups were fed the fodder containing 6, 12, 24, 48 mg/kg vitamin B2 respectively. All groups were exposed to simulated hypoxia environment (equivalent to 6000 meters above sea level) for 8 hours except control group. Nuclear magnetic resonance spectrometer was used to test the change of metabonome from collected plasma. Results After acute hypoxia exposure, the metabonome pattern in all groups showed clustering distribution in scores plot and the metabonome changes were along the trail from segregation to regression. These indicated a gradual recover

  6. β-Lactotensin derived from bovine β-lactoglobulin exhibits anxiolytic-like activity as an agonist for neurotensin NTS(2) receptor via activation of dopamine D(1) receptor in mice.

    Science.gov (United States)

    Hou, I-Ching; Suzuki, Chihiro; Kanegawa, Norimasa; Oda, Ayako; Yamada, Ayako; Yoshikawa, Masaaki; Yamada, Daisuke; Sekiguchi, Masayuki; Wada, Etsuko; Wada, Keiji; Ohinata, Kousaku

    2011-11-01

    β-Lactotensin (His-Ile-Arg-Leu) is a bioactive peptide derived from bovine milk β-lactoglobulin, acting as a natural agonist for neurotensin receptors. We found that β-lactotensin exhibited anxiolytic-like activity in an elevated plus-maze test after its intraperitoneal (i.p.) administration in mice. β-Lactotensin was also orally active. The anxiolytic-like activity of β-lactotensin after i.p. administration was blocked by levocabastine, an antagonist for the neurotensin NTS(2) receptor. β-Lactotensin had anxiolytic-like activity in wild-type but not Ntsr2-knockout mice. β-Lactotensin increased intracellular Ca(2+) flux in glial cells derived from wild-type mice but not Ntsr2 knockout mice. These results suggest that β-lactotensin acts as an NTS(2) receptor agonist having anxiolytic-like activity. The anxiolytic-like activity of β-lactotensin was also blocked by SCH23390 and SKF83566, antagonists for dopamine D(1) receptor, but not by raclopride, an antagonist for D(2) receptor. Taken together, β-lactotensin may exhibit anxiolytic-like activity via NTS(2) receptor followed by D(1) receptor.

  7. EXPOSE-R on Mission on the ISS

    Science.gov (United States)

    Panitz, Corinna; Rabbow, Elke; Rettberg, Petra; Barczyk, Simon; Kloss, Maria; Reitz, Guenther

    Currently EXPOSE-R is on mission! This astrobiological exposure facility was accommodated at the universal workplace URM-D Zenith payload site, located outside the Russian Svezda Module of the International Space Station (ISS) by extravehicular activity (EVA) on March 10th 2009. It contains 3 trays accommodating 12 sample compartments with sample carriers in three levels either open to space vacuum or kept in a defined gas environment. In its 8 experiments of biological and chemical content, more than 1200 individual samples are exposed to solar ultraviolet (UV) radiations, vacuum, cosmic rays or extreme temperature variations. In their different experiments the involved scientists are studying the question of life's origin on Earth and the results of their experiments are contributing to different aspects of the evolution and distribution of life in the Universe. Additionally integrated into the EXPOSE-R facility are several dosimeters monitoring the ionising and the solar UV-radiation during the mission to deliver useful information to complement the sample analysis. In close cooperation with the DLR and the Technical University Munich (TUM), the Rheinisch -Westfülische Technischen Hochschule Aachen (RWTH Aachen) operates the experiment "Spores". a This is one of the 6 astrobiological experiments of the ROSE-Consortium" (Response of Or-ganisms to Space Environment) of the EXPOSE-R mission. In these experiments spores of bacteria, fungi and ferns are being over layered or mixed with meteorite material. The analysis of the effect of the space parameters on different biological endpoints of the spores of the mi-croorganism Bacillus subtilis will be performed after the retrieval of the experiment scheduled for the end of 2010. Parallel to the space mission an identical set of samples was accommodated into EXPOSE-R trays identical in construction to perform the Mission Ground Reference (MGR) Test. Currently this MGR Test is carried out in the Planetary and Space

  8. Profound obesity secondary to hyperphagia in mice lacking kinase suppressor of ras 2.

    Science.gov (United States)

    Revelli, Jean-Pierre; Smith, Deon; Allen, Jason; Jeter-Jones, Sabrina; Shadoan, Melanie K; Desai, Urvi; Schneider, Matthias; van Sligtenhorst, Isaac; Kirkpatrick, Laura; Platt, Kenneth A; Suwanichkul, Adisak; Savelieva, Katerina; Gerhardt, Brenda; Mitchell, Jay; Syrewicz, James; Zambrowicz, Brian; Hamman, Brian D; Vogel, Peter; Powell, David R

    2011-05-01

    The kinase suppressor of ras 2 (KSR2) gene resides at human chromosome 12q24, a region linked to obesity and type 2 diabetes (T2D). While knocking out and phenotypically screening mouse orthologs of thousands of druggable human genes, we found KSR2 knockout (KSR2(-/-)) mice to be more obese and glucose intolerant than melanocortin 4 receptor(-/-) (MC4R(-/-)) mice. The obesity and T2D of KSR2(-/-) mice resulted from hyperphagia which was unresponsive to leptin and did not originate downstream of MC4R. The kinases AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) are each linked to food intake regulation, but only mTOR had increased activity in KSR2(-/-) mouse brain, and the ability of rapamycin to inhibit food intake in KSR2(-/-) mice further implicated mTOR in this process. The metabolic phenotype of KSR2 heterozygous (KSR2(+/minus;)) and KSR2(-/-) mice suggests that human KSR2 variants may contribute to a similar phenotype linked to human chromosome 12q24.

  9. 近红外长余辉纳米颗粒经小鼠眼部暴露后体内分布和代谢情况∗%Distribution and metabolization of near infrared-emitting long persistent luminescence nanoparticles exposed to eyes in mice

    Institute of Scientific and Technical Information of China (English)

    姜晓卫; 邓爱军; 李金磊; 史俊朋; 张洪武

    2015-01-01

    为了研究纳米颗粒通过眼部暴露后进入体内的路径及在体内的分布和代谢情况,实验采用近红外长余辉纳米探针作为示踪剂,对小鼠进行眼部暴露,随后利用活体成像技术观察其进入小鼠体内的过程及分布情况,于暴露第4天收集代谢产物,第7天取重要脏器和血液,并检测纳米探针的存在情况。结果显示纳米探针可由眼经口腔进入胃肠道中,并且纳米颗粒暴露4天后在小鼠的粪便中检测到强荧光信号,而尿液中的荧光信号较弱,暴露7d后在小鼠的眼睑结膜、胃及眼球中检测到强荧光信号,而其余器官的荧光信号较弱。这表明通过眼部暴露后,纳米颗粒主要分布在眼和消化系统中,最后大部分经消化系统代谢。%To study the procedure, distribution and metabolization of nanoparticles exposed to eyes in vivo, near infrared⁃emitting long persistent luminescence nanoprobes were used as tracer. After exposure to eyes of mice, the luminescence signal was collected on IVIS LuminaⅡimaging system. On the fourth and seventh day, we took the metabolites, major organs and blood separately. Subsequently, the luminescence signal was collected. Results showed that the nanoparticles entered the mouth and stomach after exposure to eyes. Furthermore, after four days exposure, the luminescence signal of the feces was strong, while that of the urine was weak. After seven days exposure, eye conjunctiva, stomach and eyeball showed strong luminescence signals, while other organs showed weak luminescence signals. The above results indicated that nanoparticles mainly distributed in the eyes and digestive system after exposure to eyes, and most of them were excreted from the body via digestive system.

  10. Alterations in Brain Inflammation, Synaptic Proteins, and Adult Hippocampal Neurogenesis during Epileptogenesis in Mice Lacking Synapsin2.

    Directory of Open Access Journals (Sweden)

    Deepti Chugh

    Full Text Available Synapsins are pre-synaptic vesicle-associated proteins linked to the pathogenesis of epilepsy through genetic association studies in humans. Deletion of synapsins causes an excitatory/inhibitory imbalance, exemplified by the epileptic phenotype of synapsin knockout mice. These mice develop handling-induced tonic-clonic seizures starting at the age of about 3 months. Hence, they provide an opportunity to study epileptogenic alterations in a temporally controlled manner. Here, we evaluated brain inflammation, synaptic protein expression, and adult hippocampal neurogenesis in the epileptogenic (1 and 2 months of age and tonic-clonic (3.5-4 months phase of synapsin 2 knockout mice using immunohistochemical and biochemical assays. In the epileptogenic phase, region-specific microglial activation was evident, accompanied by an increase in the chemokine receptor CX3CR1, interleukin-6, and tumor necrosis factor-α, and a decrease in chemokine keratinocyte chemoattractant/ growth-related oncogene. Both post-synaptic density-95 and gephyrin, scaffolding proteins at excitatory and inhibitory synapses, respectively, showed a significant up-regulation primarily in the cortex. Furthermore, we observed an increase in the inhibitory adhesion molecules neuroligin-2 and neurofascin and potassium chloride co-transporter KCC2. Decreased expression of γ-aminobutyric acid receptor-δ subunit and cholecystokinin was also evident. Surprisingly, hippocampal neurogenesis was reduced in the epileptogenic phase. Taken together, we report molecular alterations in brain inflammation and excitatory/inhibitory balance that could serve as potential targets for therapeutics and diagnostic biomarkers. In addition, the regional differences in brain inflammation and synaptic protein expression indicate an epileptogenic zone from where the generalized seizures in synapsin 2 knockout mice may be initiated or spread.

  11. Critical period for acoustic preference in mice

    OpenAIRE

    Yang, Eun-Jin; Lin, Eric W.; Hensch, Takao K.

    2012-01-01

    Preference behaviors are often established during early life, but the underlying neural circuit mechanisms remain unknown. Adapting a unique nesting behavior assay, we confirmed a “critical period” for developing music preference in C57BL/6 mice. Early music exposure between postnatal days 15 and 24 reversed their innate bias for silent shelter, which typically could not be altered in adulthood. Instead, exposing adult mice treated acutely with valproic acid or carrying a targeted deletion of...

  12. Parasitological characteristics of Schistosoma mansoni infection in swiss mice with underlying malnutrition

    OpenAIRE

    Simões Carla; Neves Renata Heisler; Barros Lucas de Andrade; Brito Patrícia Dias; Cravo Cristiane Oliveira; Moura Egberto Gaspar de; Machado-Silva José Roberto

    2002-01-01

    The effects of a protein-restricted diet (8% protein, 81% carbohydrate and 11% lipids) on Schistosoma mansoni infectivity, fecal egg excretion and intestinal egg distribution in Swiss (SW) mice were studied. Pregnant mice received a deficient diet from the middle of gestation until delivery. Seven-days-old mice were exposed to 50 cercariae (BH strain, Brazil). Offspring mice had a free access to the deficient diet since lactation until adulthood. The controls were fed with a commercial mice d...

  13. Subchronic exposure of mice to Love Canal soil contaminants.

    Science.gov (United States)

    Silkworth, J B; McMartin, D N; Rej, R; Narang, R S; Stein, V B; Briggs, R G; Kaminsky, L S

    1984-04-01

    The health hazard potential of soil collected from the surface of the Love Canal chemical dump site in Niagara Falls, New York, was assessed in 90-day exposure studies. Female CD-1 mice were exposed to two concentrations of the volatile components of 1 kg of soil with and without direct soil contact. Control mice were identically housed but without soil. The soil was replaced weekly and 87 compounds were detected in the air in the cages above fresh and 7-day-old soil as analyzed by gas chromatography/mass spectrometry. The concentration of many of these compounds decreased during the 7-day exposure cycle. Histopathologic, hematologic, and serum enzyme studies followed necropsy of all mice. There was no mortality of mice exposed for up to 90 days under any condition. Thymus and spleen weights relative to body weight were increased after 4 weeks of exposure by inhalation but not after 8 or 12 weeks of exposure. alpha-, beta-, and delta- Benzenehexachlorides , pentachlorobenzene, and hexachlorobenzene were detected in liver tissue from these animals. Mice exposed to 5- to 10-fold elevated concentration of volatiles had increased body and relative kidney weights. There was no chemically induced lesion in any animal exposed only to the volatile soil contaminants. Mice exposed by direct contact with the soil without elevated volatile exposure had increased body (10%) and relative liver weights (169%). Centrolobular hepatocyte hypertrophy, which involved 40 to 70% of the lobules, was observed in all mice in this group.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Disabled-2 Determines Commitment of a Pre-adipocyte Population in Juvenile Mice

    Science.gov (United States)

    Tao, Wensi; Moore, Robert; Meng, Yue; Yeasky, Toni M.; Smith, Elizabeth R.; Xu, Xiang-Xi

    2016-01-01

    Disabled-2 (Dab2) is a widely expressed clathrin binding endocytic adaptor protein and known for the endocytosis of the low-density lipoprotein (LDL) family receptors. Dab2 also modulates endosomal Ras/MAPK (Erk1/2) activity by regulating the disassembly of Grb2/Sos1 complexes associated with clathrin-coated vesicles. We found that the most prominent phenotype of Dab2 knockout mice was their striking lean body composition under a high fat and high caloric diet, although the weight of the mutant mice was indistinguishable from wild-type littermates on a regular chow. The remarkable difference in resistance to high caloric diet-induced weight gain of the dab2-deleted mice was presented only in juvenile but not in mature mice. Investigation using Dab2-deficient embryonic fibroblasts and mesenchymal stromal cells indicated that Dab2 promoted adipogenic differentiation by modulation of MAPK (Erk1/2) activity, which otherwise suppresses adipogenesis through the phosphorylation of PPARγ. The results suggest that Dab2 is required for the excessive calorie-induced differentiation of an adipocyte progenitor cell population that is present in juvenile but depleted in mature animals. The finding provides evidence for a limited pre-adipocyte population in juvenile mammals and the requirement of Dab2 in the regulation of Ras/MAPK signal in the commitment of the precursor cells to adipose tissues. PMID:27779214

  15. Chrysophanol attenuates lead exposure-induced injury to hippocampal neurons in neonatal mice

    Institute of Scientific and Technical Information of China (English)

    Ji Zhang; Chunlin Yan; Shu Wang; Yong Hou; Guiping Xue; Li Zhang

    2014-01-01

    Previous studies have shown that chrysophanol protects against learning and memory impairments in lead-exposed adult mice. In the present study, we investigated whether chrys-ophanol can alleviate learning and memory dysfunction and hippocampal neuronal injury in lead-exposed neonatal mice. At the end of lactation, chrysophanol (0.1, 1.0, 10.0 mg/kg) was administered to the neonatal mice by intraperitoneal injection for 15 days. Chrysophanol signifi-cantly alleviated injury to hippocampal neurons and improved learning and memory abilities in the lead-poisoned neonatal mice. Chrysophanol also significantly decreased lead content in blood, brain, heart, spleen, liver and kidney in the lead-exposed neonatal mice. The levels of malondialdehyde in the brain, liver and kidney were significantly reduced, and superoxide dismutase and glutathione peroxidase activities were significantly increased after chrysophanol treatment. Collectively, these findings indicate that chrysophanol can significantly reduce damage to hippocampal neurons in lead-exposed neonatal mice.

  16. 35GHz毫米波急性辐照小鼠诱发丘脑-垂体-肾上腺皮质轴功能改变和Th1/Th2失衡%Functional changes of HPA axis and Th1/Th2 imbalance in mice acutely exposed to 35 GHz millimeter-wave

    Institute of Scientific and Technical Information of China (English)

    杜丽; 孙嵘; 马琼; 李志慧; 蔡金玲; 杨晓云; 满其航; 崔玉芳

    2013-01-01

    目的 观察35 GHz毫米波诱发的急性应激反应中重要细胞因子及下丘脑-垂体-肾上腺皮质(HPA)轴相关激素的表达规律,旨在探索神经·内分泌·免疫系统之间内在的关联.方法 以420 mW/cm2功率密度的35 GHz毫米波源急性辐照BALB/c小鼠60 s.于照后不同时间,用ELISA方法检测血清中IFN-γ、IL-4等细胞因子的表达水平,并用RT-PCR和免疫组织化学方法检测下丘脑促肾上腺皮质素释放激素(CRH)和海马区糖皮质激素受体(GR)的变化.结果 Th1和Th2型细胞因子IFN-γ和IL-4在照后3d均升高至峰值(t=-6.59、-2.28,P<0.05),至照后7d仍明显高于对照组;其比值在照后1和3d明显增高,即发生了明显的Th1/Th2平衡向Th1免疫反应漂移的现象.毫米波急性辐照后下丘脑CRH mRNA含量出现持续性升高,至7d升高至峰值(t=-7.03,P <0.05);而海马GR mRNA含量在3d达到峰值后迅速降低至对照组水平.下丘脑CRH和海马GR蛋白表达的趋势与其mRNA水平变化基本一致.结论 小鼠经35 GHz毫米波急性辐照后,Th1/Th2平衡向Th1方向偏移;同时应激增加的下丘脑CRH和海马GR对IFN-γ等因子的反馈抑制,使向Th1偏移的免疫失衡现象得以改善,可缓解过度应激造成的免疫损伤.%Objective To investigate the expression pattern of cytokines and HPA axis hormones in acute stress reaction induced by 35 GHz millimeter-wave (MMW) radiation,and to explore the intrinsic association among the nerve-endocrine-immune system.Methods BALB/c mice were exposed to 35 GHz MMW with an average power density of 420 mW/cm2 for 60 s.The contents of IFN-γ and IL-4 in serum were measured and the expression level of hypothalamic corticotropin releasing hormone (CRH) and hippocampus glucocorticoid receptor (GR) in brain were analyzed at different time points after MMW exposure.Results The levels of IFN-γ and IL-4 and the cytokines of Thl and Th2 increased to peak levels (t =-6.59,-2.28,P < 0.05) at 3

  17. Antioxidants Improve the Phenotypes of Dilated Cardiomyopathy and Muscle Fatigue in Mitochondrial Superoxide Dismutase-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Takahiko Shimizu

    2013-01-01

    Full Text Available Redox imbalance elevates the reactive oxygen species (ROS level in cells and promotes age-related diseases. Superoxide dismutases (SODs are antioxidative enzymes that catalyze the degradation of ROS. There are three SOD isoforms: SOD1/CuZn-SOD, SOD2/Mn-SOD, and SOD3/EC-SOD. SOD2, which is localized in the mitochondria, is an essential enzyme required for mouse survival, and systemic knockout causes neonatal lethality in mice. To investigate the physiological function of SOD2 in adult mice, we generated a conditional Sod2 knockout mouse using a Cre-loxP system. When Sod2 was specifically deleted in the heart and muscle, all mice exhibited dilated cardiomyopathy (DCM and died by six months of age. On the other hand, when Sod2 was specifically deleted in the skeletal muscle, mice showed severe exercise disturbance without morphological abnormalities. These provide useful model of DCM and muscle fatigue. In this review, we summarize the impact of antioxidants, which were able to regulate mitochondrial superoxide generation and improve the phenotypes of the DCM and the muscle fatigue in mice.

  18. IgG Suppresses Antibody Responses in Mice Lacking C1q, C3, Complement Receptors 1 and 2, or IgG Fc-Receptors.

    Science.gov (United States)

    Bergström, Joakim J E; Heyman, Birgitta

    2015-01-01

    Antigen-specific IgG antibodies, passively administered to mice or humans together with large particulate antigens like erythrocytes, can completely suppress the antibody response against the antigen. This is used clinically in Rhesus prophylaxis, where administration of IgG anti-RhD prevents RhD-negative women from becoming immunized against RhD-positive fetal erythrocytes aquired transplacentally. The mechanisms by which IgG suppresses antibody responses are poorly understood. We have here addressed whether complement or Fc-receptors for IgG (FcγRs) are required for IgG-mediated suppression. IgG, specific for sheep red blood cells (SRBC), was administered to mice together with SRBC and the antibody responses analyzed. IgG was able to suppress early IgM- as well as longterm IgG-responses in wildtype mice equally well as in mice lacking FcγRIIB (FcγRIIB knockout mice) or FcγRI, III, and IV (FcRγ knockout mice). Moreover, IgG was able to suppress early IgM responses equally well in mice lacking C1q (C1qA knockout mice), C3 (C3 knockout mice), or complement receptors 1 and 2 (Cr2 knockout mice) as in wildtype mice. Owing to the previously described severely impaired IgG responses in the complement deficient mice, it was difficult to assess whether passively administered IgG further decreased their IgG response. In conclusion, Fc-receptor binding or complement-activation by IgG does not seem to be required for its ability to suppress antibody responses to xenogeneic erythrocytes. PMID:26619292

  19. IgG Suppresses Antibody Responses in Mice Lacking C1q, C3, Complement Receptors 1 and 2, or IgG Fc-Receptors.

    Directory of Open Access Journals (Sweden)

    Joakim J E Bergström

    Full Text Available Antigen-specific IgG antibodies, passively administered to mice or humans together with large particulate antigens like erythrocytes, can completely suppress the antibody response against the antigen. This is used clinically in Rhesus prophylaxis, where administration of IgG anti-RhD prevents RhD-negative women from becoming immunized against RhD-positive fetal erythrocytes aquired transplacentally. The mechanisms by which IgG suppresses antibody responses are poorly understood. We have here addressed whether complement or Fc-receptors for IgG (FcγRs are required for IgG-mediated suppression. IgG, specific for sheep red blood cells (SRBC, was administered to mice together with SRBC and the antibody responses analyzed. IgG was able to suppress early IgM- as well as longterm IgG-responses in wildtype mice equally well as in mice lacking FcγRIIB (FcγRIIB knockout mice or FcγRI, III, and IV (FcRγ knockout mice. Moreover, IgG was able to suppress early IgM responses equally well in mice lacking C1q (C1qA knockout mice, C3 (C3 knockout mice, or complement receptors 1 and 2 (Cr2 knockout mice as in wildtype mice. Owing to the previously described severely impaired IgG responses in the complement deficient mice, it was difficult to assess whether passively administered IgG further decreased their IgG response. In conclusion, Fc-receptor binding or complement-activation by IgG does not seem to be required for its ability to suppress antibody responses to xenogeneic erythrocytes.

  20. Life shortening and carcinogenesis in mice irradiated at the perinatal period with gamma rays

    International Nuclear Information System (INIS)

    This study elucidates the life-span radiation effects in mice irradiated at the perinatal period in comparison to mice irradiated at the young adult period. B6C3F1 female mice were irradiated at 17 days of prenatal age, at 0 days of postnatal age, or as young adults at 15 weeks of age with 190, 380, or 570 rads of 137Cs gamma rays. Mice irradiated at the late fetal period showed dose-dependent life shortening of somewhat lesser magnitude than that seen after neonatal or young adult irradiation. Mice exposed at the late fetal period were highly susceptible to induction of pituitary tumors for which the latent period was the longest of all induced neoplasms. Incidence of lung tumors in mice irradiated at the late fetal period with 190 and 380 rads was higher than in controls. Malignant lymphomas of the lymphocytic type developed in excess, after a short latent period, in mice irradiated fetally with the highest dose; susceptibility of prenatally exposed mice was lower than that of early postnatally exposed mice. Liver tumors developed more frequently in mice irradiated in utero than in controls; susceptibility to induction of this type of neoplasm was highest at the neonatal period. In general, carcinogenic response of mice exposed at the late fetal period resembled that of neonatally exposed mice but was quite different from that of young adult mice. Mice exposed as young adults have no, or low, susceptibility to induction of pituitary, lung, and liver tumors; and a higher susceptibility to induction of myeloid leukemias and Harderian gland tumors. 19 refs., 4 figs., 3 tabs

  1. Euthanasia of neonatal mice with carbon dioxide

    Science.gov (United States)

    Pritchett, K.; Corrow, D.; Stockwell, J.; Smith, A.

    2005-01-01

    Exposure to carbon dioxide (CO2) is the most prevalent method used to euthanize rodents in biomedical research. The purpose of this study was to determine the time of CO2 exposure required to euthanize neonatal mice (0 to 10 days old). Multiple groups of mice were exposed to 100% CO 2 for time periods between 5 and 60 min. Mice were placed in room air for 10 or 20 min after CO2 exposure, to allow for the chance of recovery. If mice recovered at one time point, a longer exposure was examined. Inbred and outbred mice were compared. Results of the study indicated that time to death varied with the age of the animals and could be as long as 50 min on the day of birth and differed between inbred and outbred mice. Institutions euthanizing neonatal mice with CO2 may wish to adjust their CO 2 exposure time periods according the age of the mice and their genetic background. Copyright 2005 by the American Association for Laboratory Animal Science.

  2. Keratinocyte-targeted expression of human laminin γ2 rescues skin blistering and early lethality of laminin γ2 deficient mice.

    Directory of Open Access Journals (Sweden)

    Tracy L Adair-Kirk

    Full Text Available Laminin-332 is a heterotrimeric basement membrane component comprised of the α3, ß3, and γ2 laminin chains. Laminin-332 modulates epithelial cell processes, such as adhesion, migration, and differentiation and is prominent in many embryonic and adult tissues. In skin, laminin-332 is secreted by keratinocytes and is a key component of hemidesmosomes connecting the keratinocytes to the underlying dermis. In mice, lack of expression of any of the three Laminin-332 chains result in impaired anchorage and detachment of the epidermis, similar to that seen in human junctional epidermolysis bullosa, and death occurs within a few days after birth. To bypass the early lethality of laminin-332 deficiency caused by the knockout of the mouse laminin γ2 chain, we expressed a dox-controllable human laminin γ2 transgene under a keratinocyte-specific promoter on the laminin γ2 (Lamc2 knockout background. These mice appear similar to their wild-type littermates, do not develop skin blisters, are fertile, and survive >1.5 years. Immunofluorescence analyses of the skin showed that human laminin γ2 colocalized with mouse laminin α3 and ß3 in the basement membrane zone underlying the epidermis. Furthermore, the presence of "humanized" laminin-332 in the epidermal basement membrane zone rescued the alterations in the deposition of hemidesmosomal components, such as plectin, collagen type XVII/BP180, and integrin α6 and ß4 chains, seen in conventional Lamc2 knockout mice, leading to restored formation of hemidesmosomes. These mice will be a valuable tool for studies of organs deficient in laminin-332 and the role of laminin-332 in skin, including wound healing.

  3. Advances in treating exposed fractures☆

    OpenAIRE

    Pedro Nogueira Giglio; Alexandre Fogaça Cristante; José Ricardo Pécora; Camilo Partezani Helito; Ana Lucia Lei Munhoz Lima; Jorge dos Santos Silva

    2015-01-01

    The management of exposed fractures has been discussed since ancient times and remains of great interest to present-day orthopedics and traumatology. These injuries are still a challenge. Infection and nonunion are feared complications. Aspects of the diagnosis, classification and initial management are discussed here. Early administration of antibiotics, surgical cleaning and meticulous debridement are essential. The systemic conditions of patients with multiple trauma and the local conditio...

  4. Insulin Activates Vagal Afferent Neurons Including those Innervating Pancreas via Insulin Cascade and Ca(2+ Influx: Its Dysfunction in IRS2-KO Mice with Hyperphagic Obesity.

    Directory of Open Access Journals (Sweden)

    Yusaku Iwasaki

    Full Text Available Some of insulin's functions, including glucose/lipid metabolism, satiety and neuroprotection, involve the alteration of brain activities. Insulin could signal to the brain via penetrating through the blood-brain barrier and acting on the vagal afferents, while the latter remains unproved. This study aimed to clarify whether insulin directly regulates the nodose ganglion neurons (NGNs of vagal afferents in mice. NGs expressed insulin receptor (IR and insulin receptor substrate-2 (IRS2 mRNA, and some of NGNs were immunoreactive to IR. In patch-clamp and fura-2 microfluorometric studies, insulin (10(-12∼10(-6 M depolarized and increased cytosolic Ca(2+ concentration ([Ca(2+]i in single NGNs. The insulin-induced [Ca(2+]i increases were attenuated by L- and N-type Ca(2+ channel blockers, by phosphatidylinositol 3 kinase (PI3K inhibitor, and in NGNs from IRS2 knockout mice. Half of the insulin-responsive NGNs contained cocaine- and amphetamine-regulated transcript. Neuronal fibers expressing IRs were distributed in/around pancreatic islets. The NGNs innervating the pancreas, identified by injecting retrograde tracer into the pancreas, responded to insulin with much greater incidence than unlabeled NGNs. Insulin concentrations measured in pancreatic vein was 64-fold higher than that in circulation. Elevation of insulin to 10(-7 M recruited a remarkably greater population of NGNs to [Ca(2+]i increases. Systemic injection of glibenclamide rapidly released insulin and phosphorylated AKT in NGs. Furthermore, in IRS2 knockout mice, insulin action to suppress [Ca(2+]i in orexigenic ghrelin-responsive neurons in hypothalamic arcuate nucleus was intact while insulin action on NGN was markedly attenuated, suggesting a possible link between impaired insulin sensing by NGNs and hyperphagic obese phenotype in IRS2 knockout mice These data demonstrate that insulin directly activates NGNs via IR-IRS2-PI3K-AKT-cascade and depolarization-gated Ca(2+ influx. Pancreas

  5. Effects of the light--dark cycle on a water tank social interaction test in mice.

    Science.gov (United States)

    Nejdi, A; Guastavino, J M; Lalonde, R

    1996-01-01

    Mice were exposed to a water tank interaction test in which food could be obtained either by wading in the water or by attacking littermates. A tank with progressively rising water levels caused mice in groups of four to differentiate into those willing to wade (carrier mice) from those unwilling to wade (noncarrier mice). Noncarrier mice could only obtain food by stealing it from carrier mice or from other noncarrier mice. It was found that mice during the dark period of the light--dark cycle were more willing to wade in the search for food rather than attempt to steal food from other mice. Because mice are generally more active during the dark period, this result suggests that higher activity levels increase the willingness to share the work load, a form of altruism, rather than promote parasitic behavior and aggression.

  6. Effectiveness of compensation of lymphoid defficiency in lethally exposed animals through transplantation of cryopreserved lymphoid cells

    International Nuclear Information System (INIS)

    In experiments on lethally exposed (LDsub(100/15)) (CBAxC57B1)F1 mice treated with bone marrow, it was demonstrated that transplantation of syngeneic cryopreserved lymphocytes accelerates markedly the recovery of cellularity of bone marrow, spleen and thymus and rises the level of humoral and cellular immune response of the organism

  7. Sisters Hope - the exposed self

    DEFF Research Database (Denmark)

    Lawaetz, Anna; Hallberg, Gry Worre

    ’ and the establishment of fictional spaces outside the institutional art context. In the Unfolding Academia-context Sisters Hope investigates new forms of research and (re)presentation through the creation of interactive and affective learning-spaces. At Collective Futures Sisters Hope explored questions such as: How...... can we create a ‘learning space’ or a ‘research lab’, where the participants are inspired to approach their project in a new way with the outset in bodily and somatic experiences within the space? And how can we understand and distinguish what we understand to be the exposed self and the poetic self…...

  8. Gender influences the response to experimental silica-induced lung fibrosis in mice

    Science.gov (United States)

    Brass, David M.; McGee, Sean P.; Dunkel, Mary K.; Reilly, Sarah M.; Tobolewski, Jacob M.; Sabo-Attwood, Tara

    2010-01-01

    Accumulating evidence suggests that gender can have a profound effect on incidence and severity of a variety of pulmonary diseases. To address the influence of gender on the development of silica-induced pulmonary fibrosis, we instilled 0.2 g/kg silica into male and female C57BL/6 mice and examined the fibrotic and inflammatory response at 14 days postexposure. Both silica-exposed male and female mice had significant increases in total lung hydroxyproline compared with saline controls. However, silica-exposed female mice had significantly less total lung hydroxyproline than silica-exposed male mice. This observation was confirmed by color thresholding image analysis. Interestingly, silica-exposed female mice had significantly more inflammatory cells, the majority of which were macrophages, as well as higher levels of the macrophage-specific chemokines MCP-1 and CCL9 in whole lung lavage compared with silica-exposed male mice. We also show that at baseline, estrogen receptor α (ERα) mRNA expression is lower in female mice than in males and that ERα mRNA expression is decreased by silica exposure. Finally, we show that the response of ovariectomized female mice to silica instillation is similar to that of male mice. These observations together show that gender influences the lung response to silica. PMID:20729388

  9. A comparison of UVB-carcinogenesis between nude mice and nude beige mice

    Energy Technology Data Exchange (ETDEWEB)

    Ishigaki, Yasuhito; Yasuda, Kazuhiro; Hashimoto, Noriyoshi; Hayakawa, Jun-ichiro; Nikaido, Osamu [Kanazawa Univ. (Japan). Faculty of Pharmaceutical Sciences; Hiai, Hiroshi

    1998-06-01

    To gain an insight into the relationship between UVB-carcinogenesis and natural killer activity, we examined ultraviolet light-induced carcinogenesis in mice with high natural killer activity (KSN) and mice with natural killer deficiency (KSN-bg). We exposed mice six times a week to three levels of daily ultraviolet B (UVB) doses; 320, 160 and 0 J/m{sup 2}/day. During the latency period of skin tumor development in KSN mice, we detected no suppression of the natural killer activity at both 320 and 160 J/m{sup 2}/day. Even at 1340 J/m{sup 2}/day, we could not detect any significant suppression of NK activity in KSN mice. When we irradiated spleen cells in vitro, we observed NK activity suppression. Next, we compared the carcinogenic effects of UVB-irradiation on KSN and KSN-bg mice. At 320 J/m{sup 2}/day, we detected no significant differences between them. In contrast, at 160 J/m{sup 2}/day, KSN-bg mice showed a significantly higher rate of skin tumor induction than KSN mice (p<0.05). Most UVB-induced tumors were squamous cell carcinoma, the rest were spindle cell carcinoma, papilloma and mixed type. Our results suggest that NK activity plays a protective role against UVB-carcinogenesis from low daily-doses of UVB-irradiation. (author)

  10. Advances in treating exposed fractures.

    Science.gov (United States)

    Nogueira Giglio, Pedro; Fogaça Cristante, Alexandre; Ricardo Pécora, José; Partezani Helito, Camilo; Lei Munhoz Lima, Ana Lucia; Dos Santos Silva, Jorge

    2015-01-01

    The management of exposed fractures has been discussed since ancient times and remains of great interest to present-day orthopedics and traumatology. These injuries are still a challenge. Infection and nonunion are feared complications. Aspects of the diagnosis, classification and initial management are discussed here. Early administration of antibiotics, surgical cleaning and meticulous debridement are essential. The systemic conditions of patients with multiple trauma and the local conditions of the limb affected need to be taken into consideration. Early skeletal stabilization is necessary. Definitive fixation should be considered when possible and provisional fixation methods should be used when necessary. Early closure should be the aim, and flaps can be used for this purpose. PMID:26229904

  11. Advances in treating exposed fractures

    Directory of Open Access Journals (Sweden)

    Pedro Nogueira Giglio

    2015-04-01

    Full Text Available The management of exposed fractures has been discussed since ancient times and remains of great interest to present-day orthopedics and traumatology. These injuries are still a challenge. Infection and nonunion are feared complications. Aspects of the diagnosis, classification and initial management are discussed here. Early administration of antibiotics, surgical cleaning and meticulous debridement are essential. The systemic conditions of patients with multiple trauma and the local conditions of the limb affected need to be taken into consideration. Early skeletal stabilization is necessary. Definitive fixation should be considered when possible and provisional fixation methods should be used when necessary. Early closure should be the aim, and flaps can be used for this purpose.

  12. EVALUATION OF EFFECTS OF OZONE EXPOSURE ON INFLUENZA INFECTION IN MICE USING SEVERAL INDICATORS OF SUSCEPTIBILITY (JOURNAL VERSION)

    Science.gov (United States)

    Mice were exposed to 1 ppm O3, 3hrs/day, for 5 consecutive days. A 2-fold increase in % mortality and a 3 day decrease in survival time were observed in mice infected with influenza virus after the 2nd exposure. These endpoints were not affected in mice infected after the 1st, 3r...

  13. Mild overexpression of Mecp2 in mice causes a higher susceptibility toward seizures.

    Science.gov (United States)

    Bodda, Chiranjeevi; Tantra, Martesa; Mollajew, Rustam; Arunachalam, Jayamuruga P; Laccone, Franco A; Can, Karolina; Rosenberger, Albert; Mironov, Sergej L; Ehrenreich, Hannelore; Mannan, Ashraf U

    2013-07-01

    An intriguing finding about the gene encoding methyl-CpG binding protein 2 (MeCP2) is that the loss-of-function mutations cause Rett syndrome and duplication (gain-of-function) of MECP2 leads to another neurological disorder termed MECP2 duplication syndrome. To ensure proper neurodevelopment, a precise regulation of MeCP2 expression is critical, and any gain or loss of MeCP2 over a narrow threshold level may lead to postnatal neurological impairment. To evaluate MeCP2 dosage effects, we generated Mecp2(WT_EGFP) transgenic (TG) mouse in which MeCP2 (endogenous plus TG) is mildly overexpressed (approximately 1.5×). The TG MeCP2(WT_EGFP) fusion protein is functionally active, as cross breeding of these mice with Mecp2 knockout mice led to alleviation of major phenotypes in the null mutant mice, including premature lethality. To characterize the Mecp2(WT_EGFP) mouse model, we performed an extensive battery of behavioral tests, which revealed that these mice manifest increased aggressiveness and higher pentylenetetrazole (PTZ)-induced seizure propensity. Evaluation of neuronal parameters revealed a reduction in the number of tertiary branching sites and increased spine density in Mecp2(WT_EGFP) transgenic (TG) neurons. Treatment of TG neurons with epileptogenic compound-PTZ led to a marked increase in amplitude and frequency of calcium spikes. Based on our ex vivo and in vivo data, we conclude that epileptic seizures are manifested as the first symptom when MeCP2 is mildly overexpressed in mice. PMID:23684790

  14. Control for occupationally exposed personnels

    Energy Technology Data Exchange (ETDEWEB)

    Murakami, Hiroyuki [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Momose, Takuma

    1999-03-01

    The present status of the technology for the measurement of personnel exposure dose was reviewed based on the basic concept of ICRP Recommendation on new assessment of exposure dose. The personnel dosimeter which has been mostly used by occupationally exposed personnels in Japan is film badge or thermoluminescence dosimeter. Now, photoluminescent glass dosimeter has been paid attention because pulse excitation method by UV laser has been developed. Measurement at an accuracy of 0.1 mSv or more became possible by using this dosimeter at present. In addition, characteristic studies for practical application of electronic, photostimulated luminescence and neutron dosimeters are progressing now. Revision of kinetic model of in vivo metabolism of radioactive substances is progressing based on the recent findings since ICRP Recommendation in 1990. Monitoring an individual internal exposure is made by two methods; direct measurement of the radiation emitted from the body and indirect one by radioanalysis of excretes etc. The latter is inferior to the former in respect of the accuracy of dose assessment, but the direct method is more suitable to detect a little amount of radioactive substance incorporated because of its high sensitivity. In future, it is needed to provide a considerable number of whole body counters against a large-scale nuclear accident. (M.N.)

  15. Kinematics of treadmill locomotion in mice raised in hypergravity.

    Science.gov (United States)

    Bojados, Mickael; Herbin, Marc; Jamon, Marc

    2013-05-01

    The study compared the motor performance of adult C57Bl/6J mice previously exposed to a 2G gravity environment during different periods of their development. 12 mice were housed in a large diameter centrifuge from the conception to Postnatal day 10 (P10). Another group of 10 mice was centrifuged form P10 to P30, and a third group of 9 mice was centrifuged from conception to P30. Their gait parameters, and kinematics of joint excursions were compared with 11 control mice, at the age of 2 months using a video-radiographic apparatus connected to a motorized treadmill. The mice that returned to Earth gravity level at the age of P10 showed a motor pattern similar to control mice. At variance the two groups that were centrifuged from P10 to P30 showed a different motor pattern with smaller and faster strides to walk at the same velocity as controls. On the other hand all the centrifuged mice showed significant postural changes, particularly with a more extended ankle joint, but the mice centrifuged during the whole experimental period differed even more. Our results showed that the exposure to hypergravity before P10 sufficed to modify the posture, suggesting that postural control starts before the onset of locomotion, whereas the gravity constraint perceived between P10 and P30 conditioned the tuning of quadruped locomotion with long term consequences. These results support the existence of a critical period in the acquisition of locomotion in mice. PMID:23352767

  16. Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice.

    Science.gov (United States)

    Duerr, Georg D; Dewald, Daniela; Schmitz, Eva J; Verfuerth, Luise; Keppel, Katharina; Peigney, Christine; Ghanem, Alexander; Welz, Armin; Dewald, Oliver

    2016-01-01

    Aims. Repetitive brief ischemia and reperfusion (I/R) is associated with left ventricular dysfunction during development of ischemic cardiomyopathy. We investigated the role of zinc-donor proteins metallothionein MT1 and MT2 in a closed-chest murine model of I/R. Methods. Daily 15-minute LAD-occlusion was performed for 1, 3, and 7 days in SV129 (WT)- and MT1/2 knockout (MT(-/-))-mice (n = 8-10/group). Hearts were examined with M-mode echocardiography and processed for histological and mRNA studies. Results. Expression of MT1/2 mRNA was transiently induced during repetitive I/R in WT-mice, accompanied by a transient inflammation, leading to interstitial fibrosis with left ventricular dysfunction without infarction. In contrast, MT(-/-)-hearts presented with enhanced apoptosis and small infarctions leading to impaired global and regional pump function. Molecular analysis revealed maladaptation of myosin heavy chain isoforms and antioxidative enzymes in MT1/2(-/-)-hearts. Despite their postponed chemokine induction we found a higher total neutrophil density and macrophage infiltration in small infarctions in MT(-/-)-hearts. Subsequently, higher expression of osteopontin 1 and tenascin C was associated with increased myofibroblast density resulting in predominately nonreversible fibrosis and adverse remodeling in MT1/2(-/-)-hearts. Conclusion. Cardioprotective effects of MT1/2 seem to be exerted via modulation of contractile elements, antioxidative enzymes, inflammatory response, and myocardial remodeling. PMID:27403038

  17. Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice

    Directory of Open Access Journals (Sweden)

    Georg D. Duerr

    2016-01-01

    Full Text Available Aims. Repetitive brief ischemia and reperfusion (I/R is associated with left ventricular dysfunction during development of ischemic cardiomyopathy. We investigated the role of zinc-donor proteins metallothionein MT1 and MT2 in a closed-chest murine model of I/R. Methods. Daily 15-minute LAD-occlusion was performed for 1, 3, and 7 days in SV129 (WT- and MT1/2 knockout (MT-/--mice (n = 8–10/group. Hearts were examined with M-mode echocardiography and processed for histological and mRNA studies. Results. Expression of MT1/2 mRNA was transiently induced during repetitive I/R in WT-mice, accompanied by a transient inflammation, leading to interstitial fibrosis with left ventricular dysfunction without infarction. In contrast, MT-/--hearts presented with enhanced apoptosis and small infarctions leading to impaired global and regional pump function. Molecular analysis revealed maladaptation of myosin heavy chain isoforms and antioxidative enzymes in MT1/2-/--hearts. Despite their postponed chemokine induction we found a higher total neutrophil density and macrophage infiltration in small infarctions in MT-/--hearts. Subsequently, higher expression of osteopontin 1 and tenascin C was associated with increased myofibroblast density resulting in predominately nonreversible fibrosis and adverse remodeling in MT1/2-/--hearts. Conclusion. Cardioprotective effects of MT1/2 seem to be exerted via modulation of contractile elements, antioxidative enzymes, inflammatory response, and myocardial remodeling.

  18. Prenatal alcohol exposure inducing the apoptosis of mossy cells in hippocampus of SMS2-/- mice.

    Science.gov (United States)

    Wang, Lai; Wu, Lin; Wang, Xiaoqing; Deng, Jiexin; Ma, Zhanyou; Fan, Wenjuan; He, Weiya; Deng, Jinbo

    2015-11-01

    In order to understand the mechanisms of alcohol-induced neuroapoptosis through the ceramide pathway, sphingomyelin synthase 2 knockout (SMS2-/-) mice were used to make the prenatal alcohol exposure model, and the role of ceramide regulation on alcohol-induced neuroapoptosis was studied in the offspring. Initially the levels of serum sphingomyelin (SM) were detected with enzymatic method in P0 pups after alcohol exposure in parents. Then the apoptosis of mossy cells in the offspring hippocampus was investigated after prenatal alcohol exposure with immunohistochemistry and TUNEL assay. Finally the expression of activated Caspase 8 and activated Caspase 3 in the offspring hippocampus was detected with Western blot analysis. Our results showed that SM levels were down-regulated in a dose-dependent manner (palcohol exposure in wild-type (WT) and SMS2-/- pups. However, SM levels of serum in SMS2-/- pups were significantly lower than that in WT pups (palcohol-induced neuroapoptosis. In both WT pups and SMS2-/- pups, the number of apoptotic mossy cells in the hippocampus increased after prenatal alcohol exposure in a dose dependent manner (palcohol exposure, consistent with results from TUNEL assay and immunocytochemistry. Our study suggests that mossy cells may be the easily attacked cells for fetal alcohol spectrum disorder (FASD), and ceramide is involved in the alcohol-induced neural apoptosis. The mechanism probably lies in the accumulated ceramide in SMS2 mice, and the increase of activated Caspase 8 and Caspase 3 promotes alcohol-induced neuroapoptosis.

  19. Metabolic characteristics of long-lived mice

    Directory of Open Access Journals (Sweden)

    Andrzej eBartke

    2012-12-01

    Full Text Available Genetic suppression of insulin/insulin-like growth factor signaling (IIS can extend longevity in worms, insects, and mammals. In laboratory mice, mutations with the greatest, most consistent, and best documented positive impact on lifespan are those that disrupt growth hormone (GH release or actions. These mutations lead to major alterations in IIS but also have a variety of effects that are not directly related to the actions of insulin or insulin-like growth factor (IGF-1. Long-lived GH-resistant GHRKO mice with targeted disruption of the GH receptor gene, as well as Ames dwarf (Prop1df and Snell dwarf (Pit1dw mice lacking GH (along with prolactin and TSH, are diminutive in size and have major alterations in body composition and metabolic parameters including increased subcutaneous adiposity, increased relative brain weight, small liver, hypoinsulinemia, mild hypoglycemia, increased adiponectin levels and insulin sensitivity, and reduced serum lipids. Body temperature is reduced in Ames, Snell, and female GHRKO mice. Indirect calorimetry revealed that both Ames dwarf and GHRKO mice utilize more oxygen per gram (g of body weight than sex- and age-matched normal animals from the same strain. They also have reduced respiratory quotient (RQ, implying greater reliance on fats, as opposed to carbohydrates, as an energy source. Differences in oxygen consumption (VO2 were seen in animals fed or fasted during the measurements as well as in animals that had been exposed to 30% calorie restriction or every-other-day feeding. However, at the thermoneutral temperature of 30°C, VO2 did not differ between GHRKO and normal mice. Thus, the increased metabolic rate of the GHRKO mice, at a standard animal room temperature of 23°C, is apparently related to increased energy demands for thermoregulation in these diminutive animals. We suspect that increased oxidative metabolism combined with enhanced fatty acid oxidation contribute to the extended longevity of

  20. Trauma enhanced mortality in irradiated mice

    International Nuclear Information System (INIS)

    Burn (B) or wound (W) trauma after exposure to radiation (R) may complicate 1) the elucidation of injury induction mechanisms and, 2) development of effective treatments for tissue damage and infections. Mouse models of sublethal B and W trauma with R, termed ''combined injury'' (CI), were used to evaluate dose and quality of R with type of injury, as well as responses to and therapy for bacterial challenges. B6D2F/J female mice were bilaterally exposed to doses of 60Co R (5-12 Gy), 0.4 Gy/min. Two hr after exposure, mice were anesthetized with methoxyfluorane and subjected to either 30% dorsal skin B or W. After R, W, B, RW, or RB, mice were given 0.5 ml 0.9% NaCl i.p. The LD50/30 radiation doses were: R = 9.63, RB = 8.2, and RW = 7.61 Gy. Slopes of CI survival curves were the same, but different (rho < .01) from that for R mice, and survival times of CI mice were 25-75% lower than for R mice. W, 48 hr before or 0.1, 24 or 48 hr after sublethal 7 Gy resulted in synergistic increases in mortality of 40, 25, 60 and 80%, respectively. In all CI, R, W, and B mice, intestinal bacteria were cultured from blood, spleen and liver. Challenge with opportunistic pathogens that routinely results in 5% mortality in normal mice, yielded increased mortality (95, 60, 26, 15, and 15% respectively) in RW, RB, R, W, and B animals. These CI models are used to evaluate immuno-modulators of non-specific resistance to bacterial infections

  1. ASPP2 involvement in p53-mediated HIV-1 envelope glycoprotein gp120 neurotoxicity in mice cerebrocortical neurons

    Science.gov (United States)

    Liu, Zhiying; Zang, Yunjin; Qiao, Luxin; Liu, Kai; Ouyang, Yabo; Zhang, Yulin; Chen, Dexi

    2016-01-01

    The mechanisms behind HIV-1-associated neurocognitive disorders are still unclear. Apoptosis-stimulating protein 2 of p53 (ASPP2) is a damage-inducible p53-binding protein that stimulates p53-mediated apoptosis and transactivates proapoptotic and cell cycle regulatory genes. It has been reported that ASPP2 has a specific regulatory function in the death of retinal ganglion cells and the development of Alzheimer’s disease. In this study, we used p53 and ASPP2 knockout mice and primary cerebrocortical neuron culture to analyze the role of the interaction between ASPP2 with p53 in HIV-1 envelope glycoprotein gp120-induced neurotoxicity. The results showed that 10 ng/mL gp120 protein might stimulate p53 overexpression and translocation to the nucleus, and 30 ng/mL gp120 protein could stimulate both p53 and ASPP2 translocation to the nucleus, but only with p53 overexpression. The primary cultured neurons of p53−/−ASPP2+/− mice had a higher survival rate than p53−/− mice under gp120 protein stress. The interaction of ASPP2 with p53 induced by a high dose of gp120 stimulated Bax transcription and contributed to caspase-3 cleavage, and ASPP2-siRNA attenuated gp120 induced neuron death through inhibition of Bax expression. These results suggest that ASPP2 plays an important role in p53-mediated neuronal apoptosis under gp120 stress. PMID:27625111

  2. Altered GABAA receptor expression in brainstem nuclei and SUDEP in Gabrg2(+/Q390X) mice associated with epileptic encephalopathy.

    Science.gov (United States)

    Xia, Geqing; P Pourali, Sarah; Warner, Timothy A; Zhang, Chun-Qing; L Macdonald, Robert; Kang, Jing-Qiong

    2016-07-01

    Sudden unexpected death in epilepsy (SUDEP) is the leading cause for death in individuals with epilepsy. The frequency of SUDEP correlates with the severity of epilepsies and lack of response to antiepileptic drug treatment, but the underlying mechanisms of SUDEP have not been elucidated fully. GABRG2(Q390X) is a mutation associated with the epileptic encephalopathy Dravet syndrome (DS) and with genetic epilepsy with febrile seizures plus (GEFS+) in patients. The Gabrg2(+/Q390X) knockin (KI) mouse phenocopies the major features of DS and GEFS+ and has SUDEP throughout life. The Gabrg2(+/-) knockout (KO) mouse is associated with infrequent absence seizures and represents a model of mild absence epilepsy syndrome without increased mortality. To explore the basis for SUDEP in DS and GEFS+, we compared mutant γ2 subunit and wild-type α1 and β2/3 subunit expression in mice in brainstem nuclei associated with respiratory function including the solitary tract, pre-Botzinger complex and Kolliker-Fuse nuclei. We found that synaptic GABAA receptors were reduced while intracellular nonfunctional γ2(Q390X) subunits were increased in the heterozygous DS and GEFS+ KI mice, but not in the heterozygous absence epilepsy KO mice. Given the critical role of these nuclei in cardiorespiratory function, it is likely the impaired GABAergic transmission and neuronal dysfunction in these brainstem nuclei are involved in the cardiorespiratory collapse in SUDEP. The study provides novel mechanistic insights into cardiorespiratory failure of SUDEP. PMID:27131289

  3. SLAP/SLAP2 prevent excessive platelet (hem)ITAM signaling in thrombosis and ischemic stroke in mice.

    Science.gov (United States)

    Cherpokova, Deya; Bender, Markus; Morowski, Martina; Kraft, Peter; Schuhmann, Michael K; Akbar, Sarah M; Sultan, Cheryl S; Hughes, Craig E; Kleinschnitz, Christoph; Stoll, Guido; Dragone, Leonard L; Watson, Steve P; Tomlinson, Michael G; Nieswandt, Bernhard

    2015-01-01

    Glycoprotein VI and C-type lectin-like receptor 2 are essential platelet activating receptors in hemostasis and thrombo-inflammatory disease, which signal through a (hem)immunoreceptor tyrosine-based activation motif (ITAM)-dependent pathway. The adapter molecules Src-like adapter proteins (SLAP and SLAP2) are involved in the regulation of immune cell surface expression and signaling, but their function in platelets is unknown. In this study, we show that platelets expressed both SLAP isoforms and that overexpression of either protein in a heterologous cell line almost completely inhibited glycoprotein VI and C-type lectin-like receptor 2 signaling. In mice, single deficiency of SLAP or SLAP2 had only moderate effects on platelet function, whereas double deficiency of both adapters resulted in markedly increased signal transduction, integrin activation, granule release, aggregation, procoagulant activity, and thrombin generation in response to (hem)ITAM-coupled, but not G protein-coupled, receptor activation. In vivo, constitutive SLAP/SLAP2 knockout mice displayed accelerated occlusive arterial thrombus formation and a dramatically worsened outcome after focal cerebral ischemia. This was attributed to the absence of both adapter proteins in platelets, as demonstrated by adoptive transfer of Slap(-/-)/Slap2(-/-) platelets into wild-type mice. Our results establish SLAP and SLAP2 as critical inhibitors of platelet (hem)ITAM signaling in the setting of arterial thrombosis and ischemic stroke.

  4. Neonatal periostin knockout mice are protected from hyperoxia-induced alveolar simplication.

    Directory of Open Access Journals (Sweden)

    Paul D Bozyk

    Full Text Available In bronchopulmonary dysplasia (BPD, alveolar septae are thickened with collagen and α-smooth muscle actin, transforming growth factor (TGF-β-positive myofibroblasts. Periostin, a secreted extracellular matrix protein, is involved in TGF-β-mediated fibrosis and myofibroblast differentiation. We hypothesized that periostin expression is required for hypoalveolarization and interstitial fibrosis in hyperoxia-exposed neonatal mice, an animal model for this disease. We also examined periostin expression in neonatal lung mesenchymal stromal cells and lung tissue of hyperoxia-exposed neonatal mice and human infants with BPD. Two-to-three day-old wild-type and periostin null mice were exposed to air or 75% oxygen for 14 days. Mesenchymal stromal cells were isolated from tracheal aspirates of premature infants. Hyperoxic exposure of neonatal mice increased alveolar wall periostin expression, particularly in areas of interstitial thickening. Periostin co-localized with α-smooth muscle actin, suggesting synthesis by myofibroblasts. A similar pattern was found in lung sections of infants dying of BPD. Unlike wild-type mice, hyperoxia-exposed periostin null mice did not show larger air spaces or α-smooth muscle-positive myofibroblasts. Compared to hyperoxia-exposed wild-type mice, hyperoxia-exposed periostin null mice also showed reduced lung mRNA expression of α-smooth muscle actin, elastin, CXCL1, CXCL2 and CCL4. TGF-β treatment increased mesenchymal stromal cell periostin expression, and periostin treatment increased TGF-β-mediated DNA synthesis and myofibroblast differentiation. We conclude that periostin expression is increased in the lungs of hyperoxia-exposed neonatal mice and infants with BPD, and is required for hyperoxia-induced hypoalveolarization and interstitial fibrosis.

  5. Effects of maternal exposure to nano-alumina during pregnancy on neurodevelopment in offspring mice

    Institute of Scientific and Technical Information of China (English)

    丁勇

    2013-01-01

    Objective To observe the effects of maternal exposure to nano-alumina during pregnancy on the neurodevelopment in offspring mice.Methods Female ICR mice were exposed to nano-alumina 10 d before mating,and the nano-alumina exposure lasted till offspring mice were born.All the female mice were randomly divided into 5groups:solvent control group (saline) ,nano-carbon group (11.76 mg/ml) ,microalumina group (50 mg/ml) ,50 nm alumina group (50 mg/ml) ,and 13 nm alumina group (50 mg/ml) .All the mice were treated by

  6. Loss of Endogenous Interleukin-12 Activates Survival Signals in Ultraviolet-Exposed Mouse Skin and Skin Tumors

    Directory of Open Access Journals (Sweden)

    Syed M. Meeran

    2009-09-01

    Full Text Available Interleukin-12 (IL-12-deficiency promotes photocarcinogenesis in mice; however, the molecular mechanisms underlying this effect have not been fully elucidated. Here, we report that long-term exposure to ultraviolet (UV radiation resulted in enhancement of the levels of cell survival kinases, such as phosphatidylinositol 3-kinase (PI3K, Akt (Ser473, p-ERK1/2, and p-p38 in the skin of IL-12p40 knockout (IL-12 KO mice compared with the skin of wild-type mice. UV-induced activation of nuclear factor-κB (NF-κB/p65 in the skin of IL-12 KO mice was also more prominent. The levels of NF-κB-targeted proteins, such as proliferating cell nuclear antigen (PCNA, cyclooxygenase-2, cyclin D1, and inducible nitric oxide synthase, were higher in the UV-exposed skin of IL-12 KO mice than the UV-exposed skin of wild types. In short-term UV irradiation experiments, subcutaneous treatment of IL-12 KO mice with recombinant IL-12 (rIL-12 or topical treatment with oridonin, an inhibitor of NF-κB, resulted in the inhibition of UV-induced increases in the levels of PCNA, cyclin D1, and NF-κB compared with non-rIL-12- or non-oridonin-treated IL-12 KO mice. UV-induced skin tumors of IL-12 KO mice had higher levels of PI3K, p-Akt (Ser473, p-ERK1/2, p-p38, NF-κB, and PCNA and fewer apoptotic cells than skin tumors of wild types. Together, these data suggest that the loss of endogenous IL-12 activates survival signals in UV-exposed skin and that may lead to the enhanced photocarcinogenesis in mice.

  7. Memory Deficits Are Associated with Impaired Ability to Modulate Neuronal Excitability in Middle-Aged Mice

    Science.gov (United States)

    Kaczorowski, Catherine C.; Disterhoft, John F.

    2009-01-01

    Normal aging disrupts hippocampal neuroplasticity and learning and memory. Aging deficits were exposed in a subset (30%) of middle-aged mice that performed below criterion on a hippocampal-dependent contextual fear conditioning task. Basal neuronal excitability was comparable in middle-aged and young mice, but learning-related modulation of the…

  8. Low-Dose Radiation Exposure and Atherosclerosis in ApoE(-/-) Mice

    NARCIS (Netherlands)

    Mitchel, R. E. J.; Hasu, M.; Bugden, M.; Wyatt, H.; Little, M. P.; Gola, A.; Hildebrandt, G.; Priest, N. D.; Whitman, S. C.

    2011-01-01

    The hypothesis that single low-dose exposures (0.025-0.5 Gy) to low-LET radiation given at either high (about 150 mGy/min) or low (1 mGy/min) dose rate would promote aortic atherosclerosis was tested in female C57BL/6J mice genetically predisposed to this disease (ApoE(-/-)). Mice were exposed eithe

  9. Pre-Exposure to Context Affects Learning Strategy Selection in Mice

    Science.gov (United States)

    Tunur, Tumay; Dohanich, Gary P.; Schrader, Laura A.

    2010-01-01

    The multiple memory systems hypothesis proposes that different types of learning strategies are mediated by distinct neural systems in the brain. Male and female mice were tested on a water plus-maze task that could be solved by either a place or response strategy. One group of mice was pre-exposed to the same context as training and testing (PTC)…

  10. Hyperoxia Inhibits T Cell Activation in Mice

    Science.gov (United States)

    Hughes-Fulford, M.; Meissler, J.; Aguayo, E. T.; Globus, R.; Aguado, J.; Candelario, T.

    2013-02-01

    Background: The immune response is blunted in mice and humans in spaceflight. The effects of hyperoxia in mice alter expression of some of the same immune response genes. If these two conditions are additive, there could be an increased risk of infection in long duration missions. Immunosuppression is seen in healthy astronauts who have flown in space; however little is known about the mechanisms that cause the reduced immunity in spaceflight. Here we examine the role of oxidative stress on mice exposed to periods of high O2 levels mimicking pre-breathing protocols and extravehicular activity (EVA). To prevent decompression sickness, astronauts are exposed to elevated oxygen (hyperoxia) before and during EVA activities. Spaceflight missions may entail up to 24 hours of EVA per crewmember per week to perform construction and maintenance tasks. The effectiveness and success of these missions depends on designing EVA systems and protocols that maximize human performance and efficiency while minimizing health and safety risks for crewmembers. To our knowledge, no studies have been conducted on the immune system under 100% oxygen exposures to determine the potential for immune compromise due to prolonged and repeated EVAs. Methods: Animals were exposed to hyperoxic or control conditions for 8 hours per day over a period of 3 days, initiated 4 hours into the dark cycle (12h dark/12h light), using animal environmental control cabinets and oxygen controller (Biospherix, Lacona, NY). Experimental mice were exposed to 98-100% oxygen as a model for pre-breathing and EVA conditions, while control mice were maintained in chambers supplied with compressed air. These are ground control studies where we use real-time RTPCR (qRTPCR) to measure gene expression of the early immune gene expression during bead activation of splenocytes of normoxic and hyperoxic mice. All procedures were reviewed and approved by the IACUC at Ames Research Center. After the last 8h of hyperoxic exposure

  11. 维生素E对双酚A暴露的发育期雄性小鼠生殖系统及抗氧化能力的影响%Effect of vitamin E on reproductive functions and anti-oxidant activity of adolescent male mice exposed to bisphenol A

    Institute of Scientific and Technical Information of China (English)

    房玥晖; 周逸婷; 钟燕; 高欣; 谈韬

    2013-01-01

    Objective To study the effects of bisphenol A ( BPA) on reproductive functions and oxidative stress in adolescent male mice, and to explore the effect of high dose vitamin E on reproductive functions and oxidative stress induced by BPA. Methods Thirty-two kunming male mice aged 4-5 weeks were randomly divided into 3 groups; control group ( gavaged with corn oil 0. 2ml/d, n = 10) , BPA group ( gavaged with BPA 0. 5mg/kg BW, n = 11 ) , and vitamin E intervention group (gavaged with BPA 0. 5mg/kg BW and vitamin E 150mg/kg BW, n = 11). All animals were sacrificed 3 weeks later and blood and tissue samples were collected. Results The wet weight of testis in BPA group, the wet weight and organ coefficient of spermatophore, and counts of sperm in BPA and vitamin E intervention groups were significantly lower than those in the control group ( P < 0. 05 or P <0. 01) , and the organ coefficient of spermatophore in vitamin E intervention group was significantly higher than BPA group ( P < 0. 05). The rates of teratosperm in BPA and vitamin E intervention groups were significant higher than the control group ( P < 0. 05) , and the activity ratio of sperm in BPA group was significantly lower than those in the control and vitamin E intervention groups ( P < 0. 05 ). The SOD activities of liver tissue in both BPA and vitamin E intervention groups and CAT activity in BPA group were significantly higher than the control group ( P < 0. 05 ) . The serum testosterone level in BPA group was lower than the control and vitamin E intervention group without significant difference. Conclusion Short-term BPA exposure may partly inhibit the reproductive function in adolescent male mice with certain stimulating effect on antioxidant ability, and supplementation of vitamin E during BPA exposure may have certain protective effect on reproductive inhibition caused by BPA exposure.%目的 研究双酚A(BPA)暴露对雄性小鼠生殖系统及抗氧化能力的影响,以及大剂量补充维

  12. Renoprotective effects of Moringa oleifera pods in 7,12-dimethylbenz[a]anthracene-exposed mice%油椒木豆荚提取物对二甲基苯蒽诱导小鼠肾组织损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    Veena Sharma; Ritu Paliwal; Pracheta Janmeda; Shatruhan Sharma

    2012-01-01

    目的:通过二甲基苯蒽(7,12-dimethylbenz[a]anthracene,DMBA)诱导雄性白化小鼠肾组织损伤来研究油椒木豆荚的水乙醇提取物对肾脏的保护作用.方法:予实验小鼠口服15 mg/kg DMBA两周前,分别予200和400 mg/kg的油椒木豆荚的水乙醇提取物以及浓度为0.5%和1%的叔丁基对羟基茴香醚灌胃.测定各组小鼠细胞色素(cytochrome,Cyt)P450及Cytb5、还原型谷光甘肽(reduced glutathione,GSH)、谷胱甘肽转移酶(glutathione-S-transferase,GST)以及肾组织天冬氨酸氨基转移酶( aspartate transaminase,AST)、丙氨酸氨基转移酶(alanine transaminase,ALT)、碱性磷酸酶(alkaline phosphatase,ALP)活性及总胆固醇和蛋白质含量.结果:口服15 mg/kg的DMBA可显著增加小鼠Cyt P450和Cyt b5的浓度(P<0.01).小鼠肾组织GSH、GST活性显著降低(P<0.01,P<0.05).实验小鼠在口服DMBA后,肾组织AST、ALT、ALP活性和蛋白质含量也显著降低,总胆固醇含量则显著增加(P<0.01).但是经200和400 mg/kg油椒木豆荚提取物预处理14 d的实验小鼠,其由DMBA诱发的各项组织生化指标变化发生显著逆转(P<0.01).结论:油椒木豆荚的提取物可通过提高细胞抗氧化活性、减少自由基的生成来减少DMBA的毒副作用,起到保护肾组织的作用.%OBJECTIVE:To investigate the potential of hydroethanolic extract of Moringa oleifera (MOHE) against 7,12-dimethylbenz[a]anthracene (DMBA)-induced toxicity in male Swiss albino mice.METHODS:Experimental mice were respectively pretreated with 200 and 400 mg/kg of MOHE,and 0.5% and 1% of butylated hydroxyanisole (BHA) for two weeks prior to the administration of 15 mg/kg of DMBA,respectively.Levels of xenobiotic metabolizing enzymes such as cytochrome (Cyt) P450 and Cyt b5,activities of reduced glutathione (GSH) and glutathione-S-transferase (GST) and renal aspartate aminotransaminase (AST),alanine aminotransaminase (ALT) and alkaline phosphatase (ALP),and content of

  13. Silent Victims: Children Exposed to Family Violence

    Science.gov (United States)

    Kolar, Kathryn R.; Davey, Debrynda

    2007-01-01

    Annually an estimated 3 million or more children are exposed to acts of domestic violence between adults in their homes. These children are at risk for abuse themselves as well as other immediate and long-term problems, especially if they have been exposed to repeated episodes of domestic violence. Multiple behavioral manifestations, including…

  14. Adaptive Response in Animals Exposed to Non-Ionizing Radiofrequency Fields: Some Underlying Mechanisms

    Directory of Open Access Journals (Sweden)

    Yi Cao

    2014-04-01

    Full Text Available During the last few years, our research group has been investigating the phenomenon of adaptive response in animals exposed to non-ionizing radiofrequency fields. The results from several separate studies indicated a significant increase in survival, decreases in genetic damage as well as oxidative damage and, alterations in several cellular processes in mice pre-exposed to radiofrequency fields and subsequently subjected to sub-lethal or lethal doses of γ-radiation or injected with bleomycin, a radiomimetic chemical mutagen. These observations indicated the induction of adaptive response providing the animals the ability to resist subsequent damage. Similar studies conducted by independent researchers in mice and rats have supported our observation on increased survival. In this paper, we have presented a brief review of all of our own and other independent investigations on radiofrequency fields-induced adaptive response and some underlying mechanisms discussed.

  15. 3 EXPOSE Missions - overview and lessons learned

    Science.gov (United States)

    Rabbow, E.; Willnekcer, R.; Reitz, G.; Aman, A.; Bman, B.; Cman, C.

    2011-10-01

    The International Space Station ISS provides a variety of external research platforms for experiments aiming at the utilization of space parameters like vacuum, temperature oscillation and in particular extraterrestrial short wavelength UV and ionizing radiation which cannot be simulated accurately in the laboratory. Three Missions, two past and one upcoming, will be presented. A family of astrobiological experimental ESA facilities called "EXPOSE" were and will be accommodated on these outside exposure platforms: on one of the external balconies of the European Columbus Module (EXPOSE-E) and on the URM-D platform on the Russian Zvezda Module (EXPOSE-R and EXPOSE-R2). Exobiological and radiation experiments, exposing chemical, biological and dosimetric samples to the harsh space environment are - and will be - accommodated on these facilities to increase our knowledge on the origin, evolution and distribution of life, on Earth and possibly beyond. The biological experiments investigate resistance and adaptation of organisms like bacteria, Achaea, fungi, lichens, plant seeds and small animals like mosquito larvae to extreme environmental conditions and underlying mechanisms like DNA repair. The organic chemical experiments analyse chemical reactions triggered by the extraterrestrial environment, especially short wavelength UV radiation, to better understand prebiotic chemistry. The facility is optimized to allow exposure of biological specimen and material samples under a variety of conditions, using optical filter systems. Environmental parameters like temperature and radiation are regularly recorded and down linked by telemetry. Two long term missions named according to their facility - EXPOSE-E and EXPOSE-R - are completed and a third mission is planned and currently prepared. Operations of all three missions including sample accommodation are performed by DLR. An overview of the two completed missions will be given including lessons learned as well as an outlook

  16. Early physical and motor development of mouse offspring exposed to valproic acid throughout intrauterine development.

    Science.gov (United States)

    Podgorac, Jelena; Pešić, Vesna; Pavković, Željko; Martać, Ljiljana; Kanazir, Selma; Filipović, Ljupka; Sekulić, Slobodan

    2016-09-15

    Clinical research has identified developmental delay and physical malformations in children prenatally exposed to the antiepileptic drug (AED) valproic acid (VPA). However, the early signs of neurodevelopmental deficits, their evolution during postnatal development and growth, and the dose effects of VPA are not well understood. The present study aimed to examine the influence of maternal exposure to a wide dose range (50, 100, 200 and 400mg/kg/day) of VPA during breeding and gestation on early physical and neuromotor development in mice offspring. Body weight gain, eye opening, the surface righting reflex (SRR) and tail suspension test (TST) were examined in the offspring at postnatal days 5, 10 and 15. We observed that: (1) all tested doses of VPA reduced the body weight of the offspring and the timing of eye opening; (2) offspring exposed to VPA displayed immature forms of righting and required more time to complete the SRR; (3) latency for the first immobilization in the TST is shorter in offspring exposed to higher doses of VPA; however, mice in all groups exposed to VPA exhibited atypical changes in this parameter during the examined period of maturation; (4) irregularities in swinging and curling activities were observed in animals exposed to higher doses of VPA. This study points to delayed somatic development and postponed maturation of the motor system in all of the offspring prenatally exposed to VPA, with stronger effects observed at higher doses. The results implicate that the strategy of continuous monitoring of general health and achievements in motor milestones during the early postnatal development in prenatally VPA-exposed offspring, irrespectively of the dose applied, could help to recognize early developmental irregularities. PMID:27188530

  17. Early physical and motor development of mouse offspring exposed to valproic acid throughout intrauterine development.

    Science.gov (United States)

    Podgorac, Jelena; Pešić, Vesna; Pavković, Željko; Martać, Ljiljana; Kanazir, Selma; Filipović, Ljupka; Sekulić, Slobodan

    2016-09-15

    Clinical research has identified developmental delay and physical malformations in children prenatally exposed to the antiepileptic drug (AED) valproic acid (VPA). However, the early signs of neurodevelopmental deficits, their evolution during postnatal development and growth, and the dose effects of VPA are not well understood. The present study aimed to examine the influence of maternal exposure to a wide dose range (50, 100, 200 and 400mg/kg/day) of VPA during breeding and gestation on early physical and neuromotor development in mice offspring. Body weight gain, eye opening, the surface righting reflex (SRR) and tail suspension test (TST) were examined in the offspring at postnatal days 5, 10 and 15. We observed that: (1) all tested doses of VPA reduced the body weight of the offspring and the timing of eye opening; (2) offspring exposed to VPA displayed immature forms of righting and required more time to complete the SRR; (3) latency for the first immobilization in the TST is shorter in offspring exposed to higher doses of VPA; however, mice in all groups exposed to VPA exhibited atypical changes in this parameter during the examined period of maturation; (4) irregularities in swinging and curling activities were observed in animals exposed to higher doses of VPA. This study points to delayed somatic development and postponed maturation of the motor system in all of the offspring prenatally exposed to VPA, with stronger effects observed at higher doses. The results implicate that the strategy of continuous monitoring of general health and achievements in motor milestones during the early postnatal development in prenatally VPA-exposed offspring, irrespectively of the dose applied, could help to recognize early developmental irregularities.

  18. Eryptosis in lead-exposed workers

    Energy Technology Data Exchange (ETDEWEB)

    Aguilar-Dorado, Itzel-Citlalli [Biochemistry Department, Centro de Investigación y Estudios Avanzados IPN, México, DF (Mexico); Hernández, Gerardo [Section of Methodology of Science, Centro de Investigación y Estudios Avanzados IPN, México, DF (Mexico); Quintanar-Escorza, Martha-Angelica [Faculty of Medicine, UJED, Durango, DGO (Mexico); Maldonado-Vega, María [CIATEC, León, GTO (Mexico); Rosas-Flores, Margarita [Biochemistry Department, Centro de Investigación y Estudios Avanzados IPN, México, DF (Mexico); Calderón-Salinas, José-Víctor, E-mail: jcalder@cinvestav.mx [Biochemistry Department, Centro de Investigación y Estudios Avanzados IPN, México, DF (Mexico)

    2014-12-01

    Eryptosis is a physiological phenomenon in which old and damaged erythrocytes are removed from circulation. Erythrocytes incubated with lead have exhibited major eryptosis. In the present work we found evidence of high levels of eryptosis in lead exposed workers possibly via oxidation. Blood samples were taken from 40 male workers exposed to lead (mean blood lead concentration 64.8 μg/dl) and non-exposed workers (4.2 μg/dl). The exposure to lead produced an intoxication characterized by 88.3% less δ-aminolevulinic acid dehydratase (δALAD) activity in lead exposed workers with respect to non-lead exposed workers. An increment of oxidation in lead exposed workers was characterized by 2.4 times higher thiobarbituric acid-reactive substance (TBARS) concentration and 32.8% lower reduced/oxidized glutathione (GSH/GSSG) ratio. Oxidative stress in erythrocytes of lead exposed workers is expressed in 192% higher free calcium concentration [Ca{sup 2+}]{sub i} and 1.6 times higher μ-calpain activity with respect to non-lead exposed workers. The adenosine triphosphate (ATP) concentration was not significantly different between the two worker groups. No externalization of phosphatidylserine (PS) was found in non-lead exposed workers (< 0.1%), but lead exposed workers showed 2.82% externalization. Lead intoxication induces eryptosis possibly through a molecular pathway that includes oxidation, depletion of reduced glutathione (GSH), increment of [Ca{sup 2+}], μ-calpain activation and externalization of PS in erythrocytes. Identifying molecular signals that induce eryptosis in lead intoxication is necessary to understand its physiopathology and chronic complications. - Graphical abstract: Fig. 1. (A) Blood lead concentration (PbB) and (B) phosphatidylserine externalization on erythrocyte membranes of non-lead exposed (□) and lead exposed workers (■). Values are mean ± SD. *Significantly different (P < 0.001). - Highlights: • Erythrocytes of lead exposed workers

  19. Eryptosis in lead-exposed workers

    International Nuclear Information System (INIS)

    Eryptosis is a physiological phenomenon in which old and damaged erythrocytes are removed from circulation. Erythrocytes incubated with lead have exhibited major eryptosis. In the present work we found evidence of high levels of eryptosis in lead exposed workers possibly via oxidation. Blood samples were taken from 40 male workers exposed to lead (mean blood lead concentration 64.8 μg/dl) and non-exposed workers (4.2 μg/dl). The exposure to lead produced an intoxication characterized by 88.3% less δ-aminolevulinic acid dehydratase (δALAD) activity in lead exposed workers with respect to non-lead exposed workers. An increment of oxidation in lead exposed workers was characterized by 2.4 times higher thiobarbituric acid-reactive substance (TBARS) concentration and 32.8% lower reduced/oxidized glutathione (GSH/GSSG) ratio. Oxidative stress in erythrocytes of lead exposed workers is expressed in 192% higher free calcium concentration [Ca2+]i and 1.6 times higher μ-calpain activity with respect to non-lead exposed workers. The adenosine triphosphate (ATP) concentration was not significantly different between the two worker groups. No externalization of phosphatidylserine (PS) was found in non-lead exposed workers (< 0.1%), but lead exposed workers showed 2.82% externalization. Lead intoxication induces eryptosis possibly through a molecular pathway that includes oxidation, depletion of reduced glutathione (GSH), increment of [Ca2+], μ-calpain activation and externalization of PS in erythrocytes. Identifying molecular signals that induce eryptosis in lead intoxication is necessary to understand its physiopathology and chronic complications. - Graphical abstract: Fig. 1. (A) Blood lead concentration (PbB) and (B) phosphatidylserine externalization on erythrocyte membranes of non-lead exposed (□) and lead exposed workers (■). Values are mean ± SD. *Significantly different (P < 0.001). - Highlights: • Erythrocytes of lead exposed workers showed higher PS

  20. HOST RESISTANCE TO TRICHINELLA SPIRALIS INFECTION IN RATS EXPOSED TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD)

    Science.gov (United States)

    We have previously shown decreased resistance to Trichinella spiralis (Ts) infection, and reduced parasite antigen-specific responses in mice exposed to TCDD before infection. he present study was done to characterize the effects of preinfection administration of 1, 10, or 30 ug ...

  1. Abnormal motor phenotype at adult stages in mice lacking type 2 deiodinase.

    Directory of Open Access Journals (Sweden)

    Soledad Bárez-López

    Full Text Available BACKGROUND: Thyroid hormones have a key role in both the developing and adult central nervous system and skeletal muscle. The thyroid gland produces mainly thyroxine (T4 but the intracellular concentrations of 3,5,3'-triiodothyronine (T3; the transcriptionally active hormone in the central nervous system and skeletal muscle are modulated by the activity of type 2 deiodinase (D2. To date no neurological syndrome has been associated with mutations in the DIO2 gene and previous studies in young and juvenile D2-knockout mice (D2KO did not find gross neurological alterations, possibly due to compensatory mechanisms. AIM: This study aims to analyze the motor phenotype of 3-and-6-month-old D2KO mice to evaluate the role of D2 on the motor system at adult stages in which compensatory mechanisms could have failed. RESULTS: Motor abilities were explored by validated tests. In the footprint test, D2KO showed an altered global gait pattern (mice walked slower, with shorter strides and with a hindlimb wider base of support than wild-type mice. No differences were detected in the balance beam test. However, a reduced latency to fall was found in the rotarod, coat-hanger and four limb hanging wire tests indicating impairment on coordination and prehensile reflex and a reduction of muscle strength. In histological analyses of cerebellum and skeletal muscle, D2KO mice did not present gross structural abnormalities. Thyroid hormones levels and deiodinases activities were also determined. In D2KO mice, despite euthyroid T3 and high T4 plasma levels, T3 levels were significantly reduced in cerebral cortex (48% reduction and skeletal muscle (33% reduction, but not in the cerebellum where other deiodinase (type 1 is expressed. CONCLUSIONS: The motor alterations observed in D2KO mice indicate an important role for D2 in T3 availability to maintain motor function and muscle strength. Our results suggest a possible implication of D2 in motor disorders.

  2. Memory Deficit Recovery after Chronic Vanadium Exposure in Mice

    Directory of Open Access Journals (Sweden)

    Oluwabusayo Folarin

    2016-01-01

    Full Text Available Vanadium is a transitional metal with an ability to generate reactive oxygen species in the biological system. This work was designed to assess memory deficits in mice chronically exposed to vanadium. A total of 132 male BALB/c mice (4 weeks old were used for the experiment and were divided into three major groups of vanadium treated, matched controls, and animals exposed to vanadium for three months and thereafter vanadium was withdrawn. Animals were tested using Morris water maze and forelimb grip test at 3, 6, 9, and 12 months of age. The results showed that animals across the groups showed no difference in learning but had significant loss in memory abilities after 3 months of vanadium exposure and this trend continued in all vanadium-exposed groups relative to the controls. Animals exposed to vanadium for three months recovered significantly only 9 months after vanadium withdrawal. There was no significant difference in latency to fall in the forelimb grip test between vanadium-exposed groups and the controls in all age groups. In conclusion, we have shown that chronic administration of vanadium in mice leads to memory deficit which is reversible but only after a long period of vanadium withdrawal.

  3. Effect of pulmonary irradiation from inhaled 90Y on immunity to Listeria monocytogenes in mice

    International Nuclear Information System (INIS)

    The immunological response of mice subjected to irradiation from particles deposited in the lungs and challenged with Listeria monocytogenes was investigated. Mice, exposed by inhalation to 90Y (a beta-emitting radionuclide) in relatively insoluble fused aluminosilicate particles, were immunized with L. monocytogenes either before or after exposure. Two additional groups of mice were either immunized or irradiated only. A group of control mice received no irradiation or immunization. The beta radiation dose absorbed by the lungs of each mouse at time of challenge averaged 10,000 rads. Fourteen days after immunization, all mice were challenged with 2 LD50 doses of L. monocytogenes via the respiratory route. Survival of all immunized mice either with or without exposure to 90Y varied from 90 to 100% as compared to 10 to 20% for the mice irradiated only and for control mice through 14 days after challenge. Pulmonary clearance of inhaled L. monocytogenes during the first 4 hr after challenge was suppressed in the mice irradiated only but not in those immunized only, or in the immunized and irradiated groups, and control mice. There appeared to be a suppression of proliferation of L. monocytogenes in lungs and spleen in the immunized groups 72 hr after challenge, whereas the lungs and spleens of the mice irradiated only and the control mice had extensive bacterial invasion. It was concluded that the 10,000 rads of beta radiation absorbed by the lungs did not suppress the immune mechanisms of the immunized mice

  4. Critical period for acoustic preference in mice.

    Science.gov (United States)

    Yang, Eun-Jin; Lin, Eric W; Hensch, Takao K

    2012-10-16

    Preference behaviors are often established during early life, but the underlying neural circuit mechanisms remain unknown. Adapting a unique nesting behavior assay, we confirmed a "critical period" for developing music preference in C57BL/6 mice. Early music exposure between postnatal days 15 and 24 reversed their innate bias for silent shelter, which typically could not be altered in adulthood. Instead, exposing adult mice treated acutely with valproic acid or carrying a targeted deletion of the Nogo receptor (NgR(-/-)) unmasked a strong plasticity of preference consistent with a reopening of the critical period as seen in other systems. Imaging of cFos expression revealed a prominent neuronal activation in response to the exposed music in the prelimbic and infralimbic medial prefrontal cortex only under conditions of open plasticity. Neither behavioral changes nor selective medial prefrontal cortex activation was observed in response to pure tone exposure, indicating a music-specific effect. Open-field center crossings were increased concomitant with shifts in music preference, suggesting a potential anxiolytic effect. Thus, music may offer both a unique window into the emotional state of mice and a potentially efficient assay for molecular "brakes" on critical period plasticity common to sensory and higher order brain areas. PMID:23045690

  5. Brain effects of manganese exposure in mice pups during prenatal and breastfeeding periods.

    Science.gov (United States)

    Okada, Monica Akemi; Neto, Francisco Filipak; Noso, Cassio Hideo; Voigt, Carmen Lúcia; Campos, Sandro Xavier; Alberto de Oliveira Ribeiro, Ciro

    2016-07-01

    Manganese (Mn) is a trace element essential for brain development and functioning of the central nervous system. However, there is a lack of information concerning the neurotoxicity of Mn under realistic doses in early stages of development, though excess of Mn results in a progressive disorder of the nervous system called manganism. In the current study, adult mice were exposed to three doses of Mn for 60 days through daily gavages, while mice pups were exposed to the same Mn doses during developmental period (gestational and breast-feeding). From the latter group of mice, a group was exposed for more 60 days to the same Mn doses. Chemical analysis revealed a dose-dependent bioaccumulation of Mn in mice's brain. Biochemical parameters revealed that (1) Mn affects non-protein thiol levels, glutathione S-tranferase and acetylcholinesterase activities, as well as the levels of oxidized lipids and proteins in mice brain, though lipids and proteins alterations were found only after exposure to high and unrealistic doses; (2) Realistic doses of Mn affects the activity of brain AChE and finally; (3) Pups' brain were affected by Mn even whether only the parental females had been previously exposed. The current study shows evidences of chemical stress in mice exposed to Mn during the early period of development and an efficient mechanism of Mn elimination under higher doses. These findings open new lines of investigation regarding manganese toxicity in vertebrates mainly in the early stages of development. PMID:26972613

  6. MICE IN CHINA

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ The MICE (Meetings, Incentives, Conventions, and Exhibitions) industry has exploded worldwide over the past decade. The benefits brought by meetings, incentives, conventions, and exhibitions are also benefiting other sectors involved in MICE events, including hotels, travel, and retail. Industry analysts estimate that the income from the global MICE industry will soon exceed USD 220 billion, and is expected to increase by 8-10% each year.

  7. Work ability in vibration-exposed workers

    OpenAIRE

    Gerhardsson, L; Hagberg, M

    2014-01-01

    Background Hand–arm vibration exposure may cause hand–arm vibration syndrome (HAVS) including sensorineural disturbances. Aims To investigate which factors had the strongest impact on work ability in vibration-exposed workers. Methods A cross-sectional study in which vibration-exposed workers referred to a department of occupational and environmental medicine were compared with a randomized sample of unexposed subjects from the general population of the city of Gothenburg. All participants un...

  8. Chronic treatment with LY341495 decreases 5-HT(2A) receptor binding and hallucinogenic effects of LSD in mice.

    Science.gov (United States)

    Moreno, José L; Holloway, Terrell; Rayannavar, Vinayak; Sealfon, Stuart C; González-Maeso, Javier

    2013-03-01

    Hallucinogenic drugs, such as lysergic acid diethylamide (LSD), mescaline and psilocybin, alter perception and cognitive processes. All hallucinogenic drugs have in common a high affinity for the serotonin 5-HT(2A) receptor. Metabotropic glutamate 2/3 (mGlu2/3) receptor ligands show efficacy in modulating the cellular and behavioral responses induced by hallucinogenic drugs. Here, we explored the effect of chronic treatment with the mGlu2/3 receptor antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropan-1-yl)-3-(xanth-9-yl)-propionic acid (LY341495) on the hallucinogenic-like effects induced by LSD (0.24mg/kg). Mice were chronically (21 days) treated with LY341495 (1.5mg/kg), or vehicle, and experiments were carried out one day after the last injection. Chronic treatment with LY341495 down-regulated [(3)H]ketanserin binding in somatosensory cortex of wild-type, but not mGlu2 knockout (KO), mice. Head-twitch behavior, and expression of c-fos, egr-1 and egr-2, which are responses induced by hallucinogenic 5-HT(2A) agonists, were found to be significantly decreased by chronic treatment with LY341495. These findings suggest that repeated blockade of the mGlu2 receptor by LY341495 results in reduced 5-HT(2A) receptor-dependent hallucinogenic effects of LSD.

  9. Ozone-Induced Nasal Type 2 Immunity in Mice Is Dependent on Innate Lymphoid Cells.

    Science.gov (United States)

    Kumagai, Kazuyoshi; Lewandowski, Ryan; Jackson-Humbles, Daven N; Li, Ning; Van Dyken, Steven J; Wagner, James G; Harkema, Jack R

    2016-06-01

    Epidemiological studies suggest that elevated ambient concentrations of ozone are associated with activation of eosinophils in the nasal airways of atopic and nonatopic children. Mice repeatedly exposed to ozone develop eosinophilic rhinitis and type 2 immune responses. In this study, we determined the role of innate lymphoid cells (ILCs) in the pathogenesis of ozone-induced eosinophilic rhinitis by using lymphoid-sufficient C57BL/6 mice, Rag2(-/-) mice that are devoid of T cells and B cells, and Rag2(-/-)Il2rg(-/-) mice that are depleted of all lymphoid cells including ILCs. The animals were exposed to 0 or 0.8 ppm ozone for 9 consecutive weekdays (4 h/d). Mice were killed 24 hours after exposure, and nasal tissues were selected for histopathology and gene expression analysis. ILC-sufficient C57BL/6 and Rag2(-/-) mice exposed to ozone developed marked eosinophilic rhinitis and epithelial remodeling (e.g., epithelial hyperplasia and mucous cell metaplasia). Chitinase-like proteins and alarmins (IL-33, IL-25, and thymic stromal lymphopoietin) were also increased morphometrically in the nasal epithelium of ozone-exposed C57BL/6 and Rag2(-/-) mice. Ozone exposure elicited increased expression of Il4, Il5, Il13, St2, eotaxin, MCP-2, Gob5, Arg1, Fizz1, and Ym2 mRNA in C57BL/6 and Rag2(-/-) mice. In contrast, ozone-exposed ILC-deficient Rag2(-/-)Il2rg(-/-) mice had no nasal lesions or overexpression of Th2- or ILC2-related transcripts. These results indicate that ozone-induced eosinophilic rhinitis, nasal epithelial remodeling, and type 2 immune activation are dependent on ILCs. To the best of our knowledge, this is the first study to demonstrate that ILCs play an important role in the nasal pathology induced by repeated ozone exposure. PMID:26559808

  10. Ozone-Induced Nasal Type 2 Immunity in Mice Is Dependent on Innate Lymphoid Cells.

    Science.gov (United States)

    Kumagai, Kazuyoshi; Lewandowski, Ryan; Jackson-Humbles, Daven N; Li, Ning; Van Dyken, Steven J; Wagner, James G; Harkema, Jack R

    2016-06-01

    Epidemiological studies suggest that elevated ambient concentrations of ozone are associated with activation of eosinophils in the nasal airways of atopic and nonatopic children. Mice repeatedly exposed to ozone develop eosinophilic rhinitis and type 2 immune responses. In this study, we determined the role of innate lymphoid cells (ILCs) in the pathogenesis of ozone-induced eosinophilic rhinitis by using lymphoid-sufficient C57BL/6 mice, Rag2(-/-) mice that are devoid of T cells and B cells, and Rag2(-/-)Il2rg(-/-) mice that are depleted of all lymphoid cells including ILCs. The animals were exposed to 0 or 0.8 ppm ozone for 9 consecutive weekdays (4 h/d). Mice were killed 24 hours after exposure, and nasal tissues were selected for histopathology and gene expression analysis. ILC-sufficient C57BL/6 and Rag2(-/-) mice exposed to ozone developed marked eosinophilic rhinitis and epithelial remodeling (e.g., epithelial hyperplasia and mucous cell metaplasia). Chitinase-like proteins and alarmins (IL-33, IL-25, and thymic stromal lymphopoietin) were also increased morphometrically in the nasal epithelium of ozone-exposed C57BL/6 and Rag2(-/-) mice. Ozone exposure elicited increased expression of Il4, Il5, Il13, St2, eotaxin, MCP-2, Gob5, Arg1, Fizz1, and Ym2 mRNA in C57BL/6 and Rag2(-/-) mice. In contrast, ozone-exposed ILC-deficient Rag2(-/-)Il2rg(-/-) mice had no nasal lesions or overexpression of Th2- or ILC2-related transcripts. These results indicate that ozone-induced eosinophilic rhinitis, nasal epithelial remodeling, and type 2 immune activation are dependent on ILCs. To the best of our knowledge, this is the first study to demonstrate that ILCs play an important role in the nasal pathology induced by repeated ozone exposure.

  11. Dysfunctional cerebellar Purkinje cells contribute to autism-like behaviour in Shank2-deficient mice.

    Science.gov (United States)

    Peter, Saša; Ten Brinke, Michiel M; Stedehouder, Jeffrey; Reinelt, Claudia M; Wu, Bin; Zhou, Haibo; Zhou, Kuikui; Boele, Henk-Jan; Kushner, Steven A; Lee, Min Goo; Schmeisser, Michael J; Boeckers, Tobias M; Schonewille, Martijn; Hoebeek, Freek E; De Zeeuw, Chris I

    2016-01-01

    Loss-of-function mutations in the gene encoding the postsynaptic scaffolding protein SHANK2 are a highly penetrant cause of autism spectrum disorders (ASD) involving cerebellum-related motor problems. Recent studies have implicated cerebellar pathology in the aetiology of ASD. Here we evaluate the possibility that cerebellar Purkinje cells (PCs) represent a critical locus of ASD-like pathophysiology in mice lacking Shank2. Absence of Shank2 impairs both PC intrinsic plasticity and induction of long-term potentiation at the parallel fibre to PC synapse. Moreover, inhibitory input onto PCs is significantly enhanced, most prominently in the posterior lobe where simple spike (SS) regularity is most affected. Using PC-specific Shank2 knockouts, we replicate alterations of SS regularity in vivo and establish cerebellar dependence of ASD-like behavioural phenotypes in motor learning and social interaction. These data highlight the importance of Shank2 for PC function, and support a model by which cerebellar pathology is prominent in certain forms of ASD. PMID:27581745

  12. Excitatory synapses are stronger in the hippocampus of Rett syndrome mice due to altered synaptic trafficking of AMPA-type glutamate receptors.

    Science.gov (United States)

    Li, Wei; Xu, Xin; Pozzo-Miller, Lucas

    2016-03-15

    Deficits in long-term potentiation (LTP) at central excitatory synapses are thought to contribute to cognitive impairments in neurodevelopmental disorders associated with intellectual disability and autism. Using the methyl-CpG-binding protein 2 (Mecp2) knockout (KO) mouse model of Rett syndrome, we show that naïve excitatory synapses onto hippocampal pyramidal neurons of symptomatic mice have all of the hallmarks of potentiated synapses. Stronger Mecp2 KO synapses failed to undergo LTP after either theta-burst afferent stimulation or pairing afferent stimulation with postsynaptic depolarization. On the other hand, basal synaptic strength and LTP were not affected in slices from younger presymptomatic Mecp2 KO mice. Furthermore, spine synapses in pyramidal neurons from symptomatic Mecp2 KO are larger and do not grow in size or incorporate GluA1 subunits after electrical or chemical LTP. Our data suggest that LTP is occluded in Mecp2 KO mice by already potentiated synapses. The higher surface levels of GluA1-containing receptors are consistent with altered expression levels of proteins involved in AMPA receptor trafficking, suggesting previously unidentified targets for therapeutic intervention for Rett syndrome and other MECP2-related disorders.

  13. Effects of Environmental Enrichment on Spatial Memory and Neurochemistry in Middle-Aged Mice

    OpenAIRE

    Frick, Karyn M.; Stearns, Nancy A.; Pan, Jing-Yu; Berger-Sweeney, Joanne

    2003-01-01

    The present study compared the effects of environmental enrichment on spatial memory, glutamic acid decarboxylase (GAD) activity, and synaptophysin levels in middle-aged male and female mice. Prior to testing, a subset of 18-month-old male and female C57BL/6 mice was housed with two to three toys and a running wheel in the home cage for up to 29 d. Adult mice (7 mo) of both sexes and the remaining middle-aged mice were group (social) housed, but not exposed to enrichin...

  14. Germline mutation rates in mice following in utero exposure to diesel exhaust particles by maternal inhalation

    DEFF Research Database (Denmark)

    Ritz, Caitlin; Ruminski, Wojciech; Hougaard, Karin S.;

    2011-01-01

    (PAPs) from industrial environments cause DNA damage and mutations in the sperm of adult male mice. Effects on the female and male germline during critical stages of development (in utero) are unknown. In mice, previous studies have shown that expanded simple tandem repeat (ESTR) loci exhibit high rates...... and mated with control CBA mice. The F2 descendents were collected and ESTR germline mutation rates were derived from full pedigrees (mother, father, offspring) of F1 male and female mice. We found no evidence for increased ESTR mutation rates in females exposed in utero to DEP relative to control females...

  15. A Family of Mice

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ 一、故事内容 There is a family of mice in my house. They are father mouse, mother mouse and baby mouse. Baby mouse likes dancing. He is very cute. Father mouse likes watching TV. He likes the sports on TV best. These three mice are clever.

  16. Of mice and men

    CERN Multimedia

    1973-01-01

    At the end of March , sixty mice were irradiated at the synchro-cyclotron in the course of an experimental programme studying radiation effects on mice and plants (Vicia faba bean roots) being carried out by the CERN Health Physics Group.

  17. Prenatal irradiation and spatial memory in mice: investigation of critical period

    Energy Technology Data Exchange (ETDEWEB)

    Sienkiewicz, Z.J.; Saunders, R.D.; Butland, B.K. (National Radiological Protection Board, Chilton (United Kingdom))

    1992-08-01

    Pregnant CD1 mice were exposed on various gestational or postnatal days to 1 Gy of 250 kV X-rays. Ten adult, male offspring from each exposure condition were tested in a radial arm maze. Compared to sham-exposed control mice, acquisition of spatial information was unimpaired in animals exposed on gestational days 13 or 15, or on postnatal day 10, but animals exposed on gestational day 18 or postnatal day 1 showed sustained deficits in acquisition. These results appear consistent with the known time-course for the proliferation and migration of the dentate granule cells of the hippocampus in the mouse, and are discussed in relation to the dependence on hippocampal integrity of the acquisition and use of spatial information. The results suggest that comparable deficits in mental function might be expected in humans similarly exposed to ionizing radiation during periods of proliferation and migration of the dentate granule cells. (author).

  18. Radioprotective Effect Of Green Tea Extract On GAMMA Irradiated Mice

    International Nuclear Information System (INIS)

    This study aimed to evaluate the possible radioprotective role of green tea extract (GTE) in mice exposed to gamma radiation. Eighty male mice were divided into four groups; group (A) was considered the control, group (B) received 1.5% GTE for 14 days, group (C) exposed to 4 Gy gamma radiation and group (D) received GTE and exposed to 4 Gy gamma radiation. Blood and liver tissue were collected from these groups 24 hours, 3 days and 5 days post-irradiation to measure the levels of hepatic malondialdehyde (MDA) and superoxide dismutase (SOD), serum aminotransferases (ALT and AST), Hb concentration, RBCs, WBCs and platelets counts, in addition to ultra-structure examination of the liver. The results revealed that GTE supplementation prior to irradiation significantly decreased hepatic MDA, increased hepatic antioxidant enzyme (SOD) and decreased serum ALT and AST compared to irradiated mice. Also, supplementation of mice with GTE led to regeneration and protection of hepatocytes and the levels of the hematological parameters were significantly increased in the GTE pre-treated group as compared to irradiated animals. It could be conclude that the GTE may be a good agent to attenuate radiation-induced damage to the liver and hematopoietic system.

  19. Anesthetic gases and occupationally exposed workers.

    Science.gov (United States)

    Casale, Teodorico; Caciari, Tiziana; Rosati, Maria Valeria; Gioffrè, Pier Agostino; Schifano, Maria Pia; Capozzella, Assunta; Pimpinella, Benedetta; Tomei, Gianfranco; Tomei, Francesco

    2014-01-01

    The aim of this study is to estimate whether the occupational exposure to low dose anesthetic gases could cause alterations of blood parameters in health care workers. 119 exposed subjects and 184 not exposed controls were included in the study. Each worker underwent the complete blood count test (CBC), proteinaemia, leukocyte count, serum lipids, liver and kidney blood markers. The liver blood markers show statistically significant differences in health care workers compared with controls (pGGT, total bilirubin, lymphocytes and neutrophils was statistically significant in health care workers compared with controls (p<0.05). The results suggest that occupational exposure to low dose anesthetic gases could influence some haematochemical hepatic and hematopoietic parameters in exposed health care workers. PMID:24374387

  20. Serotonin deficiency exacerbates acetaminophen-induced liver toxicity in mice.

    Science.gov (United States)

    Zhang, Jingyao; Song, Sidong; Pang, Qing; Zhang, Ruiyao; Zhou, Lei; Liu, Sushun; Meng, Fandi; Wu, Qifei; Liu, Chang

    2015-01-29

    Acetaminophen (APAP) overdose is a major cause of acute liver failure. Peripheral 5-hydroxytryptamine (serotonin, 5-HT) is a cytoprotective neurotransmitter which is also involved in the hepatic physiological and pathological process. This study seeks to investigate the mechanisms involved in APAP-induced hepatotoxicity, as well as the role of 5-HT in the liver's response to APAP toxicity. We induced APAP hepatotoxicity in mice either sufficient of serotonin (wild-type mice and TPH1-/- plus 5- Hydroxytryptophan (5-HTP)) or lacking peripheral serotonin (Tph1-/- and wild-type mice plus p-chlorophenylalanine (PCPA)). Mice with sufficient 5-HT exposed to acetaminophen have a significantly lower mortality rate and a better outcome compared with mice deficient of 5-HT. This difference is at least partially attributable to a decreased level of inflammation, oxidative stress and endoplasmic reticulum (ER) stress, Glutathione (GSH) depletion, peroxynitrite formation, hepatocyte apoptosis, elevated hepatocyte proliferation, activation of 5-HT2B receptor, less activated c-Jun NH₂-terminal kinase (JNK) and hypoxia-inducible factor (HIF)-1α in the mice sufficient of 5-HT versus mice deficient of 5-HT. We thus propose a physiological function of serotonin that serotonin could ameliorate APAP-induced liver injury mainly through inhibiting hepatocyte apoptosis ER stress and promoting liver regeneration.

  1. Genetic deletion of IL-25 (IL-17E) confers resistance to dextran sulfate sodium-induced colitis in mice

    Science.gov (United States)

    IL-25 is emerging as a key regulator of inflammation in the intestinal mucosa because of its ability to promote Th2 while suppressing Th1 and Th17 cytokine responses. We investigated the contribution of endogenous IL-25 to DSS-induced colitis in mice. Mice were exposed to DSS in drinking water ad li...

  2. Subchronic inhalation toxicity of benzene in rats and mice.

    Science.gov (United States)

    Ward, C O; Kuna, R A; Snyder, N K; Alsaker, R D; Coate, W B; Craig, P H

    1985-01-01

    A subchronic inhalation toxicity study of benzene was conducted in CD-1 mice and Sprague-Dawley rats. Four groups of animals consisting of 150 mice and 50 rats/sex each were exposed to concentrations of 1, 10, 30, and 300 ppm benzene vapor, 6 hours/day, 5 days/week, for 13 weeks. Additional groups of mice and rats, of equal size, were exposed under similar conditions to filtered air and served as control groups. Thirty mice and 10 rats/sex in each group were sacrificed after 7, 14, 28, 56, and 91 days of treatment. Criteria used to evaluate exposure-related effects included behavior, body weights, organ weights, clinical pathology, gross pathology, and histopathology. Fifty animals per sex of each species were exposed concurrently for cytogenetic studies. In addition, blood serum was obtained for immunological assays. The results of these two studies will be reported separately. No consistent exposure-related trends were seen in the clinical observations and body weight data. Exposure-related clinical pathology changes were seen in the high-level (300 ppm) animals of both species. In the mice, these changes included decreases in hematocrit, total hemoglobin, erythrocyte count, leukocyte count, platelet count, myeloid/erythroid ratios, and percentage of lymphocytes. Mean cell volume, mean cell hemoglobin, glycerol lysis time, and the incidence and severity of red cell morphologic changes were increased in the mice. In the rats, decreased lymphocyte counts and a relative increase in neutrophil percentages were the only exposure-related clinical pathology alterations. Histopathologic changes were present in the thymus, bone marrow, lymph nodes, spleen, ovaries, and testes of mice exposed to 300 ppm and in most cases the incidence and severity of the lesions were greater in the males. These changes in the testes and ovaries at 300 ppm were also seen at lower concentrations, but they were of doubtful biological significance. In rats, the only exposure-related lesion

  3. Exposing Library Services with AngularJS

    OpenAIRE

    Jakob Voß; Moritz Horn

    2014-01-01

    This article provides an introduction to the JavaScript framework AngularJS and specific AngularJS modules for accessing library services. It shows how information such as search suggestions, additional links, and availability can be embedded in any website. The ease of reuse may encourage more libraries to expose their services via standard APIs to allow usage in different contexts.

  4. Rural Canadian Youth Exposed to Physical Violence

    Science.gov (United States)

    Laye, Adele M.; Mykota, David B.

    2014-01-01

    Exposure to physical violence is an unfortunate reality for many Canadian youth as it is associated with numerous negative psychosocial effects. The study aims to assist in understanding resilience in rural Canadian youth exposed to physical violence. This is accomplished by identifying the importance of protective factors, as measured by the…

  5. Dose coefficients for individual occupationally exposed

    International Nuclear Information System (INIS)

    This Regulation refers to the requirements of the Regulation CNEN-NN.3.01, 'Basic Act of Radiological Protection', aiming its application to the dose calculation, with purposes of conformity verification with limits and restrictions of doses and level of reference for individual occupationally exposed, according to the express in its section 5

  6. Expose Mechanical Engineering Students to Biomechanics Topics

    Science.gov (United States)

    Shen, Hui

    2011-01-01

    To adapt the focus of engineering education to emerging new industries and technologies nationwide and in the local area, a biomechanics module has been developed and incorporated into a mechanical engineering technical elective course to expose mechanical engineering students at ONU (Ohio Northern University) to the biomedical engineering topics.…

  7. Stability in Effects of gamma-Irradiated Chinese Medicinal Prescriptions on Protection of Mice from Radiation

    International Nuclear Information System (INIS)

    The radioprotective effects of irradiated medicinal plants on biological system were studied to apply the irradiation technology for hygienic purpose that is usually performed by chemical preservatives. We previously reported that the three Chinese medicinal prescriptions, Si-Wu-Tang, Bu-Zhong-Yi-Qi-Tang and San-Ling-Bai-Shu-San, showed radioprotective effects in mice. In these experiments, to investigate the difference in radioprotective effects between irradiated (10 kGy) and non-irradiated medicinal plants, mice were administered with the irradiated or non-irradiated prescriptions and then the mice were exposed to gamma-rays with low and high dosage. Non-exposed mice were also prepared as a control. The effects of prescriptions on the jejunal crypt survival, endogenous spleen colony formation, and apoptosis of jejunal crypt cells in mice were investigated after exposure. All of the prescriptions showed the protective effects of the jejunal crypt (p0.05) and the adminstration of the prescriptions increased the formation of endogenous spleen colony (p0.05) and reduced the frequency of radiation-induced apoptosis (p0.05). No significant difference in effects between irradiated and non-irradiated prescreption on the parameters was found in mice administered with each prescription before exposure to gamma-rays. In non-exposed mice, there were no different findings in the parameters between irradiated and non-irradiated prescription

  8. Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition.

    Science.gov (United States)

    Zhu, Zhu; Hua, Bingxuan; Shang, Zhanxian; Yuan, Gongsheng; Xu, Lirong; Li, Ermin; Li, Xiaobo; Sun, Ning; Yan, Zuoqin; Qian, Ruizhe; Lu, Chao

    2016-01-01

    Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice) by altering exposure to light. C57 BL/6J mice (C57 mice) and ApoE-KO mice (ApoE-KO mice) exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1) levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation. PMID:27631008

  9. Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition.

    Science.gov (United States)

    Zhu, Zhu; Hua, Bingxuan; Shang, Zhanxian; Yuan, Gongsheng; Xu, Lirong; Li, Ermin; Li, Xiaobo; Sun, Ning; Yan, Zuoqin; Qian, Ruizhe; Lu, Chao

    2016-01-01

    Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice) by altering exposure to light. C57 BL/6J mice (C57 mice) and ApoE-KO mice (ApoE-KO mice) exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1) levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation.

  10. Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition

    Directory of Open Access Journals (Sweden)

    Zhu Zhu

    2016-01-01

    Full Text Available Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice by altering exposure to light. C57 BL/6J mice (C57 mice and ApoE-KO mice (ApoE-KO mice exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1 levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation.

  11. Maternal inhalation of surface-coated nanosized titanium dioxide (UV-Titan) in C57BL/6 mice

    DEFF Research Database (Denmark)

    Jackson, Petra; Halappanavar, Sabina; Hougaard, Karin Sorig;

    2013-01-01

    We investigated effects of maternal pulmonary exposure to titanium dioxide (UV-Titan) on prenatally exposed offspring. Time-mated mice (C57BL/6BomTac) were inhalation exposed (1 h/day to 42 mg UV-Titan/m(3) aerosolised powder or filtered air) during gestation days (GDs) 8-18. We evaluated DNA...

  12. Embryonic Lethality Due to Arrested Cardiac Development in Psip1/Hdgfrp2 Double-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Hao Wang

    Full Text Available Hepatoma-derived growth factor (HDGF related protein 2 (HRP2 and lens epithelium-derived growth factor (LEDGF/p75 are closely related members of the HRP2 protein family. LEDGF/p75 has been implicated in numerous human pathologies including cancer, autoimmunity, and infectious disease. Knockout of the Psip1 gene, which encodes for LEDGF/p75 and the shorter LEDGF/p52 isoform, was previously shown to cause perinatal lethality in mice. The function of HRP2 was by contrast largely unknown. To learn about the role of HRP2 in development, we knocked out the Hdgfrp2 gene, which encodes for HRP2, in both normal and Psip1 knockout mice. Hdgfrp2 knockout mice developed normally and were fertile. By contrast, the double deficient mice died at approximate embryonic day (E 13.5. Histological examination revealed ventricular septal defect (VSD associated with E14.5 double knockout embryos. To investigate the underlying molecular mechanism(s, RNA recovered from ventricular tissue was subjected to RNA-sequencing on the Illumina platform. Bioinformatic analysis revealed several genes and biological pathways that were significantly deregulated by the Psip1 knockout and/or Psip1/Hdgfrp2 double knockout. Among the dozen genes known to encode for LEDGF/p75 binding factors, only the expression of Nova1, which encodes an RNA splicing factor, was significantly deregulated by the knockouts. However the expression of other RNA splicing factors, including the LEDGF/p52-interacting protein ASF/SF2, was not significantly altered, indicating that deregulation of global RNA splicing was not a driving factor in the pathology of the VSD. Tumor growth factor (Tgf β-signaling, which plays a key role in cardiac morphogenesis during development, was the only pathway significantly deregulated by the double knockout as compared to control and Psip1 knockout samples. We accordingly speculate that deregulated Tgf-β signaling was a contributing factor to the VSD and prenatal lethality

  13. Mice Status Report: September 2010

    OpenAIRE

    Blondel, Alain; Hanson, G.

    2010-01-01

    This report is prepared for the MICE Project Board meeting of September 2010. It constitutes an update of the reports produced for the MICE Funding Agency Committee in December 20081, October 20092 and April 20103 and concentrates on the progress made since. The design of the MICE experiment can be found in the MICE proposal

  14. Exploring MICE Potential

    Institute of Scientific and Technical Information of China (English)

    LIU BO

    2006-01-01

    @@ With commerce and entertainment increasingly intertwined and the Chinese economy becoming more internationally integrated, Meetings,Incentives, Conference and Exhibitions (MICE) travel, is regarded by many travel agencies as one of the most potentially profitable tourism trends of the future.

  15. Cessation of dexamethasone exacerbates airway responses to methacholine in asthmatic mice.

    Science.gov (United States)

    Stengel, Peter W; Nickell, Laura E; Wolos, Jeffrey A; Snyder, David W

    2007-06-01

    In asthmatic mice, dexamethasone (30.0 mg/kg) was administered orally once daily on Days 24-27. One hour after dexamethasone on Day 25-27, the mice were exposed to ovalbumin aerosols. Twenty-eight days after the initial ovalbumin immunization, we found that dexamethasone reduced methacholine-induced pulmonary gas trapping and inhibited bronchoalveolar lavage eosinophils and neutrophils. However, five days after the last dose of dexamethasone and last ovalbumin aerosol exposure in other asthmatic mice, the airway obstructive response to methacholine was exacerbated in dexamethasone-treated mice compared to vehicle-treated mice on Day 32. Further, eosinophils, but not neutrophils, were still inhibited after cessation of dexamethasone. Thus, discontinuing dexamethasone worsened methacholine-induced pulmonary gas trapping of asthmatic mice in the absence of eosinophilic airway inflammation.

  16. Increased sensitivity of C. parvum treated mice to ionizing whole body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Basic, I.; Withers, R.H.; Kastelan, A.; Milas, L.

    1977-04-13

    We have investigated whether C. parvum (CP)-induced stimulation of hematopoiesis affects the survival of mice exposed to the whole body irradiation (WBI). C3Hf/Bu mice treated with CP exhibit an increased hematopoietic colony forming activity in their spleens and blood, but not in their bone marrow, as determined by the exogenous spleen colony assay. Also, CP-treated C3Hf/Bu as well as CBA mice show an increase in their endogenous colonies. This increased hematopoietic activity caused by CP treatment did not protect mice from the consequences of the WBI ranging from 650 to 950 rads. In fact, more mice died if they had been treated with CP. A decrease in the number of erythrocytes was more pronouned in mice treated with CP and irradiation than in those given irradiation alone.

  17. Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice

    Science.gov (United States)

    Dewald, Daniela; Schmitz, Eva J.; Verfuerth, Luise; Keppel, Katharina; Peigney, Christine; Ghanem, Alexander; Welz, Armin; Dewald, Oliver

    2016-01-01

    Aims. Repetitive brief ischemia and reperfusion (I/R) is associated with left ventricular dysfunction during development of ischemic cardiomyopathy. We investigated the role of zinc-donor proteins metallothionein MT1 and MT2 in a closed-chest murine model of I/R. Methods. Daily 15-minute LAD-occlusion was performed for 1, 3, and 7 days in SV129 (WT)- and MT1/2 knockout (MT−/−)-mice (n = 8–10/group). Hearts were examined with M-mode echocardiography and processed for histological and mRNA studies. Results. Expression of MT1/2 mRNA was transiently induced during repetitive I/R in WT-mice, accompanied by a transient inflammation, leading to interstitial fibrosis with left ventricular dysfunction without infarction. In contrast, MT−/−-hearts presented with enhanced apoptosis and small infarctions leading to impaired global and regional pump function. Molecular analysis revealed maladaptation of myosin heavy chain isoforms and antioxidative enzymes in MT1/2−/−-hearts. Despite their postponed chemokine induction we found a higher total neutrophil density and macrophage infiltration in small infarctions in MT−/−-hearts. Subsequently, higher expression of osteopontin 1 and tenascin C was associated with increased myofibroblast density resulting in predominately nonreversible fibrosis and adverse remodeling in MT1/2−/−-hearts. Conclusion. Cardioprotective effects of MT1/2 seem to be exerted via modulation of contractile elements, antioxidative enzymes, inflammatory response, and myocardial remodeling. PMID:27403038

  18. Antigenotoxic potential of rutin and quercetin in Swiss mice exposed to gamma radiation

    OpenAIRE

    Patil, Shrikant L.; Nageshwar B Rao; HM Somashekarappa; KP Rajashekhar

    2014-01-01

    Background: Ionizing radiation induces a variety of genetic damages through the formation free radicals such as reactive oxygen species (ROS). Appropriate antioxidant intervention may inhibit or reduce free radical toxicity and thus offer protection against radiation. Rutin (RUT) and quercetin (QRT) are flavonoids known to be potent dietary antioxidants. Methods: The present study tested the antigenotoxic effect of RUT and QRT in vivo against radiation- induced chromosomal damage. Swiss al...

  19. DNA and Chromosome Damaging Effects in Mice Exposed to an Estuary Sediment Extract

    OpenAIRE

    Pinto, Miguel; Sacadura, Joana; Louro, Henriqueta; Costa, Pedro Manuel; Lavinha, João; Silva, Maria João

    2013-01-01

    Previous studies have shown that an extract of a sediment sample collected in a fishing area of Sado Estuary, impacted by the urban and industrial pollution from the city of Setúbal, was able to induce cytotoxicity and genotoxicity in a human cell line (HepG2) and in local aquatic species, probably due to the presence of PAHs and metals. However, the assessment of the potential hazard of those contaminants to humans, through extrapolation of the in vitro data, is difficult and thereby in vivo...

  20. Micronucleus test and metaphase analyses in mice exposed to known and suspected spindle poisons.

    Science.gov (United States)

    Marrazzini, A; Betti, C; Bernacchi, F; Barrai, I; Barale, R

    1994-11-01

    Micronucleus (Mn) and metaphase chromosome analyses were performed in mouse bone marrow cells with two known and eight suspected mitotic spindle poisons. Polychromatic (PCEs) and normochromatic (NCEs) erythrocytes were scored for presence of Mn, while structural (CAs) and numerical chromosome aberrations (NCAs), i.e. hyperploid cells, were evaluated by metaphase analysis. CAs were scored in first, and NCAs in the second metaphases, identified by BrdUrd differential staining. Hydroquinone induced Mn, NCAs and CAs; colchicine, vinblastine and, to a lesser extent, chloral hydrate, diazepam and econazole induced both Mn and NCAs; cadmium chloride and thimerosal induced Mn and CAs, while pyrimethamine and thiabendazole induced Mn only. The proposed stepwise protocol allowed satisfactory statistical evaluation of the effects induced with a reduction in the number of animals killed. An acceptable agreement was found between induction of Mn and NCAs, suggesting a possible use of the Mn test for revealing compounds with aneugenic properties. PMID:7854141

  1. L-Arginine improves multiple physiological parameters in mice exposed to diet-induced metabolic disturbances

    DEFF Research Database (Denmark)

    Clemmensen, Christoffer; Madsen, Andreas Nygaard; Smajilovic, Sanela;

    2012-01-01

    L: -Arginine (L: -Arg) is a conditionally essential amino acid and a natural constituent of dietary proteins. Studies in obese rats and type 2 diabetic humans have indicated that dietary supplementation with L: -Arg can diminish gain in white adipose tissue (WAT) and improve insulin sensitivity...... on locomotor activity, substrate metabolism or expression of uncoupling proteins (UCP1 and UCP2) in adipose tissues was displayed. In conclusion, dietary L: -Arg supplementation substantially affects an array of metabolic-associated parameters including a reduction in WAT, hyperphagia, improved insulin...... groups. Glucose homeostasis experiments revealed a major effect of L: -Arg supplementation on glucose tolerance and insulin sensitivity, interestingly, independent of a parallel regulation in whole-body adiposity. Increased L: -Arg ingestion also raised energy expenditure; however, no concurrent effect...

  2. Fetotoxicity and neural tube defects on CD1 mice exposed to the mycotoxin fumonisin b1

    Science.gov (United States)

    The fumonisin mycotoxins are produced by Fusarium verticillioides and F. proliferatum. They occur commonly in maize and maize-based foods. The human health effects of fumonisins are unclear. There is however epidemiological and experimental evidence suggesting that these mycotoxins interfere with f...

  3. Modulation of pulmonary inflammatory responses and anti-microbial defenses in mice exposed to diesel exhaust

    Science.gov (United States)

    Abstract: Diesel exhaust (DE) is a major component of urban air pollution and has been shown to increase the severity of infectious and allergic lung disease. The purpose of this study was to evaluate the effects of DE exposure on pulmonary inflammation, mediator production and ...

  4. Brain activation by short-term nicotine exposure in anesthetized wild-type and beta2-nicotinic receptors knockout mice: a BOLD fMRI study

    Energy Technology Data Exchange (ETDEWEB)

    Suarez, S.V.; Changeux, J.P.; Granon, S. [Unite de Neurobiologie Integrative du Systeme Cholinergique, URA CNRS 2182, Institut Pasteur, Departement de Neuroscience, 25 rue du Dr Roux, 75015 Paris (France); Amadon, A.; Giacomini, E.; Le Bihan, D. [Service Hospitalier Frederic Joliot, 4 place du general Leclerc, 91400 Orsay (France); Wiklund, A. [Section of Anaesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm (Sweden)

    2009-07-01

    Rationale: The behavioral effects of nicotine and the role of the beta2-containing nicotinic receptors in these behaviors are well documented. However, the behaviors altered by nicotine rely on the functioning on multiple brain circuits where the high-affinity {beta}2-containing nicotinic receptors ({beta}2*nAChRs) are located. Objectives We intend to see which brain circuits are activated when nicotine is given in animals naive for nicotine and whether the {beta}2*nAChRs are needed for its activation of the blood oxygen level dependent (BOLD) signal in all brain areas. Materials and methods: We used functional magnetic resonance imaging (fMRI) to measure the brain activation evoked by nicotine (1 mg/kg delivered at a slow rate for 45 min) in anesthetized C57BL/6J mice and {beta}2 knockout (KO) mice. Results: Acute nicotine injection results in a significant increased activation in anterior frontal, motor, and somatosensory cortices and in the ventral tegmental area and the substantia nigra. Anesthetized mice receiving no nicotine injection exhibited a major decreased activation in all cortical and subcortical structures, likely due to prolonged anesthesia. At a global level, {beta}2 KO mice were not rescued from the globally declining BOLD signal. However, nicotine still activated regions of a meso-cortico-limbic circuit likely via {alpha}7 nicotinic receptors. Conclusions: Acute nicotine exposure compensates for the drop in brain activation due to anesthesia through the meso-cortico-limbic network via the action of nicotine on {beta}2*nAChRs. The developed fMRI method is suitable for comparing responses in wild-type and mutant mice. (authors)

  5. Pulmonary effects of inhaled diesel exhaust in aged mice

    International Nuclear Information System (INIS)

    Pulmonary morbidity and mortality resulting from exposure to fine particulate matter (PM) increases with age. The present studies analyzed potential mechanisms underlying increased susceptibility of the elderly to PM using diesel exhaust (DE) as a model. Mice (2 m and 18 m) were exposed to DE (0, 300, and 1000 μg/m3) for 3 h once (single) or 3 h/day for 3 days (repeated). Bronchoalveolar lavage fluid (BAL), serum and lung tissue were collected 0 and 24 h later. Exposure to DE resulted in structural alterations in the lungs of older but not younger mice, including patchy thickening of the alveolar septa and inflammatory cell localization in alveolar spaces. These effects were most pronounced 24 h after a single exposure to the higher dose of DE. Significant increases in BAL nitrogen oxides were also noted in older mice, as well as expression of lipocalin 24p3, an oxidative stress marker in the lung with no effects in younger mice. Following DE inhalation, expression of Tumor Necrosis Factor alpha (TNFα) was upregulated in lungs of both younger and older mice; however, this was attenuated in older animals. Whereas exposure to DE resulted in increases in lung Interleukin-6 (IL-6) expression in both older and younger mice, IL-8 increased only in older animals. In younger mice, constitutive expression of manganese superoxide dismutase (MnSOD) decreased after DE exposure, while in older mice, constitutive MnSOD was not detectable and DE had no effect on expression of this antioxidant. Taken together, these results suggest that altered generation of inflammatory mediators and MnSOD may contribute to increased susceptibility of older mice to inhaled DE.

  6. The study on morphologic alteration of fetal mice and the change of MeCP2 in fetal brain induced by ionizing radiation

    International Nuclear Information System (INIS)

    Objective: In order to investigate the effect and the possible mechanism of γ-rays on neuro development of fetal brain tissue as bystander effect organ. Methods: pregnant kunming mice were randomly divided into blank control group, 0.5 Gy whole-body exposed group, 0.5 Gy head exposed group, 1.0 Gy whole-body exposed group, 1.0 Gy head exposed group, 2.0 Gy whole-body exposed group and 2.0 Gy head exposed group. The exposed mice were exposed with a vertical single acute dose using 60Co therapy apparatus on the 9 th day of pregnancy, and cesarean operation were performed to gain fetal mice on the 18 th day of pregnancy. The number, the size, stillbirth, birth defects and abortion, and get fetal brains from live births were observed. Western-blot assay was used to detect the expression of MeCP2 protein. Results: Compared with the blank control group, the rates of stillbirth, birth defects and abortion ascended as the increase of doses; the expression of MeCP2 were upregulated except 0.5 Gy whole-body exposed group, there were no significant differences between groups. Conclusion: When the pregnant mice were exposed to ionizing radiation in the first trimester, bystander effect in fetal brain tissue was induced, within a certain range, the incidence of deterministic effects and stochastic effects ascended as the increase of doses. (authors)

  7. Stability of people exposed to water flows

    Directory of Open Access Journals (Sweden)

    E. Martínez-Gomariz

    2016-01-01

    Full Text Available Our cities are formed by several elements which are exposed to floods of a magnitude according to the importance of the rainfall event and the design of the urban drainage system. The most important components in the cities are the pedestrians who develop various activities during rain events. Focusing on pedestrians, the research on their stability when they are exposed to water flows provides the necessary knowledge to understand and manage the associated hazard for them. In this research, several experiments with humans were carried out in order to determine the stability limits to pedestrians crossing through a water flow in a real scale platform. The results obtained and by comparing those with human stability criteria proposed by other authors and guidelines provide a more restrictive criterion.

  8. Diabetic ketoacidosis in patients exposed to antipsychotics

    DEFF Research Database (Denmark)

    Polcwiartek, Christoffer; Vang, Torkel; Bruhn, Christina Hedegård;

    2016-01-01

    RATIONALE: Patients exposed to second-generation antipsychotics (SGAs) have approximately 10 times increased risk of diabetic ketoacidosis (DKA) compared with the general population. However, as DKA is a rare complication of type 2 diabetes mellitus, and susceptible patients exposed...... to antipsychotics may rapidly develop DKA independently of treatment duration and weight gain, this is rather suggestive of type 1 diabetes mellitus (T1DM) or latent autoimmune diabetes in adults. OBJECTIVES: We performed a systematic review of current studies regarding antipsychotic-associated DKA with type 1...... etiology and analyzed Danish adverse drug event (ADE) reports (previously unpublished cases). METHODS: PubMed, Embase, and the Cochrane Library were searched for all relevant studies, and the Danish Medicines Agency retrieved ADE reports using the Danish ADE database (up to date as of June 28, 2016...

  9. Photodynamic therapy with topical delta-aminolevulinic acid delays UV photocarcinogenesis in hairless mice.

    Science.gov (United States)

    Stender, I M; Bech-Thomsen, N; Poulsen, T; Wulf, H C

    1997-10-01

    Photodynamic therapy (PDT) with topical application of delta-aminolevulinic acid (ALA) followed by irradiation with visible light (ALA-PDT) is a relatively new and promising experimental treatment of superficial premalignant and malignant skin neoplasms. The purpose of this study was to determine whether ALA-PDT can prevent photocarcinogenesis in hairless mice exposed to solar UV. A total of 140 mice was divided into seven groups of 20 mice each. Group 1: solar-UV exposure. Group 2: solar UV and a cream base+visible light once a week. Group 3: solar UV and ALA-PDT once a week. Group 4: solar UV and ALA-PDT once every second week. Group 5: solar UV and ALA-PDT every fourth week. Group 6: ALA-PDT once a week. Group 7: no treatment. The time to first and to second tumor > or = 1 mm was registered. Predefined endpoints, such as one tumor > or = 4 mm or an area of small confluent tumors on the back of the mice were criteria for withdrawal from the experiment. The time to first and to second tumor was significantly longer in the ALA-PDT-treated mice than in mice only exposed to solar UV and solar-UV/cream base-visible light (P or = 4 mm (P = 0.0005). The UV unexposed mice developed no tumors. Repetitive treatments with ALA-PDT delay photoinduced carcinogenesis in mice. PMID:9337620

  10. Pancreatic Effects of Diesel Exhaust Particles in Mice with Type 1 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Abderrahim Nemmar

    2014-02-01

    Full Text Available Background/Aims: Epidemiologically, diabetics are more prone to the adverse health effects of particulate air pollution than healthy individuals. We recently demonstrated an increased cardiovascular and respiratory susceptibility to diesel exhaust particles (DEP in mice with type 1 diabetes. However, the pancreatic effects of DEP in healthy and diabetic mice are unknown. Methods: Presently, we evaluated the pancreatic impact of DEP in healthy mice, and mice with streptozotocin-induced type 1 diabetes. Four weeks following induction of diabetes, mice were intratracheally instilled (i.t. with either DEP (0.4 mg/kg or saline, and several histological and biochemical endpoints were measured 24 h thereafter. Results: Neither the histology nor the stain for apoptosis in the pancreatic islets and exocrine glands were affected by DEP. In diabetic mice exposed to saline, the islet cells showed cellular vacuolation and apoptotic islet cells (71.6 ± 2.6%. In diabetic mice exposed to DEP, a more marked decrease in the size and number of islet cells with cellular vacuolation along with a significant increase of apoptotic islet cells (79.1 ± 1.7 %, PConclusion: We conclude that DEP caused detrimental effects on the pancreas of diabetic mice, and that oxidative stress is responsible, at least partially, for the observed effects

  11. The effects of cues from kingsnakes on the reproductive effort of house mice

    Institute of Scientific and Technical Information of China (English)

    W.Wallace STARKEⅢ; Michael H.FERKIN

    2013-01-01

    It is not clear if rodents express inducible defenses in response to reptilian predators such as snakes.We tested the hypothesis that adult house mice Mus musculus decrease aspects of their reproductive effort upon 1 hour of exposure every 48 hours for a 25-day period to the fecal material and shed skins of a euryphagous ophidian predator,the kingsnake Lampropeltis getula,that had been fed mice.We found no significant differences in the total number of offspring born,the number of pups per litter,and the mean weight of pups in litters born to male and female mice that were exposed to predator cues and those mice that were not exposed to such cues.The lack of an inducible response may be associated with the low cost of an effective defense,or the lack of an effective defense against a generalist snake predator [Current Zoology 59 (1):135-141,2013].

  12. Structural parts exposed to gaseous hydrogen isotopes

    International Nuclear Information System (INIS)

    Tubes and parts exposed to media contg. gaseous H isotopes are coated with Mn 0.1-1 μm thick; subjected to a diffusion treatment until the surface Mn concentration is 0.5-0.8%; and annealed 15-45 h at 850-1000 degree in an oxidizing atmosphere until an oxide layer 1-10 μm thick is formed. (orig./PW)

  13. Exposing Provenance Metadata Using Different RDF Models

    OpenAIRE

    Fu, Gang; Bolton, Evan; Rosinach, Núria Queralt; Laura I Furlong; Nguyen, Vinh; Sheth, Amit; Bodenreider, Olivier; Dumontier, Michel

    2015-01-01

    A standard model for exposing structured provenance metadata of scientific assertions on the Semantic Web would increase interoperability, discoverability, reliability, as well as reproducibility for scientific discourse and evidence-based knowledge discovery. Several Resource Description Framework (RDF) models have been proposed to track provenance. However, provenance metadata may not only be verbose, but also significantly redundant. Therefore, an appropriate RDF provenance model should be...

  14. Response of male mice to odours of female mice in different stages of oestrous cycle: self-grooming behaviour and the effect of castration.

    Science.gov (United States)

    Achiraman, Shanmugam; SankarGanesh, Devaraj; Kannan, Soundarapandian; Kamalakkannan, Soundararajan; Nirmala, Natarajan; Archunan, Govindaraju

    2014-01-01

    The behavioural assays were carried out in a Y-maze wherein intact, castrated and testosterone-treated male mice were exposed to oestrus and non-oestrus urine samples. The intact male mice investigated more frequently and spent more time in the Y-maze arm with oestrus urine than in that with non-oestrus urine. In contrast, the castrated mice were not attracted to oestrus urine, whereas testosterone-treated mice showed preference for oestrus urine. The rate of self-grooming was higher in intact males in case of exposure to oestrus urine while the rate was lower with respect to non-oestrus urine. However, castrated mice exhibited less self-grooming behaviour which was partially restored by testosterone treatment. The results suggest that self-grooming behaviour is an indicator of detection and discrimination of oestrus by males, and supports the androgen role in male chemosensory ability to discriminate between oestrus and non-oestrus female odours.

  15. Embryo developmental capacity of oocytes fertilised by sperm of mouse exposed to forced swimming stress

    International Nuclear Information System (INIS)

    Objective: To assess developmental capacity of fertilised oocytes by sperm of mouse exposed to forced swimming stress. Methods: The experimental study was conducted at the Physiology Research Center of Ahvaz Jundishapur University of Medical Sciences, from August 2011 to January 2012. It comprised 20 adult male and 10 female mice. The male mice were randomly divided into two equal groups (n=10): control and experimental. Animals of the experimental group were submitted to forced swimming stress. All male mice were euthanised and the cauda epididymis removed before contents were squeezed out. A pre-incubated capacitated sperm was gently added to the freshly collected ova of the two groups of study. The combined sperm-oocyte suspension was incubated for 4-6 hours under a condition of 5% Carbon dioxide and 37 degree C temperature. The ova were then washed through several changes of medium and finally incubated. Fertilisation was assessed by recording the number of 1-cell embryos 4-6 hours after insemination. The 1-cell embryos were allowed to further develop in vitro for about 120 hours. Development of embryos everyday and during 5 days of culture was observed by using inverted microscope. SPSS 13.0.1 was used for statistical analysis. Results: The percentage of oocytes fertilised was 75:96 (78.12+-4.8%) and 50:10 (49.5+-3.9%) in the control and experimental groups, respectively. The difference was significant (p 0.05) between the two groups in terms of speed and developmental capacity of blastocysts. Conclusions: Fertilisation capacity of male mice affected by forced swimming stress and also the developmental capacity of oocyte fertilised by sperm of mouse exposed to forced swimming stress decreased. (author)

  16. Increased alcohol consumption in relaxin-3 deficient male mice.

    Science.gov (United States)

    Shirahase, Takahira; Aoki, Miku; Watanabe, Ryuji; Watanabe, Yoshihisa; Tanaka, Masaki

    2016-01-26

    Relaxin-3 is a neuropeptide expressed in the brainstem, and predominantly localized in the gray matter of the midline dorsal pons termed the nucleus incertus. Relaxin-3-expressing neurons densely project axons rostrally to various forebrain regions including the septum, hippocampus, and lateral hypothalamus. Several relaxin-3 functions have been reported including food intake, stress responses, neuroendocrine function, emotion, and spatial memory. In addition, recently relaxin-3 and its receptor, RXFP3, were shown to regulate alcohol intake using an RXFP3 antagonist and RXFP3 gene knockout mice. In the present study, we investigated alcohol consumption in relaxin-3 knockout mice, and found that male but not female mice significantly drank more alcohol than wild-type mice in the two-bottle choice test. However, after chronic alcohol vapor exposure, wild-type and mutant mice did not show this difference in alcohol intake, although both genotypes exhibited increased alcohol consumption compared with non-alcohol-exposed control mice. There was no genotype difference in sucrose or quinine preference. These results suggest that the relaxin-3 neuronal system modestly affects alcohol preference and consumption. PMID:26687275

  17. Obesity impairs lactation performance in mice by inducing prolactin resistance

    OpenAIRE

    Buonfiglio, Daniella C.; Angela M. Ramos-Lobo; Freitas, Vanessa M.; Thais T. Zampieri; Vanessa S. Nagaishi; Magna Magalhães; Jose Cipolla-Neto; Nathalie Cella; Jose Donato Jr.

    2016-01-01

    Obesity reduces breastfeeding success and lactation performance in women. However, the mechanisms involved are not entirely understood. In the present study, female C57BL/6 mice were chronically exposed to a high-fat diet to induce obesity and subsequently exhibited impaired offspring viability (only 15% survival rate), milk production (33% reduction), mammopoiesis (one-third of the glandular area compared to control animals) and postpartum maternal behaviors (higher latency to retrieving and...

  18. Pulsed Irradiation Studies in Mice, Rats and Dogs

    International Nuclear Information System (INIS)

    Radiation lethality as a function of radiation dose rate has been extensively explored over the range of less than one rad to a few hundreds of rad/min, but comparatively little is known of the biological consequences at exposure intensities of the order of 105-106 rad/min. In the present experiments radiations produced by a TRIGA reactor have been used to study the comparative acute-mortality responses (LD50/30) of mice and dogs irradiated either at moderate dose rates (40 or 100 rad/min for mice and 23 rad/min for dogs) or by a single high dose-rate radiation pulse (∼ 106 rad/min for mice and ∼2.0 X 105 rad/min for dogs). In the mouse experiments, the LD50/30 of animals exposed at the moderate dose rates of 40 rad of n/min or 100 rad for gamma-radiation/min was not significantly different from the LD50/30 of animals exposed to the same radiation given as a pulsed exposure. Likewise, in acute mortality studies conducted with unilaterally neutron-irradiated dogs, no significant differences in LDso/sowere found between groups irradiated at 23 rad/min or exposed to pulsed dose rates in excess of 1.5 x 105 rad/min. Other studies have been conducted to determine if recovery from radiation injury in mice, as estimated by the split-dose irradiation technique, is influenced by the rate at which the initial sublethal injury is produced. Recovery has been compared at 5 and 14 days post-irradiation in groups of animals exposed at either 40 or 9 x 104 rad/min and no dose-rate dependency of recovery has been detected. (author)

  19. Libby amphibole-induced mesothelial cell autoantibodies promote collagen deposition in mice.

    Science.gov (United States)

    Gilmer, John; Serve, Kinta; Davis, Chad; Anthony, Marti; Hanson, Robert; Harding, Tanner; Pfau, Jean C

    2016-06-01

    Libby amphibole (LA) causes a unique progressive lamellar pleural fibrosis (LPF) that is associated with pulmonary function decline. Pleural fibrosis among the LA-exposed population of Libby, MT, has been associated with the production of anti-mesothelial cell autoantibodies (MCAA), which induce collagen production from cultured human mesothelial cells. We hypothesized that the progressive nature of LPF could be at least partially attributed to an autoimmune process and sought to demonstrate that LA-induced MCAA trigger collagen deposition in vivo. C57BL/6 mice were exposed to LA for 7 mo, and serum was tested for MCAA by cell-based ELISA on primary mouse mesothelial cells. When treated in vitro with serum from mice exposed to LA, mesothelial cells upregulated collagen matrix production. This effect was lost when the serum was cleared of IgG using protein G beads, implicating IgG autoantibodies. Using the peritoneal cavity as a surrogate for the pleural cavity, groups of naïve (non-asbestos-exposed) mice were injected intraperitoneally with 1) control serum, 2) one dose of serum from LA-exposed mice (LA serum), 3) two doses of LA serum, or 4) two doses of LA serum cleared of IgG. After 1 mo, analysis of collagen in peritoneal walls using two-photon confocal microscopy (SHG analysis) and a hydroxyproline assay demonstrated significant increases in collagen by LA serum but not control or cleared serum. These data support the hypothesis that MCAA in LA-exposed mice induce fibrotic responses in vivo, demonstrating that an autoimmune component may be contributing to the progressive pleural fibrosis seen in LA-exposed patients. PMID:27106292

  20. Chronic exposure to trichloroethene causes early onset of SLE-like disease in female MRL +/+ mice

    OpenAIRE

    Cai, Ping; König, Rolf; Boor, Paul J; Kondraganti, Shakuntala; Kaphalia, Bhupendra S.; Khan, M. Firoze; Ansari, G.A.S.

    2007-01-01

    Trichloroethene (TCE) exacerbates the development of autoimmune responses in autoimmune-prone MRL +/+ mice. Although TCE-mediated autoimmune responses are associated with an increase in serum immunoglobulins and autoantibodies, the underlying mechanism of autoimmunity is not known. To determine the progression of TCE-mediated immunotoxicity, female MRL +/+ mice were chronically exposed to TCE through the drinking water (0.5 mg/ml of TCE) for various periods of time. Serum concentrations of an...

  1. Effects of Electromagnetic Radiation from Smartphones on Learning Ability and Hippocampal Progenitor Cell Proliferation in Mice

    OpenAIRE

    Choi, Yu-Jin; Choi, Yun-Sik

    2015-01-01

    Objectives Nonionizing radiation is emitted from electronic devices, such as smartphones. In this study, we intended to elucidate the effect of electromagnetic radiation from smartphones on spatial working memory and progenitor cell proliferation in the hippocampus. Methods Both male and female mice were randomly separated into two groups (radiated and control) and the radiated group was exposed to electromagnetic radiation for 9 weeks and 11 weeks for male and female mice, respectively. Spat...

  2. Corticosterone release in oxytocin gene deletion mice following exposure to psychogenic versus non-psychogenic stress

    OpenAIRE

    Amico, Janet A.; Cai, Hou-Ming; Vollmer, Regis R.

    2008-01-01

    Both anxiety-related behavior [3,19] and the release of corticosterone following a psychogenic stress such as exposure to platform shaker was greater in female [3,21], but not male [22], oxytocin gene deletion (OTKO) mice compared to wild type (WT) cohorts. In the present study we exposed OTKO and WT female mice to another psychogenic stress, inserting a rectal probe to record body temperature followed by brief confinement in a metabolic cage, and measured plasma corticosterone following the ...

  3. Schistosoma mansoni polypeptides immunogenic in mice vaccinated with radiation-attenuated cercariae

    Energy Technology Data Exchange (ETDEWEB)

    Dalton, J.P.; Strand, M.

    1987-10-01

    We compared the humoral immune response of mice protected against Schistosoma mansoni by vaccination with radiation-attenuated cercariae to that of patently infected mice, and we identified antigens that elicit a greater, or unique, immune response in the vaccinated mice. These comparisons were based upon radioimmunoprecipitations and immunodepletion of (/sup 35/S)methionine-labeled schistosomular and adult worm polypeptides, followed by one- and two-dimensional polyacrylamide gel analyses. The humoral responses of patently infected mice and of mice vaccinated once were remarkably similar and were directed against schistosome glycoproteins ranging in molecular size from greater than 300 to less than 10 kDa. Exposing mice to a second vaccination resulted in a marked change in the immune response, to one predominantly directed toward high molecular size glycoproteins. Sequential immunodepletion techniques identified five schistosomular and seven adult worm antigens that showed a greater or unique immunogenicity in vaccinated mice as compared with patently infected mice. These adult worm antigens were purified by preparative sequential immunoaffinity chromatography and used to prepare a polyclonal antiserum, anti-irradiated vaccine. This antiserum bound to the surface of live newly transformed and lung-stage schistosomula, as assessed by immunofluorescence assays, and was reactive with a number of /sup 125/I-labeled schistosomular surface polypeptides, including a doublet of 150 kDa that was also recognized by sera of vaccinated mice but not by sera of patently infected mice.

  4. Phenotypic Dichotomy Following Developmental Exposure to Perfluorooctanic Acid (PFOA) Exposure in CD-1 Mice: Low Doses Induce Elevated Serum, Leptin, Insulin, and Overweight in Mid-Life.

    Science.gov (United States)

    The synthetic surfactant, perfluorooctanoic acid (PFOA) is a proven developmental toxicant in mice, causing prenatal pregnancy loss, increased neonatal mortality, delayed eye opening, and abnormal mammary gland growth in animals exposed during fetal life. PFOA is found in the ser...

  5. Effect of radiation dose on the recovery of aerobic and anaerobic bacteria from mice

    Energy Technology Data Exchange (ETDEWEB)

    Brook, I.; Walker, R.I.; MacVittie, T.J.

    1986-01-01

    The presence of aerobic and anaerobic bacteria in the blood, spleen, and liver was investigated in mice that were exposed to 7, 8, 9, or 10 Gy /sup 60/Co radiation. Microorganisms were detected more often in animals exposed to higher doses of radiation. The number of mice that were culture positive and the number of isolates in one site increased with increasing dose. Bacteria were recovered in mice killed at various times after radiation, in 3 of 100 mice exposed to 7 Gy, in 13 of 100 irradiated with 8 Gy, in 23 of 90 exposed to 9 Gy, and in 34 of 87 irradiated with 10 Gy. The predominant organisms recovered were Escherichia coli, anerobic Gram-positive cocci, Proteus mirabilis, Staphylococcus aureus, and Bacteroides spp. Escherichia coli and anaerobes were more often isolated in animals exposed to 10 Gy, while S. aureus was more often recovered in those irradiated with 9 Gy. These data demonstrate a relationship between the dose of radiation and the rate of infection due to entire aerobic and anaerobic bacteria. Reprints.

  6. Neuroglobin over expressing mice

    DEFF Research Database (Denmark)

    Raida, Zindy; Hundahl, Christian Ansgar; Nyengaard, Jens R;

    2013-01-01

    thoroughly validated antibodies and oligos, we give a detailed brain anatomical characterization of transgenic mice over expressing Neuroglobin. Moreover, using permanent middle artery occlusion the effect of elevated levels of Neuroglobin on ischemic damage was studied. Lastly, the impact of mouse strain...... genetic background on ischemic damage was investigated. PRINCIPAL FINDINGS: A four to five fold increase in Neuroglobin mRNA and protein expression was seen in the brain of transgenic mice. A β-actin promoter was used to drive Neuroglobin over expression, but immunohistochemistry and in situ hybridization...... infarct volume 24 hours after ischemia. Immunohistochemistry showed no selective sparing of Neuroglobin expressing cells in the ischemic core or penumbra. A significant difference in infarct volume was found between mice of the same strain, but from different colonies. SIGNIFICANCE: In contrast to some...

  7. Habituation and memorization of spatial objects' configurations in mice from weaning to adulthood.

    Science.gov (United States)

    Chapillon, P; Roullet, P

    1997-02-01

    This experiment investigated the development of habituation and memorization capacities of C57BL/6 mice. After a first session on a classic open field, four groups of subjects (3, 4, 5 and 9 weeks of age) were exposed to objects arranged in a pre-defined spatial environment during three exploratory sessions. Subsequently, for the test session, half of the mice was exposed to the previous situation, while the other half was exposed to a novel situation with a different spatial configuration for testing animal's abilities to detect and react to a change in their environment. Analysis showed age-related differences in behavioural habituation patterns. Moreover, contrary to our expectancy based on previous studies, the youngest mice (3 week-old) didn't exhibit significant renewal of exploration of the displaced objects during the test session. This results indicated that the youngest mice react differently than the adult mice when they are confronted to a novel environment and especially seem enable to construct a long-lasting representation of their environment when this representation concerns proximal information. The results are discussed in relation to previous studies conducted on the radial maze and the Morris water maze and it seems that the abilities of the youngest mice to construct a representation of their environment are partially dependent upon the type of information available (i.e. proximal versus distal information).

  8. Inhalation developmental toxicology studies: Gallium arsenide in mice and rats

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.; Greenspan, B.J.; Dill, J.A.; Stoney, K.H.; Evanoff, J.J.; Rommereim, R.L.

    1990-12-01

    Gallium arsenide is a crystalline compound used extensively in the semiconductor industry. Workers preparing solar cells and gallium arsenide ingots and wafers are potentially at risk from the inhalation of gallium arsenide dust. The potential for gallium arsenide to cause developmental toxicity was assessed in Sprague- Dawley rats and CD-1 (Swiss) mice exposed to 0, 10, 37, or 75 mg/m{sup 3} gallium arsenide, 6 h/day, 7 days/week. Each of the four treatment groups consisted of 10 virgin females (for comparison), and {approx}30 positively mated rats or {approx}24 positively mated mice. Mice were exposed on 4--17 days of gestation (dg), and rats on 4--19 dg. The day of plug or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. Gallium and arsenic concentrations were determined in the maternal blood and uterine contents of the rats (3/group) at 7, 14, and 20 dg. 37 refs., 11 figs., 30 tabs.

  9. Radioprotectors and Tumors: Molecular Studies in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Gayle Woloschak, David Grdina

    2010-03-10

    This proposal investigated effects of radiation using a set of archival tissues. Main interests of this proposal were to investigate effects of irradiation alone or in the presence or radioprotectors; to investigate these effects on different tissues; and to use/develop molecular biology techniques that would be suitable for work with archived tissues. This work resulted in several manuscripts published or in preparation. Approach for evaluation of gene copy numbers by quantitative real time PCR has been developed and we are striving to establish methods to utilize Q-RT-PCR data to evaluate genomic instability caused by irradiation(s) and accompanying treatments. References: 1. Paunesku D, Paunesku T, Wahl A, Kataoka Y, Murley J, Grdina DJ, Woloschak GE. Incidence of tissue toxicities in gamma ray and fission neutron-exposed mice treated with Amifostine. Int J Radiat Biol. 2008, 84(8):623-34. PMID: 18661379, http://informahealthcare.com/doi/full/10.1080/09553000802241762?cookieSet=1 2. Wang Q, Paunesku T and Woloschak GE. Tissue and data archives from irradiation experiments conducted at Argonne National Laboratory over a period of four decades, in press in Radiation and Environmental Biophysics. 3. Alcantara M, Paunesku D, Rademaker A, Paunesku T and Woloschak GE. A RETROSPECTIVE ANALYSIS OF TISSUE TOXICITIES IN B6CF1 MICE IRRADIATED WITH FISSION NEUTRONS OR COBALT 60 GAMMA RAYS: Gender modulates accumulation of tissue toxicities caused by low dose rate fractionated irradiation; in preparation; this document has been uploaded as STI product 4. Wang Q, Paunesku T Wanzer B and Woloschak GE. Mitochondrial gene copy number differences in different tissues of irradiated and control mice with lymphoid cancers; in preparation 5. Wang Q, Raha, S, Paunesku T and Woloschak GE. Evaluation of gene copy number differences in different tissues of irradiated and control mice; in preparation

  10. II Infused Mice

    Directory of Open Access Journals (Sweden)

    Justin L. Wilson

    2012-01-01

    Full Text Available The anti-inflammatory properties of PPAR-α plays an important role in attenuating hypertension. The current study determines the anti-hypertensive and anti-inflammatory role of PPAR-α agonist during a slow-pressor dose of Ang II (400 ng/kg/min. Ten to twelve week old male PPAR-α KO mice and their WT controls were implanted with telemetry devices and infused with Ang II for 12 days. On day 12 of Ang II infusion, MAP was elevated in PPAR-α KO mice compared to WT (161±4 mmHg versus 145±4 mmHg and fenofibrate (145 mg/kg/day reduced MAP in WT + Ang II mice (134±7 mmHg. Plasma IL-6 levels were higher in PPAR-α KO mice on day 12 of Ang II infusion (30±4 versus 8±2 pg/mL and fenofibrate reduced plasma IL-6 in Ang II-treated WT mice (10±3 pg/mL. Fenofibrate increased renal expression of CYP4A, restored renal CYP2J expression, reduced the elevation in renal ICAM-1, MCP-1 and COX-2 in WT + Ang II mice. Our results demonstrate that activation of PPAR-α attenuates Ang II-induced hypertension through up-regulation of CYP4A and CYP2J and an attenuation of inflammatory markers such as plasma IL-6, renal MCP-1, renal expression of ICAM-1 and COX-2.

  11. Influenza virus-induced lung inflammation was modulated by cigarette smoke exposure in mice.

    Directory of Open Access Journals (Sweden)

    Yan Han

    Full Text Available Although smokers have increased susceptibility and severity of seasonal influenza virus infection, there is no report about the risk of 2009 pandemic H1N1 (pdmH1N1 or avian H9N2 (H9N2/G1 virus infection in smokers. In our study, we used mouse model to investigate the effect of cigarette smoke on pdmH1N1 or H9N2 virus infection. Mice were exposed to cigarette smoke for 21 days and then infected with pdmH1N1 or H9N2 virus. Control mice were exposed to air in parallel. We found that cigarette smoke exposure alone significantly upregulated the lung inflammation. Such prior cigarette smoke exposure significantly reduced the disease severity of subsequent pdmH1N1 or H9N2 virus infection. For pdmH1N1 infection, cigarette smoke exposed mice had significantly lower mortality than the control mice, possibly due to the significantly decreased production of inflammatory cytokines and chemokines. Similarly, after H9N2 infection, cigarette smoke exposed mice displayed significantly less weight loss, which might be attributed to lower cytokines and chemokines production, less macrophages, neutrophils, CD4+ and CD8+ T cells infiltration and reduced lung damage compared to the control mice. To further investigate the underlying mechanism, we used nicotine to mimic the effect of cigarette smoke both in vitro and in vivo. Pre-treating the primary human macrophages with nicotine for 72 h significantly decreased their expression of cytokines and chemokines after pdmH1N1 or H9N2 infection. The mice subcutaneously and continuously treated with nicotine displayed significantly less weight loss and lower inflammatory response than the control mice upon pdmH1N1 or H9N2 infection. Moreover, α7 nicotinic acetylcholine receptor knockout mice had more body weight loss than wild-type mice after cigarette smoke exposure and H9N2 infection. Our study provided the first evidence that the pathogenicity of both pdmH1N1 and H9N2 viruses was alleviated in cigarette smoke exposed

  12. Immunity to babesia in mice III. The effects of corticosteroids and anti-thymocyte serum on mice immune to babesia rodhaini

    NARCIS (Netherlands)

    Zivkovic, D.; Speksnijder, J.E.; Kuil, H.; Seinen, W.

    1985-01-01

    BALB/c mice, immunized against babesia rodhaini by an amicarbalide controlled infection, were exposed to selective immunosuppressive treatment with corticosteroids and anti-thymocyte serum (ATS) respectively. Hydrocortisone acetate, 100 mg/kg, given i.p. six times during the three weeks after challe

  13. Experimental infection of Balb/c nude mice with Hepatitis E virus

    Directory of Open Access Journals (Sweden)

    Zhu Jianguo

    2009-06-01

    Full Text Available Abstract Background Several animal species can reportedly act as reservoirs for Hepatitis E virus (HEV, a zoonotic pathogen. HEV and antibody to the virus have been detected in a variety of animals including rodents. Pig and rat models for HEV have been established for HEV, but a nude mouse has not yet been developed. Methods Balb/c nude mice were inoculated with swine HEV, both orally and via intravenous injection to insure infection. Negative control and experimental contact-exposed groups of mice were also included in the study. The liver, spleen, kidney, jejunum, ileum, cecum and colon of each mouse from all three groups were collected for reverse transcription nested polymerase chain reaction (RT-nPCR detection, indirect immunofluorescence observation and histopathologic examination. The sera from nude mice were tested for anti-HEV IgG by enzyme linked immunosorbent assay (ELISA. Activities of liver enzymes, including alanine aminotransferase (ALT, aspartate aminotransferase (AST and alkaline phosphatase (ALP, as well as total bilirubin (TBIL were also measured in the sera of the nude mice. Results HEV antigens and HEV RNA were detected in liver, spleen, kidney, jejunum, ileum and colon both by indirect immunofluorescence and by RT-nPCR in all of the inoculated and in one of the contact-exposed nude mice. Histopathological changes were observed in the liver and spleen of these mice. Infected mice showed increased levels of AST, ALP, and anti-HEV IgG in sera. The livers of contact-exposed mice showed obvious histopathological damage. Conclusion Nude mice could be readily infected by HEV isolated from pigs. The nude mouse may therefore be a useful animal model for studying the pathogenesis of HEV.

  14. Fibrosis biomarkers in workers exposed to MWCNTs.

    Science.gov (United States)

    Fatkhutdinova, Liliya M; Khaliullin, Timur O; Vasil'yeva, Olga L; Zalyalov, Ramil R; Mustafin, Ilshat G; Kisin, Elena R; Birch, M Eileen; Yanamala, Naveena; Shvedova, Anna A

    2016-05-15

    Multi-walled carbon nanotubes (MWCNT) with their unique physico-chemical properties offer numerous technological advantages and are projected to drive the next generation of manufacturing growth. As MWCNT have already found utility in different industries including construction, engineering, energy production, space exploration and biomedicine, large quantities of MWCNT may reach the environment and inadvertently lead to human exposure. This necessitates the urgent assessment of their potential health effects in humans. The current study was carried out at NanotechCenter Ltd. Enterprise (Tambov, Russia) where large-scale manufacturing of MWCNT along with relatively high occupational exposure levels was reported. The goal of this small cross-sectional study was to evaluate potential biomarkers during occupational exposure to MWCNT. All air samples were collected at the workplaces from both specific areas and personal breathing zones using filter-based devices to quantitate elemental carbon and perform particle analysis by TEM. Biological fluids of nasal lavage, induced sputum and blood serum were obtained from MWCNT-exposed and non-exposed workers for assessment of inflammatory and fibrotic markers. It was found that exposure to MWCNTs caused significant increase in IL-1β, IL6, TNF-α, inflammatory cytokines and KL-6, a serological biomarker for interstitial lung disease in collected sputum samples. Moreover, the level of TGF-β1 was increased in serum obtained from young exposed workers. Overall, the results from this study revealed accumulation of inflammatory and fibrotic biomarkers in biofluids of workers manufacturing MWCNTs. Therefore, the biomarkers analyzed should be considered for the assessment of health effects of occupational exposure to MWCNT in cross-sectional epidemiological studies. PMID:26902652

  15. After a cold conditioning swim, UCP2-deficient mice are more able to defend against the cold than wild type mice.

    Science.gov (United States)

    Abdelhamid, Ramy E; Kovács, Katalin J; Nunez, Myra G; Larson, Alice A

    2014-08-01

    Uncoupling protein 2 (UCP2) is widely distributed throughout the body including the brain, adipose tissue and skeletal muscles. In contrast to UCP1, UCP2 does not influence resting body temperature and UCP2-deficient (-/-) mice have normal thermoregulatory responses to a single exposure to cold ambient temperatures. Instead, UCP2-deficient mice are more anxious, exhibit anhedonia and have higher circulating corticosterone than wild type mice. To test the possible role of UCP2 in depressive behavior we exposed UCP2-deficient and wild type mice to a cold (26°C) forced swim and simultaneously measured rectal temperatures during and after the swim. The time that UCP2-deficient mice spent immobile did not differ from wild type mice and all mice floated more on day 2. However, UCP2-deficient mice were more able to defend against the decrease in body temperature during a second daily swim at 26°C than wild type mice (area under the curve for wild type mice: 247.0±6.4; for UCP2-deficient mice: 284.4±3.8, Pswim at 26°C correlated with their greater immobility whereas defense against the warmth during a swim at 41°C correlated better with greater immobility of UCP2-deficient mice. Together these data indicate that while the lack of UCP2 has no acute effect on body temperature, UCP2 may inhibit rapid improvements in defense against cold, in contrast to UCP1, whose main function is to promote thermogenesis.

  16. Backfilling of trenches exposed to waves

    DEFF Research Database (Denmark)

    Hjelmager Jensen, Jacob; Fredsøe, Jørgen

    1997-01-01

    -closure. The backfilling process of trenches exposed to either waves or a steady current is of importance in relation to the implementation of pipelines in the marine environment. With respect to the sedimentation of trenches, the non-dimensional Trench-Keulegan-Carpenter number, KC = a/L, where a is the excursion length...... of a particle in waves and L the trench length, is investigated in detail, and an optimal KC-number for the backfilling rate is found. Coherent structures in the non-uniform unsteady trench-flow are shown to dominate the deposition rate when present. The importance of a detailed description of the flow...

  17. Influence of prolonged dietary consumption of zeolites on a survival rate and intestine response in mice different age after irradiation

    International Nuclear Information System (INIS)

    Effect of long-term dietary consumption of zeolites on the structural-functional status of adherent mucous layers of digestive tract in mice of different age is studied as well as zeolites effect on the survival and mean life span in irradiation mice. Mice were exposed to whole-body acute irradiation at 4 Gy dose. RUM-17 X-ray apparatus was used for exposure. It is shown that the zeolites increase the survival and mean life span in mice following irradiation. Shivirtuin caused more expressed effect than that of pegasin

  18. Social stress induces changes in urinary bladder function, bladder NGF content, and generalized bladder inflammation in mice

    OpenAIRE

    Mingin, Gerald C.; Peterson, Abbey; Erickson, Cuixia Shi; Nelson, Mark T.; Vizzard, Margaret A.

    2014-01-01

    Social stress may play a role in urinary bladder dysfunction in humans, but the underlying mechanisms are unknown. In the present study, we explored changes in bladder function caused by social stress using mouse models of stress and increasing stress. In the stress paradigm, individual submissive FVB mice were exposed to C57BL/6 aggressor mice directly/indirectly for 1 h/day for 2 or 4 wk. Increased stress was induced by continuous, direct/indirect exposure of FVB mice to aggressor mice for ...

  19. The PUR Experiment on the EXPOSE-R facility: biological dosimetry of solar extraterrestrial UV radiation

    Science.gov (United States)

    Bérces, A.; Egyeki, M.; Fekete, A.; Horneck, G.; Kovács, G.; Panitz, C.

    2015-01-01

    The aim of our experiment Phage and Uracil Response was to extend the use of bacteriophage T7 and uracil biological dosimeters for measuring the biologically effective ultraviolet (UV) dose in the harsh extraterrestrial radiation conditions. The biological detectors were exposed in vacuum-tightly cases in the European Space Agency (ESA) astrobiological exposure facility attached to the external platform of Zvezda (EXPOSE-R). EXPOSE-R took off to the International Space Station (ISS) in November 2008 and was installed on the External platform of the Russian module Zvezda of the ISS in March 2009. Our goal was to determine the dose-effect relation for the formation of photoproducts (i.e. damage to phage DNA and uracil, respectively). The extraterrestrial solar UV radiation ranges over the whole spectrum from vacuum-UV (λcomponents either by photoionization or excitation. However, these wavelengths cause not only photolesions but in a wavelength-dependent efficiency the reversion of some photolesions, too. Our biological detectors measured in situ conditions the resultant of both reactions induced by the extraterrestrial UV radiation. From this aspect the role of the photoreversion in the extension of the biological UV dosimetry are discussed.

  20. Identification of novel surface-exposed proteins of Rickettsia rickettsii by affinity purification and proteomics.

    Directory of Open Access Journals (Sweden)

    Wenping Gong

    Full Text Available Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever, is the most pathogenic member among Rickettsia spp. Surface-exposed proteins (SEPs of R. rickettsii may play important roles in its pathogenesis or immunity. In this study, R. rickettsii organisms were surface-labeled with sulfo-NHS-SS-biotin and the labeled proteins were affinity-purified with streptavidin. The isolated proteins were separated by two-dimensional electrophoresis, and 10 proteins were identified among 23 protein spots by electrospray ionization tandem mass spectrometry. Five (OmpA, OmpB, GroEL, GroES, and a DNA-binding protein of the 10 proteins were previously characterized as surface proteins of R. rickettsii. Another 5 proteins (Adr1, Adr2, OmpW, Porin_4, and TolC were first recognized as SEPs of R. rickettsii herein. The genes encoding the 5 novel SEPs were expressed in Escherichia coli cells, resulting in 5 recombinant SEPs (rSEPs, which were used to immunize mice. After challenge with viable R. rickettsii cells, the rickettsial load in the spleen, liver, or lung of mice immunized with rAdr2 and in the lungs of mice immunized with other rSEPs excluding rTolC was significantly lower than in mice that were mock-immunized with PBS. The in vitro neutralization test revealed that sera from mice immunized with rAdr1, rAdr2, or rOmpW reduced R. rickettsii adherence to and invasion of vascular endothelial cells. The immuno-electron microscopic assay clearly showed that the novel SEPs were located in the outer and/or inner membrane of R. rickettsii. Altogether, the 5 novel SEPs identified herein might be involved in the interaction of R. rickettsii with vascular endothelial cells, and all of them except TolC were protective antigens.

  1. Zirconium ignition in exposed fuel channel

    Energy Technology Data Exchange (ETDEWEB)

    Elias, E., E-mail: merezra@technion.ac.il; Hasan, D.; Nekhamkin, Y.

    2015-05-15

    Highlights: • We demonstrate the idea of runaway zirconium–steam reactions in severe accidents in today's LWRs. • We predict the thermal-hydraulics conditions relevant to cladding oxidation in an exposed fuel channel of a partially uncovered core. • The Semenov theory of metal combustion is extended to define a criterion for runaway oxidation reaction in fuel cladding. - Abstract: A theoretical model based on simultaneous solution of the heat and mass transfer equations is developed for predicting the rate of thermo-chemical reaction between zirconium cladding and a hot steam environment. Ignition conditions relevant to cladding oxidation in an exposed fuel channel of a partially uncovered core are predicted based on the theory of metal combustion. A range of decay power, convective heat transfer coefficients, and initial temperatures leading to uncontrolled runaway cladding oxidation is identified. The model could be readily integrated as part of a fuel channel analysis code for predicting possible outcomes of different accident mitigation procedures in light water nuclear reactors under LOCA conditions.

  2. Occupational health care of radiation exposed workers

    International Nuclear Information System (INIS)

    The medical problems encountered by the earlier pioneer workers in radiation at the turn of the century are well known. In the 1928, the ICRP (International Committee for Radiological Protection) was instituted and the ALARA principle of radiation protection was evolved. Occupational health care is about maintaining the health and safety of workers in their workplaces. This involves using medical, nursing and engineering practices to achieve its objectives. In certain occupations, including those where workers are exposed to ionising radiation, some of these principles are enshrined in the legislation and would require statutory compliance. Occupational health care of radiation workers seek to prevent ill health arising from exposure to radiation by consolidating the benefits of exposures control and dosimetry. This is via health surveillance for spillages, contamination and exposures to unsealed sources of radiation. It is unlikely that can plan and hope to cater for a Chernobyl type of disaster. However, for the multitude of workers in industry exposed to radiation, control models are available. These are from the more in industrialize countries with a nuclear based energy industry, and where radioactive gadgetry are used in places ranging from factories and farms to construction sites. These models involve statutory requirements on the standard of work practices, assessment of fitness to work and the monitoring of both the worker and the workplace. A similar framework of activity is present in Malaysia. This will be further enhanced with the development of her general health and safety at work legislation. (author)

  3. Male mice deficient in microsomal epoxide hydrolase are not susceptible to benzene-induced toxicity.

    Science.gov (United States)

    Bauer, Alison K; Faiola, Brenda; Abernethy, Diane J; Marchan, Rosemarie; Pluta, Linda J; Wong, Victoria A; Gonzalez, Frank J; Butterworth, Byron E; Borghoff, Susan J; Everitt, Jeffrey I; Recio, Leslie

    2003-04-01

    Enzymes involved in benzene metabolism are likely genetic determinants of benzene-induced toxicity. Polymorphisms in human microsomal epoxide hydrolase (mEH) are associated with an increased risk of developing leukemia, specifically those associated with benzene. This study was designed to investigate the importance of mEH in benzene-induced toxicity. Male and female mEH-deficient (mEH-/-) mice and background mice (129/Sv) were exposed to inhaled benzene (0, 10, 50, or 100 ppm) 5 days/week, 6 h/day, for a two-week duration. Total white blood cell counts and bone marrow cell counts were used to assess hematotoxicity and myelotoxicity. Micronucleated peripheral blood cells were counted to assess genotoxicity, and the p21 mRNA level in bone marrow cells was used as a determinant of the p53-regulated DNA damage response. Male mEH-/- mice did not have any significant hematotoxicity or myelotoxicity at the highest benzene exposure compared to the male 129/Sv mice. Significant hematotoxicity or myelotoxicity did not occur in the female mEH-/- or 129/Sv mice. Male mEH-/- mice were also unresponsive to benzene-induced genotoxicity compared to a significant induction in the male 129/Sv mice. The female mEH-/- and 129/Sv mice were virtually unresponsive to benzene-induced genotoxicity. While p21 mRNA expression was highly induced in male 129/Sv mice after exposure to 100-ppm benzene, no significant alteration was observed in male mEH-/- mice. Likewise, p21 mRNA expression in female mEH-/- mice was not significantly induced upon benzene exposure whereas a significant induction was observed in female 129/Sv mice. Thus mEH appears to be critical in benzene-induced toxicity in male, but not female, mice.

  4. Emphysema is associated with increased inflammation in lungs of atherosclerosis-prone mice by cigarette smoke: implications in comorbidities of COPD

    Directory of Open Access Journals (Sweden)

    Yao Hongwei

    2010-07-01

    Full Text Available Abstract Background Chronic obstructive pulmonary disease is associated with numerous vascular effects including endothelial dysfunction, arterial stiffness and atherogenesis. It is also known that a decline in lung function is associated with increased cardiovascular comorbidity in smokers. The mechanism of this cardiopulmonary dual risk by cigarette smoke (CS is not known. We studied the molecular mechanisms involved in development of emphysema in atherosclerosis-prone apolipoprotein E-deficient (ApoE-/- mice in response to CS exposure. Methods Adult male and female wild-type (WT mice of genetic background C57BL/6J and ApoE-/- mice were exposed to CS, and lung inflammatory responses, oxidative stress (lipid peroxidation products, mechanical properties as well as airspace enlargement were assessed. Results and Discussion The lungs of ApoE-/- mice showed augmented inflammatory response and increased oxidative stress with development of distal airspace enlargement which was accompanied with decline in lung function. Interestingly, the levels and activities of matrix metalloproteinases (MMP-9 and MMP-12 were increased, whereas the level of eNOS was decreased in lungs of CS-exposed ApoE-/- mice as compared to air-exposed ApoE-/- mice or CS-exposed WT mice. Conclusion These findings suggest that CS causes premature emphysema and a decline of lung function in mice susceptible to cardiovascular abnormalities via abnormal lung inflammation, increased oxidative stress and alterations in levels of MMPs and eNOS.

  5. Inhibition of pan neurotrophin receptor p75 attenuates diesel particulate-induced enhancement of allergic airway responses in C57/B16J mice.

    Science.gov (United States)

    Farraj, Aimen K; Haykal-Coates, Najwa; Ledbetter, Allen D; Evansky, Paul A; Gavett, Stephen H

    2006-06-01

    Recent investigations have linked neurotrophins, including nerve growth factor (NGF), neurotrophin-3 (NT-3), and brain-derived neurotrophic factor (BDNF), to allergic airways diseases. Antibody blockade of NGF attenuates airway resistance in allergic mice. Diesel exhaust particle (DEP) exposure has been linked to asthma exacerbation in many cities with vehicular traffic congestion. We tested the hypothesis that DEP-induced enhancement of the hallmark features of allergic airway disease in a murine model is dependent on the function of the pan neurotrophin receptor p75. Ovalbumin (OVA)-sensitized C57B1/6J mice were intranasally instilled with an antibody against the p75 receptor or saline alone 1 h before OVA challenge. The mice were then exposed nose-only to the PM2.5 fraction of SRM2975 DEP or air alone for 5 h beginning 1 h after OVA challenge. Two days later, air-exposed OVA-allergic mice developed a small but insignificant increase in methacholine-induced airflow obstruction relative to air-exposed, vehicle-sensitized mice. DEP-exposed OVA-allergic mice had a significantly greater degree of airway obstruction than all other groups. Instillation of anti-p75 significantly attenuated the DEP-induced increase in airway obstruction in OVA-allergic mice to levels similar to non-sensitized mice. The DEP-induced exacerbation of allergic airway responses may, in part, be mediated by neurotrophins.

  6. Reproductive Toxicity to Male Mice of Nose Only Exposure to Water- Pipe Smoke

    Directory of Open Access Journals (Sweden)

    Badreldin H. Ali

    2015-01-01

    Full Text Available Background/Aims: Water-pipe smoking (WPS is popular in the Middle East and is starting to gain popularity in several Western countries as well. It is widely and erroneously perceived to be less harmful than other forms of tobacco use. The reproductive adverse effects of cigarette smoking have been studied before with conflicting results, but data on the possible adverse reproductive effects of WPS are lacking. Here, we assessed the effects of nose-only exposure to mainstream WPS generated by commercially available honey-flavored "moasel" tobacco in mice. Methods: The duration of the session was 30 min/day for one month. Control mice were exposed to air. Twenty- four h after the last exposure, mice were killed and the testes and plasma removed for analysis. In testicular homogenates total protein, alkaline phosphatase activity, several indices of oxidative damage and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2 were quantified. The plasma concentrations of leptin, testosterone, estrogen and luteinizing hormone (LH were also measured. Histological analysis of testes and lungs was also conducted. Results: WPS caused statistically significant decreases in the plasma concentrations of leptin, testosterone, and LH, and in the concentrations of total protein and the antioxidant indices measured. A statistically non - significant decrease in VEGFR2 protein in the WPS - exposed mice compared to the control mice was also found. The body and testicular weights of mice exposed to WPS, as well as their testicular alkaline phosphatase activity and light microscopic histology, and plasma estrogen concentration were all not significantly affected by WPS. Conclusion: Further studies on the functional implications of these findings in mice exposed to WPS for longer durations are warranted.

  7. Reduction of benzene metabolism and toxicity in mice that lack CYP2E1 expression.

    Science.gov (United States)

    Valentine, J L; Lee, S S; Seaton, M J; Asgharian, B; Farris, G; Corton, J C; Gonzalez, F J; Medinsky, M A

    1996-11-01

    Transgenic CYP2E1 knockout mice (cyp2e1-/-) were used to investigate the involvement of CYP2E1 in the in vivo metabolism of benzene and in the development of benzene-induced toxicity. After benzene exposure, absence of CYP2E1 protein was confirmed by Western blot analysis of mouse liver samples. For the metabolism studies, male cyp2e1-/- and wild-type control mice were exposed to 200 ppm benzene, along with a radiolabeled tracer dose of [14C]benzene (1.0 Ci/mol) by nose-only inhalation for 6 hr. Total urinary radioactivity and all radiolabeled individual metabolites were reduced in urine of cyp2e1-/- mice compared to wild-type controls during the 48-hr period after benzene exposure. In addition, a significantly greater percentage of total urinary radioactivity could be accounted for as phenylsulfate conjugates in cyp2e1-/- mice compared to wild-type mice, indicating the importance of CYP2E1 in oxidation of phenol following benzene exposure in normal mice. For the toxicity studies, male cyp2e1-/-, wild-type, and B6C3F1 mice were exposed by whole-body inhalation to 0 ppm (control) or 200 ppm benzene, 6 hr/day for 5 days. On Day 5, blood, bone marrow, thymus, and spleen were removed for evaluation of micronuclei frequencies and tissue cellularities. No benzene-induced cytotoxicity or genotoxicity was observed in cyp2e1-/- mice. In contrast, benzene exposure resulted in severe genotoxicity and cytotoxicity in both wild-type and B6C3F1 mice. These studies conclusively demonstrate that CYP2E1 is the major determinant of in vivo benzene metabolism and benzene-induced myelotoxicity in mice.

  8. Effect of Cell Phone Radiation (940 MHz on the Learning and Memory of Balb/c mice

    Directory of Open Access Journals (Sweden)

    J Baharara

    2009-07-01

    After behavioral studies, fetal heads were collected, fixed in 10% paraformaldehyde and paraffine embedded. Results: Microwave-exposed mice were slower than sham-exposed, and cage control in swim speed (WM. Error Analyses rates reveal significant exposure effect in RAM and MWM. However, in this study the exposed group had not significantly lost their hippocampal CA3 neurons comparing to controls or sham exposed group. Conclusion: Increased time to locate a submerged in water maze, reference memory (entries into unbaited arms, working memory (repeated entries into baited arms, show that acute exposure to pulsed microwaves caused a deficit in spatial reference memory in the mouse. Keywords: Mobile phone, learning, memory, hippocampus

  9. Morbidity in newborns exposed to organophosphorus pesticides

    Directory of Open Access Journals (Sweden)

    Đorđević Momčilo

    2010-01-01

    Full Text Available Introduction. Insecticides are toxines by which we destroy harmful insects. The most frequent insecticides which are used today are organophosphorus pesticides. This group of compounds make substances whose activity mechanism is based on the inhibition of acetylcho­linesterase in nerve synapsis, thus producing holynergic syndrome, resulting from the accumulation of acetylcholine which developed due to the absence of decomposition under the influence of cholinesterase. In the clinical picture of acute toxication by cholinesterase inhibitors there is a clear difference between muscarinic and nicotine effects. The basic aim of the study was to establish the effects of organophosphorus pesticides present in blood and breast milk of mothers on newborns morbidity. Material and methods. The study group consisted of 18 newborns whose mothers had isolated organophosphorus pesticides in their blood and breast­milk on the third day after delivery, and the control group consisted of 84 newborns whose mothers did not have isolated organophosphorus pesticides in their blood and breastmilk. Results. Morbidity is three times greater, often in combination with some disorders of the central nervous system, and the relative risk for its appearance is eight time greater in newborns exposed to organophosphorus pesticides. Disscusion. Disorders that appear in newborns exposed to pesticides are mutagenic, cancerogenic and neurotoxic and some agenses could disturb the immune system which is reflected in morbidity increase, primarly of the central nervous system. Conclusion. The presence of organophosphorus pesticides in blood and breast milk has negative effects on newborns. In addition to acetylcho­linesterase inhibition, organophosphorus pesticides react by means of other mechanisms as well.

  10. Self-reported hearing performance in workers exposed to solvents

    OpenAIRE

    Adrian Fuente; Bradley McPhersonY; Ximena Hormazabal

    2013-01-01

    OBJECTIVE: To compare hearing performance relating to the peripheral and central auditory system between solvent-exposed and non-exposed workers. METHODS: Forty-eight workers exposed to a mixture of solvents and 48 non-exposed control subjects of matched age, gender and educational level were selected to participate in the study. The evaluation procedures included: pure-tone audiometry (500 - 8,000 Hz), to investigate the peripheral auditory system; the Random Gap Detection test, to assess th...

  11. Mice Drawer System

    Science.gov (United States)

    Cancedda, Ranieri

    2008-01-01

    The Mice Drawer System (MDS) is an Italian Space Agency (ASI) facility which is able to support mice onboard the International Space Station during long-duration exploration missions (from 100 to 150-days) by living space, food, water, ventilation and lighting. Mice can be accommodated either individually (maximum 6) or in groups (4 pairs). MDS is integrated in the Space Shuttle middeck during transportation (uploading and downloading) to the ISS and in an EXPRESS Rack in Destiny, the US Laboratory during experiment execution. Osteoporosis is a debilitating disease that afflicts millions of people worldwide. One of the physiological changes experienced by astronauts during space flight is the accelerated loss of bone mass due to the lack of gravitational loading on the skeleton. This bone loss experienced by astronauts is similar to osteoporosis in the elderly population. MDS will help investigate the effects of unloading on transgenic (foreign gene that has been inserted into its genome to exhibit a particular trait) mice with the Osteoblast Stimulating Factor-1, OSF-1, a growth and differentiation factor, and to study the genetic mechanisms underlying the bone mass pathophysiology. MDS will test the hypothesis that mice with an increased bone density are likely to be more protected from osteoporosis, when the increased bone mass is a direct effect of a gene involved in skeletogenesis (skeleton formation). Osteoporosis is a debilitating disease that afflicts millions worldwide. One of the physiological changes experienced by astronauts during space flight is the accelerated loss of bone mass due to the lack of gravitational loading on the skeleton, a loss that is similar to osteoporosis in the elderly population on Earth. Osteoblast Stimulating Factor-1 (OSF-1), also known as pleiotrophin (PTN) or Heparin-Binding Growth- Associated Molecule (HB-GAM) belongs to a family of secreted heparin binding proteins..OSF-1 is an extracellular matrix-associated growth and

  12. Pneumocystis murina colonization in immunocompetent surfactant protein A deficient mice following environmental exposure

    Directory of Open Access Journals (Sweden)

    Ashbaugh Alan D

    2009-02-01

    Full Text Available Abstract Background Pneumocystis spp. are opportunistic pathogens that cause pneumonia in immunocompromised humans and animals. Pneumocystis colonization has also been detected in immunocompetent hosts and may exacerbate other pulmonary diseases. Surfactant protein A (SP-A is an innate host defense molecule and plays a role in the host response to Pneumocystis. Methods To analyze the role of SP-A in protecting the immunocompetent host from Pneumocystis colonization, the susceptibility of immunocompetent mice deficient in SP-A (KO and wild-type (WT mice to P. murina colonization was analyzed by reverse-transcriptase quantitative PCR (qPCR and serum antibodies were measured by enzyme-linked immunosorbent assay (ELISA. Results Detection of P. murina specific serum antibodies in immunocompetent WT and KO mice indicated that the both strains of mice had been exposed to P. murina within the animal facility. However, P. murina mRNA was only detected by qPCR in the lungs of the KO mice. The incidence and level of the mRNA expression peaked at 8–10 weeks and declined to undetectable levels by 16–18 weeks. When the mice were immunosuppressed, P. murina cyst forms were also only detected in KO mice. P. murina mRNA was detected in SCID mice that had been exposed to KO mice, demonstrating that the immunocompetent KO mice are capable of transmitting the infection to immunodeficient mice. The pulmonary cellular response appeared to be responsible for the clearance of the colonization. More CD4+ and CD8+ T-cells were recovered from the lungs of immunocompetent KO mice than from WT mice, and the colonization in KO mice depleted CD4+ cells was not cleared. Conclusion These data support an important role for SP-A in protecting the immunocompetent host from P. murina colonization, and provide a model to study Pneumocystis colonization acquired via environmental exposure in humans. The results also illustrate the difficulties in keeping mice from exposure to P

  13. Immune response to a potyvirus with exposed amino groups available for chemical conjugation

    Directory of Open Access Journals (Sweden)

    Manuel-Cabrera Carlos

    2012-03-01

    Full Text Available Abstract Background The amino terminus of the tobacco etch virus (TEV capsid protein is located on the external surface of infectious TEV particles, as proposed by previous studies and an in silico model. The epsilon amino groups on the exposed lysine residues are available for chemical conjugation to any given protein, and can thus act as antigen carriers. The availability of amino groups on the surfaces of TEV particles was determined and the immune response to TEV evaluated. Results Using a biotin-tagged molecule that reacts specifically with amino groups, we found that the TEV capsid protein has amino groups on its surface available for coupling to other molecules via crosslinkers. Intraperitoneal TEV was administered to female BALB/c mice, and both their humoral and cellular responses measured. Different IgG isotypes, particularly IgG2a, directed against TEV were induced. In a cell proliferation assay, only spleen cells from vaccinated mice that were stimulated in vitro with TEV showed significant proliferation of CD3+/CD4+ and CD3+/CD8+ subpopulations and secreted significant amounts of interferon γ. Conclusions TEV has surface amino groups that are available for chemical coupling. TEV induces both humoral and cellular responses when administered alone intraperitoneally to mice. Therefore, TEV should be evaluated as a vaccine adjuvant when chemically coupled to antigens of choice.

  14. Partial Return Yoke for MICE

    Energy Technology Data Exchange (ETDEWEB)

    Witte H.; Plate, S

    2013-05-03

    The international Muon Ionization Cooling Experiment (MICE) is a large scale experiment which is presently assembled at the Rutherford Appleton Laboratory in Didcot, UK. The purpose of MICE is to demonstrate the concept of ionization cooling experimentally. Ionization cooling is an important accelerator concept which will be essential for future HEP experiments such as a potential Muon Collider or a Neutrino Factory. The MICE experiment will house up to 18 superconducting solenoids, all of which produce a substantial amount of magnetic flux. Recently it was realized that this magnetic flux leads to a considerable stray magnetic field in the MICE hall. This is a concern as technical equipment in the MICE hall may may be compromised by this. In July 2012 a concept called partial return yoke was presented to the MICE community, which reduces the stray field in the MICE hall to a safe level. This report summarizes the general concept, engineering considerations and the expected shielding performance.

  15. Erionite induces production of autoantibodies and IL-17 in C57BL/6 mice

    Energy Technology Data Exchange (ETDEWEB)

    Zebedeo, Christian Nash; Davis, Chad [Department of Biological Sciences, Idaho State University, Pocatello, ID (United States); Peña, Cecelia [Northwest Nazarene University, Nampa, ID (United States); Ng, Kok Wei [Department of Biological Sciences, Idaho State University, Pocatello, ID (United States); Pfau, Jean C., E-mail: pfaujean@isu.edu [Department of Biological Sciences, Idaho State University, Pocatello, ID (United States)

    2014-03-15

    Background: Erionite has similar chemical and physical properties to amphibole asbestos, which induces autoantibodies in mice. Current exposures are occurring in North Dakota due to the use of erionite-contaminated gravel. While erionite is known to cause mesothelioma and other diseases associated with asbestos, there is little known about its effects on the immune system. Objectives: We performed this study to determine whether erionite evokes autoimmune reactions in mice. Methods: Bone marrow derived macrophages (BMDM) were used to measure toxicity induced by erionite. Cytokine production by BMDM and splenocytes of C57BL/6 mice was examined by bead arrays and ELISA following exposure to erionite, amphiboles and chrysotile. Wild type C57BL/6 mice were exposed to saline, erionite, amphibole asbestos (Libby 6-Mix) or chrysotile through intratracheal instillations at equal mass (60 μg/mouse). Seven months after exposure, sera were examined for anti-nuclear antibodies (ANA) and IL-17. Immunohistochemistry was used to detect immune complex deposition in the kidneys. Results: Erionite and tremolite caused increased cytokine production belonging to the T{sub H}17 profile including IL-17, IL-6, TGF-β, and TNF-α. The frequency of ANA was increased in mice treated with erionite or amphibole compared to saline-treated mice. IL-17 and TNF-α were elevated in the sera of mice treated with erionite. The frequency of immune complex deposition in the kidneys increased from 33% in saline-treated mice to 90% with erionite. Conclusions: These data demonstrate that both erionite and amphibole asbestos induce autoimmune responses in mice, suggesting a potential for adverse effects in exposed communities. - Highlights: • Erionite, a fibrous mineral, is a current public health concern in the western USA. • Erionite exposure induces antinuclear autoantibodies in exposed mice. • Erionite induces a clear Th17 cytokine response in vitro and in vivo. • These responses were

  16. The MICE PID Instrumentation

    CERN Document Server

    Bonesini, M

    2008-01-01

    The international Muon Ionization Cooling Experiment (MICE) will carry out a systematic investigation of ionization cooling of a muon beam. As the emittance measurement will be done on a particle-by-particle basis, sophisticated beam instrumentation is needed to measure particle coordinates and timing vs RF. A PID system based on three time-of-flight stations, two Aerogel Cerenkov detectors and a KLOE-like calorimeter has been constructed in order to keep beam contamination ($e, \\pi$) well below 1%. The MICE time-of-flight system will measure timing with a resolution better than 70 ps per plane, in a harsh environment due to high particle rates, fringe magnetic fields and electron backgrounds from RF dark current.

  17. Psychopharmacological Studies in Mice.

    Science.gov (United States)

    Matsuda, Toshio

    2016-01-01

    Since 1998, when the laboratory of Medicinal Pharmacology was established in the Graduate School of Pharmaceutical Sciences, Osaka University, I have been interested in psychopharmacological research topics. During this period, we identified a number of novel regulatory mechanisms that control the prefrontal dopamine system through functional interaction between serotonin1A and dopamine D2 receptors or between serotonin1A and σ1 receptors. Our findings suggest that strategies that enhance the prefrontal dopamine system may have therapeutic potential in the treatment of psychiatric disorders. We also found that environmental factors during development strongly impact the psychological state in adulthood. Furthermore, we clarified the pharmacological profiles of the acetylcholinesterase inhibitors donepezil, galantamine, and rivastigmine, providing novel insights into their mechanisms of action. Finally, we developed the female encounter test, a novel method for evaluating motivation in mice. This simple method should help advance future psychopharmacological research. In this review, we summarize the major findings obtained from our recent studies in mice.

  18. Prolonging the survival of Tsc2 conditional knockout mice by glutamine supplementation.

    Science.gov (United States)

    Rozas, Natalia S; Redell, John B; McKenna, James; Moore, Anthony N; Gambello, Michael J; Dash, Pramod K

    2015-02-20

    The genetic disease tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by loss of function mutations in either TSC1 (hamartin) or TSC2 (tuberin), which serve as negative regulators of mechanistic target of rapamycin complex 1 (mTORC1) activity. TSC patients exhibit developmental brain abnormalities and tuber formations that are associated with neuropsychological and neurocognitive impairments, seizures and premature death. Mechanistically, TSC1 and TSC2 loss of function mutations result in abnormally high mTORC1 activity. Thus, the development of a strategy to inhibit abnormally high mTORC1 activity may have therapeutic value in the treatment of TSC. mTORC1 is a master regulator of growth processes, and its activity can be reduced by withdrawal of growth factors, decreased energy availability, and by the immunosuppressant rapamycin. Recently, glutamine has been shown to alter mTORC1 activity in a TSC1-TSC2 independent manner in cells cultured under amino acid- and serum-deprived conditions. Since starvation culture conditions are not physiologically relevant, we examined if glutamine can regulate mTORC1 in non-deprived cells and in a murine model of TSC. Our results show that glutamine can reduce phosphorylation of S6 and S6 kinase, surrogate indicators of mTORC1 activity, in both deprived and non-deprived cells, although higher concentrations were required for non-deprived cultures. When administered orally to TSC2 knockout mice, glutamine reduced S6 phosphorylation in the brain and significantly prolonged their lifespan. Taken together, these results suggest that glutamine supplementation can be used as a potential treatment for TSC.

  19. Diphenyl Ditelluride Intoxication Triggers Histological Changes in Liver, Kidney, and Lung of Mice

    Science.gov (United States)

    da Luz, Sônia Cristina Almeida; Daubermann, Melissa Falster; Thomé, Gustavo Roberto; dos Santos, Matheus Mülling; Ramos, Angelica; Torres Salazar, Gerson; da Rocha, João Batista Teixeira; Barbosa, Nilda Vargas

    2015-01-01

    Tellurium compounds may be cytotoxic to different cells types. Thus, this work evaluated the effect of diphenyl ditelluride ((PhTe)2), an organotellurium commonly used in organic synthesis, on the morphology of liver, kidney, and lung. Adult mice were acutely (a subcutaneous single dose: 250 μmol/kg) or subchronically (one daily subcutaneous dose: 10 or 50 μmol/kg for 7 and 14 days) exposed to (PhTe)2. Afterwards, the histological analyses of liver, kidney, and lungs were performed. Liver histology revealed that the hepatocytes of mice subchronically exposed to (PhTe)2 presented cytoplasmic vacuolization, hydropic degeneration, and hyperchromatic nuclei. Subchronic exposure to 50 μmol/kg (PhTe)2 also caused hepatic necrosis. Microvesicular and macrovesicular steatosis were identified in liver of mice acutely exposed to (PhTe)2. Acute and subchronic intoxication with (PhTe)2 induced changes on epithelial cells of renal tubules, namely, loss of brush border and cytoplasmatic vacuolization. Atrophy and hypertrophy, cast proteinaceous formation, and acute tubular necrosis were also identified in renal tissue. Mice subchronically exposed to 50 μmol/kg (PhTe)2 developed intra-alveolar edema and alveolar wall congestion in some areas of lungs. Acute exposure to (PhTe)2 did not cause histological changes in lungs. Our data show that (PhTe)2 may be considered a histotoxic agent for liver, kidney, and lung. PMID:26236579

  20. Diphenyl Ditelluride Intoxication Triggers Histological Changes in Liver, Kidney, and Lung of Mice

    Directory of Open Access Journals (Sweden)

    Sônia Cristina Almeida da Luz

    2015-01-01

    Full Text Available Tellurium compounds may be cytotoxic to different cells types. Thus, this work evaluated the effect of diphenyl ditelluride ((PhTe2, an organotellurium commonly used in organic synthesis, on the morphology of liver, kidney, and lung. Adult mice were acutely (a subcutaneous single dose: 250 μmol/kg or subchronically (one daily subcutaneous dose: 10 or 50 μmol/kg for 7 and 14 days exposed to (PhTe2. Afterwards, the histological analyses of liver, kidney, and lungs were performed. Liver histology revealed that the hepatocytes of mice subchronically exposed to (PhTe2 presented cytoplasmic vacuolization, hydropic degeneration, and hyperchromatic nuclei. Subchronic exposure to 50 μmol/kg (PhTe2 also caused hepatic necrosis. Microvesicular and macrovesicular steatosis were identified in liver of mice acutely exposed to (PhTe2. Acute and subchronic intoxication with (PhTe2 induced changes on epithelial cells of renal tubules, namely, loss of brush border and cytoplasmatic vacuolization. Atrophy and hypertrophy, cast proteinaceous formation, and acute tubular necrosis were also identified in renal tissue. Mice subchronically exposed to 50 μmol/kg (PhTe2 developed intra-alveolar edema and alveolar wall congestion in some areas of lungs. Acute exposure to (PhTe2 did not cause histological changes in lungs. Our data show that (PhTe2 may be considered a histotoxic agent for liver, kidney, and lung.

  1. Inhalation developmental toxicology studies: Teratology study of 1,3-butadiene in mice: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Hackett, P.L.; Sikov, M.R.; Mast, T.J.; Brown, M.G.; Buschbom, R.L.; Clark, M.L.; Decker, J.R.; Evanoff, J.J.; Rommereim, R.L.; Rowe, S.E.; Westerberg, R.B.

    1987-11-01

    Maternal toxicity, reproductive performance and developmental toxicology were evaluated in CD-1 mice following whole-body, inhalation exposures to 0, 40, 200 and 1000 ppM of 1,3-butadiene. The female mice, which had mated with unexposed males were exposed to the chemical for 6 hours/day on 6 through 15 dg and sacrificed on 18 dg. Maternal animals were weighed prior to mating and on 0, 6, 11 and 18 dg; the mice were observed for mortality, morbidity and signs of toxicity during exposure and examined for gross tissue abnormalities at necropsy. Live fetuses were weighed and subjected to external, visceral and skeletal examinations to detect growth retardation and morphologic anomalies. Significant concentration-related decreases were detected in a number of maternal body weight measures. There was a significant concentration-related depression of fetal body weights and placental weights. Body weights of male fetuses of all exposed groups were significantly lower than values for control fetuses; weights of female fetuses were significantly depressed in the mice exposed to 200 and 1000 ppM. In the 200- and 1000-ppM exposure groups, weights of placentas of male fetuses were significantly decreased, but placental weights of female fetuses were significantly affected only in litters exposed to the highest 1,3-butadiene concentration. This exposure regimen produced significant signs of maternal toxicity at concentrations of 200 and 1000 ppM 1,3-butadiene.

  2. Diphenyl ditelluride intoxication triggers histological changes in liver, kidney, and lung of mice.

    Science.gov (United States)

    da Luz, Sônia Cristina Almeida; Daubermann, Melissa Falster; Thomé, Gustavo Roberto; Dos Santos, Matheus Mülling; Ramos, Angelica; Torres Salazar, Gerson; da Rocha, João Batista Teixeira; Barbosa, Nilda Vargas

    2015-01-01

    Tellurium compounds may be cytotoxic to different cells types. Thus, this work evaluated the effect of diphenyl ditelluride ((PhTe)2), an organotellurium commonly used in organic synthesis, on the morphology of liver, kidney, and lung. Adult mice were acutely (a subcutaneous single dose: 250 μmol/kg) or subchronically (one daily subcutaneous dose: 10 or 50 μmol/kg for 7 and 14 days) exposed to (PhTe)2. Afterwards, the histological analyses of liver, kidney, and lungs were performed. Liver histology revealed that the hepatocytes of mice subchronically exposed to (PhTe)2 presented cytoplasmic vacuolization, hydropic degeneration, and hyperchromatic nuclei. Subchronic exposure to 50 μmol/kg (PhTe)2 also caused hepatic necrosis. Microvesicular and macrovesicular steatosis were identified in liver of mice acutely exposed to (PhTe)2. Acute and subchronic intoxication with (PhTe)2 induced changes on epithelial cells of renal tubules, namely, loss of brush border and cytoplasmatic vacuolization. Atrophy and hypertrophy, cast proteinaceous formation, and acute tubular necrosis were also identified in renal tissue. Mice subchronically exposed to 50 μmol/kg (PhTe)2 developed intra-alveolar edema and alveolar wall congestion in some areas of lungs. Acute exposure to (PhTe)2 did not cause histological changes in lungs. Our data show that (PhTe)2 may be considered a histotoxic agent for liver, kidney, and lung.

  3. Effects of Chronic Stress on Cognition in Male SAMP8 Mice

    Directory of Open Access Journals (Sweden)

    Jinhua Wang

    2016-08-01

    Full Text Available Background/Aims: Chronic stress can lead to cognitive impairment. Senescence-accelerated mouse prone 8 (SAMP8 is a naturally occurring animal model that is useful for investigating the neurological mechanisms of Alzheimer's disease. Here we investigated the impact and mechanisms of chronic stress on cognition in male SAMP8 mice. Methods: Male 6-month- old SAMP8 and SAMR1 (senescence-accelerated mouse resistant 1 mice strains were randomly divided into 4 groups. Mice in the unpredictable chronic mild stress (UCMS groups were exposed to diverse stressors for 4 weeks. Then, these mice performed Morris water maze (MWM test to assess the effect of UCMS on learning and memory. To explore the neurological mechanisms of UCMS on cognition in mice, we evaluated changes in the expression of postsynaptic density 95 (PSD95 and synaptophysin (SYN, which are essential proteins for synaptic plasticity. Five mice from each group were randomly chosen for reverse transcription polymerase chain reaction (RT-PCR and western blotting analysis of SYN and PSD95. Results: The Morris water maze experiment revealed that the cognitive ability of the SAMP8 mice decreased with brain aging, and that chronic stress aggravated this cognitive deficit. In addition, chronic stress decreased the mRNA and protein expression of SYN and PSD95 in the hippocampus of the SAMP8 mice; however, the SAMR1 mice were unaffected. Conclusion: Our results demonstrate that decreased cognition and synaptic plasticity are related to aging. Moreover, we show that chronic stress aggravated this cognitive deficit and decreased SYN and PSD95 expression in the SAMP8 mice. Furthermore, the SAMP8 mice were more vulnerable to the detrimental effects of chronic stress on cognition than the SAMR1 mice. Our results suggest that the neurological mechanisms of chronic stress on cognition might be associated with a decrease in hippocampal SYN and PSD95 expression, which is critical for structural synaptic

  4. Chemical protection against long-term effects of whole-body exposure of mice to ionizing radiation. III. The effects of fractionated exposure to C57Bl mice

    International Nuclear Information System (INIS)

    Mice of the C57Bl/Cnb strain were exposed to four fractionated doses delivered at weekly intervals (total doses from 4 x 50 to 4 x 375 R). One group of mice received a mixture of radioprotectors. The animals were followed to their natural death and investigated for histopathology. Life-shortening showed a sigmoid dependency on the dose in nonprotected and protected mice with a dose reduction factor of 2.1 at 50% life-shorteining. Thymic lymphoma was the most predominant cause of death in irradiated C57Bl mice. Radioprotectors diminished significantly the incidence of this disease but apparently did not reduce other causes of death. Reticulum cell sarcoma B also increased at the same low doses as thymic lymphoma. Both thymic lymphoma and reticulum cell sarcoma B increased in frequency after a fractionated dose compared to a single exposure with doses of 600 to 700 R and 300 to 400 R, respectively

  5. Chronic exposure to trichloroethene causes early onset of SLE-like disease in female MRL +/+ mice

    International Nuclear Information System (INIS)

    Trichloroethene (TCE) exacerbates the development of autoimmune responses in autoimmune-prone MRL +/+ mice. Although TCE-mediated autoimmune responses are associated with an increase in serum immunoglobulins and autoantibodies, the underlying mechanism of autoimmunity is not known. To determine the progression of TCE-mediated immunotoxicity, female MRL +/+ mice were chronically exposed to TCE through the drinking water (0.5 mg/ml of TCE) for various periods of time. Serum concentrations of antinuclear antibodies increased after 36 and 48 weeks of TCE exposure. Histopathological analyses showed lymphocyte infiltration in the livers of MRL +/+ mice exposed to TCE for 36 or 48 weeks. Lymphocyte infiltration was also apparent in the pancreas, lungs, and kidneys of mice exposed to TCE for 48 weeks. Immunoglobulin deposits in kidney glomeruli were found after 48 weeks of exposure to TCE. Our results suggest that chronic exposure to TCE promotes inflammation in the liver, pancreas, lungs, and kidneys, which may lead to SLE-like disease in MRL +/+ mice

  6. The role of endothelin-1 in hyperoxia-induced lung injury in mice

    Directory of Open Access Journals (Sweden)

    Albu Gergely

    2006-03-01

    Full Text Available Abstract Background As prolonged hyperoxia induces extensive lung tissue damage, we set out to investigate the involvement of endothelin-1 (ET-1 receptors in these adverse changes. Methods Experiments were performed on four groups of mice: control animals kept in room air and a group of mice exposed to hyperoxia for 60 h were not subjected to ET-1 receptor blockade, whereas the dual ETA/ETB-receptor blocker tezosantan (TEZ was administered via an intraperitoneal pump (10 mg/kg/day for 6 days to other groups of normal and hyperoxic mice. The respiratory system impedance (Zrs was measured by means of forced oscillations in the anesthetized, paralyzed and mechanically ventilated mice before and after the iv injection of ET-1 (2 μg. Changes in the airway resistance (Raw and in the tissue damping (G and elastance (H of a constant-phase tissue compartment were identified from Zrs by model fitting. Results The plasma ET-1 level increased in the mice exposed to hyperoxia (3.3 ± 1.6 pg/ml relative to those exposed to room air (1.6 ± 0.3 pg/ml, p 2O/l, p 2O/l, p Conclusion These findings substantiate the involvement of the ET-1 receptors in the physiopathogenesis of hyperoxia-induced lung damage. Dual ET-1 receptor antagonism may well be of value in the prevention of hyperoxia-induced parenchymal damage.

  7. Delayed emergence of behavioral and electrophysiological effects following juvenile ketamine exposure in mice.

    Science.gov (United States)

    Nagy, L R; Featherstone, R E; Hahn, C G; Siegel, S J

    2015-09-15

    Frequent ketamine abuse in adulthood correlates with increased risk of psychosis, as well as cognitive deficits, including disruption of higher-order executive function and memory formation. Although the primary abusers of ketamine are adolescents and young adults, few studies have evaluated its effects on juvenile cognition. Therefore, the current study analyzes the effect of adolescent ketamine exposure on cognitive development. Juvenile mice (4 weeks of age) were exposed to chronic ketamine (20 mg kg(-1), i.p. daily) for 14 days. Mice were tested immediately after exposure in the juvenile period (7 weeks of age) and again as adults (12 weeks of age). Measures included electroencephalography (EEG) in response to auditory stimulation, the social choice test, and a 6-arm radial water maze task. Outcome measures include low-frequency EEG responses, event-related potential (ERP) amplitudes, indices of social behavior and indices of spatial working memory. Juvenile exposure to ketamine was associated with electrophysiological abnormalities in adulthood, particularly in induced theta power and the P80 ERP. The social choice test revealed that ketamine-exposed mice failed to exhibit the same age-related decrease in social interaction time as controls. Ketamine-exposed mice outperformed control mice as juveniles on the radial water maze task, but did not show the same age-related improvement as adult controls. These data support the hypothesis that juvenile exposure to ketamine produces long-lasting changes in brain function that are characterized by a failure to progress along normal developmental trajectories.

  8. Delayed emergence of behavioral and electrophysiological effects following juvenile ketamine exposure in mice.

    Science.gov (United States)

    Nagy, L R; Featherstone, R E; Hahn, C G; Siegel, S J

    2015-01-01

    Frequent ketamine abuse in adulthood correlates with increased risk of psychosis, as well as cognitive deficits, including disruption of higher-order executive function and memory formation. Although the primary abusers of ketamine are adolescents and young adults, few studies have evaluated its effects on juvenile cognition. Therefore, the current study analyzes the effect of adolescent ketamine exposure on cognitive development. Juvenile mice (4 weeks of age) were exposed to chronic ketamine (20 mg kg(-1), i.p. daily) for 14 days. Mice were tested immediately afte