Temporal stability of novelty exploration in mice exposed to different open field tests.

Science.gov (United States)

Kalueff, Allan V; Keisala, Tiina; Minasyan, Anna; Kuuslahti, Marianne; Tuohimaa, Pentti

2006-03-01

We investigated behavioural activity and temporal distribution (patterning) of mouse exploration in different open field (OF) arenas. Mice of 129S1 (S1) strain were subjected in parallel to three different OF arenas (Experiment 1), two different OF arenas in two trials (Experiment 2) or two trials of the same OF test (Experiment 3). Overall, mice demonstrated a high degree of similarity in the temporal profile of novelty-induced horizontal and vertical exploration (regardless of the size, colour and shape of the OF), which remained stable in subsequent OF exposures. In Experiments 4 and 5, we tested F1 hybrid mice (BALB/c-S1; NMRI-S1), and Vitamin D receptor knockout mice (generated on S1 genetic background), again showing strikingly similar temporal patterns of their OF exploration, despite marked behavioural strain differences in anxiety and activity. These results suggest that mice are characterised by stability of temporal organization of their exploration in different OF novelty situations.

Ethanol self-administration in serotonin transporter knockout mice: unconstrained demand and elasticity.

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Lamb, R J; Daws, L C

2013-10-01

Low serotonin function is associated with alcoholism, leading to speculation that increasing serotonin function could decrease ethanol consumption. Mice with one or two deletions of the serotonin transporter (SERT) gene have increased extracellular serotonin. To examine the relationship between SERT genotype and motivation for alcohol, we compared ethanol self-administration in mice with zero (knockout, KO), one (HET) or two copies (WT) of the SERT gene. All three genotypes learned to self-administer ethanol. The SSRI, fluvoxamine, decreased responding for ethanol in the HET and WT, but not the KO mice. When tested under a progressive ratio schedule, KO mice had lower breakpoints than HET or WT. As work requirements were increased across sessions, behavioral economic analysis of ethanol self-administration indicated that the decreased breakpoint in KO as compared to HET or WT mice was a result of lower levels of unconstrained demand, rather than differences in elasticity, i.e. the proportional decreases in ethanol earned with increasing work requirements were similar across genotypes. The difference in unconstrained demand was unlikely to result from motor or general motivational factors, as both WT and KO mice responded at high levels for a 50% condensed milk solution. As elasticity is hypothesized to measure essential value, these results indicate that KO value ethanol similarly to WT or HET mice despite having lower break points for ethanol. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Virulence differences among Francisella tularensis subsp. tularensis clades in mice.

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Claudia R Molins

Full Text Available Francisella tularensis subspecies tularensis (type A and holarctica (type B are of clinical importance in causing tularemia. Molecular typing methods have further separated type A strains into three genetically distinct clades, A1a, A1b and A2. Epidemiological analyses of human infections in the United States suggest that A1b infections are associated with a significantly higher mortality rate as compared to infections caused by A1a, A2 and type B. To determine if genetic differences as defined by molecular typing directly correlate with differences in virulence, A1a, A1b, A2 and type B strains were compared in C57BL/6 mice. Here we demonstrate significant differences between survival curves for infections caused by A1b versus A1a, A2 and type B, with A1b infected mice dying earlier than mice infected with A1a, A2 or type B; these results were conserved among multiple strains. Differences were also detected among type A clades as well as between type A clades and type B with respect to bacterial burdens, and gross anatomy in infected mice. Our results indicate that clades defined within F. tularensis subsp. tularensis by molecular typing methods correlate with virulence differences, with A1b strains more virulent than A1a, A2 and type B strains. These findings indicate type A strains are not equivalent with respect to virulence and have important implications for public health as well as basic research programs.

Effect of Different Starvation Levels on Cognitive Ability in Mice

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Li, Xiaobing; Zhi, Guoguo; Yu, Yi; Cai, Lingyu; Li, Peng; Zhang, Danhua; Bao, Shuting; Hu, Wenlong; Shen, Haiyan; Song, Fujuan

2018-01-01

Objective: To study the effect of different starvation levels on cognitive ability in mice. Method: Mice were randomly divided into four groups: normal group, dieting group A, dieting group B, dieting group C. The mice of normal group were given normal feeding amount, the rest of groups were given 3/4 of normal feeding amount, 2/4 of normal feeding amount and 1/4 of normal feeding amount. After feeding mice four days, the weight was observed and T-maze experiment, Morris water maze test, open field test and Serum Catalase activity were detected. Result: Compared with the normal group, the correct rate of the intervention group in the T-maze experiment was decreased and dieting group A> dieting group B> dieting group C. In the Morris water maze test, Compared with the normal group, the correct rate of the intervention group was increased. Among these three intervention groups, dieting group A had the highest correct rate and the difference of dieting group B and dieting group C were similar. In the open field test, Compared with the normal group, the exploration rate of the surrounding environment in the intervention group was increased. In the Serum Catalase test, Compared with the normal group, the activities of serum peroxidase in the intervention groups were decreased and dieting group A> dieting group B> dieting group C. Conclusion: A certain level of starvation could affect the cognitive ability of mice. In a certain range, the level of starvation is inversely proportional to cognitive ability in mice.

Effect of cadmium chloride on hepatic lipid peroxidation in mice

DEFF Research Database (Denmark)

Andersen, H R; Andersen, O

1988-01-01

Intraperitoneal administration of cadmium chloride to 8-12 weeks old CBA-mice enhanced hepatic lipid peroxidation. A positive correlation between cadmium chloride dose and level of peroxidation was observed in both male and female mice. A sex-related difference in mortality was not observed...... but at a dose of 25 mumol CdCl2/kg the level of hepatic lipid peroxidation was higher in male mice than in female mice. The hepatic lipid peroxidation was not increased above the control level in 3 weeks old mice, while 6 weeks old mice responded with increased peroxidation as did 8-12 weeks old mice....... The mortality after an acute toxic dose of cadmium chloride was the same in the three age groups. Pretreatment of mice with several low intraperitoneal doses of cadmium chloride alleviated cadmium induced mortality and lipid peroxidation. The results demonstrate both age dependency and a protective effect...

Sensitivity to immunodepressant action of cyclophosphamide: analysis of interstrain differences in mice.

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Pevnitsky, L A; Telegin LYu; Zhirnov, G F; Mazurov, A V; Viktorov, V V

1985-01-01

In one of our previous studies (Pevnitsky et al., Bull. exp. Biol. Med., 83, 438-440, 1977), we have found significant differences between various strains of mice in the sensitivity to immunodepressant action of cyclophosphamide (CP). The degree of these differences was not determined by the level of their immune response which indicates that the cause of the interstrain differences lies in a specific reaction of mice to the immunodepressant. The main parameters of CP effect which may be responsible for variable sensitivity to the immunodepressant action in vivo were studied in several murine strains (Balb/cJLacSto, CBA/CaLacSto, and DBA/2JSto): (1) rate of the preparation activation in liver microsomes; (2) pharmacokinetics of NBP-metabolites in the blood serum; (3) immunodepressant action of the in vivo activated CP; (4) sensitivity of immunocompetent target cells to activated CP effect. It was found that DBA/2 mice are the most sensitive to CP in vivo. The level of "active" CP in their blood serum is higher than in BALB/c mice. Besides, they are characterized by a higher sensitivity of immunocompetent cells compared to BALB/c and CBA mice.

Sex differences in obesity development in pair-fed neuronal lipoprotein lipase deficient mice

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Hong Wang

2016-10-01

Full Text Available Objective: Compared to men, postmenopausal women suffer from a disproportionate burden of many co-morbidities associated with obesity, e.g. cardiovascular disease, cancer, and dementia. The underlying mechanism for this sex difference is not well understood but is believed to relate to absence of the protective effect of estrogen through the action of estrogen receptor alpha (ERα in the central nervous system. With the recently developed neuron-specific lipoprotein lipase deficient mice (NEXLPL−/− (Wang et al., Cell Metabolism, 2011 [15], we set to explore the possible role of lipid sensing in sex differences in obesity development. Methods: Both male and female NEXLPL−/− mice and littermate WT controls were subjected to pair feeding (pf where daily food amount given was adjusted according to body weight to match the food intake of ad libitum (ad fed control WT mice. Food intake and body weight were measured daily, and pair feeding was maintained to 42 wk in male mice and to 38 wk in female mice. Various brain regions of the mice were harvested, and ERα gene expression was examined in both male and female NEXLPL−/− and WT control mice under both ad- and pf-fed conditions. Results: Although both male and female NEXLPL−/− mice developed obesity similarly on standard chow, male NEXLPL−/− mice still developed obesity under with pair feeding, but on a much delayed time course, while female NEXLPL−/− mice were protected from extra body weight and fat mass gain compared to pair-fed WT control mice. Pair feeding alone induced extra fat mass gain in both male and female WT mice, and this was mostly driven by the reduction in physical activity. LPL deficiency resulted in an increase in ERα mRNA in the hypothalamus of ad-fed female mice, while pair feeding alone also resulted in an increase of ERα in both female WT control and NEXLPL−/− mice. The effect on increasing ERα by pair feeding and LPL deficiency was additive in

Specificity in Sociality: Mice and Prairie Voles Exhibit Different Patterns of Peer Affiliation

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Beery, Annaliese K.; Christensen, Jennifer D; Lee, Nicole S.; Blandino, Katrina L.

2018-01-01

Social behavior is often described as a unified concept, but highly social (group-living) species exhibit distinct social structures and may make different social decisions. Prairie voles (Microtus ochrogaster) are socially monogamous rodents that often reside in extended family groups, and exhibit robust preferences for familiar social partners (same- and opposite-sex) during extended choice tests, although short-term preferences are not known. Mice (Mus musculus) are gregarious and colonial, but in brief laboratory tests of social preference they typically prefer social novelty. This preference for novel vs. familiar peers may represent a species-specific difference in social decision-making between mice and prairie voles. However, the tests used to measure preferences in each species differ markedly in duration and degree of contact, such that the behaviors cannot be directly compared. We assessed whether social preferences for novelty or familiarity differed between mice and prairie voles of both sexes when assessed with matching protocols: the sociability/social preference test (SPT) typically used in mice (short, no direct contact), and the partner preference test (PPT) used in voles (long, direct contact). A subset of voles also underwent a PPT using barriers (long, no direct contact). In the short SPT, behavior did not differ between species. In the longer test, pronounced partner preferences emerged in prairie voles, but mice exhibited no social preferences and rarely huddled. No sex differences were evident in either test. Direct physical contact was required for partner preferences in huddling time in voles, but preference for the partner chamber was evident with or without contact. Both prairie voles and mice are social, but they exhibit important differences in the specificity and extent of their social behavior. While mice are often used to study social approach and other behaviors, voles are a more suitable species for the study of selective social

Specificity in Sociality: Mice and Prairie Voles Exhibit Different Patterns of Peer Affiliation

Directory of Open Access Journals (Sweden)

Annaliese K. Beery

2018-03-01

Full Text Available Social behavior is often described as a unified concept, but highly social (group-living species exhibit distinct social structures and may make different social decisions. Prairie voles (Microtus ochrogaster are socially monogamous rodents that often reside in extended family groups, and exhibit robust preferences for familiar social partners (same- and opposite-sex during extended choice tests, although short-term preferences are not known. Mice (Mus musculus are gregarious and colonial, but in brief laboratory tests of social preference they typically prefer social novelty. This preference for novel vs. familiar peers may represent a species-specific difference in social decision-making between mice and prairie voles. However, the tests used to measure preferences in each species differ markedly in duration and degree of contact, such that the behaviors cannot be directly compared. We assessed whether social preferences for novelty or familiarity differed between mice and prairie voles of both sexes when assessed with matching protocols: the sociability/social preference test (SPT typically used in mice (short, no direct contact, and the partner preference test (PPT used in voles (long, direct contact. A subset of voles also underwent a PPT using barriers (long, no direct contact. In the short SPT, behavior did not differ between species. In the longer test, pronounced partner preferences emerged in prairie voles, but mice exhibited no social preferences and rarely huddled. No sex differences were evident in either test. Direct physical contact was required for partner preferences in huddling time in voles, but preference for the partner chamber was evident with or without contact. Both prairie voles and mice are social, but they exhibit important differences in the specificity and extent of their social behavior. While mice are often used to study social approach and other behaviors, voles are a more suitable species for the study of

Different perception levels of histamine-induced itch sensation in young adult mice.

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Ji, Yeounjung; Jang, Yongwoo; Lee, Wook Joo; Yang, Young Duk; Shim, Won-Sik

2018-05-01

Itch is an unpleasant sensation that evokes behavioral responses such as scratching the skin. Interestingly, it is conceived that the perception of itch sensation is influenced by age. Indeed, accumulating evidence supports the idea that even children or younger adults show distinctive itch sensation depending on age. This evidence implies the presence of a mechanism that regulates the perception of itch sensation in an age-dependent fashion. Therefore, the purpose of the present study was to investigate a putative mechanism for the age-dependent perception of itch sensation by comparing histamine-induced scratching behaviors in 45-day old (D45) and 75-day old male "young adult" mice. The results indicated that, following histamine administration, the D75 mice spent a longer time scratching than D45 mice. However, the intensity of the calcium influx induced by histamine in primary culture of dorsal root ganglia (DRG) neurons was not different between D45 and D75 mice. Moreover, no apparent difference was observed in mRNA levels of a characteristic His-related receptor and ion channel. In contrast, the mRNA levels of Toll-Like Receptor 4 (TLR4) were increased approximately by two-fold in D75 DRG compared with D45 DRG. Additionally, D75-derived DRG neurons exhibited enhanced intracellular calcium increase by lipopolysaccharide (LPS, a TLR4 agonist) than those of D45 mice. Furthermore, intensities of calcium influx induced by histamine were significantly potentiated when co-treated with LPS in D75 DRG neurons, but not in those of D45 mice. Thus, it appears that D75 mice showed enhanced histamine-induced scratching behaviors not by increased expression levels of histamine-related genes, but probably due to augmented TLR4 expression in DRG neurons. Consequently, the current study found that different perception levels of histamine-induced itch sensation are present in different age groups of young adult mice. Copyright © 2018 Elsevier Inc. All rights reserved.

Dopamine D3 receptor knockout mice exhibit abnormal nociception in a sex-different manner.

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Liu, Peng; Xing, Bo; Chu, Zheng; Liu, Fei; Lei, Gang; Zhu, Li; Gao, Ya; Chen, Teng; Dang, Yong-Hui

2017-07-01

Pain is a complex and subjective experience. Previous studies have shown that mice lacking the dopamine D3 receptor (D3RKO) exhibit hypoalgesia, indicating a role of the D3 receptor in modulation of nociception. Given that there are sex differences in pain perception, there may be differences in responses to nociceptive stimuli between male and female D3RKO mice. In the current study, we examined the role of the D3 receptor in modulating nociception in male and female D3RKO mice. Acute thermal pain was modeled by hot-plate test. This test was performed at different temperatures including 52°C, 55°C, and 58°C. The von Frey hair test was applied to evaluate mechanical pain. And persistent pain produced by peripheral tissue injury and inflammation was modeled by formalin test. In the hot-plate test, compared with wild-type (WT) mice, D3RKO mice generally exhibited longer latencies at each of the three temperatures. Specially, male D3RKO mice showed hypoalgesia compared with male WT mice when the temperature was 55°C, while for the female mice, there was a statistical difference between genotypes when the test condition was 52°C. In the von Frey hair test, both male and female D3RKO mice exhibited hypoalgesia. In the formalin test, the male D3RKO mice displayed a similar nociceptive behavior as their sex-matched WT littermates, whereas significantly depressed late-phase formalin-induced nociceptive behaviors were observed in the female mutants. These findings indicated that the D3 receptor affects nociceptive behaviors in a sex-specific manner and that its absence induces more analgesic behavior in the female knockout mice. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Live birth rates in the different combinations of the Bologna criteria poor ovarian responders: a validation study.

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La Marca, Antonio; Grisendi, Valentina; Giulini, Simone; Sighinolfi, Giovanna; Tirelli, Alessandra; Argento, Cindy; Re, Claudia; Tagliasacchi, Daniela; Marsella, Tiziana; Sunkara, Sesh Kamal

2015-06-01

to compare the baseline characteristics and chance of live birth in the different categories of poor responders identified by the combinations of the Bologna criteria and establish whether these groups comprise a homogenous population. database containing clinical and laboratory information on IVF treatment cycles carried out at the Mother-Infant Department of the University Hospital of Modena between year 2007 and 2011 was analysed. This data was collected prospectively and recorded in the registered database of the fertility centre. Eight hundred and thirty women fulfilled the inclusion/ exclusion criteria of the study and 210 women fulfilled the Bologna criteria definition for poor ovarian response (POR). Five categories of poor responders were identified by different combinations of the Bologna criteria. There were no significant differences in female age, AFC, AMH, cycle cancellation rate and number of retrieved oocytes between the five groups. The live birth rate ranged between 5.5 and 7.4 % and was not statistically different in the five different categories of women defined as poor responders according to the Bologna criteria. The study demonstrates that the different groups of poor responders based on the Bologna criteria have similar IVF outcomes. This information validates the Bologna criteria definition as women having a uniform poor prognosis and also demonstrates that the Bologna criteria poor responders in the various subgroups represent a homogenous population with similar pre-clinical and clinical outcomes.

Cultural differences in survey responding: Issues and insights in the study of response biases.

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Kemmelmeier, Markus

2016-12-01

This paper introduces the special section "Cultural differences in questionnaire responding" and discusses central topics in the research on response biases in cross-cultural survey research. Based on current conceptions of acquiescent, extreme, and socially desirable responding, the author considers current data on the correlated nature of response biases and the conditions under which different response styles they emerge. Based on evidence relating different response styles to the cultural dimension of individualism-collectivism, the paper explores how research presented as part of this special section might help resolves some tensions in this literature. The paper concludes by arguing that response styles should not be treated merely as measurement error, but as cultural behaviors in themselves. © 2016 International Union of Psychological Science.

Compulsive Addiction-like Aggressive Behavior in Mice.

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Golden, Sam A; Heins, Conor; Venniro, Marco; Caprioli, Daniele; Zhang, Michelle; Epstein, David H; Shaham, Yavin

2017-08-15

Some people are highly motivated to seek aggressive encounters, and among those who have been incarcerated for such behavior, recidivism rates are high. These observations echo two core features of drug addiction: high motivation to seek addictive substances, despite adverse consequences, and high relapse rates. Here we used established rodent models of drug addiction to determine whether they would be sensitive to "addiction-like" features of aggression in CD-1 mice. In experiments 1 and 2, we trained older CD-1 mice to lever press for opportunities to attack younger C57BL6/J mice. We then tested them for relapse to aggression seeking after forced abstinence or punishment-induced suppression of aggression self-administration. In experiment 3, we trained a large cohort of CD-1 mice and tested them for choice-based voluntary suppression of aggression seeking, relapse to aggression seeking, progressive ratio responding, and punishment-induced suppression of aggression self-administration. We then used cluster analysis to identify patterns of individual differences in compulsive "addiction-like" aggressive behavior. In experiments 1 and 2, we observed strong motivation to acquire operant self-administration of opportunities to aggress and relapse vulnerability during abstinence. In experiment 3, cluster analysis of the aggression-related measures identified a subset of "addicted" mice (∼19%) that exhibited intense operant-reinforced attack behavior, decreased likelihood to select an alternative reinforcer over aggression, heightened relapse vulnerability and progressive ratio responding, and resilience to punishment-induced suppression of aggressive behavior. Using procedures established to model drug addiction, we showed that a subpopulation of CD-1 mice demonstrate "addiction-like" aggressive behavior, suggesting an evolutionary origin for compulsive aggression. Published by Elsevier Inc.

Unexpected gender difference in sensitivity to the acute toxicity of dioxin in mice

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Pohjanvirta, Raimo, E-mail: raimo.pohjanvirta@helsinki.fi [Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014 University of Helsinki (Finland); Miettinen, Hanna, E-mail: hanna.miettinen@crl.com [Department of Environmental Health, National Institute for Health and Welfare, P.O. Box 95, FI-70701 Kuopio (Finland); Sankari, Satu, E-mail: satu.sankari@helsinki.fi [Central Laboratory of the Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, FI-00014 University of Helsinki (Finland); Hegde, Nagabhooshan [Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014 University of Helsinki (Finland); Lindén, Jere, E-mail: jere.linden@helsinki.fi [Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014 University of Helsinki (Finland); Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014 University of Helsinki (Finland)

2012-07-15

The acute toxicity of the ubiquitous environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) varies widely among species and strains. Previous studies in rats have established that females are approximately 2-fold more sensitive to TCDD lethality than males. However, there is a surprising gap in the literature regarding possible gender-related sensitivity differences in mice. In the present study, by using three substrains of TCDD-sensitive C57BL/6 mice and transgenic mice on this background, we demonstrated that: 1) in contrast to the situation in rats, female mice are the more resistant gender; 2) the magnitude of the divergence between male and female mice depends on the substrain, but can amount to over 10-fold; 3) AH receptor protein expression levels or mutations in the primary structure of this receptor are not involved in the resistance of female mice of a C57BL/6 substrain, despite their acute LD{sub 50} for TCDD being over 5000 μg/kg; 4) transgenic mice that globally express the rat wildtype AH receptor follow the mouse type of gender difference; 5) in gonadectomized mice, ovarian estrogens appear to enhance TCDD resistance, whereas testicular androgens seem to augment TCDD susceptibility; and 6) the gender difference correlates best with the severity of liver damage, which is also reflected in hepatic histopathology and the expression of pro-inflammatory cytokines, especially IL-6. Hence, the two closely related rodent species most often employed in toxicological risk characterization studies, rat and mouse, represent opposite examples of the influence of gender on dioxin sensitivity, further complicating the risk assessment of halogenated aromatic hydrocarbons. -- Highlights: ► In contrast to rats, male mice are more sensitive to TCDD toxicity than female mice. ► The resistance of female C57BL/6Kuo mice matches or exceeds that of male DBA/2 mice. ► The resistance of female C57BL/6Kuo mice is not based on AHR structure or abundance. �

Unexpected gender difference in sensitivity to the acute toxicity of dioxin in mice

International Nuclear Information System (INIS)

Pohjanvirta, Raimo; Miettinen, Hanna; Sankari, Satu; Hegde, Nagabhooshan; Lindén, Jere

2012-01-01

The acute toxicity of the ubiquitous environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) varies widely among species and strains. Previous studies in rats have established that females are approximately 2-fold more sensitive to TCDD lethality than males. However, there is a surprising gap in the literature regarding possible gender-related sensitivity differences in mice. In the present study, by using three substrains of TCDD-sensitive C57BL/6 mice and transgenic mice on this background, we demonstrated that: 1) in contrast to the situation in rats, female mice are the more resistant gender; 2) the magnitude of the divergence between male and female mice depends on the substrain, but can amount to over 10-fold; 3) AH receptor protein expression levels or mutations in the primary structure of this receptor are not involved in the resistance of female mice of a C57BL/6 substrain, despite their acute LD 50 for TCDD being over 5000 μg/kg; 4) transgenic mice that globally express the rat wildtype AH receptor follow the mouse type of gender difference; 5) in gonadectomized mice, ovarian estrogens appear to enhance TCDD resistance, whereas testicular androgens seem to augment TCDD susceptibility; and 6) the gender difference correlates best with the severity of liver damage, which is also reflected in hepatic histopathology and the expression of pro-inflammatory cytokines, especially IL-6. Hence, the two closely related rodent species most often employed in toxicological risk characterization studies, rat and mouse, represent opposite examples of the influence of gender on dioxin sensitivity, further complicating the risk assessment of halogenated aromatic hydrocarbons. -- Highlights: ► In contrast to rats, male mice are more sensitive to TCDD toxicity than female mice. ► The resistance of female C57BL/6Kuo mice matches or exceeds that of male DBA/2 mice. ► The resistance of female C57BL/6Kuo mice is not based on AHR structure or abundance. �

Renal Proteome in Mice with Different Susceptibilities to Fluorosis

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Peres-Buzalaf, Camila; Salvato, Fernanda; Labate, Carlos Alberto; Everett, Eric T.; Whitford, Gary Milton; Buzalaf, Marília Afonso Rabelo

2013-01-01

A/J and 129P3/J mouse strains have different susceptibilities to dental fluorosis due to their genetic backgrounds. They also differ with respect to several features of fluoride (F) metabolism and metabolic handling of water. This study was done to determine whether differences in F metabolism could be explained by diversities in the profile of protein expression in kidneys. Weanling, male A/J mice (susceptible to dental fluorosis, n = 18) and 129P3/J mice (resistant, n = 18) were housed in pairs and assigned to three groups given low-F food and drinking water containing 0, 10 or 50 ppm [F] for 7 weeks. Renal proteome profiles were examined using 2D-PAGE and LC-MS/MS. Quantitative intensity analysis detected between A/J and 129P3/J strains 122, 126 and 134 spots differentially expressed in the groups receiving 0, 10 and 50 ppmF, respectively. From these, 25, 30 and 32, respectively, were successfully identified. Most of the proteins were related to metabolic and cellular processes, followed by response to stimuli, development and regulation of cellular processes. In F-treated groups, PDZK-1, a protein involved in the regulation of renal tubular reabsorption capacity was down-modulated in the kidney of 129P3/J mice. A/J and 129P3/J mice exhibited 11 and 3 exclusive proteins, respectively, regardless of F exposure. In conclusion, proteomic analysis was able to identify proteins potentially involved in metabolic handling of F and water that are differentially expressed or even not expressed in the strains evaluated. This can contribute to understanding the molecular mechanisms underlying genetic susceptibility to dental fluorosis, by indicating key-proteins that should be better addressed in future studies. PMID:23308176

[Genetic differences in mice in the sensitivity to the immunodepressive action of alkylating agents].

Science.gov (United States)

Kim, N I; Telegin, L Iu; Pevnitskiĭ, L A

1983-04-01

The immunodepressant action of cyclophosphamide, thiophosphamide and sarcolysine was examined in experimental primary immune response in mice of different lines immunized with sheep red blood cells. DBA/2 and C3H/Sn mice were marked by the highest sensitivity to the immunodepressant action of the alkylating agents. BALB/c mice were relatively resistant to the immunodepressant action. Possible reasons for the interspecific differences found are discussed.

Sex differences in complex regional pain syndrome type I (CRPS-I) in mice.

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Tang, Chaoliang; Li, Juan; Tai, Wai Lydia; Yao, Weifeng; Zhao, Bo; Hong, Junmou; Shi, Si; Wang, Song; Xia, Zhongyuan

2017-01-01

Sex differences have been increasingly highlighted in complex regional pain syndrome (CRPS) in clinical practice. In CRPS type I (CRPS-I), although inflammation and oxidative stress have been implicated in its pathogenesis, whether pain behavior and the underlying mechanism are sex-specific is unclear. In the present study, we sought to explore whether sex differences have an impact on inflammation, oxidative stress, and pain sensitivity in CRPS-I. Chronic post-ischemia pain (CPIP) was established in both male and female mice as an animal model of CRPS-I. Edema and mechanical allodynia of bilateral hind paws were assessed after reperfusion. Blood samples were analyzed for serum levels of oxidative stress markers and inflammatory cytokines. Both male and female mice developed edema. Male mice developed CPIP at day 3 after reperfusion; female mice developed CPIP at day 2 after reperfusion. Female mice displayed significantly earlier and higher mechanical allodynia in the ischemic hind paw, which was associated with higher serum levels of IL-2, TNF-α, isoprostanes, 8 OhdG, and malondialdehyde at day 2 after reperfusion. Moreover, female mice showed significantly lower SOD and IL-4 compared to male mice at day 2 after reperfusion. Our results indicate that sex differences in inflammatory and oxidative stress states may play a central role in the sex-specific nociceptive hypersensitivity in CRPS-I, and offer a new insight into pharmacology treatments to improve pain management with CRPS.

Pharmacological Modulation of 5-HT2C Receptor Activity Produces Bidirectional Changes in Locomotor Activity, Responding for a Conditioned Reinforcer, and Mesolimbic DA Release in C57BL/6 Mice.

Science.gov (United States)

Browne, Caleb J; Ji, Xiaodong; Higgins, Guy A; Fletcher, Paul J; Harvey-Lewis, Colin

2017-10-01

Converging lines of behavioral, electrophysiological, and biochemical evidence suggest that 5-HT 2C receptor signaling may bidirectionally influence reward-related behavior through an interaction with the mesolimbic dopamine (DA) system. Here we directly test this hypothesis by examining how modulating 5-HT 2C receptor activity affects DA-dependent behaviors and relate these effects to changes in nucleus accumbens (NAc) DA release. In C57BL/6 mice, locomotor activity and responding for a conditioned reinforcer (CRf), a measure of incentive motivation, were examined following treatment with three 5-HT 2C receptor ligands: the agonist CP809101 (0.25-3 mg/kg), the antagonist SB242084 (0.25-1 mg/kg), or the antagonist/inverse agonist SB206553 (1-5 mg/kg). We further tested whether doses of these compounds that changed locomotor activity and responding for a CRf (1 mg/kg CP809101, 0.5 mg/kg SB242084, or 2.5 mg/kg SB206553) also altered NAc DA release using in vivo microdialysis in anesthetized mice. CP809101 reduced locomotor activity, responding for a CRf, and NAc DA release. In contrast, both SB242084 and SB206553 enhanced locomotor activity, responding for a CRf, and NAc DA release, although higher doses of SB206553 produced opposite behavioral effects. Pretreatment with the non-selective DA receptor antagonist α-flupenthixol prevented SB242084 from enhancing responding for a CRf. Thus blocking tonic 5-HT 2C receptor signaling can release serotonergic inhibition of mesolimbic DA activity and enhance reward-related behavior. The observed bidirectional effects of 5-HT 2C receptor ligands may have important implications when considering the 5-HT 2C receptor as a therapeutic target for psychiatric disorders, particularly those presenting with motivational dysfunctions.

The hidden price of repeated traumatic exposure: Different cognitive deficits in different first-responders

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Einat eLevy-Gigi

2014-08-01

Full Text Available Studies on first responders who are repeatedly exposed to traumatic events report low levels of PTSD symptoms and diagnosis. However, neuroimaging and behavioral studies show that traumatic exposure is associated with brain and cognitive dysfunctions. Taking together it may suggest that traumatic exposure have a price, which is not sufficiently defined by the standard PTSD measures. In a recent study we revealed that similar to individuals with PTSD, non-PTSD highly exposed firefighters display a selective impairment in hippocampal related functions. In the current study we aimed to test whether different first responders display a similar impairment. We concentrated on unique populations of active duty firefighters and criminal scene-investigators (CSI police, who are frequently exposed to similar levels and types of traumatic events, and compared them to civilian matched-controls with no history of trauma-exposure. We used a hippocampal dependent cue-context reversal paradigm, which separately evaluates reversal of negative and positive outcomes of cue and context related information. We predicted and found that all participants were equally able to acquire and retain stimulus-outcome associations. However, there were significant differences in reversal learning between the groups. Performance among firefighters replicated our prior findings; they struggled to learn that a previously negative context is later associated with a positive outcome. CSI police on the other hand showed a selective impairment in reversing the outcome of a negative cue. Hence after learning that a specific cue is associated with a negative outcome, they could not learn that later it is associated with a positive outcome. Performance in both groups did not correlate with levels of PTSD, anxiety, depression or behavioral inhibition symptoms. The results provide further evidence of the hidden price of traumatic exposure, suggesting that this price may differ as a

p21WAF1/Cip1/Sdi1 knockout mice respond to doxorubicin with reduced cardiotoxicity

International Nuclear Information System (INIS)

Terrand, Jerome; Xu, Beibei; Morrissy, Steve; Dinh, Thai Nho; Williams, Stuart; Chen, Qin M.

2011-01-01

Doxorubicin (Dox) is an antineoplastic agent that can cause cardiomyopathy in humans and experimental animals. As an inducer of reactive oxygen species and a DNA damaging agent, Dox causes elevated expression of p21 WAF1/Cip1/Sdi1 (p21) gene. Elevated levels of p21 mRNA and p21 protein have been detected in the myocardium of mice following Dox treatment. With chronic treatment of Dox, wild type (WT) animals develop cardiomyopathy evidenced by elongated nuclei, mitochondrial swelling, myofilamental disarray, reduced cardiac output, reduced ejection fraction, reduced left ventricular contractility, and elevated expression of ANF gene. In contrast, p21 knockout (p21KO) mice did not show significant changes in the same parameters in response to Dox treatment. In an effort to understand the mechanism of the resistance against Dox induced cardiomyopathy, we measured levels of antioxidant enzymes and found that p21KO mice did not contain elevated basal or inducible levels of glutathione peroxidase and catalase. Measurements of 6 circulating cytokines indicated elevation of IL-6, IL-12, IFNγ and TNFα in Dox treated WT mice but not p21KO mice. Dox induced elevation of IL-6 mRNA was detected in the myocardium of WT mice but not p21KO mice. While the mechanism of the resistance against Dox induced cardiomyopathy remains unclear, lack of inflammatory response may contribute to the observed cardiac protection in p21KO mice. -- Highlights: ► Doxorubicin induces p21 elevation in the myocardium. ► Doxorubicin causes dilated cardiomyopathy in wild type mice. ► p21 Knockout mice are resistant against doxorubicin induced cardiomyopathy. ► Lack of inflammatory response correlates with the resistance in p21 knockout mice.

Regulation of IgE antibody production by serum molecules. I. Serum from complete Freund's adjuvant-immune donors suppresses irradiation-enhanced IgE production in low responder mouse strains

International Nuclear Information System (INIS)

Tung, A.S.; Chiorazzi, N.; Katz, D.H.

1978-01-01

Exposure of mice to low doses of x irradiation at or near the time of primary immunization with 2,4-dinitrophenyl (DNP)-Ascaris suum extract (ASC) results in substantial enhancement of IgE anti-DNP antibody responses; the IgG antibody responses of such mice do not increase after such manipulations. This selective enhancement of IgE antibody production occurs in mice of both high and low IgE responder phenotype, although the extent of enhancement compared to unmanipulated control animals is more striking in low IgE responder mice. The studies presented here demonstrate that the irradiation-enhanced IgE antibody responses of low responder SJL and C57BL/6 mice as well as of intermediate responder AKR mice can be effectively suppressed by passive transfer of CFA-immune serum obtained from isologous donor mice. Moreover, adoptive secondary IgE antibody responses in SJL recipients of primed syngeneic spleen cells can be totally abolished by passive transfer of CFA-immune serum or ascitic fluid from CFA-immune mice. The suppressive activity of CFA-immune serum can be diminished or eliminated by exposure of CFA-primed donor mice to low dose x irradiation at an appropriate point during the priming regimen, after a single inoculation of CFA, and before collection of serum. Low dose x irradiation was not effective in eliminating suppressive activity of CFA-induced ascites fluid obtained from donor mice inoculated repeatedly with CFA. In contrast to the capacity of CFA-immune serum from isologous donors to suppress irradiation-enhanced IgE responses of low responder mice, similar sera or ascites fluids were ineffective in suppressing irradiation-enhanced responses of high responder BALB/c or (SJL x BALB/c)F 1 hybrid mice

Sex differences in insulin resistance in GABAB1 knockout mice.

Science.gov (United States)

Bonaventura, M M; Rodriguez, D; Ferreira, M L; Crivello, M; Repetto, E M; Bettler, B; Libertun, C; Lux-Lantos, V A

2013-02-27

We have previously demonstrated that the absence of functional GABA B receptors (GABABRs) disturbs glucose homeostasis in GABAB1KO mice. The aim of this work was to extend our studies of these alterations in GABAB1KO mice and investigate the sexual differences therein. Male and female, GABAB1KO and WT mice were used. Glucose and insulin tolerance tests (GTT and ITT), and insulin and glucagon secretion tests (IST and GST) were performed. Blood glucose, serum insulin and hyperglycemic hormones were determined, and HOMA-IR calculated. Skeletal muscle insulin receptor β subunit (IRβ), insulin receptor substrates 1/2 (IRS1, IRS2) and hexokinase-II levels were determined by Western blot. Skeletal muscle insulin sensitivity was assessed by in vivo insulin-induced Akt phosphorylation (Western blot). Food intake and hypothalamic NPY mRNA expression (by qPCR) were also evaluated. Fasted insulin and HOMA-IR were augmented in GABAB1KO males, with no alterations in females. Areas under the curve (AUC) for GTT and ITT were increased in GABAB1KO mice of both genders, indicating compromised insulin sensitivity. No genotype differences were observed in IST, GST or in IRβ, IRS1, IRS2 and hexokinase-II expression. Akt activation was severely impaired in GABAB1KO males while no alterations were observed in females. GABAB1KO mice showed increased food intake and NPY expression. Glucose metabolism and energy balance disruptions were more pronounced in GABAB1KO males, which develop peripheral insulin resistance probably due to augmented insulin secretion. Metabolic alterations in females were milder and possibly due to previously described reproductive disorders, such as persistent estrus. Copyright © 2012 Elsevier Inc. All rights reserved.

Apoptosis of bone marrow leukemia cells in mice after low dose radiation at different time

International Nuclear Information System (INIS)

Li Guangyu; Yu Mingming; Li Xianjun; Liu Zhixiang

2007-01-01

Objective: To investigate the apoptosis of bone marrow leukemia cell in mice after low dose radiation (LDR) at different time and the experimental basis for LDR auxiliary therapy on leukemia. Methods: WEHI-3 cells were injected into BALB/c mice through tail veins to make an experimental mice model of myelornonocytic leukemia. 60 leukemia mice models were divided half-and half. 30 mice models in experimental group were irradiated with LDR of 75mGy at the same time while the others 30 in the control group were not. 6 mice models with LDR and 6 mice models without LDR would be killed at the time the 1st day, the 2nd day, the 3rd day, the 5th day- and the l0th day after LDR in order to extract bone marrow samples. The apoptosis percentage of leukemia cells in bone marrow was examined. Results: The apoptosis percentage of leukemia cells in experimental group was increasing after LDR and went to top on the 2nd day and the 3rd day. The apoptosis percentage of leukemia cells was remarkably different between experimental and control group, all P<0.05. Conclusion: LDR could significantly increase the apoptosis percentage of bone marrow leukemia cells in mice. Its mechanism is remarkably different in kill and wound of big dose radiation to tumour cells. It is probably related to of the increase immune exciting response as to promote some cytokine secretion, in leukemia mice. (authors)

Tularemia induces different biochemical responses in BALB/c mice and common voles

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Vitula Frantisek

2009-06-01

Full Text Available Abstract Background Both BALB/c mice and common voles (Microtus arvalis are considered highly susceptible to tularemia. However, the common vole is reported to harbour Francisella tularensis in European habitats as well as to survive longer with chronic shedding of the bacterium. The purpose of the present study was to compare the response of these two rodents to a wild Francisella tularensis subsp. holarctica strain infection. Methods Rodents were evaluated for differences in the total antioxidant capacity derived from low-molecular-weight antioxidants, biochemistry including lipid metabolism, tissue bacterial burdens and histopathology following experimental intraperitoneal infection with 160 colony forming units (CFU pro toto. Results Bacterial burdens in common voles started to develop later post-exposure and amounted to lower levels than in BALB/c mice. Elevation of liver function enzymes was more pronounced in mice than common voles and there were marked differences in lipid metabolism in the course of tularemia in these two species. Hypertriglyceridemia and hypercholesterolemia developed in mice, while physiologically higher levels of triglycerides and cholesterol showed a decreasing tendency in common voles. On the other hand, the total plasma antioxidant capacity gradually dropped to 81.5% in mice on day 5 post-infection, while it increased to 130% on day 6 post-infection in common voles. Significant correlations between tissue bacterial burdens and several biochemical parameters were found. Conclusion As differences in lipid metabolism and the total antioxidant capacity of highly susceptible rodent species were demonstrated, the role of triglycerides, cholesterol and antioxidants in tularemic sepsis should be further investigated.

Individual Differences in Behavioural Reaction to a Changing Environment in Mice and Rats

NARCIS (Netherlands)

Benus, R.F.; Koolhaas, J.M.; Oortmerssen, G.A. van

1987-01-01

Aggressive and non-aggressive male mice differ in their reaction to a changing social environment. In order to investigate if this differentiation holds also for non-social situations male mice are trained in a standard maze task, whereafter a change (extramaze and intramaze, respectively) is

p21{sup WAF1/Cip1/Sdi1} knockout mice respond to doxorubicin with reduced cardiotoxicity

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Terrand, Jerome; Xu, Beibei; Morrissy, Steve; Dinh, Thai Nho [Department of Pharmacology,College of Medicine, University of Arizona, 1501 N. Campbell Ave, Tucson, AZ 85724 (United States); Williams, Stuart [Biomedical Engineering Program, College of Medicine, University of Arizona, 1501 N. Campbell Ave, Tucson, AZ 85724 (United States); Chen, Qin M., E-mail: qchen@email.arizona.edu [Department of Pharmacology,College of Medicine, University of Arizona, 1501 N. Campbell Ave, Tucson, AZ 85724 (United States)

2011-11-15

Doxorubicin (Dox) is an antineoplastic agent that can cause cardiomyopathy in humans and experimental animals. As an inducer of reactive oxygen species and a DNA damaging agent, Dox causes elevated expression of p21{sup WAF1/Cip1/Sdi1} (p21) gene. Elevated levels of p21 mRNA and p21 protein have been detected in the myocardium of mice following Dox treatment. With chronic treatment of Dox, wild type (WT) animals develop cardiomyopathy evidenced by elongated nuclei, mitochondrial swelling, myofilamental disarray, reduced cardiac output, reduced ejection fraction, reduced left ventricular contractility, and elevated expression of ANF gene. In contrast, p21 knockout (p21KO) mice did not show significant changes in the same parameters in response to Dox treatment. In an effort to understand the mechanism of the resistance against Dox induced cardiomyopathy, we measured levels of antioxidant enzymes and found that p21KO mice did not contain elevated basal or inducible levels of glutathione peroxidase and catalase. Measurements of 6 circulating cytokines indicated elevation of IL-6, IL-12, IFN{gamma} and TNF{alpha} in Dox treated WT mice but not p21KO mice. Dox induced elevation of IL-6 mRNA was detected in the myocardium of WT mice but not p21KO mice. While the mechanism of the resistance against Dox induced cardiomyopathy remains unclear, lack of inflammatory response may contribute to the observed cardiac protection in p21KO mice. -- Highlights: Black-Right-Pointing-Pointer Doxorubicin induces p21 elevation in the myocardium. Black-Right-Pointing-Pointer Doxorubicin causes dilated cardiomyopathy in wild type mice. Black-Right-Pointing-Pointer p21 Knockout mice are resistant against doxorubicin induced cardiomyopathy. Black-Right-Pointing-Pointer Lack of inflammatory response correlates with the resistance in p21 knockout mice.

Selective reward deficit in mice lacking beta-endorphin and enkephalin.

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Hayward, Michael D; Pintar, John E; Low, Malcolm J

2002-09-15

It has been impossible to unequivocally identify which endogenous opioids modulate the incentive value of rewarding stimuli because these peptides are not highly selective for any single opioid receptor subtype. Here, we present evidence based on the measurement of instrumental behavior of beta-endorphin and enkephalin knock-out mice that both opioid peptides play a positive role. A progressive ratio schedule was used to measure how hard an animal would work for food reinforcers. The loss of either opioid reduced responding under this schedule, regardless of the palatability of the three different formulas of reinforcers used. The phenotype of mice lacking both endogenous opioids was nearly identical to the phenotype of mice mutant for either individual opioid. Responses were tested in nondeprived and deprived feeding states but were reduced in beta-endorphin- and enkephalin-deficient mice only when they were maintained under nondeprived conditions. Other operant manipulations ruled out variables that might contribute nonspecifically to this result such as differences in acquisition, early satiation, motor performance deficit, and reduced resistance to extinction. In contrast to the effects on instrumental performance, the loss of either or both endogenous opioids did not influence preference for water flavored with sucrose or saccharin in a two-bottle free-choice drinking paradigm. We conclude that both beta-endorphin and enkephalin positively contribute to the incentive-motivation to acquire food reinforcers. Because the attenuation of operant responding was observed only during a nondeprived motivational state, the hedonics of feeding are likely altered rather than energy homeostasis.

Immune cells from SR/CR mice induce the regression of established tumors in BALB/c and C57BL/6 mice

DEFF Research Database (Denmark)

Koch, Janne; Hau, Jann; Pravsgaard Christensen, Jan

2013-01-01

of resistance to EL-4 lymphoma cells and J774A.1 monocyte-macrophage cancer cells. The cancer resistance against S180 sarcoma cells could be transferred to susceptible non-resistant BALB/c mice as well as C57BL/6 mice after depletion of both CD4+/CD8+ leukocytes and B-cells from SR/CR mice. In the responding...

No impact of repeated extinction exposures on operant responding maintained by different reinforcer rates.

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Bai, John Y H; Podlesnik, Christopher A

2017-05-01

Greater rates of intermittent reinforcement in the presence of discriminative stimuli generally produce greater resistance to extinction, consistent with predictions of behavioral momentum theory. Other studies reveal more rapid extinction with higher rates of reinforcers - the partial reinforcement extinction effect. Further, repeated extinction often produces more rapid decreases in operant responding due to learning a discrimination between training and extinction contingencies. The present study examined extinction repeatedly with training with different rates of intermittent reinforcement in a multiple schedule. We assessed whether repeated extinction would reverse the pattern of greater resistance to extinction with greater reinforcer rates. Counter to this prediction, resistance to extinction was consistently greater across twelve assessments of training followed by six successive sessions of extinction. Moreover, patterns of responding during extinction resembled those observed during satiation tests, which should not alter discrimination processes with repeated testing. These findings join others suggesting operant responding in extinction can be durable across repeated tests. Copyright © 2017 Elsevier B.V. All rights reserved.

Further characterization of benzodiazepine receptor differences in long-sleep and short-sleep mice

International Nuclear Information System (INIS)

Marley, R.J.; Stinchcomb, A.; Wehner, J.M.

1988-01-01

Molecular and conformational characteristics of benzodiazepine (BZ) receptors in cortex and cerebellum from long-sleep and mice were investigated using heat inactivation and beta-carboline competition techniques. To investigate differences in the allosteric coupling between GABA and BZ receptors, the protection of BZ receptors from heat inactivation, by GABA, was also evaluated. The two genotypes do not differ in the affinity or number of BZ receptors in the cortex or cerebellum. They do, however, appear to differ in the molecular structure and/or regulation of the conformational state of the receptor in the cortex, as indicated by a greater sensitivity of LS mice to both heat inactivation and beta-carboline competition of 3 H-flunitrazepam (FNZ) binding in this region. Evidence for differences in the nature of coupling between GABA and BZ receptors is provided by the finding in that in both regions, GABA protected BZ receptors from inactivation to a greater degree in LS mice. The relationship between these differences and the multiplicity of expression of BZ receptors is discussed

Papain-induced experimental pulmonary emphysema in male and female mice.

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Machado, Mariana Nascimento; Figueirôa, Silviane Fernandes da Silva; Mazzoli-Rocha, Flavia; Valença, Samuel dos Santos; Zin, Walter Araújo

2014-08-15

In papain-induced models of emphysema, despite the existing extensive description of the cellular and molecular aspects therein involved, sexual hormones may play a complex and still not fully understood role. Hence, we aimed at exploring the putative gender-related differences in lung mechanics, histology and oxidative stress in papain-exposed mice. Thirty adult BALB/c mice received intratracheally either saline (50 μL) or papain (10 U/50 μL saline) once a week for 2 weeks. In males papain increased lung resistive and viscoelastic/inhomogeneous pressures, static elastance, and viscoelastic component of elastance, while females showed higher static elastance and resistive pressure only. Both genders presented similar higher parenchymal cellularity and mean alveolar diameter, and less collagen-elastic fiber content and body weight gain than their respective controls. Increased functional residual capacity was more prominent in males. Female papain-treated mice were more susceptible to oxidative stress. Thus, male and female papain-exposed mice respond differently, which should be carefully considered to avoid confounding results. Copyright © 2014 Elsevier B.V. All rights reserved.

Racial and Social Class Differences in How Parents Respond to Inadequate Achievement: Consequences for Children's Future Achievement.

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Robinson, Keith; Harris, Angel L

2013-12-01

Despite numerous studies on parental involvement in children's academic schooling, there is a dearth of knowledge on how parents respond specifically to inadequate academic performance. This study examines whether 1) racial differences exist in parenting philosophy for addressing inadequate achievement, 2) social class has implications for parenting philosophy, and 3) parents' philosophies are consequential for children's academic achievement. Using data from the Child Development Supplement (N=1041) to the Panel Study of Income Dynamics, we sort parents into two categories-those whose parenting repertoires for addressing poor achievement include punitive responses and those whose repertoires do not. We then determine whether racial differences exist between these categories and how various responses within the aforementioned categories are related to students' academic achievement. The findings show that white and black parents have markedly different philosophies on how to respond to inadequate performance, and these differences appear to impact children's achievement in dramatically different ways. Educators and policy makers should pay particular attention to how parents respond to inadequate achievement as imploring parents of inadequately performing students to be more involved without providing them with some guidance might exacerbate the problem.

Extinction and reinstatement of an operant responding maintained by food in different models of obesity.

Science.gov (United States)

Burokas, Aurelijus; Martín-García, Elena; Espinosa-Carrasco, Jose; Erb, Ionas; McDonald, Jerome; Notredame, Cedric; Dierssen, Mara; Maldonado, Rafael

2018-03-01

A major problem in treating obesity is the high rate of relapse to abnormal food-taking habits after maintaining an energy balanced diet. Alterations of eating behavior such as compulsive-like behavior and lack of self-control over food intake play a critical role in relapse. In this study, we used an operant paradigm of food-seeking behavior on two different diet-induced obesity models, a free-choice chocolate-mixture diet and a high-fat diet with face validity for a rapid development of obesity or for unhealthy food regularly consumed in our societies. A reduced operant performance and motivation for the hedonic value of palatable chocolate pellets was revealed in both obesity mouse models. However, only mice exposed to high-fat diet showed an increased compulsive-like behavior in the absence of the reinforcer further characterized by impaired operant learning, enhanced impulsivity and intensified inflexibility. We used principal component analysis to globally identify the specific behaviors responsible for the differences among diet groups. Learning impairment and inflexible behaviors contributed to a first principal component, explaining the largest proportion of the variance in the high-fat diet mice phenotype. Reinforcement, impulsion and compulsion were the main contributors to the second principal component explaining the differences in the chocolate-mixture mice behavioral phenotype. These behaviors were not exclusive of chocolate group because some high-fat individuals showed similar values on this component. These data indicate that extended access to hypercaloric diets differentially modifies operant behavior learning, behavioral flexibility, impulsive-like and compulsive-like behavior, and these effects were dependent on the exposure to each specific diet. © 2017 Society for the Study of Addiction.

Sickle Mice Are Sensitive to Hypoxia/Ischemia-Induced Stroke but Respond to Tissue-Type Plasminogen Activator Treatment.

Science.gov (United States)

Sun, Yu-Yo; Lee, Jolly; Huang, Henry; Wagner, Mary B; Joiner, Clinton H; Archer, David R; Kuan, Chia-Yi

2017-12-01

The effects of lytic stroke therapy in patients with sickle cell anemia are unknown, although a recent study suggested that coexistent sickle cell anemia does not increase the risk of cerebral hemorrhage. This finding calls for systemic analysis of the effects of thrombolytic stroke therapy, first in humanized sickle mice, and then in patients. There is also a need for additional predictive markers of sickle cell anemia-associated vasculopathy. We used Doppler ultrasound to examine the carotid artery of Townes sickle mice tested their responses to repetitive mild hypoxia-ischemia- and transient hypoxia-ischemia-induced stroke at 3 or 6 months of age, respectively. We also examined the effects of tPA (tissue-type plasminogen activator) treatment in transient hypoxia-ischemia-injured sickle mice. Three-month-old sickle cell (SS) mice showed elevated resistive index in the carotid artery and higher sensitivity to repetitive mild hypoxia-ischemia-induced cerebral infarct. Six-month-old SS mice showed greater resistive index and increased flow velocity without obstructive vasculopathy in the carotid artery. Instead, the cerebral vascular wall in SS mice showed ectopic expression of PAI-1 (plasminogen activator inhibitor-1) and P-selectin, suggesting a proadhesive and prothrombotic propensity. Indeed, SS mice showed enhanced leukocyte and platelet adherence to the cerebral vascular wall, broader fibrin deposition, and higher mortality after transient hypoxia-ischemia. Yet, post-transient hypoxia-ischemia treatment with tPA reduced thrombosis and mortality in SS mice. Sickle mice are sensitive to hypoxia/ischemia-induced cerebral infarct but benefit from thrombolytic treatment. An increased resistive index in carotid arteries may be an early marker of sickle cell vasculopathy. © 2017 American Heart Association, Inc.

Assessment of side effects induced by injection of different adjuvant/antigen combinations in rabbits and mice

NARCIS (Netherlands)

Leenaars, P.P.A.M.; Koedam, M.A.; Wester, P.W.; Baumans, V.; Claassen, E.; Hendriksen, C.F.M.

1998-01-01

We evaluated the side effects induced by injection of Freund's adjuvant (FA) and alternative adjuvants combined with different antigens. Rabbits and mice were injected subcutaneously, intramuscularly (rabbits) and intraperitoneally (mice) with different adjuvants (FA, Specol, RIBI, TiterMax,

Gender differences in cocaine pharmacokinetics in CF-1 mice.

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Visalli, Thomas; Turkall, Rita; Abdel-Rahman, Mohamed S

2005-01-15

Hepatocellular damage is thought to occur as a result of cytochrome P450-mediated oxidation of cocaine to norcocaine (NC), a precursor of the hepatotoxic nitrosonium ion. However, this damage occurs only in male mice, with females exhibiting minimal biochemical and histological signs of hepatocellular stress. The objective of this study was to determine the plasma time course and tissue disposition of cocaine and its metabolites to further investigate the role that metabolism may play in the gender difference observed. Male and female CF-1 mice were orally administered 20mg/kg cocaine hydrochloride once daily for 7 days. Blood samples were withdrawn at various time points post-injection and analyzed for cocaine and its metabolites benzoylecgonine (BE), norcocaine, ecgonine methyl ester (EME), and ecgonine (E). In addition, tissue concentrations of cocaine and its metabolites were determined in liver, heart, brain, and kidney tissue. The results demonstrated that the plasma elimination half-life of cocaine is nearly three times longer in males versus females. Non-hepatotoxic hydrolysis metabolites BE, EME, and E were higher in female tissues while norcocaine was detected in tissues of male animals only. This study revealed that differences in cocaine pharmacokinetics and the resultant differences in the biodisposition of cocaine and its metabolites in tissues contribute to the mechanism of gender difference seen in cocaine hepatotoxicity.

Inherent and antigen-induced airway hyperreactivity in NC mice

OpenAIRE

Tetsuto Kobayashi; Toru Miura; Tomoko Haba; Miyuki Sato; Masao Takei; Isao Serizawa

1999-01-01

In order to clarify the airway physiology of NC mice, the following experiments were carried out. To investigate inherent airway reactivity, we compared tracheal reactivity to various chemical mediators in NC, BALB/c, C57BL/6 and A/J mice in vitro. NC mice showed significantly greater reactivity to acetylcholine than BALB/c and C57BL/6 mice and a reactivity comparable to that of A/J mice, which are known as high responders. Then, airway reactivity to acetylcholine was investigated in those st...

The distribution of 14C-chitosan by different molecular weight in mice

International Nuclear Information System (INIS)

Kim, Kwang Yoon; Kim, Young Ho; Bom, Hee Seung; Kim, Ji Yeul; Kim, Hee Kyung; Roh, Young Bok; Nishimura, Yoshikazu

1998-01-01

Chitosan is a nontoxic natural chealtor which was made by chitin, and reduced a contamination of radiostrontium in animals. In this experiment, a different molecular weight of C-14 chitosan was intravenously administered to mice, and then the distribution of C-14 chitosan in the body was observed. Male mice (8 to 10 weeks, body weight of 30 to 35g) of ICR strain were used. C-14 chitosan, mice was sacrificed at the 6th hour, 1st, 3rd, 5th, and 7th day. Beta radioactivities in the blood, liver, kidney, liver, muscle, testis, and urine was measured using a liquid scintillation analyzer. Most of the C-14 chitosan was excreted through urine within 6 hours. Biodistribution of C-14 chitosan was similar despite the difference of molecular weight. Higher distributions of radioactivities were found in the liver, kidney, spleen. The relative concentration in tissue increased for the 6 hours and then decreased. In conclusion, most of C-14 chitosan was excreted through urine despite the difference of molecular weight. and, low molecular weight of C-14 chitosan showed higher distribution than high molecular weight of C-14 chitosan in tissues

The Effect of Different Photoperiods in Circadian Rhythms of Per3 Knockout Mice

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D. S. Pereira

2014-01-01

Full Text Available The aim of this study was to analyse the circadian behavioural responses of mice carrying a functional knockout of the Per3 gene (Per3−/− to different light : dark (L : D cycles. Male adult wild-type (WT and Per3−/− mice were kept under 12-hour light : 12-hour dark conditions (12L : 12D and then transferred to either a short or long photoperiod and subsequently released into total darkness. All mice were exposed to both conditions, and behavioural activity data were acquired through running wheel activity and analysed for circadian characteristics during these conditions. We observed that, during the transition from 12L : 12D to 16L : 8D, Per3−/− mice take approximately one additional day to synchronise to the new L : D cycle compared to WT mice. Under these long photoperiod conditions, Per3−/− mice were more active in the light phase. Our results suggest that Per3−/− mice are less sensitive to light. The data presented here provides further evidence that Per3 is involved in the suppression of behavioural activity in direct response to light.

CD4+ T regulatory cells from the colonic lamina propria of normal mice inhibit proliferation of enterobacteria-reactive, disease-inducing Th1-cells from scid mice with colitis

DEFF Research Database (Denmark)

Gad, M; Brimnes, J; Claesson, Mogens Helweg

2003-01-01

Adoptive transfer of CD4+ T cells into scid mice leads to a chronic colitis in the recipients. The transferred CD4+ T cells accumulate in the intestinal lamina propria (LP), express an activated Th1 phenotype and proliferate vigorously when exposed ex vivo to enteric bacterial antigens. As LP CD4......+ T cells from normal BALB/c mice do not respond to enteric bacterial antigens, we have investigated whether colonic LP-derived CD4+ T cells from normal mice suppress the antibacterial response of CD4+ T cells from scid mice with colitis. LP-derived CD4+ T cells cocultured with bone marrow......-derived dendritic cells effectively suppress the antibacterial proliferative response of CD4+ T cells from scid mice with colitis. The majority of these LP T-reg cells display a nonactivated phenotype and suppression is independent of antigen exposure, is partly mediated by soluble factor(s) different from IL-10...

Female preproenkephalin-knockout mice display altered emotional responses

Science.gov (United States)

Ragnauth, A.; Schuller, A.; Morgan, M.; Chan, J.; Ogawa, S.; Pintar, J.; Bodnar, R. J.; Pfaff, D. W.

2001-01-01

The endogenous opioid system has been implicated in sexual behavior, palatable intake, fear, and anxiety. The present study examined whether ovariectomized female transgenic preproenkephalin-knockout (PPEKO) mice and their wild-type and heterozygous controls displayed alterations in fear and anxiety paradigms, sucrose intake, and lordotic behavior. To examine stability of responding, three squads of the genotypes were tested across seasons over a 20-month period. In a fear-conditioning paradigm, PPEKO mice significantly increased freezing to both fear and fear + shock stimuli relative to controls. In the open field, PPEKO mice spent significantly less time and traversed significantly less distance in the center of an open field than wild-type controls. Further, PPEKO mice spent significantly less time and tended to be less active on the light side of a dark–light chamber than controls, indicating that deletion of the enkephalin gene resulted in exaggerated responses to fear or anxiety-provoking environments. These selective deficits were observed consistently across testing squads spanning 20 months and different seasons. In contrast, PPEKO mice failed to differ from corresponding controls in sucrose, chow, or water intake across a range (0.0001–20%) of sucrose concentrations and failed to differ in either lordotic or female approach to male behaviors when primed with estradiol and progesterone, thereby arguing strongly for the selectivity of a fear and anxiety deficit which was not caused by generalized and nonspecific debilitation. These transgenic data strongly suggest that opioids, and particularly enkephalin gene products, are acting naturally to inhibit fear and anxiety. PMID:11172058

Myg1-deficient mice display alterations in stress-induced responses and reduction of sex-dependent behavioural differences.

Science.gov (United States)

Philips, Mari-Anne; Abramov, Urho; Lilleväli, Kersti; Luuk, Hendrik; Kurrikoff, Kaido; Raud, Sirli; Plaas, Mario; Innos, Jürgen; Puussaar, Triinu; Kõks, Sulev; Vasar, Eero

2010-02-11

Myg1 (Melanocyte proliferating gene 1) is a highly conserved and ubiquitously expressed gene, which encodes a protein with mitochondrial and nuclear localization. In the current study we demonstrate a gradual decline of Myg1 expression during the postnatal development of the mouse brain that suggests relevance for Myg1 in developmental processes. To study the effects of Myg1 loss-of-function, we created Myg1-deficient (-/-) mice by displacing the entire coding sequence of the gene. Initial phenotyping, covering a multitude of behavioural, cognitive, neurological, physiological and stress-related responses, revealed that homozygous Myg1 (-/-) mice are vital, fertile and display no gross abnormalities. Myg1 (-/-) mice showed an inconsistent pattern of altered anxiety-like behaviour in different tests. The plus-maze and social interaction tests revealed that male Myg1 (-/-) mice were significantly less anxious than their wild-type littermates; female (-/-) mice showed increased anxiety in the locomotor activity arena. Restraint-stress significantly reduced the expression of the Myg1 gene in the prefrontal cortex of female wild-type mice and restrained female (-/-) mice showed a blunted corticosterone response, suggesting involvement of Myg1 in stress-induced responses. The main finding of the present study was that Myg1 invalidation decreases several behavioural differences between male and female animals that were obvious in wild-type mice, indicating that Myg1 contributes to the expression of sex-dependent behavioural differences in mice. Taken together, we provide evidence for the involvement of Myg1 in anxiety- and stress-related responses and suggest that Myg1 contributes to the expression of sex-dependent behavioural differences.

Pregabalin and placebo responders show different effects on central pain processing in chronic pancreatitis patients

NARCIS (Netherlands)

Bouwense, S.A.; Olesen, S.S.; Drewes, A.M.; Goor, H. van; Wilder-Smith, O.H.G.

2015-01-01

BACKGROUND: Pain control in chronic pancreatitis is a major challenge; the mechanisms behind analgesic treatment are poorly understood. This study aims to investigate the differences in pain sensitivity and modulation in chronic pancreatitis patients, based on their clinical response (responders vs

Cell kinetics of Ehrlich ascites carcinoma transplanted in mice with different degrees of tumor resistance

International Nuclear Information System (INIS)

Brandt, K.L.B.

1974-01-01

Cell proliferation kinetics of Ehrlich ascites carcinoma grown in two strains of mice with different degrees of resistance to this tumor were examined. In the first portion of the study, growth of Ehrlich ascites carcinoma in nonresistant Swiss (Iowa) and slightly resistant CF1 mice was examined by measuring animal weight gain and host survival time after intraperitoneal injection of tumor cells. Since it appeared that CF1 mice were inherently more resistant than Swiss mice to the Ehrlich carcinoma, the second part of this investigation involved attempts to immunize CF1 mice against the tumor. Subcutaneous injections of Ehrlich cells previously exposed in vitro to 5000 R of 250 kVp x rays were utilized. One immunizing inoculation of lethally irradiated tumor cells afforded protection against an intraperitoneal challenge of 40 thousand Ehrlich cells. By varying the number and timing of immunizing inoculations it was possible to induce different degrees of tumor resistance in these mice. The most effective immunizing procedure utilized multiple inoculations of lethally irradiated tumor cells (LITC), followed by challenges with viable tumor cells (less than 1 million) which were rejected. These mice could then resist challenge inocula of 4 million viable tumor cells. In a few animals the immunizing procedures were ineffective; these animals, when challenged, developed even larger tumors than control mice. Tumor cell proliferation kinetics in these animals as well as in mice that were rejecting the tumor were examined in the third phase of the project. A shortening of the cell cycle was observed in almost all LITC-treated mice, whether tumor growth was eventually inhibited or stimulated. Decreased duration of the DNA-synthesis phase (S) of the tumor cell cycle was also a consistent finding. The role of the immune response in stimulating mitosis as well as in killing foreign cells was discussed. (U.S.)

Differential cellular responses in healthy mice and in mice with established airway inflammation when exposed to hematite nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Gustafsson, Åsa, E-mail: asa.gustafsson@foi.se [Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå (Sweden); Dept of Public Health and Clinical Medicine, Umeå University (Sweden); Bergström, Ulrika [Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå (Sweden); Dept of Organismal Biology, Uppsala University, SE-751 Uppsala (Sweden); Ågren, Lina [Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå (Sweden); Österlund, Lars [Dept of Engineering Sciences, The Ångström Laboratory, Uppsala University, SE-751 Uppsala (Sweden); Sandström, Thomas [Dept of Public Health and Clinical Medicine, Umeå University (Sweden); Bucht, Anders [Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå (Sweden); Dept of Public Health and Clinical Medicine, Umeå University (Sweden)

2015-10-01

The aim of this study was to investigate the inflammatory and immunological responses in airways and lung-draining lymph nodes (LDLNs), following lung exposure to iron oxide (hematite) nanoparticles (NPs). The responses to the hematite NPs were evaluated in both healthy non-sensitized mice, and in sensitized mice with an established allergic airway disease. The mice were exposed intratracheally to either hematite NPs or to vehicle (PBS) and the cellular responses were evaluated on days 1, 2, and 7, post-exposure. Exposure to hematite NPs increased the numbers of neutrophils, eosinophils, and lymphocytes in the airways of non-sensitized mice on days 1 and 2 post-exposure; at these time points the number of lymphocytes was also elevated in the LDLNs. In contrast, exposing sensitized mice to hematite NPs induced a rapid and unspecific cellular reduction in the alveolar space on day 1 post-exposure; a similar decrease of lymphocytes was also observed in the LDLN. The results indicate that cells in the airways and in the LDLN of individuals with established airway inflammation undergo cell death when exposed to hematite NPs. A possible explanation for this toxic response is the extensive generation of reactive oxygen species (ROS) in the pro-oxidative environment of inflamed airways. This study demonstrates how sensitized and non-sensitized mice respond differently to hematite NP exposure, and it highlights the importance of including individuals with respiratory disorders when evaluating health effects of inhaled nanomaterials. - Highlights: • Hematite NPs induce differential responses in airways of healthy and allergic mice. • Hematite induced an airway inflammation in healthy mice. • Hematite induced cellular reduction in the alveolus and lymph nodes of allergic mice. • Cell death is possible due to extensive pro-oxidative environment in allergic mice. • It is important to include sensitive individuals when valuing health effects of NPs.

Pregabalin and placebo responders show different effects on central pain processing in chronic pancreatitis patients

Directory of Open Access Journals (Sweden)

Bouwense SA

2015-07-01

Full Text Available Stefan AW Bouwense,1 Søren S Olesen,2 Asbjørn M Drewes,2 Harry van Goor,1 Oliver HG Wilder-Smith31Pain and Nociception Neuroscience Research Group, Department of Surgery, Radboud university medical center, Nijmegen, The Netherlands; 2Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark; 3Pain and Nociception Neuroscience Research Group, Department of Anaesthesiology, Pain and Palliative Medicine, Radboud university medical center, Nijmegen, The NetherlandsBackground: Pain control in chronic pancreatitis is a major challenge; the mechanisms behind analgesic treatment are poorly understood. This study aims to investigate the differences in pain sensitivity and modulation in chronic pancreatitis patients, based on their clinical response (responders vs nonresponders to placebo or pregabalin treatment. Methods: This study was part of a randomized, double-blind, placebo-controlled trial evaluating the analgesic effects of pregabalin and placebo in chronic pancreatitis. Post hoc, patients were assigned to one of four groups, ie, responders and nonresponders to pregabalin (n=16; n=15 or placebo (n=12; n=17 treatment. Responders were defined as patients with >30% pain reduction after 3 weeks of treatment. We measured change in pain sensitivity before and after the treatment using electric pain detection thresholds (ePDT in dermatomes C5 (generalized effects and Ventral T10 (segmental effects. Descending endogenous pain modulation was quantified via conditioned pain modulation (CPM paradigm. Results: Sixty patients were analyzed in a per-protocol analysis. ePDT change in C5 was significant vs baseline and greater in pregabalin (1.3 mA vs placebo responders (−0.1 mA; P=0.015. This was not so for ePDT in Ventral T10. CPM increased more in pregabalin (9% vs placebo responders (−17%; P<0.001. CPM changed significantly vs baseline only for pregabalin responders (P=0.006. Conclusion: This hypothesis

Female mice respond differently to costly foraging versus food restriction

NARCIS (Netherlands)

Schubert, Kristin A.; Vaanholt, Lobke M.; Stavasius, Fanny; Demas, Gregory E.; Daan, Serge; Visser, G. Henk

2008-01-01

Experimental manipulation of foraging costs per food reward can be used to study the plasticity of physiological systems involved in energy metabolism. This approach is useful for understanding adaptations to natural variation in food availability. Earlier studies have shown that animals foraging on

Fearing shades of grey: individual differences in fear responding towards generalisation stimuli.

Science.gov (United States)

Arnaudova, Inna; Krypotos, Angelos-Miltiadis; Effting, Marieke; Kindt, Merel; Beckers, Tom

2017-09-01

Individual differences in fear generalisation have been proposed to play a role in the aetiology and/or maintenance of anxiety disorders, but few data are available to directly support that claim. The research that is available has focused mostly on generalisation of peripheral and central physiological fear responses. Far less is known about the generalisation of avoidance, the behavioural component of fear. In two experiments, we evaluated how neuroticism, a known vulnerability factor for anxiety, modulates an array of fear responses, including avoidance tendencies, towards generalisation stimuli (GS). Participants underwent differential fear conditioning, in which one conditioned stimulus (CS+) was repeatedly paired with an aversive outcome (shock; unconditioned stimulus, US), whereas another was not (CS-). Fear generalisation was observed across measures in Experiment 1 (US expectancy and evaluative ratings) and Experiment 2 (US expectancy, evaluative ratings, skin conductance, startle responses, safety behaviours), with overall highest responding to the CS+, lowest to the CS- and intermediate responding to the GSs. Neuroticism had very little impact on fear generalisation (but did affect GS recognition rates in Experiment 1), in line with the idea that fear generalisation is largely an adaptive process.

Regulation of IgE antibody production by serum molecules. II. Strain-specificity of the suppressive activity of serum from complete Freund's adjuvant-immune low responder mouse donors

International Nuclear Information System (INIS)

Katz, D.H.; Tung, A.S.

1978-01-01

IgE antibody production in mice of high and low IgE responder phenotypes, respectively, can be appreciably enhanced in magnitude after low-dose whole-body x irradiation. Such enhanced responses, as well as adoptive secondary IgE responses, can be markedly suppressed by passive transfer of CFA-immune serum in low responder strains, but not in high responder strains. The studies presented here demonstrate that the suppressive activity of CFA-immune serum on IgE antibody production is strain specific. This is true even in reciprocal combinations of low IgE responder SJL and C57BL/6 mice, in which it was shown that serum capable of suppressing mice of the isologous strain was ineffective in diminishing IgE antibody production in the other low responder strain. Absence of suppressive activity in CFA-immune sera obtained from H-2 haplotypes while sharing many similarities in the background genome and, conversely, effective suppressive activity of H-2 congenic donor sera when H-2-identities between donor and recipient mice existed, strongly suggested a role, at least in part, of H-2 genes in dictating the strain specificity of such suppressive activity. Additional experiments provided evidence for a possible role of macrophages in catabolism of the active molecules in CFA-immune sera. These observations, together with those presented in the preceding paper, may provide valuable insight toward successful development of appropriate manipulations that could ultimately convert high IgE responder individuals into low responders

Congenital muscle dystrophy and diet consistency affect mouse skull shape differently.

Science.gov (United States)

Spassov, Alexander; Toro-Ibacache, Viviana; Krautwald, Mirjam; Brinkmeier, Heinrich; Kupczik, Kornelius

2017-11-01

The bones of the mammalian skull respond plastically to changes in masticatory function. However, the extent to which muscle function affects the growth and development of the skull, whose regions have different maturity patterns, remains unclear. Using muscle dissection and 3D landmark-based geometric morphometrics we investigated the effect of changes in muscle function established either before or after weaning, on skull shape and muscle mass in adult mice. We compared temporalis and masseter mass and skull shape in mice with a congenital muscle dystrophy (mdx) and wild type (wt) mice fed on either a hard or a soft diet. We found that dystrophy and diet have distinct effects on the morphology of the skull and the masticatory muscles. Mdx mice show a flattened neurocranium with a more dorsally displaced foramen magnum and an anteriorly placed mandibular condyle compared with wt mice. Compared with hard diet mice, soft diet mice had lower masseter mass and a face with more gracile features as well as labially inclined incisors, suggesting reduced bite strength. Thus, while the early-maturing neurocranium and the posterior portion of the mandible are affected by the congenital dystrophy, the late-maturing face including the anterior part of the mandible responds to dietary differences irrespective of the mdx mutation. Our study confirms a hierarchical, tripartite organisation of the skull (comprising neurocranium, face and mandible) with a modular division based on development and function. Moreover, we provide further experimental evidence that masticatory loading is one of the main environmental stimuli that generate craniofacial variation. © 2017 Anatomical Society.

Gender differences in cerebral metabolism for color processing in mice: A PET/MRI Study.

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Njemanze, Philip C; Kranz, Mathias; Amend, Mario; Hauser, Jens; Wehrl, Hans; Brust, Peter

2017-01-01

Color processing is a central component of mammalian vision. Gender-related differences of color processing revealed by non-invasive functional transcranial Doppler ultrasound suggested right hemisphere pattern for blue/yellow chromatic opponency by men, and a left hemisphere pattern by women. The present study measured the accumulation of [18F]fluorodeoxyglucose ([18F]FDG) in mouse brain using small animal positron emission tomography and magnetic resonance imaging (PET/MRI) with statistical parametric mapping (SPM) during light stimulation with blue and yellow filters compared to darkness condition. PET revealed a reverse pattern relative to dark condition compared to previous human studies: Male mice presented with left visual cortex dominance for blue through the right eye, while female mice presented with right visual cortex dominance for blue through the left eye. We applied statistical parametric mapping (SPM) to examine gender differences in activated architectonic areas within the orbital and medial prefrontal cortex and related cortical and sub-cortical areas that lead to the striatum, medial thalamus and other brain areas. The metabolic connectivity of the orbital and medial prefrontal cortex evoked by blue stimulation spread through a wide range of brain structures implicated in viscerosensory and visceromotor systems in the left intra-hemispheric regions in male, but in the right-to-left inter-hemispheric regions in female mice. Color functional ocular dominance plasticity was noted in the right eye in male mice but in the left eye in female mice. This study of color processing in an animal model could be applied in the study of the role of gender differences in brain disease.

Fructose- and glucose-conditioned preferences in FVB mice: strain differences in post-oral sugar appetition

Science.gov (United States)

Zukerman, Steven; Ackroff, Karen

2014-01-01

Recent studies indicate that, unlike glucose, fructose has little or no post-oral preference conditioning actions in C57BL/6J (B6) mice. The present study determined whether this is also the case for FVB mice, which overconsume fructose relative to B6 mice. In experiment 1, FVB mice strongly preferred a noncaloric 0.1% sucralose + 0.1% saccharin (S+S) solution to 8% fructose in a 2-day choice test but switched their preference to fructose after separate experience with the two sweeteners. Other FVB mice displayed a stronger preference for 8% glucose over S+S. In a second experiment, ad libitum-fed FVB mice trained 24 h/day acquired a significant preference for a flavor (CS+) paired with intragastric (IG) self-infusions of 16% fructose over a different flavor (CS−) paired with IG water infusions. IG fructose infusions also conditioned flavor preferences in food-restricted FVB mice trained 1 h/day. IG infusions of 16% glucose conditioned stronger preferences in FVB mice trained 24- or 1 h/day. Thus, fructose has post-oral flavor conditioning effects in FVB mice, but these effects are less pronounced than those produced by glucose. Further studies of the differential post-oral conditioning effects of fructose and glucose in B6 and FVB mice should enhance our understanding of the physiological processes involved in sugar reward. PMID:25320345

Sex differences in the acute locomotor response to methamphetamine in BALB/c mice.

Science.gov (United States)

Ohia-Nwoko, Odochi; Haile, Colin N; Kosten, Therese A

2017-06-01

Women use methamphetamine more frequently than men and are more vulnerable to its negative psychological effects. Rodent models have been an essential tool for evaluating the sex-dependent effects of psychostimulants; however, evidence of sex differences in the behavioral responses to methamphetamine in mice is lacking. In the present study, we investigated acute methamphetamine-induced (1mg/kg and 4mg/kg) locomotor activation in female and male BALB/c mice. We also evaluated whether basal locomotor activity was associated with the methamphetamine-induced locomotor response. The results indicated that female BALB/c mice displayed enhanced methamphetamine-induced locomotor activity compared to males, while basal locomotor activity was positively correlated with methamphetamine-induced activity in males, but not females. This study is the first to show sex-dependent locomotor effects of methamphetamine in BALB/c mice. Our observations emphasize the importance of considering sex when assessing behavioral responses to methamphetamine. Copyright © 2017 Elsevier B.V. All rights reserved.

Postnatal events in intestinal gene expression and splenic cell composition is altered in NOD mice

DEFF Research Database (Denmark)

Damlund, Dina Silke Malling; Metzdorff, Stine Broeng; Kristensen, Matilde Bylov

2013-01-01

microbiota seems to play an important role in the development and control of T1D. We hypothesized that NOD mice in the perinatal period respond differently than mice not prone to develop T1D (C57/Bl6), and we investigated the differences in postnatal expression of genes in gut, spleen, liver and pancreas......Evidence suggests that colonisation pattern of the gut in the early postnatal period is highly correlated with the risk of developing type 1 diabetes (T1D). We have recently shown that colonization in SPF mice accelerates gut maturation and that at postnatal day (PND) 1, in comparison with germ...... free mice, certain chemokines, including Cxcl2 encoding macrophage inflammatory protein (MIP)-2 and involved in attraction of neutrophils was downregulated in the gut epithelium. The non-obese diabetes (NOD) mouse is widely used as a model for studying the pathogenesis of T1D. The neonatal gut...

Reduced expression of IL-12 p35 by SJL/J macrophages responding to Theiler's virus infection is associated with constitutive activation of IRF-3

International Nuclear Information System (INIS)

Dahlberg, Angela; Auble, Mark R.; Petro, Thomas M.

2006-01-01

Macrophages responding to viral infections may contribute to autoimmune demyelinating diseases (ADD). Macrophages from ADD-susceptible SJL/J mice responding to Theiler's Virus (TMEV) infection, the TLR7 agonist loxoribine, or the TLR4 agonist-LPS expressed less IL-12 p35 but more IL-12/23 p40 and IFN-β than macrophages from ADD-resistant B10.S mice. While expression of IRF-1 and -7 was similar between B10.S and SJL/J TMEV-infected macrophages, SJL/J but not B10.S macrophages exhibited constitutively active IRF-3. In contrast to overexpressed IRF-1, IRF-5, and IRF-7, which stimulated p35 promoter reporter activity, overexpressed IRF-3 repressed p35 promoter activity in response to TMEV infection, loxoribine, IFN-γ/LPS, but not IFN-γ alone. IRF-3 lessened but did not eliminate IRF-1-stimulated p35 promoter activity. Repression by IRF-3 required bp -172 to -122 of the p35 promoter. The data suggest that pre-activated IRF-3 is a major factor in the differences in IL-12 production between B10.S and SJL/J macrophages responding to TMEV

Radiosensitivity of spermatogenous epithelium stem cells of mice of different strains and age

International Nuclear Information System (INIS)

Konoplyannikova, O.A.; Konoplyannikov, A.G.

1988-01-01

In experiments on CBA and BALB/c male mices (3 months of age) and F 1 (CBAxC57BL/6) hybrides (at the age of 3, 12, and 24 months) a difference was noted in the radiosensitivity of spermatogenous epithelium stem cells displayed by the changes in their colony-forming ability to testicular tubules 42 days following local 60 Co-γ-irradiation. The older the hybrid mice the smaller was the number of spermatogenous epithelium stem cells

PERIPHERAL SENSORY NEURONS EXPRESSING MELANOPSIN RESPOND TO LIGHT

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Anna Matynia

2016-08-01

Full Text Available The ability of light to cause pain is paradoxical. The retina detects light but is devoid of nociceptors while the trigeminal sensory ganglia (TG contain nociceptors but not photoreceptors. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs are thought to mediate light-induced pain but recent evidence raises the possibility of an alternative light responsive pathway independent of the retina and optic nerve. Here, we show that melanopsin is expressed in both human and mouse TG neurons. In mice, they represent 3% of small TG neurons that are preferentially localized in the ophthalmic branch of the trigeminal nerve and are likely nociceptive C fibers and high-threshold mechanoreceptor Aδ fibers based on a strong size-function association. These isolated neurons respond to blue light stimuli with a delayed onset and sustained firing, similar to the melanopsin-dependent intrinsic photosensitivity observed in ipRGCs. Mice with severe bilateral optic nerve crush exhibit no light-induced responses including behavioral light aversion until treated with nitroglycerin, an inducer of migraine in people and migraine-like symptoms in mice. With nitroglycerin, these same mice with optic nerve crush exhibit significant light aversion. Furthermore, this retained light aversion remains dependent on melanopsin-expressing neurons. Our results demonstrate a novel light-responsive neural function independent of the optic nerve that may originate in the peripheral nervous system to provide the first direct mechanism for an alternative light detection pathway that influences motivated behavior.

Probabilistic numerical discrimination in mice.

Science.gov (United States)

Berkay, Dilara; Çavdaroğlu, Bilgehan; Balcı, Fuat

2016-03-01

Previous studies showed that both human and non-human animals can discriminate between different quantities (i.e., time intervals, numerosities) with a limited level of precision due to their endogenous/representational uncertainty. In addition, other studies have shown that subjects can modulate their temporal categorization responses adaptively by incorporating information gathered regarding probabilistic contingencies into their time-based decisions. Despite the psychophysical similarities between the interval timing and nonverbal counting functions, the sensitivity of count-based decisions to probabilistic information remains an unanswered question. In the current study, we investigated whether exogenous probabilistic information can be integrated into numerosity-based judgments by mice. In the task employed in this study, reward was presented either after few (i.e., 10) or many (i.e., 20) lever presses, the last of which had to be emitted on the lever associated with the corresponding trial type. In order to investigate the effect of probabilistic information on performance in this task, we manipulated the relative frequency of different trial types across different experimental conditions. We evaluated the behavioral performance of the animals under models that differed in terms of their assumptions regarding the cost of responding (e.g., logarithmically increasing vs. no response cost). Our results showed for the first time that mice could adaptively modulate their count-based decisions based on the experienced probabilistic contingencies in directions predicted by optimality.

Effect of aging and radiation in mice of different genotypes

International Nuclear Information System (INIS)

Storer, J.B.

1976-01-01

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

Stressful presentations: mild cold stress in laboratory mice influences phenotype of dendritic cells in naïve and tumor-bearing mice.

Science.gov (United States)

Kokolus, Kathleen M; Spangler, Haley M; Povinelli, Benjamin J; Farren, Matthew R; Lee, Kelvin P; Repasky, Elizabeth A

2014-01-01

The ability of dendritic cells (DCs) to stimulate and regulate T cells is critical to effective anti-tumor immunity. Therefore, it is important to fully recognize any inherent factors which may influence DC function under experimental conditions, especially in laboratory mice since they are used so heavily to model immune responses. The goals of this report are to 1) briefly summarize previous work revealing how DCs respond to various forms of physiological stress and 2) to present new data highlighting the potential for chronic mild cold stress inherent to mice housed at the required standard ambient temperatures to influence baseline DCs properties in naïve and tumor-bearing mice. As recent data from our group shows that CD8(+) T cell function is significantly altered by chronic mild cold stress and since DC function is crucial for CD8(+) T cell activation, we wondered whether housing temperature may also be influencing DC function. Here we report that there are several significant phenotypical and functional differences among DC subsets in naïve and tumor-bearing mice housed at either standard housing temperature or at a thermoneutral ambient temperature, which significantly reduces the extent of cold stress. The new data presented here strongly suggests that, by itself, the housing temperature of mice can affect fundamental properties and functions of DCs. Therefore differences in basal levels of stress due to housing should be taken into consideration when interpreting experiments designed to evaluate the impact of additional variables, including other stressors on DC function.

Characterization of nasal potential difference in cftr knockout and F508del-CFTR mice.

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Emilie Lyne Saussereau

Full Text Available BACKGROUND: Treatments designed to correct cystic fibrosis transmembrane conductance regulator (CFTR defects must first be evaluated in preclinical experiments in the mouse model of cystic fibrosis (CF. Mice nasal mucosa mimics the bioelectric defect seen in humans. The use of nasal potential difference (V(TE to assess ionic transport is a powerful test evaluating the restoration of CFTR function. Nasal V(TE in CF mice must be well characterized for correct interpretation. METHODS: We performed V(TE measurements in large-scale studies of two mouse models of CF--B6;129 cftr knockout and FVB F508del-CFTR--and their respective wild-type (WT littermates. We assessed the repeatability of the test for cftr knockout mice and defined cutoff points distinguishing between WT and F508del-CFTR mice. RESULTS: We determined the typical V(TE values for CF and WT mice and demonstrated the existence of residual CFTR activity in F508del-CFTR mice. We characterized intra-animal variability in B6;129 mice and defined the cutoff points for F508del-CFTR chloride secretion rescue. Hyperpolarization of more than -2.15 mV after perfusion with a low-concentration Cl(- solution was considered to indicate a normal response. CONCLUSIONS: These data will make it possible to interpret changes in nasal V(TE in mouse models of CF, in future preclinical studies.

Mutation-related differences in exploratory, spatial and depressive-like behavior in pcd and Lurcher cerebellar mutant mice

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Jan eTuma

2015-05-01

Full Text Available The cerebellum is not only essential for motor coordination but is also involved in cognitive and affective processes. These functions of the cerebellum and mechanisms of their disorders in cerebellar injury are not completely understood. There is a wide spectrum of cerebellar mutant mice which are used as models of hereditary cerebellar degenerations. Nevertheless, they differ in pathogenesis of manifestation of the particular mutation and also in the strain background. The aim of this work was to compare spatial navigation, learning and memory in pcd and Lurcher mice, two of the most frequently used cerebellar mutants. The mice were tested in the open field for exploration behavior, in the Morris water maze with visible as well as reversal hidden platform tasks and in the forced swimming test for motivation assessment. Lurcher mice showed different space exploration activity in the open field and a lower tendency to depressive-like behavior in the forced swimming test compared with pcd mice. Severe deficit of spatial navigation was shown in both cerebellar mutants. However, the overall performance of Lurcher mice was better than that of pcd mutants. Lurcher mice showed the ability of visual guidance despite difficulties with the direct swim towards a goal. In the probe trial test, Lurcher mice preferred the visible platform rather than the more recent localization of the hidden goal.

Chronic Pelvic Pain Development and Prostate Inflammation in Strains of Mice With Different Susceptibility to Experimental Autoimmune Prostatitis.

Science.gov (United States)

Breser, Maria L; Motrich, Ruben D; Sanchez, Leonardo R; Rivero, Virginia E

2017-01-01

Experimental autoimmune prostatitis (EAP) is an autoimmune inflammatory disease of the prostate characterized by peripheral prostate-specific autoimmune responses associated with prostate inflammation. EAP is induced in rodents upon immunization with prostate antigens (PAg) plus adjuvants and shares important clinical and immunological features with the human disease chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). EAP was induced in young NOD, C57BL/6, and BALB/c male mice by immunization with PAg plus complete Freund́s adjuvant. Tactile allodynia was assessed using Von Frey fibers as a measure of pelvic pain at baseline and at different time points after immunization. Using conventional histology, immunohistochemistry, FACS analysis, and protein arrays, an interstrain comparative study of prostate cell infiltration and inflammation was performed. Chronic pelvic pain development was similar between immunized NOD and C57BL/6 mice, although the severity of leukocyte infiltration was greater in the first case. Coversely, minimal prostate cell infiltration was observed in immunized BALB/c mice, who showed no pelvic pain development. Increased numbers of mast cells, mostly degranulated, were detected in prostate samples from NOD and C57BL/6 mice, while lower total counts and resting were observed in BALB/c mice. Prostate tissue from NOD mice revealed markedly increased expression levels of inflammatory cytokines, chemokines, adhesion molecules, vascular endothelial growth factor, and metalloproteinases. Similar results, but to a lesser extent, were observed when analyzing prostate tissue from C57BL/6 mice. On the contrary, the expression of the above mediators was very low in prostate tissue from immunized BALB/c mice, showing significantly slight increments only for CXCL1 and IL4. Our results provide new evidence indicating that NOD, C57BL/6, and BALB/c mice develop different degrees of chronic pelvic pain, type, and amount of prostate cell infiltration

Rats do not respond differently in the presence of stimuli signaling wheel-running reinforcers of different durations.

Science.gov (United States)

Belke, Terry W

2007-05-01

Rats were exposed to a fixed interval 30 s schedule that produced opportunities to run of equal or unequal durations to assess the effect of differences in duration on responding. Each duration was signaled by a different stimulus. Wheel-running reinforcer duration pairs were 30 s 30 s, 50 s 10 s, and 55 s 5 s. An analysis of median postreinforcement pause duration and mean local lever-pressing rates broken down by previous reinforcer duration and duration of signaled upcoming reinforcer showed that postreinforcement pause duration was affected by the duration of the previous reinforcer but not by the stimulus signaling the duration of the upcoming reinforcer. Local lever-pressing rates were not affected by either previous or upcoming reinforcer duration. In general, the results are consistent with indifference between these durations obtained using a concurrent choice procedure.

Genetic control of eosinophilia in mice: gene(s) expressed in bone marrow-derived cells control high responsiveness

International Nuclear Information System (INIS)

Vadas, M.A.

1982-01-01

A heterogeneity in the capacity of strains of mice to mount eosinophilia is described. BALB/c and C3H are eosinophil high responder strains (EO-HR) and CBA and A/J are eosinophil low responder strains (EO-LR), judged by the response of blood eosinophils to Ascaris suum, and the response of blood, bone marrow, and spleen eosinophils to keyhole limpet hemocyanin given 2 days after 150 mg/kg cyclophosphamide. Some of the gene(s) for high responsiveness appear to be dominant because (EO-HR x EO-LR)F 1 mice were intermediate to high responders. This gene is expressed in bone marrow-derived cells because radiation chimeras of the type EO-HR→F 1 were high responders and EO-LR→F 1 were low responders. This description of a genetic control of eosinophilia in mice may be useful in understanding the role of this cell in parasite immunity and allergy

Effect of anti-gut inflammatory agent on insulin resistance and lipid profile of mice fed different diets

NARCIS (Netherlands)

Wang, Zheng; Bao, Zhijun

Purpose: To further explore the effect of 5-aminosalicylic acid (5-ASA) treatment on lipid levels in mice fed different diets. Methods: Groups of 9 - 10 mice each were randomly assigned to 6 different diets, low-fat diet (LFD) with or without 5-ASA, high-fat diet (HFD) with or without 5-ASA, and

Chronic blockade or constitutive deletion of the serotonin transporter reduces operant responding for food reward.

Science.gov (United States)

Sanders, Amy Cecilia; Hussain, Ali J; Hen, René; Zhuang, Xiaoxi

2007-11-01

The therapeutic effects of chronic selective serotonin reuptake inhibitors (SSRIs) are well documented, yet the elementary behavioral processes that are affected by such treatment have not been fully investigated. We report here the effects of chronic fluoxetine treatment and genetic deletion of the serotonin transporter (SERT) on food reinforced behavior in three paradigms: the progressive ratio operant task, the concurrent choice operant task, and the Pavlovian-to-Instrumental transfer task. We consistently find that chronic pharmacological blockade or genetic deletion of SERT result in similar behavioral consequences: reduced operant responding for natural reward. This is in line with previous studies reporting declines in operant responding for drugs and intracranial self-stimulation with fluoxetine treatment, suggesting that the effect of SERT blockade can be generalized to different reward types. Detailed analyses of behavioral parameters indicate that this reduction in operant responding affect both goal-directed and non-goal-directed behaviors without affecting the Pavlovian cue-triggered excessive operant responding. In addition, both pharmacological and genetic manipulations reduce locomotor activity in the open field novel environment. Our data contrast with the effect of dopamine in increasing operant responding for natural reward specifically in goal-directed behaviors and in increasing Pavlovian cue-triggered excessive operant responding. Serotonin and dopamine have been proposed to serve opposing functions in motivational processes. Our data suggest that their interactions do not result in simple opponency. The fact that pharmacological blockade and genetic deletion of SERT have similar behavioral consequences reinforces the utility of the SERT null mice for investigation of the mechanisms underlying chronic SSRIs treatment.

Response pattern's of immunoglobulins evaluation in different lineages of mice infected with T. cruzi

International Nuclear Information System (INIS)

Silva, Andreia dos Santos

2006-01-01

The present work has employed different mice lineages (A/J, C57BL/6, B6AF1, BXA1 and BXA2) that were challenged with different doses of T. cruzi. The objective was to evaluate the pattern of immunoglobulins response presented by resistant and susceptible mice to T. cruzi as well as the lineages developed from the matting between them. So that evaluation was done by using lineages serums' sample, analyzed by ELISA's method. In agreement with the results observed all the lineages presented higher response to IgG2a and IgG2b, if compared with the titles to IgG1. IgG1 immunoglobulins involve a type Th2 pattern response which expressed allergic immunological responses, while IgG2 involves a pattern response Th1 that expresses cellular immunological response. The different lineages used in this research also presented different immunological response pattern by the infection with T. cruzi. Mice of the lineage C57BL/6 are resistant to the infection, while the animals of the lineage A/J are susceptible. The animals of the lineage B6AF1 are more resistant to the infection than their original parental C57BL/6. The immunological response developed by hybrid mice present traces of both susceptible and resistant parental A/J and C57BL/6, respectively. The animals of the lineage BXA1 can be considered resistant to the infection, but they don't present the same control as that presented by those of the lineages B6AF1 and C57BL/6. The animals of the lineage BXA2 can be considered susceptible to the infection, but they can control it for a long period, surviving like this, longer than the animals of the lineage A/J. In addition it was observed that the IgG2b immunoglobulins are very important to the resistance of mice to T. cruzi infection. (author)

Gender differences in symptoms in partial responders to proton pump inhibitors for gastro-oesophageal reflux disease.

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Vakil, N; Niklasson, A; Denison, H; Rydén, A

2015-10-01

Gender differences may exist in the symptom experience of patients with gastro-oesophageal reflux disease (GERD) who have a partial response to proton pump inhibitors (PPIs). The purpose of this study was to analyse gender differences in partial responders to PPIs. Patients with GERD who responded partially to PPIs (n = 580; NCT00703534) completed the Reflux Symptom Questionnaire 7-day recall (RESQ-7) and the Gastrointestinal Symptom Rating Scale (GSRS). Anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale. Women had significantly higher RESQ-7 domain scores than men for Heartburn (frequency: 4.3 vs 3.9; intensity: 3.1 vs 2.8), Burping (frequency: 4.9 vs 4.4; intensity: 3.1 vs 2.8) and Hoarseness, cough and difficulty swallowing (frequency: 2.6 vs 2.2; intensity: 1.8 vs 1.5), and had higher GSRS domain discomfort scores than men for Abdominal pain (3.51 vs 3.23), Indigestion (3.80 vs 3.45) and Constipation (2.69 vs 2.17) (all p < 0.05). Anxiety and depression were significantly more prevalent in women than in men. In this population of partial responders, women had more frequent/intense heartburn and extra-oesophageal symptoms and more discomfort from abdominal pain, indigestion and constipation than men. Comorbid anxiety and depression may contribute to the increased symptom burden in women.

Analysis of mortality from different causes of death in mice exposed to fast neutrons

International Nuclear Information System (INIS)

Coppola, M.; Covelli, V.; Di Majo, V.

1985-01-01

The results of a further analysis of data obtained from a large experiment carried out at the Laboratory of Pathology of CRE Casaccia on mice irradiated with neutrons and with X-rays at different ages are reported. In particular, the attention is focused on the possible relationship of the life-span shortening observed in irradiated animals with the different causes of death. In the case of young adult mice, data have been separately analysed for tumour free and tumour bearing mice, and showed that a marked life-span shortening is associated with incidence and rate of radiation induced neoplasms. In addition the occurrence of solid tumours, evaluated as age adjusted final incidences, indicated a sharp increase already at very low doses of neutrons while for X-rays this phenomenon was essentially confined in the range of 3 to 6 Gy. From these data the possibility of evaluating neutron RBE at low doses, as well as the implications for quality factors, are discussed

Naloxone effects on behavior of inbred mice with different response to emotional stress in open field test.

Science.gov (United States)

Nadorova, A V; Kozlovskaja, M M; Seredenin, S B

2009-10-01

Effects of nonspecific opiate receptor antagonist naloxone in doses of 0.1, 0.5, 1.0, 5.0, 10.0 mg/kg on open field behavior and spontaneous motor activity were studied in male BALB/c and C57Bl/6 mice. Differently directed effects of naloxone on behavioral parameters of emotional-stress reaction in BALB/c and C57Bl/6 mice were observed. Naloxone increased motor activity in the open field test in BALB/c mice, but decreased it in C57Bl/6 mice. In the absence of stress, naloxone in the studied dose range did not affect spontaneous motor activity in C57Bl/6 mice, and significantly reduced activity in BALB/c mice in doses 0.5 and 1.0 mg/kg.

Inhibition of tumor growth in syngenetic chimeric mice mediated by a depletion of suppressor T cells

International Nuclear Information System (INIS)

Rotter, V.; Trainin, N.

1975-01-01

Syngeneic chimeric (lethally irradiated and reconstituted with syngeneic bone marrow cells) mice manifested an increased resistance to the development of Lewis lung carcinoma. In addition, these mice had a higher response to polyvinylpyrrolidone and a reduced reactivity to T mitogens. The present findings suggest that syngeneic chimeric mice lack suppressor T cells shown to regulate the development of Lewis lung tumor and the response to polyvinylpyrrolidone. Other components of the T cell population, such as helper cells responding to sheep red blood cells or cells involved in allograft rejection, assayed in these syngeneic chimeras were found unaffected. The fact that chimeric mice are deficient in a certain suppressor T cell population whereas other T activities are normal suggests the existence of different cell lines within the T cell population. (U.S.)

Strain differences of the effect of enucleation and anophthalmia on the size and growth of sensory cortices in mice.

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Massé, Ian O; Guillemette, Sonia; Laramée, Marie-Eve; Bronchti, Gilles; Boire, Denis

2014-11-07

Anophthalmia is a condition in which the eye does not develop from the early embryonic period. Early blindness induces cross-modal plastic modifications in the brain such as auditory and haptic activations of the visual cortex and also leads to a greater solicitation of the somatosensory and auditory cortices. The visual cortex is activated by auditory stimuli in anophthalmic mice and activity is known to alter the growth pattern of the cerebral cortex. The size of the primary visual, auditory and somatosensory cortices and of the corresponding specific sensory thalamic nuclei were measured in intact and enucleated C57Bl/6J mice and in ZRDCT anophthalmic mice (ZRDCT/An) to evaluate the contribution of cross-modal activity on the growth of the cerebral cortex. In addition, the size of these structures were compared in intact, enucleated and anophthalmic fourth generation backcrossed hybrid C57Bl/6J×ZRDCT/An mice to parse out the effects of mouse strains and of the different visual deprivations. The visual cortex was smaller in the anophthalmic ZRDCT/An than in the intact and enucleated C57Bl/6J mice. Also the auditory cortex was larger and the somatosensory cortex smaller in the ZRDCT/An than in the intact and enucleated C57Bl/6J mice. The size differences of sensory cortices between the enucleated and anophthalmic mice were no longer present in the hybrid mice, showing specific genetic differences between C57Bl/6J and ZRDCT mice. The post natal size increase of the visual cortex was less in the enucleated than in the anophthalmic and intact hybrid mice. This suggests differences in the activity of the visual cortex between enucleated and anophthalmic mice and that early in-utero spontaneous neural activity in the visual system contributes to the shaping of functional properties of cortical networks. Copyright © 2014 Elsevier B.V. All rights reserved.

Immunisation against PCV2 structural protein by DNA vaccination of mice

DEFF Research Database (Denmark)

Kamstrup, Søren; Barfoed, Annette Malene; Frimann, Tine

2004-01-01

the capsid protein of PCV2 was cloned in a DNA vaccination plasmid and expression of capsid protein was demonstrated in vitro. Mice were gene gun vaccinated three timesand all mice responded serologically by raising antibodies against PCV2. The results suggest, that DNA based vaccination might offer...

Differences in the immunologic reactivity of mice treated with UVB or methoxsalen plus UVA radiation

International Nuclear Information System (INIS)

Kripke, M.L.; Morison, W.L.; Parrish, J.A.

1981-01-01

Skin tumors induced in mice by chronic exposure to UVB radiation are often highly antigenic and regress when transplanted into normal syngeneic animals, but grow progressively in immunosuppressed mice. Exposure of mice to subtumorigenic doses of UVB radiation can abolish this immunologic rejection phenomenon. In this study, we have investigated the effects of treatment with 8-methoxypsoralen plus UVA radiation (PUVA) on the rejection of antigenic UVB-induced tumors. PUVA treatment, with either topical or systemic administration of the psoralen, did not alter the normal process of rejection of UVB-induced tumors. Mice treated with both minimally and markedly phototoxic doses of PUVA rejected tumors with a frequency similar to that seen in untreated animals, although these tumors grew progressively in UVB-irradiated mice. These results indicate that the effects of PUVA treatment differ from those of UVB irradiation in that PUVA treatment does not alter the immunologic rejection of UVB-induced tumors

Ectopic brown adipose tissue in muscle provides a mechanism for differences in risk of metabolic syndrome in mice.

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Almind, Katrine; Manieri, Monia; Sivitz, William I; Cinti, Saverio; Kahn, C Ronald

2007-02-13

C57BL/6 (B6) mice subjected to a high-fat diet develop metabolic syndrome with obesity, hyperglycemia, and insulin resistance, whereas 129S6/SvEvTac (129) mice are relatively protected from this disorder because of differences in higher basal energy expenditure in 129 mice, leading to lower weight gain. At a molecular level, this difference correlates with a marked higher expression of uncoupling protein 1 (UCP1) and a higher degree of uncoupling in vitro in mitochondria isolated from muscle of 129 versus B6 mice. Detailed histological examination, however, reveals that this UCP1 is in mitochondria of brown adipocytes interspersed between muscle bundles. Indeed, the number of UCP1-positive brown fat cells in intermuscular fat in 129 mice is >700-fold higher than in B6 mice. These brown fat cells are subject to further up-regulation of UCP1 after stimulation with a beta3-adrenergic receptor agonist. Thus, ectopic deposits of brown adipose tissue in intermuscular depots with regulatable expression of UCP1 provide a genetically based mechanism of protection from weight gain and metabolic syndrome between strains of mice.

Y chromosomal and sex effects on the behavioral stress response in the defensive burying test in wild house mice

NARCIS (Netherlands)

Sluyter, F; Korte, SM; Van Baal, GCM; De Ruiter, AJH; Van Oortmerssen, GA

1999-01-01

Genetically selected short attack latency (SAL) and long attack latency (LAL) male wild house mice behave differently in the defensive burying test. When challenged, SAL males respond actively with more time spent on defensive burying, whereas LAL males are more passive with more time remaining

Ectopic brown adipose tissue in muscle provides a mechanism for differences in risk of metabolic syndrome in mice

OpenAIRE

Almind, Katrine; Manieri, Monia; Sivitz, William I.; Cinti, Saverio; Kahn, C. Ronald

2007-01-01

C57BL/6 (B6) mice subjected to a high-fat diet develop metabolic syndrome with obesity, hyperglycemia, and insulin resistance, whereas 129S6/SvEvTac (129) mice are relatively protected from this disorder because of differences in higher basal energy expenditure in 129 mice, leading to lower weight gain. At a molecular level, this difference correlates with a marked higher expression of uncoupling protein 1 (UCP1) and a higher degree of uncoupling in vitro in mitochondria isolated from muscle ...

Aging-associated oxidative stress inhibits liver progenitor cell activation in mice.

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Cheng, Yiji; Wang, Xue; Wang, Bei; Zhou, Hong; Dang, Shipeng; Shi, Yufang; Hao, Li; Luo, Qingquan; Jin, Min; Zhou, Qianjun; Zhang, Yanyun

2017-04-29

Recent studies have discovered aging-associated changes of adult stem cells in various tissues and organs, which potentially contribute to the organismal aging. However, aging-associated changes of liver progenitor cells (LPCs) remain elusive. Employing young (2-month-old) and old (24-month-old) mice, we found diverse novel alterations in LPC activation during aging. LPCs in young mice could be activated and proliferate upon liver injury, whereas the counterparts in old mice failed to respond and proliferate, leading to the impaired liver regeneration. Surprisingly, isolated LPCs from young and old mice did not exhibit significant difference in their clonogenic and proliferative capacity. Later, we uncovered that the decreased activation and proliferation of LPCs were due to excessive reactive oxygen species produced by neutrophils infiltrated into niche, which was resulted from chemokine production from activated hepatic stellate cells during aging. This study demonstrates aging-associated changes in LPC activation and reveals critical roles for the stem cell niche, including neutrophils and hepatic stellate cells, in the negative regulation of LPCs during aging.

Neuronal Activation After Prolonged Immobilization: Do the Same or Different Neurons Respond to a Novel Stressor?

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Marín-Blasco, Ignacio; Muñoz-Abellán, Cristina; Andero, Raül; Nadal, Roser; Armario, Antonio

2018-04-01

Despite extensive research on the impact of emotional stressors on brain function using immediate-early genes (e.g., c-fos), there are still important questions that remain unanswered such as the reason for the progressive decline of c-fos expression in response to prolonged stress and the neuronal populations activated by different stressors. This study tackles these 2 questions by evaluating c-fos expression in response to 2 different emotional stressors applied sequentially, and performing a fluorescent double labeling of c-Fos protein and c-fos mRNA on stress-related brain areas. Results were complemented with the assessment of the hypothalamic-pituitary-adrenal axis activation. We showed that the progressive decline of c-fos expression could be related to 2 differing mechanisms involving either transcriptional repression or changes in stimulatory inputs. Moreover, the neuronal populations that respond to the different stressors appear to be predominantly separated in high-level processing areas (e.g., medial prefrontal cortex). However, in low-hierarchy areas (e.g., paraventricular nucleus of the hypothalamus) neuronal populations appear to respond unspecifically. The data suggest that the distinct physiological and behavioral consequences of emotional stressors, and their implication in the development of psychopathologies, are likely to be closely associated with neuronal populations specifically activated by each stressor.

The influence of enriched environment on spatial memory in Swiss mice of different ages

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Alessandra Fernandes Druzian

2015-08-01

Full Text Available The objective of this study was to evaluate the influence of enriched environment on spatial memory acquisition in mice of three different age groups. Weanling, young, and young adult female Swiss mice were housed in a standard control or enriched environment for 50 days, and their spatial memory was tested with the Morris Water Maze. We did not observe an experimental effect for spatial memory acquisition, and there was neither an effect of time of analysis nor an interaction between experimental group and time of analysis. Regarding effects of experimental group and training day in relation to latency in finding the hidden platform, we did find an effect in the experimental young adult mice group (p = 0.027, but there was no interaction between these factors in all three groups. Based on these findings environmental enrichment did not enhance spatial memory acquisition in female Swiss mice in the tested age groups.

Biodistribution of Different Sized Nanodiamonds in Mice.

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Purtov, Konstantin; Petunin, Alexey; Inzhevatkin, Evgeny; Burov, Andrey; Ronzhin, Nikita; Puzyr, Alexey; Bondar, Vladimir

2015-02-01

The particle size is one of critical parameters influencing the biodistribution of detonation nanodiamonds (DND) after their administration into the body. As DNDs are prone to aggregation, the difference between their sizes in aqueous and physiological solutions has to be taken into account. Radioactive I125-BSA molecules were covalently immobilized on DNDs divided in three fractions of different average size. The DND-BSAI125 conjugates were intravenously administrated into adult mice and the particle allocation in the animal's organs and blood was evaluated based on the radioactivity distribution. We conclude that most of the conjugates were taken from the bloodstream and trapped in the liver and spleen. The short-term distribution pattern for all DNDs was similar regardless of size and practically unchanged with time. No significant clearance of the particles was observed for 4 h, but the presence of DNDs was detected in the blood. It was found that the largest particles tend to accumulate more into the liver as compared to the smaller ones. However, the size effect was not well pronounced for the studied size range.

Proteomic study on gender differences in aging kidney of mice

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Cristobal Susana

2009-04-01

Full Text Available Abstract Background This study aims to analyze sex differences in mice aging kidney. We applied a proteomic technique based on subfractionation, and liquid chromatography coupled with 2-DE. Samples from male and female CD1-Swiss outbred mice from 28 weeks, 52 weeks, and 76 weeks were analysed by 2-DE, and selected proteins were identified by matrix assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS. Results This proteomic analysis detected age-related changes in protein expression in 55 protein-spots, corresponding to 22 spots in males and 33 spots in females. We found a protein expression signature (PES of aging composed by 8 spots, common for both genders. The identified proteins indicated increases in oxidative and proteolytic proteins and decreases in glycolytic proteins, and antioxidant enzymes. Conclusion Our results provide insights into the gender differences associated to the decline of kidney function in aging. Thus, we show that proteomics can provide valuable information on age-related changes in expression levels of proteins and related modifications. This pilot study is still far from providing candidates for aging-biomarkers. However, we suggest that the analysis of these proteins could suggest mechanisms of cellular aging in kidney, and improve the kidney selection for transplantation.

Distinct neurobehavioural effects of cannabidiol in transmembrane domain neuregulin 1 mutant mice.

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Leonora E Long

Full Text Available The cannabis constituent cannabidiol (CBD possesses anxiolytic and antipsychotic properties. We have previously shown that transmembrane domain neuregulin 1 mutant (Nrg1 TM HET mice display altered neurobehavioural responses to the main psychoactive constituent of cannabis, Δ(9-tetrahydrocannabinol. Here we investigated whether Nrg1 TM HET mice respond differently to CBD and whether CBD reverses schizophrenia-related phenotypes expressed by these mice. Adult male Nrg1 TM HET and wild type-like littermates (WT received vehicle or CBD (1, 50 or 100 mg/kg i.p. for 21 days. During treatment and 48 h after withdrawal we measured behaviour, whole blood CBD concentrations and autoradiographic receptor binding. Nrg1 HET mice displayed locomotor hyperactivity, PPI deficits and reduced 5-HT(2A receptor binding density in the substantia nigra, but these phenotypes were not reversed by CBD. However, long-term CBD (50 and 100 mg/kg selectively enhanced social interaction in Nrg1 TM HET mice. Furthermore, acute CBD (100 mg/kg selectively increased PPI in Nrg1 TM HET mice, although tolerance to this effect was manifest upon repeated CBD administration. Long-term CBD (50 mg/kg also selectively increased GABA(A receptor binding in the granular retrosplenial cortex in Nrg1 TM HET mice and reduced 5-HT(2A binding in the substantia nigra in WT mice. Nrg1 appears necessary for CBD-induced anxiolysis since only WT mice developed decreased anxiety-related behaviour with repeated CBD treatment. Altered pharmacokinetics in mutant mice could not explain our findings since no genotype differences existed in CBD blood concentrations. Here we demonstrate that Nrg1 modulates acute and long-term neurobehavioural effects of CBD, which does not reverse the schizophrenia-relevant phenotypes.

The probability of reinforcement per trial affects posttrial responding and subsequent extinction but not within-trial responding.

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Harris, Justin A; Kwok, Dorothy W S

2018-01-01

During magazine approach conditioning, rats do not discriminate between a conditional stimulus (CS) that is consistently reinforced with food and a CS that is occasionally (partially) reinforced, as long as the CSs have the same overall reinforcement rate per second. This implies that rats are indifferent to the probability of reinforcement per trial. However, in the same rats, the per-trial reinforcement rate will affect subsequent extinction-responding extinguishes more rapidly for a CS that was consistently reinforced than for a partially reinforced CS. Here, we trained rats with consistently and partially reinforced CSs that were matched for overall reinforcement rate per second. We measured conditioned responding both during and immediately after the CSs. Differences in the per-trial probability of reinforcement did not affect the acquisition of responding during the CS but did affect subsequent extinction of that responding, and also affected the post-CS response rates during conditioning. Indeed, CSs with the same probability of reinforcement per trial evoked the same amount of post-CS responding even when they differed in overall reinforcement rate and thus evoked different amounts of responding during the CS. We conclude that reinforcement rate per second controls rats' acquisition of responding during the CS, but at the same time, rats also learn specifically about the probability of reinforcement per trial. The latter learning affects the rats' expectation of reinforcement as an outcome of the trial, which influences their ability to detect retrospectively that an opportunity for reinforcement was missed, and, in turn, drives extinction. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Postnatal mandible growth in wild and laboratory mice: Differences revealed from bone remodeling patterns and geometric morphometrics.

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Martínez-Vargas, Jessica; Muñoz-Muñoz, Francesc; Martinez-Maza, Cayetana; Molinero, Amalia; Ventura, Jacint

2017-08-01

Comparative information on the variation in the temporospatial patterning of mandible growth in wild and laboratory mice during early postnatal ontogeny is scarce but important to understand variation among wild rodent populations. Here, we compare mandible growth between two ontogenetic series from the second to the eighth week of postnatal life, corresponding to two different groups of mice reared under the same conditions: the classical inbred strain C57BL/6J, and Mus musculus domesticus. We characterize the ontogenetic patterns of bone remodeling of the mandibles belonging to these laboratory and wild mice by analyzing bone surface, as well as examine their ontogenetic form changes and bimodular organization using geometric morphometrics. Through ontogeny, the two mouse groups display similar directions of mandible growth, according to the temporospatial distribution of bone remodeling fields. The allometric shape variation of the mandibles of these mice entails the relative enlargement of the ascending ramus. The organization of the mandible into two modules is confirmed in both groups during the last postnatal weeks. However, especially after weaning, the mandibles of wild and laboratory mice differ in the timing and localization of several remodeling fields, in addition to exhibiting different patterns of shape variation and differences in size. The stimulation of dentary bone growth derived from the harder post-weaning diet might account for some features of postnatal mandible growth common to both groups. Nonetheless, a large component of the postnatal growth of the mouse mandible appears to be driven by the inherent genetic programs, which might explain between-group differences. © 2017 Wiley Periodicals, Inc.

Sex differences in the activity of mice: modulation by postnatal gonadal hormones.

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Broida, J; Svare, B

1984-03-01

A series of six experiments was performed to examine the influence of postnatal-gonadal-hormone exposure on home-cage activity in Rockland-Swiss albino mice. Intact females were more active than their male counterparts and gonadectomy in adulthood, while reducing levels of the behavior in both sexes, did not eliminate the gender difference. Males that were castrated on the day of birth were more active than animals castrated 5, 10, or 25 days later. Also, females treated with testosterone propionate on the day of birth were less active than oil-treated controls and females exposed to the steroid 10 days after birth. Thus, perinatal exposure to gonadal hormones suppresses adult levels of home-cage activity in mice.

Distinct molecular subtypes of uterine leiomyosarcoma respond differently to chemotherapy treatment.

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An, Yang; Wang, Shuzhen; Li, Songlin; Zhang, Lulu; Wang, Dayong; Wang, Haojie; Zhu, Shibai; Zhu, Wan; Li, Yongqiang; Chen, Wenwu; Ji, Shaoping; Guo, Xiangqian

2017-09-11

Uterine leiomyosarcoma (ULMS) is an aggressive form of soft tissue tumors. The molecular heterogeneity and pathogenesis of ULMS are not well understood. Expression profiling data were used to determine the possibility and optimal number of ULMS molecular subtypes. Next, clinicopathological characters and molecular pathways were analyzed in each subtype to prospect the clinical applications and progression mechanisms of ULMS. Two distinct molecular subtypes of ULMS were defined based on different gene expression signatures. Subtype I ULMS recapitulated low-grade ULMS, the gene expression pattern of which resembled normal smooth muscle cells, characterized by overexpression of smooth muscle function genes such as LMOD1, SLMAP, MYLK, MYH11. In contrast, subtype II ULMS recapitulated high-grade ULMS with higher tumor weight and invasion rate, and was characterized by overexpression of genes involved in the pathway of epithelial to mesenchymal transition and tumorigenesis, such as CDK6, MAPK13 and HOXA1. We identified two distinct molecular subtypes of ULMS responding differently to chemotherapy treatment. Our findings provide a better understanding of ULMS intrinsic molecular subtypes, and will potentially facilitate the development of subtype-specific diagnosis biomarkers and therapy strategies for these tumors.

Sequence analysis of chromosome 1 revealed different selection patterns between Chinese wild mice and laboratory strains.

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Xu, Fuyi; Hu, Shixian; Chao, Tianzhu; Wang, Maochun; Li, Kai; Zhou, Yuxun; Xu, Hongyan; Xiao, Junhua

2017-10-01

Both natural and artificial selection play a critical role in animals' adaptation to the environment. Detection of the signature of selection in genomic regions can provide insights for understanding the function of specific phenotypes. It is generally assumed that laboratory mice may experience intense artificial selection while wild mice more natural selection. However, the differences of selection signature in the mouse genome and underlying genes between wild and laboratory mice remain unclear. In this study, we used two mouse populations: chromosome 1 (Chr 1) substitution lines (C1SLs) derived from Chinese wild mice and mouse genome project (MGP) sequenced inbred strains and two selection detection statistics: Fst and Tajima's D to identify the signature of selection footprint on Chr 1. For the differentiation between the C1SLs and MGP, 110 candidate selection regions containing 47 protein coding genes were detected. A total of 149 selection regions which encompass 7.215 Mb were identified in the C1SLs by Tajima's D approach. While for the MGP, we identified nearly twice selection regions (243) compared with the C1SLs which accounted for 13.27 Mb Chr 1 sequence. Through functional annotation, we identified several biological processes with significant enrichment including seven genes in the olfactory transduction pathway. In addition, we searched the phenotypes associated with the 47 candidate selection genes identified by Fst. These genes were involved in behavior, growth or body weight, mortality or aging, and immune systems which align well with the phenotypic differences between wild and laboratory mice. Therefore, the findings would be helpful for our understanding of the phenotypic differences between wild and laboratory mice and applications for using this new mouse resource (C1SLs) for further genetics studies.

Diurnal-and sex-related difference of metallothionein expression in mice

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Zhang Dan

2012-07-01

Full Text Available Abstract Background Metallothionein (MT is a small, cysteine-rich, metal-binding protein that plays an important role in protecting against toxicity of heavy metal and chemicals. This study was aimed to define diurnal and sex variation of MT in mice. Methods Adult mice were maintained in light- and temperature-controlled facilities for 2 weeks with light on at 8:00 and light off at 20:00. The blood, liver, and kidneys were collected every 4 h during the 24 h period. Total RNA was isolated, purified, and subjected to real-time RT-PCR analysis and MT protein was determined by western blot and the Cd/hemoglobin assay. Results The diurnal variations in mRNA levels of MT-1 and MT-2in liver were dramatic, up to a 40-foldpeak/trough ratio. MT mRNA levels in kidneys and blood also showed diurnal variation, up to 5-fold peak/trough ratio. The diurnal variation of MT mRNAs resembled the clock gene albumin site D-binding protein (Dbp, and was anti-phase to the clock gene Brain and Muscle ARNT-like Protein 1 (Bmal1 in liver and kidneys. The peaks of MT mRNA levels were higher in females than in males. Hepatic MT protein followed a similar pattern, with about a 3-fold difference. Conclusion MT mRNA levels and protein showed diurnal- and sex-variation in liver, kidney, and blood of mice, which could impact the body defense against toxic stimuli.

Histamine-dependent behavioral response to methamphetamine in 12-month-old male mice

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Acevedo, Summer F.; Raber, Jacob

2011-01-01

Methamphetamine (MA) use is a growing problem across the United States. Effects of MA include hyperactivity and increased anxiety. Using a mouse model system, we examined behavioral performance in the open field and elevated zero maze and shock-startle response of 12-month-old wild-type mice injected with MA once (1mg/kg) 30 min prior to behavioral testing. MA treatment resulted in behavioral sensitization in the open field, consistent with studies in younger mice. There was an increased activity in the elevated zero maze and an increased shock-startle response 30 and 60 min post-injection. Since histamine mediates some effects of MA in the brain, we assessed whether 12-month-old mice lacking histidine decarboxylase (Hdc−/−), the enzyme required to synthesize histamine, respond differently to MA than wild-type (Hdc+/+) mice. Compared to saline treatment, acute and repeated MA administration increased activity in the open field and measures of anxiety, though more so in Hdc−/− than Hdc+/+ mice. In the elevated zero maze, opposite effects of MA on activity and measures of anxiety were seen in Hdc+/+ mice. In contrast, MA similarly increased the shock-startle response in Hdc−/− and Hdc+/+ mice, compared to saline-treated genotype-matched mice. These results are similar to those in younger mice suggesting that the effects are not age-dependent. Overall, single or repeated MA treatment causes histamine-dependent changes in 12-month-old mice in the open field and elevated zero-maze, but not in the shock-startle response. PMID:21466792

Transcriptional changes induced by bevacizumab combination therapy in responding and non-responding recurrent glioblastoma patients

DEFF Research Database (Denmark)

Urup, Thomas; Staunstrup, Line Maersk; Michaelsen, Signe Regner

2017-01-01

Background: Bevacizumab combined with chemotherapy produces clinical durable response in 25-30% of recurrent glioblastoma patients. This group of patients has shown improved survival and quality of life. The aim of this study was to investigate changes in gene expression associated with response...... and resistance to bevacizumab combination therapy.Methods: Recurrent glioblastoma patients who had biomarker-accessible tumor tissue surgically removed both before bevacizumab treatment and at time of progression were included. Patients were grouped into responders (n = 7) and non-responders (n = 14). Gene...... expression profiling of formalin-fixed paraffin-embedded tumor tissue was performed using RNA-sequencing.Results: By comparing pretreatment samples of responders with those of non-responders no significant difference was observed. In a paired comparison analysis of pre- and posttreatment samples of non...

Experimental immunologically mediated aplastic anemia (AA) in H-2k identical, Mls (M) locus different mice

Energy Technology Data Exchange (ETDEWEB)

Knospe, W.H.; Steinberg, D.; Speck, B.

1983-07-01

Immunologically mediated aplastic anemia (AA) was experimentally induced in mice by injecting 10(7) lymph node cells (LNC) from donor mice of one inbred strain to another H-2k identical but Mls mismatched strain previously given 600 rad total body gamma irradiation (TBI). AA developed after 2 weeks to 6 months in selected strain combinations used and usually 60 to 90% of the mice died. Clinical signs of graft-versus-host disease did not occur and splenic atrophy rather than splenomegaly was the rule. Histologically these mice had a lesion of the hematopoietic microenvironment characterized by sinusoidal injury and stromal necrosis. Others have demonstrated injury to hematopoietic stem cells. C3H/He LNC induced AA whereas C3H/HeJ LNC failed to induce AA. The C3H/HeJ strain carries a macrophage defect and these results suggest that a macrophage-like cell may be a mediator of immunological injury in this experimental model. Although all strain combinations evaluated were H-2k identical and Mls mismatched, certain Mls combinations resulted in AA and identical Mls mismatched but different strains did not. Both strong (Mlsd) and weak (Mlsc) stimulating LNC induce AA but simple Mls differences do not explain the AA as similar Mls combinations but different strain combinations fail to induce AA.

Strain differences in the influence of open field exposure on sleep in mice.

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Tang, Xiangdong; Xiao, Jihua; Liu, Xianling; Sanford, Larry D

2004-09-23

The open field (OF) is thought to induce anxiety in rodents. It also allows an opportunity for exploration in a novel environment. Less activity in the OF is thought to indicate greater anxiety whereas more activity may reflect greater exploration, and possibly greater exploratory learning. Anxiety and learning have poorly understood relationships to sleep. In order to determine how anxiety and exploration in the OF could influence sleep, we recorded sleep in mouse strains (C57BL/6J (B6), BALB/cJ (C), DBA/2J (D2), and CB6F1/J (CB6)) with different levels of anxiety and exploration after 30 min in an OF. In all strains, OF exposure induced immediate decreases in rapid eye movement sleep (REM) followed by longer latency increases in REM. The time course and amount of REM decreases and increases varied among strains. Compared to less anxious B6, D2 and CB6 mice, C mice had greater and longer lasting immediate decreases in REM. C mice also displayed longer periods of decreases REM and a smaller, longer latency increase in REM. OF exploratory activity was positively correlated to percentage of REM increases from 6 to 10h after OF exposure. The results suggest that the anxiogenic component of the OF produced an immediate decrease in REM that was greater in more "anxious" mice. In contrast, exploration in the OF was associated with increased REM, with the increase greater in less anxious mice. The results are discussed with respect to the potential influences of anxiety and learning on sleep.

'Different strokes for different folks': geographically isolated strains of Lymnaea stagnalis only respond to sympatric predators and have different memory forming capabilities.

Science.gov (United States)

Orr, Michael V; Hittel, Karla; Lukowiak, Ken

2009-07-01

Gaining insight into how natural trait variation is manifest in populations shaped by differential environmental factors is crucial to understanding the evolution, ecology and sensory biology of natural populations. We have demonstrated that lab-reared Lymnaea detect and respond to the scent of a crayfish predator with specific, appropriate anti-predator behavioral responses, including enhanced long-term memory (LTM) formation, and that such predator detection significantly alters the electrophysiological activity of RPeD1, a neuron that is a necessary site for LTM formation. Here we ask: (1) do distinct populations of wild Lymnaea stagnalis respond only to sympatric predators and if so, can these traits be quantified at both the behavioral and neurophysiological levels, and (2) does the presence of a non-sympatric predator elicit anti-predator behaviors including augmentation of LTM? We tested three different populations of wild (i.e. not lab-reared) snails freshly collected from their natural habitat: (1) polders near Utrecht in The Netherlands, (2) six seasonally isolated ponds in the Belly River drainage in southern Alberta, Canada and (3) a 20-year-old human-made dugout pond in southern Alberta. We found strain-specific variations in the ability to form LTM and that only a sympatric predator evoked anti-predatory behaviors, including enhanced LTM formation and changes in RPeD1 activity.

Soil bacteria and fungi respond on different spatial scales to invasion by the legume Lespedeza cuneata

Directory of Open Access Journals (Sweden)

Anthony C Yannarell

2011-06-01

Full Text Available The spatial scale on which microbial communities respond to plant invasions may provide important clues as to the nature of potential invader-microbe interactions. Lespedeza cuneata (Dum. Cours. G. Don is an invasive legume that may benefit from associations with mycorrhizal fungi; however, it has also been suggested that the plant is allelopathetic and may alter the soil chemistry of invaded sites through secondary metabolites in its root exudates or litter. Thus, L. cuneata invasion may interact with soil microorganisms on a variety of scales. We investigated L. cuneata-related changes to soil bacterial and fungal communities at two spatial scales using multiple sites from across its invaded N. American range. Using whole community DNA fingerprinting, we characterized microbial community variation at the scale of entire invaded sites and at the scale of individual plants. Based on permutational multivariate analysis of variance, soil bacterial communities in heavily invaded sites were significantly different from those of uninvaded sites, but bacteria did not show any evidence of responding at very local scales around individual plants. In contrast, soil fungi did not change significantly at the scale of entire sites, but there were significant differences between fungal communities of native versus exotic plants within particular sites. The differential scaling of bacterial and fungal responses indicates that L. cuneata interacts differently with soil bacteria and soil fungi, and these microorganisms may play very different roles in the invasion process of this plant.

Inherent and antigen-induced airway hyperreactivity in NC mice

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Tetsuto Kobayashi

1999-01-01

Full Text Available In order to clarify the airway physiology of NC mice, the following experiments were carried out. To investigate inherent airway reactivity, we compared tracheal reactivity to various chemical mediators in NC, BALB/c, C57BL/6 and A/J mice in vitro. NC mice showed significantly greater reactivity to acetylcholine than BALB/c and C57BL/6 mice and a reactivity comparable to that of A/J mice, which are known as high responders. Then, airway reactivity to acetylcholine was investigated in those strains in vivo. NC mice again showed comparable airway reactivity to that seen in A/J mice and a significantly greater reactivity than that seen in BALB/c and C57BL/6 mice. To investigate the effects of airway inflammation on airway reactivity to acetylcholine in vivo, NC and BALB/c mice were sensitized to and challenged with antigen. Sensitization to and challenge with antigen induced accumulation of inflammatory cells, especially eosinophils, in lung and increased airway reactivity in NC and BALB/c mice. These results indicate that NC mice exhibit inherent and antigen-induced airway hyperreactivity. Therefore, NC mice are a suitable strain to use in investigating the mechanisms underlying airway hyperreactivity and such studies will provide beneficial information for understanding the pathophysiology of asthma.

Exploring the response process of culturally differing survey respondents with a response style: A sequential mixed-methods study

NARCIS (Netherlands)

Morren, M.H.; Gelissen, J.P.T.M.; Vermunt, J.K.

2013-01-01

This article presents a mixed methods approach that integrates quantitative and qualitative methods to analyze why the four largest minorities in the Netherlands-Turks, Moroccans, Antilleans, and Surinamese-respond differently to items treating cultural topics. First, we conducted latent class

Transgenic mice expressing constitutive active MAPKAPK5 display gender-dependent differences in exploration and activity

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Moens Ugo

2007-11-01

Full Text Available Abstract Background The mitogen-activated protein kinases, MAPKs for short, constitute cascades of signalling pathways involved in the regulation of several cellular processes that include cell proliferation, differentiation and motility. They also intervene in neurological processes like fear conditioning and memory. Since little remains known about the MAPK-Activated Protein Kinase, MAPKAPK5, we constructed the first MAPKAPK knockin mouse model, using a constitutive active variant of MAPKAPK5 and analyzed the resulting mice for changes in anxiety-related behaviour. Methods We performed primary SHIRPA observations during background breeding into the C57BL/6 background and assessed the behaviour of the background-bred animals on the elevated plus maze and in the light-dark test. Our results were analyzed using Chi-square tests and homo- and heteroscedatic T-tests. Results Female transgenic mice displayed increased amounts of head dips and open arm time on the maze, compared to littermate controls. In addition, they also explored further into the open arm on the elevated plus maze and were less active in the closed arm compared to littermate controls. Male transgenic mice displayed no differences in anxiety, but their locomotor activity increased compared to non-transgenic littermates. Conclusion Our results revealed anxiety-related traits and locomotor differences between transgenic mice expressing constitutive active MAPKAPK5 and control littermates.

Galectins expressed differently in genetically susceptible C57BL/6 and resistant BALB/c mice during acute ocular Toxoplasma gondii infection.

Science.gov (United States)

Chen, S-J; Zhang, Y-X; Huang, S-G; Lu, F-L

2017-07-01

Ocular toxoplasmosis (OT) caused by Toxoplasma gondii is a major cause of infectious uveitis, however little is known about its immunopathological mechanism. Susceptible C57BL/6 (B6) and resistant BALB/c mice were intravitreally infected with 500 tachyzoites of the RH strain of T. gondii. B6 mice showed more severe ocular pathology and higher parasite loads in the eyes. The levels of galectin (Gal)-9 and its receptors (Tim-3 and CD137), interferon (IFN)-γ, IL-6 and IL-10 were significantly higher in the eyes of B6 mice than those of BALB/c mice; however, the levels of IFN-α and -β were significantly decreased in the eyes and CLNs of B6 mice but significantly increased in BALB/c mice after infection. After blockage of galectin-receptor interactions by α-lactose, neither ocular immunopathology nor parasite loads were different from those of infected BALB/c mice without α-lactose treatment. Although the expressions of Gal-9/receptor were significantly increased in B6 mice and Gal-1 and -3 were upregulated in both strains of mice upon ocular T. gondii infection, blockage of galectins did not change the ocular pathogenesis of genetic resistant BALB/c mice. However, IFN-α and -β were differently expressed in B6 and BALB/c mice, suggesting that type I IFNs may play a protective role in experimental OT.

Acquisition of peak responding: what is learned?

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Balci, Fuat; Gallistel, Charles R; Allen, Brian D; Frank, Krystal M; Gibson, Jacqueline M; Brunner, Daniela

2009-01-01

We investigated how the common measures of timing performance behaved in the course of training on the peak procedure in C3H mice. Following fixed interval (FI) pre-training, mice received 16 days of training in the peak procedure. The peak time and spread were derived from the average response rates while the start and stop times and their relative variability were derived from a single-trial analysis. Temporal precision (response spread) appeared to improve in the course of training. This apparent improvement in precision was, however, an averaging artifact; it was mediated by the staggered appearance of timed stops, rather than by the delayed occurrence of start times. Trial-by-trial analysis of the stop times for individual subjects revealed that stops appeared abruptly after three to five sessions and their timing did not change as training was prolonged. Start times and the precision of start and stop times were generally stable throughout training. Our results show that subjects do not gradually learn to time their start or stop of responding. Instead, they learn the duration of the FI, with robust temporal control over the start of the response; the control over the stop of response appears abruptly later.

Sex differences in circadian food anticipatory activity are not altered by individual manipulations of sex hormones or sex chromosome copy number in mice.

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Aguayo, Antonio; Martin, Camille S; Huddy, Timothy F; Ogawa-Okada, Maya; Adkins, Jamie L; Steele, Andrew D

2018-01-01

Recent studies in mice have demonstrated a sexual dimorphism in circadian entrainment to scheduled feeding. On a time restricted diet, males tend to develop food anticipatory activity (FAA) sooner than females and with a higher amplitude of activity. The underlying cause of this sex difference remains unknown. One study suggests that sex hormones, both androgens and estrogens, modulate food anticipatory activity in mice. Here we present results suggesting that the sex difference in FAA is unrelated to gonadal sex hormones. While a sex difference between males and females in FAA on a timed, calorie restricted diet was observed there were no differences between intact and gonadectomized mice in the onset or magnitude of FAA. To test other sources of the sex difference in circadian entrainment to scheduled feeding, we used sex chromosome copy number mutants, but there was no difference in FAA when comparing XX, XY-, XY-;Sry Tg, and XX;Sry Tg mice, demonstrating that gene dosage of sex chromosomes does not mediate the sex difference in FAA. Next, we masculinized female mice by treating them with 17-beta estradiol during the neonatal period; yet again, we saw no difference in FAA between control and masculinized females. Finally, we observed that there was no longer a sex difference in FAA for older mice, suggesting that the sex difference in FAA is age-dependent. Thus, our study demonstrates that singular manipulations of gonadal hormones, sex chromosomes, or developmental patterning are not able to explain the difference in FAA between young male and female mice.

[Neonatal Semax and saline injections induce open-field behavior changes in mice of different genotypes].

Science.gov (United States)

Shilova, O B; Markina, N V; Perepelkina, O V; Gichenok, I V; Korochkin, L I; Poletaeva, I I

2004-01-01

DBA/2, CBA mice, and their F1 hybrids (first series) and 101/HY and C3H mice (second series) were injected as neonates (2-7 days of life) with Semax (sc., 7 microg per animal). Semax is a peptide analogue of ACHT4-10 fragment which is resistant to degradation. The common feature of remote effects of both Semax and saline injections was the set of changes in the open-field behavior in adult (2.5- to 3-month-old) animals as compared to intact mice. Unexpectedly, the neonatal saline injections induced many changes in adult behavior, part of these effects being genotype-dependent. The most conspicuous shifts (genotype-dependent increase or decline) in freezing, grooming and rearing scores were displayed by DBA/2 and C3H mice, whereas the hole-poke frequencies were significantly changed in CBA and C3H mice. Squares crossed in the center of arena and rearing number were significantly increased in saline group of DBA/2 mice, whereas in Semax-injected DBA/2 group they were approximately equal to the level of intact mice. This means that the remote effects of noxious stimulation (injections of saline) were in some ways "compensated" as the result of concomitant peptide effect. At the same time, the numbers of freezing and grooming episodes were also increased in these groups. Because exploratory behavior and manifestations of anxiety increased or decreased simultaneously, it proves to be difficult to ascribe these changes to behavioral modulation along the "novelty seeking--anxiety" axis. In mice of other genotypes, changes in the same indices of the open-field behavior were revealed, but these changes were different in their direction. It was suggested that the complex patterns of postnatal behavior was the result of neonatal injections modulating subsequent brain development.

Sex Differences in the Effect of Resveratrol on DSS-Induced Colitis in Mice

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Alexandra Wagnerova

2017-01-01

Full Text Available Resveratrol is a natural polyphenol studied for its possible protective properties in inflammatory bowel diseases. Moreover, it has been shown to interact with estrogen receptors. In the present study, we aimed to investigate possible diverse effects of resveratrol on female and male mice in DSS-induced colitis. Thirty-seven C57BL/6 mice (21 female and 16 male were divided into three groups for each sex. The first group received pure water (CTRL. The other two groups received 1.5% dextran sulfate sodium (DSS to induce colitis from which one group was treated with resveratrol (DSS + RSV. Intake of 1.5% DSS caused weight loss in all DSS groups compared to control mice. Weight loss, stool consistency, and discomfort did not show any protective effect of resveratrol in males and showed even adverse effects in females. In females, the activity of myeloperoxidase was lower compared to that in males. However, colon length and spleen weight showed no sex differences, which can indicate the induction of only mild colitis in mice. Resveratrol did not have any effect on TNF-alpha levels. Taken together, these results for the first time propose possible diverse effects of resveratrol in DSS-induced colitis model depending on the sex of the animal. However, this conclusion must be confirmed by further analyses.

Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

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Lingappan, Krithika, E-mail: lingappa@bcm.edu [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I. [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Barrios, Roberto [Department of Pathology and Genomic Medicine, The Methodist Hospital Physician Organization, 6565 Fannin Street, Suite M227, Houston, TX 77030 (United States); Moorthy, Bhagavatula [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States)

2013-10-15

Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO{sub 2} > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F{sub 2} alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure.

Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

International Nuclear Information System (INIS)

Lingappan, Krithika; Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I.; Barrios, Roberto; Moorthy, Bhagavatula

2013-01-01

Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO 2 > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F 2 alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure

High frequency mechanical ventilation affects respiratory system mechanics differently in C57BL/6J and BALB/c adult mice.

Science.gov (United States)

Hadden, Hélène

2013-01-15

We tested the hypothesis that high frequency ventilation affects respiratory system mechanical functions in C57BL/6J and BALB/c mice. We measured respiratory mechanics by the forced oscillation technique over 1h in anesthetized, intubated, ventilated BALB/c and C57BL/6J male mice. We did not detect any change in airway resistance, Rn, tissue damping, G, tissue elastance, H and hysteresivity, eta in BALB/c mice during 1h of ventilation at 150 or at 450 breaths/min; nor did we find a difference between BALB/c mice ventilated at 150 breaths/min compared with 450 breaths/min. Among C57BL/6J mice, except for H, all parameters remained unchanged over 1h of ventilation in mice ventilated at 150 breaths/min. However, after 10 and 30 min of ventilation at 450 breaths/min, Rn, and respiratory system compliance were lower, and eta was higher, than their starting value. We conclude that high frequency mechanical ventilation affects respiratory system mechanics differently in C57BL/6J and BALB/c adult mice. Copyright © 2012 Elsevier B.V. All rights reserved.

Drug use among complete responders, partial responders and non-responders in a longitudinal survey of nonagenarians

DEFF Research Database (Denmark)

Wastesson, Jonas W; Rasmussen, Lotte; Oksuzyan, Anna

2017-01-01

PURPOSE: In observational studies, non-response can limit representativity and introduce bias. We aimed to investigate the longitudinal changes in the number of used drugs among complete responders, partial responders, and non-responders in a whole birth cohort of Danish nonagenarians participati...

Effect of Sex Differences on Brain Mitochondrial Function and Its Suppression by Ovariectomy and in Aged Mice.

Science.gov (United States)

Gaignard, Pauline; Savouroux, Stéphane; Liere, Philippe; Pianos, Antoine; Thérond, Patrice; Schumacher, Michael; Slama, Abdelhamid; Guennoun, Rachida

2015-08-01

Sex steroids regulate brain function in both normal and pathological states. Mitochondria are an essential target of steroids, as demonstrated by the experimental administration of 17β-estradiol or progesterone (PROG) to ovariectomized female rodents, but the influence of endogenous sex steroids remains understudied. To address this issue, mitochondrial oxidative stress, the oxidative phosphorylation system, and brain steroid levels were analyzed under 3 different experimental sets of endocrine conditions. The first set was designed to study steroid-mediated sex differences in young male and female mice, intact and after gonadectomy. The second set concerned young female mice at 3 time points of the estrous cycle in order to analyze the influence of transient variations in steroid levels. The third set involved the evaluation of the effects of a permanent decrease in gonadal steroids in aged male and female mice. Our results show that young adult females have lower oxidative stress and a higher reduced nicotinamide adenine dinucleotide (NADH)-linked respiration rate, which is related to a higher pyruvate dehydrogenase complex activity as compared with young adult males. This sex difference did not depend on phases of the estrous cycle, was suppressed by ovariectomy but not by orchidectomy, and no longer existed in aged mice. Concomitant analysis of brain steroids showed that pregnenolone and PROG brain levels were higher in females during the reproductive period than in males and decreased with aging in females. These findings suggest that the major male/female differences in brain pregnenolone and PROG levels may contribute to the sex differences observed in brain mitochondrial function.

Adipogenic differentiation by adipose-derived stem cells harvested from GFP transgenic mice - including relationship of sex differences

International Nuclear Information System (INIS)

Ogawa, Rei; Mizuno, Hiroshi; Watanabe, Atsushi; Migita, Makoto; Hyakusoku, Hiko; Shimada, Takashi

2004-01-01

We have previously demonstrated that adipose-derived stromal cells (ASCs) as well as bone marrow-derived stromal cells (BSCs) differentiate into a variety of cell lineages both in vitro and in vivo. Both types are considered to include mesenchymal stem cells. Taking advantage of homogeneously marked cells from green fluorescent protein (GFP) transgenic mice, we have also previously reported the plasticity of BSCs and ASCs. In this study, we focused on adipogenic differentiation in vitro by ASCs harvested from GFP transgenic mice. Moreover, preadipocytes and mature adipocytes were harvested at the same time, and the cells were cultured to compare them with ASCs. Inguinal fat pads from GFP transgenic mice were used for the isolation of ASCs, preadipocytes, and mature adipocytes. After expansion to three passages of ASCs, the cells were incubated in an adipogenic medium for two weeks. Adipogenic differentiation of ASCs was assessed by Oil Red O staining and the expression of the adipocyte specific peroxisome proliferative activated receptor γ2 (PPAR-γ2) gene. These ASCs stained positively, and expression of PPAR-γ2 was detected. Moreover, we also tried to characterize the influence of sex differences on the adipogenic differentiation of ASCs harvested from both male and female mice. This was assessed by the expression levels of the PPAR-γ2 gene using real-time PCR. The results showed that the expression levels of ASCs harvested from female mice were a maximum of 2.89 times greater than those harvested from male mice. This suggests that the adipogenic differentiation of ASCs is closely related to sex differences

Differences in Susceptibility of Inbred Mice to Bacillus anthracis

Science.gov (United States)

1985-04-26

dilutions of the mixture were prepared and injected into A/J and CBA/J mice via the tail vein, as described by Ezzell et al. (9). Five mice per strain were...xylazine (Rompun, Miles Laboratories, Shawnee, Kansas) in 50 pl, and were dissected iwnmediately. Gross pathological changes were noted, heart blood and...anthracis; a histopathological study of skin lesions produced by B. anthracis in susceptible and resistant animal species. J. Infect. Dis. 80:1-13. 9. Ezzell

Uptake of 51Cr-SRBC in low- and high-responder mouse strains (C57BL/10ScSn/A/J mouse strains)

International Nuclear Information System (INIS)

Rihova, B.; Vetvicka, V.

1984-01-01

51 Cr-SRBC (sheep red blood cells) antigen clearance was studied in two strains of mice differing in the capacity to react with IgG antibody formation. In the B10 strain which is a poor IgG anti SRBC producer, before immunization 80.3% of the injected radioactivity was taken up by the liver, whereas after primary stimulation the uptake was only 31.1%. This value further decreases to 22.8% after secondary stimulation. The well IgG antibody producing A/J strain accumulated less antigen in the liver before immunization than the poorly responding strain (69.8%). On the 10th day after primary immunization a higher uptake of the radioactivity in the liver was shown than in the poor responder strain (53.8%) and this difference was even more pronounced after the secondary stimulation (49.6%). Interaction between peritoneal macrophages of the B10 and A/J strains before and after immunization with SRBC antigen was assessed from the formation of rosettes. Before immunization the low-responder strain B10 exhibited a three times higher level of rosette-forming macrophages (RFM), i.e. 6.1% than the high-responder strain A/J (2.0%). However, after immunization the RFM level in the A/J strain increased sevenfold (13.5%) whereas that in the low-responder strain B10 remained unaffected. These results suggested a role of macrophage population in the control of IgG antibody response. (author)

Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice

International Nuclear Information System (INIS)

Guo, Yixian; Zhang, Lanfang; Wan, Suigui; Sun, Xuejing; Wu, Yongxia; Yu, Xue-Zhong; Xia, Chang-Qing

2014-01-01

Highlights: • Injection of UVB-irradiated iDCs induces alloantigen tolerance. • This alloantigen tolerance may be associated regulatory T cell induction. • Tolerant mice serve as bone marrow donors reduces GVHD to their F1 recipients in allo-HSCT. • Tolerance is maintained in F1 recipients for long time post HSCT. - Abstract: Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) has been employed worldwide in recent years and led to favorable outcome in a group of patients who do not have human leukocyte antigen (HLA)-matched donors. However, the high incidence of severe graft-versus-host disease (GVHD) is a major problem for Haplo-HSCT. In the current study, we performed a proof of concept mouse study to test whether induction of allogeneic tolerance between two different parental strains was able to attenuate GVHD in Haplo-HSCT to the F1 mice. We induced alloantigen tolerance in C3H mice (H-2k) using ultraviolet B (UVB) irradiated immature dendritic cells (iDCs) derived from the cultures of Balb/c bone marrow cells. Then, we performed Haplo-HSCT using tolerant C3H mice as donors to F1 mice (C3H × Balb/c). The results demonstrated that this approach markedly reduced GVHD-associated death and significantly prolonged the survival of recipient mice in contrast to the groups with donors (C3H mice) that received infusion of non-UVB-irradiated DCs. Further studies showed that there were enhanced Tregs in the tolerant mice and alloantigen-specific T cell response was skewed to more IL-10-producing T cells, suggesting that these regulatory T cells might have contributed to the attenuation of GVHD. This study suggests that it is a feasible approach to preventing GVHD in Haplo-HSCT in children by pre-induction of alloantigen tolerance between the two parents. This concept may also lead to more opportunities in cell-based immunotherapy for GVHD post Haplo-HSCT

Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice

Energy Technology Data Exchange (ETDEWEB)

Guo, Yixian; Zhang, Lanfang; Wan, Suigui; Sun, Xuejing; Wu, Yongxia [Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Yu, Xue-Zhong [Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425 (United States); Xia, Chang-Qing, E-mail: cqx65@yahoo.com [Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China)

2014-04-18

Highlights: • Injection of UVB-irradiated iDCs induces alloantigen tolerance. • This alloantigen tolerance may be associated regulatory T cell induction. • Tolerant mice serve as bone marrow donors reduces GVHD to their F1 recipients in allo-HSCT. • Tolerance is maintained in F1 recipients for long time post HSCT. - Abstract: Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) has been employed worldwide in recent years and led to favorable outcome in a group of patients who do not have human leukocyte antigen (HLA)-matched donors. However, the high incidence of severe graft-versus-host disease (GVHD) is a major problem for Haplo-HSCT. In the current study, we performed a proof of concept mouse study to test whether induction of allogeneic tolerance between two different parental strains was able to attenuate GVHD in Haplo-HSCT to the F1 mice. We induced alloantigen tolerance in C3H mice (H-2k) using ultraviolet B (UVB) irradiated immature dendritic cells (iDCs) derived from the cultures of Balb/c bone marrow cells. Then, we performed Haplo-HSCT using tolerant C3H mice as donors to F1 mice (C3H × Balb/c). The results demonstrated that this approach markedly reduced GVHD-associated death and significantly prolonged the survival of recipient mice in contrast to the groups with donors (C3H mice) that received infusion of non-UVB-irradiated DCs. Further studies showed that there were enhanced Tregs in the tolerant mice and alloantigen-specific T cell response was skewed to more IL-10-producing T cells, suggesting that these regulatory T cells might have contributed to the attenuation of GVHD. This study suggests that it is a feasible approach to preventing GVHD in Haplo-HSCT in children by pre-induction of alloantigen tolerance between the two parents. This concept may also lead to more opportunities in cell-based immunotherapy for GVHD post Haplo-HSCT.

[Effects of nootropic drugs on hippocampal and cortical BDNF levels in mice with different exploratory behavior efficacy].

Science.gov (United States)

Firstova, Iu Iu; Dolotov, O V; Kondrakhin, e A; Dubynina, E V; Grivennikov, I A; Kovalev, G I

2009-01-01

The influence of subchronic administration of nootropic drugs (piracetam, phenotropil, meclophenoxate, pantocalcine, semax, nooglutil) on the brain-derived neurotrophic factor (BDNF) content in hippocampal and cortical tissues in mice with different exploratory behavior--high efficacy (HE) against low efficacy (LE)--in cross-maze test has been studied. The initial BDNF concentration in hippocamp (but not in cortex) of control HE mice was higher than that in LE mice (LE, 0.091 +/- 0.005 pg/microg; HE, 0.177 +/- 0.005 pg/microg; p nootrope effects, at least partially, via increase in hippocampal BDNF level, which is achieved only under conditions of cognitive deficiency.

An integrative transcriptomic approach to identify depot differences in genes and microRNAs in adipose tissues from high fat fed mice.

Science.gov (United States)

Wijayatunga, Nadeeja N; Pahlavani, Mandana; Kalupahana, Nishan S; Kottapalli, Kameswara Rao; Gunaratne, Preethi H; Coarfa, Cristian; Ramalingam, Latha; Moustaid-Moussa, Naima

2018-02-06

Obesity contributes to metabolic disorders such as diabetes and cardiovascular disease. Characterization of differences between the main adipose tissue depots, white (WAT) [including subcutaneous (SAT) and visceral adipose tissue (VAT)] and brown adipose tissue (BAT) helps to identify their roles in obesity. Thus, we studied depot-specific differences in whole transcriptome and miRNA profiles of SAT, VAT and BAT from high fat diet (HFD/45% of calories from fat) fed mice using RNA sequencing and small RNA-Seq. Using quantitative real-time polymerase chain reaction, we validated depot-specific differences in endoplasmic reticulum (ER) stress related genes and miRNAs using mice fed a HFD vs. low fat diet (LFD/10% of calories from fat). According to the transcriptomic analysis, lipogenesis, adipogenesis, inflammation, endoplasmic reticulum (ER) stress and unfolded protein response (UPR) were higher in VAT compared to BAT, whereas energy expenditure, fatty acid oxidation and oxidative phosphorylation were higher in BAT than in VAT of the HFD fed mice. In contrast to BAT, ER stress marker genes were significantly upregulated in VAT of HFD fed mice than the LFD fed mice. For the first time, we report depot specific differences in ER stress related miRNAs including; downregulation of miR-125b-5p, upregulation miR-143-3p, and miR-222-3p in VAT following HFD and upregulation of miR-30c-2-3p only in BAT following a HFD in mice than the LFD mice. In conclusion, HFD differentially regulates miRNAs and genes in different adipose depots with significant induction of genes related to lipogenesis, adipogenesis, inflammation, ER stress, and UPR in WAT compared to BAT.

Electroacupuncture in conscious free-moving mice reduces pain by ameliorating peripheral and central nociceptive mechanisms

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Wang, Ying; Lei, Jianxun; Gupta, Mihir; Peng, Fei; Lam, Sarah; Jha, Ritu; Raduenz, Ellis; Beitz, Al J.; Gupta, Kalpna

2016-01-01

Integrative approaches such as electroacupuncture, devoid of drug effects are gaining prominence for treating pain. Understanding the mechanisms of electroacupuncture induced analgesia would benefit chronic pain conditions such as sickle cell disease (SCD), for which patients may require opioid analgesics throughout life. Mouse models are instructive in developing a mechanistic understanding of pain, but the anesthesia/restraint required to administer electroacupuncture may alter the underlying mechanisms. To overcome these limitations, we developed a method to perform electroacupuncture in conscious, freely moving, unrestrained mice. Using this technique we demonstrate a significant analgesic effect in transgenic mouse models of SCD and cancer as well as complete Freund’s adjuvant-induced pain. We demonstrate a comprehensive antinociceptive effect on mechanical, cold and deep tissue hyperalagesia in both genders. Interestingly, individual mice showed a variable response to electroacupuncture, categorized into high-, moderate-, and non-responders. Mechanistically, electroacupuncture significantly ameliorated inflammatory and nociceptive mediators both peripherally and centrally in sickle mice correlative to the antinociceptive response. Application of sub-optimal doses of morphine in electroacupuncture-treated moderate-responders produced equivalent antinociception as obtained in high-responders. Electroacupuncture in conscious freely moving mice offers an effective approach to develop a mechanism-based understanding of analgesia devoid of the influence of anesthetics or restraints. PMID:27687125

The spleen as an extramedullary source of inflammatory cells responding to acetaminophen-induced liver injury

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Mandal, Mili; Gardner, Carol R.; Sun, Richard; Choi, Hyejeong; Lad, Sonali; Mishin, Vladimir; Laskin, Jeffrey D.; Laskin, Debra L.

2016-01-01

Macrophages have been shown to play a role in acetaminophen (APAP)-induced hepatotoxicity, contributing to both pro- and anti-inflammatory processes. In these studies, we analyzed the role of the spleen as an extramedullary source of hepatic macrophages. APAP administration (300 mg/kg, i.p.) to control mice resulted in an increase in CD11b + infiltrating Ly6G + granulocytic and Ly6G − monocytic cells in the spleen and the liver. The majority of the Ly6G + cells were also positive for the monocyte/macrophage activation marker, Ly6C, suggesting a myeloid derived suppressor cell (MDSC) phenotype. By comparison, Ly6G − cells consisted of 3 subpopulations expressing high, intermediate, and low levels of Ly6C. Splenectomy was associated with increases in mature (F4/80 + ) and immature (F4/80 − ) pro-inflammatory Ly6C hi macrophages and mature anti-inflammatory (Ly6C lo ) macrophages in the liver after APAP; increases in MDSCs were also noted in the livers of splenectomized (SPX) mice after APAP. This was associated with increases in APAP-induced expression of chemokine receptors regulating pro-inflammatory (CCR2) and anti-inflammatory (CX3CR1) macrophage trafficking. In contrast, APAP-induced increases in pro-inflammatory galectin-3 + macrophages were blunted in livers of SPX mice relative to control mice, along with hepatic expression of TNF-α, as well as the anti-inflammatory macrophage markers, FIZZ-1 and YM-1. These data demonstrate that multiple subpopulations of pro- and anti-inflammatory cells respond to APAP-induced injury, and that these cells originate from distinct hematopoietic reservoirs. - Highlights: • Multiple inflammatory cell subpopulations accumulate in the spleen and liver following acetaminophen (APAP) intoxication. • Splenectomy alters liver inflammatory cell populations responding to APAP. • Inflammatory cells accumulating in the liver in response to APAP originate from the spleen and the bone marrow. • Hepatotoxicity is reduced in

The spleen as an extramedullary source of inflammatory cells responding to acetaminophen-induced liver injury

Energy Technology Data Exchange (ETDEWEB)

Mandal, Mili, E-mail: milimandal@gmail.com [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Gardner, Carol R., E-mail: cgardner@pharmacy.rutgers.edu [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Sun, Richard, E-mail: fishpower52@gmail.com [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Choi, Hyejeong, E-mail: choi@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Lad, Sonali, E-mail: sonurose92@gmail.com [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Mishin, Vladimir, E-mail: mishinv@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Jeffrey D., E-mail: jlaskin@eohsi.rutgers.edu [Department of Environmental and Occupational Health, School of Public Health, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Debra L., E-mail: laskin@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States)

2016-08-01

Macrophages have been shown to play a role in acetaminophen (APAP)-induced hepatotoxicity, contributing to both pro- and anti-inflammatory processes. In these studies, we analyzed the role of the spleen as an extramedullary source of hepatic macrophages. APAP administration (300 mg/kg, i.p.) to control mice resulted in an increase in CD11b{sup +} infiltrating Ly6G{sup +} granulocytic and Ly6G{sup −} monocytic cells in the spleen and the liver. The majority of the Ly6G{sup +} cells were also positive for the monocyte/macrophage activation marker, Ly6C, suggesting a myeloid derived suppressor cell (MDSC) phenotype. By comparison, Ly6G{sup −} cells consisted of 3 subpopulations expressing high, intermediate, and low levels of Ly6C. Splenectomy was associated with increases in mature (F4/80{sup +}) and immature (F4/80{sup −}) pro-inflammatory Ly6C{sup hi} macrophages and mature anti-inflammatory (Ly6C{sup lo}) macrophages in the liver after APAP; increases in MDSCs were also noted in the livers of splenectomized (SPX) mice after APAP. This was associated with increases in APAP-induced expression of chemokine receptors regulating pro-inflammatory (CCR2) and anti-inflammatory (CX3CR1) macrophage trafficking. In contrast, APAP-induced increases in pro-inflammatory galectin-3{sup +} macrophages were blunted in livers of SPX mice relative to control mice, along with hepatic expression of TNF-α, as well as the anti-inflammatory macrophage markers, FIZZ-1 and YM-1. These data demonstrate that multiple subpopulations of pro- and anti-inflammatory cells respond to APAP-induced injury, and that these cells originate from distinct hematopoietic reservoirs. - Highlights: • Multiple inflammatory cell subpopulations accumulate in the spleen and liver following acetaminophen (APAP) intoxication. • Splenectomy alters liver inflammatory cell populations responding to APAP. • Inflammatory cells accumulating in the liver in response to APAP originate from the spleen and the

Partial promoter substitutions generating transcriptional sentinels of diverse signaling pathways in embryonic stem cells and mice

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Palle Serup

2012-11-01

Extracellular signals in development, physiology, homeostasis and disease often act by regulating transcription. Herein we describe a general method and specific resources for determining where and when such signaling occurs in live animals and for systematically comparing the timing and extent of different signals in different cellular contexts. We used recombinase-mediated cassette exchange (RMCE to test the effect of successively deleting conserved genomic regions of the ubiquitously active Rosa26 promoter and substituting the deleted regions for regulatory sequences that respond to diverse extracellular signals. We thereby created an allelic series of embryonic stem cells and mice, each containing a signal-responsive sentinel with different fluorescent reporters that respond with sensitivity and specificity to retinoic acids, bone morphogenic proteins, activin A, Wnts or Notch, and that can be adapted to any pathway that acts via DNA elements.

Partial promoter substitutions generating transcriptional sentinels of diverse signaling pathways in embryonic stem cells and mice

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Serup, Palle; Gustavsen, Carsten; Klein, Tino; Potter, Leah A.; Lin, Robert; Mullapudi, Nandita; Wandzioch, Ewa; Hines, Angela; Davis, Ashley; Bruun, Christine; Engberg, Nina; Petersen, Dorthe R.; Peterslund, Janny M. L.; MacDonald, Raymond J.; Grapin-Botton, Anne; Magnuson, Mark A.; Zaret, Kenneth S.

2012-01-01

SUMMARY Extracellular signals in development, physiology, homeostasis and disease often act by regulating transcription. Herein we describe a general method and specific resources for determining where and when such signaling occurs in live animals and for systematically comparing the timing and extent of different signals in different cellular contexts. We used recombinase-mediated cassette exchange (RMCE) to test the effect of successively deleting conserved genomic regions of the ubiquitously active Rosa26 promoter and substituting the deleted regions for regulatory sequences that respond to diverse extracellular signals. We thereby created an allelic series of embryonic stem cells and mice, each containing a signal-responsive sentinel with different fluorescent reporters that respond with sensitivity and specificity to retinoic acids, bone morphogenic proteins, activin A, Wnts or Notch, and that can be adapted to any pathway that acts via DNA elements. PMID:22888097

Increased hepatic Th2 and Treg subsets are associated with biliary fibrosis in different strains of mice caused by Clonorchis sinensis

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Fang, Fan; Du, Ying; Ma, Rui; Li, Xiang-Yang; Yu, Qian; Meng, Di; Tang, Ren-Xian; Zheng, Kui-Yang

2017-01-01

Previous studies showed that CD4+T cells responses might be involved in the process of biliary fibrosis. However, the underlying mechanism resulting in biliary fibrosis caused by Clonorchis sinensis remains not yet fully elucidated. The objectives of the present study were to investigate the different profiles of hepatic CD4+T cell subsets (Th1, Th2, Th17 and Treg cells) and their possible roles in the biliary fibrosis of different strains of mice (C57BL/6, BALB/c and FVB mice) induced by C. sinensis infection. C57BL/6, BALB/c and FVB mice were orally gavaged with 45 metacercariae. All mice were sacrificed on 28 days post infection in deep anesthesia conditions. The leukocytes in the liver were separated to examine CD4+T cell subsets by flow cytometry and the left lobe of liver was used to observe pathological changes, collagen depositions and the concentrations of hydroxyproline. The most serious cystic and fibrotic changes appeared in FVB infected mice indicated by gross observation, Masson’s trichrome staining and hydroxyproline content detection. In contrast to C57BL/6 infected mice, diffuse nodules and more intensive fibrosis were observed in the BALB/c infected mice. No differences of the hepatic Th1 subset and Th17 subset were found among the three strains, but the hepatic Th2 and Treg cells and their relative cytokines were dramatically increased in the BALB/c and FVB infected groups compared with the C57BL/6 infected group (Psinensis-infected mice. PMID:28151995

Humoral immune response of mice injected with tocopherol after exposure to X-radiation

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Roy, R.M.; Petrella, M.

1987-01-01

Serum haemagglutination (HA) titers have been determined for irradiated and non-irradiated mice responding to injection of two different concentrations of sheep red blood cells (SRBC) 24 to 48 hours after irradiation and immediate intraperitoneal injection of 2.5 mg DL alpha-tocopherol, the emulsifying vehicle, or saline. Mice maintained on tocopherol-deficient diets for 8 weeks post-weaning and those on regular diets exhibited increased IgG titers during peak response when injected with vitamin E. This partially alleviated the radiation-depression of the primary immune response induced by the smaller SRBC injection. This stimulatory effect was most significant in mice maintained on vitamin E-deficient diets. The HA titers of irradiated and non-irradiated mice maintained on normal rations were determined following a 10-fold increase in the SRBC inoculation. Antibody titer was greater following injection of the higher concentration of SRBC but post-irradiation injection of tocopherol immediately or 24 hours after irradiation did not enhance immune response. At the higher SRBC concentration maximum observed HA titers decreased with increasing dose of radiation; however, tocopherol had no significant dose-reducing effect. Tocopherol toxicity as manifested by depressed HA titers was observed occasionally in non-irradiated mice challenged with the higher concentration of SRBC

Susceptibility of Mice to Trypanosoma evansi Treated with Human Plasma Containing Different Concentrations of Apolipoprotein L-1

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Fanfa, Vinicius R.; Otto, Mateus A.; Gressler, Lucas T.; Tavares, Kaio C.S.; Lazzarotto, Cícera R.; Tonin, Alexandre A.; Miletti, Luiz C.; Duarte, Marta M.M.F.; Monteiro, Silvia G.

2011-01-01

The aim of this study was to test the susceptibility of mice to Trypanosoma evansi treated with human plasma containing different concentrations of apolipoprotein L-1 (APOL1). For this experiment, a strain of T. evansi and human plasma (plasmas 1, 2, and 3) from 3 adult males clinically healthy were used. In vivo test used 50 mice divided in 5 groups (A to E) with 10 animals in each group. Animals of groups B to E were infected, and then treated with 0.2 ml of human plasma in the following outline: negative control (A), positive control (B), treatment with plasma 1 (C), treatment with plasma 2 (D), and treatment with plasma 3 (E). Mice treated with human plasma showed an increase in longevity of 40.9±0.3 (C), 20±9.0 (D) and 35.6±9.3 (E) days compared to the control group (B) which was 4.3±0.5 days. The number of surviving mice and free of the parasite (blood smear and PCR negative) at the end of the experiment was 90%, 0%, and 60% for groups C, D, and E, respectively. The quantification of APOL1 was performed due to the large difference in the treatments that differed in the source plasma. In plasmas 1, 2, and 3 was detected the concentration of 194, 99, and 115 mg/dl of APOL1, respectively. However, we believe that this difference in the treatment efficiency is related to the level of APOL1 in plasmas. PMID:22355213

Intravitreal injection of anti-Interleukin (IL)-6 antibody attenuates experimental autoimmune uveitis in mice.

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Tode, Jan; Richert, Elisabeth; Koinzer, Stefan; Klettner, Alexa; Pickhinke, Ute; Garbers, Christoph; Rose-John, Stefan; Nölle, Bernhard; Roider, Johann

2017-08-01

To evaluate the effect of an intravitreally applied anti-IL-6 antibody for the treatment of experimental autoimmune uveitis (EAU). EAU was induced in female B10.RIII mice by Inter-Photoreceptor-Binding-Protein (IRBP) in complete Freund's adjuvant, boosted by Pertussis toxin. Single blinded intravitreal injections of anti-IL-6 antibody were applied 5-7days as well as 8-10days (3day interval) after EAU induction into the randomized treatment eye and phosphate buffered saline (PBS) into the fellow control eye. Clinical and fluorescein angiography scoring (6 EAU grades) was done at each injection day and at enucleation day 14. Enucleated eyes were either scored histologically (6 EAU grades) or examined by ELISA for levels of IL-6, IL-17 and IL-6 soluble Receptor (sIL-6R). Uveitis developed in all 12 mice. Clinical uveitis score was significantly reduced (p=0.035) in treated eyes (median 2.0, range 0-4.0, n=12) compared to the fellow control eyes (median 3.0, range 1.0-4.0, n=12). Angiography scores were reduced in 9/12 treated eyes and histological scores in 3/4 treated eyes compared to the fellow control eyes. Cytokine levels were determined in 8 mice, of which 4 responded to anti-IL-6 treatment and 4 did not respond. All mice responding to treatment had a significant reduction of IL-6 (ptreatment significantly attenuates experimental autoimmune uveitis in mice. EAU activity correlates with ocular IL-6 and IL-17 levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Experimental reinfection of BALB/c mice with different recombinant type I/III strains of Toxoplasma gondii: involvement of IFN-gamma and IL-10.

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Brandão, Geane Peroni; Melo, Maria Norma; Gazzinelli, Ricardo Tostes; Caetano, Braulia Costa; Ferreira, Adriana Melo; Silva, Letícia Azevedo; Vitor, Ricardo Wagner Almeida

2009-03-01

To assess reinfection of BALB/c mice with different Toxoplasma gondii strains, the animals were prime infected with the non-virulent D8 strain and challenged with virulent recombinant strains. Thirty days after challenge, brain cysts were obtained from surviving BALB/c mice and inoculated in Swiss mice to obtain tachyzoites for DNA extraction and PCR-RFLP analysis to distinguish the different T. gondii strains present in possible co-infections. Anti-Toxoplasma immune responses were evaluated in D8-primed BALB/c mice by detecting IFN-gamma and IL-10 produced by T cells and measuring immunoglobulin levels in serum samples. PCR-RFLP demonstrated that BALB/c mice were reinfected with the EGS strain at 45 days post prime infection (dpi) and with the EGS and CH3 strains at 180 dpi. High levels of IFN-gamma were detected after D8 infection, with no significant difference between 45 and 180-day intervals. However, higher IL-10 levels and higher plasmatic IgG1 and IgA were detected from samples obtained 180 days after infection. BALB/c mice were susceptible to reinfection with different recombinant T. gondii strains and this susceptibility correlated with enhancement of IL-10 production.

Phylogeny and adaptation shape the teeth of insular mice.

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Ledevin, Ronan; Chevret, Pascale; Ganem, Guila; Britton-Davidian, Janice; Hardouin, Emilie A; Chapuis, Jean-Louis; Pisanu, Benoit; da Luz Mathias, Maria; Schlager, Stefan; Auffray, Jean-Christophe; Renaud, Sabrina

2016-02-10

By accompanying human travels since prehistorical times, the house mouse dispersed widely throughout the world, and colonized many islands. The origin of the travellers determined the phylogenetic source of the insular mice, which encountered diverse ecological and environmental conditions on the various islands. Insular mice are thus an exceptional model to disentangle the relative role of phylogeny, ecology and climate in evolution. Molar shape is known to vary according to phylogeny and to respond to adaptation. Using for the first time a three-dimensional geometric morphometric approach, compared with a classical two-dimensional quantification, the relative effects of size variation, phylogeny, climate and ecology were investigated on molar shape diversity across a variety of islands. Phylogeny emerged as the factor of prime importance in shaping the molar. Changes in competition level, mostly driven by the presence or absence of the wood mouse on the different islands, appeared as the second most important effect. Climate and size differences accounted for slight shape variation. This evidences a balanced role of random differentiation related to history of colonization, and of adaptation possibly related to resource exploitation. © 2016 The Author(s).

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

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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.

Effect of three different cultivars of Lepidium meyenii (Maca on learning and depression in ovariectomized mice

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Gonzales Gustavo F

2006-06-01

Full Text Available Abstract Background Lepidium meyenii Walp. (Brassicaceae, known as Maca, is a Peruvian hypocotyl growing exclusively between 4000 and 4500 m altitude in the central Peruvian Andes, particularly in Junin plateau and is used traditionally to enhance fertility. Maca is a cultivated plant and different cultivars are described according to the color of the hypocotyls. Methods The study aimed to elucidate the effect of Yellow, Red and Black Maca on cognitive function and depression in ovariectomized (OVX mice. In all experiments OVX mice were treated during 21 days and divided in four groups: control group, Yellow Maca, Red Maca and Black Maca. Latent learning was assessed using the water finding task and the antidepressant activity of the three varieties of Maca was evaluated using the forced swimming test. Animals were sacrificed at the end of each treatment and the uterus were excised and weighed. Results Black Maca was the variety that showed the best response in the water finding task, particularly in the trained mice. The three varieties were effective to reduce finding latency in non trained and trained mice (P Conclusion Black Maca appeared to have more beneficial effects on latent learning in OVX mice; meanwhile, all varieties of Maca showed antidepressant activity.

Sex differences in the effects of adolescent social deprivation on alcohol consumption in μ-opioid receptor knockout mice.

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Moriya, Yuki; Kasahara, Yoshiyuki; Hall, F Scott; Sakakibara, Yasufumi; Uhl, George R; Tomita, Hiroaki; Sora, Ichiro

2015-04-01

Evidence based on clinical and experimental animal studies indicates that adolescent social deprivation influences alcohol consumption in a sex-dependent manner, perhaps by influencing stress responses. However, the mechanisms underlying the interaction between these phenomena remain to be elucidated. Since the μ-opioid receptor (MOP) has been reported to have key roles in social stress responses as well as the reinforcing/addictive effects of ethanol, MOP is a candidate molecule that may link adolescent social deprivation and subsequent alterations in alcohol consumption. To evaluate the involvement of MOP and social isolation-induced changes in alcohol consumption, as well as the effect of sex differences on responses to social isolation, alcohol consumption was assessed using a two-bottle home-cage consumption procedure (8 % ethanol vs. water) in MOP knockout (MOP-KO) and wild type (WT) mice of both sexes exposed to adolescent social deprivation or reared socially. Isolation rearing had no effects upon alcohol consumption of WT mice, whereas it significantly altered alcohol consumption in both male and female MOP-KO mice. Interestingly, social isolation affected ethanol consumption differently in male and female mice. Ethanol consumption was increased in male MOP-KO mice, but decreased in female MOP-KO mice, by isolation rearing. These results indicate that disturbances of MOP function influence the effects of isolation rearing on ethanol consumption in a sex-dependent manner. Consequently, this suggests the possibility that genetic variation that influences MOP function may have differential roles in alcoholism in men and women, and alcoholism treatments that target MOP function may be differentially effective in males and females.

Differentiation of bone marrow cells to functional T lymphocytes following implantation of thymus grafts and thymic stroma in nude and ATxBM mice

International Nuclear Information System (INIS)

Splitter, G.A.; McGuire, T.C.; Davis, W.C.

1977-01-01

Cardiac allografts were used to compare the immunologic capacity of nude mice and adult, thymectomized, lethally irradiated, bone marrow-reconstituted (AT x BM) mice. Neither nude nor AT x BM mice were able to reject cardiac allografts of any party. However, both rejected grafts of any party following implantation of neonatal thymus or thymus from 3-week-old syngeneic mice. Irradiated syngeneic thymus grafts (800 R) were equally effective in restoring host responsiveness against allografts. In contrast, allogeneic thymus grafts restored the capacity to reject second-party heart grafts only in AT x BM mice. Second-party grafts persisted indefintely when placed on nude mice implanted with an allogeneic, unirradiated thymus graft. Third-party grafts transplanted 17 weeks after reconstitution, however, were rejected. Irradiated nude mice given normal littermate bone marrow and simultaneously grafted with second-party thymus and heart allografts also failed to reject their second-party heart grafts. The difference in ultimate capacity to respond between AT x BM and nude mice suggests that a maturational defect exists in the nude mouse environment which impedes development of precursor T lymphocytes

Caregiver functioning following early childhood TBI: do moms and dads respond differently?

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Wade, Shari L; Walz, Nicolay C; Cassedy, Amy; Taylor, H Gerry; Stancin, Terry; Yeates, Keith Owen

2010-01-01

Research suggests that pediatric TBI results in injury-related stress and burden and psychological distress for parents. However, existing studies have focused almost exclusively on mothers, so that we know relatively little about the impact of childhood TBI on fathers. The aims were to prospectively examine differences in maternal and paternal response to early childhood TBI over time relative to a comparison cohort of mothers and fathers of children with orthopedic injuries (OI). The concurrent cohort/prospective research design involved repeated assessments of children aged 3-6 years with TBI or OI requiring hospitalization and their families. Shortly after injury and at 6, 12, and 18 months post injury, parents of 48 children with TBI (11 severe and 37 moderate) and 89 with OI completed standardized assessments of injury-related stress and burden, parental distress, and coping strategies. Mixed models analyses and Generalized Estimating Equations examined differences in maternal versus paternal burden, distress, and coping over time. The analyses included interactions of parent sex with group (severe TBI, moderate TBI, OI) and time since injury, to examine the moderating effects of injury severity on parental response to injury over time. Fathers were more likely than mothers to use denial to cope following moderate and severe TBI, but not OI. Conversely, mothers were more likely to prefer acceptance and emotion-focused strategies than fathers regardless of the type of injury. The use of active coping strategies varied as a function of injury type, parent sex, and time since injury. Fathers reported greater injury-related stress and distress than mothers over time, with pronounced differences in the severe TBI and OI groups. Mothers and fathers appear to respond differently following TBI. The different types of responses may serve to exacerbate emerging family dysfunction.

The metabotropic glutamate 5 receptor modulates extinction and reinstatement of methamphetamine-seeking in mice.

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Rose Chesworth

Full Text Available Methamphetamine (METH is a highly addictive psychostimulant with no therapeutics registered to assist addicts in discontinuing use. Glutamatergic dysfunction has been implicated in the development and maintenance of addiction. We sought to assess the involvement of the metabotropic glutamate 5 receptor (mGlu5 in behaviours relevant to METH addiction because this receptor has been implicated in the actions of other drugs of abuse, including alcohol, cocaine and opiates. mGlu5 knockout (KO mice were tested in intravenous self-administration, conditioned place preference and locomotor sensitization. Self-administration of sucrose was used to assess the response of KO mice to a natural reward. Acquisition and maintenance of self-administration, as well as the motivation to self-administer METH was intact in mGlu5 KO mice. Importantly, mGlu5 KO mice required more extinction sessions to extinguish the operant response for METH, and exhibited an enhanced propensity to reinstate operant responding following exposure to drug-associated cues. This phenotype was not present when KO mice were tested in an equivalent paradigm assessing operant responding for sucrose. Development of conditioned place preference and locomotor sensitization were intact in KO mice; however, conditioned hyperactivity to the context previously paired with drug was elevated in KO mice. These data demonstrate a role for mGlu5 in the extinction and reinstatement of METH-seeking, and suggests a role for mGlu5 in regulating contextual salience.

Perinatal Exposure to Insecticide Methamidophos Suppressed Production of Proinflammatory Cytokines Responding to Virus Infection in Lung Tissues in Mice

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Wataru Watanabe

2013-01-01

Full Text Available Methamidophos, a representative organophosphate insecticide, is regulated because of its severe neurotoxicity, but it is suspected of contaminating agricultural foods in many countries due to illicit use. To reveal unknown effects of methamidophos on human health, we evaluated the developmental immunotoxicity of methamidophos using a respiratory syncytial virus (RSV infection mouse model. Pregnant mice were exposed to methamidophos (10 or 20 ppm in their drinking water from gestation day 10 to weaning on postnatal day 21. Offsprings born to these dams were intranasally infected with RSV. The levels of interleukin-6 (IL-6 and interferon-gamma in the bronchoalveolar lavage fluids after infection were significantly decreased in offspring mice exposed to methamidophos. Treatment with methamidophos did not affect the pulmonary viral titers but suppressed moderately the inflammation of lung tissues of RSV-infected offspring, histopathologically. DNA microarray analysis revealed that gene expression of the cytokines in the lungs of offspring mice exposed to 20 ppm of methamidophos was apparently suppressed compared with the control. Methamidophos did not suppress IL-6 production in RSV-infected J774.1 cell cultures. Thus, exposure of the mother to methamidophos during pregnancy and nursing was suggested to cause an irregular immune response in the lung tissues in the offspring mice.

CAST/EiJ and C57BL/6J Mice Differ in Their Oral and Postoral Attraction to Glucose and Fructose.

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Sclafani, Anthony; Vural, Austin S; Ackroff, Karen

2017-03-01

A recent study indicated that CAST/EiJ and C57BL/6J mice differ in their taste preferences for maltodextrin but display similar sucrose preferences. The present study revealed strain differences in preferences for the constituent sugars of sucrose. Whereas B6 mice preferred 8% glucose to 8% fructose in 2-day tests, the CAST mice preferred fructose to glucose. These preferences emerged with repeated testing which suggested post-oral influences. In a second experiment, 2-day choice tests were conducted with the sugars versus a sucralose + saccharin (SS) mixture which is highly preferred in brief access tests. B6 mice strongly preferred glucose but not fructose to the non-nutritive SS whereas CAST mice preferred SS to both glucose and fructose even when food restricted. This implied that CAST mice are insensitive to the postoral appetite stimulating actions of the 2 sugars. A third experiment revealed, however, that intragastric glucose and fructose infusions conditioned significant but mild flavor preferences in CAST mice, whereas in B6 mice glucose conditioned a robust preference but fructose was ineffective. Thus, unlike other mouse strains and rats, glucose is not more reinforcing than fructose in CAST mice. Their oral preference for fructose over glucose may be related to a subsensitive maltodextrin receptor or glucose-specific receptor which is stimulated by glucose but not fructose. The failure of CAST mice to prefer glucose to a non-nutritive sweetener distinguishes this strain from other mouse strains and rats. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Radiosensitivity of mice of different lines and age as determinated with reference to ''intestinal'' death and DNA repair in intestinal epithelium cells

International Nuclear Information System (INIS)

Konoplyannikova, O.A.; Sklobovskaya, M.V.; Konoplyannikov, A.G.; Saenko, A.S.

1982-01-01

A study was made of the influence of strain- and age-related differences on mouse mortality after irradiation with doses lying within the ''intest+nal'' dose range, and also damages to stem cells of intestinal epithelium and induction and repair of single-strand DNA breaks in intestinal epitherium cells. Mice of different lines and age vary in LDsub(50/4) and stem cell radiosensitivity. There are no differences in the sedimentation constants of DNA fragments in alkaline lysates of intestinal crypts of intact mice of different age. Radiosensitivity determined with reference to single-strand breaks induction in DNA is similar with different mo use groups. Repair of single-strand DNA breaks of eldery mice is slower than that of young animals

Academics respond

DEFF Research Database (Denmark)

Hazel, Spencer

2015-01-01

Contribution to the article "Academics respond: Brexit would weaken UK university research and funding", Guardian Witness, The Guardian, UK......Contribution to the article "Academics respond: Brexit would weaken UK university research and funding", Guardian Witness, The Guardian, UK...

Experimental reinfection of BALB/c mice with different recombinant type I/III strains of Toxoplasma gondii: involvement of IFN-³ and IL-10

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Geane Peroni Brandão

2009-03-01

Full Text Available To assess reinfection of BALB/c mice with different Toxoplasma gondii strains, the animals were prime infected with the non-virulent D8 strain and challenged with virulent recombinant strains. Thirty days after challenge, brain cysts were obtained from surviving BALB/c mice and inoculated in Swiss mice to obtain tachyzoites for DNA extraction and PCR-RFLP analysis to distinguish the different T. gondii strains present in possible co-infections. Anti-Toxoplasma immune responses were evaluated in D8-primed BALB/c mice by detecting IFN-³ and IL-10 produced by T cells and measuring immunoglobulin levels in serum samples. PCR-RFLP demonstrated that BALB/c mice were reinfected with the EGS strain at 45 days post prime infection (dpi and with the EGS and CH3 strains at 180 dpi. High levels of IFN-³ were detected after D8 infection, with no significant difference between 45 and 180-day intervals. However, higher IL-10 levels and higher plasmatic IgG1 and IgA were detected from samples obtained 180 days after infection. BALB/c mice were susceptible to reinfection with different recombinant T. gondii strains and this susceptibility correlated with enhancement of IL-10 production.

Differences in the acute intestinal syndrome after partial and total abdominal irradiation in mice

International Nuclear Information System (INIS)

Dewit, L.; Oussoren, Y.; Bartelink, H.; Stewart, F.A.

1985-01-01

The acute intestinal syndrome in mice was analysed after partial (PAI) and total abdominal irradiation (TAI). The LDsub(50/15) was significantly higher after PAI (16.3 Gy) than after TAI(14.3 Gy). The dose-response curve for maximal weight loss also showed a shift of 1.8-2 Gy to higher doses after PAI compared with TAI. The X-ray survival curve for duodenal crypt cells was shifted by only 0.6 Gy for PAI and TAI. In order to assess the possible role of radiation-induced leucopenia and the influence of irradiating the spleen (shielded with PAI), lethality, weight loss and blood leucocyte counts were compared after PAI and TAI in splenectomized and non-splenectomized mice. No major difference in leucopenia was found between the different treatment groups, whereas the differences in lethality and weight loss between PAI and TAI remained the same. Shielding the spleen in the partial abdominal field therefore did not contribute to the difference in LDsub(50/15). These findings imply that the increased LDsub(50/15) after PAI compared with TAI was mainly due to shielding of a small part of the bowel (about 13 per cent of the abdominal area). (author)

Variable Suppression of Serum Thyroxine in Female Mice of Different Inbred Strains by Triiodothyronine Administered in Drinking Water

Science.gov (United States)

Hamidi, Sepehr; Aliesky, Holly; Chen, Chun-Rong; Rapoport, Basil

2010-01-01

Background Recombinant-inbred mouse strains differ in their susceptibility to Graves'-like hyperthyroidism induced by immunization with adenovirus expressing the human thyrotropin (TSH) receptor. Because one genetic component contributing to this susceptibility is altered thyroid sensitivity to TSH receptor agonist stimulation, we wished to quantify thyroid responsiveness to TSH. For such studies, it is necessary to suppress endogenous TSH by administering L-3,5,3′-triiodothyronine (L-T3), with the subsequent decrease in serum thyroxine (T4) reflecting endogenous TSH suppression. Our two objectives were to assess in different inbred strains of mice (i) the extent of serum T4 suppression after L-T3 administration and (ii) the magnitude of serum T4 increase induced by TSH. Methods Mice were tail-bled to establish baseline-serum T4 before L-T3 administration. We initially employed a protocol of L-T3-supplemented drinking water for 7 days. In subsequent experiments, we injected L-T3 intraperitoneally (i.p.) daily for 3 days. Mice were then injected i.p. with bovine TSH (10 mU) and euthanized 5 hours later. Serum T4 was assayed before L-T3 administration, and before and after TSH injection. In some experiments, serum T3 and estradiol were measured in pooled sera. Results Oral L-T3 (3 or 5 μg/mL) suppressed serum T4 levels by 26%–64% in female BALB/c mice but >95% in males. T4 suppression in female B6 mice ranged from 0% to 90%. In C3H mice, L-T3 at 3 μg/mL was ineffective but 5 μg/mL achieved >80% serum T4 reduction. Unlike inbred mice, in outbred CF1 mice the same protocol was more effective: 83% in females and 100% suppression in males. The degree of T4 suppression was unrelated to baseline T4, T3, or estradiol, but was related to mouse weight and postmortem T3, with greater suppression in larger mice (outbred CF1 animals and inbred males). Among females with serum T4 suppression >80%, the increase in serum T4 after TSH injection was greater for BALB

Increased hepatic Th2 and Treg subsets are associated with biliary fibrosis in different strains of mice caused by Clonorchis sinensis.

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Bei-Bei Zhang

Full Text Available Previous studies showed that CD4+T cells responses might be involved in the process of biliary fibrosis. However, the underlying mechanism resulting in biliary fibrosis caused by Clonorchis sinensis remains not yet fully elucidated. The objectives of the present study were to investigate the different profiles of hepatic CD4+T cell subsets (Th1, Th2, Th17 and Treg cells and their possible roles in the biliary fibrosis of different strains of mice (C57BL/6, BALB/c and FVB mice induced by C. sinensis infection. C57BL/6, BALB/c and FVB mice were orally gavaged with 45 metacercariae. All mice were sacrificed on 28 days post infection in deep anesthesia conditions. The leukocytes in the liver were separated to examine CD4+T cell subsets by flow cytometry and the left lobe of liver was used to observe pathological changes, collagen depositions and the concentrations of hydroxyproline. The most serious cystic and fibrotic changes appeared in FVB infected mice indicated by gross observation, Masson's trichrome staining and hydroxyproline content detection. In contrast to C57BL/6 infected mice, diffuse nodules and more intensive fibrosis were observed in the BALB/c infected mice. No differences of the hepatic Th1 subset and Th17 subset were found among the three strains, but the hepatic Th2 and Treg cells and their relative cytokines were dramatically increased in the BALB/c and FVB infected groups compared with the C57BL/6 infected group (P<0.01. Importantly, increased Th2 subset and Treg subset all positively correlated with hydroxyproline contents (P<0.01. This result for the first time implied that the increased hepatic Th2 and Treg cell subsets were likely to play potential roles in the formation of biliary fibrosis in C. sinensis-infected mice.

Lymphoma induction by heterocyclic amines in Eu-pim-1 transgenic mice

DEFF Research Database (Denmark)

Sørensen, Ilona Kryspin; Kristiansen, E.; Mortensen, Alicja

1997-01-01

The usefulness of transgenic E mu-pim-1 mice bearing in their genome the pim-1 oncogene supplemented with an upstream immunoglobulin enhancer and a downstream murine leukaemia virus long terminal repeat, as sensitive test organisms was studied in two short-term carcinogenicity studies. The mice...... to bacteria and cultured mammalian cells. PhIP is a potent mouse lymphomagen, while IQ is a liver, lung and forestomach carcinogen in mice. We found that transgenic E mu-pim-1 mice are highly susceptible to PhIP induced lymphomagenesis but do not respond to IQ treatment. PhIP feeding of E mu-pim-1 mice...... not only increased the total number of T-cell lymphomas but also decreased the latency time compared to either transgenic or wild-type controls. The effect was most pronounced in the treated female E mu-pim-1 mice, which showed a higher incidence of PhIP induced T-cell lymphomas than transgenic males...

Sexual dimorphism and the effects of the X-linked Tfm locus on hexobarbitone metabolism and action in mice.

Science.gov (United States)

King, D K; Shapiro, B H

1981-09-01

1 Normal males of the testicular feminized strain of mice (Tfm) had longer hexobarbitone-induced sleeping times than females, and hepatic hexobarbitone hydroxylase activity different in that the Km was higher and the Vmax lower in the male. 2 Castration and androgen replacement studies indicated that testicular androgens were responsible for the sexual differences in drug metabolism found in this mouse strain. 3 Hepatic hexobarbitone metabolism and action were feminized in the intact, androgen-insensitive, genetically male Tfm mouse. Furthermore, hexobarbitone hydroxylase activities were less responsive to large doses of testosterone in Tfm mice than in normal males. 4 The Tfm mouse with a deficiency in androgen receptors responded to the enzyme-inductive effects of phenobarbitone and softwood bedding, indicating that these inducers do not act through the androgen receptors.

Mutation types and aging differently affect revertant fiber expansion in dystrophic mdx and mdx52 mice.

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Yusuke Echigoya

Full Text Available Duchenne muscular dystrophy (DMD, one of the most common and lethal genetic disorders, and the mdx mouse myopathies are caused by a lack of dystrophin protein. These dystrophic muscles contain sporadic clusters of dystrophin-expressing revertant fibers (RFs, as detected by immunohistochemistry. RFs are known to arise from muscle precursor cells with spontaneous exon skipping (alternative splicing and clonally expand in size with increasing age through the process of muscle degeneration/regeneration. The expansion of revertant clusters is thought to represent the cumulative history of muscle regeneration and proliferation of such precursor cells. However, the precise mechanisms by which RFs arise and expand are poorly understood. Here, to test the effects of mutation types and aging on RF expansion and muscle regeneration, we examined the number of RFs in mdx mice (containing a nonsense mutation in exon 23 and mdx52 mice (containing deletion mutation of exon 52 with the same C57BL/6 background at 2, 6, 12, and 18months of age. Mdx mice displayed a significantly higher number of RFs compared to mdx52 mice in all age groups, suggesting that revertant fiber expansion largely depends on the type of mutation and/or location in the gene. A significant increase in the expression and clustering levels of RFs was found beginning at 6months of age in mdx mice compared with mdx52 mice. In contrast to the significant expansion of RFs with increasing age, the number of centrally nucleated fibers and embryonic myosin heavy chain-positive fibers (indicative of cumulative and current muscle regeneration, respectively decreased with age in both mouse strains. These results suggest that mutation types and aging differently affect revertant fiber expansion in mdx and mdx52 mice.

Sex Differences in the Hepatic Cholesterol Sensing Mechanisms in Mice

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Ingemar Björkhem

2013-09-01

Full Text Available Cholesterol is linked to many multifactorial disorders, including different forms of liver disease where development and severity depend on the sex. We performed a detailed analysis of cholesterol and bile acid synthesis pathways at the level of genes and metabolites combined with the expression studies of hepatic cholesterol uptake and transport in female and male mice fed with a high-fat diet with or without cholesterol. Lack of dietary cholesterol led to a stronger response of the sterol sensing mechanism in females, resulting in higher expression of cholesterogenic genes compared to males. With cholesterol in the diet, the genes were down-regulated in both sexes; however, males maintained a more efficient hepatic metabolic flux through the pathway. Females had higher content of hepatic cholesterol but this was likely not due to diminished excretion but rather due to increased synthesis and absorption. Dietary cholesterol and sex were not important for gallbladder bile acids composition. Neither sex up-regulated Cyp7a1 upon cholesterol loading and there was no compensatory up-regulation of Abcg5 or Abcg8 transporters. On the other hand, females had higher expression of the Ldlr and Cd36 genes. These findings explain sexual dimorphism of cholesterol metabolism in response to dietary cholesterol in a high-fat diet in mice, which contributes to understanding the sex-basis of cholesterol-associated liver diseases.

Innate and Adaptive Immune Response to Pneumonia Virus of Mice in a Resistant and a Susceptible Mouse Strain

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Ellen R. T. Watkiss

2013-01-01

Full Text Available Respiratory syncytial virus (RSV is the leading cause of infant bronchiolitis. The closely related pneumonia virus of mice (PVM causes a similar immune-mediated disease in mice, which allows an analysis of host factors that lead to severe illness. This project was designed to compare the immune responses to lethal and sublethal doses of PVM strain 15 in Balb/c and C57Bl/6 mice. Balb/c mice responded to PVM infection with an earlier and stronger innate response that failed to control viral replication. Production of inflammatory cyto- and chemokines, as well as infiltration of neutrophils and IFN-γ secreting natural killer cells into the lungs, was more predominant in Balb/c mice. In contrast, C57Bl/6 mice were capable of suppressing both viral replication and innate inflammatory responses. After a sublethal infection, PVM-induced IFN-γ production by splenocytes was stronger early during infection and weaker at late time points in C57Bl/6 mice when compared to Balb/c mice. Furthermore, although the IgG levels were similar and the mucosal IgA titres lower, the virus neutralizing antibody titres were higher in C57Bl/6 mice than in Balb/c mice. Overall, the difference in susceptibility of these two strains appeared to be related not to an inherent T helper bias, but to the capacity of the C57Bl/6 mice to control both viral replication and the immune response elicited by PVM.

Two Genetically Similar H9N2 Influenza A Viruses Show Different Pathogenicity in Mice

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Qingtao Liu

2016-11-01

Full Text Available H9N2 Avian influenza virus has repeatedly infected humans and other mammals, which highlights the need to determine the pathogenicity and the corresponding mechanism of this virus for mammals. In this study, we found two H9N2 viruses with similar genetic background but with different pathogenicity in mice. The A/duck/Nanjing/06/2003 (NJ06 virus was highly pathogenic for mice, with a 50% mouse lethal dose of 102.83 50% egg infectious dose, whereas the A/duck/Nanjing/01/1999 (NJ01 virus was low pathogenic for mice, with a 50% mouse lethal dose of >106.81 50% egg infectious dose. Further studies showed that the NJ06 virus grew faster and reached significantly higher titers than NJ01 in vivo and in vitro. Moreover, the NJ06 virus induced more severe lung lesions, and higher levels of inflammatory cellular infiltration and cytokine response in lungs than NJ01 did. However, only twelve different amino acid residues (HA-K157E, NA-A9T, NA-R435K, PB2-T149P, PB2-K627E, PB1-R187K, PA-L548M, PA-M550L, NP-G127E, NP-P277H, NP-D340N, NS1-D171N were found between the two viruses, and all these residues except for NA-R435K were located in the known functional regions involved in interaction of viral proteins or between the virus and host factors. Summary, our results suggest that multiple amino acid differences may be responsible for the higher pathogenicity of the NJ06 virus for mice, resulting in lethal infection, enhanced viral replication, severe lung lesions, and excessive inflammatory cellular infiltration and cytokine response in lungs. These observations will be helpful for better understanding the pathogenic potential and the corresponding molecular basis of H9N2 viruses that might pose threats to human health in the future.

The concentration of fear: mice's behavioural and physiological stress responses to different degrees of predation risk

Science.gov (United States)

Sánchez-González, Beatriz; Planillo, Aimara; Navarro-Castilla, Álvaro; Barja, Isabel

2018-02-01

Predation is an unavoidable and dangerous fact in the lifetime of prey animals and some sign of the proximity of a predator may be enough to trigger a response in the prey. We investigated whether different degrees of predation risk by red foxes ( Vulpes vulpes) evoke behavioural and physiological stress responses in wood mice ( Apodemus sylvaticus) . We examined the variation in mice responses due to individual factors (sex and reproductive status) and related them to the concentration of the volatile compounds from fox faeces over time. In our experiment, we introduced predation cues into four plots, each subjected to a different concentration treatment (0, 10, 50 and 100% concentration of fresh faeces of red fox), based on the following outline: initial odourless phase 0, phase1 in which predation treatment was renewed daily, and phase 2 in which we renewed the treatment only on the first day. Wood mice were live trapped during all three phases and the physiological response was measured non-invasively by analysing faecal corticosterone metabolites (FCM) in freshly collected faeces. Data were analysed by Generalized Linear Mixed Models. Overall, males were trapped less often than females, and reproductively active individuals from both sexes avoided traps more than non-reproductively active individuals, especially in medium- and high- concentration plots. Variations in FCM concentrations were explained by plot, the interaction between plot and treatment phase, and the interaction between the treatment phase and the reproductive status. During phase 1, we detected a significant rise in FCM levels that increased with predator faecal odour concentration. Additionally, reproductively active individuals showed a strong physiological response during both phases 1 and 2 in all plots, except the control plot. Our results indicated that wood mice are able to discriminate different degrees of predation risk, which allows them to trigger gradual changes in their

Acquisition of steady-state operant behavior in long-living Ames Dwarf mice.

Science.gov (United States)

Derenne, Adam; Brown-Borg, Holly; Feltman, Kathryn; Corbett, Grant; Lackman, Serena

2011-10-24

Ames dwarf mice have a Prop-1 mutation that has been identified with increased levels of IGF-I in the central nervous system, upregulation of neuroprotective systems, and increased lifespan. To elucidate the behavioral effects of the Prop-1 mutation, 8 Ames dwarf and 7 normal mice (all of whom were 8 months of age or younger) were compared on a differential-reinforcement-of-low-rate-of-responding schedule of reinforcement and a matching-to-sample task. On both tasks, nosepokes were reinforced with access to a saccharin solution. Comparisons were based on several measures of behavioral efficiency: pause durations, intertrial intervals, and numbers of responses. Ames dwarf mice were generally less efficient than normal mice. One possible cause of this outcome is that relatively young Ames dwarf mice show less cognitive development than age-matched normal mice. Copyright © 2011 Elsevier Inc. All rights reserved.

Exercise training-induced different improvement profile of endothelial progenitor cells function in mice with or without myocardial infarction.

Science.gov (United States)

Guo, Yuan; Peng, Ran; Liu, Qiong; Xu, Danyan

2016-10-15

Neovascularization in response to ischemia after myocardial infarction (MI) has been widely considered as being initiated by endothelial progenitor cells (EPCs). Well-documented evidences in recent years have proved exercise training (ET) improving EPC function. However, whether ET-induced improvement of EPC function under or without ischemic state is different has not been reported. Mice performed ET following an exercise prescription 1week after MI or non-MI surgery respectively. Bone marrow-derived EPCs were isolated at 0day, 3days, 1week, 2weeks, 4weeks, and 8weeks of ET. After 7days cultivation, EPC functions including proliferation, adhesion, migration, and in vitro angiogenesis were measured. AKT/glycogen synthase kinase 3β (GSK3β) signaling pathway was tested by western blotting. EPC function in mice underwent non-MI surgery was attenuated overtime, while ET ameliorated this tendency. EPC function was peaked at 4weeks ET in non-MI surgery mice and maintained with an extended exercise time. Besides, simple ischemia was sufficient to enhanced EPC function, with a maximum at 2weeks of MI surgery. In MI mice, ET further improved EPC function and achieved peak at 2weeks exercise. Furthermore, AKT/GSK3β signaling pathway activation was consistent with EPC function change after ischemia, which was further promoted by 4weeks exercise. ET significantly increased EPC function in mice both with and without MI, but the time points of peak function were different. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Th2 Regulation of Viral Myocarditis in Mice: Different Roles for TLR3 versus TRIF in Progression to Chronic Disease

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Eric D. Abston

2012-01-01

Full Text Available Viral infections are able to induce autoimmune inflammation in the heart. Here, we investigated the role of virus-activated Toll-like receptor (TLR3 and its adaptor TRIF on the development of autoimmune coxsackievirus B3 (CVB3 myocarditis in mice. Although TLR3- or TRIF-deficient mice developed similarly worse acute CVB3 myocarditis and viral replication compared to control mice, disease was significantly worse in TRIF compared to TLR3-deficient mice. Interestingly, TLR3-deficient mice developed an interleukin (IL-4-dominant T helper (Th2 response during acute CVB3 myocarditis with elevated markers of alternative activation, while TRIF-deficient mice elevated the Th2-associated cytokine IL-33. Treatment of TLR3-deficient mice with recombinant IL-33 improved heart function indicating that elevated IL-33 in the context of a classic Th2-driven response protects against autoimmune heart disease. We show for the first time that TLR3 versus TRIF deficiency results in different Th2 responses that uniquely influence the progression to chronic myocarditis.

Experimental reinfection of BALB/c mice with different recombinant type I/III strains of Toxoplasma gondii: involvement of IFN-³ and IL-10

OpenAIRE

Brandão,Geane Peroni; Melo,Maria Norma; Gazzinelli,Ricardo Tostes; Caetano,Braulia Costa; Ferreira,Adriana Melo; Silva,Letícia Azevedo; Vitor,Ricardo Wagner Almeida

2009-01-01

To assess reinfection of BALB/c mice with different Toxoplasma gondii strains, the animals were prime infected with the non-virulent D8 strain and challenged with virulent recombinant strains. Thirty days after challenge, brain cysts were obtained from surviving BALB/c mice and inoculated in Swiss mice to obtain tachyzoites for DNA extraction and PCR-RFLP analysis to distinguish the different T. gondii strains present in possible co-infections. Anti-Toxoplasma immune responses were evaluated ...

Species differences in methanol and formic acid pharmacokinetics in mice, rabbits and primates

International Nuclear Information System (INIS)

Sweeting, J. Nicole; Siu, Michelle; McCallum, Gordon P.; Miller, Lutfiya; Wells, Peter G.

2010-01-01

Methanol (MeOH) is metabolized primarily by alcohol dehydrogenase in humans, but by catalase in rodents, with species variations in the pharmacokinetics of its formic acid (FA) metabolite. The teratogenic potential of MeOH in humans is unknown, and its teratogenicity in rodents may not accurately reflect human developmental risk due to differential species metabolism, as for some other teratogens. To determine if human MeOH metabolism might be better reflected in rabbits than rodents, the plasma pharmacokinetics of MeOH and FA were compared in male CD-1 mice, New Zealand white rabbits and cynomolgus monkeys over time (24, 48 and 6 h, respectively) following a single intraperitoneal injection of 0.5 or 2 g/kg MeOH or its saline vehicle. Following the high dose, MeOH exhibited saturated elimination kinetics in all 3 species, with similar peak concentrations and a 2.5-fold higher clearance in mice than rabbits. FA accumulation within 6 h in primates was 5-fold and 43-fold higher than in rabbits and mice respectively, with accumulation being 10-fold higher in rabbits than mice. Over 48 h, FA accumulation was nearly 5-fold higher in rabbits than mice. Low-dose MeOH in mice and rabbits resulted in similarly saturated MeOH elimination in both species, but with approximately 2-fold higher clearance rates in mice. FA accumulation was 3.8-fold higher in rabbits than mice. Rabbits more closely than mice reflected primates for in vivo MeOH metabolism, and particularly FA accumulation, suggesting that developmental studies in rabbits may be useful for assessing potential human teratological risk.

The intestinal flora is required to support antibody responses to systemic immunization in infant and germ free mice.

Science.gov (United States)

Lamousé-Smith, Esi S; Tzeng, Alice; Starnbach, Michael N

2011-01-01

The presence of a complex and diverse intestinal flora is functionally important for regulating intestinal mucosal immune responses. However, the extent to which a balanced intestinal flora regulates systemic immune responses is still being defined. In order to specifically examine whether the acquisition of a less complex flora influences responses to immunization in the pre-weaning stages of life, we utilize a model in which infant mice acquire an intestinal flora from their mothers that has been altered by broad-spectrum antibiotics. In this model, pregnant dams are treated with a cocktail of antibiotics that alters both the density and microbial diversity of the intestinal flora. After challenge with a subcutaneous immunization, the antibiotic altered flora infant mice have lower antigen specific antibody titers compared to control age-matched mice. In a second model, we examined germ free (GF) mice to analyze how the complete lack of flora influences the ability to mount normal antibody responses following subcutaneous immunization. GF mice do not respond well to immunization and introduction of a normal flora into GF mice restores the capacity of these mice to respond. These results indicate that a gastrointestinal flora reduced in density and complexity at critical time points during development adversely impacts immune responses to systemic antigens.

Dietary Animal Plasma Proteins Improve the Intestinal Immune Response in Senescent Mice.

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Miró, Lluïsa; Garcia-Just, Alba; Amat, Concepció; Polo, Javier; Moretó, Miquel; Pérez-Bosque, Anna

2017-12-11

Increased life expectancy has promoted research on healthy aging. Aging is accompanied by increased non-specific immune activation (inflammaging) which favors the appearance of several disorders. Here, we study whether dietary supplementation with spray-dried animal plasma (SDP), which has been shown to reduce the activation of gut-associated lymphoid tissue (GALT) in rodents challenged by S. aureus enterotoxin B (SEB), and can also prevent the effects of aging on immune system homeostasis. We first characterized GALT in a mouse model of accelerated senescence (SAMP8) at different ages (compared to mice resistant to accelerated senescence; SAMR1). Second, we analyzed the SDP effects on GALT response to an SEB challenge in SAMP8 mice. In GALT characterization, aging increased the cell number and the percentage of activated Th lymphocytes in mesenteric lymph nodes and Peyer's patches (all, p < 0.05), as well as the expression of IL-6 and TNF-α in intestinal mucosa (both, p < 0.05). With respect to GALT response to the SEB challenge, young mice showed increased expression of intestinal IL-6 and TNF-α, as well as lymphocyte recruitment and activation (all, p < 0.05). However, the immune response of senescent mice to the SEB challenge was weak, since SEB did not change cell recruitment or the percentage of activated Th lymphocytes. Mice supplemented with SDP showed improved capacity to respond to the SEB challenge, similar to the response of the young mice. These results indicate that senescent mice have an impaired mucosal immune response characterized by unspecific GALT activation and a weak specific immune response. SDP supplementation reduces non-specific basal immune activation, allowing for the generation of specific responses.

The characteristics of non-respondents and respondents of a mental health survey among evacuees in a disaster: The Fukushima Health Management Survey.

Science.gov (United States)

Horikoshi, Naoko; Iwasa, Hajime; Yasumura, Seiji; Maeda, Masaharu

2017-12-19

The Fukushima Medical University conducted a mental health care program for evacuees after the Fukushima Daiichi nuclear power plant accident. However, the mental health status of non-respondents has not been considered for surveys using questionnaires. Therefore, the aim of this study was to clarify the characteristics of non-respondents and respondents. The target population of the survey (FY2011-2013) is people living in the nationally designated evacuation zone of Fukushima prefecture. Among these, the participants were 967 people (20 years or older). We examined factors that affected the difference between the groups of participants (i.e., non-respondents and respondents) using multivariate logistic regression analysis. Employment was higher in non-respondents (p=0.022) and they were also more socially isolated (p=0.047) when compared to respondents; non-respondents had a higher proportional risk of psychological distress compared to respondents (pemployment status (OR=1.99, 95% confidence interval [CI]:1.12-3.51) and psychological distress (OR=2.17, 95% CI:1.01-4.66). We found that non-respondents had a significantly higher proportion of psychological distress compared to the respondents. Although the non-respondents were the high-risk group, it is not possible to grasp the complexity of the situation by simply using questionnaire surveys. Therefore, in the future it is necessary to direct our efforts towards the mental health of non-respondents and respondents alike.

Experimental Tityus serrulatus scorpion envenomation: age- and sex-related differences in symptoms and mortality in mice

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Pucca MB

2011-01-01

Full Text Available Among the various methods for evaluating animal venom toxicity, the calculation of the median lethal dose (LD50 is the most widely used. Although different protocols can be used to calculate the LD50, the source of the venom and the method of extraction, as well as the strain, age, and sex of the animal model employed, should be taken into consideration. The objective of the present study was to evaluate the influence of sex and age on the toxicity of Tityus serrulatus scorpion venom in Swiss mice. Although the symptoms of envenomation were similar in male and female animals, female mice proved to be more resistant to the venom. In females, age had no impact on the susceptibility to scorpion envenomation. Male mice were more sensitive to T. serrulatus venom. Moreover, in males, age was an important parameter since sensitivity to the venom increased with age.

Interviewer-Respondent Interactions in Conversational and Standardized Interviewing

Science.gov (United States)

Mittereder, Felicitas; Durow, Jen; West, Brady T.; Kreuter, Frauke; Conrad, Frederick G.

2018-01-01

Standardized interviewing (SI) and conversational interviewing are two approaches to collect survey data that differ in how interviewers address respondent confusion. This article examines interviewer-respondent interactions that occur during these two techniques, focusing on requests for and provisions of clarification. The data derive from an…

Sunitinib-ibuprofen drug interaction affects the pharmacokinetics and tissue distribution of sunitinib to brain, liver, and kidney in male and female mice differently.

Science.gov (United States)

Lau, Christine Li Ling; Chan, Sook Tyng; Selvaratanam, Manimegahlai; Khoo, Hui Wen; Lim, Adeline Yi Ling; Modamio, Pilar; Mariño, Eduardo L; Segarra, Ignacio

2015-08-01

Tyrosine kinase inhibitor sunitinib (used in GIST, advanced RCC, and pancreatic neuroendocrine tumors) undergoes CYP3A4 metabolism and is an ABCB1B and ABCG2 efflux transporters substrate. We assessed the pharmacokinetic interaction with ibuprofen (an NSAID used by patients with cancer) in Balb/c male and female mice. Mice (study group) were coadministered (30 min apart) 30 mg/kg of ibuprofen and 60 mg/kg of sunitinib PO and compared with the control groups, which received sunitinib alone (60 mg/kg, PO). Sunitinib concentration in plasma, brain, kidney, and liver was measured by HPLC as scheduled and noncompartmental pharmacokinetic parameters estimated. In female control mice, sunitinib AUC0→∞ decreased in plasma (P brain (P male control mice. After ibuprofen coadministration, female mice showed lower AUC0→∞ in plasma (P brain, liver, and kidney (all P male mice, AUC0→∞ remained unchanged in plasma, increased in liver and kidney, and decreased in brain (all P male and female control mice, but changed after ibuprofen coadministration: Male mice showed 1.6-fold higher liver-to-plasma ratio (P female mice and in kidney (male and female mice) but decreased 55% in brain (P differences. The results illustrate the relevance of this DDI on sunitinib pharmacokinetics and tissue uptake. These may be due to gender-based P450 and efflux/transporters differences. © 2015 Société Française de Pharmacologie et de Thérapeutique.

Species-relevant inescapable stress differently influences memory consolidation and retrieval of mice in a spatial radial arm maze.

Science.gov (United States)

Janitzky, K; Schwegler, H; Kröber, A; Roskoden, T; Yanagawa, Y; Linke, R

2011-05-16

Stress affects learning and there are both facilitating and impairing actions of stressors on memory processes. Here we investigated the influence of acute exposure to 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), an ethological relevant stressor for rodents, on spatial memory formation and performance in a radial arm maze (RAM) task and studied TMT effects on corticosterone levels in GAD67-GFP knock-in mice and their wildtype littermates. Our results suggest that predator odor-exposure differently affects consolidation and retrieval of memory in a hippocampus-dependent spatial learning task in adult male mice, independently from their genotypes. Acute TMT-stress before retrieval facilitates performance, whereas repeated TMT-stress during consolidation exerts no influence. Additionally, we found genotype specific effects of TMT on corticosterone release. While TMT-stress tend to result in increased corticosterone release in wildtypes there was a significant decrease in transgenic mice. Taken together, these findings indicate that biologically significant predator odor-induced stress can have different actions on the strength of spatial memory formation depending on the timing with regard to memory phases. Furthermore, we suppose an impact of GABAergic mechanisms on HPA-stress axis activation to TMT resulting in absent peripheral corticosterone release of GAD67-GFP mice. Copyright © 2011 Elsevier B.V. All rights reserved.

Numerical variation of cell lysosomes of the proximal convoluted tubules of mice Kidneys submitted to different X-ray doses

International Nuclear Information System (INIS)

Silva Lapa, R. de C.R. da; Pacheco, I.P.; Segreto, C.

1984-01-01

The number of cell lysosomes of the proximal convoluted tubules of mice Kidneys (Mus musculus) before and after whole-body irradiation with different X-ray doses is confronted. The mice were sacrificed after 72 hours and the cortex fragments were conduct to electron microscopy. A statistically significant numerical reduction of the lysosomas was observed in 72 hours. (M.A.C.) [pt

Beryllium-induced immune response in C3H mice

Energy Technology Data Exchange (ETDEWEB)

Benson, J.M.; Bice, D.E.; Nikula, K.J. [and others

1995-12-01

Studies conducted at ITRI over the past several years have investigated whether Beagle dogs, monkeys, and mice are suitable models for human chronic beryllium-induced lung disease (CBD). Recent studies have focused on the histopathological and immunopathological changes occurring in A/J and C3H/HeJ mice acutely exposed by inhalation to Be metal. Lung lesions in both strains of mice included focal lymphocyte aggregates comprised primarily of B lymphocytes and lesser amounts of T-helper lymphocytes and microgranulomas consisting chiefly of macrophages and T-helper lymphocytes. The distribution of proliferating cells within the microgranulomas was similar to the distribution of T-helper cells. These results strongly suggested that A/J and C3H/HeJ mice responded to inhaled Be metal in a fashion similar to humans in terms of pulmonary lesions and the apparent in situ proliferation of T-helper cells. Results of these studies confirm lymphocyte involvement in the pulmonary response to inhaled Be metal.

Influence of different types of bedding materials on immune response and serum biochemical profile of caged mice

Directory of Open Access Journals (Sweden)

Vijayakumar . R

Full Text Available Contact bedding material is an important environmental factor and welfare creator for laboratory mice. It can alter important physiological process and create potential chance for experimental variation which puts hurdle for comparability. The present experiment was conducted to assess the possible impact of different types of bedding material viz CPS, NWS and PH with fifty one albino mice for a period of fifteen weeks in Laboratory Animal Facility. It was observed that local immunity in mice was enhanced in NWS. During in vitro immune assays, mice from NWS showed higher OD value for reactive oxygen radical, produced more NO2 and higher stimulation index i.e. 0.71 ± 0.01, 30.67 ± 0.88 μM and 7.90 ± 0.17, respectively than PH (0.23 ± 0.01, 17.0 ± 1.15 μM and 6.33 ± 0.21 and CPS (0.33 ± 0.03, 15.67 ± 1.20 μM and 6.46 ± 0.27. There was no influence of bedding type on systemic response. Reduced glutathione value in liver was higher in NWS than PH and CPS i.e. 8.54 ± 0.2, 7.09 ± 0.18 and 6.96 ± 0.14 μmole/ gm of tissue. But heart reduced glutathione showed no variation among different types of bedding materials. Serum analysis showed significantly (p<0.05 higher total protein and albumin value for enriched groups. But globulin value was not significantly differing for enriched and non-enriched groups. [Veterinary World 2010; 3(9.000: 417-420

Transcriptome-based identification and characterization of genes commonly responding to five different insecticides in the diamondback moth, Plutella xylostella.

Science.gov (United States)

Gao, Yue; Kim, Kyungmun; Kwon, Deok Ho; Jeong, In Hong; Clark, J Marshall; Lee, Si Hyeock

2018-01-01

When the 3rd instar larvae of the diamondback moth (DBM), Plutella xylostella, were pretreated with sublethal doses (LC 10 ) and then subsequently exposed to lethal doses (LC 50 ) of chlorantraniliprole, cypermethrin, dinotefuran, indoxacarb and spinosad via leaf dipping, their tolerance to insecticides was significantly enhanced. To identify genes that commonly respond to the treatment of different insecticides and are responsible for the tolerance enhancement, transcriptomic profiles of larvae treated with sublethal doses of the five insecticides were compared with that of untreated control. A total of 117,181 transcripts with a mean length of 662bp were generated by de novo assembly, of which 35,329 transcripts were annotated. Among them, 125, 143, 182, 215 and 149 transcripts were determined to be up-regulated whereas 67, 45, 60, 60 and 38 genes were down-regulated following treatments with chlorantraniliprole, cypermethrin, dinotefuran, indoxacarb and spinosad, respectively. Gene ontology (GO) analysis of differentially expressed genes (DEGs) revealed little differences in their GO profiles between treatments with different insecticides except for spinosad. Finally, the DEGs commonly responding to all insecticides were selected for further characterization, and some of their over-transcription levels were confirmed by quantitative PCR. The most notable examples of commonly responding over-transcribed genes were two cytochrome P450 genes (Cyp301a1 and Cyp9e2) and nine cuticular protein genes. In contrast, several genes composing the mitochondrial energy generation system were significantly down-regulated in all treated larvae. Considering the distinct structure and mode of action of the five insecticides tested, the differentially expressed genes identified in this study appear to be involved in general chemical defense at the initial stage of intoxication. Their possible roles in the tolerance/resistance development were discussed. Copyright © 2017 Elsevier

Rate of red blood cell destruction varies in different strains of mice infected with Plasmodium berghei-ANKA after chronic exposure

Directory of Open Access Journals (Sweden)

Kikuchi Mihoko

2009-05-01

Full Text Available Abstract Background Severe malaria anaemia in the semi-immune individuals in the holo-endemic area has been observed to occur at low parasite density with individual variation in the responses. Thus the following has been thought to be involved: auto-immune-mediated mechanisms of uninfected red blood cell destruction, and host genetic factors to explain the differences in individual responses under the same malaria transmission. In this study, the extent of red blood cell (RBC destruction in different strains of semi-immune mice model at relatively low parasitaemia was studied. Methodology To generate semi-immunity, four strains of mice were taken through several cycles of infection and treatment. By means of immunofluorescent assay and ELISA, sera were screened for anti-erythrocyte auto-antibodies, and their relationship with haematological parameters and parasitaemia in the strains of semi-immune mice was investigated. Results Upon challenge with Plasmodium berghei ANKA after generating semi-immune status, different mean percentage haemoglobin (Hb drop was observed in the mice strains (Balb/c = 47.1%; NZW = 30.05%; C57BL/6 = 28.44%; CBA = 25.1%, which occurred on different days for each strain (for Balb/c, mean period = 13.6 days; for C57BL/6, NZW, and CBA mean period = 10.6, 10.8, 10.9 days respectively. Binding of antibody to white ghost RBCs was observed in sera of the four strains of semi-immune mice by immunofluorescence. Mean percentage Hb drop per parasitaemia was highest in Balb/c (73.6, followed by C57BL/6 (8.6, CBA (6.9 and NZW (4.0, p = 0.0005. Consequently, auto-antibodies level to ghost RBC were correlated with degree of anaemia and were highest in Balb/c, when compared with the other strains, p Conclusion The results presented in this study seem to indicate that anti-RBC auto-antibodies may be involved in the destruction of uninfected RBC in semi-immune mice at relatively low parasite burden. Host genetic factors may also

Careless responding in internet-based quality of life assessments.

Science.gov (United States)

Schneider, Stefan; May, Marcella; Stone, Arthur A

2018-04-01

Quality of life (QoL) measurement relies upon participants providing meaningful responses, but not all respondents may pay sufficient attention when completing self-reported QoL measures. This study examined the impact of careless responding on the reliability and validity of Internet-based QoL assessments. Internet panelists (n = 2000) completed Patient-Reported Outcomes Measurement Information System (PROMIS®) short-forms (depression, fatigue, pain impact, applied cognitive abilities) and single-item QoL measures (global health, pain intensity) as part of a larger survey that included multiple checks of whether participants paid attention to the items. Latent class analysis was used to identify groups of non-careless and careless responders from the attentiveness checks. Analyses compared psychometric properties of the QoL measures (reliability of PROMIS short-forms, correlations among QoL scores, "known-groups" validity) between non-careless and careless responder groups. Whether person-fit statistics derived from PROMIS measures accurately discriminated careless and non-careless responders was also examined. About 7.4% of participants were classified as careless responders. No substantial differences in the reliability of PROMIS measures between non-careless and careless responder groups were observed. However, careless responding meaningfully and significantly affected the correlations among QoL domains, as well as the magnitude of differences in QoL between medical and disability groups (presence or absence of disability, depression diagnosis, chronic pain diagnosis). Person-fit statistics significantly and moderately distinguished between non-careless and careless responders. The results support the importance of identifying and screening out careless responders to ensure high-quality self-report data in Internet-based QoL research.

Criticality Safety Basics for INL Emergency Responders

Energy Technology Data Exchange (ETDEWEB)

Valerie L. Putman

2012-08-01

This document is a modular self-study guide about criticality safety principles for Idaho National Laboratory emergency responders. This guide provides basic criticality safety information for people who, in response to an emergency, might enter an area that contains much fissionable (or fissile) material. The information should help responders understand unique factors that might be important in responding to a criticality accident or in preventing a criticality accident while responding to a different emergency.

This study guide specifically supplements web-based training for firefighters (0INL1226) and includes information for other Idaho National Laboratory first responders. However, the guide audience also includes other first responders such as radiological control personnel.

For interested readers, this guide includes clearly marked additional information that will not be included on tests. The additional information includes historical examples (Been there. Done that.), as well as facts and more in-depth information (Did you know …).

INL criticality safety personnel revise this guide as needed to reflect program changes, user requests, and better information. Revision 0, issued May 2007, established the basic text. Revision 1 incorporates operation, program, and training changes implemented since 2007. Revision 1 increases focus on first responders because later responders are more likely to have more assistance and guidance from facility personnel and subject matter experts. Revision 1 also completely reorganized the training to better emphasize physical concepts behind the criticality controls that help keep emergency responders safe. The changes are based on and consistent with changes made to course 0INL1226.

Types and rate of cataract development in mice irradiated at different ages

International Nuclear Information System (INIS)

Gajewski, A.K.; Majewska, K.; Slowikowska, M.G.; Chomiczewski, K.; Kulig, A.

1977-01-01

The effect of age on the development of radiation cataract has been investigated in an inbred A strain of mice and, as a result, the patterns of age dependence and senile mice cataract development were obtained. In general, the lenses of mice 1 to 3 days old were the most sensitive to radiation; the maximum resistance was noted in 5-day-old mice, and from this age up to 3 to 7 weeks of life there was a period of increasing sensitivity. In older animals the lens sensitivity tends to level off. The early stages of cataract occurred in all irradiated groups at a younger age than in the control group, but the late stages occurred in irradiated groups at the same age as the senile cataract occurred in the control group. Two types of cataract were observed. One was typical for young irradiated mice 1 to 5 days of age and the other was typical for all remaining irradiated groups and for a control group. Also, an attempt was made to correlate the obtained results with the cell kinetics in normal lens epithelium

Effect of chronic pain on fentanyl self-administration in mice.

Directory of Open Access Journals (Sweden)

Carrie L Wade

Full Text Available The development of opioid addiction in subjects with established chronic pain is an area that is poorly understood. It is critically important to clearly understand the neurobiology associated with propensity toward conversion to addiction under conditions of chronic pain. To pose the question whether the presence of chronic pain influences motivation to self-administer opioids for reward, we applied a combination of rodent models of chronic mechanical hyperalgesia and opioid self-administration. We studied fentanyl self-administration in mice under three conditions that induce chronic mechanical hyperalgesia: inflammation, peripheral nerve injury, and repeated chemotherapeutic injections. Responding for fentanyl was compared among these conditions and their respective standard controls (naïve condition, vehicle injection or sham surgery. Acquisition of fentanyl self-administration behavior was reduced or absent in all three conditions of chronic hyperalgesia relative to control mice with normal sensory thresholds. To control for potential impairment in ability to learn the lever-pressing behavior or perform the associated motor tasks, all three groups were evaluated for acquisition of food-maintained responding. In contrast to the opioid, chronic hyperalgesia did not interfere with the reinforcing effect of food. These studies indicate that the establishment of chronic hyperalgesia is associated with reduced or ablated motivation to seek opioid reward in mice.

Over-expression of two different forms of the alpha-secretase ADAM10 affects learning and memory in mice.

Science.gov (United States)

Schmitt, Ulrich; Hiemke, Christoph; Fahrenholz, Falk; Schroeder, Anja

2006-12-15

Members of the ADAM family (adisintegrin and metalloprotease) are the main candidates for physiologically relevant alpha-secretases. The alpha-secretase cleaves in the non-amyloidogenic pathway the amyloid precursor protein within the region of the Abeta peptides preventing their aggregation in the brain. The increase of alpha-secretase activity in the brain provides a plausible strategy to prevent Abeta formation. Concerning this possibility two transgenic mouse lines (FVB/N) have been created: mice over-expressing the bovine form of the alpha-secretase (ADAM10) and mice over-expressing an inactive form of the alpha-secretase (ADAM10-E348A-HA; ADAM10-dn). For behavioral examination a F1 generation of transgenic mice (C57Bl/6 x FVB/N (tg)) was generated and compared to wild type F1 generation (C57Bl/6 x FVB/N). Behavior was characterized in the following tasks: standard open field, enriched open field, elevated plus-maze, and the Morris water maze hidden platform task. Concerning basal activity, exploration, and anxiety, transgenic mice behaved similar to controls. With respect to learning and memory both transgenic lines showed a significant deficit compared to controls. ADAM10 mice however, showed thigmotaxis with passive floating behavior in the Morris water maze indicating differences in motivation, whereas, ADAM10-dn mice displayed an inconspicuous but limited goal-directed search pattern. Thus variation of the enzymatic activity of alpha-secretase ADAM10 alters learning and memory differentially. Nevertheless, it could be concluded that both, ADAM10 and ADAM10-dn mice are suitable control mice for the assessment of alpha-secretase-related effects in animal models of Alzheimer's disease.

Chronic Co-species Housing Mice and Rats Increased the Competitiveness of Male Mice.

Science.gov (United States)

Liu, Ying-Juan; Li, Lai-Fu; Zhang, Yao-Hua; Guo, Hui-Fen; Xia, Min; Zhang, Meng-Wei; Jing, Xiao-Yuan; Zhang, Jing-Hua; Zhang, Jian-Xu

2017-03-01

Rats are predators of mice in nature. Nevertheless, it is a common practice to house mice and rats in a same room in some laboratories. In this study, we investigated the behavioral and physiological responsively of mice in long-term co-species housing conditions. Twenty-four male mice were randomly assigned to their original raising room (control) or a rat room (co-species-housed) for more than 6 weeks. In the open-field and light-dark box tests, the behaviors of the co-species-housed mice and controls were not different. In a 2-choice test of paired urine odors [rabbit urine (as a novel odor) vs. rat urine, cat urine (as a natural predator-scent) vs. rabbit urine, and cat urine vs. rat urine], the co-species-housed mice were more ready to investigate the rat urine odor compared with the controls and may have adapted to it. In an encounter test, the rat-room-exposed mice exhibited increased aggression levels, and their urines were more attractive to females. Correspondingly, the levels of major urinary proteins were increased in the co-species-housed mouse urine, along with some volatile pheromones. The serum testosterone levels were also enhanced in the co-species-housed mice, whereas the corticosterone levels were not different. The norepinephrine, dopamine, and 5-HT levels in the right hippocampus and striatum were not different between the 2. Our findings indicate that chronic co-species housing results in adaptation in male mice; furthermore, it appears that long-term rat-odor stimuli enhance the competitiveness of mice, which suggests that appropriate predator-odor stimuli may be important to the fitness of prey animals. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Sex differences in diurnal rhythms of food intake in mice caused by gonadal hormones and complement of sex chromosomes.

Science.gov (United States)

Chen, Xuqi; Wang, Lixin; Loh, Dawn H; Colwell, Christopher S; Taché, Yvette; Reue, Karen; Arnold, Arthur P

2015-09-01

We measured diurnal rhythms of food intake, as well as body weight and composition, while varying three major classes of sex-biasing factors: activational and organizational effects of gonadal hormones, and sex chromosome complement (SCC). Four Core Genotypes (FCG) mice, comprising XX and XY gonadal males and XX and XY gonadal females, were either gonad-intact or gonadectomized (GDX) as adults (2.5months); food intake was measured second-by-second for 7days starting 5weeks later, and body weight and composition were measured for 22weeks thereafter. Gonadal males weighed more than females. GDX increased body weight/fat of gonadal females, but increased body fat and reduced body weight of males. After GDX, XX mice had greater body weight and more fat than XY mice. In gonad-intact mice, males had greater total food intake and more meals than females during the dark phase, but females had more food intake and meals and larger meals than males during the light phase. GDX reduced overall food intake irrespective of gonad type or SCC, and eliminated differences in feeding between groups with different gonads. Diurnal phase of feeding was influenced by all three sex-biasing variables. Gonad-intact females had earlier onset and acrophase (peak) of feeding relative to males. GDX caused a phase-advance of feeding, especially in XX mice, leading to an earlier onset of feeding in GDX XX vs. XY mice, but earlier acrophase in GDX males relative to females. Gonadal hormones and SCC interact in the control of diurnal rhythms of food intake. Copyright © 2015 Elsevier Inc. All rights reserved.

Different effects of bisphenol-A on memory behavior and synaptic modification in intact and estrogen-deprived female mice.

Science.gov (United States)

Xu, Xiaohong; Gu, Ting; Shen, Qiaoqiao

2015-03-01

Bisphenol-A (BPA) has the capability of interfering with the effects of estrogens on modulating brain function. The purpose of this study was to investigate the effects of BPA on memory and synaptic modification in the hippocampus of female mice under different levels of cycling estrogen. BPA exposure (40, 400 μg/kg/day) for 8 weeks did not affect spatial memory and passive avoidance task of gonadally intact mice but improved ovariectomy (Ovx)-induced memory impairment, whereas co-exposure of BPA with estradiol benzoate (EB) diminished the rescue effect of EB on memory behavior of Ovx mice. The results of morphometric measurement showed that BPA positively modified the synaptic interface structure and increased the synaptic density of CA1 pyramidal cell in the hippocampus of Ovx females, but inhibited the enhancement of EB on synaptic modification and synaptogenesis of Ovx mice. Furthermore, BPA up-regulated synaptic proteins synapsin I and PSD-95 and NMDA receptor NR2B but inhibited EB-induced increase in PSD-95 and NR2B in the hippocampus of Ovx mice. These results suggest that BPA interfered with normal hormonal regulation in synaptic plasticity and memory of female mice as a potent estrogen mimetic and as a disruptor of estrogen under various concentrations of cycling estrogen. © 2014 International Society for Neurochemistry.

Functional antigen binding by the defective B cells of CBA/N mice.

Science.gov (United States)

Snippe, H; Merchant, B; Lizzio, E F; Inman, J K

1982-01-01

CBA/N mice have an X-linked B cell defect which prevents them from responding to nonmitogenic thymic independent (TI-2) antigens such as dinitrophenylated DNP-Ficoll (1,2). The F1 male progeny of CBA/N female mice express the same defect. Spleen cell suspensions from such defective mice (CBA/N X C3H/HeN F1 males) could not respond to DNP-Ficoll following in vitro immunization and subsequent transfer into irradiated, syngeneic, F1 male recipients as expected. In contrast, normal CBA/N X C3H/HeN F1 female spleen cells could respond and effect a "rescue"; they mounted strong plaque-forming cell responses 7 days after in vitro exposure to DNP-Ficoll and subsequent transfer into irradiated F1 male recipients. Defective F1 male spleen cells, however, could bind significant quantities of 125I-DNP-Ficoll after in vitro exposure. Extensive washing of these spleen cells could not reverse this binding. Such DNP-Ficoll-exposed and washed F1 male spleen cells could, after transfer, aid normal untreated F1 female cells in their rescue function. The defective F1 male spleen cells could convey immunogenic quantities of DNP-Ficoll to the "rescuing" F1 female cells. Mitomycin treatment of F1 male cells did not interfere with their conveyor function. Goat anti-mouse mu serum impeded the passive antigen conveyor function of defective F1 male cells as did prior exposure to high concentrations of free DNP hapten. Our data support the view that the B cell defect of CBA/N X C3H/HeN F1 male mice does not relate to antigen binding, but rather to an inability to be effectively triggered by certain cell-bound polymeric antigens.

Strain-specific aggressive behavior of male mice submitted to different husbandry procedures

NARCIS (Netherlands)

Loo, P.L.P. van; Meer, E. van der; Kruitwagen, C.L.J.J.; Koolhaas, J.M.; Zutphen, L.F.M. van; Baumans, V.

Severe aggression within groups of male laboratory mice can cause serious welfare problems. Previous experiments have shown that the transfer of specific olfactory cues during cage cleaning and the provision of nesting material decrease aggression and stress in group-housed male mice. In this study,

Responding to emergencies: How organization and management make a difference

International Nuclear Information System (INIS)

Metlay, D.S.; Haber, S.B.; Luckas, W.J.

1989-01-01

There is an observable and definable process that occurs during the course of responding to an abnormal event at a nuclear power plant. Each of the elements that comprise that process involves collective action and consequently is influenced by the character and effectiveness of organizational and managerial arrangements. Factors which affect each element include overt ones like the allocation of authority and responsibility and the skill of personnel, as well as covert factors like the methods used to resolve uncertainty. The purpose of this research project is to examine the process of response that occurs to an abnormal event at a nuclear power plant and where possible to identify the organizational and management factors that influence that process

Responding to emergencies: How organization and management make a difference

International Nuclear Information System (INIS)

Metlay, D.S.; Haber, S.B.; Luckas, W.J.

1990-01-01

There is an observable and definable process that occurs during the course of responding to an abnormal event at a nuclear power plant. Each of the elements that comprise that process involves collective action and consequently is influenced by the character and effectiveness of organizational and managerial arrangements. Factors which affect each element include overt ones like the allocation of authority and responsibility and the skill of personnel, as well as covert factors like the methods used to resolve uncertainty. The purpose of this research project is to examine the process of response that occurs to an abnormal event at a nuclear power plant and where possible to identify the organizational and management factors that influence that process

State machine operation of the MICE cooling channel

International Nuclear Information System (INIS)

Hanlet, Pierrick

2014-01-01

The Muon Ionization Cooling Experiment (MICE) is a demonstration experiment to prove the feasibility of cooling a beam of muons for use in a Neutrino Factory and/or Muon Collider. The MICE cooling channel is a section of a modified Study II cooling channel which will provide a 10% reduction in beam emittance. In order to ensure a reliable measurement, MICE will measure the beam emittance before and after the cooling channel at the level of 1%, a relative measurement of 0.001. This renders MICE a precision experiment which requires strict controls and monitoring of all experimental parameters in order to control systematic errors. The MICE Controls and Monitoring system is based on EPICS and integrates with the DAQ, Data monitoring systems, and a configuration database. The cooling channel for MICE has between 12 and 18 superconductnig solenoid coils in 3 to 7 magnets, depending on the staged development of the experiment. The magnets are coaxial and in close proximity which requires coordinated operation of the magnets when ramping, responding to quench conditions, and quench recovery. To reliably manage the operation of the magnets, MICE is implementing state machines for each magnet and an over-arching state machine for the magnets integrated in the cooling channel. The state machine transitions and operating parameters are stored/restored to/from the configuration database and coupled with MICE Run Control. Proper implementation of the state machines will not only ensure safe operation of the magnets, but will help ensure reliable data quality. A description of MICE, details of the state machines, and lessons learned from use of the state machines in recent magnet training tests will be discussed.

Dietary Animal Plasma Proteins Improve the Intestinal Immune Response in Senescent Mice

Directory of Open Access Journals (Sweden)

Lluïsa Miró

2017-12-01

Full Text Available Increased life expectancy has promoted research on healthy aging. Aging is accompanied by increased non-specific immune activation (inflammaging which favors the appearance of several disorders. Here, we study whether dietary supplementation with spray-dried animal plasma (SDP, which has been shown to reduce the activation of gut-associated lymphoid tissue (GALT in rodents challenged by S. aureus enterotoxin B (SEB, and can also prevent the effects of aging on immune system homeostasis. We first characterized GALT in a mouse model of accelerated senescence (SAMP8 at different ages (compared to mice resistant to accelerated senescence; SAMR1. Second, we analyzed the SDP effects on GALT response to an SEB challenge in SAMP8 mice. In GALT characterization, aging increased the cell number and the percentage of activated Th lymphocytes in mesenteric lymph nodes and Peyer’s patches (all, p < 0.05, as well as the expression of IL-6 and TNF-α in intestinal mucosa (both, p < 0.05. With respect to GALT response to the SEB challenge, young mice showed increased expression of intestinal IL-6 and TNF-α, as well as lymphocyte recruitment and activation (all, p < 0.05. However, the immune response of senescent mice to the SEB challenge was weak, since SEB did not change cell recruitment or the percentage of activated Th lymphocytes. Mice supplemented with SDP showed improved capacity to respond to the SEB challenge, similar to the response of the young mice. These results indicate that senescent mice have an impaired mucosal immune response characterized by unspecific GALT activation and a weak specific immune response. SDP supplementation reduces non-specific basal immune activation, allowing for the generation of specific responses.

Depletion of cytotoxic T-cells does not protect NUP98-HOXD13 mice from myelodysplastic syndrome but reveals a modest tumor immunosurveillance effect.

Directory of Open Access Journals (Sweden)

Sheryl M Gough

Full Text Available Myelodysplastic syndrome (MDS and aplastic anemia (AA patients both present with symptoms of bone marrow failure. In many AA patients, these features are thought to result from an oligoclonal expansion of cytotoxic T-cells that destroy haematopoietic stem or progenitor cells. This notion is supported by the observation that AA patients respond to immunosuppressive therapy. A fraction of MDS patients also respond well to immunosuppressive therapy suggesting a similar role for cytotoxic T-cells in the etiology of MDS, however the role of cytotoxic T-cells in MDS remains unclear. Mice that express a NUP98-HOXD13 (NHD13 transgene develop a MDS that closely mimics the human condition in terms of dysplasia, ineffective hematopoiesis, and transformation to acute myeloid leukemia (AML. We followed a cohort of NHD13 mice lacking the Rag1 protein (NHD13/Rag1KO to determine if the absence of lymphocytes might 1 delay the onset and/or diminish the severity of the MDS, or 2 effect malignant transformation and survival of the NHD13 mice. No difference was seen in the onset or severity of MDS between the NHD13 and NHD13/Rag1KO mice. However, NHD13/Rag1KO mice had decreased survival and showed a trend toward increased incidence of transformation to AML compared to the NHD13 mice, suggesting protection from AML transformation by a modest immuno-surveillance effect. In the absence of functional Tcrb signaling in the NHD13/Rag1KO T-cell tumors, Pak7 was identified as a potential Tcrb surrogate survival signal.

Differences in basal and stress-induced HPA regulation of wild house mice selected for high and low aggression

NARCIS (Netherlands)

Veenema, AH; Meijer, OC; de Kloet, ER; Koolhaas, JM; Bohus, BG; Meijer, Onno C.; Koolhaas, J M

Male wild house mice, selected for short (SAL) and long (LAL) attack latency, show distinctly different behavioral strategies in coping with environmental challenges. In this study, we tested the hypothesis that this difference in coping style is associated with a differential stress responsiveness

The minute virus of mice exploits different endocytic pathways for cellular uptake

International Nuclear Information System (INIS)

Garcin, Pierre O.; Panté, Nelly

2015-01-01

The minute virus of mice, prototype strain (MVMp), is a non-enveloped, single-stranded DNA virus of the family Parvoviridae. Unlike other parvoviruses, the mechanism of cellular uptake of MVMp has not been studied in detail. We analyzed MVMp endocytosis in mouse LA9 fibroblasts and a tumor cell line derived from epithelial–mesenchymal transition through polyomavirus middle T antigen transformation in transgenic mice. By a combination of immunofluorescence and electron microscopy, we found that MVMp endocytosis occurs at the leading edge of migrating cells in proximity to focal adhesion sites. By using drug inhibitors of various endocytic pathways together with immunofluorescence microscopy and flow cytometry analysis, we discovered that MVMp can use a number of endocytic pathways, depending on the host cell type. At least three different mechanisms were identified: clathrin-, caveolin-, and clathrin-independent carrier-mediated endocytosis, with the latter occurring in transformed cells but not in LA9 fibroblasts. - Highlights: • MVMp uptake takes place at the leading edge of migrating cells. • MVMp exploits a variety of endocytic pathways. • MVMp could use clathrin- and caveolin-mediated endocytosis. • MVMp could also use clathrin-independent carriers for cellular uptake

The minute virus of mice exploits different endocytic pathways for cellular uptake

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Garcin, Pierre O.; Panté, Nelly, E-mail: pante@zoology.ubc.ca

2015-08-15

The minute virus of mice, prototype strain (MVMp), is a non-enveloped, single-stranded DNA virus of the family Parvoviridae. Unlike other parvoviruses, the mechanism of cellular uptake of MVMp has not been studied in detail. We analyzed MVMp endocytosis in mouse LA9 fibroblasts and a tumor cell line derived from epithelial–mesenchymal transition through polyomavirus middle T antigen transformation in transgenic mice. By a combination of immunofluorescence and electron microscopy, we found that MVMp endocytosis occurs at the leading edge of migrating cells in proximity to focal adhesion sites. By using drug inhibitors of various endocytic pathways together with immunofluorescence microscopy and flow cytometry analysis, we discovered that MVMp can use a number of endocytic pathways, depending on the host cell type. At least three different mechanisms were identified: clathrin-, caveolin-, and clathrin-independent carrier-mediated endocytosis, with the latter occurring in transformed cells but not in LA9 fibroblasts. - Highlights: • MVMp uptake takes place at the leading edge of migrating cells. • MVMp exploits a variety of endocytic pathways. • MVMp could use clathrin- and caveolin-mediated endocytosis. • MVMp could also use clathrin-independent carriers for cellular uptake.

Differences in ultrasonic vocalizations between wild and laboratory California mice (Peromyscus californicus.

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Matina C Kalcounis-Rueppell

Full Text Available BACKGROUND: Ultrasonic vocalizations (USVs emitted by muroid rodents, including laboratory mice and rats, are used as phenotypic markers in behavioral assays and biomedical research. Interpretation of these USVs depends on understanding the significance of USV production by rodents in the wild. However, there has never been a study of muroid rodent ultrasound function in the wild and comparisons of USVs produced by wild and laboratory rodents are lacking to date. Here, we report the first comparison of wild and captive rodent USVs recorded from the same species, Peromyscus californicus. METHODOLOGY AND PRINCIPAL FINDINGS: We used standard ultrasound recording techniques to measure USVs from California mice in the laboratory (Peromyscus Genetic Stock Center, SC, USA and the wild (Hastings Natural History Reserve, CA, USA. To determine which California mouse in the wild was vocalizing, we used a remote sensing method that used a 12-microphone acoustic localization array coupled with automated radio telemetry of all resident Peromyscus californicus in the area of the acoustic localization array. California mice in the laboratory and the wild produced the same types of USV motifs. However, wild California mice produced USVs that were 2-8 kHz higher in median frequency and significantly more variable in frequency than laboratory California mice. SIGNIFICANCE: The similarity in overall form of USVs from wild and laboratory California mice demonstrates that production of USVs by captive Peromyscus is not an artifact of captivity. Our study validates the widespread use of USVs in laboratory rodents as behavioral indicators but highlights that particular characteristics of laboratory USVs may not reflect natural conditions.

[Distributions of H3K27me3 and its modification enzymes in different tissues of mice].

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Wang, Yuying; Wang, Xinli; Zhang, Ran; Zhang, Zhiyan; Wang, Yu; Yang, Bo; Wang, Guanjie; Zhang, Xin; Ma, Fuhao; Xu, Hongye; Wu, Xiaohui; Zhang, Feng; Li, Qing

2017-11-01

Objective To investigate the levels of trimethylated histone 3 at lysine residue 27 (H3K27me3) and its modification enzymes Zeste gene enhancer homolog 2 (EZH2), lysine-specific demethylase 6B (Kdm6B/JMJD3) and lysine-specific demethylase 6A (Kdm6A/UTX) in tissues and organs of 7-day and 2-month postnatal mice. Methods Immunohistochemistry was used to detect the expressions of H3K27me3 and its modification enzymes EZH2, JMJD3 and UTX in the brain, salivary glands, back fat, thymus, lung, heart, stomach, intestines, liver, testes, and skin of 7-day and 2-month mice. Real-time quantitative PCR was used to confirm the results. The relationships between H3K27me3 and its modification enzymes were analyzed statistically. Results Immunohistochemistry showed H3K27me3 persistently present in all examined tissues of 7-day and 2-month mice. EZH2 was persistently expressed in the brain, heart, liver, and skin of 7-day and 2-month mice, but only expressed in the salivary glands, adipose tissues, thymus, lung, intestines, and testes of 2-month mice. JMJD3 was expressed in the brain, salivary glands, adipose tissues, lung, heart, stomach, intestines, testes, skin of 7-day mice, but was not expressed in the lung, adipose tissues and stomach of 2-month mice. UTX was expressed in the brain, salivary glands, adipose tissues, lung, heart, testes, skin of 7-day mice, but only expressed in the testes of 2-month mice. Most mRNA of H3K27 modification enzymes were moderately or highly expressed as their immunohistochemical results were positive. Conclusion There was H3K27me3 persistently present in the all examined tissues at different stages. EZH2 was mostly expressed in the brain, salivary glands, adipose tissues, thymus, lung, heart, intestines, liver, testes and skin of 2-month-old mice. JMJD3 and UTX were mostly expressed in the brain, salivary glands, adipose tissues, lung, heart, skin and testes of 7-day-old mice. No significant association was found between the distribution of H3K

Interaction in the Research Interview and Drug-Related Disclosures among Respondents.

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Myers, Vincent

1979-01-01

Interviewers and respondents judged interview interactions during a survey of drug-related sentiments. Pronounced variability in interviewer-respondent judgements occurred in unanticipated ways related to gender, role, and ethnicity of participants. Positive interaction yielded different respondent cognitions and reports of illicit drug ingestion…

Corticotropin-releasing factor overexpression in mice abrogates sex differences in body weight, visceral fat, and food intake response to a fast and alters levels of feeding regulatory hormones.

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Wang, Lixin; Goebel-Stengel, Miriam; Yuan, Pu-Qing; Stengel, Andreas; Taché, Yvette

2017-01-01

Corticotropin-releasing factor overexpressing (CRF-OE) male mice showed an inhibited feeding response to a fast, and lower plasma acyl ghrelin and Fos expression in the arcuate nucleus compared to wild-type (WT) mice. We investigated whether hormones and hypothalamic feeding signals are impaired in CRF-OE mice and the influence of sex. Male and female CRF-OE mice and WT littermates (4-6 months old) fed ad libitum or overnight fasted were assessed for body, adrenal glands and perigonadal fat weights, food intake, plasma hormones, blood glucose, and mRNA hypothalamic signals. Under fed conditions, compared to WT, CRF-OE mice have increased adrenal glands and perigonadal fat weight, plasma corticosterone, leptin and insulin, and hypothalamic leptin receptor and decreased plasma acyl ghrelin. Compared to male, female WT mice have lower body and perigonadal fat and plasma leptin but higher adrenal glands weights. CRF-OE mice lost these sex differences except for the adrenals. Male CRF-OE and WT mice did not differ in hypothalamic expression of neuropeptide Y (NPY) and proopiomelanocortin (POMC), while female CRF-OE compared to female WT and male CRF-OE had higher NPY mRNA levels. After fasting, female WT mice lost more body weight and ate more food than male WT, while CRF-OE mice had reduced body weight loss and inhibited food intake without sex difference. In male WT mice, fasting reduced plasma insulin and leptin and increased acyl ghrelin and corticosterone while female WT showed only a rise in corticosterone. In CRF-OE mice, fasting reduced insulin while leptin, acyl ghrelin and corticosterone were unchanged with no sex difference. Fasting blood glucose was higher in CRF-OE with female > male. In WT mice, fasting increased hypothalamic NPY expression in both sexes and decreased POMC only in males, while in CRF-OE mice, NPY did not change, and POMC decreased in males and increased in females. These data indicate that CRF-OE mice have abnormal basal and fasting

The R21C Mutation in Cardiac Troponin I Imposes Differences in Contractile Force Generation between the Left and Right Ventricles of Knock-In Mice

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Jingsheng Liang

2015-01-01

Full Text Available We investigated the effect of the hypertrophic cardiomyopathy-linked R21C (arginine to cysteine mutation in human cardiac troponin I (cTnI on the contractile properties and myofilament protein phosphorylation in papillary muscle preparations from left (LV and right (RV ventricles of homozygous R21C+/+ knock-in mice. The maximal steady-state force was significantly reduced in skinned papillary muscle strips from the LV compared to RV, with the latter displaying the level of force observed in LV or RV from wild-type (WT mice. There were no differences in the Ca2+ sensitivity between the RV and LV of R21C+/+ mice; however, the Ca2+ sensitivity of force was higher in RV-R21C+/+ compared with RV-WT and lower in LV- R21C+/+ compared with LV-WT. We also observed partial loss of Ca2+ regulation at low [Ca2+]. In addition, R21C+/+-KI hearts showed no Ser23/24-cTnI phosphorylation compared to LV or RV of WT mice. However, phosphorylation of the myosin regulatory light chain (RLC was significantly higher in the RV versus LV of R21C+/+ mice and versus LV and RV of WT mice. The difference in RLC phosphorylation between the ventricles of R21C+/+ mice likely contributes to observed differences in contractile force and the lower tension monitored in the LV of HCM mice.

Secondary IgG responses to type III pneumococcal polysaccharide. II. Different cellular requirements for induction and elicitation.

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Braley-Mullen, H

1976-04-01

Mice primed with a thymus- (T) dependent form of Type III pneumococcal polysaccharide (S3), i.e., S3 coupled to erythrocytes (S3-RBC) produce S3-specific IgG antibody after secondary challenge with either S3 or S3-RBC. The production of IgG antibody by mice challenged with S3 was shown to be T independent since secondary responses were enhanced when mice were treated with anti-lymphocyte serum (ALS) at the time of secondary challenge with S3 and T-depleted spleen cells responded as well as unfractionated spleen cells to S3 in an adoptive transfer system. Secondary S3-specific IgG responses in mice challenged with S3-RBC were shown to be T dependent by the same criteria. The results obtained by using S3 as the antigen indicate that IgG-producing B cells (B lambda cells) can recognize and respond to antigen in the absence of helper T cells. On the other hand, T cells were required for the induction of S3-specific memory B lambda cells since mice depleted of T cells by treatment with ALS at the time of priming with S3-RBC failed to produce S3-specific IgG antibody after secondary challenge with either S3-specific IgG antibody after secondary chall-nge with either S3 or S3rbc. Since RBC-specific memory cells were induced in T-deprived mice the results suggest that T cell regulation of IgG antibody production may vary for different antigens.

Sex differences between CRF1 receptor deficient mice following naloxone-precipitated morphine withdrawal in a conditioned place aversion paradigm: implication of HPA axis.

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Juan-Antonio García-Carmona

Full Text Available Extinction period of positive affective memory of drug taking and negative affective memory of drug withdrawal, as well as the different response of men and women might be important for the clinical treatment of drug addiction. We investigate the role of corticotropin releasing factor receptor type one (CRF1R and the different response of male and female mice in the expression and extinction of the aversive memory.We used genetically engineered male and female mice lacking functional CRF1R. The animals were rendered dependent on morphine by intraperitoneally injection of increasing doses of morphine (10-60 mg/kg. Negative state associated with naloxone (1 mg/kg s.c.-precipitated morphine withdrawal was examined by using conditioned place aversion (CPA paradigm. No sex differences for CPA expression were found in wild-type (n = 29 or CRF1R knockout (KO mice (n = 29. However, CRF1R KO mice presented less aversion score than wild-type mice, suggesting that CRF1R KO mice were less responsive than wild-type to continuous associations between drug administration and environmental stimuli. In addition, CPA extinction was delayed in wild-type and CRF1R KO male mice compared with females of both genotypes. The genetic disruption of the CRF1R pathway decreased the period of extinction in males and females suggesting that CRF/CRF1R is implicated in the duration of aversive memory. Our results also showed that the increase in adrenocorticotropic hormone (ACTH levels observed in wild-type (n = 11 mice after CPA expression, were attenuated in CRF1R KO mice (n = 10. In addition, ACTH returned to the baseline levels in males and females once CPA extinction was finished.These results suggest that, at least, CPA expression is partially due to an increase in plasma ACTH levels, through activation of CRF1R, which can return when CPA extinction is finished.

Relative effects of different modalities of brachytherapy on late responding tissues and tumours

International Nuclear Information System (INIS)

Malgieri, F.

1996-01-01

To compare the effects of different available modalities of brachytherapy (continuous LDR, fractionated HDR and pulsed MDR) for late responding normal tissues and tumours, we have set up a 'unitary' L-Q model, based on Liversage's and Dale's works, that include also the dose rate value and a correction factor of the β parameter depending on the sublethal damage repair time constant, on the length of time of each irradiation and on the time interval between following irradiation for to realize the effect of the incomplete repair when the time interval is short, as in the PMDR. This 'unitary' L-Q model is, of course, usable in the same way also in external beam therapy and in the cases of integration of brachytherapy and external beam therapy. We show and discuss the resulting relationships of the ratio BED 'late'/BED tumour changing the time-dose parameters, expressing the different modalities of radiotherapy, and the values of the biological characteristic parameters T p , α/β and μ, for defined size of tumour control. The general results are largely in accordance with clinical evidence and the application of the model would give basic indications in the definition of clinical protocols. Its preliminary use could have made it possible to avoid the numerous and documented consequences produced in even recent clinical trials

Differences in correlation of mRNA gene expression in mice sensitive and resistant to radiation-induced pulmonary fibrosis

International Nuclear Information System (INIS)

Johnston, C.J.; Piedboeuf, B.; Finkelstein, J.N.; Baggs, R.; Rubin, P.

1995-01-01

Fibrosis, characterized by the accumulation of collagen, is a late result of thoracic irradiation. The purpose of this study was to determine if extracellular matrix protein and transforming growth factor β mRNA expression are altered late in the course of pulmonary fibrosis after irradiation, and then to determine if these changes differ between two strains of mice which vary in their sensitivity to radiation. Radiation-sensitive (C57BL/6) and radiation-resistant (C3H/HeJ) mice were irradiated with a single dose of 5 or 12.5 Gy to the thorax. Total lung RNA was prepared and immobilized by Northern and slot blotting and hybridized with radiolabeled cDNA probes for collagens I, III and IV, fibronectin, and transforming growth factor β 1 and β 3 . Autoradiographic data were quantified by video densitometry and results normalized to a control probe encoding for glyceralde-hyde-3-phosphate dehydrogenase. Alterations in mRNA abundance were observed in the sensitive mice at all times, while levels in the resistant mice were unaffected until 26 weeks after irradiation. The relationship between extracellular matrix protein per se and increased mRNA abundance suggests that late matrix protein accumulation may be a function of gene expression. Differences in levels of transforming growth factor βmRNA may lead to strain-dependent variation in fibrotic response and may also contribute to the radiation-induced component of pulmonary fibrosis. 32 refs., 5 figs

The influence of chronic stress on anxiety-like behavior and cognitive function in different human GFAP-ApoE transgenic adult male mice.

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Meng, Fan-Tao; Zhao, Jun; Fang, Hui; Liu, Ya-Jing

2015-01-01

The apolipoprotein E (ApoE) ɛ4 allele (ApoE4) is an important genetic risk factor for the pathogenesis of Alzheimer's disease (AD). In addition to genetic factors, environmental factors such as stress may play a critical role in AD pathogenesis. This study was designed to investigate the anxiety-like behavioral and cognitive changes in different human glial fibrillary acidic protein (GFAP)-ApoE transgenic adult male mice under chronic stress conditions. On the open field test, anxiety-like behavior was increased in the non-stressed GFAP-ApoE4 transgenic mice relative to the corresponding GFAP-ApoE3 (ApoE ɛ3 allele) mice. Anxiety-like behavior was increased in the stressed GFAP-ApoE3 mice relative to non-stressed GFAP-ApoE3 mice, but was unexpectedly decreased in the stressed GFAP-ApoE4 mice relative to non-stressed GFAP-ApoE4 mice. On the novel object recognition task, both GFAP-ApoE4 and GFAP-ApoE3 mice exhibited long-term non-spatial memory impairment after chronic stress. Interestingly, short-term non-spatial memory impairment (based on the novel object recognition task) was observed only in the stressed GFAP-ApoE4 male mice relative to non-stressed GFAP-ApoE4 transgenic mice. In addition, short-term spatial memory impairment was observed in the stressed GFAP-ApoE3 transgenic male mice relative to non-stressed GFAP-ApoE3 transgenic male mice; however, short-term spatial memory performance of GFAP-ApoE4 transgenic male mice was not reduced compared to non-stressed control mice based on the Y-maze task. In conclusion, our findings suggested that chronic stress affects anxiety-like behavior and spatial and non-spatial memory in GFAP-ApoE transgenic mice in an ApoE isoform-dependent manner.

Are voluntary wheel running and open-field behavior correlated in mice? Different answers from comparative and artificial selection approaches.

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Careau, Vincent; Bininda-Emonds, Olaf R P; Ordonez, Genesis; Garland, Theodore

2012-09-01

Voluntary wheel running and open-field behavior are probably the two most widely used measures of locomotion in laboratory rodents. We tested whether these two behaviors are correlated in mice using two approaches: the phylogenetic comparative method using inbred strains of mice and an ongoing artificial selection experiment on voluntary wheel running. After taking into account the measurement error and phylogenetic relationships among inbred strains, we obtained a significant positive correlation between distance run on wheels and distance moved in the open-field for both sexes. Thigmotaxis was negatively correlated with distance run on wheels in females but not in males. By contrast, mice from four replicate lines bred for high wheel running did not differ in either distance covered or thigmotaxis in the open field as compared with mice from four non-selected control lines. Overall, results obtained in the selection experiment were generally opposite to those observed among inbred strains. Possible reasons for this discrepancy are discussed.

Partial promoter substitutions generating transcriptional sentinels of diverse signaling pathways in embryonic stem cells and mice

DEFF Research Database (Denmark)

Serup, Palle; Gustavsen, Carsten; Klein, Tino

2012-01-01

Extracellular signals in development, physiology, homeostasis and disease often act by regulating transcription. Herein we describe a general method and specific resources for determining where and when such signaling occurs in live animals and for systematically comparing the timing and extent...... extracellular signals. We thereby created an allelic series of embryonic stem cells and mice, each containing a signal-responsive sentinel with different fluorescent reporters that respond with sensitivity and specificity to retinoic acids, bone morphogenic proteins, activin A, Wnts or Notch, and that can...

Pregnane X Receptor-Humanized Mice Recapitulate Gender Differences in Ethanol Metabolism but Not Hepatotoxicity.

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Spruiell, Krisstonia; Gyamfi, Afua A; Yeyeodu, Susan T; Richardson, Ricardo M; Gonzalez, Frank J; Gyamfi, Maxwell A

2015-09-01

Both human and rodent females are more susceptible to developing alcoholic liver disease following chronic ethanol (EtOH) ingestion. However, little is known about the relative effects of acute EtOH exposure on hepatotoxicity in female versus male mice. The nuclear receptor pregnane X receptor (PXR; NR1I2) is a broad-specificity sensor with species-specific responses to toxic agents. To examine the effects of the human PXR on acute EtOH toxicity, the responses of male and female PXR-humanized (hPXR) transgenic mice administered oral binge EtOH (4.5 g/kg) were analyzed. Basal differences were observed between hPXR males and females in which females expressed higher levels of two principal enzymes responsible for EtOH metabolism, alcohol dehydrogenase 1 and aldehyde dehydrogenase 2, and two key mediators of hepatocyte replication and repair, cyclin D1 and proliferating cell nuclear antigen. EtOH ingestion upregulated hepatic estrogen receptor α, cyclin D1, and CYP2E1 in both genders, but differentially altered lipid and EtOH metabolism. Consistent with higher basal levels of EtOH-metabolizing enzymes, blood EtOH was more rapidly cleared in hPXR females. These factors combined to provide greater protection against EtOH-induced liver injury in female hPXR mice, as revealed by markers for liver damage, lipid peroxidation, and endoplasmic reticulum stress. These results indicate that female hPXR mice are less susceptible to acute binge EtOH-induced hepatotoxicity than their male counterparts, due at least in part to the relative suppression of cellular stress and enhanced expression of enzymes involved in both EtOH metabolism and hepatocyte proliferation and repair in hPXR females. U.S. Government work not protected by U.S. copyright.

Increased litter size and super-ovulation rate in congenic C57BL mice carrying a polymorphic fragment of NFR/N origin at the Fecq4 locus of chromosome 9

DEFF Research Database (Denmark)

Liljander, Maria; Andersson, Åsa Inga Maria; Holmdahl, Rikard

2009-01-01

. In addition, embryos containing the Fecq4 fragment were easy to cultivate in vitro, resulting in a higher yield of embryos reaching the blastocyst stage. We propose that B10.Q.NFR/N-Fecq4 congenic mice may be used to improve breeding or super-ovulation rate in different types of genetically modified mice (on...... describe how the Fecq4 fragment originating form the NFR/N mouse strain will affect B10.Q mice by means of breeding capacity, super-ovulation rate and embryonic development in vitro. Our results show that both the breeding capacity (number of pups produced/breeding cage during a 5 months period......) and the mean litter size are significantly increased in B10.Q.NFR/N-Fecq4 congenic mice. Furthermore. B10.Q.NFR/N-Fecq4 congenic mice (both homozygous and heterozygous) did respond much better to super-ovulation than wild-type mice, resulting in a dramatically increased yield of fertilized 1-cell embryos...

Standardized Index of Shape (SIS): a quantitative DCE-MRI parameter to discriminate responders by non-responders after neoadjuvant therapy in LARC

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Petrillo, Antonella; Fusco, Roberta; Petrillo, Mario; Granata, Vincenza [Istituto Nazionale Tumori Fondazione Giovanni Pascale - IRCCS, Naples (Italy). Div. of Radiology; Sansone, Mario [Naples Univ. ' ' Federico II' ' (Italy). Dept. of Biomedical, Electronics and Telecommunications Engineering; Avallone, Antonio [Istituto Nazionale Tumori Fondazione Giovanni Pascale - IRCCS, Naples (Italy). Div. of Gastrointestinal Medical Oncology; Delrio, Paolo [Istituto Nazionale Tumori Fondazione Giovanni Pascale - IRCCS, Naples (Italy). Div. of Gastrointestinal surgical Oncology; Pecori, Biagio [Istituto Nazionale Tumori Fondazione Giovanni Pascale - IRCCS, Naples (Italy). Div. of Radiotherapy; Tatangelo, Fabiana [Istituto Nazionale Tumori Fondazione Giovanni Pascale - IRCCS, Naples (Italy). Div. of Diagnostic Pathology; Ciliberto, Gennaro [Istituto Nazionale Tumori Fondazione Giovanni Pascale - IRCCS, Naples (Italy)

2015-07-15

To investigate the potential of DCE-MRI to discriminate responders from non-responders after neoadjuvant chemo-radiotherapy (CRT) for locally advanced rectal cancer (LARC). We investigated several shape parameters for the time-intensity curve (TIC) in order to identify the best combination of parameters between two linear parameter classifiers. Seventy-four consecutive patients with LARC were enrolled in a prospective study approved by our ethics committee. Each patient gave written informed consent. After surgery, pathological TNM and tumour regression grade (TRG) were estimated. DCE-MRI semi-quantitative analysis (sqMRI) was performed to identify the best parameter or parameter combination to discriminate responders from non-responders in response monitoring to CRT. Percentage changes of TIC shape descriptors from the baseline to the presurgical scan were assessed and correlated with TRG. Receiver operating characteristic analysis and linear classifier were applied. Forty-six patients (62.2 %) were classified as responders, while 28 subjects (37.8 %) were considered as non-responders. sqMRI reached a sensitivity of 93.5 % and a specificity of 82.1 % combining the percentage change in Maximum Signal Difference (ΔMSD) and Wash-out Slope (ΔWOS), the Standardized Index of Shape (SIS). SIS obtains the best result in discriminating responders from non-responders after CRT in LARC, with a cut-off value of -3.0 %. (orig.)

Oxygen tension measurements of tumors growing in mice

International Nuclear Information System (INIS)

Adam, Markus F.; Dorie, Mary Jo; Brown, J. Martin

1999-01-01

Purpose: Clinical studies using the Eppendorf histograph have shown that patients whose tumors have a low pO 2 have worse local control after radiotherapy, and have higher metastatic rates. Because preclinical studies of methods of overcoming, or exploiting, hypoxia generally use transplanted tumors in mice, we have compared the oxygenation of mouse tumors with human tumors to determine the appropriateness of the transplanted mouse model for such preclinical studies. Methods and Materials: We evaluated the oxygenation status of subcutaneous (s.c.) tissue and of 12 intradermally (i.d.)- and 7 s.c.-growing mouse or human transplanted tumors in mice using the Eppendorf histograph, and compared the values obtained with measurements of human head and neck nodes. Results: The normal tissue pO 2 profile of air-breathing mice showed a nearly Gaussian distribution (38.2 ± 14.9 mmHg). Breathing 10% O 2 or carbogen resulted in dramatic changes in normal tissue oxygenation. Tumors growing intradermally in the back of air-breathing mice were extremely hypoxic and resistant to expected changes in oxygenation (carbogen breathing, size, and use of anesthetics). Tumors growing s.c. in the foot showed higher oxygen profiles with marked changes in oxygenation when exposing the animals to different levels of oxygen. However, the oxygenation of the mouse tumors transplanted in either site was only a fraction of that of the majority of human tumors. Conclusion: Experimental mouse tumors are markedly hypoxic, with median values of 10-20% of those of human tumors. Hence, mouse tumors are probably good models for the most hypoxic human tumors that respond poorly to radiotherapy; however, caution has to be exercised in extrapolating data from mouse to man

Delayed-type hypersensitivity to Babesia microti-infected erythrocytes in mice

International Nuclear Information System (INIS)

Ruebush, M.J.; Troutman, E.H.; Kennedy, D.A.

1986-01-01

Strong delayed-type hypersensitivity (DTH) to Babesia microti was elicited when intraerythrocytic parasites (IEP) were inoculated subcutaneously into the flank of normal mice 6 to 14 days before challenge in the ipsilateral footpad with 10(8) IEP. Intraperitoneal or intravenous administration of antigen did not sensitize mice for DTH. When challenge was given 21 days after immunization, the response was approximately half of the maximum and then rose again slowly over the next 3 weeks to levels that were not significantly different from those maximal values. The response was classified as a true DTH reaction on the basis of kinetics, histology, and the transfer of responsiveness with immune T lymphocytes of the Ly 1+ phenotype, but not with serum. The reaction was specific for IEP since control groups given two injections of red blood cells from uninfected syngeneic mice (NRBC) or one injection of NRBC or sheep red blood cells (SRBC) and one of IEP never developed significant footpad swelling. Freed parasites obtained by osmotic rupture, density gradient sedimentation, and lethally irradiated IEP were also effective for elicitation of DTH. Anti-IEP DTH was expressed in a dose-dependent fashion with 10(6), 10(7), or 10(8) parasites sufficing for immunizing inoculum as long as 10(8) parasites were used as the challenge dose. Mice immunized and challenged with 10(8) lethally irradiated IEP (60 krad, 60Co), were protected against subsequent intraperitoneal challenge with 10(8) viable IEP. If mice were infected intraperitoneally with 10(8) IEP at any time between 21 days before immunization to 2 hr after challenge, their ability to respond to immunization and challenge was profoundly depressed. Development of a strong anti-parasite DTH response can occur in parallel with resistance to infection, but is not a rapid sequela of bloodborne infection

Cytokine gene expression and pathology in mice experimentally infected with different isolates of Trypanosoma evansi.

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Krishnamoorthy, P; Sengupta, P P; Das, Sangita; Ligi, M; Shome, B R; Rahman, H

2016-11-01

Aim of the present study was to assess the cytokine gene expression in liver, kidney and spleen and histopathological changes in mice infected with buffalo and dog isolates of Trypanosoma evansi. Forty-four Swiss albino mice was divided into eleven groups of four mice each and injected subcutaneously with 1 × 10 5 trypanosomes of buffalo and dog isolate to twenty mice each, four mice served as control. Mice were examined for clinical signs, blood smear for trypanosome counts. Blood for PCR, liver, kidney, spleen, heart, lung, testis and abdominal muscle for histopathology and liver, kidney, spleen for cytokine gene expression studies, were collected. Mice showed dullness, lethargy, hunched back, sluggish movements on D4 and D5 in buffalo and dog isolate, respectively. Parasite count in blood varied between the two isolates of T. evansi. By PCR, trypanosome DNA was detected on D1 and D2 for buffalo and dog isolate, respectively. Splenomegaly was observed in mice infected with buffalo isolate but not with dog isolate. Histopathological changes were observed in liver, kidney, spleen and heart of mice but no changes in testis and abdominal muscles. Blood vessels of liver, heart, lung showed presence of trypanosomes in mice infected with buffalo isolate but not for dog isolate. Cytokine gene expression of IL-2, IL-4, IL-6, IL-12, TNF-α and IFN-γ increased in liver, kidney and spleen in both these isolates. However, the buffalo isolate exhibited pronounced increase in cytokine gene expression when compare to dog isolate of T. evansi. Anti-inflammatory cytokine gene IL-10 showed 50-60 and 10-20 folds increment in buffalo and dog isolates, respectively. This is the first report of IL-4, IL-6, IL-10 and IL-12 cytokine changes in mice infected with T. evansi. A variation in pathogenicity between buffalo and dog isolates was recorded indicating buffalo isolate of T. evansi remained more pathogenic in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

The spectrum of resistance in SR/CR mice: the critical role of chemoattraction in the cancer/leukocyte interaction.

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Riedlinger, Gregory; Adams, Jonathan; Stehle, John R; Blanks, Michael J; Sanders, Anne M; Hicks, Amy M; Willingham, Mark C; Cui, Zheng

2010-05-03

Spontaneous regression/complete resistance (SR/CR) mice are a unique colony of mice that possess an inheritable, natural cancer resistance mediated primarily by innate cellular immunity. This resistance is effective against sarcoma 180 (S180) at exceptionally high doses and these mice remain healthy. In this study, we challenged SR/CR mice with additional lethal transplantable mouse cancer cell lines to determine their resistance spectrum. The ability of these transplantable cancer cell lines to induce leukocyte infiltration was quantified and the percentage of different populations of responding immune cells was determined using flow cytometry. In comparison to wild type (WT) mice, SR/CR mice showed significantly higher resistance to all cancer cell lines tested. However, SR/CR mice were more sensitive to MethA sarcoma (MethA), B16 melanoma (B16), LL/2 lung carcinoma (LL/2) and J774 lymphoma (J774) than to sarcoma 180 (S180) and EL-4 lymphoma (EL-4). Further mechanistic studies revealed that this lower resistance to MethA and LL/2 was due to the inability of these cancer cells to attract SR/CR leukocytes, leading to tumor cell escape from resistance mechanism. This escape mechanism was overcome by co-injection with S180, which could attract SR/CR leukocytes allowing the mice to resist higher doses of MethA and LL/2. S180-induced cell-free ascites fluid (CFAF) co-injection recapitulated the results obtained with live S180 cells, suggesting that this chemoattraction by cancer cells is mediated by diffusible molecules. We also tested for the first time whether SR/CR mice were able to resist additional cancer cell lines prior to S180 exposure. We found that SR/CR mice had an innate resistance against EL-4 and J774. Our results suggest that the cancer resistance in SR/CR mice is based on at least two separate processes: leukocyte migration/infiltration to the site of cancer cells and recognition of common surface properties on cancer cells. The infiltration of SR

The spectrum of resistance in SR/CR mice: the critical role of chemoattraction in the cancer/leukocyte interaction

International Nuclear Information System (INIS)

Riedlinger, Gregory; Adams, Jonathan; Stehle, John R Jr; Blanks, Michael J; Sanders, Anne M; Hicks, Amy M; Willingham, Mark C; Cui, Zheng

2010-01-01

Spontaneous regression/complete resistance (SR/CR) mice are a unique colony of mice that possess an inheritable, natural cancer resistance mediated primarily by innate cellular immunity. This resistance is effective against sarcoma 180 (S180) at exceptionally high doses and these mice remain healthy. In this study, we challenged SR/CR mice with additional lethal transplantable mouse cancer cell lines to determine their resistance spectrum. The ability of these transplantable cancer cell lines to induce leukocyte infiltration was quantified and the percentage of different populations of responding immune cells was determined using flow cytometry. In comparison to wild type (WT) mice, SR/CR mice showed significantly higher resistance to all cancer cell lines tested. However, SR/CR mice were more sensitive to MethA sarcoma (MethA), B16 melanoma (B16), LL/2 lung carcinoma (LL/2) and J774 lymphoma (J774) than to sarcoma 180 (S180) and EL-4 lymphoma (EL-4). Further mechanistic studies revealed that this lower resistance to MethA and LL/2 was due to the inability of these cancer cells to attract SR/CR leukocytes, leading to tumor cell escape from resistance mechanism. This escape mechanism was overcome by co-injection with S180, which could attract SR/CR leukocytes allowing the mice to resist higher doses of MethA and LL/2. S180-induced cell-free ascites fluid (CFAF) co-injection recapitulated the results obtained with live S180 cells, suggesting that this chemoattraction by cancer cells is mediated by diffusible molecules. We also tested for the first time whether SR/CR mice were able to resist additional cancer cell lines prior to S180 exposure. We found that SR/CR mice had an innate resistance against EL-4 and J774. Our results suggest that the cancer resistance in SR/CR mice is based on at least two separate processes: leukocyte migration/infiltration to the site of cancer cells and recognition of common surface properties on cancer cells. The infiltration of SR

Striatum-dependent habits are insensitive to both increases and decreases in reinforcer value in mice.

Science.gov (United States)

Quinn, Jennifer J; Pittenger, Christopher; Lee, Anni S; Pierson, Jamie L; Taylor, Jane R

2013-03-01

The mouse has emerged as an advantageous species for studying the brain circuitry that underlies complex behavior and for modeling neuropsychiatric disease. The transition from flexible, goal-directed actions to inflexible, habitual responses is argued to be a valid and reliable behavioral model for studying a core aspect of corticostriatal systems that is implicated in certain forms of psychopathology. This transition is thought to correspond to a progression of behavioral control from associative to sensorimotor corticobasal ganglia networks. Habits form following extensive training and are characterized by reduced sensitivity of instrumental responding to reinforcer revaluation; few studies have examined this form of behavioral control in mice. Here we examined the involvement of the dorsolateral and dorsomedial striatum in this transition in the C57BL/6 inbred mouse strain. We provided evidence that damage to the dorsolateral striatum disrupted habitual responding, i.e. it preserved sensitivity to changes in outcome value following either outcome devaluation or, shown for the first time in mice, outcome inflation. Together, these data show that instrumental responding in lesioned mice tracks the current value of a reinforcer and provide evidence that neuroanatomical mechanisms underlying habit learning in rats are preserved in the mouse. This will allow for the genetic and molecular dissection of neural factors involved in decision-making and mechanisms of aberrant habit formation. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

The acquisition of conditioned responding.

Science.gov (United States)

Harris, Justin A

2011-04-01

This report analyzes the acquisition of conditioned responses in rats trained in a magazine approach paradigm. Following the suggestion by Gallistel, Fairhurst, and Balsam (2004), Weibull functions were fitted to the trial-by-trial response rates of individual rats. These showed that the emergence of responding was often delayed, after which the response rate would increase relatively gradually across trials. The fit of the Weibull function to the behavioral data of each rat was equaled by that of a cumulative exponential function incorporating a response threshold. Thus, the growth in conditioning strength on each trial can be modeled by the derivative of the exponential--a difference term of the form used in many models of associative learning (e.g., Rescorla & Wagner, 1972). Further analyses, comparing the acquisition of responding with a continuously reinforced stimulus (CRf) and a partially reinforced stimulus (PRf), provided further evidence in support of the difference term. In conclusion, the results are consistent with conventional models that describe learning as the growth of associative strength, incremented on each trial by an error-correction process.

Early differences in metabolic flexibility between obesity-resistant and obesity-prone mice

Czech Academy of Sciences Publication Activity Database

Bardová, Kristina; Horáková, Olga; Janovská, Petra; Hansíková, Jana; Kůs, Vladimír; van Schothorst, E. M.; Hoevenaars, F.P.M.; Uil, M.; Hensler, Michal; Keijer, J.; Kopecký, Jan

2016-01-01

Roč. 124, May (2016), s. 163-170 ISSN 0300-9084 R&D Projects: GA MŠk(CZ) 7E10059; GA ČR(CZ) GB14-36804G Institutional support: RVO:67985823 Keywords : indirect calorimetry * glucose tolerance * weaning * C57BL/6J mice * A/J mice * metabolic flexibility Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.112, year: 2016

Discriminant cognitive factors in responder and non-responder patients with schizophrenia.

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Stip, E; Lussier, I; Ngan, E; Mendrek, A; Liddle, P

1999-12-01

To identify which improvements in cognitive function are associated with symptom resolution in schizophrenic patients treated with atypical antipsychotics. a prospective open trial with atypical neuroleptics (risperidone, clozapine, quetiapine). Inpatient and outpatient units, Institute of Psychiatry. Thirty-nine patients with schizophrenia according to DSM-IV criteria were included. Clinical and cognitive assessment were done at baseline (T0) and again after six months of treatment (T2). Twenty-five patients completed the trial. New-generation antipsychotics during six months. Patients were considered as responders if their PANSS score decreased at least 20% (n = 15) and non-responders if it did not (n = 10). a computerized cognitive assessment comprised tests of short-term-memory (digit span), explicit long-term memory (word pair learning), divided attention, selective attention and verbal fluency (orthographic and semantic). Clinical assessment included PANSS and ESRS. A discriminant function analysis was performed to determine which changes in cognitive performance predicted symptomatic response status. Semantic fluency and orthographic fluency were significant predictors. Together they correctly predicted responder status in 88% of cases. Memory was not a significant predictor of symptomatic response. Verbal fluency discriminated the responder from the non-responder group during a pharmacological treatment.

Influence of conditioned psychological stress on immunological recovery in mice exposed to low-dose x irradiation

International Nuclear Information System (INIS)

Sato, K.; Flood, J.F.; Makinodan, T.

1984-01-01

A study was initiated to determine the effects of psychological stress on the immune response in BALB/c mice recovering from exposure to a low dose of ionizing radiation. Mice were first subjected to conditioning training for 12 days, then exposed to 200 R, subjected to psychological stress for 14 days, and assessed for peak anti-sheep RBC response. The seven treatment groups included two unirradiated groups and five irradiated groups. Mice exposed to 200 R and then subjected to conditioned psychological stress responded less vigorously to antigenic stimulation than those of the other irradiated groups. The psychological stress imposed upon these mice did not influence the antibody-forming capacity of unirradiated mice. These results indicate that a psychological stress which did not affect the immunological activity of unirradiated mice can curtail the immunological recovery of mice exposed to low doses of ionizing radiation

Pam heterozygous mice reveal essential role for Cu in amygdalar behavioral and synaptic function.

Science.gov (United States)

Gaier, Eric D; Eipper, Betty A; Mains, Richard E

2014-05-01

Copper (Cu) is an essential element with many biological roles, but its roles in the mammalian nervous system are poorly understood. Mice deficient in the cuproenzyme peptidylglycine α-amidating monooxygenase (Pam(+/-) mice) were initially generated to study neuropeptide amidation. Pam(+/-) mice exhibit profound deficits in a few behavioral tasks, including enhancements in innate fear along with deficits in acquired fear. Interestingly, several Pam(+/-) phenotypes were recapitulated in Cu-restricted wild-type mice and rescued in Cu-supplemented Pam(+/-) mice. These behaviors correspond to enhanced excitability and deficient synaptic plasticity in the amygdala of Pam(+/-) mice, which are also rescued by Cu supplementation. Cu and ATP7A are present at synapses, in key positions to respond to and influence synaptic activity. Further study demonstrated that extracellular Cu is necessary for wild-type synaptic plasticity and sufficient to induce long-term potentiation. These experiments support roles for PAM in Cu homeostasis and for synaptic Cu in amygdalar function. © 2014 New York Academy of Sciences.

Glucocorticoid cell reception in mice of different strains with natural killer cell activity depressed during immobilization stress

International Nuclear Information System (INIS)

Lyashko, V.N.; Sukhikh, G.T.

1987-01-01

The authors study differences in stress-induced depression of natural killer cell activity in mice of different inbred lines, depending on parameters of glucocorticoid binding with glucorticoid receptors of spleen cells and on the hormonal status of the animals. In determining the parameters of glucocorticoid binding on intact splenocytes, aliquots of a suspension of washed splenocytes were incubated with tritium-labeled dexamethasone

Obese mice exhibit an altered behavioural and inflammatory response to lipopolysaccharide

Directory of Open Access Journals (Sweden)

Catherine B. Lawrence

2012-09-01

Obesity is associated with an increase in the prevalence and severity of infections. Genetic animal models of obesity (ob/ob and db/db mice display altered centrally-mediated sickness behaviour in response to acute inflammatory stimuli such as lipopolysaccharide (LPS. However, the effect of diet-induced obesity (DIO on the anorectic and febrile response to LPS in mice is unknown. This study therefore determined how DIO and ob/ob mice respond to a systemic inflammatory challenge. C57BL/6 DIO and ob/ob mice, and their respective controls, were given an intraperitoneal (i.p. injection of LPS. Compared with controls, DIO and ob/ob mice exhibited an altered febrile response to LPS (100 μg/kg over 8 hours. LPS caused a greater and more prolonged anorexic effect in DIO compared with control mice and, in ob/ob mice, LPS induced a reduction in food intake and body weight earlier than it did in controls. These effects of LPS in obese mice were also seen after a fixed dose of LPS (5 μg. LPS (100 μg/kg induced Fos protein expression in several brain nuclei of control mice, with fewer Fos-positive cells observed in the brains of obese mice. An altered inflammatory response to LPS was also observed in obese mice compared with controls: changes in cytokine expression and release were detected in the plasma, spleen, liver and peritoneal macrophages in obese mice. In summary, DIO and ob/ob mice displayed an altered behavioural response and cytokine release to systemic inflammatory challenge. These findings could help explain why obese humans show increased sensitivity to infections.

Species differences in drug glucuronidation: Humanized UDP-glucuronosyltransferase 1 mice and their application for predicting drug glucuronidation and drug-induced toxicity in humans.

Science.gov (United States)

Fujiwara, Ryoichi; Yoda, Emiko; Tukey, Robert H

2018-02-01

More than 20% of clinically used drugs are glucuronidated by a microsomal enzyme UDP-glucuronosyltransferase (UGT). Inhibition or induction of UGT can result in an increase or decrease in blood drug concentration. To avoid drug-drug interactions and adverse drug reactions in individuals, therefore, it is important to understand whether UGTs are involved in metabolism of drugs and drug candidates. While most of glucuronides are inactive metabolites, acyl-glucuronides that are formed from compounds with a carboxylic acid group can be highly toxic. Animals such as mice and rats are widely used to predict drug metabolism and drug-induced toxicity in humans. However, there are marked species differences in the expression and function of drug-metabolizing enzymes including UGTs. To overcome the species differences, mice in which certain drug-metabolizing enzymes are humanized have been recently developed. Humanized UGT1 (hUGT1) mice were created in 2010 by crossing Ugt1-null mice with human UGT1 transgenic mice in a C57BL/6 background. hUGT1 mice can be promising tools to predict human drug glucuronidation and acyl-glucuronide-associated toxicity. In this review article, studies of drug metabolism and toxicity in the hUGT1 mice are summarized. We further discuss research and strategic directions to advance the understanding of drug glucuronidation in humans. Copyright © 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Regional Differences in Striatal Neuronal Ensemble Excitability Following Cocaine and Extinction Memory Retrieval in Fos-GFP Mice.

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Ziminski, Joseph J; Sieburg, Meike C; Margetts-Smith, Gabriella; Crombag, Hans S; Koya, Eisuke

2018-03-01

Learned associations between drugs of abuse and the drug administration environment have an important role in addiction. In rodents, exposure to a drug-associated environment elicits conditioned psychomotor activation, which may be weakened following extinction (EXT) learning. Although widespread drug-induced changes in neuronal excitability have been observed, little is known about specific changes within neuronal ensembles activated during the recall of drug-environment associations. Using a cocaine-conditioned locomotion (CL) procedure, the present study assessed the excitability of neuronal ensembles in the nucleus accumbens core and shell (NAc core and NAc shell ), and dorsal striatum (DS) following cocaine conditioning and EXT in Fos-GFP mice that express green fluorescent protein (GFP) in activated neurons (GFP+). During conditioning, mice received repeated cocaine injections (20 mg/kg) paired with a locomotor activity chamber (Paired) or home cage (Unpaired). Seven to 13 days later, both groups were re-exposed to the activity chamber under drug-free conditions and Paired, but not Unpaired, mice exhibited CL. In a separate group of mice, CL was extinguished by repeatedly exposing mice to the activity chamber under drug-free conditions. Following the expression and EXT of CL, GFP+ neurons in the NAc core (but not NAc shell and DS) displayed greater firing capacity compared to surrounding GFP- neurons. This difference in excitability was due to a generalized decrease in GFP- excitability following CL and a selective increase in GFP+ excitability following its EXT. These results suggest a role for both widespread and ensemble-specific changes in neuronal excitability following recall of drug-environment associations.

Growth hormone receptor antagonist transgenic mice are protected from hyperinsulinemia and glucose intolerance despite obesity when placed on a HF diet.

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Yang, Tianxu; Householder, Lara A; Lubbers, Ellen R; List, Edward O; Troike, Katie; Vesel, Clare; Duran-Ortiz, Silvana; Kopchick, John J; Berryman, Darlene E

2015-02-01

Reduced GH levels have been associated with improved glucose metabolism and increased longevity despite obesity in multiple mouse lines. However, one mouse line, the GH receptor antagonist (GHA) transgenic mouse, defies this trend because it has reduced GH action and increased adiposity, but glucose metabolism and life span are similar to controls. Slight differences in glucose metabolism and adiposity profiles can become exaggerated on a high-fat (HF) diet. Thus, in this study, male and female GHA and wild-type (WT) mice in a C57BL/6 background were placed on HF and low-fat (LF) diets for 11 weeks, starting at 10 weeks of age, to assess how GHA mice respond to additional metabolic stress of HF feeding. On a HF diet, all mice showed significant weight gain, although GHA gained weight more dramatically than WT mice, with males gaining more than females. Most of this weight gain was due to an increase in fat mass with WT mice increasing primarily in the white adipose tissue perigonadal depots, whereas GHA mice gained in both the sc and perigonadal white adipose tissue regions. Notably, GHA mice were somewhat protected from detrimental glucose metabolism changes on a HF diet because they had only modest increases in serum glucose levels, remained glucose tolerant, and did not develop hyperinsulinemia. Sex differences were observed in many measures with males reacting more dramatically to both a reduction in GH action and HF diet. In conclusion, our findings show that GHA mice, which are already obese, are susceptible to further adipose tissue expansion with HF feeding while remaining resilient to alterations in glucose homeostasis.

Effectiveness of a high-throughput genetic analysis in the identification of responders/non-responders to CYP2D6-metabolized drugs.

Science.gov (United States)

Savino, Maria; Seripa, Davide; Gallo, Antonietta P; Garrubba, Maria; D'Onofrio, Grazia; Bizzarro, Alessandra; Paroni, Giulia; Paris, Francesco; Mecocci, Patrizia; Masullo, Carlo; Pilotto, Alberto; Santini, Stefano A

2011-01-01

Recent studies investigating the single cytochrome P450 (CYP) 2D6 allele *2A reported an association with the response to drug treatments. More genetic data can be obtained, however, by high-throughput based-technologies. Aim of this study is the high-throughput analysis of the CYP2D6 polymorphisms to evaluate its effectiveness in the identification of patient responders/non-responders to CYP2D6-metabolized drugs. An attempt to compare our results with those previously obtained with the standard analysis of CYP2D6 allele *2A was also made. Sixty blood samples from patients treated with CYP2D6-metabolized drugs previously genotyped for the allele CYP2D6*2A, were analyzed for the CYP2D6 polymorphisms with the AutoGenomics INFINITI CYP4502D6-I assay on the AutoGenomics INFINITI analyzer. A higher frequency of mutated alleles in responder than in non-responder patients (75.38 % vs 43.48 %; p = 0.015) was observed. Thus, the presence of a mutated allele of CYP2D6 was associated with a response to CYP2D6-metabolized drugs (OR = 4.044 (1.348 - 12.154). No difference was observed in the distribution of allele *2A (p = 0.320). The high-throughput genetic analysis of the CYP2D6 polymorphisms better discriminate responders/non-responders with respect to the standard analysis of the CYP2D6 allele *2A. A high-throughput genetic assay of the CYP2D6 may be useful to identify patients with different clinical responses to CYP2D6-metabolized drugs.

A comparison of physical and psychological features of responders and non-responders to cervical facet blocks in chronic whiplash

Science.gov (United States)

2013-01-01

Background Cervical facet block (FB) procedures are often used as a diagnostic precursor to radiofrequency neurotomies (RFN) in the management of chronic whiplash associated disorders (WAD). Some individuals will respond to the FB procedures and others will not respond. Such responders and non-responders provided a sample of convenience to question whether there were differences in their physical and psychological features. This information may inform future predictive studies and ultimately the clinical selection of patients for FB procedures. Methods This cross-sectional study involved 58 individuals with chronic WAD who responded to cervical FB procedures (WAD_R); 32 who did not respond (WAD_NR) and 30 Healthy Controls (HC)s. Measures included: quantitative sensory tests (pressure; thermal pain thresholds; brachial plexus provocation test); nociceptive flexion reflex (NFR); motor function (cervical range of movement (ROM); activity of the superficial neck flexors during the cranio-cervical flexion test (CCFT). Self-reported measures were gained from the following questionnaires: neuropathic pain (s-LANSS); psychological distress (General Health Questionnaire-28), post-traumatic stress (PDS) and pain catastrophization (PCS). Individuals with chronic whiplash attended the laboratory once the effects of the blocks had abated and symptoms had returned. Results Following FB procedures, both WAD groups demonstrated generalized hypersensitivity to all sensory tests, decreased neck ROM and increased superficial muscle activity with the CCFT compared to controls (p 0.05). Both WAD groups demonstrated psychological distress (GHQ-28; p < 0.05), moderate post-traumatic stress symptoms and pain catastrophization. The WAD_NR group also demonstrated increased medication intake and elevated PCS scores compared to the WAD_R group (p < 0.05). Conclusions Chronic WAD responders and non-responders to FB procedures demonstrate a similar presentation of sensory disturbance, motor

The use of a responder analysis to identify clinically meaningful differences in chronic urticaria patients following placebo- controlled treatment with rupatadine 10 and 20 mg.

Science.gov (United States)

Giménez-Arnau, A; Izquierdo, I; Maurer, M

2009-09-01

According to the EAACI/GA(2)LEN/EDF guidelines for urticaria management, modern non-sedating H1-antihistamines are the first-line symptomatic treatment for chronic urticaria. Two previous randomized clinical trials demonstrated rupatadine efficacy and safety in chronic urticaria treatment. However, a responder analysis to identify clinically meaningful differences in patients with chronic urticaria has not yet been performed. This analysis includes the pooled data from two randomized, double-blind, placebo-controlled, multicentre studies in which chronic urticaria patients were treated with rupatadine at different doses. Responder rates were defined as the percentage of patients after 4 weeks of treatment who exhibited a reduction of symptoms by at least 50% or 75% as compared to baseline. The variables analysed were as follows: Mean Pruritus Score (MPS), Mean Number of Wheals (MNW), and Mean Urticaria Activity Score (UAS). A total of 538 patients were included. This responder analysis, using different response levels, shows that the efficacy of rupatadine 10 mg and 20 mg is significantly better as compared to placebo in the treatment of chronic urticaria patients. Notably, treatment with rupatadine 20 mg daily resulted in a higher percentage of patients with response of 75% symptom reduction or better than rupatadine 10 mg. Our results support the use of higher than standard doses of non sedating antihistamines in chronic urticaria. We strongly recommend performing and reporting responder analyses for established and new drugs used by patients with chronic urticaria.

Comparison of MicroRNAs Mediated in Reactivation of the γ-Globin in β-Thalassemia Patients, Responders and Non-Responders to Hydroxyurea.

Science.gov (United States)

Hojjati, Mohammad T; Azarkeivan, Azita; Pourfathollah, Ali A; Amirizadeh, Naser

2017-03-01

Drug induction of Hb F seems to be an ideal therapy for patients with hemoglobin (Hb) disorders, and many efforts have been made to reveal the mechanism behind it. Thus, we examined in vivo expression of some microRNAs (miRNAs) that are thought to be involved in this process. Among β-thalassemia (β-thal) patients who were undergoing hydroxyurea (HU) therapy in the past 3 months and five healthy individuals, five responders and five non-responders, were also included in the study. Erythroid progenitors were isolated by magnetic activated cell sorting (MACS) and miRNA expression analyzed using reverse transcription-polymerase chain reaction (RT-PCR). We showed that γ-globin, miR-210 and miR-486-3p had higher levels in the responders than the non-responders group. Moreover, miR-150 and miR-320 had higher levels in the healthy group than both non-responders and responders groups, but the expression of miR-96 did not show any significant difference between the study groups. To the best of our knowledge, this is the first study proposing that 'induction of cellular hypoxic condition by Hb F inducing agents' could be the milestone of possible mechanisms that explain why responders are able to reactivate γ-globin genes and subsequently, more production of Hb F, in response to these agents in comparison to non-responders. However, further investigations need to be performed to verify this hypothesis.

Identifying activated T cells in reconstituted RAG deficient mice using retrovirally transduced Pax5 deficient pro-B cells.

Directory of Open Access Journals (Sweden)

Nadesan Gajendran

Full Text Available Various methods have been used to identify activated T cells such as binding of MHC tetramers and expression of cell surface markers in addition to cytokine-based assays. In contrast to these published methods, we here describe a strategy to identify T cells that respond to any antigen and track the fate of these activated T cells. We constructed a retroviral double-reporter construct with enhanced green fluorescence protein (EGFP and a far-red fluorescent protein from Heteractis crispa (HcRed. LTR-driven EGFP expression was used to enrich and identify transduced cells, while HcRed expression is driven by the CD40Ligand (CD40L promoter, which is inducible and enables the identification and cell fate tracing of T cells that have responded to infection/inflammation. Pax5 deficient pro-B cells that can give rise to different hematopoietic cells like T cells, were retrovirally transduced with this double-reporter cassette and were used to reconstitute the T cell pool in RAG1 deficient mice that lack T and B cells. By using flow cytometry and histology, we identified activated T cells that had developed from Pax5 deficient pro-B cells and responded to infection with the bacterial pathogen Listeria monocytogenes. Microscopic examination of organ sections allowed visual identification of HcRed-expressing cells. To further characterize the immune response to a given stimuli, this strategy can be easily adapted to identify other cells of the hematopoietic system that respond to infection/inflammation. This can be achieved by using an inducible reporter, choosing the appropriate promoter, and reconstituting mice lacking cells of interest by injecting gene-modified Pax5 deficient pro-B cells.

SPLEEN-CELLS FROM ANTIGEN-MINIMIZED MICE ARE SUPERIOR TO SPLEEN-CELLS FROM GERM-FREE AND CONVENTIONAL MICE IN THE STIMULATION OF PRIMARY IN-VITRO PROLIFERATIVE RESPONSES TO NOMINAL ANTIGENS

NARCIS (Netherlands)

HOOPER, DC; MOLOWITZ, EH; BOS, NA; PLOPLIS, VA; CEBRA, JJ

T lymphocytes from mice reared under conditions of differential exposure to food, environmental and microbial antigens were compared for phenotypic shifts that may be associated with prior exposure to antigens as well as functional variations in the ability to respond to antigens ne novo. While the

Report 10. Cooperative immune responses of different generations of mice

International Nuclear Information System (INIS)

Savtsova, Z.D.; Kovbasyuk, S.A.; Yudina, O.Yu.; Zaritskaya, M.Yu.; Voejkova, I.M.; Orlovskij, A.A.; Indyk, V.M.; Serkiz, Ya.I.

1991-01-01

The immune status of mice has been assessed by the whole complex of data. The permanent action of low-level radiation has been shown to suppress considerably the rate of reactions of the delayed-type hypersensitivity and graft-versus host disease, as well as NK and specific cytolytic T-lymphocyte activity. The dynamics of accumulation and the levels of antibodies in the serum, lung and trachea extracts are virtually invariable. The resistance of experimental animals to influenza is lower than that of non-irradiated mice of the same line and age. The data obtained indicate that the immune disturbances revealed are connected not only with the alteration of lymphoid cell populations, but also with the alteration of the immune regulation mechanisms

Gender Differences in Response to Prolonged Every-Other-Day Feeding on the Proliferation and Apoptosis of Hepatocytes in Mice.

Science.gov (United States)

Piotrowska, Katarzyna; Tarnowski, Maciej; Zgutka, Katarzyna; Pawlik, Andrzej

2016-03-19

Intermittent fasting decreases glucose and insulin levels and increases insulin sensitivity and lifespan. Decreased food intake influences the liver. Previous studies have shown gender differences in response to various types of caloric restriction, including every-other-day (EOD) feeding, in humans and rodents. Our goal was to show the influence of prolonged EOD feeding on the morphology, proliferation and apoptosis of livers from male and female mice. After nine months of an EOD diet, the livers from male and female mice were collected. We examined their morphology on histological slides using the Hematoxilin and Eosine (H_E) method and Hoechst staining of cell nuclei to evaluate the nuclear area of hepatocytes. We also evaluated the expression of mRNA for proto-oncogens, pro-survival proteins and apoptotic markers using Real Time Polimerase Chain Reaction (PCR). We noted increased lipid content in the livers of EOD fed female mice. EOD feeding lead to a decrease of proliferation and apoptosis in the livers of female and male mice, which suggest that tissue maintenance occurred during EOD feeding. Our experiment revealed sex-specific expression of mRNA for proto-oncogenes and pro-survival and pro-apoptotic genes in mice as well as sex-specific responses to the EOD treatment.

Gender Differences in Response to Prolonged Every-Other-Day Feeding on the Proliferation and Apoptosis of Hepatocytes in Mice

Directory of Open Access Journals (Sweden)

Katarzyna Piotrowska

2016-03-01

Full Text Available Intermittent fasting decreases glucose and insulin levels and increases insulin sensitivity and lifespan. Decreased food intake influences the liver. Previous studies have shown gender differences in response to various types of caloric restriction, including every-other-day (EOD feeding, in humans and rodents. Our goal was to show the influence of prolonged EOD feeding on the morphology, proliferation and apoptosis of livers from male and female mice. After nine months of an EOD diet, the livers from male and female mice were collected. We examined their morphology on histological slides using the Hematoxilin and Eosine (H_E method and Hoechst staining of cell nuclei to evaluate the nuclear area of hepatocytes. We also evaluated the expression of mRNA for proto-oncogens, pro-survival proteins and apoptotic markers using Real Time Polimerase Chain Reaction (PCR. We noted increased lipid content in the livers of EOD fed female mice. EOD feeding lead to a decrease of proliferation and apoptosis in the livers of female and male mice, which suggest that tissue maintenance occurred during EOD feeding. Our experiment revealed sex-specific expression of mRNA for proto-oncogenes and pro-survival and pro-apoptotic genes in mice as well as sex-specific responses to the EOD treatment.

Phospholipase C δ4 regulates cold sensitivity in mice.

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Yudin, Yevgen; Lutz, Brianna; Tao, Yuan-Xiang; Rohacs, Tibor

2016-07-01

The cold- and menthol-activated transient receptor potential melastatin 8 (TRPM8) channels are thought to be regulated by phospholipase C (PLC), but neither the specific PLC isoform nor the in vivo relevance of this regulation has been established. Here we identify PLCδ4 as the key PLC isoform involved in regulation of TRPM8 channels in vivo. We show that in small PLCδ4(-/-) TRPM8-positive dorsal root ganglion neurons cold, menthol and WS-12, a selective TRPM8 agonist, evoked significantly larger currents than in wild-type neurons, and action potential frequencies induced by menthol or by current injections were also higher in PLCδ4(-/-) neurons. PLCδ4(-/-) mice showed increased behavioural responses to evaporative cooling, and this effect was inhibited by a TRPM8 antagonist; behavioural responses to heat and mechanical stimuli were not altered. We provide evidence for the involvement of a specific PLC isoform in the regulation of cold sensitivity in mice by regulating TRPM8 activity. The transient receptor potential melastatin 8 (TRPM8) ion channel is a major sensor of environmental low temperatures. Ca(2+) -induced activation of phospholipase C (PLC) has been implied in the regulation of TRPM8 channels during menthol- and cold-induced desensitization in vitro. Here we identify PLCδ4 as the key PLC isoform involved in regulation of TRPM8 in sensory dorsal root ganglion (DRG) neurons. We identified two TRPM8-positive neuronal subpopulations, based on their cell body size. Most TRPM8-positive small neurons also responded to capsaicin, and had significantly larger menthol-induced inward current densities than medium-large cells, most of which did not respond to capsaicin. Small, but not medium-large, PLCδ4(-/-) neurons showed significantly larger currents induced by cold, menthol or WS-12, a specific TRPM8 agonist, compared to wild-type (WT) neurons, but TRPM8 protein levels were not different between the two groups. In current-clamp experiments small neurons

What is wrong with non-respondents?

DEFF Research Database (Denmark)

Christensen, Anne Illemann; Ekholm, Ola; Gray, Linsay

2015-01-01

AIM: Response rates in health surveys have diminished over the last two decades, making it difficult to obtain reliable information on health and health-related risk factors in different population groups. This study compared cause-specific mortality and morbidity among survey respondents and dif...

MULTIVARIANT AND UNIVARIANT INTERGROUP DIFFERENCES IN THE INVESTIGATED SPECIFIC MOTOR SPACE BETWEEN RESPONDENTS JUNIORS AND SENIORS MEMBERS OF THE MACEDONIAN NATIONAL KARATE TEAM

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Kеnan Аsani

2013-07-01

Full Text Available The aim is to establish intergroup multivariant and univariant investigated differences in specific motor space between respondents juniors and seniors members of the Macedonian karate team. The sample of 30 male karate respondents covers juniors on 16,17 and seniors over 18 years.In the research were applied 20 specific motor tests. Based on Graph 1 where it is presented multivariant analysis of variance Manova and Anova can be noted that respondents juniors and seniors, although not belonging to the same population are not different in multivariant understudied area.W. lambda of .19, Rao-wool R - Approximation of 1.91 degrees of freedom df 1 = 20 and df 2 = 9 provides the level of significance of p =, 16. Based on univariant analysis for each variable separately can be seen that has been around intergroup statistically significant difference in seven SMAEGERI (kick in the sack with favoritism leg mae geri for 10 sec., SMAVASI (kick in the sack with favoritism foot mavashi geri by 10 sec., SUSIRO (kick in the sack with favoritism leg ushiro geri for 10 sec., SKIZAME (kick in the sack with favoritism hand kizame cuki for 10 sec., STAPNSR (taping with foot in sagital plane for 15 sec. SUDMNR (hitting a moving target with weaker hand and SUDMPN (hitting a moving target with favoritism foot of twenty applied manifest variables. There are no intergroup differences in multivariant investigated specific - motor space among the respondents juniors and seniors members of the Macedonian karate team. Based on univariant analysis for each variable separately can be seen that has been around intergroup statistically significant difference in seven SMAEGERI (kick in the sack with favoritism leg mae geri for 10 sec., SMAVASI (kick in the sack with favoritism foot mavashi geri by 10 sec., SUSIRO (kick in the sack with favoritism leg ushiro geri for 10 sec., SKIZAME (kick in the sack with favoritism hand kizame cuki for 10 sec., STAPNSR (taping with foot in

Herpes simplex virus ophthalmic disease induced using two different methods of mice inoculation

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Sílvia Regina Ferreira Gonçalves Pereira

Full Text Available Two different procedures for inoculation of HSV on corneas of BALB/c mice were evaluated. The first was by the use of HSV suspensions directly on the corneas and the other was after corneal scarification. Animals by this later method presented greater morbidity and mortality than those of first group, suggesting that inoculation of HSV without scarification of the cornea should be the method of choice for the study of HSV ophthalmic infection. This model showed also be an efficient experimental system to testing antiviral drugs.

Attentional processing in C57BL/6J mice exposed to developmental vitamin D deficiency.

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Lauren R Harms

Full Text Available Epidemiological evidence suggests that Developmental Vitamin D (DVD deficiency is associated with an increased risk of schizophrenia. DVD deficiency in mice is associated with altered behaviour, however there has been no detailed investigation of cognitive behaviours in DVD-deficient mice. The aim of this study was to determine the effect of DVD deficiency on a range of cognitive tasks assessing attentional processing in C57BL/6J mice. DVD deficiency was established by feeding female C57BL/6J mice a vitamin D-deficient diet from four weeks of age. After six weeks on the diet, vitamin D-deficient and control females were mated with vitamin D-normal males and upon birth of the pups, all dams were returned to a diet containing vitamin D. The adult offspring were tested on a range of cognitive behavioural tests, including the five-choice serial reaction task (5C-SRT and five-choice continuous performance test (5C-CPT, as well as latent inhibition using a fear conditioning paradigm. DVD deficiency was not associated with altered attentional performance on the 5C-SRT. In the 5C-CPT DVD-deficient male mice exhibited an impairment in inhibiting repetitive responses by making more perseverative responses, with no changes in premature or false alarm responding. DVD deficiency did not affect the acquisition or retention of cued fear conditioning, nor did it affect the expression of latent inhibition using a fear conditioning paradigm. DVD-deficient mice exhibited no major impairments in any of the cognitive domains tested. However, impairments in perseverative responding in DVD-deficient mice may indicate that these animals have specific alterations in systems governing compulsive or reward-seeking behaviour.

Derivation of hybrid ES cell lines from two different strains of mice

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Ho-Tak Lau

2016-03-01

Full Text Available Parental origin-dependent expression of the imprinted genes is essential for mammalian development. Zfp57 maintains genomic imprinting in mouse embryos and ES cells. To examine the allelic expression patterns of the imprinted genes in ES cells, we obtained multiple hybrid ES clones that were directly derived from the blastocysts generated from the cross between mice on two different genetic backgrounds. The blastocyst-derived ES clones displayed largely intact DNA methylation imprint at the tested imprinted regions. These hybrid ES clones will be useful for future studies to examine the allelic expression of the imprinted genes in ES cells and their differentiated progeny.

Mice: progesterone and the regulation of strain differences in pregnancy-induced nest building.

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Broida, J; Svare, B

1983-12-01

Pregnant DBA/2J females built significantly larger and more completely enclosed nests than did pregnant C57BL/6J mice. This strain difference was restricted to the last half of gestation and was not observed during either the virgin state or lactation. Genotype-based differences in pregnancy-induced nest building were not related to circulating levels of progesterone (P), core temperature, or body weight. Exposure to supplemented P during pregnancy elevated nest building exhibited by pregnant C57BL females but did not induce DBA-like levels of the behavior. Also, virgin DBA females built larger nests in response to P than did C57BL females. These findings suggest that differences in the sensitivity of central neural tissue to steroid hormones may account for genotypically determined variation in patterns of pregnancy-induced nest building.

Does the Length of Fielding Period Matter? Examining Response Scores of Early Versus Late Responders

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Sigman Richard

2014-12-01

Full Text Available This article discusses the potential effects of a shortened fielding period on an employee survey’s item and index scores and respondent demographics. Using data from the U.S. Office of Personnel Management’s 2011 Federal Employee Viewpoint Survey, we investigate whether early responding employees differ from later responding employees. Specifically, we examine differences in item and index scores related to employee engagement and global satisfaction. Our findings show that early responders tend to be less positive, even after adjusting their weights for nonresponse. Agencies vary in their prevalence of late responders, and score differences become magnified as this proportion increases. We also examine the extent to which early versus late responders differ on demographic characteristics such as grade level, supervisory status, gender, tenure with agency, and intention to leave, noting that nonminorities and females are the two demographic characteristics most associated with responding early.

Radiosensitivity of mice of different lines and age as determinated with reference to ''intestinal'' death and DNA repair in intestinal epithelium cells

Energy Technology Data Exchange (ETDEWEB)

Konoplyannikova, O.A.; Sklobovskaya, M.V.; Konoplyannikov, A.G.; Saenko, A.S. (Akademiya Meditsinskikh Nauk SSSR, Obninsk. Nauchno-Issledovatel' skij Inst. Meditsinskoj Radiologii)

A study was made of the influence of strain- and age-related differences on mouse mortality after irradiation with doses lying within the ''intestinal'' dose range, and also damages to stem cells of intestinal epithelium and induction and repair of single-strand DNA breaks in intestinal epitherium cells. Mice of different lines and age vary in LDsub(50/4) and stem cell radiosensitivity. There are no differences in the sedimentation constants of DNA fragments in alkaline lysates of intestinal crypts of intact mice of different age. Radiosensitivity determined with reference to single-strand breaks induction in DNA is similar with different mouse groups. Repair of single-strand DNA breaks of elderly mice is slower than that of young animals.

Differences Between Tg2576 and Wild Type Mice in the NMDA Receptor-Nitric Oxide Pathway After Prolonged Application of a Diet High in Advanced Glycation End Products.

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Kristofikova, Zdena; Ricny, Jan; Sirova, Jana; Ripova, Daniela; Lubitz, Irit; Schnaider-Beeri, Michal

2015-08-01

It has been suggested that advanced glycation end (AGE) products, via cognate receptor activation, are implicated in several diseases, including Alzheimer's disease. The NMDA receptor-nitric oxide pathway appears to be influenced by AGE products and involved in the pathogenesis of this type of dementia. In this study, C57BL/6J (WT) and transgenic (Tg2576) mice expressing human mutant amyloid precursor protein were kept on prolonged (8 months) diets containing regular or high amounts of AGE products. After the decapitation of 11-months old mice, brain tissue analyses were performed [expressions of the NR1, NR2A and NR2B subunits of NMDA receptors, activities of neuronal, endothelial and inducible nitric oxide synthase (nNOS, eNOS and iNOS)]. Moreover, levels of malondialdehyde and of human amyloid β 1-42 were estimated. We found increased activity of nNOS in WT mice maintained on a high compared to regular AGE diet; however, no similar differences were found in Tg2576 mice. In addition, we observed an increase in NR1 expression in Tg2576 compared to WT mice, both kept on a diet high in AGE products. Correlation analyses performed on mice kept on the regular AGE diet supported close links between particular subunits (NR2A-NR2B, in WT as well as in Tg2576 mice), between subunits and synthase (NR2A/NR2B-nNOS, only in WT mice) or between particular synthases (nNOS-iNOS, only in WT). Correlation analysis also revealed differences between WT mice kept on both diets (changed correlations between NR2A/NR2B-nNOS, between nNOS-eNOS and between eNOS-iNOS). Malondialdehyde levels were increased in both Tg2576 groups when compared to the corresponding WT mice, but no effects of the diets were observed. Analogously, no significant effects of diets were found in the levels of soluble or insoluble amyloid β 1-42 in Tg2576 mice. Our results demonstrate that prolonged ingestion of AGE products can influence the NMDA receptor-nitric oxide pathway in the brain and that only WT mice

Different kinetic in incorporation and depletion of n-3 fatty acids in erythrocytes and leukocytes of mice

DEFF Research Database (Denmark)

Mu, Huiling; Thogersen, Regitze Louise; Maaetoft-Udsen, Kristina

2006-01-01

during a 6-wk feeding period. Over the first 3-wk period (the incorporation period) the mice were fed a special diet with a high n-3/n-6 PUFA ratio. In the following 3-wk period (the depletion period) the mice were fed a standard chow diet. A linear increase of the concentration of EPA and DHA...... in erythrocyte membranes was observed during the incorporation period, whereas a stagnation was observed after the second week for leukocytes. The level of EPA did not fall to the background level after the depletion period, and the level of DHA was kept almost constant during the depletion period...... in the erythrocyte membranes. In leukocytes the concentration of both EPA and DHA decreased during the depletion period, but did not reach the background level after the 3-wk depletion. In conclusion, the kinetics of EPA and DHA in the different cells are different. The rate of incorporation is faster than...

Comparison of particle-exposure triggered pulmonary and systemic inflammation in mice fed with three different diets.

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Götz, Alexander A; Rozman, Jan; Rödel, Heiko G; Fuchs, Helmut; Gailus-Durner, Valérie; Hrabě de Angelis, Martin; Klingenspor, Martin; Stoeger, Tobias

2011-09-27

Obesity can be linked to disease risks such as diabetes and cardiovascular disorders, but recently, the adipose tissue (AT) macrophage also emerges as actively participating in inflammation and immune function, producing pro- and anti-inflammatory factors. Connections between the AT and chronic lung diseases, like emphysema and asthma and a protective role of adipocyte-derived proteins against acute lung injury were suggested.In this study we addressed the question, whether a diet challenge increases the inflammatory response in the alveolar and the blood compartment in response to carbon nanoparticles (CNP), as a surrogate for ambient/urban particulate air pollutants. Mice were fed a high caloric carbohydrate-rich (CA) or a fat-rich (HF) diet for six weeks and were compared to mice kept on a purified low fat (LF) diet, respectively. Bronchoalveolar lavage (BAL) and blood samples were taken 24 h after intratracheal CNP instillation and checked for cellular and molecular markers of inflammation. The high caloric diets resulted in distinct effects when compared with LF mice, respectively: CA resulted in increased body and fat mass without affecting blood cellular immunity. Conversely, HF activated the blood system, increasing lymphocyte and neutrophil counts, and resulted in slightly increased body fat content. In contrast to higher pro-inflammatory BAL Leptin in CA and HF mice, on a cellular level, both diets did not lead to an increased pro-inflammatory basal status in the alveolar compartment per se, nor did result in differences in the particle-triggered response. However both diets resulted in a disturbance of the alveolar capillary barrier as indicated by enhanced BAL protein and lactate-dehydrogenase concentrations. Systemically, reduced serum Adiponectin in HF mice might be related to the observed white blood cell increase. The increase in BAL pro-inflammatory factors in high caloric groups and reductions in serum concentrations of anti-inflammatory factors

Comparison of particle-exposure triggered pulmonary and systemic inflammation in mice fed with three different diets

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Hrabě de Angelis Martin

2011-09-01

Full Text Available Abstract Background Obesity can be linked to disease risks such as diabetes and cardiovascular disorders, but recently, the adipose tissue (AT macrophage also emerges as actively participating in inflammation and immune function, producing pro- and anti-inflammatory factors. Connections between the AT and chronic lung diseases, like emphysema and asthma and a protective role of adipocyte-derived proteins against acute lung injury were suggested. In this study we addressed the question, whether a diet challenge increases the inflammatory response in the alveolar and the blood compartment in response to carbon nanoparticles (CNP, as a surrogate for ambient/urban particulate air pollutants. Methods Mice were fed a high caloric carbohydrate-rich (CA or a fat-rich (HF diet for six weeks and were compared to mice kept on a purified low fat (LF diet, respectively. Bronchoalveolar lavage (BAL and blood samples were taken 24 h after intratracheal CNP instillation and checked for cellular and molecular markers of inflammation. Results and discussion The high caloric diets resulted in distinct effects when compared with LF mice, respectively: CA resulted in increased body and fat mass without affecting blood cellular immunity. Conversely, HF activated the blood system, increasing lymphocyte and neutrophil counts, and resulted in slightly increased body fat content. In contrast to higher pro-inflammatory BAL Leptin in CA and HF mice, on a cellular level, both diets did not lead to an increased pro-inflammatory basal status in the alveolar compartment per se, nor did result in differences in the particle-triggered response. However both diets resulted in a disturbance of the alveolar capillary barrier as indicated by enhanced BAL protein and lactate-dehydrogenase concentrations. Systemically, reduced serum Adiponectin in HF mice might be related to the observed white blood cell increase. Conclusion The increase in BAL pro-inflammatory factors in high caloric

T-cell-dependent control of acute Giardia lamblia infections in mice.

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Singer, S M; Nash, T E

2000-01-01

We have studied immune mechanisms responsible for control of acute Giardia lamblia and Giardia muris infections in adult mice. Association of chronic G. lamblia infection with hypogammaglobulinemia and experimental infections of mice with G. muris have led to the hypothesis that antibodies are required to control these infections. We directly tested this hypothesis by infecting B-cell-deficient mice with either G. lamblia or G. muris. Both wild-type mice and B-cell-deficient mice eliminated the vast majority of parasites between 1 and 2 weeks postinfection with G. lamblia. G. muris was also eliminated in both wild-type and B-cell-deficient mice. In contrast, T-cell-deficient and scid mice failed to control G. lamblia infections, as has been shown previously for G. muris. Treatment of wild-type or B-cell-deficient mice with antibodies to CD4 also prevented elimination of G. lamblia, confirming a role for T cells in controlling infections. By infecting mice deficient in either alphabeta- or gammadelta-T-cell receptor (TCR)-expressing T cells, we show that the alphabeta-TCR-expressing T cells are required to control parasites but that the gammadelta-TCR-expressing T cells are not. Finally, infections in mice deficient in production of gamma interferon or interleukin 4 (IL-4) and mice deficient in responding to IL-4 and IL-13 revealed that neither the Th1 nor the Th2 subset is absolutely required for protection from G. lamblia. We conclude that a T-cell-dependent mechanism is essential for controlling acute Giardia infections and that this mechanism is independent of antibody and B cells.

Tibial loading increases osteogenic gene expression and cortical bone volume in mature and middle-aged mice.

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Matthew J Silva

Full Text Available There are conflicting data on whether age reduces the response of the skeleton to mechanical stimuli. We examined this question in female BALB/c mice of different ages, ranging from young to middle-aged (2, 4, 7, 12 months. We first assessed markers of bone turnover in control (non-loaded mice. Serum osteocalcin and CTX declined significantly from 2 to 4 months (p<0.001. There were similar age-related declines in tibial mRNA expression of osteoblast- and osteoclast-related genes, most notably in late osteoblast/matrix genes. For example, Col1a1 expression declined 90% from 2 to 7 months (p<0.001. We then assessed tibial responses to mechanical loading using age-specific forces to produce similar peak strains (-1300 µε endocortical; -2350 µε periosteal. Axial tibial compression was applied to the right leg for 60 cycles/day on alternate days for 1 or 6 weeks. qPCR after 1 week revealed no effect of loading in young (2-month mice, but significant increases in osteoblast/matrix genes in older mice. For example, in 12-month old mice Col1a1 was increased 6-fold in loaded tibias vs. controls (p = 0.001. In vivo microCT after 6 weeks revealed that loaded tibias in each age group had greater cortical bone volume (BV than contralateral control tibias (p<0.05, due to relative periosteal expansion. The loading-induced increase in cortical BV was greatest in 4-month old mice (+13%; p<0.05 vs. other ages. In summary, non-loaded female BALB/c mice exhibit an age-related decline in measures related to bone formation. Yet when subjected to tibial compression, mice from 2-12 months have an increase in cortical bone volume. Older mice respond with an upregulation of osteoblast/matrix genes, which increase to levels comparable to young mice. We conclude that mechanical loading of the tibia is anabolic for cortical bone in young and middle-aged female BALB/c mice.

Strain differences in paroxetine-induced reduction of immobility time in the forced swimming test in mice: role of serotonin.

Science.gov (United States)

Guzzetti, Sara; Calcagno, Eleonora; Canetta, Alessandro; Sacchetti, Giuseppina; Fracasso, Claudia; Caccia, Silvio; Cervo, Luigi; Invernizzi, Roberto W

2008-10-10

We studied the antidepressant-like effect of paroxetine in strains of mice carrying different isoforms of tryptophan hydroxylase-2 (TPH-2), the enzyme responsible for the synthesis of brain serotonin (5-HT). The effect of paroxetine alone and in combination with pharmacological treatments enhancing or lowering 5-HT synthesis or melatonin was assessed in the forced swimming test in mice carrying allelic variants of TPH-2 (1473C in C57BL/6 and 1473G in DBA/2 and BALB/c). Changes in brain 5-hydroxytryptophan (5-HTP) accumulation and melatonin levels were measured by high-performance liquid chromatography. Paroxetine (2.5 and 5 mg/kg) reduced immobility time in C57BL/6J and C57BL/6N mice but had no such effect in DBA/2J, DBA/2N and BALB/c mice, even at 10 mg/kg. Enhancing 5-HT synthesis with tryptophan reinstated the antidepressant-like effect of paroxetine in DBA/2J, DBA/2N and BALB/c mice whereas inhibition of 5-HT synthesis prevented the effect of paroxetine in C57BL/6N mice. The response to paroxetine was not associated with changes in locomotor activity, brain melatonin or brain levels of the drug measured at the end of the behavioral test. These results support the importance of 5-HT synthesis in the response to SSRIs and suggest that melatonin does not contribute to the ability of tryptophan to rescue the antidepressant-like effect of paroxetine.

Oral Immunization with Recombinant Norwalk Virus-Like Particles Induces a Systemic and Mucosal Immune Response in Mice

OpenAIRE

Ball, Judith M.; Hardy, Michele E.; Atmar, Robert L.; Conner, Margaret E.; Estes, Mary K.

1998-01-01

Recombinant Norwalk virus-like particles (rNV VLPs) produced in insect cells were evaluated as an oral immunogen in CD1 and BALB/c mice by monitoring rNV-specific serum total and subclass immunoglobulin G (IgG) and intestinal IgA responses. Dose and kinetics of response were evaluated in the presence and absence of the mucosal adjuvant cholera toxin (CT). rNV-specific serum IgG and intestinal IgA were detected in the absence of CT, and the number of responders was not significantly different ...

Effect of different stressors on voluntary ethanol intake in ethanol-dependent and nondependent C57BL/6J mice.

Science.gov (United States)

Lopez, Marcelo F; Anderson, Rachel I; Becker, Howard C

2016-03-01

Several animal models have evaluated the effect of stress on voluntary ethanol intake with mixed results. The experiments reported here examined the effects of different stressors on voluntary ethanol consumption in dependent and nondependent adult male C57BL/6J mice. In Experiment 1, restraint, forced swim, and social defeat stress procedures all tended to reduce ethanol intake in nondependent mice regardless of whether the stress experience occurred 1 h or 4 h prior to ethanol access. The reduction in ethanol consumption was most robust following restraint stress. Experiment 2 examined the effects of forced swim stress and social defeat stress on drinking in a dependence model that involved repeated cycles of chronic intermittent ethanol (CIE) exposure. Repeated exposure to forced swim stress prior to intervening test drinking periods that followed repeated cycles of CIE exposure further increased ethanol consumption in CIE-exposed mice while not altering intake in nondependent mice. In contrast, repeated exposure to the social defeat stressor in a similar manner reduced ethanol consumption in CIE-exposed mice while not altering drinking in nondependent mice. Results from Experiment 3 confirmed this selective effect of forced swim stress increasing ethanol consumption in mice with a history of CIE exposure, and also demonstrated that enhanced drinking is only observed when the forced swim stressor is administered during each test drinking week, but not if it is applied only during the final test week. Collectively, these studies point to a unique interaction between repeated stress experience and CIE exposure, and also suggest that such an effect depends on the nature of the stressor. Future studies will need to further explore the generalizability of these results, as well as mechanisms underlying the ability of forced swim stress to selectively further enhance ethanol consumption in dependent (CIE-exposed) mice but not alter intake in nondependent animals

Timing of growth hormone treatment affects trabecular bone microarchitecture and mineralization in growth hormone deficient mice.

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Kristensen, Erika; Hallgrímsson, Benedikt; Morck, Douglas W; Boyd, Steven K

2010-08-01

Growth hormone (GH) is essential in the development of bone mass, and a growth hormone deficiency (GHD) in childhood is frequently treated with daily injections of GH. It is not clear what effect GHD and its treatment has on bone. It was hypothesized that GHD would result in impaired microarchitecture, and an early onset of treatment would result in a better recovery than late onset. Growth hormone deficient homozygous (lit/lit) mice of both sexes were divided into two treatment groups receiving daily injections of GH, starting at an early (21 days of age) or a late time point (35 days of age, corresponding to the end of puberty). A group of heterozygous mice with normal levels of growth hormone served as controls. In vivo micro-computed tomography scans of the fourth lumbar vertebra were obtained at five time points between 21 and 60 days of age, and trabecular morphology and volumetric BMD were analyzed to determine the effects of GH on bone microarchitecture. Early GH treatment led to significant improvements in bone volume ratio (p=0.006), tissue mineral density (p=0.005), and structure model index (p=0.004) by the study endpoint (day 60), with no detected change in trabecular thickness. Trabecular number increased and trabecular separation decreased in GHD mice regardless of treatment compared to heterozygous mice. This suggests fundamental differences in the structure of trabecular bone in GHD and GH treated mice, reflected by an increased number of thinner trabeculae in these mice compared to heterozygous controls. There were no significant differences between the late treatment group and GHD mice except for connectivity density. Taken together, these results indicate that bone responds to GH treatment initiated before puberty but not to treatment commencing post-puberty, and that GH treatment does not rescue the structure of trabecular bone to that of heterozygous controls. Copyright 2010 Elsevier Inc. All rights reserved.

[Immunosuppressant effect of cyclophosphamide activated in vitro by liver microsomes from different strains of mice].

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Telegin, L Iu; Zhirnov, G F; Mazurov, A V; Pevnitskiĭ, L A

1981-07-01

The paper is concerned with activation of cyclophosphamide by mouse liver microsomes in vitro. Liver microsomes from BALB/c mice metabolize cyclophosphamide more effectively as compared with those from DBA/2 mice, which manifested by a more intense output of products having alkylating or immunodepressant properties. This seems likely to be a consequence of the increased P-450 cytochrome content in liver microsomes from BALB/c mice, as well as of its structural characteristics in the mouse. The relationship between the immunodepressant effect of cyclophosphamide in vivo and in vitro in mice of varied genotypes is discussed.

Immunomodulatory activities of different solvent extracts from Tricholoma matsutake (S. Ito et S. Imai) singer (higher basidiomycetes) on normal mice.

Science.gov (United States)

Yin, Xiulian; You, Qinghong; Jiang, Zhonghai

2012-01-01

The immunomodulatory activities of different solvent extracts from the culinary-medicinal mushroom Tricholoma matsutake were studied in vivo in normal mice. The extracts were prepared using different solvents in an order of increasing polarity. The immunomodulatory activities were investigated by measuring the thymus and spleen index, phagocytic rate of macrophage phagocytosis, delayed-type hypersensitivity, plaque-forming cell, and proliferation of splenocytes. Results demonstrated that water extract (WE) and n-butyl alcohol extract (BAE) of T. matsutake could enhance the immunity of mice significantly compared with the control group. Main components of WE and BAE were polysaccharides, proteins, and flavonoids; we presume that these may be the main immunomodulating and immuno-enhancing agents in T. matsutake.

Spatial learning and psychomotor performance of C57BL/6 mice: age sensitivity and reliability of individual differences.

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de Fiebre, Nancyellen C; Sumien, Nathalie; Forster, Michael J; de Fiebre, Christopher M

2006-09-01

Two tests often used in aging research, the elevated path test and the Morris water maze test, were examined for their application to the study of brain aging in a large sample of C57BL/6JNia mice. Specifically, these studies assessed: (1) sensitivity to age and the degree of interrelatedness among different behavioral measures derived from these tests, (2) the effect of age on variation in the measurements, and (3) the reliability of individual differences in performance on the tests. Both tests detected age-related deficits in group performance that occurred independently of each other. However, analysis of data obtained on the Morris water maze test revealed three relatively independent components of cognitive performance. Performance in initial acquisition of spatial learning in the Morris maze was not highly correlated with performance during reversal learning (when mice were required to learn a new spatial location), whereas performance in both of those phases was independent of spatial performance assessed during a single probe trial administered at the end of acquisition training. Moreover, impaired performance during initial acquisition could be detected at an earlier age than impairments in reversal learning. There were modest but significant age-related increases in the variance of both elevated path test scores and in several measures of learning in the Morris maze test. Analysis of test scores of mice across repeated testing sessions confirmed reliability of the measurements obtained for cognitive and psychomotor function. Power calculations confirmed that there are sufficiently large age-related differences in elevated path test performance, relative to within age variability, to render this test useful for studies into the ability of an intervention to prevent or reverse age-related deficits in psychomotor performance. Power calculations indicated a need for larger sample sizes for detection of intervention effects on cognitive components of the

Respiratory syncytial virus, pneumonia virus of mice, and influenza A virus differently affect respiratory allergy in mice

NARCIS (Netherlands)

Barends, M.; de Rond, L. G. H.; Dormans, J.; van Oosten, M.; Boelen, A.; Neijens, H. J.; Osterhaus, A. D. M. E.; Kimman, T. G.

2004-01-01

Respiratory viral infections in early childhood may interact with the immune system and modify allergen sensitization and/or allergic manifestations. In mice, respiratory syncytial virus (RSV) infection during allergic provocation aggravates the allergic T helper (Th) 2 immune response,

A different role of angiotensin II type 1a receptor in the development and hypertrophy of plantaris muscle in mice.

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Zempo, Hirofumi; Suzuki, Jun-Ichi; Ogawa, Masahito; Watanabe, Ryo; Isobe, Mitsuaki

2016-02-01

The role of angiotensin II type 1 (AT1) receptors in muscle development and hypertrophy remains unclear. This study was designed to reveal the effects that a loss of AT1 receptors has on skeletal muscle development and hypertrophy in mice. Eight-week-old male AT1a receptor knockout (AT1a(-/-)) mice were used for this experiment. The plantaris muscle to body weight ratio, muscle fiber cross-sectional area, and number of muscle fibers of AT1a(-/-) mice was significantly greater than wild type (WT) mice in the non-intervention condition. Next, the functional overload (OL) model was used to induce plantaris muscle hypertrophy by surgically removing the two triceps muscles consisting of the calf, soleus, and gastrocnemius muscles in mice. After 14 days of OL intervention, the plantaris muscle weight, the amount of fiber, and the fiber area increased. However, the magnitude of the increment of plantaris weight was not different between the two strains. Agtr1a mRNA expression did not change after OL in WT muscle. Actually, the Agt mRNA expression level of WT-OL was lower than WT-Control (C) muscle. An atrophy-related gene, atrogin-1 mRNA expression levels of AT1a(-/-)-C, WT-OL, and AT1a(-/-)-OL muscle were lower than that of WT-C muscle. Our findings suggest that AT1 receptor contributes to plantaris muscle development via atrogin-1 in mice.

[Anatomy and histology characteristics of lymph node in nude mice].

Science.gov (United States)

Sun, R; Gao, B; Guo, C B

2017-10-18

To compare the differences of anatomical and histological characteristics of lymph nodes between BALB/c nude mice and BALB/c mice. Firstly, twenty BALB/c nude mice and twenty BALB/c mice were dissected by using a surgical microscope. Secondly, the differences of T cells and B cells at the lymph node were compared by the expressions of CD 3 and CD 20 immunohistochemistry dyes. There were, on average, 23 nodes per mouse contained within the large lymph node assembly in the BALB/c nude mouse. The anatomical features of the lymph node distribution in the nude mice were mainly found in the neck with relatively higher density. There were two lymph nodes both in the submandible lymph nodes group and in the superficial cervical lymph nodes group (the constituent ratios were 95% and 90%, respectively) in the BALB/c nude mice, but there were four lymph nodes (the constituent ratios were 95% and 90%, respectively) in the BALB/c mice. There were significant difference between the BALB/c nude mice and the BALB/c mice. Mostly there were two lymph nodes of deep cervical lymph nodes both in the BALB/c nude mice and the BALB/c mice (the constituent ratios were 95% and 100%, respectively). There were no significant difference between the BALB/c nude mice and the BALB/c mice. We confirmed that the number of CD 3 -positive T lymphocytes in lymph nodes of the nude mice decreased greatly as compared with the BALB/c mice. Expressions of CD3 in T cells were 95% and 100% in the BALB/c nude mice and in the BALB/c mice, respectively. There were significant differences between the BALB/c nude mice and the BALB/c mice. Expressions of CD20 in B cells were 95% and 100% in the BALB/c nude mice and in the BALB/c mice, respectively. There was no significant difference between the BALB/c nude mice and BALB/c mice. The anatomical pictures of lymph node distribution in the nude mouse will be benefit to those who are interested. The anatomical features of the lymph node local higher density in neck of

不同频率音乐对小鼠空间学习记忆能力的影响%Impact of music of different frequencies on the spatial learning and memory ability of mice

Institute of Scientific and Technical Information of China (English)

袁徐蕾; 杨梅; 韩文莉; 谭冬梅; 范尧; 谭毅

2017-01-01

目的 初步探究音乐对成年小鼠学习记忆能力是否产生影响.方法 80只C57小鼠随机分成10组,每组雌雄各半.空白对照组:不给予音乐刺激,高频音乐3组、中频音乐3组、低频音乐3组,分别用高频、中频、低频各3首进行音乐刺激,每天5 h,连续6 d.第7天进行水迷宫测试,期间保持音乐刺激不变,测试指标为潜伏期,经过平台次数和平台象限停留时间.结果 音乐组与空白组相比,小鼠逃避潜伏期明显缩短(P0.05).各音乐组之间检测指标差异无显著性(P>0.05).结论 所选9首音乐能提高成年小鼠学习记忆能力,而不同频率音乐之间产生的影响未发现显著性差异.推测音乐刺激对小鼠的影响与音乐分类的标准、刺激周期长短、刺激时间点选择等因素密切相关.%Objective To explore the impact of music of different frequencies on the spatial learning and memory a?bility of mice. Methods A total of 80 healthy 6～8 weeks old C57 mice were randomly divided into 10 groups, half male and half female in each group. The mice in the control group were not stimulated by music. The mice of the 3 groups of high?frequency music, 3 groups of medium?frequency music and 3 groups of low?frequency music were stimulated by music in cor?responding range of frequency, respectively, for 5 h each day. After 6 d, the ability of spatial learning and memory of the mice was tested in the Morris water maze, with the same stimulation of music during the test. The indicators of the test in?cluded the avoiding latency, the frequency of passing the platform and the time spent to pass the quadrant of the mice in each group. Results Compared with the control group, the avoiding latency of the mice in the groups with stimulation by music was significantly shorter (P 0. 05). Moreover, there was no significant difference between the indica?tors of the 9 groups receiving music stimulation (P> 0. 05). Conclusions The 9 pieces of music we have

Tetracycline-inducible system for regulation of skeletal muscle-specific gene expression in transgenic mice

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Grill, Mischala A.; Bales, Mark A.; Fought, Amber N.; Rosburg, Kristopher C.; Munger, Stephanie J.; Antin, Parker B.

2003-01-01

Tightly regulated control of over-expression is often necessary to study one aspect or time point of gene function and, in transgenesis, may help to avoid lethal effects and complications caused by ubiquitous over-expression. We have utilized the benefits of an optimized tet-on system and a modified muscle creatine kinase (MCK) promoter to generate a skeletal muscle-specific, doxycycline (Dox) controlled over-expression system in transgenic mice. A DNA construct was generated in which the codon optimized reverse tetracycline transactivator (rtTA) was placed under control of a skeletal muscle-specific version of the mouse MCK promoter. Transgenic mice containing this construct expressed rtTA almost exclusively in skeletal muscles. These mice were crossed to a second transgenic line containing a bi-directional promoter centered on a tet responder element driving both a luciferase reporter gene and a tagged gene of interest; in this case the calpain inhibitor calpastatin. Compound hemizygous mice showed high level, Dox dependent muscle-specific luciferase activity often exceeding 10,000-fold over non-muscle tissues of the same mouse. Western and immunocytochemical analysis demonstrated similar Dox dependent muscle-specific induction of the tagged calpastatin protein. These findings demonstrate the effectiveness and flexibility of the tet-on system to provide a tightly regulated over-expression system in adult skeletal muscle. The MCKrtTA transgenic lines can be combined with other transgenic responder lines for skeletal muscle-specific over-expression of any target gene of interest.

Effects of social isolation, re-socialization and age on cognitive and aggressive behaviors of Kunming mice and BALB/c mice.

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An, Dong; Chen, Wei; Yu, De-Qin; Wang, Shi-Wei; Yu, Wei-Zhi; Xu, Hong; Wang, Dong-Mei; Zhao, Dan; Sun, Yi-Ping; Wu, Jun-Cheng; Tang, Yi-Yuan; Yin, Sheng-Ming

2017-05-01

Both Kunming (KM) mice and BALB/c mice have been widely used as rodent models to investigate stress-associated mental diseases. However, little is known about the different behaviors of KM mice and BALB/c mice after social isolation, particularly cognitive and aggressive behaviors. In this study, the behaviors of KM and BALB/c mice isolated for 2, 4 and 8 weeks and age-matched controls were evaluated using object recognition, object location and resident-intruder tests. The recovery of behavioral deficits by re-socialization was also examined for the isolated mice in adolescence. Our study showed that isolation for 2, 4 and 8 weeks led to cognitive deficits and increased aggressiveness for both KM and BALB/c mice. An important finding is that re-socialization could completely recover spatial/non-spatial cognitive deficits resulted from social isolation for both KM and BALB/c mice. In addition, age only impacted aggressiveness of KM mice. Moreover, isolation duration showed different impacts on cognitive and aggressive behaviors for both KM and BALB/c mice. Furthermore, BALB/c mice showed weak spatial/non-spatial memory and low aggressiveness when they were at the same age and isolation duration, compared to KM mice. In conclusion, KM mice and BALB/c mice behaved characteristically under physiology and isolation conditions. © 2016 Japanese Society of Animal Science.

Differences between seizure-prone and non-seizure-prone mice with regard to glutamate and GABA receptor binding in the hippocampus and other regions of the brain

DEFF Research Database (Denmark)

Frandsen, A; Belhage, B; Schousboe, A

1987-01-01

Quisqualate-preferring glutamate receptors were determined in membranes from frontal cortex, occipital cortex, hippocampus and cerebellum, from seizure-prone DBA/2J BOM and seizure-resistant C57/BL mice. The animals were studied 21, 27 and 40 days postnatally, i.e., before, during and after the age...... at which DBA mice are most susceptible to seizures. Radio-binding assays were performed using [3H]AMPA in the presence of 100 nM glutamate. Except for the occipital cortex, where no significant differences between the two strains were observed, all areas of the brain of DBA mice exhibited significantly (P...... less than 0.001, t test) higher AMPA binding than the corresponding areas of C57/BL mice at 27 days of age. At pre- and post-susceptible ages, the two strains showed no significant differences in the hippocampus and occipital cortex. A significant difference was observed, however, in the frontal cortex...

RhD Specific Antibodies Are Not Detectable in HLA-DRB11501* Mice Challenged with Human RhD Positive Erythrocytes

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Lidice Bernardo

2014-01-01

Full Text Available The ability to study the immune response to the RhD antigen in the prevention of hemolytic disease of the fetus and newborn has been hampered by the lack of a mouse model of RhD immunization. However, the ability of transgenic mice expressing human HLA DRB11501* to respond to immunization with purified RhD has allowed this question to be revisited. In this work we aimed at inducing anti-RhD antibodies by administering human RhD+ RBCs to mice transgenic for the human HLA DRB11501* as well as to several standard inbred and outbred laboratory strains including C57BL/6, DBA1/J, CFW(SW, CD1(ICR, and NSA(CF-1. DRB11501* mice were additionally immunized with putative extracellular immunogenic RhD peptides. DRB11501* mice immunized with RhD+ erythrocytes developed an erythrocyte-reactive antibody response. Antibodies specific for RhD could not however be detected by flow cytometry. Despite this, DRB11501* mice were capable of recognizing immunogenic sequences of Rh as injection with Rh peptides induced antibodies reactive with RhD sequences, consistent with the presence of B cell repertoires capable of recognizing RhD. We conclude that while HLA DRB11501* transgenic mice may have the capability of responding to immunogenic sequences within RhD, an immune response to human RBC expressing RhD is not directly observed.

Modest vasomotor dysfunction induced by low doses of C60 fullerenes in apolipoprotein E knockout mice with different degree of atherosclerosis

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Loft Steffen

2009-02-01

Full Text Available Abstract Background Exposure to small size particulate matter in urban air is regarded as a risk factor for cardiovascular effects, whereas there is little information about the impact on the cardiovascular system by exposure to pure carbonaceous materials in the nano-size range. C60 fullerenes are nano-sized particles that are expected to have a widespread use, including cosmetics and medicines. Methods We investigated the association between intraperitoneal injection of pristine C60 fullerenes and vasomotor dysfunction in the aorta of 11–13 and 40–42 weeks old apolipoprotein E knockout mice (apoE-/- with different degree of atherosclerosis. Results The aged apoE-/-mice had lower endothelium-dependent vasorelaxation elicited by acetylcholine in aorta segments mounted in myographs and the phenylephrine-dependent vasoconstriction response was increased. One hour after an intraperitoneal injection of 0.05 or 0.5 mg/kg of C60 fullerenes, the young apoE-/- mice had slightly reduced maximal endothelium-dependent vasorelaxation. A similar tendency was observed in the old apoE-/- mice. Hampered endothelium-independent vasorelaxation was also observed as slightly increased EC50 of sodium nitroprusside-induced vasorelaxation response in young apoE-/- mice. Conclusion Treatment with C60 fullerenes affected mainly the response to vasorelaxation in young apoE-/- mice, whereas the vasomotor dysfunction in old apoE-/- mice with more advanced atherosclerosis was less affected by acute C60 fullerene treatment. These findings represent an important step in the hazard characterization of C60 fullerenes by showing that intraperitoneal administration is associated with a moderate decrease in the vascular function of mice with atherosclerosis.

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

International Nuclear Information System (INIS)

Umezu, Toyoshi; Shibata, Yasuyuki

2014-01-01

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

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.

Evaluation of Respondent-Driven Sampling

Science.gov (United States)

McCreesh, Nicky; Frost, Simon; Seeley, Janet; Katongole, Joseph; Tarsh, Matilda Ndagire; Ndunguse, Richard; Jichi, Fatima; Lunel, Natasha L; Maher, Dermot; Johnston, Lisa G; Sonnenberg, Pam; Copas, Andrew J; Hayes, Richard J; White, Richard G

2012-01-01

Background Respondent-driven sampling is a novel variant of link-tracing sampling for estimating the characteristics of hard-to-reach groups, such as HIV prevalence in sex-workers. Despite its use by leading health organizations, the performance of this method in realistic situations is still largely unknown. We evaluated respondent-driven sampling by comparing estimates from a respondent-driven sampling survey with total-population data. Methods Total-population data on age, tribe, religion, socioeconomic status, sexual activity and HIV status were available on a population of 2402 male household-heads from an open cohort in rural Uganda. A respondent-driven sampling (RDS) survey was carried out in this population, employing current methods of sampling (RDS sample) and statistical inference (RDS estimates). Analyses were carried out for the full RDS sample and then repeated for the first 250 recruits (small sample). Results We recruited 927 household-heads. Full and small RDS samples were largely representative of the total population, but both samples under-represented men who were younger, of higher socioeconomic status, and with unknown sexual activity and HIV status. Respondent-driven-sampling statistical-inference methods failed to reduce these biases. Only 31%-37% (depending on method and sample size) of RDS estimates were closer to the true population proportions than the RDS sample proportions. Only 50%-74% of respondent-driven-sampling bootstrap 95% confidence intervals included the population proportion. Conclusions Respondent-driven sampling produced a generally representative sample of this well-connected non-hidden population. However, current respondent-driven-sampling inference methods failed to reduce bias when it occurred. Whether the data required to remove bias and measure precision can be collected in a respondent-driven sampling survey is unresolved. Respondent-driven sampling should be regarded as a (potentially superior) form of convenience

Evaluation of respondent-driven sampling.

Science.gov (United States)

McCreesh, Nicky; Frost, Simon D W; Seeley, Janet; Katongole, Joseph; Tarsh, Matilda N; Ndunguse, Richard; Jichi, Fatima; Lunel, Natasha L; Maher, Dermot; Johnston, Lisa G; Sonnenberg, Pam; Copas, Andrew J; Hayes, Richard J; White, Richard G

2012-01-01

Respondent-driven sampling is a novel variant of link-tracing sampling for estimating the characteristics of hard-to-reach groups, such as HIV prevalence in sex workers. Despite its use by leading health organizations, the performance of this method in realistic situations is still largely unknown. We evaluated respondent-driven sampling by comparing estimates from a respondent-driven sampling survey with total population data. Total population data on age, tribe, religion, socioeconomic status, sexual activity, and HIV status were available on a population of 2402 male household heads from an open cohort in rural Uganda. A respondent-driven sampling (RDS) survey was carried out in this population, using current methods of sampling (RDS sample) and statistical inference (RDS estimates). Analyses were carried out for the full RDS sample and then repeated for the first 250 recruits (small sample). We recruited 927 household heads. Full and small RDS samples were largely representative of the total population, but both samples underrepresented men who were younger, of higher socioeconomic status, and with unknown sexual activity and HIV status. Respondent-driven sampling statistical inference methods failed to reduce these biases. Only 31%-37% (depending on method and sample size) of RDS estimates were closer to the true population proportions than the RDS sample proportions. Only 50%-74% of respondent-driven sampling bootstrap 95% confidence intervals included the population proportion. Respondent-driven sampling produced a generally representative sample of this well-connected nonhidden population. However, current respondent-driven sampling inference methods failed to reduce bias when it occurred. Whether the data required to remove bias and measure precision can be collected in a respondent-driven sampling survey is unresolved. Respondent-driven sampling should be regarded as a (potentially superior) form of convenience sampling method, and caution is required

[Sensitivity of the splenic immunocompetent cells of mice with different genotypes to the action of alkylating agents].

Science.gov (United States)

Pevnitskiĭ, L A; Telegin, L Iu; Ir, K N

1985-08-01

It has been established in experiments in vitro that splenocytes of DBA/2GSto mice are more sensitive to the immunosuppressant action of the alkylating agents (cyclophosphamide, sarcolysine and thiophosphamide) than splenocytes of BALB/cGLacSto mice. Splenocytes of C3H/SnRap mice exhibit and intermediate type of sensitivity. T-lymphocytes of the spleen of BALB/cGLacSto and DBA/2GSto mice are more sensitive in vitro to the action of active metabolites of cyclophosphamide as compared to B-lymphocytes, with both types of the cells of DBA/2GSto mice being affected to a greater extent than the cells of BALB/cGLacSto mice.

Brain GLUT4 Knockout Mice Have Impaired Glucose Tolerance, Decreased Insulin Sensitivity, and Impaired Hypoglycemic Counterregulation

Science.gov (United States)

Reno, Candace M.; Puente, Erwin C.; Sheng, Zhenyu; Daphna-Iken, Dorit; Bree, Adam J.; Routh, Vanessa H.; Kahn, Barbara B.

2017-01-01

GLUT4 in muscle and adipose tissue is important in maintaining glucose homeostasis. However, the role of insulin-responsive GLUT4 in the central nervous system has not been well characterized. To assess its importance, a selective knockout of brain GLUT4 (BG4KO) was generated by crossing Nestin-Cre mice with GLUT4-floxed mice. BG4KO mice had a 99% reduction in GLUT4 protein expression throughout the brain. Despite normal feeding and fasting glycemia, BG4KO mice were glucose intolerant, demonstrated hepatic insulin resistance, and had reduced glucose uptake in the brain. In response to hypoglycemia, BG4KO mice had impaired glucose sensing, noted by impaired epinephrine and glucagon responses and impaired c-fos activation in the hypothalamic paraventricular nucleus. Moreover, in vitro glucose sensing of glucose-inhibitory neurons from the ventromedial hypothalamus was impaired in BG4KO mice. In summary, BG4KO mice are glucose intolerant, insulin resistant, and have impaired glucose sensing, indicating a critical role for brain GLUT4 in sensing and responding to changes in blood glucose. PMID:27797912

Over-Expression of Porcine Myostatin Missense Mutant Leads to A Gender Difference in Skeletal Muscle Growth between Transgenic Male and Female Mice.

Science.gov (United States)

Ma, Dezun; Gao, Pengfei; Qian, Lili; Wang, Qingqing; Cai, Chunbo; Jiang, Shengwang; Xiao, Gaojun; Cui, Wentao

2015-08-24

Myostatin, a transforming growth factor-β family member, is a negative regulator of skeletal muscle development and growth. Piedmontese cattle breeds have a missense mutation, which results in a cysteine to tyrosine substitution in the mature myostatin protein (C313Y). This loss-of-function mutation in myostatin results in a double-muscled phenotype in cattle. Myostatin propeptide is an inhibitor of myostatin activity and is considered a potential agent to stimulate muscle growth in livestock. In this study, we generated transgenic mice overexpressing porcine myostatin missense mutant (pmMS), C313Y, and wild-type porcine myostatin propeptide (ppMS), respectively, to examine their effects on muscle growth in mice. Enhanced muscle growth was observed in both pmMS and ppMS transgenic female mice and also in ppMS transgenic male mice. However, there was no enhanced muscle growth observed in pmMS transgenic male mice. To explore why there is such a big difference in muscle growth between pmMS and ppMS transgenic male mice, the expression level of androgen receptor (AR) mutant AR45 was measured by Western blot. Results indicated that AR45 expression significantly increased in pmMS transgenic male mice while it decreased dramatically in ppMS transgenic male mice. Our data demonstrate that both pmMS and ppMS act as myostatin inhibitors in the regulation of muscle growth, but the effect of pmMS in male mice is reversed by an increased AR45 expression. These results provide useful insight and basic theory to future studies on improving pork quality by genetically manipulating myostatin expression or by regulating myostatin activity.

Genetic differences in hemoglobin function between highland and lowland deer mice

DEFF Research Database (Denmark)

Storz, Jay F.; Runck, Amy M.; Moriyama, Hideaki

2010-01-01

In high-altitude vertebrates, adaptive changes in blood–O2 affinity may be mediated by modifications of hemoglobin (Hb) structure that affect intrinsic O2 affinity and/or responsiveness to allosteric effectors that modulate Hb–O2 affinity. This mode of genotypic specialization is considered typical...... of mammalian species that are high-altitude natives. Here we investigated genetically based differences in Hb–O2 affinity between highland and lowland populations of the deer mouse (Peromyscus maniculatus), a generalist species that has the broadest altitudinal distribution of any North American mammal....... The results of a combined genetic and proteomic analysis revealed that deer mice harbor a high level of Hb isoform diversity that is attributable to allelic polymorphism at two tandemly duplicated -globin genes and two tandemly duplicated β-globin genes. This high level of isoHb diversity translates...

Different responsiveness to a high-fat/cholesterol diet in two inbred mice and underlying genetic factors: a whole genome microarray analysis

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Jin Gang

2009-10-01

Full Text Available Abstract Background To investigate different responses to a high-fat/cholesterol diet and uncover their underlying genetic factors between C57BL/6J (B6 and DBA/2J (D2 inbred mice. Methods B6 and D2 mice were fed a high-fat/cholesterol diet for a series of time-points. Serum and bile lipid profiles, bile acid yields, hepatic apoptosis, gallstones and atherosclerosis formation were measured. Furthermore, a whole genome microarray was performed to screen hepatic genes expression profile. Quantitative real-time PCR, western blot and TUNEL assay were conducted to validate microarray data. Results After fed the high-fat/cholesterol diet, serum and bile total cholesterol, serum cholesterol esters, HDL cholesterol and Non-HDL cholesterol levels were altered in B6 but not significantly changed in D2; meanwhile, biliary bile acid was decreased in B6 but increased in D2. At the same time, hepatic apoptosis, gallstones and atherosclerotic lesions occurred in B6 but not in D2. The hepatic microarray analysis revealed distinctly different genes expression patterns between B6 and D2 mice. Their functional pathway groups included lipid metabolism, oxidative stress, immune/inflammation response and apoptosis. Quantitative real time PCR, TUNEL assay and western-blot results were consistent with microarray analysis. Conclusion Different genes expression patterns between B6 and D2 mice might provide a genetic basis for their distinctive responses to a high-fat/cholesterol diet, and give us an opportunity to identify novel pharmaceutical targets in related diseases in the future.

Characterisation of innate lymphoid cell populations at different sites in mice with defective T cell immunity [version 3; referees: 2 approved

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Emma E. Dutton

2018-03-01

Full Text Available Background: Innate lymphoid cells (ILCs have now been identified within most tissues of the body and current evidence indicates that this family of cells play a fundamental role in maintaining tissue homeostasis. However, few studies have compared the ILC populations between several tissues. Methods: We sought to generate a comprehensive characterisation of the ILC populations in different tissues of C57BL/6 WT and genetically modified mice targeting costimulatory pathways, using transcription factor expression to define specific groups. Results: Consistent with studies individually describing the ILC composition in different tissues, our analysis revealed different ILC groups dominate the ILC population in different tissues. Additionally, we observed a population of  IL-7Rα+Id2+ cells lacking expression of lineage markers but also lacking expression of GATA-3, RORgt or T-bet. This population was most evident in ear skin where it outnumbered the defined ILC groups, however, further experiments demonstrated that detection of these cells was influenced by how the tissue was digested, raising concerns as to its real nature. Since both ILC2 and ILC3 express ICOS, we then investigated the requirement for ICOS:ICOSL interactions in the homeostasis of ILC populations at these sites. Surprisingly, no significant differences were detected in the number of ILC1, ILC2 or ILC3 between WT and ICOSL-/- mice in any tissue, indicating that this pathway is not required for ILC homeostasis at these sites. These data were compared with CD80-/-CD86-/- mice given evidence of CD28 expression by some ILC and ILC crosstalk with activated T cells. Notably, the absence of CD28 ligands resulted in a significant increase in ILC2 and ILC3 numbers in the intestine. Conclusions: Together, these data provide new insight into ILC composition in different tissues in both WT and genetically modified mice where key costimulatory pathways are genetically deleted, providing a

29 CFR 98.1000 - Respondent.

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Respondent. 98.1000 Section 98.1000 Labor Office of the Secretary of Labor GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 98.1000 Respondent. Respondent means a person against whom an agency has initiated a debarment or suspension action. ...

Skewed X-inactivation in cloned mice

International Nuclear Information System (INIS)

Senda, Sho; Wakayama, Teruhiko; Yamazaki, Yukiko; Ohgane, Jun; Hattori, Naka; Tanaka, Satoshi; Yanagimachi, Ryuzo; Shiota, Kunio

2004-01-01

In female mammals, dosage compensation for X-linked genes is accomplished by inactivation of one of two X chromosomes. The X-inactivation ratio (a percentage of the cells with inactivated maternal X chromosomes in the whole cells) is skewed as a consequence of various genetic mutations, and has been observed in a number of X-linked disorders. We previously reported that phenotypically normal full-term cloned mouse fetuses had loci with inappropriate DNA methylation. Thus, cloned mice are excellent models to study abnormal epigenetic events in mammalian development. In the present study, we analyzed X-inactivation ratios in adult female cloned mice (B6C3F1). Kidneys of eight naturally produced controls and 11 cloned mice were analyzed. Although variations in X-inactivation ratio among the mice were observed in both groups, the distributions were significantly different (Ansary-Bradley test, P < 0.01). In particular, 2 of 11 cloned mice showed skewed X-inactivation ratios (19.2% and 86.8%). Similarly, in intestine, 1 of 10 cloned mice had a skewed ratio (75.7%). Skewed X-inactivation was observed to various degrees in different tissues of different individuals, suggesting that skewed X-inactivation in cloned mice is the result of secondary cell selection in combination with stochastic distortion of primary choice. The present study is the first demonstration that skewed X-inactivation occurs in cloned animals. This finding is important for understanding both nuclear transfer technology and etiology of X-linked disorders

Amitriptyline converts non-responders into responders to low-frequency electroacupuncture-induced analgesia in rats.

Science.gov (United States)

Fais, Rafael S; Reis, G M; Rossaneis, A C; Silveira, J W S; Dias, Q M; Prado, W A

2012-07-26

The purpose of this study was to examine whether the use of intraperitoneal or intrathecal amitriptyline combined with electroacupuncture modifies the tail-flick reflex and incision pain in rats that normally do not have analgesia to electroacupuncture in the tail-flick test (non-responder rats). Changes in the nociceptive threshold of intraperitoneal or intrathecal saline- or amitriptyline-treated non-responder rats were evaluated using the tail-flick or incision pain tests before, during and after a 20-min period of electroacupuncture, applied at 2 Hz to the Zusanli and Sanynjiao acupoints. Amitriptyline was used at doses of 0.8 mg/kg or 30 μg/kg by intraperitoneal or intrathecal route, respectively. At these doses, amitriptyline has no effect against thermal or incision pain in rats. Rats selected as non-responders to the analgesic effect of electroacupuncture 2 Hz in tail-flick and incision pain tests become responders after an intraperitoneal or intrathecal injection of amitriptyline. Amitriptyline converts non-responder rats to rats that respond to electroacupuncture with analgesia in a model of thermal phasic pain and anti-hyperalgesia in a model of incision pain. Copyright © 2012 Elsevier Inc. All rights reserved.

SU-C-204-02: Behavioral and Pathologic Differences in Mice Exposed to Proton Minibeam Arrays Versus Proton Broad Beams

International Nuclear Information System (INIS)

Eley, J; Zhang, C; Wolfe, T; Vichaya, E; Quini, C; Chadha, A; Sahoo, N; Krishnan, S; Davis, J; Dilmanian, F

2016-01-01

Purpose: Minibeam therapy using protons or light-ions offers a theoretical reduction of biologic damage to tissues upstream of a tumor compared to broad-beam therapy while providing equal tumor control. The purpose of this study was to investigate behavioral and pathologic differences in mice after exposure of healthy brain to proton minibeam arrays versus proton broad beams. Methods: Twenty-four C57BL/6J juvenile mice were divided into 5 study arms: sham irradiation (NoRT), broad-beam 10 Gy (BB10), minibeam 10Gy (MB10), broad-beam 30 Gy (BB30), and minibeam 30 Gy (MB30), approximate integral entrance doses. Circular beams of 100 MeV protons with 7-mm diameter were delivered laterally through the brain, either as broad beams or as planar minibeam arrays having 300-micron beam width and 1-mm spacing on center. Mice were followed for 8 months using standard behavioral tests. Pathologic studies were carried out at 8 months after irradiation. Results: Peak entrance doses were 10.0, 23.8, 30.0, and 71.3 Gy for mice in BB10, MB10, BB30, and MB30, respectively. Despite the high single-fraction doses, no animals showed signs of radiation sickness or neurophysical impairment over the 8-month study duration. The Morris water maze alternate-starting-position trial showed significant evidence of better spatial learning for mice in MB10 versus BB10 (p=0.026), but other behavioral tests showed no significant differences. Glial fibrillary acidic protein stains showed gliosis in arms BB10, BB30, and MB30 but not in NoRT or MB10. A secondary finding was categorically higher epilation in broad-beam arms compared with their minibeam dose counterparts. Conclusion: Our findings indicate trends that, despite the higher peak doses, proton minibeam therapy can reduce radiation side effects in shallow tissue and brain compared to proton broadbeam therapy. As the behavioral findings were mixed, confirmation studies are needed with larger numbers of animals. AAPM Research Seed Funding Grant

SU-C-204-02: Behavioral and Pathologic Differences in Mice Exposed to Proton Minibeam Arrays Versus Proton Broad Beams

Energy Technology Data Exchange (ETDEWEB)

Eley, J; Zhang, C [University of Maryland School of Medicine, Baltimore, MD (United States); Wolfe, T; Vichaya, E; Quini, C; Chadha, A; Sahoo, N; Krishnan, S [The University of Texas MD Anderson Cancer Center, Houston, TX (United States); Davis, J; Dilmanian, F [Stony Brook University Medical Center, Stony Brook, NY (United States)

2016-06-15

Purpose: Minibeam therapy using protons or light-ions offers a theoretical reduction of biologic damage to tissues upstream of a tumor compared to broad-beam therapy while providing equal tumor control. The purpose of this study was to investigate behavioral and pathologic differences in mice after exposure of healthy brain to proton minibeam arrays versus proton broad beams. Methods: Twenty-four C57BL/6J juvenile mice were divided into 5 study arms: sham irradiation (NoRT), broad-beam 10 Gy (BB10), minibeam 10Gy (MB10), broad-beam 30 Gy (BB30), and minibeam 30 Gy (MB30), approximate integral entrance doses. Circular beams of 100 MeV protons with 7-mm diameter were delivered laterally through the brain, either as broad beams or as planar minibeam arrays having 300-micron beam width and 1-mm spacing on center. Mice were followed for 8 months using standard behavioral tests. Pathologic studies were carried out at 8 months after irradiation. Results: Peak entrance doses were 10.0, 23.8, 30.0, and 71.3 Gy for mice in BB10, MB10, BB30, and MB30, respectively. Despite the high single-fraction doses, no animals showed signs of radiation sickness or neurophysical impairment over the 8-month study duration. The Morris water maze alternate-starting-position trial showed significant evidence of better spatial learning for mice in MB10 versus BB10 (p=0.026), but other behavioral tests showed no significant differences. Glial fibrillary acidic protein stains showed gliosis in arms BB10, BB30, and MB30 but not in NoRT or MB10. A secondary finding was categorically higher epilation in broad-beam arms compared with their minibeam dose counterparts. Conclusion: Our findings indicate trends that, despite the higher peak doses, proton minibeam therapy can reduce radiation side effects in shallow tissue and brain compared to proton broadbeam therapy. As the behavioral findings were mixed, confirmation studies are needed with larger numbers of animals. AAPM Research Seed Funding Grant.

Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine.

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Jedynak, Paulina; Kos, Tomasz; Sandi, Carmen; Kaczmarek, Leszek; Filipkowski, Robert K

2014-09-01

The neurogenesis hypothesis of major depression has two main facets. One states that the illness results from decreased neurogenesis while the other claims that the very functioning of antidepressants depends on increased neurogenesis. In order to verify the latter, we have used cyclin D2 knockout mice (cD2 KO mice), known to have virtually no adult brain neurogenesis, and we demonstrate that these mice successfully respond to chronic fluoxetine. After unpredictable chronic mild stress, mutant mice showed depression-like behavior in forced swim test, which was eliminated with chronic fluoxetine treatment, despite its lack of impact on adult hippocampal neurogenesis in cD2 KO mice. Our results suggest that new neurons are not indispensable for the action of antidepressants such as fluoxetine. Using forced swim test and tail suspension test, we also did not observe depression-like behavior in control cD2 KO mice, which argues against the link between decreased adult brain neurogenesis and major depression. Copyright © 2014 Elsevier Ltd. All rights reserved.

Infant differential behavioral responding to discrete emotions.

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Walle, Eric A; Reschke, Peter J; Camras, Linda A; Campos, Joseph J

2017-10-01

Emotional communication regulates the behaviors of social partners. Research on individuals' responding to others' emotions typically compares responses to a single negative emotion compared with responses to a neutral or positive emotion. Furthermore, coding of such responses routinely measure surface level features of the behavior (e.g., approach vs. avoidance) rather than its underlying function (e.g., the goal of the approach or avoidant behavior). This investigation examined infants' responding to others' emotional displays across 5 discrete emotions: joy, sadness, fear, anger, and disgust. Specifically, 16-, 19-, and 24-month-old infants observed an adult communicate a discrete emotion toward a stimulus during a naturalistic interaction. Infants' responses were coded to capture the function of their behaviors (e.g., exploration, prosocial behavior, and security seeking). The results revealed a number of instances indicating that infants use different functional behaviors in response to discrete emotions. Differences in behaviors across emotions were clearest in the 24-month-old infants, though younger infants also demonstrated some differential use of behaviors in response to discrete emotions. This is the first comprehensive study to identify differences in how infants respond with goal-directed behaviors to discrete emotions. Additionally, the inclusion of a function-based coding scheme and interpersonal paradigms may be informative for future emotion research with children and adults. Possible developmental accounts for the observed behaviors and the benefits of coding techniques emphasizing the function of social behavior over their form are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Sex chromosome complement influences operant responding for a palatable food in mice.

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Seu, Emanuele; Groman, Stephanie M; Arnold, Arthur P; Jentsch, J David

2014-07-01

The procurement and consumption of palatable, calorie-dense foods is influenced by the nutritional and hedonic value of foods. Although many factors can influence the control over behavior by foods rich in sugar and fat, emerging evidence indicates that biological sex may play a particularly crucial role in the types of foods individuals seek out, as well as the level of motivation individuals will exert to obtain those foods. However, a systematic investigation of food-seeking and consumption that disentangles the effects of the major sex-biasing factors, including sex chromosome complement and organizational and activational effects of sex hormones, has yet to be conducted. Using the four core genotypes mouse model system, we separated and quantified the effects of sex chromosome complement and gonadal sex on consumption of and motivation to obtain a highly palatable solution [sweetened condensed milk (SCM)]. Gonadectomized mice with an XY sex chromosome complement, compared with those with two X chromosomes, independent of gonadal sex, appeared to be more sensitive to the reward value of the SCM solution and were more motivated to expend effort to obtain it, as evidenced by their dramatically greater expended effort in an instrumental task with progressively larger response-to-reward ratios. Gonadal sex independently affected free consumption of the solution but not motivation to obtain it. These data indicate that gonadal and chromosomal sex effects independently influence reward-related behaviors, contributing to sexually dimorphic patterns of behavior related to the pursuit and consumption of rewards. © 2014 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Sex-dependent Differences in Intestinal Tumorigenesis Induced in Apc1638N/+ Mice by Exposure to {gamma} Rays

Energy Technology Data Exchange (ETDEWEB)

Trani, Daniela [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, District of Columbia (United States); Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Maastricht Radiation Oncology (MaastRO) Lab, GROW-School for Oncology and Developmental Biology, University of Maastricht (Netherlands); Moon, Bo-Hyun [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, District of Columbia (United States); Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Kallakury, Bhaskar; Hartmann, Dan P. [Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Datta, Kamal [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, District of Columbia (United States); Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Fornace, Albert J., E-mail: af294@georgetown.edu [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, District of Columbia (United States); Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah (Saudi Arabia)

2013-01-01

Purpose: The purpose of the present study was to assess the effect of 1 and 5 Gy radiation doses and to investigate the interplay of gender and radiation with regard to intestinal tumorigenesis in an adenomatous polyposis coli (APC) mutant mouse model. Methods and Materials: Apc1638N/+ female and male mice were exposed whole body to either 1 Gy or 5 Gy of {gamma} rays and euthanized when most of the treated mice became moribund. Small and large intestines were processed to determine tumor burden, distribution, and grade. Expression of proliferation marker Ki-67 and estrogen receptor (ER)-{alpha} were also assessed by immunohistochemistry. Results: We observed that, with both 1 Gy and 5 Gy of {gamma} rays, females displayed reduced susceptibility to radiation-induced intestinal tumorigenesis compared with males. As for radiation effect on small intestinal tumor progression, although no substantial differences were found in the relative frequency and degree of dysplasia of adenomas in irradiated animals compared with controls, invasive carcinomas were found in 1-Gy- and 5-Gy-irradiated animals. Radiation exposure was also shown to induce an increase in protein levels of proliferation marker Ki-67 and sex-hormone receptor ER-{alpha} in both non tumor mucosa and intestinal tumors from irradiated male mice. Conclusions: We observed important sex-dependent differences in susceptibility to radiation-induced intestinal tumorigenesis in Apc1638N/+ mutants. Furthermore, our data provide evidence that exposure to radiation doses as low as 1 Gy can induce a significant increase in intestinal tumor multiplicity as well as enhance tumor progression in vivo.

Mice divergently selected for high and low basal metabolic rates evolved different cell size and organ mass.

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Maciak, S; Bonda-Ostaszewska, E; Czarnołęski, M; Konarzewski, M; Kozłowski, J

2014-03-01

Evolution of metabolic rates of multicellular organisms is hypothesized to reflect the evolution of their cell architecture. This is likely to stem from a tight link between the sizes of cells and nuclei, which are expected to be inversely related to cell metabolism. Here, we analysed basal metabolic rate (BMR), internal organ masses and the cell/nucleus size in different tissues of laboratory mice divergently selected for high/low mass-corrected BMR and four random-bred mouse lines. Random-bred lines had intermediate levels of BMR as compared to low- and high-BMR lines. Yet, this pattern was only partly consistent with the between-line differences in cell/nucleus sizes. Erythrocytes and skin epithelium cells were smaller in the high-BMR line than in other lines, but the cells of low-BMR and random-bred mice were similar in size. On the other hand, the size of hepatocytes, kidney proximal tubule cells and duodenum enterocytes were larger in high-BMR mice than other lines. All cell and nucleus sizes were positively correlated, which supports the role of the nucleus in cell size regulation. Our results suggest that the evolution of high BMR involves a reduction in cell size in specialized tissues, whose functions are primarily dictated by surface-to-volume ratios, such as erythrocytes. High BMR may, however, also incur an increase in cell size in tissues with an intense transcription and translation, such as hepatocytes. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Zinc metabolism in genetically obese mice

International Nuclear Information System (INIS)

Kennedy, M.L.; Failla, M.L.

1986-01-01

Recent reports indicate that the concentrations and total amounts of several essential trace metals in various tissues of genetically obese rodents differ markedly from lean controls. In the present studies the absorption, retention and tissue distribution of zinc was compared in obese (ob/ob) and lean (+/?) C57BL/6J mice. When administered 0.1 and 1 umole 65 Zn by stomach tube and killed after 4 h, fasted 10 week old obese mice had 2.7 and 2.2 times more radioactivity in their carcasses, respectively, than age-matched lean mice. Higher levels of 65 Zn were also present in the intestinal mucosa of obese mice. To eliminate possible differences in the effects of fasting and gastric emptying rates between the phenotypes, zinc absorption and retention were determined according to the method of Heth and Hoekstra. Analysis of data revealed that obese and lean mice absorbed 43 and 18% of the oral dose, respectively. Also, the rate of 65 Zn excretion between 2 and 6 days post-treatment was similar for obese and lean mice. After 6 days obese mice had significantly lower levels of radioisotope in skin, muscle plus bone, spleen and testes and higher levels of 65 Zn in liver, small intestine and adipose tissue compared to tissues from lean mice. These results demonstrate increased absorption, altered tissue distribution and similar excretion of zinc in ob/ob mice

Prejudice control and interracial relations: the role of motivation to respond without prejudice.

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Butz, David A; Plant, E Ashby

2009-10-01

A decade of research indicates that individual differences in motivation to respond without prejudice have important implications for the control of prejudice and interracial relations. In reviewing this work, we draw on W. Mischel and Y. Shoda's (1995, 1999) Cognitive-Affective Processing System (CAPS) to demonstrate that people with varying sources of motivation to respond without prejudice respond in distinct ways to situational cues, resulting in differing situation-behavior profiles in interracial contexts. People whose motivation is self-determined (i.e., the internally motivated) effectively control prejudice across situations and strive for positive interracial interactions. In contrast, people who respond without prejudice to avoid social sanction (i.e., the primarily externally motivated) consistently fail at regulating difficult to control prejudice and respond with anxiety and avoidance in interracial interactions. We further consider the nature of the cognitive-affective units of personality associated with motivation to respond without prejudice and their implications for the quality of interracial relations.

Verticalization of behavior elicited by dopaminergic mobilization is qualitatively different between C57BL/6J and DBA/2J mice.

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Tirelli, E; Witkin, J M

1994-10-01

Behavioral effects of dopaminergic stimulation were evaluated in C57BL/6J mice and compared to the effects occurring in DBA/2J mice, an inbred strain with reduced densities of striatal dopamine receptors. Effects of apomorphine (0.5-64 mg/kg) alone and in combination with cocaine (30 mg/kg) were assessed using a time-sampling technique that classified climbing and leaning in separate categories. Locomotion was also assessed in a separate experiment. Climbing occurred in DBA/2J mice only at doses of apomorphine that were 16 times higher than the smallest effective dose in C57BL/6J mice; nevertheless, relative to baseline values, effects were fairly comparable. By contrast, whereas DBA/2J mice showed dose-dependent leaning under apomorphine, C57BL/6J mice exhibited little leaning even at doses not producing climbing, and only after the highest apomorphine dose was leaning significantly increased. Apomorphine was equipotent in inducing gnawing across strains, although somewhat less efficacious in DBA/2J mice. When given alone, cocaine produced significant climbing, but not leaning or gnawing, in either strain. Whereas cocaine potentiated apomorphine-induced climbing and gnawing in both strains, apomorphine-induced leaning was not consistently changed by cocaine in either strain. These effects were not indirectly due to hyperkinesia, since neither apomorphine alone nor apomorphine and cocaine in combination was stimulant; apomorphine alone reduced locomotor activity and attenuated cocaine-induced hyperkinesia. The present data do not support a unitary, purely quantitative, account of insensitivity to dopaminergic stimulation based upon low densities of striatal dopamine receptors in DBA/2J mice. Rather, this constellation of results is suggestive of qualitative interstrain dissimilarities in dopaminergic responsiveness that could reflect organizational differences in receptor populations.

The relevance of inter- and intrastrain differences in mice and rats and their implications for models of seizures and epilepsy.

Science.gov (United States)

Löscher, Wolfgang; Ferland, Russell J; Ferraro, Thomas N

2017-08-01

It is becoming increasingly clear that the genetic background of mice and rats, even in inbred strains, can have a profound influence on measures of seizure susceptibility and epilepsy. These differences can be capitalized upon through genetic mapping studies to reveal genes important for seizures and epilepsy. However, strain background and particularly mixed genetic backgrounds of transgenic animals need careful consideration in both the selection of strains and in the interpretation of results and conclusions. For instance, mice with targeted deletions of genes involved in epilepsy can have profoundly disparate phenotypes depending on the background strain. In this review, we discuss findings related to how this genetic heterogeneity has and can be utilized in the epilepsy field to reveal novel insights into seizures and epilepsy. Moreover, we discuss how caution is needed in regards to rodent strain or even animal vendor choice, and how this can significantly influence seizure and epilepsy parameters in unexpected ways. This is particularly critical in decisions regarding the strain of choice used in generating mice with targeted deletions of genes. Finally, we discuss the role of environment (at vendor and/or laboratory) and epigenetic factors for inter- and intrastrain differences and how such differences can affect the expression of seizures and the animals' performance in behavioral tests that often accompany acute and chronic seizure testing. Copyright © 2017 Elsevier Inc. All rights reserved.

Operant learning and differential-reinforcement-of-low-rate 36-s responding in 5-HT1A and 5-HT1B receptor knockout mice.

NARCIS (Netherlands)

Pattij, T.; Broersen, L.M.; Linde, J. van der; Groenink, L.; Gugten, J. van der; Maes, R.A.A.; Olivier, B.

2003-01-01

Previous studies with mice lacking 5-HT(1A) (1AKO) and 5-HT(1B) (1BKO) receptors in hippocampus-dependent learning and memory paradigms, suggest that these receptors play an important role in learning and memory, although their precise role is unclear. In the present study, 1AKO and 1BKO mice were

Effects of melatonin administration on embryo implantation and offspring growth in mice under different schedules of photoperiodic exposure.

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Zhang, Lu; Zhang, Zhenzhen; Wang, Feng; Tian, Xiuzhi; Ji, Pengyun; Liu, Guoshi

2017-10-02

Embryo implantation is crucial for animal reproduction. Unsuccessful embryo implantation leads to pregnancy failure, especially in human-assisted conception. Environmental factors have a profound impact on embryo implantation. Because people are being exposed to more light at night, the influence of long-term light exposure on embryo implantation should be explored. The effects of long photoperiodic exposure and melatonin on embryo implantation and offspring growth were examined. Long photoperiodic exposure (18:6 h light:dark) was selected to resemble light pollution. Melatonin (10 -2 , 10 -3 , 10 -4 , 10 -5  M) was added to the drinking water of mice starting at Day 1 (vaginal plugs) until delivery. Melatonin treatment (10 -4 ,10 -5  M) significantly increased litter sizes compared to untreated controls (12.9 ± 0.40 and 12.2 ± 1.01 vs. 11.5 ± 0.43; P melatonin (10 -4  M) was selected for further investigation. No remarkable differences were found between melatonin-treated mice and controls in terms of the pups' birth weights, weaning survival rates, and weaning weights. Long photoperiodic exposure significantly reduced the number of implantation sites in treated mice compared to controls (light/dark, 12/12 h), and melatonin rescued this negative effect. Mechanistic studies revealed that melatonin enhanced the serum 17β-estradiol (E 2 ) levels in the pregnant mice and upregulated the expression of the receptors MT1 and MT2 and p53 in uterine tissue. All of these factors may contribute to the beneficial effects of melatonin on embryo implantation in mice. Melatonin treatment was associated with beneficial effects in pregnant mice, especially those subjected to long photoperiodic exposure. This was achieved by enhanced embryo implantation. At the molecular level, melatonin administration probably increases the E 2 level during pregnancy and upregulates p53 expression by activating MT1/2 in the uterus. All of the changes may improve the

Photoperiod mediated changes in olfactory bulb neurogenesis and olfactory behavior in male white-footed mice (Peromyscus leucopus.

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James C Walton

Full Text Available Brain plasticity, in relation to new adult mammalian neurons generated in the subgranular zone of the hippocampus, has been well described. However, the functional outcome of new adult olfactory neurons born in the subventricular zone of the lateral ventricles is not clearly defined, as manipulating neurogenesis through various methods has given inconsistent and conflicting results in lab mice. Several small rodent species, including Peromyscus leucopus, display seasonal (photoperiodic brain plasticity in brain volume, hippocampal function, and hippocampus-dependent behaviors; plasticity in the olfactory system of photoperiodic rodents remains largely uninvestigated. We exposed adult male P. leucopus to long day lengths (LD and short day lengths (SD for 10 to 15 weeks and then examined olfactory bulb cell proliferation and survival using the thymidine analog BrdU, olfactory bulb granule cell morphology using Golgi-Cox staining, and behavioral investigation of same-sex conspecific urine. SD mice did not differ from LD counterparts in granular cell morphology of the dendrites or in dendritic spine density. Although there were no differences due to photoperiod in habituation to water odor, SD mice rapidly habituated to male urine, whereas LD mice did not. In addition, short day induced changes in olfactory behavior were associated with increased neurogenesis in the caudal plexiform and granule cell layers of the olfactory bulb, an area known to preferentially respond to water-soluble odorants. Taken together, these data demonstrate that photoperiod, without altering olfactory bulb neuronal morphology, alters olfactory bulb neurogenesis and olfactory behavior in Peromyscus leucopus.

Effects of repeated treatment with MDMA on working memory and behavioural flexibility in mice.

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Viñals, Xavier; Maldonado, Rafael; Robledo, Patricia

2013-03-01

Repeated administration of 3,4-methylenedioxymethamphetamine (MDMA) produces dopaminergic neurotoxicity in mice. However, it is still not clear whether this exposure induces deficits in cognitive processing related to specific subsets of executive functioning. We evaluated the effects of neurotoxic and non-neurotoxic doses of MDMA (0, 3 and 30 mg/kg, twice daily for 4 days) on working memory and attentional set-shifting in mice, and changes in extracellular levels of dopamine (DA) in the striatum. Treatment with MDMA (30 mg/kg) disrupted performance of acquired operant alternation, and this impairment was still apparent 5 days after the last drug administration. Decreased alternation was not related to anhedonia because no differences were observed between groups in the saccharin preference test under similar experimental conditions. Correct responding on delayed alternation was increased 1 day after repeated treatment with MDMA (30 mg/kg), probably because of general behavioural quiescence. Notably, the high dose regimen of MDMA impaired attentional set-shifting related to an increase in total perseveration errors. Finally, basal extracellular levels of DA in the striatum were not modified in mice repeatedly treated with MDMA with respect to controls. However, an acute challenge with MDMA (10 mg/kg) failed to increase DA outflow in mice receiving the highest MDMA dose (30 mg/kg), corroborating a decrease in the functionality of DA transporters. Seven days after this treatment, the effects of MDMA on DA outflow were recovered. These results suggest that repeated neurotoxic doses of MDMA produce lasting impairments in recall of alternation behaviour and reduce cognitive flexibility in mice. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

Immunobiology of congenitally athymic-asplenic mice

International Nuclear Information System (INIS)

Gershwin, M.E.; Ahmed, A.; Ikeda, R.M.; Shifrine, M.; Wilson, F.

1978-01-01

A study has been made of congenitally athymic-asplenic mice obtained by the mating of nude by hereditarily asplenic (Dh/+) mice. The mice survived for up to 9 months, under specific pathogen-free conditions, with no evidence for increased risk of spontaneous neoplasia. Although lymphocyte surface markers and sera immunoglobulin levels of athymic-asplenic mice were similar to those of their nude and asplenic littermates, there were a number of major immunologic differences. The athymic-asplenic mice appeared more immunologically compromised than nude mice. There was an elevated rate of growth and a lower inoculated cell threshold needed for successful transplantation of a human malignant melanoma. There was no evidence for auto-antibody production in mice up to 9 months of age. Congenitally athymic-asplenic mice can be used for a variety of studies in which other immunologically deprived mouse mutants are desired. (author)

AβPP/PS1 Transgenic Mice Show Sex Differences in the Cerebellum Associated with Aging.

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Ordoñez-Gutierrez, Lara; Fernandez-Perez, Ivan; Herrera, Jose Luis; Anton, Marta; Benito-Cuesta, Irene; Wandosell, Francisco

2016-09-06

Cerebellar pathology has been related to presenilin 1 mutations in certain pedigrees of familial Alzheimer's disease. However, cerebellum tissue has not been intensively analyzed in transgenic models of mutant presenilins. Furthermore, the effect of the sex of the mice was not systematically analyzed, despite the fact that important gender differences in the evolution of the disease in the human population have been described. We analyzed whether the progression of amyloidosis in a double transgenic mouse, AβPP/PS1, is susceptible to aging and differentially affects males and females. The accumulation of amyloid in the cerebellum differentially affects males and females of the AβPP/PS1 transgenic line, which was found to be ten-fold higher in 15-month-old females. Amyloid-β accumulation was more evident in the molecular layer of the cerebellum, but glia reaction was only observed in the granular layer of the older mice. The sex divergence was also observed in other neuronal, survival, and autophagic markers. The cerebellum plays an important role in the evolution of the pathology in this transgenic mouse model. Sex differences could be crucial for a complete understanding of this disease. We propose that the human population could be studied in this way. Sex-specific treatment strategies in human populations could show a differential response to the therapeutic approach.

Male and female meadow voles Microtus pennsylvanicus respond differently to scent marks from the top- middle-, and bottom-scent donors of an over-mark

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Michael H. FERKIN, Nicholas J. HOBBS, Benjamin D. FERKIN, Adam C.FERKIN, Daniel A. FERKIN

2011-08-01

Full Text Available Previous studies have shown that individuals responded preferentially to the mark of the top-scent donor relative to that of the bottom-scent donor of an over-mark. However, terrestrial mammals are likely to encounter over-marks consisting of the scent marks of more than two same-sex conspecifics in the intersections of runways, near the nests of sexually receptive female conspecifics, and inside and along the borders of the territories of conspecifics. We determined how meadow voles, Microtus pennsylvanicus, respond to the marks of the top-, middle-, and bottom-scent donors of an over-mark. We tested the hypothesis that voles exposed to an over-mark will respond preferentially to the scent marks that were deposited more recently, the scent marks that were on top or near the top of the over-mark, compared to the scent marks that were deposited earlier or near the bottom of the over-mark. Voles spent more time investigating the mark of the top-scent donor than that of the either the middle- or bottom-scent donor. However, males but not female voles spent more time investigating the middle-scent mark than the bottom-scent mark. We also tested the hypothesis that voles evaluate and respond to over-marks differently from single scent marks. Voles spent more time investigating the marks of the top-, middle-, and bottom-scent donors compared to scent marks that were not part of the over-mark. Voles can distinguish among the overlapping scent marks of three scent donors and sex differences exist in the values they appear to attach to each of these scent marks [Current Zoology 57 (4: 441–448, 2011].

Early metabolic adaptation in C57BL/6 mice resistant to high fat diet induced weight gain involves an activation of mitochondrial oxidative pathways.

Science.gov (United States)

Boulangé, Claire L; Claus, Sandrine P; Chou, Chieh J; Collino, Sebastiano; Montoliu, Ivan; Kochhar, Sunil; Holmes, Elaine; Rezzi, Serge; Nicholson, Jeremy K; Dumas, Marc E; Martin, François-Pierre J

2013-04-05

We investigated the short-term (7 days) and long-term (60 days) metabolic effect of high fat diet induced obesity (DIO) and weight gain in isogenic C57BL/6 mice and examined the specific metabolic differentiation between mice that were either strong-responders (SR), or non-responders (NR) to weight gain. Mice (n = 80) were fed a standard chow diet for 7 days prior to randomization into a high-fat (HF) (n = 56) or a low-fat (LF) (n = 24) diet group. The (1)H NMR urinary metabolic profiles of LF and HF mice were recorded 7 and 60 days after the diet switch. On the basis of the body weight gain (BWG) distribution of HF group, we identified NR mice (n = 10) and SR mice (n = 14) to DIO. Compared with LF, HF feeding increased urinary excretion of glycine conjugates of β-oxidation intermediate (hexanoylglycine), branched chain amino acid (BCAA) catabolism intermediates (isovalerylglycine, α-keto-β-methylvalerate and α-ketoisovalerate) and end-products of nicotinamide adenine dinucleotide (NAD) metabolism (N1-methyl-2-pyridone-5-carboxamide, N1-methyl-4-pyridone-3-carboxamide) suggesting up-regulation of mitochondrial oxidative pathways. In the HF group, NR mice excreted relatively more hexanoylglycine, isovalerylglycine, and fewer tricarboxylic acid (TCA) cycle intermediate (succinate) in comparison to SR mice. Thus, subtle regulation of ketogenic pathways in DIO may alleviate the saturation of the TCA cycle and mitochondrial oxidative metabolism.

On the mechanistic differences of benzene-induced leukemogenesis between wild type and p53 knockout mice

International Nuclear Information System (INIS)

Hirabayashi, Yoko; Yoon, Byung-Il; Kawasaki, Yasushi; Li, Guang-Xun; Kanno, Jun; Inoue, Tohru

2003-01-01

Leukemia induction by benzene inhalation was first reported by Le Noire in 1887, described multiple cases of leukemia among Parisian cobblers. However, experimental induction of leukemia by benzene exposure was not succeeded for a hundred years, until Snyder et al. and our group reported it nearly 20 years ago. Nevertheless, the mechanistic background of benzene-induced leukemia was still an enigma until recently a benzene-induced peculiar cell kinetics of the stem/progenitor cells has been elucidated by our study, demonstrated a marked repeated oscillatory decrease in peripheral blood and bone marrow (BM) cellularity during and after benzene exposure, which epigenetically preceded and developed the leukemia more than a year later. We utilized the BUUV (bromodeoxyuridine + UV exposure) method to study stem/progenitor cell kinetics during and/or after benzene exposure. Using these methods, we were able to measure the labeling rate, cycling fraction of clonogenic progenitor cells, and other cell cycle parameters. The cycling fraction of stem/progenitor cells was found not to turn into an active hematopoiesis but to remain low during benzene inhalation and further we found evidence that the cycling fraction depression may be mediated in part by a slowing of stem/progenitor cell cycling perse by up-regulation of p21. The benzene induced leukemogenicity between mice carrying wild-type p53 and mice lacking p53 seem to differ from one another. In the case of p53 knockout mouse, DNA damage such as weak mutagenicity and or chromosomal damages are retained, and those damages participated in the induction of a consequent activation of proto-oncogenes and the like, which led cells to further neoplastic changes. In contrast, in the case of wild type mice, a dramatic oscillational change in the cell cycle of the stem cell compartment seems to be an important factor for mice carrying the p53 gene. (author)

Prenatal lipopolysaccharide exposure affects sexual dimorphism in different germlines of mice with a depressive phenotype.

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Reis-Silva, Thiago M; Cohn, Daniel W H; Sandini, Thaísa M; Udo, Mariana S B; Teodorov, Elizabeth; Bernardi, Maria Martha

2016-03-15

The objective of the present study was to investigate whether prenatal lipopolysaccharide (LPS) administration modifies the expression of depressive and non-depressive-like behavior in male and female mice across two generations. The sexual dimorphism of these mice was also examined in the open-field test. Male and female mice of the parental (F0) generation were selected for depressive- or non-depressive-like behavioral profiles using the tail suspension test (TST). Animals with similar profiles were matched for further mating. On gestation day (GD) 15, pregnant F0 mice received LPS (100μg/kg, i.p.) and were allowed to nurture their offspring freely. Adult male and female of the F1 generation were then selected according to behavioral profiles and observed in the open field. Male and female mice of the two behavioral profiles were then mated to obtain the F2 generation. Adults from the F2 generation were also behaviorally phenotyped, and open field behavior was assessed. Male mice that were selected for depressive- and non-depressive-like behaviors and treated or not with LPS in the parental generation exhibited similar proportions of behavioral profiles in both filial lines, but LPS exposure increased the number of depressive-like behavior. An effect of gender was observed in the F1 and F2 generations, in which male mice were more sensitive to the intergenerational effects of LPS in the TST. These data indicate that prenatal LPS exposure on GD15 in the F0 generation influenced the transmission of depressive- and non-depressive-like behavior across filial lines, with sexual dimorphism between phenotypes. Copyright © 2016 Elsevier Inc. All rights reserved.

Knowledge about Sounds – Context-Specific Meaning Differently Activates Cortical Hemispheres, Auditory Cortical Fields and Layers in House Mice

Directory of Open Access Journals (Sweden)

Diana B. Geissler

2016-03-01

Full Text Available Activation of the auditory cortex (AC by a given sound pattern is plastic, depending, in largely unknown ways, on the physiological state and the behavioral context of the receiving animal and on the receiver's experience with the sounds. Such plasticity can be inferred when house mouse mothers respond maternally to pup ultrasounds right after parturition and naïve females have to learn to respond. Here we use c-FOS immunocytochemistry to quantify highly activated neurons in the AC fields and layers of seven groups of mothers and naïve females who have different knowledge about and are differently motivated to respond to acoustic models of pup ultrasounds of different behavioral significance. Profiles of FOS-positive cells in the AC primary fields (AI, AAF, the ultrasonic field (UF, the secondary field (AII, and the dorsoposterior field (DP suggest that activation reflects in AI, AAF, and UF the integration of sound properties with animal state-dependent factors, in the higher-order field AII the news value of a given sound in the behavioral context, and in the higher-order field DP the level of maternal motivation and, by left-hemisphere activation advantage, the recognition of the meaning of sounds in the given context. Anesthesia reduced activation in all fields, especially in cortical layers 2/3. Thus, plasticity in the AC is field-specific preparing different output of AC fields in the process of perception, recognition and responding to communication sounds. Further, the activation profiles of the auditory cortical fields suggest the differentiation between brains hormonally primed to know (mothers and brains which acquired knowledge via implicit learning (naïve females. In this way, auditory cortical activation discriminates between instinctive (mothers and learned (naïve females cognition.

The Effects of Different Doses of Curcuma longa Aqueous Extract on Memory Retention and Retrieval in Male Mice

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2016-12-01

Full Text Available Background and Objectives: Curcumin belongs to ginger family, which is used as food and drug from ancient times. Different studies have shown beneficial effects of curcumin on peptic ulcer, rheumatoid arthritis, asthma, and various types of cancer. In this study, the effect of different doses of Curcuma longa aqueous extract on memory retention and retrieval of mice, was investigated using passive avoidance apparatus. Methods: Mice were divided into 6 groups of 8 each for memory retention test and 6 groups of 8 each for memory retrieval test {experimental groups receiving the extract intraperitoneally at doses of 100, 200, 400, 800mg/kg, blank group, and control group}. In memory retention test, the curcumin extract was administered immediately after electric shock, while in the memory retrieval test, it was administered 24 h after receiving electric shock. To compare the complete stepping in the experiment days, One-way ANOVA and post-test LSD were used. The level of significance was considered p<0.05. Results: In this study, curcuma longa aqueous extract significantly increased memory retention and retrieval on the 4th day compared to blank and control groups. The best response for memory retention was obtained at the dose of 100mg/kg and for memory retrieval at the dose of 200mg/kg. Conclusion: According to the results of this study, it seems that Curcuma longa aqueous extract improves memory retention and retrieval in healthy mice.  

Sex differences in the rapid and the sustained antidepressant-like effects of ketamine in stress-naïve and "depressed" mice exposed to chronic mild stress.

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Franceschelli, A; Sens, J; Herchick, S; Thelen, C; Pitychoutis, P M

2015-04-02

During the past decade, one of the most striking discoveries in the treatment of major depression was the clinical finding that a single infusion of a sub-anesthetic dose of the N-methyl-d-aspartate receptor antagonist ketamine produces a rapid (i.e. within a few hours) and long-lasting (i.e. up to two weeks) antidepressant effect in both treatment-resistant depressed patients and in animal models of depression. Notably, converging clinical and preclinical evidence support that responsiveness to antidepressant drugs is sex-differentiated. Strikingly, research regarding the antidepressant-like effects of ketamine has focused almost exclusively on the male sex. Herein we report that female C57BL/6J stress-naïve mice are more sensitive to the rapid and the sustained antidepressant-like effects of ketamine in the forced swim test (FST). In particular, female mice responded to lower doses of ketamine (i.e. 3mg/kg at 30 min and 5mg/kg at 24h post-injection), doses that were not effective in their male counterparts. Moreover, tissue levels of the excitatory amino acids glutamate and aspartate, as well as serotonergic activity, were affected in a sex-dependent manner in the prefrontal cortex and the hippocampus, at the same time-points. Most importantly, a single injection of ketamine (10mg/kg) induced sex-dependent behavioral effects in mice subjected to the chronic mild stress (CMS) model of depression. Intriguingly, female mice were more reactive to the earlier effects of ketamine, as assessed in the open field and the FST (at 30 min and 24h post-treatment, respectively) but the antidepressant potential of the drug proved to be longer lasting in males, as assessed in the splash test and the FST (days 5 and 7 post-treatment, respectively). Taken together, present data revealed that ketamine treatment induces sex-dependent rapid and sustained neurochemical and behavioral antidepressant-like effects in stress-naïve and CMS-exposed C57BL/6J mice. Copyright © 2015 IBRO

The Relational Responding Task: Toward a New Implicit Measure of Beliefs

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Jan eDe Houwer

2015-03-01

Full Text Available We introduce the Relational Responding Task (RRT as a tool for capturing beliefs at the implicit level. Flemish participants were asked to respond as if they believed that Flemish people are more intelligent than immigrants (e.g., respond true to the statement Flemish people are wiser than immigrants or to respond as if they believed that immigrants are more intelligent than Flemish people (e.g., respond true to the statement Flemish people are dumber than immigrants. The difference in performance between these two tasks correlated with ratings of the extent to which participants explicitly endorsed the belief that Flemish people are more intelligent than immigrants and with questionnaire measures of subtle and blatant racism. The current study provides a first step towards validating RRT effects as a viable measure of implicit beliefs.

Garlic (Allium sativum L.) as a potential antidote for cadmium and lead intoxication: cadmium and lead distribution and analysis in different mice organs.

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Massadeh, A M; Al-Safi, S A; Momani, I F; Alomary, A A; Jaradat, Q M; AlKofahi, A S

2007-01-01

Analysis and distribution of Pb and Cd in different mice organs including liver, kidney, spleen, heart and blood were evaluated after treatment with different aqueous concentrations of garlic (12.5-100 mg/l). Atomic absorption spectrometry (AAS) was used for analysis of Pb and Cd in these organs. Treatment of Cd-Pb exposed mice with garlic (12.5-100 mg/l) reduced Pb concentrations by 44.65, 42.61, 38.4, 47.56, and 66.62% in liver, kidney, heart, spleen and blood respectively. Moreover, garlic reduced Cd levels by 72.5, 87.7, 92.6, 95.6, and 71.7% in liver, kidney, heart, spleen and blood respectively. The suppressed immune responses in mice pretreated with Cd-Pb mixture were reversed by 48.85, 55.82, 81.4 and 90.7 in the presence of 100, 50, 25, and 12.5 mg/ml of garlic extract.

Do lake littoral benthic invertebrates respond differently to eutrophication, hydromorphological alteration, land use and fish stocking?

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Šiling Rebeka

2016-01-01

Full Text Available In order to provide adequate guidelines in freshwater management, managers need reliable bioindicators that can respond differently to varied stressors. Managers also have to consider hierarchical structure of environmental factors. Thus, our research aims to test the independence of taxa responses along environmental gradients and to examine in what order natural and anthropogenic factors constrain the structure of littoral benthic assemblages. The rank of explained variance of littoral benthic assemblage's variable group hierarchy was: land use > landscape characteristics > eutrophication > fish stocking > hydromorphological alteration. We determined nine gradients (two natural and seven stressor gradients, separated into five groups based on statistically significant differences in responsiveness of taxa. Apart from responsiveness to natural factors, littoral benthic invertebrates could be used as bioindicators for stressors reflecting urbanization, eutrophication, hydromorphological alteration and fish stocking. The taxonomical composition of littoral benthic invertebrates, especially when taxa with preference for certain relatively narrow environmental conditions along gradients are present, can be used to identify effects of key stressors. Our findings have profound implications for ecological assessment and management of lakes, as they indicate that benthic invertebrates can be used when the effects of multiple stressors need to be disentangled.

Genetics of the α 1,6-dextran response: expression of the QUPC52 idiotype in different inbred and congenic strains of mice

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D'Hoostelaere, L.; Potter, M.

1982-01-01

Antibodies to dextran B512 were raised in various strains of mice and were assayed by a radioimunoassay procedure. Idiotypic antibodies to the IgA(k) dextran B512 binding myeloma proteins QUOC52 and W3129 of BALB/c origin were prepred in rabbits. After adsorption, each antiserum was specific for the immunizing myeloma protein and did not react with hundreds of other myeloma proteins; nonetheless, antibodies to dextran B512 from various strains of mice cross-reacted in these test systems. Of the 2 idiotypes tested, the W3129 idiotype was more universally expressed in different strains of mice. The QUPC52 idiotype was the predominant idiotype in BALB/c anti-dextran B512 antibodies and was found in only a few other inbred strains. Using a battery of congenic and inbred strains, it was shown that the QUPC52 idiotype was controlled by genes linked to the Igh complex locus (chromosome 12) and to the Ig k complex locus (chromosome 6). The W3129 idiotype was found in a number of stocks of mice in the genus Mus recently isolated from the wild. The QUPC52 idiotype thus far was found only in inbred mice

Antidepressant-like effects of guanfacine and sex-specific differences in effects on c-fos immunoreactivity and paired-pulse ratio in male and female mice.

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Mineur, Yann S; Bentham, Matthew P; Zhou, Wen-Liang; Plantenga, Margreet E; McKee, Sherry A; Picciotto, Marina R

2015-10-01

The a2A-noradrenergic agonist guanfacine can decreases stress-induced smoking in female, but not male, human smokers. It is not known whether these effects are due to effects on mood regulation and/or result from nicotinic-cholinergic interactions. The objective of the study was to determine whether there are sex differences in the effect of guanfacine in tests of anxiolytic and antidepressant efficacy in mice at baseline and in a hypercholinergic model of depression induced by the acetylcholinesterase inhibitor physostigmine. The effects of guanfacine were measured in the light/dark box, tail suspension, and the forced swim test in female and male C57BL/6J mice. In parallel, electrophysiological properties were evaluated in the prefrontal cortex, a critical brain region involved in stress responses. c-fos immunoreactivity was measured in other brain regions known to regulate mood. Despite a baseline sex difference in behavior in the forced swim test (female mice were more immobile), guanfacine had similar, dose-dependent, antidepressant-like effects in mice of both sexes (optimal dose, 0.15 mg/kg). An antidepressant-like effect of guanfacine was also observed following pre-treatment with physostigmine. A sex difference in the paired-pulse ratio in the prefrontal cortex (PFC) (male, 1.4; female, 2.1) was observed at baseline that was normalized by guanfacine. Other brain areas involved in cholinergic control of depression-like behaviors, including the basolateral amygdala and lateral septum, showed sex-specific changes in c-fos expression. Guanfacine has a robust antidepressant-like effect and can reverse a depression-like state induced by increased acetylcholine (ACh) signaling. These data suggest that different brain areas are recruited in female and male mice, despite similar behavioral responses to guanfacine.

Effect of Different Concentrations of Melatonin on Live Births Resulting from the Transfer of Two-Cell Embryos of NMRI Mice

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Mahdi Saadati

2014-12-01

Full Text Available Background & objectives : Infertility is a global problem affecting millions of men and women in developed and developing countries. In this regard, in-vitro fertilization (IVF plays an important role in improving the quality of life in infertile patients. However, studies have shown that the implantation failure in IVF is the main challenge of this procedure. Melatonin can increase the survival rate of embryos and IVF success rate through eliminating free radicals and removing reactive oxygen species. So, this study is conducted to investigate the effects of different concentrations of melatonin on the rate of newborns of mice following transfer oftwo-cell embryos .   Methods : In this study, female mice with average age of six to eight weeks were superovulated by administering pregnant mares serum gonadotropin (PMSG intraperitoneally (7.5 IU. ip, and followed after 48h by human chorionic gonadotropin (hCG (7.5 IU. ip. Two-cell mouse embryos were obtained from female mice oviduct after 48 h. The embryos transferred bilaterally into pseudopregnant mice of the same strain through surgical procedure and 8-14 embryos were transferred to each tube. The study included 4 treatment groups and one control group (6 mice in each group. The treatment groups were exposed to subcutaneous injection of concentrations of 100 µm , 10 µm , 1 µm and 100 nm of melatonin. After the cesarean on 18th day of pregnancy, the percentage of live births was assessed. The outcomes of the live birth rate were as­sessed using the chi-square test and statistical analyses were carried out using SPSS version 16.0. Percentage of live birth was calculated and compared with the control group.   Results: A total of 701 two-cell mouse embryos were transferred into one control group and four experimental groups. The number and percentage of live births at concentrations of 100 µm and 10 µm of melatonin and the control groups were 21 (15.55%, 13 (9.15% and 9 (6

Differences in micronucleus induction in peripheral blood reticulocytes of mice exposed to N-ethyl-N-nitrosourea at light and dark dosing times.

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Itoh, Keiichi; Masumori, Shoji; Nakajima, Madoka; Hayashi, Makoto; Sakakibara, Hiroyuki; Shimoi, Kayoko

2012-01-01

Mammals, including human beings, have a circadian clock system to regulate behavioral and physiological processes. In this study, we investigated the effect of dosing time on micronucleus induction in the bone marrow by evaluating the frequencies of micronucleated peripheral reticulocytes (MNRETs) in mice exposed to N-ethyl-N-nitrosourea (ENU) to assess any difference in genotoxic sensitivity to chemicals between light and dark periods (inactive phase for rodents and active phase for rodents). Male C3H/He mice were treated intraperitoneally with ENU (12.5 or 25 mg/kg body weight) at zeitgeber time (ZT) 3 in the light period or ZT15 in the dark period, and then the time courses of the frequencies of the MNRETs were determined. The frequencies of the MNRETs induced by ENU increased time-dependently and peaked at 48 hr after treatment for ZT3 and ZT15, and were obviously higher in the ZT15 treatment group than the ZT3 treatment group. The MNRETs were measured at 48 hr after treatment with ENU (25 mg/kg body weight) at various dosing times (ZT0, 3, 6, 12, 15 and 18). The frequencies of the MNRETs in mice treated at ZT0, 15 and 18 were significantly higher than those in mice treated at ZT3, 6 and 12. These results suggest that genotoxic sensitivity to chemicals in mouse bone marrow is different between light and dark periods maybe due to different biological responses (detoxification, cell cycle, DNA repair, etc.) related to circadian rhythms.

Microvascular dysfunction with increased vascular leakage response in mice systemically exposed to arsenic.

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Chen, Shih-Chieh; Huang, Shin-Yin; Lu, Chi-Yu; Hsu, Ya-Hung; Wang, Dean-Chuan

2014-09-01

The mechanisms underlying cardiovascular disease induced by arsenic exposure are not completely understood. The objectives of this study were to investigate whether arsenic-fed mice have an increased vascular leakage response to vasoactive agents and whether enhanced type-2 protein phosphatase (PP2A) activity is involved in mustard oil-induced leakage. ICR mice were fed water or sodium arsenite (20 mg/kg) for 4 or 8 weeks. The leakage response to vasoactive agents was quantified using the Evans blue (EB) technique or vascular labeling with carbon particles. Increased EB leakage and high density of carbon-labeled microvessels were detected in arsenic-fed mice treated with mustard oil. Histamine induced significantly higher vascular leakage in arsenic-fed mice than in water-fed mice. Pretreatment with the PP2A inhibitor okadaic acid or the neurokinin 1 receptor (NK1R) blocker RP67580 significantly reduced mustard oil-induced vascular leakage in arsenic-fed mice. The protein levels of PP2Ac and NK1R were similar in both groups. PP2A activity was significantly higher in the arsenic-fed mice compared with the control group. These findings indicate that microvessels generally respond to vasoactive agents, and that the increased PP2A activity is involved in mustard oil-induced vascular leakage in arsenic-fed mice. Arsenic may initiate endothelial dysfunction, resulting in vascular leakage in response to vasoactive agents.

Ablation of neurons expressing melanin-concentrating hormone (MCH) in adult mice improves glucose tolerance independent of MCH signaling.

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Whiddon, Benjamin B; Palmiter, Richard D

2013-01-30

Melanin-concentrating hormone (MCH)-expressing neurons have been ascribed many roles based on studies of MCH-deficient mice. However, MCH neurons express other neurotransmitters, including GABA, nesfatin, and cocaine-amphetamine-regulated transcript. The importance of these other signaling molecules made by MCH neurons remains incompletely characterized. To determine the roles of MCH neurons in vivo, we targeted expression of the human diphtheria toxin receptor (DTR) to the gene for MCH (Pmch). Within 2 weeks of diphtheria toxin injection, heterozygous Pmch(DTR/+) mice lost 98% of their MCH neurons. These mice became lean but ate normally and were hyperactive, especially during a fast. They also responded abnormally to psychostimulants. For these phenotypes, ablation of MCH neurons recapitulated knock-out of MCH, so MCH appears to be the critical neuromodulator released by these neurons. In contrast, MCH-neuron-ablated mice showed improved glucose tolerance when compared with MCH-deficient mutant mice and wild-type mice. We conclude that MCH neurons regulate glucose tolerance through signaling molecules other than MCH.

Skin mites in mice (Mus musculus): high prevalence of Myobia sp. (Acari, Arachnida) in Robertsonian mice.

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Sastre, Natalia; Calvete, Oriol; Martínez-Vargas, Jessica; Medarde, Nuria; Casellas, Joaquim; Altet, Laura; Sánchez, Armand; Francino, Olga; Ventura, Jacint

2018-05-04

Myobia sp. and Demodex sp. are two skin mites that infest mice, particularly immunodeficient or transgenic lab mice. In the present study, wild house mice from five localities from the Barcelona Roberstonian system were analysed in order to detect skin mites and compare their prevalence between standard (2n = 40) and Robertsonian mice (2n > 40). We found and identified skin mites through real-time qPCR by comparing sequences from the mitochondrial 16S rRNA and the nuclear 18S rRNA genes since no sequences are available so far using the mitochondrial gene. Fourteen positive samples were identified as Myobia musculi except for a deletion of 296 bp out to 465 bp sequenced, and one sample was identified as Demodex canis. Sampling one body site, the mite prevalence in standard and Robertsonian mice was 0 and 26%, respectively. The malfunction of the immune system elicits an overgrowth of skin mites and consequently leads to diseases such as canine demodicosis in dogs or rosacea in humans. In immunosuppressed mice, the probability of developing demodicosis is higher than in healthy mice. Since six murine toll-like receptors (TLRs) are located in four chromosomes affected by Robertsonian fusions, we cannot dismiss that differences in mite prevalence could be the consequence of the interruption of TLR function. Although ecological and/or morphological factors cannot be disregarded to explain differences in mite prevalence, the detection of translocation breakpoints in TLR genes or the analysis of TLR gene expression are needed to elucidate how Robertsonian fusions affect the immune system in mice.

The differential mice response to cat and snake odor.

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de Oliveira Crisanto, Karen; de Andrade, Wylqui Mikael Gomes; de Azevedo Silva, Kayo Diogenes; Lima, Ramón Hypolito; de Oliveira Costa, Miriam Stela Maris; de Souza Cavalcante, Jeferson; de Lima, Ruthnaldo Rodrigues Melo; do Nascimento, Expedito Silva; Cavalcante, Judney Cley

2015-12-01

Studies from the last two decades have pointed to multiple mechanisms of fear. For responding to predators, there is a group of highly interconnected hypothalamic nuclei formed by the anterior hypothalamic nucleus, the ventromedial hypothalamic nucleus and the dorsal premammillary nucleus—the predator-responsive hypothalamic circuit. This circuit expresses Fos in response to predator presence or its odor. Lesion of any component of this system blocks or reduces the expression of fear and consequently defensive behavior when faced with a predator or its cue. However, most of the knowledge about that circuit has been obtained using the rat as a model of prey and the cat as a source of predator cues. In the present study, we exposed mice to strong cat or snake odors, two known mice predators, and then we used the rat exposure test (RET) to study their behavior when confronted with the same predator's odor. Our data point to a differential response of mice exposed to these odors. When Swiss mice were exposed to the cat odor, they show defensive behavior and the predator-responsive hypothalamic circuit expressed Fos. The opposite was seen when they faced snake's odor. The acute odor exposure was not sufficient to activate the mouse predator-responsive hypothalamic circuit and the mice acted like they were not in a stressful situation, showing almost no sign of fear or defensive posture. This leads us to the conclusion that not all the predator cues are sufficient to activate the predator-responsive hypothalamic circuit of mice and that their response depends on the danger that these predators represent in the natural history of the prey.

CBT for childhood anxiety disorders: differential changes in selective attention between treatment responders and non-responders.

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Legerstee, Jeroen S; Tulen, Joke H M; Dierckx, Bram; Treffers, Philip D A; Verhulst, Frank C; Utens, Elisabeth M W J

2010-02-01

This study examined whether treatment response to stepped-care cognitive-behavioural treatment (CBT) is associated with changes in threat-related selective attention and its specific components in a large clinical sample of anxiety-disordered children. Ninety-one children with an anxiety disorder were included in the present study. Children received a standardized stepped-care CBT. Three treatment response groups were distinguished: initial responders (anxiety disorder free after phase one: child-focused CBT), secondary responders (anxiety disorder free after phase two: child-parent-focused CBT), and treatment non-responders. Treatment response was determined using a semi-structured clinical interview. Children performed a pictorial dot-probe task before and after stepped-care CBT (i.e., before phase one and after phase two CBT). Changes in selective attention to severely threatening pictures, but not to mildly threatening pictures, were significantly associated with treatment success. At pre-treatment assessment, initial responders selectively attended away from severely threatening pictures, whereas secondary responders selectively attended toward severely threatening pictures. After stepped-care CBT, initial and secondary responders did not show any selectivity in the attentional processing of severely threatening pictures. Treatment non-responders did not show any changes in selective attention due to CBT. Initial and secondary treatment responders showed a reduction of their predisposition to selectively attend away or toward severely threatening pictures, respectively. Treatment non-responders did not show any changes in selective attention. The pictorial dot-probe task can be considered a potentially valuable tool in assigning children to appropriate treatment formats as well as for monitoring changes in selective attention during the course of CBT.

Different gonadotropin releasing hormone agonist doses for the final oocyte maturation in high-responder patients undergoing in vitro fertilization/intra-cytoplasmic sperm injection

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Emre Goksan Pabuccu

2015-01-01

Full Text Available Context: Efficacy of gonadotropin releasing hormone agonists (GnRH-a for ovulation in high-responders. Aims: The aim of the current study is to compare the impact of different GnRH-a doses for the final oocyte maturation on cycle outcomes and ovarian hyperstimulation syndrome (OHSS rates in high-responder patients undergoing ovarian stimulation. Settings And Designs: Electronic medical records of a private in vitro fertilization center, a retrospective analysis. Subjects and Methods: A total of 77 high-responder cases were detected receiving GnRH-a. Group I consisted of 38 patients who received 1 mg of agonist and Group II consisted of 39 patients who received 2 mg of agonist. Statistical Analysis: In order to compare groups, Student′s t-test, Mann-Whitney U-test, Pearson′s Chi-square test or Fisher′s exact test were used where appropriate. A P < 0.05 was considered as statistically significant. Result: Number of retrieved oocytes (17.5 vs. 15.0, P = 0.510, implantation rates (46% vs. 55.1%, P = 0.419 and clinical pregnancy rates (42.1% vs. 38.5%, P = 0.744 were similar among groups. There were no mild or severe OHSS cases detected in Group I. Only 1 mild OHSS case was detected in Group II. Conclusion: A volume of 1 or 2 mg leuprolide acetate yields similar outcomes when used for the final oocyte maturation in high-responder patients.

Effects of fisetin on oxaliplatin-induced neuropathic pain in mice

OpenAIRE

Hong Liu; Chaohua Wang; Hua Yang; Fengjie Wang

2015-01-01

Common chemotherapeutic agents such as oxaliplatin often cause neuropathic pain during cancer treatment in patients. Such neuropathic pain is difficult to treat and responds poorly to common analgesics, which represents a challenging clinical issue. Fisetin is a naturally occurring flavonoid and this study tested the potential anti-hyperalgesic effects of fisetin in a mice model of oxaliplatin-induced neuropathic pain. Fisetin (1-4 mg/kg, i.p.) did not significantly alter the mechanical hyper...

Brain GLUT4 Knockout Mice Have Impaired Glucose Tolerance, Decreased Insulin Sensitivity, and Impaired Hypoglycemic Counterregulation.

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Reno, Candace M; Puente, Erwin C; Sheng, Zhenyu; Daphna-Iken, Dorit; Bree, Adam J; Routh, Vanessa H; Kahn, Barbara B; Fisher, Simon J

2017-03-01

GLUT4 in muscle and adipose tissue is important in maintaining glucose homeostasis. However, the role of insulin-responsive GLUT4 in the central nervous system has not been well characterized. To assess its importance, a selective knockout of brain GLUT4 (BG4KO) was generated by crossing Nestin-Cre mice with GLUT4-floxed mice. BG4KO mice had a 99% reduction in GLUT4 protein expression throughout the brain. Despite normal feeding and fasting glycemia, BG4KO mice were glucose intolerant, demonstrated hepatic insulin resistance, and had reduced glucose uptake in the brain. In response to hypoglycemia, BG4KO mice had impaired glucose sensing, noted by impaired epinephrine and glucagon responses and impaired c-fos activation in the hypothalamic paraventricular nucleus. Moreover, in vitro glucose sensing of glucose-inhibitory neurons from the ventromedial hypothalamus was impaired in BG4KO mice. In summary, BG4KO mice are glucose intolerant, insulin resistant, and have impaired glucose sensing, indicating a critical role for brain GLUT4 in sensing and responding to changes in blood glucose. © 2017 by the American Diabetes Association.

Different effects of deep inspirations on central and peripheral airways in healthy and allergen-challenged mice

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Dahlén Sven-Erik

2008-02-01

Full Text Available Abstract Background Deep inspirations (DI have bronchodilatory and bronchoprotective effects in healthy human subjects, but these effects appear to be absent in asthmatic lungs. We have characterized the effects of DI on lung mechanics during mechanical ventilation in healthy mice and in a murine model of acute and chronic airway inflammation. Methods Balb/c mice were sensitized to ovalbumin (OVA and exposed to nebulized OVA for 1 week or 12 weeks. Control mice were challenged with PBS. Mice were randomly selected to receive DI, which were given twice during the minute before assessment of lung mechanics. Results DI protected against bronchoconstriction of central airways in healthy mice and in mice with acute airway inflammation, but not when OVA-induced chronic inflammation was present. DI reduced lung resistance induced by methacholine from 3.8 ± 0.3 to 2.8 ± 0.1 cmH2O·s·mL-1 in healthy mice and 5.1 ± 0.3 to 3.5 ± 0.3 cmH2O·s·mL-1 in acute airway inflammation (both P P P P P Conclusion We have tested a mouse model of potential value for defining mechanisms and sites of action of DI in healthy and asthmatic human subjects. Our current results point to potent protective effects of DI on peripheral parts of chronically inflamed murine lungs and that the presence of DI may blunt airway hyperreactivity.

Myostatin deficiency partially rescues the bone phenotype of osteogenesis imperfecta model mice.

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Oestreich, A K; Carleton, S M; Yao, X; Gentry, B A; Raw, C E; Brown, M; Pfeiffer, F M; Wang, Y; Phillips, C L

2016-01-01

Mice with osteogenesis imperfecta (+/oim), a disorder of bone fragility, were bred to mice with muscle over growth to test whether increasing muscle mass genetically would improve bone quality and strength. The results demonstrate that femora from mice carrying both mutations have greater mechanical integrity than their +/oim littermates. Osteogenesis imperfecta is a heritable connective tissue disorder due primarily to mutations in the type I collagen genes resulting in skeletal deformity and fragility. Currently, there is no cure, and therapeutic strategies encompass the use of antiresorptive pharmaceuticals and surgical bracing, with limited success and significant potential for adverse effects. Bone, a mechanosensing organ, can respond to high mechanical loads by increasing new bone formation and altering bone geometry to withstand increased forces. Skeletal muscle is a major source of physiological loading on bone, and bone strength is proportional to muscle mass. To test the hypothesis that congenic increases in muscle mass in the osteogenesis imperfecta murine model mouse (oim) will improve their compromised bone quality and strength, heterozygous (+/oim) mice were bred to mice deficient in myostatin (+/mstn), a negative regulator of muscle growth. The resulting adult offspring were evaluated for hindlimb muscle mass, and bone microarchitecture, physiochemistry, and biomechanical integrity. +/oim mice deficient in myostatin (+/mstn +/oim) were generated and demonstrated that myostatin deficiency increased body weight, muscle mass, and biomechanical strength in +/mstn +/oim mice as compared to +/oim mice. Additionally, myostatin deficiency altered the physiochemical properties of the +/oim bone but did not alter bone remodeling. Myostatin deficiency partially improved the reduced femoral bone biomechanical strength of adult +/oim mice by increasing muscle mass with concomitant improvements in bone microarchitecture and physiochemical properties.

Flow cytometry analysis reveals different activation profiles of thrombin- or TRAP-stimulated platelets in db/db mice. The regulatory role of PAR-3.

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Kassassir, Hassan; Siewiera, Karolina; Talar, Marcin; Przygodzki, Tomasz; Watala, Cezary

2017-06-01

Recent studies have shown that it may be the concentration of thrombin, which is discriminative in determining of the mechanism of platelet activation via protease activated receptors (PARs). Whether the observed phenomenon of differentiated responses of mouse platelets to various thrombin concentrations in non-diabetic db/+ and diabetic db/db mice depends upon the concerted action of various PARs, remains to be established. We found elevated reactivity of platelets, as well as the enhanced PAR-3 expression in response to both the used concentrations of AYPGKF in db/db mice, as compared to db/+ heterozygotes. At low concentration of thrombin platelets from diabetic mice demonstrated hyperreactivity, reflected by higher expression of PAR-3. For higher thrombin concentration, blood platelets from db/db mice appeared hyporeactive, compared to db/+ animals, while no significant differences in PAR-3 expression were observed between diabetic and non-diabetic mice. The novel and previously unreported finding resulting from our study is that the increased expression of PAR-3 in response to either TRAP for PAR-4 or low thrombin (when PAR-4 is not the efficient thrombin receptor) may be one of the key events contributing to higher reactivity of platelets in db/db mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Bodyweight Assessment of Enamelin Null Mice

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Albert H.-L. Chan

2013-01-01

Full Text Available The Enam null mice appear to be smaller than wild-type mice, which prompted the hypothesis that enamel defects negatively influence nutritional intake and bodyweight gain (BWG. We compared the BWG of Enam−/− and wild-type mice from birth (D0 to Day 42 (D42. Wild-type (WT and Enam−/− (N mice were given either hard chow (HC or soft chow (SC. Four experimental groups were studied: WTHC, WTSC, NHC, and NSC. The mother’s bodyweight (DBW and the average litter bodyweight (ALBW were obtained from D0 to D21. After D21, the pups were separated from the mother and provided the same type of food. Litter bodyweights were measured until D42. ALBW was compared at 7-day intervals using one-way ANOVA, while the influence of DBW on ALBW was analyzed by mixed-model analyses. The ALBW of Enam−/− mice maintained on hard chow (NHC was significantly lower than the two WT groups at D21 and the differences persisted into young adulthood. The ALBW of Enam−/− mice maintained on soft chow (NSC trended lower, but was not significantly different than that of the WT groups. We conclude that genotype, which affects enamel integrity, and food hardness influence bodyweight gain in postnatal and young adult mice.

Nickel sensitisation in mice: a critical appraisal.

Science.gov (United States)

Johansen, Pål; Wäckerle-Men, Ying; Senti, Gabriela; Kündig, Thomas M

2010-06-01

The market release of new domestic and industrial chemical and metal products requires certain safety certification, including testing for skin sensitisation. Although various official guidelines have described how such testing is to be done, the validity of the available test models are in part dubious, for which reason regulatory agencies and research aim to further improve and generalise the models for testing of skin sensitisation. We applied a recently published murine model of nickel allergy as to test its applicability in a regulatory setting and to study and better understand the events leading to type-IV hypersensitivity. Nickel was chosen as model hapten since it induces allergic contact dermatitis with high incidence in the general population. Typically, C57BL/6 mice were sensitised and challenged by intradermal applications of nickel, and cutaneous inflammation was analysed by the mouse ear-swelling test, by histology, and by lymphocyte reactivity in vitro. Surprisingly, the study suggested that the skin reactions observed were results of irritant reactions rather than of adaptive immune responses. Non-sensitised mice responded with cutaneous inflammation and in vitro lymphocyte reactivity which were comparable with nickel-sensitised mice. Furthermore, histological examinations as well as experiments in T-cell deficient mice demonstrated that lymphocytes were not involved and that nickel caused an irritant contact dermatitis rather a true allergic type-IV contact dermatitis. The authors question the validity of the described murine model of nickel allergy. Copyright 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

An experimental analysis of the specificity of actively acquired tolerance in mice

Energy Technology Data Exchange (ETDEWEB)

Doria, G.

1963-08-15

Tolerance to CBA skin was induced in C3H mice by neonatal injection of CBA spleen cells. When two months old, the C3H recipients were grafted with CBA skin. These skin grafts showed no signs of rejection during the observation time of three months, whereas CBA skins grafted onto C3H mice non injected at birth showed complete necrosis in 11.7 days. Normal C3H and C3H mice tolerant to CBA skin were injected with rat RBC and sacrificed 12 days later for serum titration of anti-rat RBC agglutinins. The agglutinin titer was the same in both groups. This indicates that the unresponsiveness of C3H mice to CBA skin was specific, for the tolerant mice were able to respond with normal vigor to antigens (rat RBC) unrelated to C3H and CBA. Whether this response was due to the host immune system or to the CBA spleen cells which may have colonized the C3H newborns was subsequently investigated. Spleen cells from tolerant C3H mice sensitized to rat RBC were injected into two groups of lethally irradiated recipients: C3H mice preimmunized against CBA and CBA mice preimmunized against C3H. Both groups were given rat RBC immediately after the spleen cell transfer from the tolerant mice and sacrified a week later for serum titration of anti-rat RBC agglutinins. These agglutinins, due to the secondary response of the transferred spleen cells, could be detected only in the group of C3H recipients preimmunized against CBA. This shows that anti-rat RBC agglutinins in tolerant mice were produced y the immune system of the C3H host. The theoretical implications of this finding are discussed. (auth)

Launch of the "MICE Procurement" website for your future events

CERN Multimedia

The MICE Office team

2014-01-01

The number of MICE (Meeting, Incentive, Conference and Event) requests is on the increase and our hotel offer is constantly being developed.   The MICE Office has decided to create a dedicated website in order to offer the best possible service to its users. This site is accessible from the FP webpage (MICE Procurement) using your NICE login. It gives you access to the list of the establishments which have a contract with CERN, grouped by geographic area/star rating, and all related information. The establishments listed on this website can accommodate your local events, organised by CERN or in partnership with an institution. They were selected following a market survey and as a result of a price enquiry in accordance with CERN's Purchasing Rules. We offer a number of standard packages, but we will try to respond to any specific requirements. On the same site you can also access a longer list of hotels (also accessible via the GS website) for which prices and conditions have been nego...

Sex differences during the course of diet-induced obesity in mice: adipose tissue expandability and glycemic control

Czech Academy of Sciences Publication Activity Database

Medříková, Daša; Jílková, Zuzana; Bardová, Kristina; Janovská, Petra; Rossmeisl, Martin; Kopecký, Jan

2012-01-01

Roč. 36, č. 2 (2012), s. 262-272 ISSN 0307-0565 R&D Projects: GA MŠk(CZ) 7E10059; GA MŠk(CZ) OC08008; GA ČR(CZ) GA303/08/0664 Institutional research plan: CEZ:AV0Z50110509 Keywords : sex differences * inflammation * adipose tissue expandability * insulin sensitivity * mice Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 5.221, year: 2012

Acclimatization of mice to different cage types and social groupings with respect to fecal secretion of IgA and corticosterone metabolites

DEFF Research Database (Denmark)

Bundgaard, Cathrine Juel; Kalliokoski, Otto; Abelson, Klas Sp

2012-01-01

genders were housed either in groups of eight in different cage types in open conventional cages, in Individual Ventilated Cages (IVC), in open conventional cages inside a plastic isolator, or in different group sizes (8, 4, 8, 10 or 12 mice in each group) in open conventional cages. Feces were collected...

Soil bacterial and fungal communities respond differently to various isothiocyanates added for biofumigation

Directory of Open Access Journals (Sweden)

Ping eHu

2015-01-01

Full Text Available The meals from many oilseed crops have potential for biofumigation due to their release of biocidal compounds such as isothiocyanates (ITCs. Various ITCs are known to inhibit numerous pathogens; however, much less is known about how the soil microbial community responds to the different types of ITCs released from oilseed meals (SMs. To simulate applying ITC-releasing SMs to soil, we amended soil with 1% flax SM (contains no biocidal chemicals along with four types of ITCs (allyl, butyl, phenyl, and benzyl ITC in order to determine their effects on soil fungal and bacterial communities in a replicated microcosm study. Microbial communities were analyzed based on the ITS region for fungi and 16S rRNA gene for bacteria using qPCR and tag-pyrosequencing with 454 GS FLX titanium technology. A dramatic decrease in fungal populations (~85% reduction was observed after allyl ITC addition. Fungal community compositions also shifted following ITC amendments (e.g., Humicola increased in allyl and Mortierella in butyl ITC amendments. Bacterial populations were less impacted by ITCs, although there was atransient increase in the proportion of Firmicutes, related to bacteria know to be antagonistic to plant pathogens, following amendment with allyl ITC. Our results indicate that the type of ITC released from SMs can result in differential impacts on soil microorganisms. This information will aid selection and breeding of plants for biofumigation-based control of soil-borne pathogens while minimizing the impacts on non-target microorganisms.

Humility when responding to the abuse of adults with mental disabilities.

Science.gov (United States)

Skowron, Paul

Legal theorists often reduce the ethics of responding to the abuse of another person to a clash between the principles of autonomy and protection. This reduction is a problem. Responding to suspected abuse requires humility - the potential responder must be aware of and respect their own limits - but humility cannot be usefully reduced to protection and autonomy. Using examples from the Court of Protection of England and Wales, this article examines the different ways that someone responding to abuse should respect their own limits, and suggests that a failure to do so will disproportionately affect people with mental disabilities. It is therefore necessary to attend to whether the law fosters humility among those who respond to abuse, although this must be tempered by humility about legal reform itself. Finally, the article shows how attention to humility can assist the interpretation of Article 16 of the UN Convention on the Rights of Persons with Disabilities; and suggests that, so interpreted, the Convention may help to promote humility when responding to abuse. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Increased susceptibility to diet-induced obesity in histamine-deficient mice

DEFF Research Database (Denmark)

Jørgensen, Emilie A; Vogelsang, Thomas W; Knigge, Ulrich

2006-01-01

in the development of high-fat diet (HFD)-induced obesity. METHODS: Histamine-deficient histidine decarboxylase knock-out (HDC-KO) mice and C57BL/6J wild-type (WT) mice were given either a standard diet (STD) or HFD for 8 weeks. Body weight, 24-hour caloric intake, epididymal adipose tissue size, plasma leptin...... weeks, whereas a significant difference in body weight gain was first observed after 5 weeks in WT mice. After 8 weeks 24-hour caloric intake was significantly lower in HFD- than in STD-fed WT mice. In HDC-KO mice no difference in caloric intake was observed between HFD- and STD-fed mice. After 8 weeks...

Collagen-induced arthritis in mice

NARCIS (Netherlands)

Bevaart, Lisette; Vervoordeldonk, Margriet J.; Tak, Paul P.

2010-01-01

Collagen-induced arthritis (CIA) in mice is an animal model for rheumatoid arthritis (RA) and can be induced in DBA/1 and C57BL/6 mice using different protocols. The CIA model can be used to unravel mechanisms involved in the development of arthritis and is frequently used to study the effect of new

Radiation genetic injury and metabolic difference of tritiated thymidine in testis of young and adult mice

Energy Technology Data Exchange (ETDEWEB)

Mingyue, Lun; Shoupeng, Zhu

1990-04-01

The radiogenetoxicological effects on the adult testis and the metabolic difference of tritiated thymidine between the testis of young and adult BALB/C mice were studied. When 0.037 MBq/g.b.w. of tritiated thymidine was given i.v. to mice, the initial burden of tritium in the adult was larger than that of tritium in the young. But the retention of tritium in testis of the young gradually become larger than that of tritium in the adult with the passing time. Tritiated thymidine which was incorporated into DNA of the male germ cell nuclei damaged the genetic materials and caused the rising of the rates of the dominant lethal and the dominant mutation which produced skeletal abnomalities in the offspring. The relationship between the dominant lethal mutation index (Y) and the injected activity of tritiated thymidine (I, MBq/g.b.w.) is described by Y = 74.13 + 80.20 I (r = 0.95). The relationship between the incidence of the dominant skeletal mutation in the offspring (B) and the injected activity is B = 0.16 + 0.079 I ( r = 0.85).

Radiation genetic injury and metabolic difference of tritiated thymidine in testis of young and adult mice

International Nuclear Information System (INIS)

Lun Mingyue; Zhu Shoupeng.

1990-01-01

The radiogenetoxicological effects on the adult testis and the metabolic difference of tritiated thymidine between the testis of young and adult BALB/C mice were studied. When 0.037 MBq/g.b.w. of tritiated thymidine was given i.v. to mice, the initial burden of tritium in the adult was larger than that of tritium in the young. But the retention of tritium in testis of the young gradually become larger than that of tritium in the adult with the passing time. Tritiated thymidine which was incorporated into DNA of the male germ cell nuclei damaged the genetic materials and caused the rising of the rates of the dominant lethal and the dominant mutation which produced skeletal abnomalities in the offspring. The relationship between the dominant lethal mutation index (Y) and the injected activity of tritiated thymidine (I, MBq/g.b.w.) is described by Y = 74.13 + 80.20 I (r = 0.95). The relationship between the incidence of the dominant skeletal mutation in the offspring (B) and the injected activity is B = 0.16 + 0.079 I ( r = 0.85)

Benzophenone guttiferone A from Garcinia achachairu Rusby (Clusiaceae presents genotoxic effects in different cells of mice.

Directory of Open Access Journals (Sweden)

Peterson Menezes Terrazas

Full Text Available Benzophenones from natural sources and those of synthetic analogues present several reports of potent biological properties, and Guttiferone A represents a promising medicinal natural compound with analgesic and gastroprotective profiles. Considering that there are no reports that assess the genetic toxicity of Guttiferone A, the present study was undertaken to investigate the genotoxic potential of this benzophenone isolated from seeds of Garcinia achachairu in terms of DNA damage in different cells of Swiss albino mice using the comet assay, and its clastogenic/aneugenic effects in bone marrow cells in vivo by the micronucleus test. Cytotoxicity was assessed by scoring polychromatic (PCE and normochromatic (NCE erythrocytes ratio. Guttiferone A was administered by oral gavage at doses of 15, 30 and 60 mg/kg. The results showed that Guttiferone A produced genotoxic effects in leukocytes, liver, bone marrow, brain and testicle cells and clastogenic/aneugenic effects in bone marrow erythrocytes of mice. The PCE/NCE ratio indicated no cytotoxicity. Since guttiferone A is harmful to the genetic material we suggest caution in its use by humans.

Species difference in reactivity to lignin-like enzymatically polymerized polyphenols on interferon-γ synthesis and involvement of interleukin-2 production in mice.

Science.gov (United States)

Yamanaka, Daisuke; Ishibashi, Ken-Ichi; Adachi, Yoshiyuki; Ohno, Naohito

2016-09-01

Recent studies have revealed that lignin-like polymerized polyphenols can activate innate immune systems. In this study, we aimed to evaluate whether these polymerized polyphenols could activate leukocytes from different murine strains. Splenocytes from 12 mouse strains were investigated. Our results revealed species differences in reactivity to phenolic polymers on interferon-γ (IFN-γ) release. Mice that possessed the H2(a) or H2(k) haplotype antigens were the highly responsive strains. To clarify these different points in soluble factors, multiplex cytokine profiling analysis was carried out and we identified interleukin (IL)-2 as a key molecule for IFN-γ induction by polymerized polyphenols. Furthermore, inhibition of IL-2 and IL-2Rα by neutralizing antibodies significantly decreased cytokine production in the highly responsive mice strains. Our results indicate that species difference in reactivity to phenolic polymers is mediated by adequate release of IL-2 and its receptor, IL-2Rα. Copyright © 2016 Elsevier B.V. All rights reserved.

The Conscientious Responders Scale Helps Researchers Verify the Integrity of Personality Questionnaire Data.

Science.gov (United States)

Marjanovic, Zdravko; Bajkov, Lisa; MacDonald, Jennifer

2018-01-01

The Conscientious Responders Scale is a five-item embeddable validity scale that differentiates between conscientious and indiscriminate responding in personality-questionnaire data (CR & IR). This investigation presents further evidence of its validity and generalizability across two experiments. Study 1 tests its sensitivity to questionnaire length, a known cause of IR, and tries to provoke IR by manipulating psychological reactance. As expected, short questionnaires produced higher Conscientious Responders Scale scores than long questionnaires, and Conscientious Responders Scale scores were unaffected by reactance manipulations. Study 2 tests concerns that the Conscientious Responders Scale's unusual item content could potentially irritate and baffle responders, ironically increasing rates of IR. We administered two nearly identical questionnaires: one with an embedded Conscientious Responders Scale and one without the Conscientious Responders Scale. Psychometric comparisons revealed no differences across questionnaires' means, variances, interitem response consistencies, and Cronbach's alphas. In sum, the Conscientious Responders Scale is highly sensitive to questionnaire length-a known correlate of IR-and can be embedded harmlessly in questionnaires without provoking IR or changing the psychometrics of other measures.

Loss of sugar detection by GLUT2 affects glucose homeostasis in mice.

Directory of Open Access Journals (Sweden)

Emilie Stolarczyk

Full Text Available BACKGROUND: Mammals must sense the amount of sugar available to them and respond appropriately. For many years attention has focused on intracellular glucose sensing derived from glucose metabolism. Here, we studied the detection of extracellular glucose concentrations in vivo by invalidating the transduction pathway downstream from the transporter-detector GLUT2 and measured the physiological impact of this pathway. METHODOLOGY/PRINCIPAL FINDINGS: We produced mice that ubiquitously express the largest cytoplasmic loop of GLUT2, blocking glucose-mediated gene expression in vitro without affecting glucose metabolism. Impairment of GLUT2-mediated sugar detection transiently protected transgenic mice against starvation and streptozotocin-induced diabetes, suggesting that both low- and high-glucose concentrations were not detected. Transgenic mice favored lipid oxidation, and oral glucose was slowly cleared from blood due to low insulin production, despite massive urinary glucose excretion. Kidney adaptation was characterized by a lower rate of glucose reabsorption, whereas pancreatic adaptation was associated with a larger number of small islets. CONCLUSIONS/SIGNIFICANCE: Molecular invalidation of sugar sensing in GLUT2-loop transgenic mice changed multiple aspects of glucose homeostasis, highlighting by a top-down approach, the role of membrane glucose receptors as potential therapeutic targets.

[Analgesia evoked by combined effect of corvitin and low-intensity microwaves on acupuncture points in mice of different genetic strains with somatic pain].

Science.gov (United States)

Hura, O V; Bahats'ka, O V; Lymans'kyĭ, Iu P

2011-01-01

The level of analgesia has been investigated in mice of two genotypes C57BL/6J Bl/6j and CBA/CaLac with the somatic pain caused by the formalin test after irradiation of acupuncture point E-36 by microwaves of low intensity (30-300 GHz, density of a stream of capacity of 3-10-9 B(T)/cm2) on a background entered corvitin (20 mg/kg). It is shown, that the action of these two factors causes significant analgesia with different levels: 43% in C57BL/6J Bl/6j mice and 33% in CBA/CaLac mice. The intensity of analgesia after action of microwaves and corvitin exceeds the level attained during separate use of these factors.

Comparative genomics of Streptococcus pyogenes M1 isolates differing in virulence and propensity to cause systemic infection in mice

NARCIS (Netherlands)

Fiebig, A.; Loof, T.G.; Babbar, A.; Itzeg, A.; Koehorst, J.J.; Schaap, P.J.; Nitsche-Schmitz, D.P.

2015-01-01

Streptococcus pyogenes serotype M1 is a frequent cause of severe infections in humans. Some M1 isolates are pathogenic in mice and used in studies on infection pathogenesis. We observed marked differences in murine infections caused by M1 strain SF370, 5448, 5448AP or AP1 which prompted us to

Effect of Oxidized Dextran on Cytokine Production and Activation of IRF3 Transcription Factor in Macrophages from Mice of Opposite Strains with Different Sensitivity to Tuberculosis Infection.

Science.gov (United States)

Chechushkov, A V; Kozhin, P M; Zaitseva, N S; Gainutdinov, P I; Men'shchikova, E B; Troitskii, A V; Shkurupy, V A

2018-04-16

We studied differences in the production of pro- and anti-inflammatory cytokines and IRF3 transcription factor by peritoneal macrophages from mice of opposite strains CBA/J and C57Bl/6 and the effect of 60-kDa oxidized dextran on these parameters. Macrophages from C57Bl/6 mice were mainly characterized by the production of proinflammatory cytokines TNFα, IL-12, and MCP-1 (markers of M1 polarization). By contrast, CBA/J mice exhibited a relatively high level of anti-inflammatory cytokine IL-10 and lower expression of proinflammatory cytokines (M2 phenotype). IRF3 content in peritoneal macrophages of CBA/J mice was higher than in C57Bl/6 mice. Oxidized dextran decreased the expression of IRF3 upon stimulation of cells from CBA/J mice with LPS, but increased this process in C57Bl/6 mice. Despite a diversity of oxidized dextran-induced changes in cytokine production, the data confirm our hypothesis that this agent can stimulate the alternative activation of macrophages.

Craniofacial Statistical Deformation Models of Wild-type mice and Crouzon mice

DEFF Research Database (Denmark)

Ólafsdóttir, Hildur; Darvann, Tron Andre; Ersbøll, Bjarne Kjær

2007-01-01

Crouzon syndrome is characterised by the premature fusion of cranial sutures and synchondroses leading to craniofacial growth disturbances. The gene causing the syndrome was discovered approximately a decade ago and recently the first mouse model of the syndrome was generated. In this study, a set...... of Micro CT scannings of the heads of wild-type (normal) mice and Crouzon mice were investigated. Statistical deformation models were built to assess the anatomical differences between the groups, as well as the within-group anatomical variation. Following the approach by Rueckert et al. we built an atlas...

Cost per responder of TNF-α therapies in Germany.

Science.gov (United States)

Gissel, Christian; Repp, Holger

2013-12-01

Tumor necrosis factor α (TNF-α) inhibitors ranked highest in German pharmaceutical expenditure in 2011. Their most important application is the treatment of rheumatoid arthritis (RA). Our objective is to analyze cost per responder of TNF-α inhibitors for RA from the German Statutory Health Insurance funds' perspective. We aim to conduct the analysis based on randomized comparative effectiveness studies of the relevant treatments for the German setting. For inclusion of effectiveness studies, we require results in terms of response rates as defined by European League Against Rheumatism (EULAR) or American College of Rheumatology (ACR) criteria. We identify conventional triple therapy as the relevant comparator. We calculate cost per responder based on German direct medical costs. Direct clinical comparisons could be identified for both etanercept and infliximab compared to triple therapy. For infliximab, cost per responder was 216,392 euros for ACR50 and 432,784 euros for ACR70 responses. For etanercept, cost per ACR70 responder was 321,527 euros. Cost was lower for response defined by EULAR criteria, but data was only available for infliximab. Cost per responder is overestimated by 40% due to inclusion of taxes and mandatory rebates in German drugs' list prices. Our analysis shows specific requirements for cost-effectiveness analysis in Germany. Cost per responder for TNF-α treatment in the German setting is more than double the cost estimated in a similar analysis for the USA, which measured against placebo. The difference in results shows the critical role of the correct comparator for a specific setting.

Exceptional Responders Initial Feasibility Results

Science.gov (United States)

A pilot study evaluating identification of cancer patients who respond to treatment that is ineffective in at least 90 percent of patients found that it was indeed able to confirm a majority of proposed patients as exceptional responders based on clinical

Microsatellite analysis in two populations of Kunming mice

DEFF Research Database (Denmark)

Shang, Haitao; Wei, Hong; Yue, Bingfei

2009-01-01

populations are unclear. Fifteen microsatellite markers were screened by a fluorescence-based semi-automated genotyping method for the two main populations of Kunming mice from Beijing (BJ) and Shanghai (SH) in China. The observed number of alleles, effective number of alleles, observed heterozygosity......Kunming mice are the most widely used outbred colony in China. Differences in biological characters and drug reactions among different populations have been observed when using Kunming mice. But the molecular genetic profiles of Kunming mice and the extent of genetic differentiation among...... that there is abundant genetic variation in the populations of Kunming mice. Population differentiation was shown by shared alleles, F-statistics, Nei genetic distance and Nei genetic identity. In population BJ and population SH, respectively, only 35 of 61 and 35 of 63 alleles were shared by both. The Fst per locus...

Reduced alcohol consumption in mice lacking preprodynorphin.

Science.gov (United States)

Blednov, Yuri A; Walker, Danielle; Martinez, Marni; Harris, R Adron

2006-10-01

Many studies suggest a role for endogenous opioid peptides and their receptors in regulation of ethanol intake. It is commonly accepted that the kappa-opioid receptors and their endogenous ligands, dynorphins, produce a dysphoric state and therefore may be responsible for avoidance of alcohol. We used mutant mice lacking preprodynorphin in a variety of behavioral tests of alcohol actions. Null mutant female, but not male, mice showed significantly lower preference for alcohol and consumed lower amounts of alcohol in a two-bottle choice test as compared with wild-type littermates. In the same test, knockout mice of both sexes showed a strong reduction of preference for saccharin compared to control mice. In contrast, under conditions of limited (4 h) access (light phase of the light/dark cycle), null mutant mice did not show any differences in consumption of saccharin, but they showed significantly reduced intake of sucrose. To determine the possible cause for reduction of ethanol preference and intake, we studied other ethanol-related behaviors in mice lacking the preprodynorphin gene. There were no differences between null mutant and wild-type mice in ethanol-induced loss of righting reflex, acute ethanol withdrawal, ethanol-induced conditioned place preference, or conditioned taste aversion to ethanol. These results indicate that deletion of preprodynorphin leads to substantial reduction of alcohol intake in female mice, and suggest that this is caused by decreased orosensory reward of alcohol (sweet taste and/or palatability).

Economics of food intake in mice: energy yield of the reinforcer.

Science.gov (United States)

Rowland, Neil E; Giddings, Ashley M; Minervini, Vanessa; Robertson, Kimberly L

2014-09-01

One of the Zeitgeists of the field for the study of ingestive behavior is that organisms are endowed with internal self-regulatory mechanisms that ensure optimal nutrition. However, the alarming increase in the prevalence of obesity challenges us to reconsider the extent to which internal regulatory mechanisms affect food intake, especially in a free market economy. Cued by the pioneering work of George Collier and his students, we have been examining food intake (demand) in mice when the effort or price of food is manipulated. We present two new experiments in mice that investigate the effect of energy yield per unit of food earned on working for food. The first experiment shows that when the nominal energy yield of each food pellet is halved by cellulose dilution, mice show relatively inelastic calorie-related demand despite the fact the cellulose diluted diet is unpalatable. The second experiment shows that the size of the pellet reinforcer does not have a major effect on food demand except in the extreme condition of small reward and high unit price. New analyses of distributions of responding are presented which suggest that mice work for "target" numbers of food rewards with only a small influence of price or energy gain. Copyright © 2014 Elsevier Inc. All rights reserved.

Difference in Perseverative Errors during a Visual Attention Task with Auditory Distractors in Alpha-9 Nicotinic Receptor Subunit Wild Type and Knock-Out Mice.

Science.gov (United States)

Jorratt, Pascal; Delano, Paul H; Delgado, Carolina; Dagnino-Subiabre, Alexies; Terreros, Gonzalo

2017-01-01

The auditory efferent system is a neural network that originates in the auditory cortex and projects to the cochlear receptor through olivocochlear (OC) neurons. Medial OC neurons make cholinergic synapses with outer hair cells (OHCs) through nicotinic receptors constituted by α9 and α10 subunits. One of the physiological functions of the α9 nicotinic receptor subunit (α9-nAChR) is the suppression of auditory distractors during selective attention to visual stimuli. In a recent study we demonstrated that the behavioral performance of alpha-9 nicotinic receptor knock-out (KO) mice is altered during selective attention to visual stimuli with auditory distractors since they made less correct responses and more omissions than wild type (WT) mice. As the inhibition of the behavioral responses to irrelevant stimuli is an important mechanism of the selective attention processes, behavioral errors are relevant measures that can reflect altered inhibitory control. Errors produced during a cued attention task can be classified as premature, target and perseverative errors. Perseverative responses can be considered as an inability to inhibit the repetition of an action already planned, while premature responses can be considered as an index of the ability to wait or retain an action. Here, we studied premature, target and perseverative errors during a visual attention task with auditory distractors in WT and KO mice. We found that α9-KO mice make fewer perseverative errors with longer latencies than WT mice in the presence of auditory distractors. In addition, although we found no significant difference in the number of target error between genotypes, KO mice made more short-latency target errors than WT mice during the presentation of auditory distractors. The fewer perseverative error made by α9-KO mice could be explained by a reduced motivation for reward and an increased impulsivity during decision making with auditory distraction in KO mice.

An Examination of the Role of L-Glutamate and Inosine 5'-Monophosphate in Hedonic Taste-Guided Behavior by Mice Lacking the T1R1 + T1R3 Receptor.

Science.gov (United States)

Blonde, Ginger D; Spector, Alan C

2017-06-01

The heterodimeric T1R1 + T1R3 receptor is considered critical for normal signaling of L-glutamate and 5'-ribonucleotides in the oral cavity. However, some taste-guided responsiveness remains in mice lacking one subunit of the receptor, suggesting that other receptors are sufficient to support some behaviors. Here, mice lacking both receptor subunits (KO) and wild-type (WT, both n = 13) mice were tested in a battery of behavioral tests. Mice were trained and tested in gustometers with a concentration series of Maltrin-580, a maltodextrin, in a brief-access test (10-s trials) as a positive control. Similar tests followed with monosodium glutamate (MSG) with and without the ribonucleotide inosine 5'-monophosphate (IMP), but always in the presence of the epithelial sodium channel blocker amiloride (A). Brief-access tests were repeated following short-term (30-min) and long-term (48-h) exposures to MSG + A + IMP and were also conducted with sodium gluconate replacing MSG. Finally, progressive ratio tests were conducted with Maltrin-580 or MSG + A + IMP, to assess appetitive behavior while minimizing satiation. Overall, MSG generated little concentration-dependent responding in either food-restricted WT or KO mice, even in combination with IMP. However, KO mice licked less to the amino acid stimuli, a measure of consummatory behavior in the brief-access tests. In contrast, both groups initiated a similar number of trials and had a similar breakpoint in the progressive ratio task, both measures of appetitive (approach) behavior. Collectively, these results suggest that while the T1R1 + T1R3 receptor is necessary for consummatory responding to MSG (+IMP), other receptors are sufficient to maintain appetitive responding to this "umami" stimulus complex in food-restricted mice. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

7 CFR 3017.1000 - Respondent.

Science.gov (United States)

2010-01-01

... 7 Agriculture 15 2010-01-01 2010-01-01 false Respondent. 3017.1000 Section 3017.1000 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF THE CHIEF FINANCIAL OFFICER, DEPARTMENT OF AGRICULTURE GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 3017.1000 Respondent...

Different radiosensitivities of mast-cell precursors in the bone marrow and skin of mice

International Nuclear Information System (INIS)

Kitamura, Y.; Yokoyama, M.; Sonoda, T.; Mori, K.J.

1983-01-01

Although tissue mast cells are derived from the bone marrow, some descendants of bone marrow-derived precursors retain the ability to proliferate and differentiate into mast cells even after localization in the skin. The purpose of the present study was to determine the D0 values for mast-cell precursors in the bone marrow and those localized in the skin. Bone marrow cells were removed from (WB X C57BL/6)F1-+/+ mice after various doses of irradiation and injected into the skin of the congenic W/Wv mice which were genetically without mast cells. Radiosensitivity of mast-cell precursors in the bone marrow was evaluated by determining the proportion of the injection sites at which mast cells did not appear. For the assay of the radiosensitivity of mast-cell precursors localized in the skin, pieces of skin were removed from beige C57BL/6 (bgJ/bgJ. Chediak-Higashi syndrome) mice after various doses of irradiation and grafted onto the back of the normal C57BL/6 mice. Radiosensitivity of mast-cell precursors in the skin was evaluated by determining the decrease of beige-type mast cells which possessed giant granules. Mast-cell precursors in the bone marrow were much more radiosensitive than those localized in the skin. D0 value was about 100 rad for the former and about 800 rad for the latter

Methamidophos alters sperm function and DNA at different stages of spermatogenesis in mice

International Nuclear Information System (INIS)

Urióstegui-Acosta, Mayrut; Hernández-Ochoa, Isabel; Sánchez-Gutiérrez, Manuel; Piña-Guzmán, Belem; Rafael-Vázquez, Leticia; Solís-Heredia, M.J.; Martínez-Aguilar, Gerardo; Quintanilla-Vega, Betzabet

2014-01-01

Methamidophos (MET) is a highly toxic organophosphate (OP) pesticide that is widely used in developing countries. MET has male reproductive effects, including decreased fertility. We evaluated MET effects on sperm quality, fertilization and DNA integrity, exploring the sensitivity of different stages of spermatogenesis. Adult male mice received MET (3.75 or 5 mg/kg-bw/ip/day/4 days) and were euthanized 1, 28 or 45 days post-treatment (dpt) to evaluate MET's effects on epididymal maturation, meiosis or mitosis, respectively. Spermatozoa were obtained from the cauda epididymis–vas deferens and were evaluated for sperm quality, acrosome reaction (AR; Coomassie staining), mitochondrial membrane potential (by JC-1), DNA damage (comet assay), oxidative damage (malondialdehyde (MDA) production), in vitro fertilization and protein phosphorylation (immunodetection), and erythrocyte acetylcholinesterase (AChE) activity. At 1-dpt, MET inhibited AChE (43–57%) and increased abnormal cells (6%). While at 28- and 45-dpt, sperm motility and viability were significantly reduced with an increasing MET dose, and abnormal morphology increased at 5 mg/kg/day/4 days. MDA and mitochondrial activity were not affected at any dose or time. DNA damage (OTM and %DNA) was observed at 5 mg/kg/day/4 days in a time-dependent manner, whereas both parameters were altered in cells from mice exposed to 3.75 mg/kg/day/4 days only at 28-dpt. Depending on the time of collection, initial-, spontaneous- and induced-AR were altered at 5 mg/kg/day/4 days, and the fertilization capacity also decreased. Sperm phosphorylation (at serine and tyrosine residues) was observed at all time points. Data suggest that meiosis and mitosis are the more sensitive stages of spermatogenesis for MET reproductive toxicity compared to epididymal maturation. - Highlights: • Methamidophos alters sperm cell function at different stages of spermatogenesis. • Testicular stages of spermatogenesis are more sensitive to

Methamidophos alters sperm function and DNA at different stages of spermatogenesis in mice

Energy Technology Data Exchange (ETDEWEB)

Urióstegui-Acosta, Mayrut; Hernández-Ochoa, Isabel [Departamento de Toxicología, CINVESTAV-IPN, D.F. (Mexico); Sánchez-Gutiérrez, Manuel [Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Hidalgo (Mexico); Piña-Guzmán, Belem [Instituto Politécnico Nacional-UPIBI, D.F. (Mexico); Rafael-Vázquez, Leticia; Solís-Heredia, M.J.; Martínez-Aguilar, Gerardo [Departamento de Toxicología, CINVESTAV-IPN, D.F. (Mexico); Quintanilla-Vega, Betzabet, E-mail: mquintan@cinvestav.mx [Departamento de Toxicología, CINVESTAV-IPN, D.F. (Mexico)

2014-09-15

Methamidophos (MET) is a highly toxic organophosphate (OP) pesticide that is widely used in developing countries. MET has male reproductive effects, including decreased fertility. We evaluated MET effects on sperm quality, fertilization and DNA integrity, exploring the sensitivity of different stages of spermatogenesis. Adult male mice received MET (3.75 or 5 mg/kg-bw/ip/day/4 days) and were euthanized 1, 28 or 45 days post-treatment (dpt) to evaluate MET's effects on epididymal maturation, meiosis or mitosis, respectively. Spermatozoa were obtained from the cauda epididymis–vas deferens and were evaluated for sperm quality, acrosome reaction (AR; Coomassie staining), mitochondrial membrane potential (by JC-1), DNA damage (comet assay), oxidative damage (malondialdehyde (MDA) production), in vitro fertilization and protein phosphorylation (immunodetection), and erythrocyte acetylcholinesterase (AChE) activity. At 1-dpt, MET inhibited AChE (43–57%) and increased abnormal cells (6%). While at 28- and 45-dpt, sperm motility and viability were significantly reduced with an increasing MET dose, and abnormal morphology increased at 5 mg/kg/day/4 days. MDA and mitochondrial activity were not affected at any dose or time. DNA damage (OTM and %DNA) was observed at 5 mg/kg/day/4 days in a time-dependent manner, whereas both parameters were altered in cells from mice exposed to 3.75 mg/kg/day/4 days only at 28-dpt. Depending on the time of collection, initial-, spontaneous- and induced-AR were altered at 5 mg/kg/day/4 days, and the fertilization capacity also decreased. Sperm phosphorylation (at serine and tyrosine residues) was observed at all time points. Data suggest that meiosis and mitosis are the more sensitive stages of spermatogenesis for MET reproductive toxicity compared to epididymal maturation. - Highlights: • Methamidophos alters sperm cell function at different stages of spermatogenesis. • Testicular stages of spermatogenesis are more sensitive to

Sarcopenia in older mice is characterized by a decreased anabolic response to a protein meal.

Science.gov (United States)

van Dijk, Miriam; Nagel, Jolanda; Dijk, Francina J; Salles, Jerôme; Verlaan, Sjors; Walrand, Stephane; van Norren, Klaske; Luiking, Yvette

Ageing is associated with sarcopenia, a progressive decline of skeletal muscle mass, muscle quality and muscle function. Reduced sensitivity of older muscles to respond to anabolic stimuli, i.e. anabolic resistance, is part of the underlying mechanisms. Although, muscle parameters have been studied in mice of various ages/strains; the aim was to study if mice display similar deteriorating processes as human ageing. Therefore, 10,16,21 and 25 months-old C57BL6/6J male mice were studied to measure parameters of sarcopenia and factors contributing to its pathophysiology, with the aim of characterizing sarcopenia in old mice. Muscle mass of the hind limb was lower in 25 as compared to 10 month-old mice. A significant decrease in physical daily activity, muscle grip strength and ex vivo muscle maximal force production was observed in 25 compared to 10 month-old mice. The muscle anabolic response to a single protein meal showed increased muscle protein synthesis in young, but not in old mice, indicative to anabolic resistance. However, by increasing the protein content in meals, anabolic resistance could be overcome, similar as in human elderly. Additionally, aged mice showed higher fasted insulin and hepatic malondialdehyde (MDA) levels (=marker oxidative stress). This study shows clear characteristics of sarcopenia that coincide with anabolic resistance, insulin resistance and oxidative stress in 25 month-old C57/BL6 male mice, similar to human ageing. Furthermore, similar decline in muscle mass, strength and function was observed in this aged-mice-model. These observations offer potential for the future to explore in old mice the effects of interventions targeting sarcopenia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Application of a naturalistic psychogenic stressor in periadolescent mice: effect on serum corticosterone levels differs by strain but not sex

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Klein Laura C

2010-06-01

Full Text Available Abstract Background As a first step in determining whether psychogenic stressors might be incorporated into periadolescent mouse models of stress, we evaluated whether a commonly used psychogenic stressor, exposure to red fox urine, alters serum corticosterone levels in periadolescent C57BL/6J and DBA/2J mice. Findings In a 1-day experiment, forty-eight 38-day-old C57BL/6J (N = 12 males; N = 12 females and DBA/2J (N = 12 males; N = 12 females mice were exposed to 10-min of red fox urine via cotton ball (N = 12 C57BL/6J mice; N = 12 DBA/2J mice or to a non-saturated cotton ball (N = 12 C57BL/6J mice; N = 12 DBA/2J mice. All mice were sacrificed 15-min after cotton ball exposure and serum was collected for corticosterone assessment. Overall, there was a main effect for strain such that C57BL/6J male and female mice displayed higher corticosterone levels than did male and female DBA/2J mice. There were no main effects for sex or odor exposure. However, there was a significant strain by odor exposure interaction, whereby, within odor-exposed mice, DBA/2J mice displayed lower corticosterone levels (ng/mL compared to C57BL/6J mice, regardless of sex. Further, among DBA/2J mice, predator odor exposure reduced corticosterone levels compared to no odor exposure. Conclusions Findings indicate that mouse strain, but not sex, may play an important role in the efficacy of a predator odor among periadolescent mice.

The perception for Good Death of community dwelling Japanese and Thailand respondents

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Michiyo Ando

2016-11-01

Full Text Available Having a “good death” is a very important goal of palliative care, and it is useful for nurses to understand cultural differences in the perception of a good death to propose nursing care. The purpose of this study was to compare the perception of a “good death” among community-dwelling Japanese and Thai people. Three hundred sixty-nine respondents completed the Good Death Questionnaire. The research design was a cross-sectional study. The scores of the Japanese respondents on “good relationships with medical staff,” “being respected as an individual,” and “fighting against cancer” were higher among Thai respondents. On the other hand, “environmental comfort,” “unawareness of death,” “control over the future,” and “religious and spiritual comfort” were higher among the Japanese respondents. Among the Japanese, the score for “life completion” was significantly correlated with “role accomplishment and contribution to others.” Among the Thai respondents, the score for “good relationships with family” was significantly correlated with “physical and cognitive control.” The implications of these results were that Japanese respondents preferred medical treatments, maintaining a good relationship with physicians, and demanding to be respected as an individual. Thai respondent’s preferred “environmental comfort” and “religious and spiritual comfort.” In the future, medical staff members will need to consider these cultural differences when proposing nursing care.

Of mice and (Viking?) men: phylogeography of British and Irish house mice.

Science.gov (United States)

Searle, Jeremy B; Jones, Catherine S; Gündüz, Islam; Scascitelli, Moira; Jones, Eleanor P; Herman, Jeremy S; Rambau, R Victor; Noble, Leslie R; Berry, R J; Giménez, Mabel D; Jóhannesdóttir, Fríoa

2009-01-22

The west European subspecies of house mouse (Mus musculus domesticus) has gained much of its current widespread distribution through commensalism with humans. This means that the phylogeography of M. m. domesticus should reflect patterns of human movements. We studied restriction fragment length polymorphism (RFLP) and DNA sequence variations in mouse mitochondrial (mt) DNA throughout the British Isles (328 mice from 105 localities, including previously published data). There is a major mtDNA lineage revealed by both RFLP and sequence analyses, which is restricted to the northern and western peripheries of the British Isles, and also occurs in Norway. This distribution of the 'Orkney' lineage fits well with the sphere of influence of the Norwegian Vikings and was probably generated through inadvertent transport by them. To form viable populations, house mice would have required large human settlements such as the Norwegian Vikings founded. The other parts of the British Isles (essentially most of mainland Britain) are characterized by house mice with different mtDNA sequences, some of which are also found in Germany, and which probably reflect both Iron Age movements of people and mice and earlier development of large human settlements. MtDNA studies on house mice have the potential to reveal novel aspects of human history.

Effect of Different Thermal Neutron Fluxes on Blood of Male Mice

International Nuclear Information System (INIS)

Abd El-Latif, A.A.; Saeid, Kh. S.; Abd El-Latif, A.A.; Emara, N.M.; Emara, N.M.

2010-01-01

This work deals with the exposing of male mice to different fluxes of thermal neutron .Investigation has been performed by calculating of thermal neutron fluxes(0.27x10 8 N/cm 2 . 1h , 0.54x10 8 N/cm 2 . 1h, 1.08x10 8 N/cm 2 . 1h, 2.16x10 8 N/cm 2 . 3h and 4.32x10 8 N/cm 2 . 6h) which emitted from neutron irradiation cell with source Ra - Be (α,n) have activity 3 m. Ci made by leybold(55930) . The number and differential leucocytes counts types of white blood cells in million per cubic millimeter (W. B. Cs. mm -3 ) ,the number of platelets mm -3 ,the number of red blood cells in million per cubic millimeter (R. B. Cs. mm -3 ), the hemoglobin in Blood (mg/dl), the lymphocytes ,and the eosiniphil leucocytes in blood decrease with increasing thermal neutron fluxes. But neutrophile and monocytes in blood increase with increasing the thermal neutron fluxes

Different importance of the volatile and non-volatile fractions of an olfactory signature for individual social recognition in rats versus mice and short-term versus long-term memory.

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Noack, Julia; Richter, Karin; Laube, Gregor; Haghgoo, Hojjat Allah; Veh, Rüdiger W; Engelmann, Mario

2010-11-01

When tested in the olfactory cued social recognition/discrimination test, rats and mice differ in their retention of a recognition memory for a previously encountered conspecific juvenile: Rats are able to recognize a given juvenile for approximately 45 min only whereas mice show not only short-term, but also long-term recognition memory (≥ 24 h). Here we modified the social recognition/social discrimination procedure to investigate the neurobiological mechanism(s) underlying the species differences. We presented a conspecific juvenile repeatedly to the experimental subjects and monitored the investigation duration as a measure for recognition. Presentation of only the volatile fraction of the juvenile olfactory signature was sufficient for both short- and long-term recognition in mice but not rats. Applying additional volatile, mono-molecular odours to the "to be recognized" juveniles failed to affect short-term memory in both species, but interfered with long-term recognition in mice. Finally immunocytochemical analysis of c-Fos as a marker for cellular activation, revealed that juvenile exposure stimulated areas involved in the processing of olfactory signals in both the main and the accessory olfactory bulb in mice. In rats, we measured an increased c-Fos synthesis almost exclusively in cells of the accessory olfactory bulb. Our data suggest that the species difference in the retention of social recognition memory is based on differences in the processing of the volatile versus non-volatile fraction of the individuals' olfactory signature. The non-volatile fraction is sufficient for retaining a short-term social memory only. Long-term social memory - as observed in mice - requires a processing of both the volatile and non-volatile fractions of the olfactory signature. Copyright © 2010 Elsevier Inc. All rights reserved.

Gene expression-based classifiers identify Staphylococcus aureus infection in mice and humans.

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Sun Hee Ahn

Full Text Available Staphylococcus aureus causes a spectrum of human infection. Diagnostic delays and uncertainty lead to treatment delays and inappropriate antibiotic use. A growing literature suggests the host's inflammatory response to the pathogen represents a potential tool to improve upon current diagnostics. The hypothesis of this study is that the host responds differently to S. aureus than to E. coli infection in a quantifiable way, providing a new diagnostic avenue. This study uses Bayesian sparse factor modeling and penalized binary regression to define peripheral blood gene-expression classifiers of murine and human S. aureus infection. The murine-derived classifier distinguished S. aureus infection from healthy controls and Escherichia coli-infected mice across a range of conditions (mouse and bacterial strain, time post infection and was validated in outbred mice (AUC>0.97. A S. aureus classifier derived from a cohort of 94 human subjects distinguished S. aureus blood stream infection (BSI from healthy subjects (AUC 0.99 and E. coli BSI (AUC 0.84. Murine and human responses to S. aureus infection share common biological pathways, allowing the murine model to classify S. aureus BSI in humans (AUC 0.84. Both murine and human S. aureus classifiers were validated in an independent human cohort (AUC 0.95 and 0.92, respectively. The approach described here lends insight into the conserved and disparate pathways utilized by mice and humans in response to these infections. Furthermore, this study advances our understanding of S. aureus infection; the host response to it; and identifies new diagnostic and therapeutic avenues.

Survey sustainability Biomass. Appendix. Results of the international respondents

Energy Technology Data Exchange (ETDEWEB)

Bergsma, G.C.; Groot, M.I.

2006-06-15

As part of an array of strategies to combat climate change, biomass is being used increasingly as a substitute for fossil fuels. It is important that the sustainability benefits thus accruing to the Netherlands are not at the expense of sustainable development in producer countries. Against this background the 'Sustainable biomass imports' project group is developing a set of criteria for evaluating the sustainability of biomass projects. To assess support for such criteria, CE conducted an internet survey among the various stakeholders (NGOs, industry, government), drawing a total of 104 responses. This report presents all the results and conclusions of the survey, for each category of stakeholders and overall. Among the most striking conclusions are the following: The majority of respondents see a sustainability audit on biomass as feasible, provided the sustainability criteria are adequate for the purpose (68%); Almost all the respondents are of the opinion that such sustainability criteria should apply to all applications of biomass (90%); On the issue of whether these criteria should vary according to the producer region concerned, respondents were divided (50% for, 50% against); Many NGOs state there should be different sustainability criteria in force for different biomass flows (50%), in contrast to industry, which argues for a uniform set of criteria for all flows; Most respondents hold that any biomass criteria should apply to both subsidised and unsubsidised projects; At the same time, a sizable majority of respondents state that subsidisation of biomass projects should depend on the degree of sustainability (72%) and in particular on the CO2 emission cuts achieved, this being regarded as the single most important factor; When it comes to the issue of GMO, opinions differ markedly between NGOs and industry, with some 75% of NGOs wanting this aspect included, but only 10% of industry; Respondents also commented on a number of additional issues

Differences in muscarinic acetylcholine receptor subtypes in the central nervous system of long sleep and short sleep mice

International Nuclear Information System (INIS)

Watson, M.; Ming, X.; McArdle, J.J.

1989-01-01

Differences in voluntary ethanol consumption have been noted in various inbred strains of mice and pharmacogenetic approaches have been used to study the mechanisms of action of many drugs such as ethanol. Long-sleep (LS) and short-sleep (SS) mice, selectively bred for differences in ethanol induced narcosis, provide a method by which a relationship between the differential responsiveness of these geno-types and muscarinic acetylcholine receptors (mAChR) may be evaluated. Sleep times after injection of 3ml ethanol/kg (i.p.) verified the higher sensitivity of LS vs. SS. Mean body weights of LS (26.5g) vs. SS (22g) were also significantly (p 3 H](-) quinuclidinylbenzilate ([ 3 H](-)QNB), a specific but nonsubtype selective mAChR antagonist, [ 3 H]pirenzepine ([ 3 H]PZ), a specific M1 mAChR antagonist and [ 3 H]11-2-[[2-[(diethylamino) methyl]-1-piperidinyl] acetyl]-5,11-dihydro-6H-pyrido (2,3-b) (1,4) benzodiazepine-6-one, ([ 3 H]AF-DX 116), an M2 selective antagonist were performed to determine mAChR affinity (K d ) and density (B max ) in CNS regions such as the cerebral cortex, hippocampus, corpus striatum and other areas. Significantly lower (30-40%) [ 3 H](-)QNB binding suggests that SS have fewer mAChR's than LS in many areas. These differences may relate to their differential ethanol sensitivity

Altered Expression of Somatostatin Receptors in Pancreatic Islets from NOD Mice Cultured at Different Glucose Concentrations In Vitro and in Islets Transplanted to Diabetic NOD Mice In Vivo

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Eva Ludvigsen

2011-01-01

Full Text Available Somatostatin acts via five receptors (sst1-5. We investigated if the changes in pancreatic islet sst expression in diabetic NOD mice compared to normoglycemic mice are a consequence of hyperglycemia or the ongoing immune reaction in the pancreas. Pancreatic islets were isolated from NOD mice precultured for 5 days and further cultured for 3 days at high or low glucose before examined. Islets were also isolated from NOD mice and transplanted to normal or diabetic mice in a number not sufficient to cure hyperglycemia. After three days, the transplants were removed and stained for sst1-5 and islet hormones. Overall, changes in sst islet cell expression were more common in islets cultured in high glucose concentration in vitro as compared to the islet transplantation in vivo to diabetic mice. The beta and PP cells exhibited more frequent changes in sst expression, while the alpha and delta cells were relatively unaffected by the high glucose condition. Our findings suggest that the glucose level may alter sst expressed in islets cells; however, immune mechanisms may counteract such changes in islet sst expression.

Add-On Aliskiren Elicits Stronger Renoprotection Than High-Dose Valsartan in Type 2 Diabetic KKAy Mice That Do Not Respond to Low-Dose Valsartan

Science.gov (United States)

Lei, Bai; Nakano, Daisuke; Fan, Yu-Yan; Kitada, Kento; Hitomi, Hirofumi; Kobori, Hiroyuki; Mori, Hirohito; Masaki, Tsutomu; Nishiyama, Akira

2012-01-01

We hypothesized that aliskiren provides renoprotection in diabetic animals that did not receive sufficient renoprotection by AT1-receptor antagonist treatment. Type 2 diabetic KKAy mice were treated with group 1: vehicle or group 2: valsartan (15 mg/kg per day) from 12 to 16 weeks of age. The mice were subsequently divided into 4 groups and treated with the following combinations of drugs for another 6 weeks: 1: group 1 kept receiving vehicle, 2: group 2 continuously received 15 mg/kg per day of valsartan (Val-Val15), 3: group 2 received 50 mg/kg per day of valsartan (Val-Val50), 4: group 2 continuously received 15 mg/kg per day of valsartan with 25 mg/kg per day of aliskiren (Val-Val+Ali). Aliskiren exerted significant anti-albuminuric effects, whereas valsartan failed to ameliorate the albuminuria in the first four weeks. Surprisingly, the increasing dosage of valsartan in the Val-Val50 group showed non-significant tendencies to attenuate the albuminuria compared with vehicle infusion. Val-Val+Ali significantly suppressed the development of albuminuria and podocyte injury. Val-Val50 and Val-Val+Ali showed similar suppression of angiotensin II contents in the kidney of KKAy mice. In conclusion, the anti-albuminuric effect that was observed in the type 2 diabetic mice showing no anti-albuminuric effect by valsartan can be attributed to the add-on aliskiren. PMID:22673148

Lifespan studies on different strains of mice exposed chronically to low levels of whole body gamma irradiation

International Nuclear Information System (INIS)

Fox, L.A.; Klein, A.K.; Cain, G.R.; Rosenblatt, L.S.

1982-01-01

Several strains of mice, chosen for their predisposition to immunohematological disorders, were exposed to low levels of 60 irradiation continuously for four weeks. All individuals were subsequently followed throughout their lifetimes. W/W/sup v/ mice, which are tyically subject to a stem cell deficiency, had a lower cumulative survival rate for the irradiated group than for the unirradiated controls. Irradiated RF/sub j/ mice had a dramatically lower cumulative survival rate than their unirradiated controls. Conversely, BXSB mice, which have a lumphoproliferative autoimmune disorder, had a higher cumulative survival rate after chronic irradiation than did unirradiated BXSBs. Irradiation had no effect upon the survival rate curves of the NZB strain, the murine model for Lupus Erythematosus

Selection for high and low oxygen consumption-induced differences in maintenance energy requirements of mice.

Science.gov (United States)

Darhan, Hongyu; Kikusato, Motoi; Toyomizu, Masaaki; Roh, Sang-Gun; Katoh, Kazuo; Sato, Masahiro; Suzuki, Keiichi

2017-07-01

Maintenance energy requirements (MER) of mice selected for high (H) or low (L) oxygen consumption (OC) were compared. Forty-four mice from H and L OC lines were weaned at 3 weeks and divided into four experimental groups: group A were sacrificed at 4 weeks; group B were fed ad libitum, and groups C and D were fed 2.8 and 2.4 g/day, respectively, from 4 to 8 weeks of age. Groups B-D were sacrificed at 8 weeks. Chemical components were estimated for all groups. MER was estimated using a model that partitioned metabolizable energy intake into that used for maintenance, and protein and fat deposition. The feed conversion ratio for the B group was significantly higher in the H than in the L line. Feed intake for metabolic energy content per metabolic body size was significantly also higher in the H line, whereas accumulated energy content per metabolic body size was significantly higher in the L line. MER of the H line was greater than that of the L line (P < 0.10). These results suggest that selection for H or L OC produced differences in chemical components, feed efficiency, and MER between the H and L lines. © 2016 Japanese Society of Animal Science.

Mobile-Only Web Survey Respondents

NARCIS (Netherlands)

Lugtig, P.J.|info:eu-repo/dai/nl/304824658; Toepoel, V.|info:eu-repo/dai/nl/304576034; amin, alerk

2016-01-01

Web surveys are no longer completed on just a desktop or laptop computer. Respondents increasingly use mobile devices, such as tablets and smartphones to complete web surveys. In this article, we study how respondents in the American Life Panel complete surveys using varying devices. We show that

Nicotine response and nicotinic receptors in long-sleep and short-sleep mice.

Science.gov (United States)

De Fiebre, C M; Medhurst, L J; Collins, A C

1987-01-01

Nicotine response and nicotinic receptor binding were characterized in long-sleep (LS) and short-sleep (SS) mice which have been selectively bred for differential "sleep-time" following ethanol administration. LS mice are more sensitive than SS mice to nicotine as measured by a battery of behavioral and physiological tests and as measured by sensitivity to nicotine-induced seizures. The greater sensitivity of the LS mice is not due to differences in binding of [3H]nicotine. Unlike inbred mouse strains which differ in sensitivity to nicotine-induced seizures, these selected mouse lines do not differ in levels of binding of [125I]alpha-bungarotoxin (BTX) in the hippocampus. Significant differences in BTX binding were found in the cerebellum and striatum. Although these two mouse lines do not differ in blood levels of nicotine following nicotine administration, they differ slightly in brain levels of nicotine indicating differential distribution of the drug. Since this distribution difference is much smaller than the observed behavioral differences, these mice probably differ in CNS sensitivity to nicotine; however, follow-up studies are necessary to test whether the differential response of these mice is due to subtle differences in distribution of nicotine to the brain.

Two-year body composition analyses of long-lived GHR null mice.

Science.gov (United States)

Berryman, Darlene E; List, Edward O; Palmer, Amanda J; Chung, Min-Yu; Wright-Piekarski, Jacob; Lubbers, Ellen; O'Connor, Patrick; Okada, Shigeru; Kopchick, John J

2010-01-01

Growth hormone receptor gene-disrupted (GHR-/-) mice exhibit increased life span and adipose tissue mass. Although this obese phenotype has been reported extensively for young adult male GHR-/- mice, data for females and for other ages in either gender are lacking. Thus, the purpose of this study was to evaluate body composition longitudinally in both male and female GHR-/- mice. Results show that GHR-/- mice have a greater percent fat mass with no significant difference in absolute fat mass throughout life. Lean mass shows an opposite trend with percent lean mass not significantly different between genotypes but absolute mass reduced in GHR-/- mice. Differences in body composition are more pronounced in male than in female mice, and both genders of GHR-/- mice show specific enlargement of the subcutaneous adipose depot. Along with previously published data, these results suggest a consistent and intriguing protective effect of excess fat mass in the subcutaneous region.

The difference a word makes: responding to questions on 'disability' and 'difficulty' in South Africa.

Science.gov (United States)

Schneider, Marguerite

2009-01-01

This article discusses the current efforts to measure disability in a comparable manner internationally, the effects of using different types of wording in questions, and the implications of the approach of asking about 'difficulties' rather than 'disability' on the use of disability statistics. The study design was qualitative. Twenty-one focus groups were run with adults responding for themselves. Nine groups were classified a priori by the author as 'disabled', six as 'unsure', and the last six as 'non-disabled'. The participants completed a questionnaire using the Washington Group on Disability Statistics (WG) Short Set, the South African Census 2001 question, and the question 'Are you disabled?'. This was followed by group discussion on these questions and on how the concept of disability is understood by group participants. Participants understand disability as being a permanent, unchangeable state, mostly physical, and where a person is unable to do anything. The participants in the three groups of allocated disability status (disabled, unsure and non-disabled) provided quite different responses on the three questions. All participants in the 'disabled' and 'unsure' groups reported having 'difficulty' on the WG questions, but the 'unsure' groups did not identify as being 'disabled' on either of the two other questions. Using questions that ask about 'difficulty' rather than 'disability' provides a more comprehensive and inclusive measure of disability with a clearer understanding of what is being measured. Asking about 'difficulty' provides an improved measure of disability status for effective data collection and analysis to promote development, implementation and monitoring of disability-inclusive policies.

AGEMAP: a gene expression database for aging in mice.

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Jacob M Zahn

2007-11-01

Full Text Available We present the AGEMAP (Atlas of Gene Expression in Mouse Aging Project gene expression database, which is a resource that catalogs changes in gene expression as a function of age in mice. The AGEMAP database includes expression changes for 8,932 genes in 16 tissues as a function of age. We found great heterogeneity in the amount of transcriptional changes with age in different tissues. Some tissues displayed large transcriptional differences in old mice, suggesting that these tissues may contribute strongly to organismal decline. Other tissues showed few or no changes in expression with age, indicating strong levels of homeostasis throughout life. Based on the pattern of age-related transcriptional changes, we found that tissues could be classified into one of three aging processes: (1 a pattern common to neural tissues, (2 a pattern for vascular tissues, and (3 a pattern for steroid-responsive tissues. We observed that different tissues age in a coordinated fashion in individual mice, such that certain mice exhibit rapid aging, whereas others exhibit slow aging for multiple tissues. Finally, we compared the transcriptional profiles for aging in mice to those from humans, flies, and worms. We found that genes involved in the electron transport chain show common age regulation in all four species, indicating that these genes may be exceptionally good markers of aging. However, we saw no overall correlation of age regulation between mice and humans, suggesting that aging processes in mice and humans may be fundamentally different.

Voluntary exercise inhibits intestinal tumorigenesis in ApcMin/+ mice and azoxymethane/dextran sulfate sodium-treated mice

International Nuclear Information System (INIS)

Ju, Jihyeung; Nolan, Bonnie; Cheh, Michelle; Bose, Mousumi; Lin, Yong; Wagner, George C; Yang, Chung S

2008-01-01

Epidemiological studies suggest that physical activity reduces the risk of colon cancer in humans. Results from animal studies, however, are inconclusive. The present study investigated the effects of voluntary exercise on intestinal tumor formation in two different animal models, Apc Min/+ mice and azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice. In Experiments 1 and 2, five-week old female Apc Min/+ mice were either housed in regular cages or cages equipped with a running wheel for 6 weeks (for mice maintained on the AIN93G diet; Experiment 1) or 9 weeks (for mice on a high-fat diet; Experiment 2). In Experiment 3, male CF-1 mice at 6 weeks of age were given a dose of AOM (10 mg/kg body weight, i.p.) and, 12 days later, 1.5% DSS in drinking fluid for 1 week. The mice were then maintained on a high-fat diet and housed in regular cages or cages equipped with a running wheel for 16 weeks. In the Apc Min/+ mice maintained on either the AIN93G or the high-fat diet, voluntary exercise decreased the number of small intestinal tumors. In the AOM/DSS-treated mice maintained on a high-fat diet, voluntary exercise also decreased the number of colon tumors. In Apc Min/+ mice, voluntary exercise decreased the ratio of serum insulin like growth factor (IGF)-1 to IGF binding protein (BP)-3 levels. It also decreased prostaglandin E 2 and nuclear β-catenin levels, but increased E-cadherin levels in the tumors. These results indicate hat voluntary exercise inhibited intestinal tumorigenesis in Apc Min/+ mice and AOM/DSS-treated mice, and the inhibitory effect is associated with decreased IGF-1/IGFBP-3 ratio, aberrant β-catenin signaling, and arachidonic acid metabolism

Energy metabolism in BPH/2J genetically hypertensive mice.

Science.gov (United States)

Jackson, Kristy L; Nguyen-Huu, Thu-Phuc; Davern, Pamela J; Head, Geoffrey A

2014-05-01

Recent evidence indicates that genetic hypertension in BPH/2J mice is sympathetically mediated, but these mice also have lower body weight (BW) and elevated locomotor activity compared with BPN/3J normotensive mice, suggestive of metabolic abnormalities. The aim of the present study was to determine whether hypertension in BPH/2J mice is associated with metabolic differences. Whole-body metabolic and cardiovascular parameters were measured over 24 h by indirect calorimetry and radiotelemetry respectively, in conscious young (10-13 weeks) and older (22-23 weeks) BPH/2J, normotensive BPN/3J and C57Bl6 mice. Blood pressure (BP) was greater in BPH/2J compared with both normotensive strains at both ages (PBPH/2J compared with BPN/3J mice (PBPH/2J and normotensive mice when adjusted for activity (P>0.1) suggesting differences in this relationship are not responsible for hypertension. EchoMRI revealed that percentage body composition was comparable in BPN/3J and BPH/2J mice (P>0.1) and both strains gained weight similarly with age (P=0.3). Taken together, the present findings indicate that hypertension in BPH/2J mice does not appear to be related to altered energy metabolism.

Dark reticular cells in the thymus of mice

Energy Technology Data Exchange (ETDEWEB)

Jaerplid, B [Foersvarets Forskningsanstalt, Stockholm (Sweden)

1974-01-01

The morphology and distribution of dark reticular cells in the thymus of normal mice, of irradiated mice, and of mice with thymic lymphoma are described. It is concluded that dark cells are epithelial reticular cells and the hypothesis is suggested that dark and light epithelial reticular cells may be different modes of expression of the same cell type. (auth)

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.

Infanticide: accounting for genetic variation in mice.

Science.gov (United States)

Svare, B; Kinsley, C H; Mann, M A; Broida, J

1984-07-01

Infanticide, the killing of young, is one of a number of sexually-dimorphic traits in mice that is dependent upon androgen stimulation during perinatal life and during adulthood. Genotype also influences infanticide in that males of some strains of mice (C57BL/6J) exhibit high levels of this behavior while males of other strains (DBA/2J) seldom kill young. The experiments conducted here show that strain differences in pup killing behavior exhibited by males are not related to postweaning social factors nor are they due to differences in perinatal, pubertal, or adult levels of circulating hormones. These results, in combination with those previously reported, suggest that strain differences in the tendency of mice to kill young may instead depend upon the interaction of genotypic features such as prenatal hormone titers and/or sensitivity to these hormones, as well as on extra organismic factors such as intrauterine position. A model for understanding the manner in which genes and hormones may interact to influence infanticide and other hormone dependent sexually-dimorphic behaviors in mice is presented.

Hexachlorobenzene stimulates uroporphyria in low affinity AHR mice without increasing CYP1A2

International Nuclear Information System (INIS)

Gorman, Nadia; Trask, Heidi S.; Robinson, Susan W.; Sinclair, Jacqueline F.; Gerhard, Glenn S.; Smith, Andrew G.; Sinclair, Peter R.

2007-01-01

Hexachlorobenzene (HCB), a weak ligand of the aryl hydrocarbon receptor (AHR), causes hepatic uroporphyrin (URO) accumulation (uroporphyria) in humans and animals. CYP1A2 has been shown to be necessary in the development of uroporphyria in mice. Using mice expressing the low affinity form of the AH receptor (AHRd), we investigated whether the enhancement of uroporphyria by HCB involves an obligatory increase in CYP1A2 as measured by specific enzyme assays and immunoblotting. We compared the ability of HCB, in combination with iron dextran and the porphyrin precursor, 5-aminolevulinate (ALA), to cause uroporphyria in a strain of mice (C57BL/6) which expresses the high affinity form of the receptor (AHRb 1 ), with three strains of mice (SWR and two 129 sublines) expressing the low affinity AHRd. In C57BL/6 mice, HCB-enhanced uroporphyria was associated with a doubling of CYP1A2. HCB treatment produced uroporphyria in iron-loaded mice expressing AHRd, even though there was little or no increase in CYP1A2. Cyp1a2(-/-) mice in a 129 background were completely resistant to HCB-induced uroporphyria, and female Hfe(-/-) 129 mice, in which the levels of hepatic CYP1A2 were half of those of the male levels, responded poorly. The effect of exogenous iron, administered in the form of iron dextran, on HCB enhancement of uroporphryia could be replicated utilizing the endogenous hepatic iron accumulated in 129 Hfe(-/-) mice. In conclusion, some minimal basal expression of CYP1A2 is essential for HCB-mediated enhancement of uroporphyria, but increases in CYP1A2 above that level are not essential

T-helper 17 and interleukin-17-producing lymphoid tissue inducer-like cells make different contributions to colitis in mice.

Science.gov (United States)

Ono, Yuichi; Kanai, Takanori; Sujino, Tomohisa; Nemoto, Yasuhiro; Kanai, Yasumasa; Mikami, Yohei; Hayashi, Atsushi; Matsumoto, Atsuhiro; Takaishi, Hiromasa; Ogata, Haruhiko; Matsuoka, Katsuyoshi; Hisamatsu, Tadakazu; Watanabe, Mamoru; Hibi, Toshifumi

2012-11-01

T helper (Th) 17 cells that express the retinoid-related orphan receptor (ROR) γt contribute to the development of colitis in mice, yet are found in normal and inflamed intestine. We investigated their development and functions in intestines of mice. We analyzed intestinal Th17 cells in healthy and inflamed intestinal tissues of mice. We analyzed expression of lymphotoxin (LT)α by Th17 cells and lymphoid tissue inducer-like cells. LTα(-/-) and RORγt(-/-) mice had significantly lower percentages of naturally occurring Th17 cells in the small intestine than wild-type mice. Numbers of CD3(-)CD4(+/-)interleukin-7Rα(+)c-kit(+)CCR6(+)NKp46(-) lymphoid tissue inducer-like cells that produce interleukin-17A were increased in LTα(-/-) and LTα(-/-) × recombination activating gene (RAG)-2(-/-) mice, compared with wild-type mice, but were absent from RORγt(-/-) mice. Parabiosis of wild-type and LTα(-/-) mice and bone marrow transplant experiments revealed that LTα-dependent gut-associated lymphoid tissue structures are required for generation of naturally occurring Th17 cells. However, when wild-type or LTα(-/-) CD4(+)CD45RB(high) T cells were transferred to RAG-2(-/-) or LTα(-/-)×RAG-2(-/-) mice, all groups, irrespective of the presence or absence of LTα on the donor or recipient cells, developed colitis and generated Th1, Th17, and Th17/Th1 cells. RAG-2(-/-) mice that received a second round of transplantation, with colitogenic but not naturally occurring Th17 cells, developed intestinal inflammation. The presence of naturally occurring Th17 cells in the colons of mice inhibited development of colitis after transfer of CD4(+)CD45RB(high) T cells and increased the numbers of Foxp3(+) cells derived from CD4(+)CD45RB(high) T cells. Gut-associated lymphoid tissue structures are required to generate naturally occurring Th17 cells that have regulatory activities in normal intestines of mice, but not for colitogenic Th17 and Th17/Th1 cells during inflammation

Responder Technology Alert (February 2015)

Energy Technology Data Exchange (ETDEWEB)

Upton, Jaki F. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Stein, Steven L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2015-04-10

As part of technology foraging for the Responder Technology Alliance, established by the Department of Homeland Science and Technologies First Responders Group, this report summarizes technologies that are relevant in the area of “wearables,” with the potential for use by first responders. The content was collected over the previous month(s) and reproduced from a general Internet search using the term wearables. Additional information is available at the websites provided. This report is not meant to be an exhaustive list nor an endorsement of any technology described herein. Rather, it is meant to provide useful information about current developments in the areas wearable technology.

Different radiosensitivities of mast-cell precursors in the bone marrow and skin of mice

International Nuclear Information System (INIS)

Kitamura, Y.; Yokoyama, M.; Sonoda, T.; Mori, K.J.

1983-01-01

Although tissue mast cells are derived from the bone marrow, some descendants of bone marrow-derived precursors retain the ability to proliferate and differentiate into mast cells even after localization in the skin. The purpose of the present study was to determine the D 0 values for mast-cell precursors in the bone marrow and those localized in the skin. Bone marrow cells were removed from (WB X C57BL/6)F 1 +/+ mice after various doses of irradiation and injected into the skin of the congenic W/W/sup v/ mice which were genetically without mast cells. Radiosensitivity of mast-cell precursors in the bone marrow was evaluated by determining the proportion of the injection sites at which mast cells did not appear. For the assay of the radiosensitivity of mast-cell precursors localized in the skin, pieces of skin were removed from beige C57BL/6 (bg/sup J//bg/sup J/, Chediak-Higashi syndrome) mice after various doses of irradiation and grafted onto the backs of the normal C57BL/6 mice. Radiosensitivity of mast-cell precursors in the skin was evaluated by determining the decrease of beige-type mast cells which possessed giant granules. Mast-cell precursors in the bone marrow were much more radiosenitive than those localized in the skin. D 0 value was about 100 rad for the former and about 800 rad for the latter

Dominant lethal mutations in male mice fed γ-irradiated diet

International Nuclear Information System (INIS)

Chauhan, P.S.; Aravindakshan, M.; Aiyer, A.S.; Sundaram, K.

1975-01-01

Three groups of Swiss male mice were fed a stock ration of an unirradiated or irradiated (2.5 Mrad) test diet for 8 wk. After the feeding period, the males were mated with groups of untreated female mice for 4 consecutive weeks. The females were autopsied at mid-term pregnancy for evaluation of dominant lethal mutations. Numbers of dead implantations, including deciduomas and dead embryos, showed no significant differences among the different groups, thus producing no evidence of any induced post-implantation lethality in mice fed on irradiated diet. Similarly, there was no indication of preimplantation lethality, since implantation rates remained comparable among different groups. Consumption of irradiated diet did not affect the fertility of mice. Total pre- and post-implantation loss, as indicated by the numbers of live implantations remained comparable among all the groups of mice. (author)

A conditioned aversion study of sucrose and SC45647 taste in TRPM5 knockout mice.

Science.gov (United States)

Eddy, Meghan C; Eschle, Benjamin K; Peterson, Darlene; Lauras, Nathan; Margolskee, Robert F; Delay, Eugene R

2012-06-01

Previously, published studies have reported mixed results regarding the role of the TRPM5 cation channel in signaling sweet taste by taste sensory cells. Some studies have reported a complete loss of sweet taste preference in TRPM5 knockout (KO) mice, whereas others have reported only a partial loss of sweet taste preference. This study reports the results of conditioned aversion studies designed to motivate wild-type (WT) and KO mice to respond to sweet substances. In conditioned taste aversion experiments, WT mice showed nearly complete LiCl-induced response suppression to sucrose and SC45647. In contrast, TRPM5 KO mice showed a much smaller conditioned aversion to either sweet substance, suggesting a compromised, but not absent, ability to detect sweet taste. A subsequent conditioned flavor aversion experiment was conducted to determine if TRPM5 KO mice were impaired in their ability to learn a conditioned aversion. In this experiment, KO and WT mice were conditioned to a mixture of SC45647 and amyl acetate (an odor cue). Although WT mice avoided both components of the stimulus mixture, they avoided SC45647 more than the odor cue. The KO mice also avoided both stimuli, but they avoided the odor component more than SC45647, suggesting that while the KO mice are capable of learning an aversion, to them the odor cue was more salient than the taste cue. Collectively, these findings suggest the TRPM5 KO mice have some residual ability to detect SC45647 and sucrose, and, like bitter, there may be a TRPM5-independent transduction pathway for detecting these substances.

Changes in the pharmacokinetics of digoxin in polyuria in streptozotocin-induced diabetic mice and lithium carbonate-treated mice.

Science.gov (United States)

Ikarashi, Nobutomo; Kagami, Mai; Kobayashi, Yasushi; Ishii, Makoto; Toda, Takahiro; Ochiai, Wataru; Sugiyama, Kiyoshi

2011-06-01

In humans, digoxin is mainly eliminated through the kidneys unchanged, and renal clearance represents approximately 70% of the total clearance. In this study, we used the mouse models to examine digoxin pharmacokinetics in polyuria induced by diabetes mellitus and lithium carbonate (Li(2)CO(3)) administration, including mechanistic evaluation of the contribution of glomerular filtration, tubular secretion, and tubular reabsorption. After digoxin administration to streptozotocin (STZ)-induced diabetic mice, digoxin CL/F increased to approximately 2.2 times that in normal mice. After treatment with Li(2)CO(3) (0.2%) for 10 days, the CL/F increased approximately 1.1 times for normal mice and 1.6 times for STZ mice. Creatinine clearance (CLcr) and the renal mRNA expression levels of mdr1a did not differ significantly between the normal, STZ, and Li(2)CO(3)-treated mice. The urine volume of STZ mice was approximately 26 mL/day, 22 times that of normal mice. The urine volume of Li(2)CO(3)-treated mice increased approximately 7.3 times for normal mice and 2.3 times for STZ mice. These results suggest that the therapeutic effect of digoxin may be significantly reduced in the presence of polyuria either induced by diabetes mellitus or manifested as an adverse effect of Li(2)CO(3) in diabetic patients, along with increased urine volume.

Factors related to resistance to hematopoietic death in mice

International Nuclear Information System (INIS)

Mori, Nobuko; Okumoto, Masaaki; Yonezawa, Morio; Nishikawa, Ryosuke; Takamori, Yasuhiko; Esaki, Kozaburo.

1994-01-01

Mouse strain difference in the radiosensitivity to hematopoietic death is thought to be determined by several factors besides radiosensitivity and the initial number of hematopoietic stem cells. Factors related to the survival of mice exposed to X-irradiation were analyzed using BALB/cHeA and STS/A strains whose LD 50/30 values differ markedly (BALB/cHeA, 5.55 Gy; STS/A, 8.45 Gy). STS/A mice exposed to 4 Gy of X-irradiation showed a small reduction but rapid recovery of blood cells (leukocytes, erythrocytes, and thrombocytes) when compared with BALB/cHeA mice. The survival of endogenous and exogenous CFU-S was much higher, by a magnitude of one log or more, in STS/A mice than those in BALB/cHeA mice; whereas the initial numbers of femoral CFU-S were similar for the two strains. The recovery of exogenous CFU-S was much more rapid in STS/A mice than it was in BALB/cHeA mice after 4 Gy of X-irradiation. Furthermore, spleen colonies produced by the transfusion of STS/A marrow cells into syngeneic recipients were significantly larger than those produced by BALB/cHeA marrow cells, regardless of whether the mice used for sources of marrow cells had been irradiated. But, there was no such difference when unirradiated marrow cells from the two strains were transfused into (BALB/cHeA X STS/A) F 1 recipients. These results indicate the possible contribution of a host factor (s) that stimulates the growth of spleen colonies after radiation to the radioresistance of STS/A mice, in addition to the primary effect of higher number of survivals of endogenous and exogenous CFU-S in STS/A mice. (author)

Perception of sweet taste is important for voluntary alcohol consumption in mice.

Science.gov (United States)

Blednov, Y A; Walker, D; Martinez, M; Levine, M; Damak, S; Margolskee, R F

2008-02-01

To directly evaluate the association between taste perception and alcohol intake, we used three different mutant mice, each lacking a gene expressed in taste buds and critical to taste transduction: alpha-gustducin (Gnat3), Tas1r3 or Trpm5. Null mutant mice lacking any of these three genes showed lower preference score for alcohol and consumed less alcohol in a two-bottle choice test, as compared with wild-type littermates. These null mice also showed lower preference score for saccharin solutions than did wild-type littermates. In contrast, avoidance of quinine solutions was less in Gnat3 or Trpm5 knockout mice than in wild-type mice, whereas Tas1r3 null mice were not different from wild type in their response to quinine solutions. There were no differences in null vs. wild-type mice in their consumption of sodium chloride solutions. To determine the cause for reduction of ethanol intake, we studied other ethanol-induced behaviors known to be related to alcohol consumption. There were no differences between null and wild-type mice in ethanol-induced loss of righting reflex, severity of acute ethanol withdrawal or conditioned place preference for ethanol. Weaker conditioned taste aversion (CTA) to alcohol in null mice may have been caused by weaker rewarding value of the conditioned stimulus (saccharin). When saccharin was replaced by sodium chloride, no differences in CTA to alcohol between knockout and wild-type mice were seen. Thus, deletion of any one of three different genes involved in detection of sweet taste leads to a substantial reduction of alcohol intake without any changes in pharmacological actions of ethanol.

Citric Acid and Quinine Share Perceived Chemosensory Features Making Oral Discrimination Difficult in C57BL/6J Mice

Science.gov (United States)

Treesukosol, Yada; Mathes, Clare M.

2011-01-01

Evidence in the literature shows that in rodents, some taste-responsive neurons respond to both quinine and acid stimuli. Also, under certain circumstances, rodents display some degree of difficulty in discriminating quinine and acid stimuli. Here, C57BL/6J mice were trained and tested in a 2-response operant discrimination task. Mice had severe difficulty discriminating citric acid from quinine and 6-n-propylthiouracil (PROP) with performance slightly, but significantly, above chance. In contrast, mice were able to competently discriminate sucrose from citric acid, NaCl, quinine, and PROP. In another experiment, mice that were conditioned to avoid quinine by pairings with LiCl injections subsequently suppressed licking responses to quinine and citric acid but not to NaCl or sucrose in a brief-access test, relative to NaCl-injected control animals. However, mice that were conditioned to avoid citric acid did not display cross-generalization to quinine. These mice significantly suppressed licking only to citric acid, and to a much lesser extent NaCl, compared with controls. Collectively, the findings from these experiments suggest that in mice, citric acid and quinine share chemosensory features making discrimination difficult but are not perceptually identical. PMID:21421543

Differences in the mechanical properties of the developing cerebral cortical proliferative zone between mice and ferrets at both the tissue and single-cell levels

Directory of Open Access Journals (Sweden)

Arata Nagasaka

2016-11-01

Full Text Available Cell-producing events in developing tissues are mechanically dynamic throughout the cell cycle. In many epithelial systems, cells are apicobasally tall, with nuclei and somata that adopt different apicobasal positions because nuclei and somata move in a cell cycle–dependent manner. This movement is apical during G2 phase and basal during G1 phase, whereas mitosis occurs at the apical surface. These movements are collectively referred to as interkinetic nuclear migration, and such epithelia are called pseudostratified. The embryonic mammalian cerebral cortical neuroepithelium is a good model for highly pseudostratified epithelia, and we previously found differences between mice and ferrets in both horizontal cellular density (greater in ferrets and nuclear/somal movements (slower during G2 and faster during G1 in ferrets. These differences suggest that neuroepithelial cells alter their nucleokinetic behavior in response to physical factors that they encounter, which may form the basis for evolutionary transitions towards more abundant brain-cell production from mice to ferrets and primates. To address how mouse and ferret neuroepithelia may differ physically in a quantitative manner, we used atomic force microscopy to determine that the vertical stiffness of their apical surface is greater in ferrets (Young’s modulus = 1700 Pa than in mice (1400 Pa. We systematically analyzed factors underlying the apical-surface stiffness through experiments to pharmacologically inhibit actomyosin or microtubules and to examine recoiling behaviors of the apical surface upon laser ablation and also through electron microscopy to observe adherens junction. We found that although both actomyosin and microtubules are partly responsible for the apical-surface stiffness, the mouse

How Rice (Oryza sativa L.) Responds to Elevated As under Different Si-Rich Soil Amendments.

Science.gov (United States)

Teasley, William A; Limmer, Matthew A; Seyfferth, Angelia L

2017-09-19

Several strategies exist to mitigate As impacts on rice and each has its set of trade-offs with respect to yield, inorganic As content in grain, and CH 4 emissions. The addition of Si to paddy soil can decrease As uptake by rice but how rice will respond to elevated As when soil is amended with Si-rich materials is unresolved. Here, we evaluated yield impacts and grain As content and speciation in rice exposed to elevated As in response to different Si-rich soil amendments including rice husk, rice husk ash, and CaSiO 3 in a pot study. We found that As-induced yield losses were alleviated by Husk amendment, partially alleviated by Ash amendment, and not affected by CaSiO 3 amendment. Furthermore, Husk was the only tested Si-amendment to significantly decrease grain As concentrations. Husk amendment was likely effective at decreasing grain As and improving yield because it provided more plant-available Si, particularly during the reproductive and ripening phases. Both Husk and Ash provided K, which also played a role in yield improvement. This study demonstrates that while Si-rich amendments can affect rice uptake of As, the kinetics of Si dissolution and nutrient availability can also affect As uptake and toxicity in rice.

Substrains of Inbred Mice Differ in Their Physical Activity as a Behavior

Directory of Open Access Journals (Sweden)

Dario Coletti

2013-01-01

Full Text Available Recent studies strengthen the belief that physical activity as a behavior has a genetic basis. Screening wheel-running behavior in inbred mouse strains highlighted differences among strains, showing that even very limited genetic differences deeply affect mouse behavior. We extended this observation to substrains of the same inbred mouse strain, that is, BALB/c mice. We found that only a minority of the population of one of these substrains, the BALB/c J, performs spontaneous physical activity. In addition, the runners of this substrain cover a significantly smaller distance than the average runners of two other substrains, namely, the BALB/c ByJ and the BALB/c AnNCrl. The latter shows a striking level of voluntary activity, with the average distance run/day reaching up to about 12 kilometers. These runners are not outstanders, but they represent the majority of the population, with important scientific and economic fallouts to be taken into account during experimental planning. Spontaneous activity persists in pathological conditions, such as cancer-associated cachexia. This important amount of physical activity results in a minor muscle adaptation to endurance exercise over a three-week period; indeed, only a nonsignificant increase in NADH transferase+ fibers occurs in this time frame.

Effects of different levels of food restriction on passive-avoidance memory and the expression of synapsin I in young mice.

Science.gov (United States)

Deng, L; Wu, Z-N; Han, P-Z

2009-01-01

The present study investigated the effects of food restriction (FR) on memory and the expression of synapsin I in the brain of young mice. The results showed that 20% FR did not retard the body weight gain of mice, while the 60% and 80% FR reduced the mice's body weight. The memory after 24 hr of learning was not changed by FR, whereas long-term memory was improved significantly in 20% FR mice. In addition, 60% and 80% FR did not impair the mice's memory. The transcriptional expression of synapsin I in mice brain was up-regulated by 20% FR, and down-regulated by 60% and 80% FR.