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Sample records for congenic c57bl mice

  1. Genomic structure and genetic drift in C57BL/6 congenic metabolic mutant mice.

    PubMed

    Almodovar, Alvin J O; Luther, Rita J; Stonebrook, Caron L; Wood, Philip A

    2013-11-01

    We used a genome-wide single nucleotide polymorphism (SNP) approach to characterize the genomic structures of four representative C57BL/6 (B6) congenic mutant mouse lines to include the A) long-chain acyl-CoA dehydrogenase (Acadl), B) melanocortin 3 receptor (Mc3r), C) endothelial nitric oxide synthase (Nos3), and D) a replacement of mouse apolipoprotein E (Apoe) by human apolipoprotein E-2 (APOE2). We wanted to evaluate the size and flanking genes of the 129 strain origin mutant allele intervals on the B6 background. Additionally, we wanted to evaluate genetic drift among not only the four mutant lines and their respective B6 origin substrains, but also the drift between two commonly used B6 lines obtained from Jackson Laboratory and Taconic. Overall, we found a range of 129 origin interval sizes in the congenic mutant lines analyzed that ranged from a ~2.8 kb human sequence for APOE2 embedded in a 129S6 interval to the largest being a ~16 Mb fragment containing the targeted Nos3 (eNos) gene. Given the range of 129 strain interval sizes, we found 129 strain flanking genes via annotation in genome data bases ranging from one gene both upstream and downstream of the APOE2 allele to seven genes-upstream and five genes-downstream at the Nos3 locus. Furthermore, we found fourteen SNP differences between the Jackson Laboratory and Taconic B6 mice. These genetic differences were associated with marked adiposity differences between the two B6 substrains. This study demonstrates both the fidelity and the caveats of using congenic gene targeted mouse models and recognizing the importance of selecting the appropriately matched wild-type control mouse line.

  2. Comparison of the acute ultraviolet photoresponse in congenic albino hairless C57BL/6J mice relative to outbred SKH1 hairless mice.

    PubMed

    Konger, Raymond L; Derr-Yellin, Ethel; Hojati, Delaram; Lutz, Cathleen; Sundberg, John P

    2016-09-01

    Hairless albino Crl:SKH1-Hr(hr) mice are commonly utilized for studies in which hair or pigmentation would introduce an impediment to observational studies. Being an outbred strain, the SKH1 model suffers from key limitations that are not seen with congenic mouse strains. Inbred and congenic C57BL/6J mice are commonly utilized for modified genetic mouse models. We compare the acute UV-induced photoresponse between outbred SKH1 mice and an immune competent, hairless, albino C57BL/6J congenic mouse line [B6.Cg-Tyr(c-2J) Hr(hr) /J]. Histologically, B6.Cg-Tyr(c-2J) Hr(hr) /J skin is indistinguishable from that of SKH1 mice. The skin of both SKH1 and B6.Cg-Tyr(c-2J) Hr(hr) /J mice exhibited a reduction in hypodermal adipose tissue, the presence of utricles and dermal cystic structures, the presence of dermal granulomas and epidermal thickening. In response to a single 1500 J/m(2) ultraviolet B dose, the oedema and apoptotic responses were equivalent in both mouse strains. However, B6.Cg-Tyr(c-2J) Hr(hr) /J mice exhibited a more robust delayed sunburn reaction, with an increase in epidermal erosion, scab formation and myeloperoxidase activity relative to SKH1 mice. Compared with SKH1 mice, B6.Cg-Tyr(c-2J) Hr(hr) /J also exhibited an aberrant proliferative response to this single UV exposure. Epidermal Ki67 immunopositivity was significantly suppressed in B6.Cg-Tyr(c-2J) Hr(hr) /J mice at 24 h post-UV. A smaller non-significant reduction in Ki67 labelling was observed in SKH1 mice. Finally, at 72 h post-UV, SKH1 mice, but not B6.Cg-Tyr(c-2J) Hr(hr) /J mice, exhibited a significant increase in Ki67 immunolabelling relative to non-irradiated controls. Thus, B6.Cg-Tyr(c-2J) Hr(hr) /J mice are suitable for photobiology experiments. PMID:27095432

  3. Differential toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in C57BL/6J mice congenic at the Ah Locus.

    PubMed

    Birnbaum, L S; McDonald, M M; Blair, P C; Clark, A M; Harris, M W

    1990-07-01

    The acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was examined in male C57BL/6J mice differing only at the Ah locus. Wild type mice (Ahb/b, "b/b") were treated once with 0, 50, 100, 200, 300, and 400 micrograms TCDD/kg po while congenic mice (Ahd/d, "d/d") received a single dose of 0, 400, 800, 1600, 2400, and 3200 micrograms TCDD/kg. Mice were checked daily, weighed twice a week, and those that survived, killed 35 days post-treatment. The LD50 values were 159 and 3351 micrograms/kg for b/b and d/d mice, respectively. Mean time to death was 22 days and was independent of dose and genotype. Decrease in body weight gain was noted in both strains 5 days after treatment and occurred at doses greater than or equal to 100 micrograms/kg in b/b mice and 1600 micrograms/kg in d/d mice. Dose-related increases in liver weight (both absolute and relative to body weight) and decreases in thymus, spleen, testes, and epididymal fat pad weights were observed at 8-24-fold higher doses in d/d than in b/b mice. A dose-related increase in segmented neutrophils was observed in both strains. Serum chemistry values indicated that 8-24X greater doses of TCDD were needed to elevate sorbitol dehydrogenase, alanine aminotransferase, and 5'-nucleotidase and to decrease total and esterified cholesterol in d/d than in b/b mice. Few effects were seen on total bile acids, serum triglycerides, glucose, or nonesterified cholesterol. In the liver, hepatocellular cytomegaly, fatty change, and bile duct hyperplasia occurred in both strains in a dose-related manner, as did thymic and splenic atrophy. Necrosis of germinal epithelium in the testes and edema in the stomach submucosa occurred at acutely toxic doses. These lesions also occurred at doses 8-24X greater in d/d than in b/b mice. Thus, the spectrum of toxicity is independent of the allele at the Ah locus, but the relative dose needed to bring about various acute responses is approximately 8-24X greater in congenic mice homozygous

  4. MHC-congenic mice (C57BL/6J and B6-H-2K) show differences in speed but not accuracy in learning the Hebb-Williams Maze.

    PubMed

    Stanford, Lianne; Brown, Richard E

    2003-09-15

    We compared spatial learning and memory in male and female mice of two MHC-congenic strains (C57BL/6J and B6-H-2K) in two versions of the Hebb-Williams Maze. In the food-reward paradigm, males required fewer sessions to learn than females, but there were no strain differences in acquisition. There were no strain or sex differences in the number of errors during the test phase, but the B6-H-2K mice reached the goal box faster than the C57BL/6J mice. In the water-escape paradigm, the C57BL/6J mice required more sessions than the B6-H-2K mice during acquisition. There were no strain or sex differences in the number of errors or in the latency to swim to the goal box in the test phase of the water-escape task. There were no significant correlations between the number of sessions to learn the two mazes; the number of errors made or the latencies to reach the goal box in each maze. These results indicate that these two strains show differences in performance in the Hebb-Williams Maze, but do not differ in cognitive ability.

  5. Photoperiod modulates melanoma growth in C57BL/6 mice.

    PubMed

    Lang, Roland; Hintner, Helmut; Hermann, Anton; Brandstaetter, Roland

    2003-08-01

    Seasonal variations can be found in almost any parameter of an organism's biochemistry, physiology, endocrinology, and behaviour. This phenomenon, generally called photoperiodism, results from one of the major functions of the circadian system, i.e. the translation of environmental information into rhythmic intraorganismic signals, which then regulate or influence physiology and pathology. We induced melanoma in three groups of syngeneic C57BL/6 mice synchronised to different photoperiods (8, 12, or 18 h of light within 24-h days) by subcutaneous injections of HFH18 melanoma cell suspensions. All animals from all three photoperiodic groups developed exponentially growing tumors. The average tumor volume on day 31 post injection was significantly smaller in animals exposed to light/dark conditions (LD) 8 : 16 h as compared with animals held in LD 18 : 6 h and intermediate in animals from the equinox group. These results indicate that C57BL/6 mice react to photoperiod, which can exert a significant effect on tumor growth. PMID:12930310

  6. Postnatal Hematopoiesis and Gut Microbiota in NOD Mice Deviate from C57BL/6 Mice

    PubMed Central

    Damlund, Dina Silke Malling; Metzdorff, Stine Broeng; Hasselby, Jane Preuss; Wiese, Maria; Lundsager, Mia; Buschard, Karsten Stig; Hansen, Axel Kornerup; Frøkiær, Hanne

    2016-01-01

    Neonatal studies in different mouse strains reveal that early life colonization affects the development of adaptive immunity in mice. The nonobese diabetic (NOD) mouse spontaneously develops autoimmune diabetes, but neonatal studies of NOD mice are lacking. We hypothesized that NOD mice deviate from another much used mouse strain, C57BL/6, with respect to postnatal microbiota and/or hematopoiesis and compared this in newborn mice of dams housed under the same conditions. A distinct bacteria profile rich in staphylococci was found at postnatal days (PND) 1–4 in NOD mice. Furthermore, a distinct splenic cell profile high in a granulocytic phenotype was evident in the neonatal NOD mice whereas neonatal C57BL/6 mice showed a profile rich in monocytes. Neonatal expression of Reg3g and Muc2 in the gut was deviating in NOD mice and coincided with fewer bacteria attaching to the Mucosal surface in NOD compared to C57BL/6 mice. PMID:26783537

  7. PATHOGENESIS OF METHANOL-INDUCED CRANIOFACIAL DEFECTS IN C57BL/6J MICE

    EPA Science Inventory

    BACKGROUND: Methanol administered to C57BL/6J mice during gastrulation causes severe craniofacial dysmorphology. We describe dysmorphogenesis, cell death, cell cycle assessment, and effects on development of cranial ganglia and nerves observed following administration of methanol...

  8. Postnatal Development of the Craniofacial Skeleton in Male C57BL/6J Mice

    PubMed Central

    2016-01-01

    C57BL/6J is one of the most commonly used inbred mouse strains in biomedical research, including studies of craniofacial development and teratogenic studies of craniofacial malformation. The current study quantitatively assessed the development of the skull in male C57BL/6J mice by using high-resolution 3D imaging of 55 landmarks from 48 male mice over 10 developmental time points from postnatal day 0 to 90. The growth of the skull plateaued at approximately postnatal day 60, and the shape of the skull did not change markedly thereafter. The amount of asymmetry in the craniofacial skeleton seemed to peak at birth, but considerable variation persisted in all age groups. For C57BL/6J male mice, postnatal day 60 is the earliest time point at which the skull achieves its adult shape and proportions. In addition, C57BL/6J male mice appear to have an inherent susceptibility to craniofacial malformation. PMID:27025802

  9. DEVELOPMENTAL TOXICITY OF METHANOL: PATHOGENESIS IN CD-1 AND C57BL/6J MICE EXPOSED IN WHOLE EMBRYO CULTURE

    EPA Science Inventory

    BACKGROUND: Methanol causes axial skeleton and craniofacial defects in both CD-1 and C57BL/6J mice during gastrulation, but C57BL/6J embryos are more severely affected. We evaluated methanol-induced pathogenesis in CD-1 and C57BL/6J embryos exposed during gastrulation in whole em...

  10. Clinical Chemistry Reference Intervals for C57BL/6J, C57BL/6N, and C3HeB/FeJ Mice (Mus musculus).

    PubMed

    Otto, Gordon P; Rathkolb, Birgit; Oestereicher, Manuela A; Lengger, Christoph J; Moerth, Corinna; Micklich, Kateryna; Fuchs, Helmut; Gailus-Durner, Valérie; Wolf, Eckhard; Hrabě de Angelis, Martin

    2016-01-01

    Although various mouse inbred strains are widely used to investigate disease mechanisms and to establish new therapeutic strategies, sex-specific reference intervals for laboratory diagnostic analytes that are generated from large numbers of animals have been unavailable. In this retrospective study, we screened data from more than 12,000 mice phenotyped in the German Mouse Clinic from January 2006 through June 2014 and selected animals with the genetic background of C57BL/6J, C57BL/6N, or C3HeB/FeJ. In addition, we distinguished between the C57BL/6NTac substrain and C57BL/6N mice received from other vendors. The corresponding data sets of electrolytes (sodium, potassium, calcium, chloride, inorganic phosphate), lipids (cholesterol, triglyceride), and enzyme activities (ALT, AST, ALP, α-amylase) and urea, albumin, and total protein levels were analyzed. Significant effects of age and sex on these analytes were identified, and strain- or substrain- and sex-specific reference intervals for 90- to 135-d-old mice were calculated. In addition, we include an overview of the literature that reports clinical chemistry values for wild-type mice of different strains. Our results support researchers interpreting clinical chemistry values from various mouse mutants and corresponding wild-type controls based on the examined strains and substrains. PMID:27423143

  11. Clinical Chemistry Reference Intervals for C57BL/6J, C57BL/6N, and C3HeB/FeJ Mice (Mus musculus).

    PubMed

    Otto, Gordon P; Rathkolb, Birgit; Oestereicher, Manuela A; Lengger, Christoph J; Moerth, Corinna; Micklich, Kateryna; Fuchs, Helmut; Gailus-Durner, Valérie; Wolf, Eckhard; Hrabě de Angelis, Martin

    2016-01-01

    Although various mouse inbred strains are widely used to investigate disease mechanisms and to establish new therapeutic strategies, sex-specific reference intervals for laboratory diagnostic analytes that are generated from large numbers of animals have been unavailable. In this retrospective study, we screened data from more than 12,000 mice phenotyped in the German Mouse Clinic from January 2006 through June 2014 and selected animals with the genetic background of C57BL/6J, C57BL/6N, or C3HeB/FeJ. In addition, we distinguished between the C57BL/6NTac substrain and C57BL/6N mice received from other vendors. The corresponding data sets of electrolytes (sodium, potassium, calcium, chloride, inorganic phosphate), lipids (cholesterol, triglyceride), and enzyme activities (ALT, AST, ALP, α-amylase) and urea, albumin, and total protein levels were analyzed. Significant effects of age and sex on these analytes were identified, and strain- or substrain- and sex-specific reference intervals for 90- to 135-d-old mice were calculated. In addition, we include an overview of the literature that reports clinical chemistry values for wild-type mice of different strains. Our results support researchers interpreting clinical chemistry values from various mouse mutants and corresponding wild-type controls based on the examined strains and substrains.

  12. Hypolipidemic effect of young persimmon fruit in C57BL/6.KOR-ApoEshl mice.

    PubMed

    Matsumoto, Kenji; Yokoyama, Shin-ichiro; Gato, Nobuki

    2008-10-01

    We investigated the hypolipidemic effects of young persimmon fruit (YP) on apolipoprotein E-deficient C57BL/6.KOR-ApoEshl mice. These mice exhibited higher plasma cholesterols, except for high-density lipoprotein (HDL), and lower plasma HDL cholesterol than C57BL/6.Cr mice that had the same genetic background as the C57BL/6.KOR-ApoEshl mice. Male C57BL/6.KOR-ApoEshl mice (n=5) were fed a diet supplemented with dry YP, Hachiya-kaki, at a concentration of 5% (w/w) for 10 weeks. YP treatment significantly lowered plasma chylomicron, very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) cholesterols, and triglyceride, and this response was accompanied by an elevation of fecal bile acid excretion. In the liver, sterol regulatory element binding protein-2 gene expression was significantly higher in mice fed YP, while the mRNA and protein levels of the LDL receptor did not change. These results indicate that acceleration of fecal bile acid excretion is a major mechanism of the hypolipidemic effect induced by YP in C57BL/6.KOR-ApoEshl mice. PMID:18838807

  13. Inhibitory effects of sweet cherry anthocyanins on the obesity development in C57BL/6 mice.

    PubMed

    Wu, Tao; Tang, Qiong; Yu, Zhuoping; Gao, Zichun; Hu, Hao; Chen, Wei; Zheng, Xiaodong; Yu, Ting

    2014-05-01

    In the present study, purified sweet cherry anthocyanins (CACN) were evaluated to determine their inhibitory effects on adipocyte differentiation of 3T3-L1 cells and their anti-obesity properties in male C57BL/6 mice fed with high-fat diet (HFD). CACN prevented HFD-induced obesity in C57BL/6 mice. In vivo experiment revealed that 40 and 200 mg/kg of CACN in food reduced the body weight by 5.2% and 11.2%, respectively. CACN supplementation could also reduce the size of adipocytes, leptin secretion, serum glucose, triglyceride, total cholesterol, LDL-cholesterol and liver triglycerides. Furthermore, CACN could effectively reduce the expression levels of IL-6 and TNFα genes, markedly increase the SOD and GPx activity. Our results indicated that CACN slowed down the development of HFD-induced obesity in male C57BL/6 mice. PMID:24224922

  14. The inhibitory efficacy of methylseleninic acid against colon cancer xenografts in C57BL/6 mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Data indicate that methylselenol is a critical selenium (Se) metabolite for anticancer activity in vivo. We tested the hypoththesis that oral dosing methylseleninic acid (MSeA), a methylselenol precursor, inhibits the growth of colon cancer xenografts in C57BL/6 mice fed a Se adequate diet. In this...

  15. CHRONIC EXPOSURE TO ARSENITE IN DRINKING WATER IMPAIRS GLUCOSE TOLERANCE IN C57BL/6 MICE

    EPA Science Inventory

    Chronic exposures to inorganic arsenic (iAs) have been associated with increased prevalence of type 2 diabetes mellitus. This study examines in vivo diabetogenic effects of iAs in an animal model. Here, weanling male C57BL/6 mice received deionized water containing iAs(III) (25 ...

  16. Variation in airway responsiveness of male C57BL/6 mice from 5 vendors.

    PubMed

    Chang, Herng-Yu Sucie; Mitzner, Wayne; Watson, Julie

    2012-07-01

    Mice are now the most commonly used animal model for the study of asthma. The mouse asthma model has many characteristics of the human pathology, including allergic sensitization and airway hyperresponsiveness. Inbred strains are commonly used to avoid variations due to genetic background, but variations due to rearing environment are not as well recognized. After a change in mouse vendors and a switch from C57BL/6J mice to C57BL/6N mice, we noted significant differences in airway responsiveness between the substrains. To further investigate the effect of vendor, we tested C57BL/6N mice from 3 other vendors and found significant differences between several of the substrains. To test whether this difference was due to genetic drift or rearing environment, we purchased new groups of mice from all 5 vendors, bred them in separate vendor-specific groups under uniform environmental conditions, and tested male first generation (F1) offspring at 8 to 10 wk of age. These F1 mice showed no significant differences in airway responsiveness, indicating that the rearing environment rather than genetic differences was responsible for the initial variation in pulmonary phenotype. The environmental factors that caused the phenotypic variation are unknown. However, differences between vendor in feed components, bedding type, or microbiome could have contributed. Whatever the basis, investigators using mouse models of asthma should be cautious in comparing data from mice obtained from different vendors.

  17. Effect of chronic corticosterone application on depression-like behavior in C57BL/6N and C57BL/6J mice.

    PubMed

    Sturm, M; Becker, A; Schroeder, A; Bilkei-Gorzo, A; Zimmer, A

    2015-03-01

    Many studies using genetic mouse models are performed with animals on either one of the two closely related genetic backgrounds, C57BL/6J or C57BL/6N. These strains differ only in a few genetic loci, but have some phenotypic differences that also affect behavior. In order to determine the effects of chronic stress hormone exposure, which is relevant for the pathogenesis of psychiatric disorders, we investigated here the behavioral manifestations of long-term increase in corticosterone levels. Thus, male mice from both sub-strains were subcutaneously implanted with corticosterone (20 mg) or placebo pellets that released the hormone for a period of 21 days and resulted in significantly elevated plasma corticosterone levels. Corticosterone significantly increased food intake in B6N, but not in B6J mice. At various time points after pellet implantation, we performed tests relevant to activity and emotional behaviors. B6J mice displayed a generally higher activity in the home cage and the open field. Corticosterone decreased the activity. In B6N mice, corticosterone also decreased sucrose preference, worsened the coat state and increased forced swim immobility, while it had no effect in the B6J strain. Altogether, these results indicate that B6N mice are more sensitive to some of the effects of chronic corticosterone treatment than B6J mice.

  18. β-Aminopropionitrile monofumarate induces thoracic aortic dissection in C57BL/6 mice

    PubMed Central

    Ren, Weihong; Liu, Yan; Wang, Xuerui; Jia, Lixin; Piao, Chunmei; Lan, Feng; Du, Jie

    2016-01-01

    Thoracic aortic dissection (TAD) is a catastrophic disease with high mortality and morbidity, characterized by fragmentation of elastin and loss of smooth muscle cells. However, the underlying pathological mechanisms of this disease remain elusive because there are no appropriate animal models, limiting discovery of effective therapeutic strategies. We treated mice on C57BL/6 and FVB genetic backgrounds with β-aminopropionitrile monofumarate (BAPN), an irreversible inhibitor of lysyl oxidase, for 4 wk, followed by angiotensin II (Ang II) infusion for 24 h. We found that the BAPN plus Ang II treatment induced formation of aortic dissections in 100% of mice on both genetic backgrounds. BAPN without Ang II caused dissections in few FVB mice, but caused 87% of C57BL/6 mice to develop TAD, with 37% dying from rupture of the aortic dissection. Moreover, a lower dose of BAPN induced TAD formation and rupture earlier with fewer effects on body weight. Therefore, we have generated a reliable and convenient TAD model in C57BL/6 mice for studying the pathological process and exploring therapeutic targets of TAD. PMID:27329825

  19. Investigations on the physiological controls of water and saline intake in C57BL/6 mice.

    PubMed

    Johnson, Ralph F; Beltz, Terry G; Thunhorst, Robert L; Johnson, Alan Kim

    2003-08-01

    To examine the behavioral and neural control of body fluid homeostasis, water and saline intake of C57BL/6 mice was monitored under ad libitum conditions, after treatments that induce water or salt intake, and after ablation of the periventricular tissue of the anteroventral third ventricle (AV3V). Mice have nocturnal drinking that is most prevalent after the offset and before the onset of lights. When given ad libitum choice, C57BL/6 mice show no preference for saline over water at concentrations up to 0.9% NaCl and a progressive aversion to saline above that concentration. Systemic hypertonic saline, isoproterenol, and polyethylene glycol treatments are dipsogenic; however, systemic ANG II is not. Intracerebroventricular injections of both hypertonic saline and ANG II are dipsogenic, and diuretic treatment followed by a short period of sodium deprivation induces salt intake. After ablation of the AV3V, mice can be nursed to recovery from initial adipsia and, similar to rats, show chronic deficits to dipsogenic treatments. Taken together, the data indicate that mechanisms controlling thirst in response to cellular dehydration in C57BL/6 mice are similar to rats, but there are differences in the efficacy of extracellular dehydration-related mechanisms, especially for systemic ANG II, controlling thirst and salt appetite.

  20. EXPERIMENTAL SUBCUTANEOUS CYSTICERCOSIS BY Taenia crassiceps IN BALB/c AND C57BL/6 MICE

    PubMed Central

    PEREIRA, Íria Márcia; LIMA, Sarah Buzaim; FREITAS, Aline de Araújo; VINAUD, Marina Clare; JUNIOR, Ruy de Souza LINO

    2016-01-01

    SUMMARY Human cysticercosis is one of the most severe parasitic infections affecting tissues. Experimental models are needed to understand the host-parasite dynamics involved throughout the course of the infection. The subcutaneous experimental model is the closest to what is observed in human cysticercosis that does not affect the central nervous system. The aim of this study was to evaluate macroscopically and microscopically the experimental subcutaneous cysticercosis caused by Taenia crassiceps cysticerci in BALB/c and C57BL/6 mice. Animals were inoculated in the dorsal subcutaneous region and macroscopic and microscopic aspects of the inflammatory process in the host-parasite interface were evaluated until 90 days after the inoculation (DAI). All the infected animals presented vesicles containing cysticerci in the inoculation site, which was translucent at 7 DAI and then remained opaque throughout the experimental days. The microscopic analysis showed granulation tissue in BALB/c mice since the acute phase of infection evolving to chronicity without cure, presenting 80% of larval stage cysticerci at 90 DAI. While C57BL/6 mice presented 67% of final stage cysticerci at 90 DAI, the parasites were surrounded by neutrophils evolving to the infection control. It is possible to conclude that the genetic features of susceptibility (BALB/c) or resistance (C57BL/6) were confirmed in an experimental subcutaneous model of cysticercosis. PMID:27410915

  1. EXPERIMENTAL SUBCUTANEOUS CYSTICERCOSIS BY Taenia crassiceps IN BALB/c AND C57BL/6 MICE.

    PubMed

    Pereira, Íria Márcia; Lima, Sarah Buzaim; Freitas, Aline de Araújo; Vinaud, Marina Clare; Junior, Ruy de Souza Lino

    2016-07-11

    Human cysticercosis is one of the most severe parasitic infections affecting tissues. Experimental models are needed to understand the host-parasite dynamics involved throughout the course of the infection. The subcutaneous experimental model is the closest to what is observed in human cysticercosis that does not affect the central nervous system. The aim of this study was to evaluate macroscopically and microscopically the experimental subcutaneous cysticercosis caused by Taenia crassiceps cysticerci in BALB/c and C57BL/6 mice. Animals were inoculated in the dorsal subcutaneous region and macroscopic and microscopic aspects of the inflammatory process in the host-parasite interface were evaluated until 90 days after the inoculation (DAI). All the infected animals presented vesicles containing cysticerci in the inoculation site, which was translucent at 7 DAI and then remained opaque throughout the experimental days. The microscopic analysis showed granulation tissue in BALB/c mice since the acute phase of infection evolving to chronicity without cure, presenting 80% of larval stage cysticerci at 90 DAI. While C57BL/6 mice presented 67% of final stage cysticerci at 90 DAI, the parasites were surrounded by neutrophils evolving to the infection control. It is possible to conclude that the genetic features of susceptibility (BALB/c) or resistance (C57BL/6) were confirmed in an experimental subcutaneous model of cysticercosis. PMID:27410915

  2. Distinct granuloma responses in C57BL/6J and BALB/cByJ mice in response to pristane

    PubMed Central

    Chen, Huaiyong; Liao, Dongmei; Cain, Derek; McLeod, Ian; Ueda, Yoshihiro; Guan, Ziqiang; Raetz, Christian; Kelsoe, Garnett

    2010-01-01

    Granuloma formation is an inflammatory response of the host against invading pathogens or indigestible substances. We generated mesenteric oil granulomas by injecting pristane into the peritoneal cavity (PC) of mice, and compared oil granuloma formation in the C57BL/6J and BALB/cByJ strains of mice. The formation and kinetics of oil granulomas were distinct between the two strains. In C57BL/6J mice, injected pristane induced oil granuloma formation at both the mesenteric centers (MG) and margins (SG). MG was resolving by 11 weeks, and SG persisted. In BALB/cByJ mice, MG developed slower but persisted longer than in C57BL/6J mice, and SG resolved sooner than in C57BL/6J mice. Injection of India ink revealed that phagocytes were localised mainly to the SG in C57BL/6J mice, but were located diffusely in both MG and SG of BALB/cByJ mice. SG cells expressed more monocyte chemotactic protein-1 (MCP-1) mRNA than MG cells in C57BL/6J mice, but there was no difference in MCP-1 expression between the MG and SG in BALB/cByJ mice. These observations suggest that the recruitment of inflammatory leucocytes under the direction of chemokines differentiates the patterns of granuloma responses to pristane in C57BL/6J and BALB/cByJ mice. PMID:20681981

  3. Efficient gene-driven germ-line point mutagenesis of C57BL/6J mice

    PubMed Central

    Michaud, Edward J; Culiat, Cymbeline T; Klebig, Mitchell L; Barker, Paul E; Cain, KT; Carpenter, Debra J; Easter, Lori L; Foster, Carmen M; Gardner, Alysyn W; Guo, ZY; Houser, Kay J; Hughes, Lori A; Kerley, Marilyn K; Liu, Zhaowei; Olszewski, Robert E; Pinn, Irina; Shaw, Ginger D; Shinpock, Sarah G; Wymore, Ann M; Rinchik, Eugene M; Johnson, Dabney K

    2005-01-01

    Background Analysis of an allelic series of point mutations in a gene, generated by N-ethyl-N-nitrosourea (ENU) mutagenesis, is a valuable method for discovering the full scope of its biological function. Here we present an efficient gene-driven approach for identifying ENU-induced point mutations in any gene in C57BL/6J mice. The advantage of such an approach is that it allows one to select any gene of interest in the mouse genome and to go directly from DNA sequence to mutant mice. Results We produced the Cryopreserved Mutant Mouse Bank (CMMB), which is an archive of DNA, cDNA, tissues, and sperm from 4,000 G1 male offspring of ENU-treated C57BL/6J males mated to untreated C57BL/6J females. Each mouse in the CMMB carries a large number of random heterozygous point mutations throughout the genome. High-throughput Temperature Gradient Capillary Electrophoresis (TGCE) was employed to perform a 32-Mbp sequence-driven screen for mutations in 38 PCR amplicons from 11 genes in DNA and/or cDNA from the CMMB mice. DNA sequence analysis of heteroduplex-forming amplicons identified by TGCE revealed 22 mutations in 10 genes for an overall mutation frequency of 1 in 1.45 Mbp. All 22 mutations are single base pair substitutions, and nine of them (41%) result in nonconservative amino acid substitutions. Intracytoplasmic sperm injection (ICSI) of cryopreserved spermatozoa into B6D2F1 or C57BL/6J ova was used to recover mutant mice for nine of the mutations to date. Conclusions The inbred C57BL/6J CMMB, together with TGCE mutation screening and ICSI for the recovery of mutant mice, represents a valuable gene-driven approach for the functional annotation of the mammalian genome and for the generation of mouse models of human genetic diseases. The ability of ENU to induce mutations that cause various types of changes in proteins will provide additional insights into the functions of mammalian proteins that may not be detectable by knockout mutations. PMID:16300676

  4. Efficient gene-driven germ-line point mutagenesis of C57BL/6J mice

    SciTech Connect

    Michaud III, Edward J; Culiat, Cymbeline T; Klebig, Mitch; Barker, Gene; Cain, K T; Carpenter, Debra J S; Easter, Lori L; Foster, Carmen M; Gardner, Alysyn Wallace; Guo, ZY; Houser, Kay J; Hughes, Lori A; Kerley, Marilyn K; Liu, Zhaowei; Olszewski, Robert Edward; Pinn, Irina; Shaw, Ginger D; Shinpock, Sarah G; Wymore, Ann; Rinchik, Eugene M; Johnson, Dabney K

    2005-01-01

    Background: Analysis of an allelic series of point mutations in a gene, generated by N-ethyl-N-nitrosourea (ENU) mutagenesis, is a valuable method for discovering the full scope of its biological function. Here we present an efficient gene-driven approach for identifying ENU-induced point mutations in any gene in C57BL/6J mice. The advantage of such an approach is that it allows one to select any gene of interest in the mouse genome and to go directly from DNA sequence to mutant mice. Results: We produced the Cryopreserved Mutant Mouse Bank (CMMB), which is an archive of DNA, cDNA, tissues, and sperm from 4,000 G1 male offspring of ENU-treated C57BL/6J males mated to untreated C57BL/6J females. Each mouse in the CMMB carries a large number of random heterozygous point mutations throughout the genome. High-throughput Temperature Gradient Capillary Electrophoresis (TGCE) was employed to perform a 32-Mbp sequence-driven screen for mutations in 38 PCR amplicons from 11 genes in DNA and/or cDNA from the CMMB mice. DNA sequence analysis of heteroduplex-forming amplicons identified by TGCE revealed 22 mutations in 10 genes for an overall mutation frequency of 1 in 1.45 Mbp. All 22 mutations are single base pair substitutions, and nine of them (41%) result in nonconservative amino acid substitutions. Intracytoplasmic sperm injection (ICSI) of cryopreserved spermatozoa into B6D2F1 or C57BL/6J ova was used to recover mutant mice for nine of the mutations to date. Conclusions: The inbred C57BL/6J CMMB, together with TGCE mutation screening and ICSI for the recovery of mutant mice, represents a valuable gene-driven approach for the functional annotation of the mammalian genome and for the generation of mouse models of human genetic diseases. The ability of ENU to induce mutations that cause various types of changes in proteins will provide additional insights into the functions of mammalian proteins that may not be detectable by knockout mutations.

  5. The C57BL/6 genetic background confers cardioprotection in iron-overloaded mice

    PubMed Central

    Musumeci, Marco; Maccari, Sonia; Sestili, Paola; Massimi, Alessia; Corritore, Elisa; Marano, Giuseppe; Catalano, Liviana

    2013-01-01

    Background Chronic transfusion therapy causes a progressive iron overload that damages many organs including the heart. Recent evidence suggests that L-type calcium channels play an important role in iron uptake by cardiomyocytes under conditions of iron overload. Given that beta-adrenergic stimulation significantly enhances L-type calcium current, we hypothesised that beta-adrenergic blocking drugs could reduce the deleterious effects of iron overload on the heart. Methods Iron overload was generated by intraperitoneal injections of iron dextran (1g/kg) administered once a week for 8 weeks in male C57bl/6 mice, while propranolol was administered in drinking water at the dose of 40 mg/kg/day. Cardiac function and ventricular remodelling were evaluated by echocardiography and histological methods. Results As compared to placebo, iron injection caused cardiac iron deposition. Surprisingly, despite iron overload, myocardial function and ventricular geometry in the iron-treated mice resulted unchanged as compared to those in the placebo-treated mice. Administration of propranolol increased cardiac performance in iron-overloaded mice. Specifically, as compared to the values in the iron-overloaded group, in iron-overloaded animals treated with propranolol left ventricular fractional shortening increased (from 31.6% to 44.2%, P =0.01) whereas left ventricular end-diastolic diameter decreased (from 4.1±0.1 mm to 3.5±0.1 mm, P =0.03). Propranolol did not alter cardiac systolic function or left ventricular sizes in the placebo group. Conclusions These results demonstrate that C57bl/6 mice are resistant to iron overload-induced myocardial injury and that treatment with propranolol is able to increase cardiac performance in iron-overloaded mice. However, since C57bl/6 mice were resistant to iron-induced injury, it remains to be evaluated further whether propranolol could prevent iron-overload cardiomyopathy. PMID:22790263

  6. Effect of eicosapentaenoic acid on cholesterol gallstone formation in C57BL/6J mice.

    PubMed

    Cho, Soo-Min; Park, Jin-A; Kim, Na-Hyun; Kim, Dong-Soon; Zhang, Dan; Yi, Hee; Cho, Hee-Jung; Kim, Ja Kyung; Lee, Dong Ki; Kim, Jin-Suk; Shin, Ho-Chul

    2015-01-01

    The present study investigated the preventive effect of ω-3 fatty acids against cholesterol gallstone (CG) formation. CG formation was induced in C57BL/6J mice using a lithogenic diet (LD). The mice were divided into four treatment groups: i) LD, ii) LD plus eicosapentaenoic acid (EPA), iii) LD plus docosahexaenoic acid (DHA) and iv) LD plus EPA plus DHA. Subsequent to feeding the mice the LD for four weeks, EPA and/or DHA (70 mg/kg/day) were orally administered for eight weeks. The mice in the EPA treatment groups exhibited significantly less gallstone formation than those in the LD group. By contrast, DHA treatment only slightly suppressed gallstone formation. The expression of mucin 2, 5AC, 5B and 6 was significantly decreased in the gallbladders of mice in the EPA groups (70-90%) and the LD plus DHA group (30-50%), compared with that in the mice in the LD group. In addition, the mRNA expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase was significantly decreased in the livers of mice in the EPA treatment group compared with that in the livers of mice in the LD group. In conclusion, EPA was found to have a dominant anti-lithogenic effect in C57BL/6J mice. PMID:25333303

  7. Codonopsis lanceolata Extract Prevents Diet-Induced Obesity in C57BL/6 Mice

    PubMed Central

    Lee, Jong Seok; Kim, Kui-Jin; Kim, Young-Hyun; Kim, Dan-Bi; Shin, Gi-Hae; Cho, Ju-Hyun; Kim, Bong Kyun; Lee, Boo-Yong; Lee, Ok-Hwan

    2014-01-01

    Codonopsis lanceolata extract (CLE) has been used in traditional medicine in the Asian-Pacific region for the treatment of bronchitis, cough, and inflammation. However, it is still unclear whether obesity in mice can be altered by diet supplementation with CLE. To investigate whether CLE could have preventative effects on high fat diet (HFD)-induced obesity, male C57BL/6 mice were placed on either a normal chow diet, 60% HFD, or a HFD supplemented with CLE (60, 180, and 360 mg/kg/day) for 12 weeks. CLE decreased body weight and subcutaneous and visceral fat weights in HFD-induced obese mice. CLE group mice showed lower fat accumulation and a smaller adipocyte area in the adipose tissue compared with the HFD group mice. CLE group mice exhibited lower serum levels of triglycerides, total cholesterol, low density lipoprotein (LDL), glucose, and insulin compared with the HFD group mice. In addition, CLE decreased liver weight and lowered the increase in aspartate aminotransferase (AST) and alanine transaminase (ALT) levels in HFD-induced obese mice. These results indicate that CLE can inhibit the development of diet-induced obesity and hyperlipidemia in C57BL/6 mice. PMID:25353662

  8. Effects of housing density and cage floor space on C57BL/6J mice

    USGS Publications Warehouse

    Smith, A.L.; Mabus, S.L.; Stockwell, J.D.; Muir, C.

    2004-01-01

    The Guide for the Care and Use of Laboratory Animals (the Guide) is widely accepted as the housing standard by most Institutional Animal Care and Use Committees. The recommendations are based on best professional judgment rather than experimental data. Current efforts are directed toward replacing these guidelines with data-driven, species-appropriate standards. Our studies were undertaken to determine the optimum housing density for C57BL/6J mice, the most commonly used inbred mouse strain. Four-week-old mice were housed for 8 weeks at four densities (the recommended ???12 in2 [ca. 77.4 cm 2]/mouse down to 5.6 in2 [ca. 36.1 cm2]/mouse) in three cage types with various amounts of floor space. Housing density did not affect a variety of physiologic parameters but did affect certain micro-environmental parameters, although these remained within accepted ranges. A second study was undertaken housing C57BL/6J mice with as little as 3.2 in2/mouse (ca. 20.6 cm2). The major effect was elevated ammonia concentrations that exceeded limits acceptable in the workplace at increased housing densities; however, the nasal passages and eyeballs of the mice remained microscopically normal. On the basis of these results, we conclude that C57BL/6J mice as large as 29 g may be housed with 5.6 in2 of floor space per mouse. This area is approximately half the floor space recommended in the Guide. The role of the Guide is to ensure that laboratory animals are well treated and housed in a species-appropriate manner. Our data suggest that current policies could be altered in order to provide the optimal habitation conditions matched to this species' social needs. Copyright 2004 by the American Association for Laboratory Animal Science.

  9. Home improvement: C57BL/6J mice given more naturalistic nesting materials build better nests.

    PubMed

    Hess, Sarah E; Rohr, Stephanie; Dufour, Brett D; Gaskill, Brianna N; Pajor, Edmond A; Garner, Joseph P

    2008-11-01

    Environmental enrichment of laboratory mice can improve the quality of research, but debate arises over the means of enrichment and its ability to be used in a sterile environment. One important form of enrichment is nesting material. Mice in the wild build dome-shaped, complex, multilayered nests, but this behavior is not seen in the laboratory, perhaps due to inappropriate nesting material rather than the nest-building ability of the mice. Here we focus on the use of naturalistic nesting materials to test whether they improve nest quality through the use of a 'naturalistic nest score' system; we also focus on materials that can be sterilized and easily used in existing housing systems. We first determined whether C57BL/6J mice build naturalistic nests when given shredded paper strips. We then compared these shredded paper strips with other commonly used nesting enrichments (facial tissues and compressed cotton squares). Nests were scored for 6 d. We found that the shredded paper strips allowed the mice to build higher quality nests than those built with any of the other materials. Nests built with tissues were of intermediate quality, and nests built with compressed cotton squares were of poor quality, similar to those built by the control group. These results suggest that C57BL/6J mice given appropriate nesting materials can build nests similar to those built by their wild counterparts.

  10. Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice.

    PubMed

    Flores-Montoya, Mayra Gisel; Sobin, Christina

    2015-07-01

    Research has suggested that chronic low-level lead exposure diminishes neurocognitive function in children. Tests that are sensitive to behavioral effects at lowest levels of lead exposure are needed for the development of animal models. In this study we investigated the effects of chronic low-level lead exposure on exploratory activity (unbaited nose poke task), exploratory ambulation (open field task) and motor coordination (Rotarod task) in pre-adolescent mice. C57BL/6J pups were exposed to 0 ppm (controls), 30 ppm (low-dose) or 230 ppm (high-dose) lead acetate via dams' drinking water administered from birth to postnatal day 28, to achieve a range of blood lead levels (BLLs) from not detectable to 14.84 µg dl(-1) ). At postnatal day 28, mice completed behavioral testing and were killed (n = 61). BLLs were determined by inductively coupled plasma mass spectrometry. The effects of lead exposure on behavior were tested using generalized linear mixed model analyses with BLL, sex and the interaction as fixed effects, and litter as the random effect. BLL predicted decreased exploratory activity and no threshold of effect was apparent. As BLL increased, nose pokes decreased. The C57BL/6J mouse is a useful model for examining effects of early chronic low-level lead exposure on behavior. In the C57BL/6J mouse, the unbaited nose poke task is sensitive to the effects of early chronic low-level lead exposure. This is the first animal study to show behavioral effects in pre-adolescent lead-exposed mice with BLL below 5 µg dl(-1).

  11. Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice.

    PubMed

    Flores-Montoya, Mayra Gisel; Sobin, Christina

    2015-07-01

    Research has suggested that chronic low-level lead exposure diminishes neurocognitive function in children. Tests that are sensitive to behavioral effects at lowest levels of lead exposure are needed for the development of animal models. In this study we investigated the effects of chronic low-level lead exposure on exploratory activity (unbaited nose poke task), exploratory ambulation (open field task) and motor coordination (Rotarod task) in pre-adolescent mice. C57BL/6J pups were exposed to 0 ppm (controls), 30 ppm (low-dose) or 230 ppm (high-dose) lead acetate via dams' drinking water administered from birth to postnatal day 28, to achieve a range of blood lead levels (BLLs) from not detectable to 14.84 µg dl(-1) ). At postnatal day 28, mice completed behavioral testing and were killed (n = 61). BLLs were determined by inductively coupled plasma mass spectrometry. The effects of lead exposure on behavior were tested using generalized linear mixed model analyses with BLL, sex and the interaction as fixed effects, and litter as the random effect. BLL predicted decreased exploratory activity and no threshold of effect was apparent. As BLL increased, nose pokes decreased. The C57BL/6J mouse is a useful model for examining effects of early chronic low-level lead exposure on behavior. In the C57BL/6J mouse, the unbaited nose poke task is sensitive to the effects of early chronic low-level lead exposure. This is the first animal study to show behavioral effects in pre-adolescent lead-exposed mice with BLL below 5 µg dl(-1). PMID:25219894

  12. Total glucosides of peony attenuates experimental autoimmune encephalomyelitis in C57BL/6 mice.

    PubMed

    Huang, Qiling; Ma, Xiaomeng; Zhu, Dong Liang; Chen, Li; Jiang, Ying; Zhou, Linli; Cen, Lei; Pi, Rongbiao; Chen, Xiaohong

    2015-07-15

    Total glucosides of peony (TGP), an active compound extracted from the roots of Paeonia lactiflora Pall, has wide pharmacological effects on nervous system. Here we examined the effects of TGP on experimental autoimmune encephalomyelitis (EAE), an established model of multiple sclerosis (MS). The results showed that TGP can reduce the severity and progression of EAE in C57 BL/6 mice. In addition, TGP also down-regulated the Th1/Th17 inflammatory response and prevented the reduced expression of brain-derived neurotrophic factor and 2',3'-cyclic nucleotide 3'-phosphodiesterase of EAE. These findings suggest that TGP could be a potential therapeutic agent for MS.

  13. Total glucosides of peony attenuates experimental autoimmune encephalomyelitis in C57BL/6 mice.

    PubMed

    Huang, Qiling; Ma, Xiaomeng; Zhu, Dong Liang; Chen, Li; Jiang, Ying; Zhou, Linli; Cen, Lei; Pi, Rongbiao; Chen, Xiaohong

    2015-07-15

    Total glucosides of peony (TGP), an active compound extracted from the roots of Paeonia lactiflora Pall, has wide pharmacological effects on nervous system. Here we examined the effects of TGP on experimental autoimmune encephalomyelitis (EAE), an established model of multiple sclerosis (MS). The results showed that TGP can reduce the severity and progression of EAE in C57 BL/6 mice. In addition, TGP also down-regulated the Th1/Th17 inflammatory response and prevented the reduced expression of brain-derived neurotrophic factor and 2',3'-cyclic nucleotide 3'-phosphodiesterase of EAE. These findings suggest that TGP could be a potential therapeutic agent for MS. PMID:26025060

  14. Lack of Evidence for Neonatal Misoprostol Neurodevelopmental Toxicity in C57BL6/J Mice

    PubMed Central

    Koenig, Claire M.; Walker, Cheryl K.; Qi, Lihong; Pessah, Isaac N.; Berman, Robert F.

    2012-01-01

    Misoprostol is a synthetic analogue of prostaglandin E1 that is administered to women at high doses to induce uterine contractions for early pregnancy termination and at low doses to aid in cervical priming during labor. Because of the known teratogenic effects of misoprostol when given during gestation and its effects on axonal growth in vitro, we examined misoprostol for its potential as a neurodevelopmental toxicant when administered to neonatal C57BL6/J mice. Mice were injected subcutaneously (s.c.) with 0.4, 4 or 40 µg/kg misoprostol on postnatal day 7, the approximate developmental stage in mice of human birth, after which neonatal somatic growth, and sensory and motor system development were assessed. These doses were selected to span the range of human exposure used to induce labor. In addition, adult mice underwent a battery of behavioral tests relevant to neurodevelopmental disorders such as autism including tests for anxiety, stereotyped behaviors, social communication and interactions, and learning and memory. No significant effects of exposure were found for any measure of development or behavioral endpoints. In conclusion, the results of the present study in C57BL/6J mice do not provide support for neurodevelopmental toxicity after misoprostol administration approximating human doses and timed to coincide with the developmental stage of human birth. PMID:22719983

  15. Respiratory syncytial virus increases lung cellular bioenergetics in neonatal C57BL/6 mice

    SciTech Connect

    Alsuwaidi, Ahmed R.; Albawardi, Alia; Almarzooqi, Saeeda; Benedict, Sheela; Othman, Aws R.; Hartwig, Stacey M.; Varga, Steven M.; Souid, Abdul-Kader

    2014-04-15

    We have previously reported that lung cellular bioenergetics (cellular respiration and ATP) increased in 4–10 week-old BALB/c mice infected with respiratory syncytial virus (RSV). This study examined the kinetics and changes in cellular bioenergetics in ≤2-week-old C57BL/6 mice following RSV infection. Mice (5–14 days old) were inoculated intranasally with RSV and the lungs were examined on days 1–10 post-infection. Histopathology and electron microscopy revealed preserved pneumocyte architectures and organelles. Increased lung cellular bioenergetics was noted from days 1–10 post-infection. Cellular GSH remained unchanged. These results indicate that the increased lung cellular respiration (measured by mitochondrial O{sub 2} consumption) and ATP following RSV infection is independent of either age or genetic background of the host. - Highlights: • RSV infection increases lung cellular respiration and ATP in neonatal C57BL/6 mice. • Increased lung cellular bioenergetics is a biomarker of RSV infection. • Lung cellular glutathione remains unchanged in RSV infection.

  16. Red ginseng delays age-related hearing and vestibular dysfunction in C57BL/6 mice.

    PubMed

    Tian, Chunjie; Kim, Yeon Ju; Lim, Hye Jin; Kim, Young Sun; Park, Hun Yi; Choung, Yun-Hoon

    2014-09-01

    Since Korean red ginseng (KRG) has been proven to protect against gentamicin-induced vestibular and hearing dysfunction, the effects of KRG on age-related inner ear disorder in C57BL/6 mice were investigated. While age-related hearing loss was detected at the age of 6months (32kHz) and 9months (16kHz) in the control group, it was significantly delayed (p<0.05) in the 150mg/kg KRG-treated group. Vestibular dysfunction was observed in the tail-hanging and swimming tests, with significantly different severity scores and swimming times detected between the control and 150mg/kg KRG-treated group at the age of 12months (p<0.05). Mice treated with 500mg/kg KRG exhibited irritability and aggravated inner ear dysfunction. Histological observation supported the findings of hearing and vestibular function defects. In conclusion, C57BL/6 mice showed early-onset hearing loss and progressive vestibular dysfunction with aging, which were delayed by treatment with 150mg/kg KRG. However, 500mg/kg KRG treatment may induce aggressive behavior. PMID:24952098

  17. Maternal behavior and offspring resiliency to maternal separation in C57Bl/6 mice.

    PubMed

    Own, Lawrence S; Patel, Paresh D

    2013-03-01

    Adverse early life experience, such as childhood abuse, neglect, and trauma, increases lifetime risk for mental illness. To investigate underlying mechanisms, the maternal separation (MS) paradigm was developed and validated as an animal model of early adversity in rats, reliably effecting long-term changes to anxiety, gene expression, and stress response. However, across-species validation of core findings in mice has met with limited success. To re-visit parameters governing the effectiveness of MS in mice, this study investigated the effect of MS on maternal care, offspring behavior, and offspring stress-induced corticosterone response in the c57bl/6 mouse strain. The results from this study suggest that: (i) levels of maternal care increase as a function of separation duration immediately after daily MS, but long-term care remains unchanged; and (ii) c57bl/6 mice are resilient to MS, exhibiting subtle decreases in anxiety and unchanged stress-induced corticosterone response as adults, irrespective of separation duration. PMID:23195752

  18. Brain plasticity and cognitive functions after ethanol consumption in C57BL/6J mice

    PubMed Central

    Stragier, E; Martin, V; Davenas, E; Poilbout, C; Mongeau, R; Corradetti, R; Lanfumey, L

    2015-01-01

    Acute or chronic administrations of high doses of ethanol in mice are known to produce severe cognitive deficits linked to hippocampal damage. However, we recently reported that chronic and moderate ethanol intake in C57BL/6J mice induced chromatin remodeling within the Bdnf promoters, leading to both enhanced brain-derived neurotrophic factor (BDNF) expression and hippocampal neurogenesis under free-choice protocol. We performed here a series of cellular and behavioral studies to analyze the consequences of these modifications. We showed that a 3-week chronic free-choice ethanol consumption in C57BL/6J mice led to a decrease in DNA methylation of the Bdnf gene within the CA1 and CA3 subfields of the hippocampus, and upregulated hippocampal BDNF signaling pathways mediated by ERK, AKT and CREB. However, this activation did not affect long-term potentiation in the CA1. Conversely, ethanol intake impaired learning and memory capacities analyzed in the contextual fear conditioning test and the novel object recognition task. In addition, ethanol increased behavioral perseveration in the Barnes maze test but did not alter the mouse overall spatial capacities. These data suggested that in conditions of chronic and moderate ethanol intake, the chromatin remodeling leading to BDNF signaling upregulation is probably an adaptive process, engaged via epigenetic regulations, to counteract the cognitive deficits induced by ethanol. PMID:26670281

  19. Brain plasticity and cognitive functions after ethanol consumption in C57BL/6J mice.

    PubMed

    Stragier, E; Martin, V; Davenas, E; Poilbout, C; Mongeau, R; Corradetti, R; Lanfumey, L

    2015-01-01

    Acute or chronic administrations of high doses of ethanol in mice are known to produce severe cognitive deficits linked to hippocampal damage. However, we recently reported that chronic and moderate ethanol intake in C57BL/6J mice induced chromatin remodeling within the Bdnf promoters, leading to both enhanced brain-derived neurotrophic factor (BDNF) expression and hippocampal neurogenesis under free-choice protocol. We performed here a series of cellular and behavioral studies to analyze the consequences of these modifications. We showed that a 3-week chronic free-choice ethanol consumption in C57BL/6J mice led to a decrease in DNA methylation of the Bdnf gene within the CA1 and CA3 subfields of the hippocampus, and upregulated hippocampal BDNF signaling pathways mediated by ERK, AKT and CREB. However, this activation did not affect long-term potentiation in the CA1. Conversely, ethanol intake impaired learning and memory capacities analyzed in the contextual fear conditioning test and the novel object recognition task. In addition, ethanol increased behavioral perseveration in the Barnes maze test but did not alter the mouse overall spatial capacities. These data suggested that in conditions of chronic and moderate ethanol intake, the chromatin remodeling leading to BDNF signaling upregulation is probably an adaptive process, engaged via epigenetic regulations, to counteract the cognitive deficits induced by ethanol. PMID:26670281

  20. FXR agonist GW4064 increases plasma glucocorticoid levels in C57BL/6 mice.

    PubMed

    Hoekstra, Menno; van der Sluis, Ronald J; Li, Zhaosha; Oosterveer, Maaike H; Groen, Albert K; Van Berkel, Theo J C

    2012-10-15

    Since high expression of farnesoid X receptor (FXR) has been detected in glucocorticoid-producing adrenocortical cells, we evaluated the potential role of FXR in adrenal glucocorticoid production. FXR agonist GW4064 increased fasting plasma corticosterone levels (+45%; P<0.01) in C57BL/6 mice, indicative of enhanced adrenal steroidogenesis. GW4064 treatment did not affect plasma ACTH levels, adrenal weight, or adrenal expression of steroidogenic genes. Scavenger receptor BI (SR-BI) mRNA and protein expression, respectively, increased 1.9-fold (P<0.01) and 1.5-fold, which suggests a stimulated lipoprotein-associated cholesterol uptake into the adrenals upon GW4064 treatment. In line with an enhanced flux of cellular cholesterol into the steroidogenic pathway, adrenal unesterified and esterified cholesterol stores were 21-41% decreased (P<0.01) upon GW4064 treatment. In conclusion, we have shown that the FXR agonist GW4064 stimulates plasma corticosterone levels in C57BL/6 mice. Our findings suggest a novel role for FXR in the modulation of adrenal cholesterol metabolism and glucocorticoid synthesis in mice.

  1. Brain plasticity and cognitive functions after ethanol consumption in C57BL/6J mice.

    PubMed

    Stragier, E; Martin, V; Davenas, E; Poilbout, C; Mongeau, R; Corradetti, R; Lanfumey, L

    2015-01-01

    Acute or chronic administrations of high doses of ethanol in mice are known to produce severe cognitive deficits linked to hippocampal damage. However, we recently reported that chronic and moderate ethanol intake in C57BL/6J mice induced chromatin remodeling within the Bdnf promoters, leading to both enhanced brain-derived neurotrophic factor (BDNF) expression and hippocampal neurogenesis under free-choice protocol. We performed here a series of cellular and behavioral studies to analyze the consequences of these modifications. We showed that a 3-week chronic free-choice ethanol consumption in C57BL/6J mice led to a decrease in DNA methylation of the Bdnf gene within the CA1 and CA3 subfields of the hippocampus, and upregulated hippocampal BDNF signaling pathways mediated by ERK, AKT and CREB. However, this activation did not affect long-term potentiation in the CA1. Conversely, ethanol intake impaired learning and memory capacities analyzed in the contextual fear conditioning test and the novel object recognition task. In addition, ethanol increased behavioral perseveration in the Barnes maze test but did not alter the mouse overall spatial capacities. These data suggested that in conditions of chronic and moderate ethanol intake, the chromatin remodeling leading to BDNF signaling upregulation is probably an adaptive process, engaged via epigenetic regulations, to counteract the cognitive deficits induced by ethanol.

  2. Multi-walled carbon nanotube instillation impairs pulmonary function in C57BL/6 mice

    PubMed Central

    2011-01-01

    Background Multi-walled carbon nanotubes (MWCNTs) are widely used in many disciplines due to their unique physical and chemical properties. Therefore, some concerns about the possible human health and environmental impacts of manufactured MWCNTs are rising. We hypothesized that instillation of MWCNTs impairs pulmonary function in C57BL/6 mice due to development of lung inflammation and fibrosis. Methods MWCNTs were administered to C57BL/6 mice by oropharyngeal aspiration (1, 2, and 4 mg/kg) and we assessed lung inflammation and fibrosis by inflammatory cell infiltration, collagen content, and histological assessment. Pulmonary function was assessed using a FlexiVent system and levels of Ccl3, Ccl11, Mmp13 and IL-33 were measured by RT-PCR and ELISA. Results Mice administered MWCNTs exhibited increased inflammatory cell infiltration, collagen deposition and granuloma formation in lung tissue, which correlated with impaired pulmonary function as assessed by increased resistance, tissue damping, and decreased lung compliance. Pulmonary exposure to MWCNTs induced an inflammatory signature marked by cytokine (IL-33), chemokine (Ccl3 and Ccl11), and protease production (Mmp13) that promoted the inflammatory and fibrotic changes observed within the lung. Conclusions These results further highlight the potential adverse health effects that may occur following MWCNT exposure and therefore we suggest these materials may pose a significant risk leading to impaired lung function following environmental and occupational exposures. PMID:21851604

  3. Responses of Male C57BL/6N Mice to Observing the Euthanasia of Other Mice.

    PubMed

    Boivin, Gregory P; Bottomley, Michael A; Grobe, Nadja

    2016-01-01

    The AVMA Panel on Euthanasia recommends that sensitive animals should not be present during the euthanasia of others, especially of their own species, but does not provide guidelines on how to identify a sensitive species. To determine if mice are a sensitive species we reviewed literature on empathy in mice, and measured the cardiovascular and activity response of mice observing euthanasia of conspecifics. We studied male 16-wk-old C57BL/6N mice and found no increase in cardiovascular parameters or activity in the response of the mice to observing CO2 euthanasia. Mice observing decapitation had an increase in all values, but this was paralleled by a similar increase during mock decapitations in which no animals were handled or euthanized. We conclude that CO2 euthanasia of mice does not have an impact on other mice in the room, and that euthanasia by decapitation likely only has an effect due to the noise of the guillotine. We support the conceptual idea that mice are both a sensitive species and display empathy, but under the controlled circumstances of the euthanasia procedures used in this study there was no signaling of stress to witnessing inhabitants in the room. PMID:27423146

  4. High-energy proton irradiation of C57Bl6 mice under hindlimb unloading

    NASA Astrophysics Data System (ADS)

    Mendonca, Marc; Todd, Paul; Orschell, Christie; Chin-Sinex, Helen; Farr, Jonathan; Klein, Susan; Sokol, Paul

    2012-07-01

    Solar proton events (SPEs) pose substantial risk for crewmembers on deep space missions. It has been shown that low gravity and ionizing radiation both produce transient anemia and immunodeficiencies. We utilized the C57Bl/6 based hindlimb suspension model to investigate the consequences of hindlimb-unloading induced immune suppression on the sensitivity to whole body irradiation with modulated 208 MeV protons. Eight-week old C57Bl/6 female mice were conditioned by hindlimb-unloading. Serial CBC and hematocrit assays by HEMAVET were accumulated for the hindlimb-unloaded mice and parallel control animals subjected to identical conditions without unloading. One week of hindlimb-unloading resulted in a persistent, statistically significant 10% reduction in RBC count and a persistent, statistically significant 35% drop in lymphocyte count. This inhibition is consistent with published observations of low Earth orbit flown mice and with crewmember blood analyses. In our experiments the cell count suppression was sustained for the entire six-week period of observation and persisted for at least 7 days beyond the period of active hindlimb-unloading. C57Bl/6 mice were also irradiated with 208 MeV Spread Out Bragg Peak (SOBP) protons at the Midwest Proton Radiotherapy Institute at the Indiana University Cyclotron Facility. We found that at 8.5 Gy hindlimb-unloaded mice were significantly more radiation sensitive with 35 lethalities out of 51 mice versus 15 out of 45 control (non-suspended) mice within 30 days of receiving 8.5 Gy of SOBP protons (p =0.001). Both control and hindlimb-unloaded stocktickerCBC analyses of 8.5 Gy proton irradiated and control mice by HEMAVET demonstrated severe reductions in WBC counts (Lymphocytes and PMNs) by day 2 post-irradiation, followed a week to ten days later by reductions in platelets, and then reductions in RBCs about 2 weeks post-irradiation. Recovery of all blood components commenced by three weeks post-irradiation. CBC analyses of 8

  5. Effects of Excess Energy Intake on Glucose and Lipid Metabolism in C57BL/6 Mice.

    PubMed

    Pang, Jing; Xi, Chao; Huang, Xiuqing; Cui, Ju; Gong, Huan; Zhang, Tiemei

    2016-01-01

    Excess energy intake correlates with the development of metabolic disorders. However, different energy-dense foods have different effects on metabolism. To compare the effects of a high-fat diet, a high-fructose diet and a combination high-fat/high-fructose diet on glucose and lipid metabolism, male C57BL/6 mice were fed with one of four different diets for 3 months: standard chow; standard diet and access to fructose water; a high fat diet; and a high fat diet with fructose water. After 3 months of feeding, the high-fat and the combined high-fat/high-fructose groups showed significantly increased body weights, accompanied by hyperglycemia and insulin resistance; however, the high-fructose group was not different from the control group. All three energy-dense groups showed significantly higher visceral fat weights, total cholesterol concentrations, and low-density lipoprotein cholesterol concentrations compared with the control group. Assays of basal metabolism showed that the respiratory quotient of the high-fat, the high-fructose, and the high-fat/high-fructose groups decreased compared with the control group. The present study confirmed the deleterious effect of high energy diets on body weight and metabolism, but suggested that the energy efficiency of the high-fructose diet was much lower than that of the high-fat diet. In addition, fructose supplementation did not worsen the detrimental effects of high-fat feeding alone on metabolism in C57BL/6 mice. PMID:26745179

  6. Effects of Excess Energy Intake on Glucose and Lipid Metabolism in C57BL/6 Mice

    PubMed Central

    Huang, Xiuqing; Cui, Ju; Gong, Huan; Zhang, Tiemei

    2016-01-01

    Excess energy intake correlates with the development of metabolic disorders. However, different energy-dense foods have different effects on metabolism. To compare the effects of a high-fat diet, a high-fructose diet and a combination high-fat/high-fructose diet on glucose and lipid metabolism, male C57BL/6 mice were fed with one of four different diets for 3 months: standard chow; standard diet and access to fructose water; a high fat diet; and a high fat diet with fructose water. After 3 months of feeding, the high-fat and the combined high-fat/high-fructose groups showed significantly increased body weights, accompanied by hyperglycemia and insulin resistance; however, the high-fructose group was not different from the control group. All three energy-dense groups showed significantly higher visceral fat weights, total cholesterol concentrations, and low-density lipoprotein cholesterol concentrations compared with the control group. Assays of basal metabolism showed that the respiratory quotient of the high-fat, the high-fructose, and the high-fat/high-fructose groups decreased compared with the control group. The present study confirmed the deleterious effect of high energy diets on body weight and metabolism, but suggested that the energy efficiency of the high-fructose diet was much lower than that of the high-fat diet. In addition, fructose supplementation did not worsen the detrimental effects of high-fat feeding alone on metabolism in C57BL/6 mice. PMID:26745179

  7. Hydrolyzed casein reduces diet-induced obesity in male C57BL/6J mice.

    PubMed

    Lillefosse, Haldis H; Tastesen, Hanne Sørup; Du, Zhen-Yu; Ditlev, Ditte B; Thorsen, Frits A; Madsen, Lise; Kristiansen, Karsten; Liaset, Bjørn

    2013-09-01

    The digestion rate of dietary protein is a regulating factor for postprandial metabolism both in humans and animal models. However, few data exist about the habitual consumption of proteins with different digestion rates with regard to the development of body mass and diet-induced obesity. Here, we used a factorial ANOVA design to investigate the effects of protein form (intact vs. hydrolyzed casein) and protein level (16 vs. 32 energy percent protein) on body mass gain and adiposity in obesity-prone male C57BL/6J mice fed Western diets with 35 energy percent fat. Mice fed the hydrolyzed casein diets had higher spontaneous locomotor activity than mice fed intact casein. During the light phase, mice fed hydrolyzed casein tended (P = 0.08) to have a lower respiratory exchange ratio, indicating lower utilization of carbohydrates as energy substrate relative to those fed intact casein. In further support of less carbohydrate oxidation, plasma concentrations of glucose and those of the glucose metabolite lactate were lower in fed mice that consumed the hydrolyzed compared with the intact casein diet. Concomitantly, the plasma insulin concentration was strongly reduced in fed mice given hydrolyzed casein relative to those given intact casein. The mice fed hydrolyzed casein had greater ex vivo inguinal white adipose tissue non-CO2 β-oxidation capacity along with induced expression of genes involved in mitochondrial fatty acid oxidation and mitochondrial uncoupling. The physiological changes induced by hydrolyzed casein ingestion translated into decreased body and adipose tissue masses. We conclude that chronic consumption of extensively hydrolyzed casein reduces body mass gain and diet-induced obesity in male C57BL/6J mice.

  8. Decline in muscle strength and running endurance in klotho deficient C57BL/6 mice.

    PubMed

    Phelps, Michael; Pettan-Brewer, Christina; Ladiges, Warren; Yablonka-Reuveni, Zipora

    2013-12-01

    Alpha klotho (known as klotho) is a multifunctional protein that may be linked to age-associated decline in tissue homeostasis. The original klotho hypomorphic (klotho (hm) ) mouse, produced on a mixed C57BL/6 and C3H background, is short lived and exhibits extensive aging-like deterioration of several body systems. Differently, klotho (hm) mice on a pure C57BL/6 background do not appear sickly nor die young, which has permitted us to gain insight into the effect of klotho deficiency in adult life. First, analyzing klotho transcript levels in the kidney, the main site of klotho production, we demonstrated a 71-fold decline in klotho (hm) females compared to wildtype females versus only a 4-fold decline in mutant males. We then examined the effect of klotho deficiency on muscle-related attributes in adult mice, focusing on 7-11 month old females. Body weight and forelimb grip strength were significantly reduced in klotho (hm) mice compared to wildtype and klotho overexpressing mice. The female mice were also subjected to voluntary wheel running for a period of 6 days. Running endurance was markedly reduced in klotho (hm) mice, which exhibited a sporadic running pattern that may be characteristic of repeated bouts of exhaustions. When actually running, klotho (hm) females ran at the same speed as wildtype and klotho overexpressing mice, but spent about 65 % less time running compared to the other two groups. Our novel results suggest an important link between klotho deficiency and muscle performance. This study provides a foundation for further research on klotho involvement as a potential inhibitor of age-associated muscle deterioration.

  9. Effect of Fenbendazole on Three Behavioral Tests in Male C57BL/6N Mice

    PubMed Central

    Gadad, Bharathi S; Daher, João P L; Hutchinson, Eric K; Brayton, Cory F; Dawson, Ted M; Pletnikov, Mikhail V; Watson, Julie

    2010-01-01

    Pinworms are highly contagious parasites of laboratory rodents that often are treated with fenbendazole. To our knowledge, the effect of fenbendazole at therapeutic dosages on behavioral tests in mice has not been evaluated. Here we studied 6-wk-old male C57BL/6N mice. We compared the behavior of control mice (fed regular diet) with 3 groups of mice treated with dietary fenbendazole. Treatment groups were 4 wk of fenbendazole, 2 wk of fenbendazole followed by 2 wk of regular diet, and 2 wk of regular diet followed by 2 wk of fenbendazole. At the end of dietary treatment all groups were tested by open field for central, peripheral and vertical activity; elevated plus maze for anxiety; and rotarod for motor ability and then evaluated by clinical pathology and selected histopathology. Treated and control groups showed no differences in open field or elevated plus maze testing, histopathology, or clinical pathology. However mice treated for 4 wk with fenbendazole or 2 wk of fenbendazole followed by 2 wk regular diet stayed on the rotarod for shorter periods than did controls, and mice treated with 2 wk of regular diet followed by 2 wk fenbendazole showed a trend toward shorter rotarod times. In light of this study, we suggest that open field and elevated plus maze testing is unlikely to be affected by 4 wk fenbendazole treatment in male C57BL/6 mice; however, behavioral tests of motor ability such as rotarod tests may be affected during and for at least 2 wk after fenbendazole treatment. PMID:21205447

  10. Effect of fenbendazole on three behavioral tests in male C57BL/6N mice.

    PubMed

    Gadad, Bharathi S; Daher, João P L; Hutchinson, Eric K; Brayton, Cory F; Dawson, Ted M; Pletnikov, Mikhail V; Watson, Julie

    2010-11-01

    Pinworms are highly contagious parasites of laboratory rodents that often are treated with fenbendazole. To our knowledge, the effect of fenbendazole at therapeutic dosages on behavioral tests in mice has not been evaluated. Here we studied 6-wk-old male C57BL/6N mice. We compared the behavior of control mice (fed regular diet) with 3 groups of mice treated with dietary fenbendazole. Treatment groups were 4 wk of fenbendazole, 2 wk of fenbendazole followed by 2 wk of regular diet, and 2 wk of regular diet followed by 2 wk of fenbendazole. At the end of dietary treatment all groups were tested by open field for central, peripheral and vertical activity; elevated plus maze for anxiety; and rotarod for motor ability and then evaluated by clinical pathology and selected histopathology. Treated and control groups showed no differences in open field or elevated plus maze testing, histopathology, or clinical pathology. However mice treated for 4 wk with fenbendazole or 2 wk of fenbendazole followed by 2 wk regular diet stayed on the rotarod for shorter periods than did controls, and mice treated with 2 wk of regular diet followed by 2 wk fenbendazole showed a trend toward shorter rotarod times. In light of this study, we suggest that open field and elevated plus maze testing is unlikely to be affected by 4 wk fenbendazole treatment in male C57BL/6 mice; however, behavioral tests of motor ability such as rotarod tests may be affected during and for at least 2 wk after fenbendazole treatment.

  11. Sex differences in novelty- and psychostimulant-induced behaviors of C57BL/6 mice

    PubMed Central

    Van Swearingen, Amanda E. D.; Walker, Q. David; Kuhn, Cynthia M.

    2012-01-01

    Rationale Women are more sensitive than men to psychostimulants and progress from initial use to drug addiction more quickly. The mouse has been an under-utilized model to study sex differences in psychostimulant action. Mice could serve as an ideal genetically-tractable model for mechanistic studies into sex and hormone effects on psychostimulant behavior. Objectives To characterize psychostimulant effects in male and female mice with a combination of automated data collection and behavioral observation. Methods Male and female C57BL/6 mice (Charles River) were given a single dose or sequential ascending binge doses of d-amphetamine (AMPH) or cocaine (COC). Behavior was assessed in open field chambers using both automated photobeam interruptions and behavioral observations. Brain psychostimulant concentrations were determined at the time of maximum behavioral stimulation. Results Psychostimulants induced behavioral activation in mice including both increased locomotion as detected with an automated system and a sequence of behaviors progressing from stereotyped sniffing at low doses to patterned locomotion and rearing at high doses. Females exhibited more patterned locomotion and a shift towards higher behavior scores after either psychostimulant despite having lower AMPH and equivalent COC brain levels as males. Conclusions Female C57BL/6 mice exhibit enhanced psychostimulant-induced behavior compared to males, similar to reports in rats. The combination of automated behavioral measures and behavioral observation was essential for verifying the existence of these differences. These results indicate the importance of testing both sexes when characterizing genetically manipulated mice to control for potential sex-specific effects. PMID:22975726

  12. Blueberry and Mulberry Juice Prevent Obesity Development in C57BL/6 Mice

    PubMed Central

    Wu, Tao; Tang, Qiong; Gao, Zichun; Yu, Zhuoping; Song, Haizhao; Zheng, Xiaodong; Chen, Wei

    2013-01-01

    Objectives To establish whether blueberry (Vaccinium ashei) and mulberry (Morus australis Poir) juice, anthocyanin rich fruit juice, may help counteract obesity. Design And Methods: Four-week-old C57BL/6 mice were fed a high-fat diet (HFD) with or without blueberry and mulberry juice for 12 weeks. Body weight, serum and hepatic lipids, liver and adipose tissues morphology, insulin and leptin were assessed. Results Mice fed HFD exhibited increased body weight, insulin resistance, serum and hepatic lipids. In comparison, blueberry and mulberry juice inhibited body weight gain, decreased the serum cholesterol, reduced the resistance to insulin, attenuated lipid accumulation and decreased the leptin secretin. Conclusion These results indicate that blueberry and mulberry juice may help counteract obesity. PMID:24143244

  13. Effect of Chlorovirus ATCV-1 infection on behavior of C57Bl/6 mice.

    PubMed

    Petro, Marilyn S; Agarkova, Irina V; Petro, Thomas M

    2016-08-15

    Neuroinflammation induced during immune responses to viral infections in the brain affect behavior. Unexpected evidence that oral gavage of an algal virus in its host algal cells could alter cognition was further examined by directly injecting purified algal virus ATCV-1 intracranially into C57BL/6 mice. After 4weeks, the ATCV-1 infection impaired delayed location recognition memory, and also reduced and anxiety. Corresponding to these effects, heightened ATCV-1, IL-6, iNOS, IFN-γ, and CD11b expression in brains was observed 3-days and/or 8-weeks post infection compared with control mice. These results imply that ATCV-1 infection damages the hippocampus via induction of inflammatory factors. PMID:27397075

  14. Post-training cocaine exposure facilitates spatial memory consolidation in C57BL/6 mice.

    PubMed

    Iñiguez, Sergio D; Charntikov, Sergios; Baella, Shelley A; Herbert, Matthew S; Bolaños-Guzmán, Carlos A; Crawford, Cynthia A

    2012-04-01

    In this study, we examined the ability of post-training injections of cocaine to facilitate spatial memory performance using the Morris water maze (MWM). We also investigated the role that hippocampal protein kinase A (PKA) and extracellular signal-regulated kinase 1/2 (ERK) signaling may play in cocaine-mediated spatial memory consolidation processes. Male and female C57BL/6 mice were first trained in a MWM task (eight consecutive trials) then injected with cocaine (0, 1.25, 2.5, 5, or 20 mg/kg), and memory for the platform location was retested after a 24 h delay. Cocaine had a dose-dependent effect on spatial memory performance because only the mice receiving 2.5 mg/kg cocaine displayed a significant reduction in latency to locate the platform. No sex differences in MWM performance were observed; however, females showed higher hippocampal levels of PKA when compared with males. A second experiment demonstrated that 2.5 mg/kg cocaine enhanced MWM performance only when administered within 2, but not 4 h after spatial training. We also found that cocaine (2.5 mg/kg) increased ERK2 phosphorylation within the hippocampus and one of its downstream targets (ribosomal S6 kinase), a mechanism that may be responsible, at least in part, for the enhanced cocaine-mediated spatial memory performance. Overall, these data demonstrate that a low dose of cocaine (2.5 mg/kg) administered within 2 h after training facilitates MWM spatial memory performance in C57BL/6 mice.

  15. Cornu cervi pantotrichum Pharmacopuncture Solution Facilitate Hair Growth in C57BL/6 Mice

    PubMed Central

    Lee, Seon-Yong; Lee, Dong-Jin; Kwon, Kang; Lee, Chang-Hyun; Shin, Hyun Jong; Kim, Jai Eun; Ha, Ki-Tae; Jeong, Han-Sol

    2016-01-01

    Objectives: Cornu cervi pantotrichum (CCP) has been widely used in Korean and China, as an anti-fatigue, anti-aging, and tonic agent to enhance the functions of the reproductive and the immune systems. Because CCP has various growth factors that play important roles in the development of hair follicles, we examined whether CCP pharmacopuncture solution (CCPPS) was capable of promoting hair growth in an animal model. Methods: One day after hair depilation, CCPPS were topically applied to the dorsal skin of C57BL/6 mice once a day for 15 days. Hair growth activity was evaluated by using macro- and microscopic observations. Dorsal skin tissues were stained with hematoxylin and eosin. Expressions of bromodeoxyuridine (BrdU), proliferating cell nuclear antigen (PCNA), and fibroblast growth factor (FGF)-7 were examined by using immunohistochemical staining. A reverse transcription polymerase chain reaction (RT-PCR) analysis was also conducted to measure the messenger RNA (mRNA) expression of FGF-7. Results: CCPPS induced more active hair growth than normal saline. Histologic analysis showed enlargement of the dermal papilla, elongation of the hair shaft, and expansion of hair thickness in CCPPS treated mice, indicating that CCPPS effectively induced the development of anagen. CCPPS treatment markedly increased the expressions of BrdU and PCNA in the hair follicles of C57BL/6 mice. In addition, CCPPS up regulated the expression of FGF-7, which plays an important role in the development of hair follicles. Conclusion: These results reveal that CCPPS facilitates hair re-growth by proliferation of hair follicular cells and up-regulation of FGF-7 and suggest that CCPPS can potentially be applied as an alternative treatment for patients with alopecia. PMID:27386145

  16. Brain energy stores in C57BL/6 mice after C. parvum injection.

    PubMed

    Sheng, W S; Lin, J C; Apple, F; Hu, S; Peterson, P K; Chao, C C

    1999-01-18

    Activation of the immune system has been associated with the development of fatigue of unknown cause. We were interested in brain energy stores (e.g., phosphocreatine (PCr) and creatine kinase) after immune activation to investigate whether this system was altered. In this model, fatigue (defined as > 50% reduction in spontaneous running) was induced in C57BL/6 mice after a single injection of Corynebacterium parvum antigen. Maximal fatigue (about 86% reduction on day 10 post injection) was associated with reduced (about 29%) brain PCr/gamma-ATP and increased creatine kinase levels (approximately 31%), suggesting an active process of brain ATP depletion and replenishment. These findings need to be further delineated to establish the relationship between immune activation, reduced brain energy pools and fatigue. PMID:10094158

  17. Characterization of age-associated changes in peripheral organ and brain region weights in C57BL/6 mice.

    PubMed

    Lessard-Beaudoin, Mélissa; Laroche, Mélissa; Demers, Marie-Josée; Grenier, Guillaume; Graham, Rona K

    2015-03-01

    In order to further understand age-related physiological changes and to have in depth reference values for C57BL/6 mice, we undertook a study to assess the effects of aging on peripheral organ weights, and brain region weights in wild type C57BL/6 male mice. Peripheral organs, body and brain region weights were collected from young (3-4 months), mid (12 months), old (23-28 months) and very old (>30 months) mice. Significant increases are observed with aging in body, liver, heart, kidney and spleen organ weights. A decrease in organ weight is observed with aging in liver and kidney only in the very old mice. In contrast, testes weight decreases with age. Within the brain, hippocampi, striata and olfactory bulbs weight decreases with age. These data further our knowledge of the anatomical and biological changes that occur with aging and provide reference values for physiological-based pharmacokinetic studies in C57BL/6 mice.

  18. Sweetener preference of C57BL/6ByJ and 129P3/J mice.

    PubMed

    Bachmanov, A A; Tordoff, M G; Beauchamp, G K

    2001-09-01

    Previous studies have shown large differences in taste responses to several sweeteners between mice of the C57BL/6ByJ (B6) and 129P3/J (129) inbred strains. The goal of this study was to compare behavioral responses of B6 and 129 mice to a wider variety of sweeteners. Seventeen sweeteners were tested using two-bottle preference tests with water. Three main patterns of strain differences were evident. First, sucrose, maltose, saccharin, acesulfame-K, sucralose and SC-45647 were preferred by both strains, but the B6 mice had lower preference thresholds and higher solution intakes. Second, the amino acids D-phenylalanine, D-tryptophan, L-proline and glycine were highly preferred by B6 mice, but not by 129 mice. Third, glycyrrhizic acid, neohesperidin dihydrochalcone, thaumatin and cyclamate did not evoke strong preferences in either strain. Aspartame was neutral to all 129 and some B6 mice, but other B6 mice strongly preferred it. Thus, compared with the 129 mice the B6 mice had higher preferences for sugars, sweet tasting amino acids and several but not all non-caloric sweeteners. Glycyrrhizic acid, neohesperidin, thaumatin and cyclamate are not palatable to B6 or 129 mice.

  19. Erionite induces production of autoantibodies and IL-17 in C57BL/6 mice

    SciTech Connect

    Zebedeo, Christian Nash; Davis, Chad; Peña, Cecelia; Ng, Kok Wei; Pfau, Jean C.

    2014-03-15

    Background: Erionite has similar chemical and physical properties to amphibole asbestos, which induces autoantibodies in mice. Current exposures are occurring in North Dakota due to the use of erionite-contaminated gravel. While erionite is known to cause mesothelioma and other diseases associated with asbestos, there is little known about its effects on the immune system. Objectives: We performed this study to determine whether erionite evokes autoimmune reactions in mice. Methods: Bone marrow derived macrophages (BMDM) were used to measure toxicity induced by erionite. Cytokine production by BMDM and splenocytes of C57BL/6 mice was examined by bead arrays and ELISA following exposure to erionite, amphiboles and chrysotile. Wild type C57BL/6 mice were exposed to saline, erionite, amphibole asbestos (Libby 6-Mix) or chrysotile through intratracheal instillations at equal mass (60 μg/mouse). Seven months after exposure, sera were examined for anti-nuclear antibodies (ANA) and IL-17. Immunohistochemistry was used to detect immune complex deposition in the kidneys. Results: Erionite and tremolite caused increased cytokine production belonging to the T{sub H}17 profile including IL-17, IL-6, TGF-β, and TNF-α. The frequency of ANA was increased in mice treated with erionite or amphibole compared to saline-treated mice. IL-17 and TNF-α were elevated in the sera of mice treated with erionite. The frequency of immune complex deposition in the kidneys increased from 33% in saline-treated mice to 90% with erionite. Conclusions: These data demonstrate that both erionite and amphibole asbestos induce autoimmune responses in mice, suggesting a potential for adverse effects in exposed communities. - Highlights: • Erionite, a fibrous mineral, is a current public health concern in the western USA. • Erionite exposure induces antinuclear autoantibodies in exposed mice. • Erionite induces a clear Th17 cytokine response in vitro and in vivo. • These responses were

  20. SAP suppresses the development of experimental autoimmune encephalomyelitis in C57BL/6 mice.

    PubMed

    Ji, Zhe; Ke, Zun-Ji; Geng, Jian-Guo

    2012-04-01

    Experimental autoimmune encephalomyelitis (EAE) is a CD4(+) T cell-mediated disease of the central nervous system. Serum amyloid P component (SAP) is a highly conserved plasma protein named for its universal presence in amyloid deposits. Here we report that SAP-transgenic mice had unexpectedly attenuated EAE due to impaired encephalitogenic responses. Following induction with myelin oligodendroglial glycoprotein (MOG) peptide 35-55 in complete Freund's adjuvant, SAP-transgenic mice showed reduced spinal cord inflammation with lower severity of EAE attacks as compared with control C57BL/6 mice. However, in SAP-Knockout mice, the severity of EAE is enhanced. Adoptive transfer of Ag-restimulated T cells from wild type to SAP-transgenic mice, or transfer of SAP-transgenic Ag-restimulated T cells to control mice, induced milder EAE. T cells from MOG-primed SAP-transgenic mice showed weak proliferative responses. Furthermore, in SAP-transgenic mice, there is little infiltration of CD45-positive cells in the spinal cord. In vitro, SAP suppressed the secretion of interleukin-2 stimulated by P-selectin and blocked P-selectin binding to T cells. Moreover, SAP could change the affinity between α4-integrin and T cells. These data suggested that SAP could antagonize the development of the acute phase of inflammation accompanying EAE by modulating the function of P-selectin.

  1. Data on morphometric analysis of the pancreatic islets from C57BL/6 and BALB/c mice.

    PubMed

    da Silva, Thiago Aparecido; Lemes, Robertha Mariana; Oliveira, Carlo Jose Freire; Almeida, Aline da Silva; Chica, Javier Emílio Lazo

    2016-09-01

    The endocrine portion of the pancreas, which is characterized by pancreatic islets, has been widely investigated among different species. The BALB/c and C57BL/6 mice are extensively used in experimental research, and the morphometric differences in the pancreatic islets of these animals have not been evaluated so far. Thus, our data have a comparative perspective related to the morphometric analysis of area, diameters, circularity, and density of pancreatic islets from BALB/c and C57BL/6 mice. The data presented here are focused to evaluate the differences in morphology of pancreatic islets of two common laboratory mouse strains.

  2. Chronic pharmacologic inhibition of EGFR leads to cardiac dysfunction in C57BL/6J mice

    SciTech Connect

    Barrick, Cordelia J.; Yu Ming; Chao, H.-H.; Threadgill, David W.

    2008-05-01

    Molecule-targeted therapies like those against the epidermal growth factor receptor (EGFR) are becoming widely used in the oncology clinic. With improvements in treatment efficacy, many cancers are being treated as chronic diseases, with patients having prolonged exposure to several therapies that were previously only given acutely. The consequence of chronic suppression of EGFR activity may lead to unexpected toxicities like altered cardiac physiology, a common organ site for adverse drug effects. To explore this possibility, we treated C57BL/6J (B6) mice with two EGFR small molecule tyrosine kinase inhibitors (TKIs), irreversible EKB-569 and reversible AG-1478, orally for 3 months. In B6 female mice, chronic exposure to both TKIs depressed body weight gain and caused significant changes in left ventricular (LV) wall thickness and cardiac function. No significant differences were observed in heart weight or cardiomyocyte size but histological analysis revealed an increase in fibrosis and in the numbers of TUNEL-positive cells in the hearts from treated female mice. Consistent with histological results, LV apoptotic gene expression was altered, with significant downregulation of the anti-apoptotic gene Bcl2l1. Although there were no significant differences in any of these endpoints in treated male mice, suggesting sex may influence susceptibility to TKI mediated toxicity, the LVs of treated male mice had significant upregulation of Egf, Erbb2 and Nppb over controls. Taken together, these data suggest that chronic dietary exposure to TKIs may result in pathological and physiological changes in the heart.

  3. Development of high-grade lymphoma in Helicobacter pylori-infected C57BL/6 mice.

    PubMed

    Wang, X; Willén, R; Andersson, C; Wadström, T

    2000-01-01

    Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer disease, gastric adenocarcinoma and MALT lymphoma. Mice with H. pylori infection develop severe gastritis and atrophic changes in their stomachs after 6 months. We followed H. pylori-infected animals for 13 months to find out whether dysplasia, carcinoma or lymphoma developed. Six-week-old C57BL/6 mice were infected with the CagA-positive and VacA-positive H. pylori mouse-passaged strain 119/95, fed a low antioxidant diet, and kept in microisolated cages. Histopathological changes were examined after 13 months' infection. All H. pylori-inoculated mice (n = 5) developed a gastric squamous papilloma with nagging of the lamina muscularis after 13 months. Three out of five animals developed high-grade B-cell lymphoma derived from a MALT lymphoma at the squamous-corpus border with manifestations also in the liver, spleen and kidney. There was a suspicion of local gastric lymphoma in the two remaining mice but with no significant changes in the liver, spleen or kidney. The normal control mice showed no pathological changes in any of these organs. It is concluded that this mouse model with infection by the CagA-positive, vac-toxin-producing H. pylori strain 119/95 is suitable for use in the study of lymphoma development and also development of squamous cell papilloma with proliferative features.

  4. Accelerated atherosclerosis in hyperlipidemic C57BL/6 mice treated with cyclosporin A.

    PubMed Central

    Emeson, E. E.; Shen, M. L.

    1993-01-01

    We and others have demonstrated that T lymphocytes are prominent components of atherosclerotic lesions. We hypothesized that if T cells were necessary for the development of atherosclerosis it would be possible to demonstrate its prevention or retardation in T-cell-suppressed mice. To test this hypothesis, CyA, a potent suppressor of T-cell activation, was used to treat C57BL/6 mice undergoing lipid hyperalimentation. Mice receiving normal mouse chow were completely free of atherosclerotic lesions. In mice receiving the atherogenic diet plus control oil injections, lesions of the aorta and coronary arteries were observed at 135 days and increased progressively in area until 310 days. Somewhat surprisingly, mice given the atherogenic diet plus CyA injections displayed even larger lesions at all three observed time intervals. Although CyA did suppress T-cell reactivity sufficiently to obtain the expected prolongation of skin allografts, it did not suppress the development or progression of atherosclerotic lesions. Images Figure 4 Figure 5 Figure 6 PMID:8506958

  5. The discriminative stimulus properties of methylphenidate in C57BL/6J mice.

    PubMed

    McGovern, Robin W; Middaugh, Lawrence D; Patrick, Kennerly S; Griffin, William C

    2011-02-01

    Methylphenidate (MPH) therapy for attention-deficit/hyperactivity disorder is common in children and adults. Concerns regarding abuse of MPH prompted studies to better understand its pharmacology. We used an established drug discrimination task to determine whether MPH could be discriminated by C57BL/6J (B6) mice. B6 mice learned to discriminate cues produced by racemic MPH (dl-MPH 5.0 mg/kg) or half the dose of pure d-isomer (2.5 mg/kg), and dose-response tests established appropriate reductions in discrimination with declining dose. Importantly, the two drug forms generalized to each other completely in substitution tests; consistent with reports that the l-isomer is pharmacodynamically inactive. An additional experiment indicated that lower doses (1 and 2 mg/kg) of dl-MPH did not support acquisition of MPH discrimination despite extensive training. Mice acquired discrimination of dl-MPH only when the dose was increased to 4 mg/kg. Thus, although these lower doses increased drug lever responding in mice trained on the higher dose, their stimuli were not sufficient to support acquisition of the discrimination task. These findings correspond to earlier studies conducted in our laboratory on threshold doses needed to produce stimulatory effects of motor activity in B6 mice. These preclinical findings provide insight into the relative potency, and by extension, efficacy of dl-MPH versus d-MPH doses. PMID:21160424

  6. Genetically determined cholinergic deficiency in the forebrain of C57BL/6 mice.

    PubMed

    Bentivoglio, A R; Altavista, M C; Granata, R; Albanese, A

    1994-02-21

    This study demonstrates that a deficiency of forebrain cholinergic neurons occurs in C57BL/6 (C57) mice, a strain characterized by poor learning capabilities. The brains of 21-day-old and 18-week-old C57 and DBA/2 (DBA) mice were studied by means of acetylcholinesterase (AChE) histochemistry and of choline acetyltransferase (ChAT) immunocytochemistry. Computer-assisted image analysis was performed on sections through the medial septum, the diagonal band of Broca, the basal nucleus of Meynert and the neostriatum. As compared to the DBA strain, C57 mice had a reduced number of forebrain cholinergic neurons. This feature was present at the age of 21 days and persisted to 18 weeks. Between-strain variations in the density of neurons were more obvious in ChAT-stained material than in AChE-stained sections. These data show that C57 mice can be regarded as a genetic mutant, whose phenotype is characterized by a reduced number of forebrain cholinergic neurons and by cognitive abnormalities. C57 mice represent a valuable model for studying the influence of genetic factors on central nervous system cholinergic mechanisms and the effects of genetically determined cholinergic deficiency on behavior and learning.

  7. Modulation of renal superoxide dismutase by telmisartan therapy in C57BL/6-Ins2Akita diabetic mice

    PubMed Central

    Fujita, Hiroki; Fujishima, Hiromi; Morii, Tsukasa; Sakamoto, Takuya; Komatsu, Koga; Hosoba, Mihoko; Narita, Takuma; Takahashi, Keiko; Takahashi, Takamune; Yamada, Yuichiro

    2012-01-01

    Renal superoxide excess, which is induced by an imbalance of the superoxide-producing enzyme NAD(P)H oxidase and the superoxide-scavenging enzyme superoxide dismutase (SOD) under hyperglycemia, increases oxidative stress and contributes to the development of diabetic nephropathy. In this study, we treated non-obese and hypoinsulinemic C57BL/6-Ins2Akita (C57BL/6-Akita) diabetic mice with telmisartan (5 mg kg−1 per day), an angiotensin II type 1 receptor blocker, or amlodipine (5 mg kg−1 per day), a calcium channel blocker, for 4 weeks and compared the effects of these two anti-hypertensive drugs on renal NAD(P)H oxidase, SOD and transcription factor Nrf2 (NF-E2-related factor 2), which is known to upregulate several antioxidant enzymes including SOD. Vehicle-treated C57BL/6-Akita mice exhibited higher renal NAD(P)H oxidase and lower renal SOD activity with increased levels of renal superoxide than the C57BL/6-wild-type non-diabetic mice. Interestingly, telmisartan treatment not only reduced NAD(P)H oxidase activity but also enhanced SOD activity in C57BL/6-Akita mouse kidneys, leading to a reduction of renal superoxide levels. Furthermore, telmisartan-treated C57BL/6-Akita mice increased the renal protein expression of SOD and Nrf2. In parallel with the reduction of renal superoxide levels, a reduction of urinary albumin levels and a normalization of elevated glomerular filtration rate were observed in telmisartan-treated C57BL/6-Akita mice. In contrast, treatment with amlodipine failed to modulate renal NAD(P)H oxidase, SOD and Nrf2. Finally, treatment of C57BL/6-Akita mice with apocynin, an NAD(P)H oxidase inhibitor, also increased the renal protein expression of SOD and Nrf2. Collectively, our data suggest that NAD(P)H oxidase negatively regulates renal SOD, possibly by downregulation of Nrf2, and that telmisartan could upregulate renal SOD by the suppression of NAD(P)H oxidase and subsequent upregulation of Nrf2, leading to the amelioration of

  8. Advantame sweetener preference in C57BL/6J mice and Sprague-Dawley rats.

    PubMed

    Sclafani, Anthony; Ackroff, Karen

    2015-03-01

    Advantame is a new ultrahigh-intensity noncaloric sweetener derived from aspartame and approved for human use. Rats and mice are not attracted to the taste of aspartame and this study determined their preference for advantame. In 24-h choice tests with water, C57BL/6J mice and Sprague-Dawley rats were indifferent to advantame at concentrations of 0.01, 0.03, and 0.1mM but significantly preferred 0.3 and 1mM advantame to water. Both species also preferred 1mM advantame to 1mM saccharin in direct choice tests, but preferred 10mM saccharin to 1mM advantame, which is near the solubility limit for this sweetener. Mice also preferred 1mM advantame to 1mM sucralose or acesulfame K, but preferred both sweeteners at 10mM to 1mM advantame. In addition, mice preferred 1mM advantame to 1 and 10mM aspartame. Thus, advantame is a potent sweetener for rodents but, because of limited solubility, is not an effective alternative to saccharin, sucralose, or acesulfame K at higher concentrations. PMID:25560795

  9. Behavioral analysis of male and female Fmr1 knockout mice on C57BL/6 background.

    PubMed

    Ding, Qi; Sethna, Ferzin; Wang, Hongbing

    2014-09-01

    Fragile X syndrome (FXS) is a monogenic disease caused by mutations in the FMR1 gene. The Fmr1 knockout (KO) mice show many aspects of FXS-related phenotypes, and have been used as a major pre-clinical model for FXS. Although FXS occurs in both male and female patients, most studies on the mouse model use male animals. Few studies test whether gender affects the face validity of the mouse model. Here, we examined multiple behavioral phenotypes with male hemizygous and female homozygous Fmr1 KO mice on C57BL/6 background. For each behavioral paradigm, we examined multiple cohorts from different litters. We found that both male and female Fmr1 KO mice displayed significant audiogenic seizures, hyperactivity in the open field test, deficits in passive avoidance and contextual fear memory, and significant enhancement of PPI at low stimulus intensity. Male and female Fmr1 KO mice also showed more transitional movement between the lit and dark chambers in the light-dark tests. The lack of gender effects suggests that the Fmr1 KO mouse is a reasonable tool to test the efficacy of potential FXS therapies.

  10. Behavioral and Neural Correlates of Acute and Scheduled Hunger in C57BL/6 Mice

    PubMed Central

    Gunapala, Keith M.; Parfyonov, Maksim; Chang, Chris H.; Mistlberger, Ralph E.; Steele, Andrew D.

    2014-01-01

    In rodents, daily feeding schedules induce food anticipatory activity (FAA) rhythms with formal properties suggesting mediation by food-entrained circadian oscillators (FEOs). The search for the neuronal substrate of FEOs responsible for FAA is an active area of research, but studies spanning several decades have yet to identify unequivocally a brain region required for FAA. Variability of results across studies leads to questions about underlying biology versus methodology. Here we describe in C57BL/6 male mice the effects of varying the ‘dose’ of caloric restriction (0%, 60%, 80%, 110%) on the expression of FAA as measured by a video-based analysis system, and on the induction of c-Fos in brain regions that have been implicated in FAA. We determined that more severe caloric restriction (60%) leads to a faster onset of FAA with increased magnitude. Using the 60% caloric restriction, we found little evidence for unique signatures of neuronal activation in the brains of mice anticipating a daily mealtime compared to mice that were fasted acutely or fed ad-libitum–even in regions such as the dorsomedial and ventrolateral hypothalamus, nucleus accumbens, and cerebellum that have previously been implicated in FAA. These results underscore the importance of feeding schedule parameters in determining quantitative features of FAA in mice, and demonstrate dissociations between behavioral FAA and neural activity in brain areas thought to harbor FEOs or participate in their entrainment or output. PMID:24806659

  11. Photoperiodic modulation of voluntary ethanol intake in C57BL/6 mice.

    PubMed

    Rosenwasser, A M; Fixaris, M C; McCulley, W D

    2015-08-01

    Seasonal and geographic variations in light exposure influence human mood and behavior, including alcohol consumption. Similarly, manipulation of the environmental lighting regimen modulates voluntary ethanol intake in experimental animals. Nevertheless, previous studies in rats and hamsters have been somewhat inconsistent, and little is known concerning such effects in mice. In the present study, we maintained male C57Bl/6 mice in running-wheel cages under either short- or long-photoperiod light-dark cycles (LD 6:18 vs. LD 18:6); subsequently, the same animals were maintained under short or long "skeleton photoperiods", consisting of two daily 15-min light pulses signaling dusk and dawn (SP 6:18 vs. SP 18:6). Running wheels were locked mechanically for half the animals under each photoperiod. Analysis of running wheel patterns showed that mice displayed stable circadian adaptation to both standard LD cycles and skeleton photoperiods. Mice consumed more ethanol and less water, and thus showed higher ethanol preference, under LD 6:18 and SP 6:18 relative to the corresponding long-photoperiod regimens. While running-wheel access increased water intake, ethanol intake was unaffected by this manipulation. These effects are consistent with previous studies showing that short photoperiods or constant darkness increases ethanol intake in rodents. Further, the similarity of the effects of complete and skeleton photoperiods suggests that these effects are mediated by photoperiod-induced alterations in the circadian entrainment pattern, rather than by light exposure per se.

  12. Delayed matching-to-position performance in C57BL/6N mice.

    PubMed

    Goto, Kazuhiro; Kurashima, Ryo; Watanabe, Shigeru

    2010-06-01

    Delayed matching-to-sample is one of the most frequently employed behavioral tasks for assessing spatial working memory in animals. Although the advantages of the task have been widely acknowledged and it is used in the study of a variety of species, its application to mice has been rare. In the present study, we reported the efficacy of a delayed matching-to-position task in C57BL mice lever-pressing in an operant-conditioning chamber. Each trial started with the press of a back lever, followed by the presentation of either a left or right front lever. When the ratio requirement for presses to the front lever (sample) was met, a delay interval started. Delay interval continued until the mice made the first response after the elapse of the programmed delay interval. This was followed by the presentation of a choice of left or right front levers. The choice of the same front lever as the sample was reinforced, whereas the other was not. The proportion of correct choices showed a delay-dependent decrement. A higher ratio of response requirement to the sample resulted in increased accuracy, but the duration of the intertrial interval had no effect. Preceding trials also influenced response accuracy, indicating proactive interference. Overall, the results replicated the effects of parametric manipulations reported in other species, and thus, our findings validate the efficacy of the task for assessing spatial working memory in laboratory mice.

  13. Methionine-choline deprivation alters liver and brain acetylcholinesterase activity in C57BL6 mice.

    PubMed

    Vučević, Danijela B; Cerović, Ivana B; Mladenović, Dušan R; Vesković, Milena N; Stevanović, Ivana; Jorgačević, Bojan Z; Ješić Vukićević, Rada; Radosavljević, Tatjana S

    2016-07-01

    Choline and methionine are precursors of acetylcholine, whose hydrolysis is catalyzed by acetylcholinesterase (AChE). Considering the possibility of their common deficiency, we investigated the influence of methionine-choline deprivation on AChE activity in liver and various brain regions (hypothalamus, hippocampus, cerebral cortex and striatum) in mice fed with methionine-choline deficient (MCD) diet. Male C57BL/6 mice (n = 28) were randomly and equally divided into following groups: control group fed with standard diet for 6 weeks (C) and groups fed with MCD diet for 2 weeks (MCD2), 4 weeks (MCD4) and for 6 weeks (MCD6). After the diet, mice were sacrificied and AChE activity in liver and brain was determined spectrophotometrically. Hepatic AChE activity was higher in MCD2, MCD4 and MCD6 compared to control (p < 0.01), with most prominent increase in MCD6. AChE activity in hypothalamus was higher in MCD4 and MCD6 vs. control (p < 0.05 and p < 0.01, respectively), as well as in MCD6 compared to MCD4 (p < 0.01). In hippocampus, increase in AChE activity was shown in MCD6 compared to control (p < 0.01). In cortex and striatum, increase in AChE activity was noted in MCD6 compared to control (p < 0.05). Our findings indicate the increase of hepatic and brain AChE activity in mice caused by methionine-choline deprivation.

  14. Photoperiodic modulation of voluntary ethanol intake in C57BL/6 mice.

    PubMed

    Rosenwasser, A M; Fixaris, M C; McCulley, W D

    2015-08-01

    Seasonal and geographic variations in light exposure influence human mood and behavior, including alcohol consumption. Similarly, manipulation of the environmental lighting regimen modulates voluntary ethanol intake in experimental animals. Nevertheless, previous studies in rats and hamsters have been somewhat inconsistent, and little is known concerning such effects in mice. In the present study, we maintained male C57Bl/6 mice in running-wheel cages under either short- or long-photoperiod light-dark cycles (LD 6:18 vs. LD 18:6); subsequently, the same animals were maintained under short or long "skeleton photoperiods", consisting of two daily 15-min light pulses signaling dusk and dawn (SP 6:18 vs. SP 18:6). Running wheels were locked mechanically for half the animals under each photoperiod. Analysis of running wheel patterns showed that mice displayed stable circadian adaptation to both standard LD cycles and skeleton photoperiods. Mice consumed more ethanol and less water, and thus showed higher ethanol preference, under LD 6:18 and SP 6:18 relative to the corresponding long-photoperiod regimens. While running-wheel access increased water intake, ethanol intake was unaffected by this manipulation. These effects are consistent with previous studies showing that short photoperiods or constant darkness increases ethanol intake in rodents. Further, the similarity of the effects of complete and skeleton photoperiods suggests that these effects are mediated by photoperiod-induced alterations in the circadian entrainment pattern, rather than by light exposure per se. PMID:25992479

  15. Advantame sweetener preference in C57BL/6J mice and Sprague-Dawley rats.

    PubMed

    Sclafani, Anthony; Ackroff, Karen

    2015-03-01

    Advantame is a new ultrahigh-intensity noncaloric sweetener derived from aspartame and approved for human use. Rats and mice are not attracted to the taste of aspartame and this study determined their preference for advantame. In 24-h choice tests with water, C57BL/6J mice and Sprague-Dawley rats were indifferent to advantame at concentrations of 0.01, 0.03, and 0.1mM but significantly preferred 0.3 and 1mM advantame to water. Both species also preferred 1mM advantame to 1mM saccharin in direct choice tests, but preferred 10mM saccharin to 1mM advantame, which is near the solubility limit for this sweetener. Mice also preferred 1mM advantame to 1mM sucralose or acesulfame K, but preferred both sweeteners at 10mM to 1mM advantame. In addition, mice preferred 1mM advantame to 1 and 10mM aspartame. Thus, advantame is a potent sweetener for rodents but, because of limited solubility, is not an effective alternative to saccharin, sucralose, or acesulfame K at higher concentrations.

  16. Hippocampus-dependent place learning enables spatial flexibility in C57BL6/N mice

    PubMed Central

    Kleinknecht, Karl R.; Bedenk, Benedikt T.; Kaltwasser, Sebastian F.; Grünecker, Barbara; Yen, Yi-Chun; Czisch, Michael; Wotjak, Carsten T.

    2012-01-01

    Spatial navigation is a fundamental capability necessary in everyday life to locate food, social partners, and shelter. It results from two very different strategies: (1) place learning which enables for flexible way finding and (2) response learning that leads to a more rigid “route following.” Despite the importance of knockout techniques that are only available in mice, little is known about mice' flexibility in spatial navigation tasks. Here we demonstrate for C57BL6/N mice in a water-cross maze (WCM) that only place learning enables spatial flexibility and relearning of a platform position, whereas response learning does not. This capability depends on an intact hippocampal formation, since hippocampus lesions by ibotenic acid (IA) disrupted relearning. In vivo manganese-enhanced magnetic resonance imaging revealed a volume loss of ≥60% of the hippocampus as a critical threshold for relearning impairments. In particular the changes in the left ventral hippocampus were indicative of relearning deficits. In summary, our findings establish the importance of hippocampus-dependent place learning for spatial flexibility and provide a first systematic analysis on spatial flexibility in mice. PMID:23293591

  17. [Immune responses in C57BL/6J mice with the inverted pattern of behavior during social conflict].

    PubMed

    Devoĭno, L V; Al'perina, E L; Pavina, T A

    1999-12-01

    Inversion of aggressive behaviour into a submissive one led to immunosuppression in C57BL/6J mice as well as in those mice which did not change their behaviour, whereas inversion of submissive behaviour into aggressive one resulted in immunostimulation. A possibility to influence immune response changing the brain neurochemical pattern by reversing behaviour under conditions of a social conflict, is discussed.

  18. METHANOL EXPOSURE DURING GASTRULATION CAUSES HOLOPROSENCEPHALY, FACIAL DYSGENESIS AND CERVICAL VERTEBRAL MALFORMATIONS IN C57BL/6J MICE

    EPA Science Inventory

    Exposure of pregnant CD-1 mice to methanol during the period of gastrulation results in exencephaly, cleft palate, and cervical vertebra malformations (Rogers and Mole, 1997, Teratology 55, 364). C57BL/6J mice are sensitive to the teratogenicity of ethanol; fetuses of this strai...

  19. Ulcerative dermatitis in C57BL/6 mice lacking stearoyl CoA desaturase 1.

    PubMed

    Krugner-Higby, Lisa; Brown, Richard; Rassette, Matthew; Behr, Melissa; Okwumabua, Ogi; Cook, Mark; Bell, Cynthia; Flowers, Matthew T; Ntambi, James; Gendron, Annette

    2012-08-01

    Ulcerative dermatitis (UD) is a common cause of morbidity and euthanasia in mice with a C57BL/6 (B6) background. The purposes of the current study were to determine whether UD lesions could be reliably produced in B6 mice lacking stearoyl-CoA desaturase 1 (SCD1(-/-) mice), to ascertain whether the UD lesions in SCD1(-/-) mice were similar to those found in other B6 mice, and to characterize the cell invasion phenotype of Staphlococcus xylosus cultured from the lesions. S. xylosus isolates from the environment and human skin were used as controls. SCD1(-/-) (n = 8 per group) and nontransgenic B6 control mice (n = 22 mice pooled from 3 groups that received different concentrations of conjugated linoleic acid) were fed standard rodent chow or a semipurified diet (NIH AIN76A) for 4 wk. Samples from other B6 mice with UD (field cases; n = 7) also were submitted for histology and culture. All of the SCD1(-/-) mice developed UD lesions by 4 wk on NIH AIN76A. None of SCD1(-/-) fed standard rodent chow and none of the wildtype B6 mice fed NIH AIN76A developed UD. Supplementation with conjugated linoleic acid did not affect ulcerogenesis. UD lesions in SCD1(-/-) mice and field cases were grossly and histologically similar. S. xylosus was isolated from SCD1(-/-) mice with UD (71%) and field cases of UD (43%). These isolates were the most cell-invasive, followed by the environmental isolate, and finally the human skin isolate. Our results provide a basis for further pathologic and clinical study of UD.

  20. Ulcerative Dermatitis in C57BL/6 Mice Lacking Stearoyl CoA Desaturase 1

    PubMed Central

    Krugner-Higby, Lisa; Brown, Richard; Rassette, Matthew; Behr, Melissa; Okwumabua, Ogi; Cook, Mark; Bell, Cynthia; Flowers, Matthew T; Ntambi, James; Gendron, Annette

    2012-01-01

    Ulcerative dermatitis (UD) is a common cause of morbidity and euthanasia in mice with a C57BL/6 (B6) background. The purposes of the current study were to determine whether UD lesions could be reliably produced in B6 mice lacking stearoyl-CoA desaturase 1 (SCD1–/– mice), to ascertain whether the UD lesions in SCD1–/– mice were similar to those found in other B6 mice, and to characterize the cell invasion phenotype of Staphlococcus xylosus cultured from the lesions. S. xylosus isolates from the environment and human skin were used as controls. SCD1–/– (n = 8 per group) and nontransgenic B6 control mice (n = 22 mice pooled from 3 groups that received different concentrations of conjugated linoleic acid) were fed standard rodent chow or a semipurified diet (NIH AIN76A) for 4 wk. Samples from other B6 mice with UD (field cases; n = 7) also were submitted for histology and culture. All of the SCD1–/– mice developed UD lesions by 4 wk on NIH AIN76A. None of SCD1–/– fed standard rodent chow and none of the wildtype B6 mice fed NIH AIN76A developed UD. Supplementation with conjugated linoleic acid did not affect ulcerogenesis. UD lesions in SCD1–/– mice and field cases were grossly and histologically similar. S. xylosus was isolated from SCD1–/– mice with UD (71%) and field cases of UD (43%). These isolates were the most cell-invasive, followed by the environmental isolate, and finally the human skin isolate. Our results provide a basis for further pathologic and clinical study of UD. PMID:23043777

  1. Developmental vitamin D deficiency alters learning in C57Bl/6J mice.

    PubMed

    Fernandes de Abreu, Diana Andrea; Nivet, Emmanuel; Baril, Nathalie; Khrestchatisky, Michel; Roman, François; Féron, François

    2010-04-01

    Epidemiological studies have highlighted a season of birth effect in multiple sclerosis and schizophrenia. As a result, low prenatal vitamin D has been proposed as a candidate risk factor for these brain diseases, with cognitive impairments. In order to further investigate the long-term consequences of a transient gestational hypovitaminosis D, we used a mouse developmental vitamin D (DVD) deficiency model. Female C57Bl/6J mice were fed a vitamin D-free diet for 6 weeks prior to conception and during gestation. At birth, dams and their offspring were fed a normal vitamin D-containing diet. The adult offspring underwent a learning test based on olfactory cues, at 30 weeks and 60 weeks of age. In addition, using magnetic resonance imaging (MRI), volumes of cerebrum, hippocampus and lateral ventricles were measured at 30 weeks and 70 weeks of age. We found that DVD-deficient mice, when compared to control animals at Week 30, displayed impaired learning and smaller lateral ventricles. At Weeks 60-70, both groups deteriorated when compared to young mice and no significant difference was observed between groups. This study confirms that transient prenatal vitamin D deficiency alters brain development and functioning and induces cognitive impairments in the young adult offspring. PMID:20079764

  2. Maternal Deprivation Influences Pup Ultrasonic Vocalizations of C57BL/6J Mice

    PubMed Central

    Yin, Xiaowen; Chen, Ling; Yang, Yan; Wang, Zhaoxin; Wang, Haojie; Dong, Jianshu; Ding, Yuqiang

    2016-01-01

    Maternal deprivation (MD) is frequently used as an early life stress model in rodents to investigate behavioral and neurological responses under stressful conditions. However, the effect of MD on the early postnatal development of rodents, which is when multiple neural systems become established, is rarely investigated due to methodological limitations. Ultrasonic vocalizations (USVs) are one of the few responses produced by neonatal rodents that can be quantitatively analyzed, and the quantification of USVs is regarded as a novel approach to investigate possible alterations in the neurobehavioral and emotional development of infant rodents under stress. To investigate the effect of MD on pup mice, we subjected C57BL/6J mice to MD and recorded the USVs of pups on postnatal days 1, 3, 7, 8, and 14. To determine whether the effect of MD on USVs was acute or cumulative, pre- and post-separation USV groups were included; sex differences in pup USV emission were also investigated. Our results suggest that (i) USV activity was high on postnatal days 3–8; (ii) the MD effect on USVs was acute, and a cumulative effect was not found; (iii) the MD mice vocalized more and longer than the controls at a lower frequency, and the effect was closely related to age; and (iv) female pups were more susceptible than males to the effect of MD on USV number and duration between postnatal days 3–8. PMID:27552099

  3. Metabolic Effects of Social Isolation in Adult C57BL/6 Mice

    PubMed Central

    Sun, Meng; Choi, Eugene Y.; Magee, Daniel J.; Stets, Colin W.; During, Matthew J.; Lin, En-Ju D.

    2014-01-01

    Obesity and metabolic dysfunction are risk factors for a number of chronic diseases, such as type 2 diabetes, hypertension, heart disease, stroke, and certain forms of cancers. Both animal studies and human population-based and clinical studies have suggested that chronic stress is a risk factor for metabolic disorders. A good social support system is known to exert positive effects on the mental and physical well-being of an individual. On the other hand, long-term deprivation of social contacts may represent a stressful condition that has negative effects on health. In the present study, we investigated the effects of chronic social isolation on metabolic parameters in adult C57BL/6 mice. We found that individually housed mice had increased adipose mass compared to group-housed mice, despite comparable body weight. The mechanism for the expansion of white adipose tissue mass was depot-specific. Notably, food intake was reduced in the social isolated animals, which occurred around the light-dark phase transition periods. Similarly, reductions in heat generated and the respiratory exchange ratio were observed during the light-dark transitions. These phase-specific changes due to long-term social isolation have not been reported previously. Our study shows social isolation contributes to increased adiposity and altered metabolic functions. PMID:27433503

  4. Activation of basolateral amygdala in juvenile C57BL/6J mice during social approach behavior.

    PubMed

    Ferri, Sarah L; Kreibich, Arati S; Torre, Matthew; Piccoli, Cara T; Dow, Holly; Pallathra, Ashley A; Li, Hongzhe; Bilker, Warren B; Gur, Ruben C; Abel, Ted; Brodkin, Edward S

    2016-10-29

    There is a strong need to better understand the neurobiology of juvenile sociability (tendency to seek social interaction), a phenotype of central relevance to autism spectrum disorders (ASD). Although numerous genetic mouse models of ASD showing reduced sociability have been reported, and certain brain regions, such as the amygdala, have been implicated in sociability, there has been little emphasis on delineating brain structures and circuits activated during social interactions in the critical juvenile period of the mouse strain that serves as the most common genetic background for these models-the highly sociable C57BL/6J (B6) strain. We measured expression of the immediate early genes Fos and Egr-1 to map activation of brain regions following the Social Approach Test (SAT) in juvenile male B6 mice. We hypothesized that juvenile B6 mice would show activation of the amygdala during social interactions. The basolateral amygdala (BLA) was activated by social exposure in highly sociable, 4-week-old B6 mice. In light of these data, and the many lines of evidence indicating alteration of amygdala circuits in human ASD, future studies are warranted to assess structural and functional alterations in the BLA, particularly at BLA synapses, in various mouse models of ASD. PMID:27520082

  5. Effects of fludrocortisone on water and sodium intake of C57BL/6 mice.

    PubMed

    Johnson, Ralph F; Beltz, Terry G; Johnson, Alan Kim; Thunhorst, Robert L

    2015-08-01

    Little is known about steroidal control of thirst- and salt-appetite behaviors of mice. The current study investigates effects of fludrocortisone acetate (FCA), a steroid with potent glucocorticoid and mineralocorticoid effects, on thirst- and salt-appetite responses of C57BL/6 mice. Treatment with FCA produced dose-dependent (5, 10, and 25 mg/kg) increases in both magnitude and duration of water and sodium intake. Chronic elevation of water and saline intake was achieved with daily injections of FCA. Daily injection of FCA, when only 0.9% saline was available, produced a remarkably rapid increase in saline intake. A single injection of FCA stimulated brisk diuresis and natriuresis in fluid-restricted animals. This work is the first to demonstrate copious water drinking by mice in response to FCA. The results are discussed in terms of the possibility that the renal effects of FCA promote increases in water and sodium turnover and thereby, increases in water and sodium ingestion.

  6. Inflammation has a role in urethane‑induced lung cancer in C57BL/6J mice.

    PubMed

    Xu, Cai; Zhou, Lingyu; Lu, Lei; Chen, Ting; Wei, Siyu; Lin, Xiaojing; Lian, Xuemei

    2016-10-01

    Lung cancer is a common and highly frequent cause of cancer‑associated mortality worldwide. Several studies have indicated that chronic inflammation is associated with an increased risk of several types of human cancer. The lung is vulnerable to various chemical and biological insults, and persistent exposure to these factors may result in the release of several inflammatory cytokines from inflammatory cells, thus leading to chronic inflammation and a risk of lung cancer. Due to the extensive application of C57BL/6J mice in lipid metabolism‑related research, it appears important to establish a lung cancer model based on C57BL/6J mice. Therefore, the present study designed an experimental model, in which C57BL/6J mice received several injections of urethane. The study aimed to explore whether inflammation has a role in this model of lung cancer. The results demonstrated that 10 weekly intraperitoneal injections of urethane induced a 100% lung tumor incidence, and urethane‑treated mice possessed higher numbers of immune cells. In addition, the expression levels of cytokines and chemokines in bronchoalveolar lavage fluid were significantly different between the two groups. Activation of the transcription factor nuclear factor‑κB was increased in the lung tissues of urethane‑treated mice, and its expression was upregulated in a time‑dependent manner. These results suggested that the accumulation of lung inflammation may be associated with the occurrence of lung cancer in C57BL/6J mice. PMID:27572483

  7. Aniracetam Does Not Alter Cognitive and Affective Behavior in Adult C57BL/6J Mice

    PubMed Central

    Elston, Thomas W.; Pandian, Ashvini; Smith, Gregory D.; Holley, Andrew J.; Gao, Nanjing; Lugo, Joaquin N.

    2014-01-01

    There is a growing community of individuals who self-administer the nootropic aniracetam for its purported cognitive enhancing effects. Aniracetam is believed to be therapeutically useful for enhancing cognition, alleviating anxiety, and treating various neurodegenerative conditions. Physiologically, aniracetam enhances both glutamatergic neurotransmission and long-term potentiation. Previous studies of aniracetam have demonstrated the cognition-restoring effects of acute administration in different models of disease. No previous studies have explored the effects of aniracetam in healthy subjects. We investigated whether daily 50 mg/kg oral administration improves cognitive performance in naïve C57BL/6J mice in a variety of aspects of cognitive behavior. We measured spatial learning in the Morris water maze test; associative learning in the fear conditioning test; motor learning in the accelerating rotarod test; and odor discrimination. We also measured locomotion in the open field test, anxiety through the elevated plus maze test and by measuring time in the center of the open field test. We measured repetitive behavior through the marble burying test. We detected no significant differences between the naive, placebo, and experimental groups across all measures. Despite several studies demonstrating efficacy in impaired subjects, our findings suggest that aniracetam does not alter behavior in normal healthy mice. This study is timely in light of the growing community of healthy humans self-administering nootropic drugs. PMID:25099639

  8. Effects of Intermittent Fasting on Experimental Autoimune Encephalomyelitis in C57BL/6 Mice.

    PubMed

    Razeghi Jahromi, Soodeh; Ghaemi, Amir; Alizadeh, Akram; Sabetghadam, Fatemeh; Moradi Tabriz, Hedieh; Togha, Mansoureh

    2016-06-01

    Several religions recommend periods of fasting. One of the most frequently asked questions of MS patients before the holy month of Ramadan is weather fasting might have an unfavorable effect on their disease course. This debate became more challenging after the publication of experimental studies suggesting that calorie restriction prior to disease induction attenuates disease severity. We conducted this study to assess early and late effects of fasting on the animal model of MS, known as autoimmune encephalomyelitis. EAE was induced in the C57BL/6 mice, using Myelin Oligodendrocyte Glycopeptide  (MOG) 35-55 and they fasted every other day either after the appearance of the first clinical sign or 30 days after disease induction for ten days. Thereafter, the mice were sacrificed for further histological and immunological evaluations. Intermittent fasting after the establishment of EAE did not have any unfavorable effect on the course of disease. Moreover, fasting at the early phase of disease alleviated EAE severity by ameliorating spinal cord demyelination. Fasting suppressed the secretion of IFN-γ, TNF-α and raised IL-10 production in splenocytes. Fasting was also associated with a lower percent of cytotoxicity. Intermittent fasting not only had no unfavorable effect on EAE but also reduced EAE severity if started at early phase of disease. PMID:27424136

  9. Retroviral induction of acute lymphoproliferative disease and profound immunosuppression in adult C57BL/6 mice

    PubMed Central

    1985-01-01

    We have shown that a mixture of murine leukemia viruses (MuLV) causes the acute onset of lymphoproliferation and immunosuppression when injected into adult C57BL/6 mice. The ecotropic/MCF (mink cell focus- inducing) mixture of MuLV stimulates polyclonal B lymphocyte proliferation and differentiation to antibody-secreting cells. Serum Ig levels are elevated for all isotypes except IgA. The viral infection leads to a rapid decline in T lymphocyte responses to mitogens and alloantigens, as well as a decrease in helper cell activity. Specific antibody responses to both T-dependent and T-independent antigens are impaired, and the response of B lymphocytes to mitogens is abolished. The profound immunosuppression seems to be due to the MuLV-induced polyclonal activation of lymphocytes. No active suppression of normal lymphocyte responses by cells from virus-infected mice was observed. The disease induced by the LP-BM5 MuLV isolate thus seems a promising model for the study of lymphocyte activation and the mechanisms of retrovirus-induced immunosuppression. PMID:2984305

  10. Hair Growth-Promoting Effects of Lavender Oil in C57BL/6 Mice

    PubMed Central

    Lee, Boo Hyeong; Lee, Jae Soon; Kim, Young Chul

    2016-01-01

    The purpose of this study was to determine the hair growth effects of lavender oil (LO) in female C57BL/6 mice. The experimental animals were divided into a normal group (N: saline), a vehicle control group (VC: jojoba oil), a positive control group (PC: 3% minoxidil), experimental group 1 (E1: 3% LO), and experimental group 2 (E2: 5% LO). Test compound solutions were topically applied to the backs of the mice (100 μL per application), once per day, 5 times a week, for 4 weeks. The changes in hair follicle number, dermal thickness, and hair follicle depth were observed in skin tissues stained with hematoxylin and eosin, and the number of mast cells was measured in the dermal and hypodermal layers stained with toluidine blue. PC, E1, and E2 groups showed a significantly increased number of hair follicles, deepened hair follicle depth, and thickened dermal layer, along with a significantly decreased number of mast cells compared to the N group. These results indicated that LO has a marked hair growth-promoting effect, as observed morphologically and histologically. There was no significant difference in the weight of the thymus among the groups. However, both absolute and relative weights of the spleen were significantly higher in the PC group than in the N, VC, E1, or E2 group at week 4. Thus, LO could be practically applied as a hair growth-promoting agent. PMID:27123160

  11. Hair Growth-Promoting Effects of Lavender Oil in C57BL/6 Mice.

    PubMed

    Lee, Boo Hyeong; Lee, Jae Soon; Kim, Young Chul

    2016-04-01

    The purpose of this study was to determine the hair growth effects of lavender oil (LO) in female C57BL/6 mice. The experimental animals were divided into a normal group (N: saline), a vehicle control group (VC: jojoba oil), a positive control group (PC: 3% minoxidil), experimental group 1 (E1: 3% LO), and experimental group 2 (E2: 5% LO). Test compound solutions were topically applied to the backs of the mice (100 μL per application), once per day, 5 times a week, for 4 weeks. The changes in hair follicle number, dermal thickness, and hair follicle depth were observed in skin tissues stained with hematoxylin and eosin, and the number of mast cells was measured in the dermal and hypodermal layers stained with toluidine blue. PC, E1, and E2 groups showed a significantly increased number of hair follicles, deepened hair follicle depth, and thickened dermal layer, along with a significantly decreased number of mast cells compared to the N group. These results indicated that LO has a marked hair growth-promoting effect, as observed morphologically and histologically. There was no significant difference in the weight of the thymus among the groups. However, both absolute and relative weights of the spleen were significantly higher in the PC group than in the N, VC, E1, or E2 group at week 4. Thus, LO could be practically applied as a hair growth-promoting agent.

  12. Hair Growth-Promoting Effects of Lavender Oil in C57BL/6 Mice.

    PubMed

    Lee, Boo Hyeong; Lee, Jae Soon; Kim, Young Chul

    2016-04-01

    The purpose of this study was to determine the hair growth effects of lavender oil (LO) in female C57BL/6 mice. The experimental animals were divided into a normal group (N: saline), a vehicle control group (VC: jojoba oil), a positive control group (PC: 3% minoxidil), experimental group 1 (E1: 3% LO), and experimental group 2 (E2: 5% LO). Test compound solutions were topically applied to the backs of the mice (100 μL per application), once per day, 5 times a week, for 4 weeks. The changes in hair follicle number, dermal thickness, and hair follicle depth were observed in skin tissues stained with hematoxylin and eosin, and the number of mast cells was measured in the dermal and hypodermal layers stained with toluidine blue. PC, E1, and E2 groups showed a significantly increased number of hair follicles, deepened hair follicle depth, and thickened dermal layer, along with a significantly decreased number of mast cells compared to the N group. These results indicated that LO has a marked hair growth-promoting effect, as observed morphologically and histologically. There was no significant difference in the weight of the thymus among the groups. However, both absolute and relative weights of the spleen were significantly higher in the PC group than in the N, VC, E1, or E2 group at week 4. Thus, LO could be practically applied as a hair growth-promoting agent. PMID:27123160

  13. Intermittent Administration of Rapamycin Extends the Life Span of Female C57BL/6J Mice.

    PubMed

    Arriola Apelo, Sebastian I; Pumper, Cassidy P; Baar, Emma L; Cummings, Nicole E; Lamming, Dudley W

    2016-07-01

    Inhibition of the mTOR (mechanistic target of rapamycin) signaling pathway by the FDA-approved drug rapamycin promotes life span in numerous model organisms and delays age-related disease in mice. However, the utilization of rapamycin as a therapy for age-related diseases will likely prove challenging due to the serious metabolic and immunological side effects of rapamycin in humans. We recently identified an intermittent rapamycin treatment regimen-2mg/kg administered every 5 days-with a reduced impact on glucose homeostasis and the immune system as compared with chronic treatment; however, the ability of this regimen to extend life span has not been determined. Here, we report for the first time that an intermittent rapamycin treatment regimen starting as late as 20 months of age can extend the life span of female C57BL/6J mice. Our work demonstrates that the anti-aging potential of rapamycin is separable from many of its negative side effects and suggests that carefully designed dosing regimens may permit the safer use of rapamycin and its analogs for the treatment of age-related diseases in humans. PMID:27091134

  14. Flagella of Salmonella typhimurium are a virulence factor in infected C57BL/6J mice.

    PubMed Central

    Carsiotis, M; Weinstein, D L; Karch, H; Holder, I A; O'Brien, A D

    1984-01-01

    To determine whether flagella, chemotaxis, and motility of Salmonella typhimurium are virulence factors in infected C57BL/6J mice, we constructed isogenic pairs of derivatives of the nonfimbriated virulent strain SL3201. Of each pair, one member contained a mutation in a single gene that is required for expression of normal chemotactically directed motility, whereas the other member contained the wild-type form of the gene. No additional differences between the members of a pair were evident. The phenotypic parameters examined for all derivatives included in vitro growth rate, sensitivity to P22 phage, amino acid auxotrophy, and biotype. For a flagellated and nonflagellated pair, the electron microscopic appearance of each member was examined as well as its lipopolysaccharide and outer membrane profiles by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The virulence of the various derivatives was then assessed in mice challenged orally, intraperitoneally, or intravenously. The results established that flagella, whether functional or nonfunctional as organelles of motility, were S. typhimurium virulence factors and that neither chemotaxis nor motility was required for virulence. Images PMID:6389363

  15. Behaviour and prefrontal protein differences in C57BL/6N and 129 X1/SvJ mice.

    PubMed

    Zhang, Xiaofan; Li, Qi; Wong, Naikei; Zhang, Min; Wang, Wei; Bu, Bitao; McAlonan, Grainne Mary

    2015-07-01

    Experimental animals provide valuable opportunities to establish aetiological mechanisms and test new treatments for neurodevelopmental psychiatric conditions. However, it is increasingly appreciated that inter-strain differences cannot be neglected in the experimental design. In addition, the importance of including females in preclinical - but also clinical - research is now recognised. Here, we compared behaviour and prefrontal protein differences in male and female C57BL/6N and 129X1/SvJ mice as both are commonly used experimental rodents. Relative to 129X1/SvJ mice, both sexes of C57BL/6N mice had weaker sensorimotor gating, measured in the prepulse inhibition (PPI) of startle paradigm, and were more sensitive to amphetamine challenge in the open field. The pattern of protein expression in the prefrontal cortex of C57BL6N mice was also clearly distinct from 129X1/SvJ mice. Proteins differentially expressed were those associated with oxidative metabolism, receptor protein signalling, cell communication and signal transduction and energy pathways. We suggest that the C57BL/6N mouse may usefully proxy features of the neurodevelopmental disorders and could have application in pre-translational screening of new therapeutic approaches. The 129X1/SvJ strain in contrast, might be better suited to experimental studies of causal risk factors expected to lower PPI and increase amphetamine sensitivity.

  16. Abrogation of resistance to Theiler's virus-induced demyelination in C57BL mice by total body irradiation.

    PubMed

    Rodriguez, M; Patick, A K; Pease, L R

    1990-03-01

    Theiler's murine encephalitis virus (TMEV) produces an unusual biphasic disease in susceptible mice characterized by poliomyelitis with early viral replication in neurons, followed by chronic demyelination with viral antigen expression in spinal cord white matter. In addition, infectious virus persists in the central nervous system (CNS) throughout the chronic phase of disease. Previous studies have indicated an important role for major histocompatibility complex (MHC)-gene products in determining resistance/susceptibility to disease. In particular, certain class I gene products of the D region of the H-2 gene complex render mice of the C57BL lineage resistant to induction of demyelination. Intracerebral infection of B10.S(DS) mice results in demyelination in the spinal cord while infection of C57BL/10(Db) or B10.S(9R)(Dd) fails to produce white matter destruction. In this study we showed that immunosuppression with gamma irradiation renders normally resistant B10.S(9R) and C57BL/10 mice susceptible to TMEV-induced demyelination and allowed for increased viral replication. In addition, the majority of irradiated C57BL/10 mice infected with virus showed extensive areas of CNS remyelination by oligodendrocytes beginning at 63 days post-infection. In contrast, immunosuppression of normally susceptible B10.S mice resulted in acute disease and high mortality accompanied by overwhelming destruction of neurons. The study supports the hypothesis that MHC-conferred resistance in C57BL mice is associated with MHC D region products and indicate an important active role for the immune system early in infection in limiting vital infection during disease induction in nonimmunosuppressed mice.

  17. Stochastic variation of transcript abundance in C57BL/6J mice

    PubMed Central

    2011-01-01

    Background Transcripts can exhibit significant variation in tissue samples from inbred laboratory mice. We have designed and carried out a microarray experiment to examine transcript variation across samples from adipose, heart, kidney, and liver tissues of C57BL/6J mice and to partition variation into within-mouse and between-mouse components. Within-mouse variance captures variation due to heterogeneity of gene expression within tissues, RNA-extraction, and array processing. Between-mouse variance reflects differences in transcript abundance between genetically identical mice. Results The nature and extent of transcript variation differs across tissues. Adipose has the largest total variance and the largest within-mouse variance. Liver has the smallest total variance, but it has the most between-mouse variance. Genes with high variability can be classified into groups with correlated patterns of expression that are enriched for specific biological functions. Variation between mice is associated with circadian rhythm, growth hormone signaling, immune response, androgen regulation, lipid metabolism, and the extracellular matrix. Genes showing correlated patterns of within-mouse variation are also associated with biological functions that largely reflect heterogeneity of cell types within tissues. Conclusions Genetically identical mice can experience different individual outcomes for medically important traits. Variation in gene expression observed between genetically identical mice can identify functional classes of genes that are likely to vary in the absence of experimental perturbations, can inform experimental design decisions, and provides a baseline for the interpretation of gene expression data in interventional studies. The extent of transcript variation among genetically identical mice underscores the importance of stochastic and micro-environmental factors and their phenotypic consequences. PMID:21450099

  18. REPRODUCTIVE EFFECTS OF THE WATER DISINFECTANT BYPRODUCT BROMOCHLOROACETIC ACID (BCA) IN ADULT AND JUVENILE MALE C57BL/6 MICE

    EPA Science Inventory

    REPRODUCTIVE EFFECTS OF THE WATER DISINFECTANT BYPRODUCT BROMOCHLOROACETIC ACID (BCA) IN ADULT AND JUVENILE MALE C57BL/6 MICE.
    JC Rockett, JC Luft, JB Garges and DJ Dix. Reproductive Toxicology Division, USEPA, RTP, NC, USA.
    Sponsor: G Klinefelter
    The development of wate...

  19. Effects of Differing Response-Force Requirements on Food-Maintained Responding in C57BL/6J Mice

    ERIC Educational Resources Information Center

    Zarcone, Troy J.; Chen, Rong; Fowler, Stephen C.

    2009-01-01

    The effect of force requirements on response effort was examined using inbred C57BL/6J mice trained to press a disk with their snout. Lateral peak forces greater than 2 g were defined as responses (i.e., all responses above the measurement threshold). Different, higher force requirements were used to define criterion responses (a subclass of all…

  20. Chronobiology of alcohol: studies in C57BL/6J and DBA/2J inbred mice.

    PubMed

    Rosenwasser, Alan M; Fixaris, Michael C

    2013-02-17

    Human alcoholics display dramatic disruptions of circadian rhythms that may contribute to the maintenance of excessive drinking, thus creating a vicious cycle. While clinical studies cannot establish direct causal mechanisms, recent animal experiments have revealed bidirectional interactions between circadian rhythms and ethanol intake, suggesting that the chronobiological disruptions seen in human alcoholics are mediated in part by alterations in circadian pacemaker function. The present study was designed to further explore these interactions using C57BL/6J (B6) and DBA/2J (D2) inbred mice, two widely employed strains differing in both circadian and alcohol-related phenotypes. Mice were maintained in running-wheel cages with or without free-choice access to ethanol and exposed to a variety of lighting regimens, including standard light-dark cycles, constant darkness, constant light, and a "shift-lag" schedule consisting of repeated light-dark phase shifts. Relative to the standard light-dark cycle, B6 mice showed reduced ethanol intake in both constant darkness and constant light, while D2 mice showed reduced ethanol intake only in constant darkness. In contrast, shift-lag lighting failed to affect ethanol intake in either strain. Access to ethanol altered daily activity patterns in both B6 and D2 mice, and increased activity levels in D2 mice, but had no effects on other circadian parameters. Thus, the overall pattern of results was broadly similar in both strains, and consistent with previous observations that chronic ethanol intake alters circadian activity patterns while environmental perturbation of circadian rhythms modulates voluntary ethanol intake. These results suggest that circadian-based interventions may prove useful in the management of alcohol use disorders.

  1. UVB Activates Hypothalamic-Pituitary-Adrenal Axis in C57BL/6 Mice.

    PubMed

    Skobowiat, Cezary; Slominski, Andrzej T

    2015-06-01

    To test the hypothesis that UVB can activate the hypothalamic-pituitary-adrenal (HPA) axis, the shaved back skin of C57BL/6 mice was exposed to 400 mJ cm(-2) of UVB or was sham irradiated. After 12 and 24 hours of exposure, plasma, skin, brain, and adrenals were collected and processed to measure corticotropin-releasing hormone (CRH), urocortin (Ucn), β-endorphin (β-END), ACTH, and corticosterone (CORT) or the brain was fixed for immunohistochemical detection of CRH. UVB stimulated plasma levels of CRH, Ucn, β-END, ACTH, and CORT and increased skin expression of Ucn, β-END, and CORT at the gene and protein/peptide levels. UVB stimulated CRH gene and protein expression in the brain that was localized to the paraventricular nucleus of the hypothalamus. In adrenal glands, it increased mRNAs of melanocortin receptor type 2, steroidogenic acute regulatory protein (StAR), and gene coding of steroid 11β-hydroxylase (CYP11B1). Hypophysectomy abolished UVB stimulation of plasma, but not of skin CORT levels, and had no effect on UVB stimulation of CRH and Ucn levels in the plasma, demonstrating the requirement of an intact pituitary for the systemic effect. In conclusion, we identify mechanisms regulating body homeostasis by UVB through activation of the HPA axis that originate in the skin and require the pituitary for systemic effects. PMID:25317845

  2. Endpoint Refinement for Total Body Irradiation of C57BL/6 Mice

    PubMed Central

    Nunamaker, Elizabeth A; Artwohl, James E; Anderson, Robert J; Fortman, Jeffrey D

    2013-01-01

    Acute radiation syndrome is a life-threatening condition that has the potential to affect large populations of humans. Although several animal models of this syndrome are available, the total-body–irradiated mouse has emerged as an important tool to evaluate the efficacy of prospective prophylaxis, mitigation, and treatment compounds. Despite the widespread use of this model, humane endpoints have not been clearly identified. To address this issue, we developed a cageside observation-based scoring system specifically for total-body–irradiated mice to assess the progression of clinical signs associated with acute radiation syndrome. Male C57BL/6 mice (n = 175; age, 8 to 9 wk) received an anticipated LD50 dose of radiation and were observed for progression of clinical signs of acute radiation syndrome for 30 d. All mice were scored individually through cageside observation of their body posture (score, 0 to 3), eye appearance (0 to 3), and activity level (0 to 3). Retrospective analysis of the score data indicated that death could be predicted accurately by using increasing cumulative scores (0 to 9). Total scores of 6, 7, 8, and 9 were associated with mortality rates of 78.6%, 86.4%, 93.3%, and 100%, respectively. Furthermore, scores of 6, 7, and 8 predicted death within 3, 1.5, and 0.5 d, respectively. The use of this scoring system provides investigators and IACUCs with predictive humane, surrogate endpoints for total-body–irradiated mice. This system allows preemptive euthanasia of mice before they become moribund, thereby minimizing pain and distress associated with acute radiation syndrome and improving animal welfare. PMID:23561934

  3. DEVELOPMENT OF HOME CAGE SOCIAL BEHAVIORS IN BALB/cJ vs. C57BL/6J MICE

    PubMed Central

    Fairless, Andrew H.; Katz, Julia M.; Vijayvargiya, Neha; Dow, Holly C.; Kreibich, Arati Sadalge; Berrettini, Wade H.; Abel, Ted; Brodkin, Edward S.

    2012-01-01

    BALB/cJ and C57BL/6J inbred mouse strains have been proposed as useful models of low and high levels of sociability (tendency to seek social interaction), respectively, based primarily on behaviors of ~30-day-old mice in the Social Approach Test (SAT). In the SAT, approach and sniffing behaviors of a test mouse toward an unfamiliar stimulus mouse are measured in a novel environment. However, it is unclear whether such results generalize to a familiar environment with a familiar social partner, such as with a littermate in a home cage environment. We hypothesized that C57BL/6J mice would show higher levels of social behaviors than BALB/cJ mice in the home cage environment, particularly at 30 days-of-age. We measured active and passive social behaviors in home cages by pairs of BALB/cJ or C57BL/6J littermates at ages 30, 41, and 69 days. The strains did not differ robustly in their active social behaviors. C57BL/6J mice were more passively social than BALB/cJ mice at 30 days, and C57BL/6J levels of passive social behaviors declined to BALB/cJ levels by 69 days. The differences in passive social behaviors at 30 days-of-age were primarily attributable to differences in huddling. These results indicate that different test conditions (SAT conditions vs. home cage conditions) elicit strain differences in distinct types of behaviors (approach/sniffing vs. huddling behaviors, respectively). Assessment of the more naturalistic social interactions in the familiar home cage environment with a familiar littermate will provide a useful component of a comprehensive assessment of social behaviors in mouse models relevant to autism. PMID:22982070

  4. Welfare Assessment following Heterotopic or Orthotopic Inoculation of Bladder Cancer in C57BL/6 Mice

    PubMed Central

    Miller, Amy; Burson, Hannah; Söling, Ariane

    2016-01-01

    Few studies have assessed whether mice used as cancer models experience pain. Despite this possibility, the usual practice is to withhold analgesics as these are generally viewed as confounding. However, pain also alters cancer progression, so preventing it might not only be beneficial to welfare but also to study validity. Establishing the extent to which different cancer models result in pain is an important first step towards their refinement. We used conditioned place preference (CPP) testing and body-weight and behaviour analyses to evaluate the assumption that heterotopically implanted tumours result in less pain and fewer welfare concerns than those implanted orthotopically. C57Bl/6 mice received MB49Luc luciferase expressing bladder cancer cells or saline implanted subcutaneously or into the bladder. These tumour-bearing or control groups underwent 2 daily 45 minute conditioning trials to saline or morphine (2mg/kg) and then a 15 minute drug-free preference test on day 3 of a 3 day cycle, continuing until the study ended. Tumours were imaged and behaviour data obtained following preference tests. Development of preference for the morphine-paired chamber (morphine-seeking) was determined over time. Heterotopic tumour development had no effect on morphine-seeking, and although the restraint used for heterotopic inoculation caused greater initial weight losses than anaesthesia, these mice steadily gained weight and behaved comparatively normally throughout the study. Orthotopic tumour inoculation caused no initial weight losses, but over the final 7 days these mice became less active and lost more body weight than cancer-free controls. This indicated orthotopic implantation probably caused a more negative impact on welfare or conceivably pain; but only according to the current test methods. Pain could not be confirmed because morphine-seeking in the tumour-bearing groups was similar to that seen in controls. Imaging was not found to be an effective method of

  5. Neurobehavioral phenotype of C57BL/6J mice prenatally and neonatally exposed to cigarette smoke

    PubMed Central

    Amos-Kroohs, Robyn M.; Williams, Michael T.; Braun, Amanda A.; Graham, Devon L; Webb, Cynthia L.; Birtles, Todd S.; Greene, Robert M.; Vorhees, Charles V.; Pisano, M. Michele

    2013-01-01

    Although maternal cigarette smoking during pregnancy is a well-documented risk factor for a variety of adverse pregnancy outcomes, how prenatal cigarette smoke exposure affects postnatal neurobehavioral/cognitive development remains poorly defined. In order to investigate the cause of an altered behavioral phenotype, mice developmentally exposed to a paradigm of ‘active’ maternal cigarette smoke is needed. Accordingly, cigarette smoke exposed (CSE) and air-exposed C57BL/6J mice were treated for 6 h per day in paired inhalation chambers throughout gestation and lactation and were tested for neurobehavioral effects while controlling for litter effects. CSE mice exhibited less than normal anxiety in the elevated zero maze, transient hypoactivity during a 1 h locomotor activity test, had longer latencies on the last day of cued Morris water maze testing, impaired hidden platform learning in the Morris water maze during acquisition, reversal, and shift trials, and impaired retention for platform location on probe trials after reversal but not after acquisition or shift. CSE mice also showed a sexually dimorphic response in central zone locomotion to a methamphetamine challenge (males under-responded and females over-responded), and showed reduced anxiety in the light-dark test by spending more time on the light side. No differences on tests of marble burying, acoustic startle response with prepulse inhibition, Cincinnati water maze, matching-to-sample Morris water maze, conditioned fear, forced swim, or MK-801-induced locomotor activation were found. Collectively, the data indicate that developmental cigarette smoke exposure induces subnormal anxiety in a novel environment, impairs spatial learning and reference memory while sparing other behaviors (route-based learning, fear conditioning, and forced swim immobility). The findings add support to mounting evidence that developmental cigarette smoke exposure has long-term adverse effects on brain function. PMID

  6. Neurobehavioral phenotype of C57BL/6J mice prenatally and neonatally exposed to cigarette smoke.

    PubMed

    Amos-Kroohs, Robyn M; Williams, Michael T; Braun, Amanda A; Graham, Devon L; Webb, Cynthia L; Birtles, Todd S; Greene, Robert M; Vorhees, Charles V; Pisano, M Michele

    2013-01-01

    Although maternal cigarette smoking during pregnancy is a well-documented risk factor for a variety of adverse pregnancy outcomes, how prenatal cigarette smoke exposure affects postnatal neurobehavioral/cognitive development remains poorly defined. In order to investigate the cause of an altered behavioral phenotype, mice developmentally exposed to a paradigm of 'active' maternal cigarette smoke is needed. Accordingly, cigarette smoke exposed (CSE) and air-exposed C57BL/6J mice were treated for 6h per day in paired inhalation chambers throughout gestation and lactation and were tested for neurobehavioral effects while controlling for litter effects. CSE mice exhibited less than normal anxiety in the elevated zero maze, transient hypoactivity during a 1h locomotor activity test, had longer latencies on the last day of cued Morris water maze testing, impaired hidden platform learning in the Morris water maze during acquisition, reversal, and shift trials, and impaired retention for platform location on probe trials after reversal but not after acquisition or shift. CSE mice also showed a sexually dimorphic response in central zone locomotion to a methamphetamine challenge (males under-responded and females over-responded), and showed reduced anxiety in the light-dark test by spending more time on the light side. No differences on tests of marble burying, acoustic startle response with prepulse inhibition, Cincinnati water maze, matching-to-sample Morris water maze, conditioned fear, forced swim, or MK-801-induced locomotor activation were found. Collectively, the data indicate that developmental cigarette smoke exposure induces subnormal anxiety in a novel environment, impairs spatial learning and reference memory while sparing other behaviors (route-based learning, fear conditioning, and forced swim immobility). The findings add support to mounting evidence that developmental cigarette smoke exposure has long-term adverse effects on brain function. PMID:23314114

  7. Neurobehavioral phenotype of C57BL/6J mice prenatally and neonatally exposed to cigarette smoke.

    PubMed

    Amos-Kroohs, Robyn M; Williams, Michael T; Braun, Amanda A; Graham, Devon L; Webb, Cynthia L; Birtles, Todd S; Greene, Robert M; Vorhees, Charles V; Pisano, M Michele

    2013-01-01

    Although maternal cigarette smoking during pregnancy is a well-documented risk factor for a variety of adverse pregnancy outcomes, how prenatal cigarette smoke exposure affects postnatal neurobehavioral/cognitive development remains poorly defined. In order to investigate the cause of an altered behavioral phenotype, mice developmentally exposed to a paradigm of 'active' maternal cigarette smoke is needed. Accordingly, cigarette smoke exposed (CSE) and air-exposed C57BL/6J mice were treated for 6h per day in paired inhalation chambers throughout gestation and lactation and were tested for neurobehavioral effects while controlling for litter effects. CSE mice exhibited less than normal anxiety in the elevated zero maze, transient hypoactivity during a 1h locomotor activity test, had longer latencies on the last day of cued Morris water maze testing, impaired hidden platform learning in the Morris water maze during acquisition, reversal, and shift trials, and impaired retention for platform location on probe trials after reversal but not after acquisition or shift. CSE mice also showed a sexually dimorphic response in central zone locomotion to a methamphetamine challenge (males under-responded and females over-responded), and showed reduced anxiety in the light-dark test by spending more time on the light side. No differences on tests of marble burying, acoustic startle response with prepulse inhibition, Cincinnati water maze, matching-to-sample Morris water maze, conditioned fear, forced swim, or MK-801-induced locomotor activation were found. Collectively, the data indicate that developmental cigarette smoke exposure induces subnormal anxiety in a novel environment, impairs spatial learning and reference memory while sparing other behaviors (route-based learning, fear conditioning, and forced swim immobility). The findings add support to mounting evidence that developmental cigarette smoke exposure has long-term adverse effects on brain function.

  8. Ulcerative Dermatitis in C57BL/6 Mice Exhibits an Oxidative Stress Response Consistent with Normal Wound Healing

    PubMed Central

    Williams, Lisa K; Csaki, Lauren S; Cantor, Rita M; Reue, Karen; Lawson, Greg W

    2012-01-01

    Ulcerative dermatitis (UD) is a common syndrome of unknown etiology that results in profound morbidity in C57BL/6 mice and lines on a C57BL/6 background. The lesions are due to severe pruritus-induced self-trauma, progressing from superficial excoriations to deep ulcerations. UD may be behavioral in origin, with ulcerative lesions resulting from self-mutilating behavior in response to unresolved inflammation or compulsion. Alternatively, abnormal oxidative damage may be a mechanism underlying UD. To evaluate whether UD behaves similarly to normal wounds, consistent with a secondary self-inflicted lesion, or is a distinct disorder with abnormal wound response, we evaluated expression levels of genes representing various arms of the oxidative stress response pathway UD-affected and unwounded C57BL/6J mice. No evidence indicated that UD wounds have a defect in the oxidative stress response. Our findings are consistent with an understanding of C57BL/6 UD lesions as typical rather than atypical wounds. PMID:22776048

  9. Ulcerative dermatitis in C57BL/6 mice exhibits an oxidative stress response consistent with normal wound healing.

    PubMed

    Williams, Lisa K; Csaki, Lauren S; Cantor, Rita M; Reue, Karen; Lawson, Greg W

    2012-06-01

    Ulcerative dermatitis (UD) is a common syndrome of unknown etiology that results in profound morbidity in C57BL/6 mice and lines on a C57BL/6 background. The lesions are due to severe pruritus-induced self-trauma, progressing from superficial excoriations to deep ulcerations. UD may be behavioral in origin, with ulcerative lesions resulting from self-mutilating behavior in response to unresolved inflammation or compulsion. Alternatively, abnormal oxidative damage may be a mechanism underlying UD. To evaluate whether UD behaves similarly to normal wounds, consistent with a secondary self-inflicted lesion, or is a distinct disorder with abnormal wound response, we evaluated expression levels of genes representing various arms of the oxidative stress response pathway UD-affected and unwounded C57BL/6J mice. No evidence indicated that UD wounds have a defect in the oxidative stress response. Our findings are consistent with an understanding of C57BL/6 UD lesions as typical rather than atypical wounds.

  10. Characterization of the 3D angular vestibulo-ocular reflex in C57BL6 mice.

    PubMed

    Migliaccio, Americo A; Meierhofer, Robert; Della Santina, Charles C

    2011-05-01

    We characterized the three-dimensional angular vestibulo-ocular reflex (3D aVOR) of adult C57BL6 mice during static tilt testing, sinusoidal, and high-acceleration rotations and compared it with that of another lateral-eyed mammal with afoveate retinae (chinchilla) and two primate species with forward eye orientation and retinal foveae (human and squirrel monkey). Noting that visual acuity in mice is poor compared to chinchillas and even worse compared to primates, we hypothesized that the mouse 3D aVOR would be relatively low in gain (eye-velocity/head-velocity) compared to other species and would fall off for combinations of head rotation velocity and frequency for which peak-to-peak position changes fall below the minimum visual angle resolvable by mice. We also predicted that as in chinchilla, the mouse 3D aVOR would be more isotropic (eye/head velocity gain independent of head rotation axis) and better aligned with the axis of head rotation than the 3D aVOR of primates. In 12 adult C57BL6 mice, binocular 3D eye movements were measured in darkness during whole-body static tilts, 20-100°/s whole-body sinusoidal rotations (0.02-10 Hz) and acceleration steps of 3,000°/s² to a 150°/s plateau (dominant spectral content 8-12 Hz). Our results show that the mouse has a robust static tilt counter-roll response gain of ~0.35 (eye-position Δ/head-position Δ) and mid-frequency aVOR gain (~0.6-0.8), but relatively low aVOR gain for high-frequency sinusoidal head rotations and for steps of head rotation acceleration (~0.5). Due to comparatively poor static visual acuity in the mouse, a perfectly compensatory 3D aVOR would confer relatively little benefit during high-frequency, low-amplitude movements. Therefore, our data suggest that the adaptive drive for maintaining a compensatory 3D aVOR depends on the static visual acuity in different species. Like chinchillas, mice have a much more nearly isotropic 3D aVOR than do the primates for which comparable data are

  11. Pifithrin-μ Attenuates Acute Sickness Response to Lipopolysaccharide in C57BL/6J Mice.

    PubMed

    Zhang, Rongping; Wang, Jili; Hu, Yanling; Lu, Xu; Jiang, Bo; Zhang, Wei; Huang, Chao

    2016-01-01

    Sickness behavior is a coordinated set of behavioral changes that happen as a response to acute infectious pathogens. Its well-known benefit is to reorganize the organism's priorities to cope with infection, but the uncontrolled development of sickness behavior may trigger negative feelings or chronic depressive events. This study aims at investigating the potential effect of pifithrin-μ, an inhibitor of heat shock protein 70 substrate binding activity, on lipopolysaccharide (LPS)-induced sickness response. C57BL/6J mice were submitted to the forced swimming test (FST), tail suspension test (TST), open field test (OFT) and light-dark box test. Food intake and body weight were also evaluated. The serum corticosterone level was measured using an ELISA kit. Treatment of mice with LPS (0.33 mg/kg, i.p.) markedly increased the floating and immobility time in the FST and TST, respectively, and depressed locomotor activity in the OFT. LPS administration prolonged the latency to first transition and reduced the total number of transitions in the light-dark box test. In addition, LPS induced anorexia and increased serum corticosterone levels. Pretreatment with pifithrin-μ (1 or 5 mg/kg) attenuated behavioral changes induced by LPS in the FST, TST, OFT and light-dark box test. Pifithrin-μ also prevented the formation of anorexia as well as the increase in serum corticosterone levels in LPS-treated mice. Our previous studies showed that pifithrin-μ prevents the production of pro-inflammatory factors in both microglia and macrophages. These findings presented here extend the role of pifithrin-μ beyond an anti-inflammatory molecule to a modulator of sickness behavior.

  12. Early deprivation induces competitive subordinance in C57BL/6 male mice.

    PubMed

    Benner, Seico; Endo, Toshihiro; Endo, Nozomi; Kakeyama, Masaki; Tohyama, Chiharu

    2014-10-01

    Rodent models have been widely used to investigate the impact of early life stress on adult health and behavior. However, the social dimension has rarely been incorporated into the analysis due to methodological limitations. This study characterized the effects of neonatal social isolation (early deprivation, ED) on adult C57BL/6 mouse behavior in a social context using our recently developed behavioral test protocols for group-housed mice. During the first two postnatal weeks, half of the pups per dam were separated from their dam and littermates for 3h per day (ED group). Post weaning, ED and control pups were electronically tagged and co-housed. At 12weeks, the mixed cohorts were transferred to IntelliCages, equipped with computer-controlled operant chambers. Access to the chambers was used as an index to analyze novel object response, behavioral flexibility, and competitive dominance with minimal experimenter intervention. In general, ED had greater effects on males; ED males exhibited reduced body weight, increased novelty response, and were subordinate to control littermates when competing for reward access. Male ED mice also demonstrated mildly impaired reversal learning. Analyzing gene expression changes in brain regions controlling emotion, stress, spatial memory, and executive function revealed reduced BDNF and c-Fos in hippocampal CA1, enhanced c-Fos in the basolateral amygdala, reduced Map2 while enhanced HSD11β2 in prefrontal cortex of ED males. In male mice, it was suggested that neonatal social isolation results in sustained changes in social behavior with altered function of limbic and frontal cortices.

  13. Inhibition of phosphodiesterase 4 reduces ethanol intake and preference in C57BL/6J mice.

    PubMed

    Blednov, Yuri A; Benavidez, Jillian M; Black, Mendy; Harris, R Adron

    2014-01-01

    Some anti-inflammatory medications reduce alcohol consumption in rodent models. Inhibition of phosphodiesterases (PDE) increases cAMP and reduces inflammatory signaling. Rolipram, an inhibitor of PDE4, markedly reduced ethanol intake and preference in mice and reduced ethanol seeking and consumption in alcohol-preferring fawn-hooded rats (Hu et al., 2011; Wen et al., 2012). To determine if these effects were specific for PDE4, we compared nine PDE inhibitors with different subtype selectivity: propentofylline (nonspecific), vinpocetine (PDE1), olprinone, milrinone (PDE3), zaprinast (PDE5), rolipram, mesopram, piclamilast, and CDP840 (PDE4). Alcohol intake was measured in C57BL/6J male mice using 24-h two-bottle choice and two-bottle choice with limited (3-h) access to alcohol. Only the selective PDE4 inhibitors reduced ethanol intake and preference in the 24-h two-bottle choice test. For rolipram, piclamilast, and CDP840, this effect was observed after the first 6 h but not after the next 18 h. Mesopram, however, produced a long-lasting reduction of ethanol intake and preference. In the limited access test, rolipram, piclamilast, and mesopram reduced ethanol consumption and total fluid intake and did not change preference for ethanol, whereas CDP840 reduced both consumption and preference without altering total fluid intake. Our results provide novel evidence for a selective role of PDE4 in regulating ethanol drinking in mice. We suggest that inhibition of PDE4 may be an unexplored target for medication development to reduce excessive alcohol consumption.

  14. Hypolipidemic effects of Myrica rubra extracts and main compounds in C57BL/6j mice.

    PubMed

    He, Kai; Li, Xuegang; Xiao, Yubo; Yong, Yang; Zhang, Zaiqi; Li, Shuping; Zhou, Taimei; Yang, Daqing; Gao, Pincao; Xin, Xiaoliang

    2016-08-10

    The present study evaluated the antihyperlipidemic activity of myricetin, myricetrin, the alcohol fraction (AF) and the ethyl acetate fraction (EF) obtained from the bark of Myrica rubra (MR) in high-fat and high-cholesterol (HFHC) induced hyperlipidemic C57BL/6j mice. Mice were treated with myricetin, myricetrin, AF and EF with a dose of 130 mg per kg per day for 35 days. After treatment, serum parameters including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), total bile acids (TBA), etc., were examined. The results revealed that EF showed the highest weight lowering activity (P < 0.01). All tested samples decreased the levels of the TC, TG, LDL-C, TBA and LPS (lipopolysaccharide) content in the serum of mice to different extents. Liver fat deposition was significantly reduced after myricetin, myricetrin, AF and EF therapy (P < 0.01). Additionally, the cell size of epididymal adipose tissue was also decreased in myricetin, AF and EF groups (P < 0.05). The antihyperlipidemic activity of these samples may be attributed to the inhibition of lipid synthesis via suppressing the expression of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) and ACC1 (acetyl-CoA carboxylase), promoting the metabolism and excretion of lipids via up-regulating the expression of SREBP2 (sterol regulatory element binding proteins), LDLR (low density lipoprotein receptor), UCP2 (uncoupling protein 2) and CYP7A1 (cholesterol 7α-hydroxylase). These results may provide a powerful foundation for seeking and utilizing Myrica rubra bio-active compounds for the treatment of hyperlipidemia and cardiovascular diseases. PMID:27459037

  15. Role of whiskers in sensorimotor development of C57BL/6 mice

    PubMed Central

    Arakawa, Hiroyuki; Erzurumlu, Reha S.

    2015-01-01

    The mystacial vibrissae (whiskers) of nocturnal rodents play a major role in their sensorimotor behaviors. Relatively little information exists on the role of whiskers during early development. We characterized the contribution of whiskers to sensorimotor development in postnatal C57BL/6 mice. A comparison between intact and whisker-clipped mice in a battery of behavioral tests from postnatal day (P) 4 to 17 revealed that both male and female pups develop reflexive motor behavior even when the whiskers are clipped. Daily whisker trimming from P3 onwards results in diminished weight gain by P17, and impairment in whisker sensorimotor coordination behaviors, such as cliff avoidance and littermate huddling from P4 through P17, while facilitation of righting reflex at P4 and grasp response at P12. Since active whisker palpation does not start until 2 weeks of age, passive whisker touch during early neonatal stage must play a role in regulating these behaviors. Around the onset of exploratory behaviors (P12) neonatal whisker-clipped pups also display persistent searching movements when they encounter cage walls as a compensatory mechanism of sensorimotor development. Spontaneous whisker motion (whisking) is distinct from respiratory fluttering of whiskers. It is a symmetrical vibration of whiskers at a rate of approximately ∼8 Hz, and begins around P10. Oriented, bundled movements of whiskers at higher frequencies of ∼12 Hz during scanning object surfaces, i.e., palpation whisking, emerges at P14. The establishment of locomotive body coordination before eyes open accompanies palpation whisking, indicating an important role in the guidance of exploratory motor behaviors. PMID:25823761

  16. Effects of Embryo Transfer on Emotional Behaviors in C57BL/6 Mice.

    PubMed

    Lerch, Sandra; Tolksdorf, Gabriele; Schütz, Patrizia; Brandwein, Christiane; Dormann, Christof; Gass, Peter; Chourbaji, Sabine

    2016-01-01

    Microbiologic standardization plays a key role in the management of animal facilities because contamination of stock could affect the health status and wellbeing of animals and thereby induce artifacts in biomedical research. One common method to avoid the dissemination of pathogens is embryo transfer (ET). Although disturbances in the perinatal environment may cause long-lasting effects on the behavior and physiology of mouse offspring, the influences of ET during this sensitive phase have not yet been addressed. Our study investigated the effects of various components of ET (anesthesia, surgery, recipient strain) on the behavior of dams (exploration, nest-building) and offspring (nest-building, exploration, anxiety, and social and depressive-like behaviors). For ET, the donor strain C57BL/6N and a standard protocol were used. Whereas treatment with anesthesia-analgesia did not affect maternal behavior, female offspring demonstrated overall effects on weight gain and corticosterone levels. Compared with naturally delivered female offspring, dams obtained through ET demonstrated decreased exploration and nest-building. In addition, female ET-derived offspring had enhanced levels of anxiety and increased social interest. Furthermore, ET-derived dams obtained by using NMRI as the recipient strain showed increased exploratory behavior compared with that of dams obtained by using C57 mice as recipients. Compared with using C57 as recipients, both sexes of offspring transferred into NMRI recipients weighed more, and female mice showed a depressive-like phenotype. Our findings suggest that ET, now considered to be a routine procedure in animal husbandry, bears the risk of introducing artifacts. PMID:27657704

  17. Auditory brainstem responses to clicks and tone bursts in C57 BL/6J mice.

    PubMed

    Scimemi, P; Santarelli, R; Selmo, A; Mammano, F

    2014-08-01

    In auditory research, hearing function of mouse mutants is assessed in vivo by evoked potential recording. Evaluation of the response parameters should be performed with reference to the evoked responses recorded from wild-type mice. This study reports normative data calculated on auditory brainstem responses (ABRs) obtained from 20 wild-type C57 BL/6J mice at a postnatal age between 21 and 45 days. Acoustic stimuli consisted tone bursts at 8, 14, 20, 26, 32 kHz, and clicks. Each stimulus was delivered in free field at stimulation intensity starting from a maximum of 100 dB peak equivalent SPL (dB peSPL) at decreasing steps of 10 dB with a repetition rate of 13/sec. Evoked responses were recorded by needle electrodes inserted subcutaneously. At high intensity stimulation, five response waveforms, each consisting of a positive peak and a subsequent negative valley, were identified within 7 msec, and were labelled with sequential capital Roman numerals from I to V. Peak IV was the most robust and stable at low intensities for both tone burst and click stimuli, and was therefore utilized to estimate hearing thresholds. Both latencies and amplitudes of ABR peaks showed good reproducibility with acceptable standard deviations. Mean wave IV thresholds measured across all animals ranged from a maximum of 23 dB peSPL for clicks to a minimum of 7 dB peSPL for 20 kHz-tone burst stimuli. Statistical analysis of the distribution of latencies and amplitudes of peaks from I to V performed for each stimulus type yielded a normative data set which was utilised to obtain the most consistent fitting-curve model. This could serve as a reference for further studies on murine models of hearing loss.

  18. Cytokeratin Expression at Different Stages in Sweat Gland Development of C57BL/6J Mice.

    PubMed

    Xie, Jiangfan; Yao, Bin; Han, Yutong; Shang, Tao; Gao, Dongyun; Yang, Siming; Ma, Kui; Huang, Sha; Fu, Xiaobing

    2015-12-01

    Sweat glands exhibit a documented role in epidermal reepithelialization after wounding. However, the regenerative potential of sweat glands has remained underappreciated due to the absence of useful markers for the analysis of determination and differentiation processes in the developing eccrine sweat gland from epithelium. Although the current knowledge of keratin expression in most of the different origins has been described, it remains widely shared and not unified in eccrine sweat glands of C57BL/6J mice that are commonly used as animal models for sweat gland and wound healing studies, both at the molecular and cellular levels. Aiming to answer this question, we have investigated the changes in cytokeratin expression patterns during the embryonic, neonatal, juvenile, and young adult stages (E12.5, E17.5, P0.5, P5, and P28). In this article, we demonstrate that the morphology of murine sweat gland progenitor cells are similar to epidermal stem cells before birth (E12.5 and E17.5); at postnatal stages, the duct formed gradually and curled to glob. K8 and K19 were expressed in the eccrine sweat gland cells at all times and highly expressed after birth at both gene and protein levels. Also, histological results revealed K8 and K19 positive cells localized in the secretary portion of glands. Meanwhile, K14 strongly expressed both in vivo and in vitro at E12.5, while it weakly expressed at other stages. Moreover, K10 was rarely detected before birth, but it expressed positively in vivo and in vitro only at the protein level after birth. These data indicate the pattern of main cytokeratin expression at different stages during murine sweat gland development and might provide an efficient tool for sweat gland research and exciting potential for developing targeted therapies for wound healing.

  19. Cytokeratin Expression at Different Stages in Sweat Gland Development of C57BL/6J Mice.

    PubMed

    Xie, Jiangfan; Yao, Bin; Han, Yutong; Shang, Tao; Gao, Dongyun; Yang, Siming; Ma, Kui; Huang, Sha; Fu, Xiaobing

    2015-12-01

    Sweat glands exhibit a documented role in epidermal reepithelialization after wounding. However, the regenerative potential of sweat glands has remained underappreciated due to the absence of useful markers for the analysis of determination and differentiation processes in the developing eccrine sweat gland from epithelium. Although the current knowledge of keratin expression in most of the different origins has been described, it remains widely shared and not unified in eccrine sweat glands of C57BL/6J mice that are commonly used as animal models for sweat gland and wound healing studies, both at the molecular and cellular levels. Aiming to answer this question, we have investigated the changes in cytokeratin expression patterns during the embryonic, neonatal, juvenile, and young adult stages (E12.5, E17.5, P0.5, P5, and P28). In this article, we demonstrate that the morphology of murine sweat gland progenitor cells are similar to epidermal stem cells before birth (E12.5 and E17.5); at postnatal stages, the duct formed gradually and curled to glob. K8 and K19 were expressed in the eccrine sweat gland cells at all times and highly expressed after birth at both gene and protein levels. Also, histological results revealed K8 and K19 positive cells localized in the secretary portion of glands. Meanwhile, K14 strongly expressed both in vivo and in vitro at E12.5, while it weakly expressed at other stages. Moreover, K10 was rarely detected before birth, but it expressed positively in vivo and in vitro only at the protein level after birth. These data indicate the pattern of main cytokeratin expression at different stages during murine sweat gland development and might provide an efficient tool for sweat gland research and exciting potential for developing targeted therapies for wound healing. PMID:26680749

  20. Physiological and behavioral responses to intermittent starvation in C57BL/6J mice.

    PubMed

    Zhang, Li-Na; Mitchell, Sharon E; Hambly, Catherine; Morgan, David G; Clapham, John C; Speakman, John R

    2012-01-18

    The dual intervention point model states that body mass is controlled by upper and lower intervention points, above and below which animals (and humans) intervene physiologically to bring their body mass back into the acceptable range. It has been further suggested that the lower intervention point may be defined by the risk of starvation, while the upper intervention point may be defined by the risk of predation. The objective of the present study was to test whether the risk of starvation determines the lower intervention point and to examine the physiological and behavioral mechanisms that underpin the regulation of body mass, when the risk of starvation is increased. Sixty-four mice were exposed to random days of complete fasting or 50% food restriction and their body mass and fat mass responses were measured. Food intake, physical activity and body temperature were measured throughout the experiment. In addition, plasma leptin and insulin, triglyceride and non-esterified fatty acids, along with hypothalamic neuropeptides gene expression in the arcuate nucleus were assessed after 13 and 42 days of treatment. We found that C57BL/6J mice increased body mass and fatness in response to a short-term (13 days) intermittent fasting, which was restored to baseline as the treatment was prolonged. In contrast, intermittently 50% food restricted mice showed no significant changes in body mass or fatness. Over the first 13 days of treatment the data were consistent with the dual intervention point model as the mice showed both increased body mass and adiposity over this period. Over the more protracted period of 42 days the effect waned and was therefore inconsistent with the model. The body mass and fat mass gains in intermittently fasted mice were mainly accounted for by increased food intake. Elevated NPY gene expression after 13 days (three 24 h fasting events) may have driven the increase in food intake. However, no changes were observed in such neuropeptides as POMC

  1. Indomethacin treatment prevents diet-induced obesity and insulin resistance, but not glucose intolerance in C57BL/6J mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    OBJECTIVE: We performed experiments to examine the metabolic consequences of inhibition of cyclooxygenase (COX) activity in obesity-prone C57BL/6J mice fed a high fat/high sucrose (HF/HS) diet. RESEARCH DESIGN AND METHODS: C57BL/6J mice were fed a HF/HS diet for 7 weeks under thermoneutral conditio...

  2. Ethanol, nicotine, amphetamine, and aspartame consumption and preferences in C57BL/6 and DBA/2 mice.

    PubMed

    Meliska, C J; Bartke, A; McGlacken, G; Jensen, R A

    1995-04-01

    Using a two-bottle choice paradigm, adult C57BL/6 and DBA/2 mice (11 males an 10 females per strain) were given access to tapwater and an ascending series of concentrations of ethanol, nicotine, amphetamine, and th artificial sweetener, aspartame. The C57 mice consumed more ethanol, nicotine, and amphetamine, and showed greater preferences for these substances, than did the DBA/2 mice. In contrast, DBAs consumed more and showed greater preference for aspartame than C57s. However, measures of drug and aspartame consumption and preference were moderately intercorrelated when the effects of gender and strain were controlled for. This pattern of results suggests that factors modulating differences between C57BL/6 and DBA/2 mice in ethanol consumption and preference also modulate differences in consumption of nicotine and amphetamine.

  3. Effects of naltrexone on post-abstinence alcohol drinking in C57BL/6NCRL and DBA/2J mice.

    PubMed

    Tomie, Arthur; Azogu, Idu; Yu, Lei

    2013-07-01

    The present experiment evaluated the effects of naltrexone, a non-selective opioid receptor antagonist, on post-abstinence alcohol drinking in C57BL/6NCRL and DBA/2J male mice. Home cage 2-bottle (alcohol vs. water) free-choice procedures were employed. During the pre-abstinence period, alcohol intake was much lower for the DBA/2J mice relative to the C57BL/6NCRL mice, and this strain difference was observed for groups receiving either 3% or 10% alcohol concentrations. The four-day abstinence period effectively reduced alcohol intakes (i.e., a negative alcohol deprivation effect, negative ADE) in both groups of DBA/2J mice, but had no effect on alcohol intakes in either group of C57BL/6NCRL mice. Both groups trained with 3% alcohol received the second four-day abstinence period, where the effects of acute administration of either naltrexone or saline on post-abstinence alcohol drinking were assessed. Naltrexone was more effective in reducing post-abstinence drinking of 3% alcohol in the DBA/2J mice than in the C57BL/6NCRL mice. In the DBA/2J mice, naltrexone further reduced, relative to saline-injected controls, the low levels of post-abstinence alcohol intake. Thus, the low baseline levels of alcohol drinking in DBA/2J mice were further diminished by the four-day abstinence period (negative ADE), and this suppressed post-abstinence level of alcohol drinking was still further reduced by acute administration of naltrexone. The results indicate that naltrexone is effective in reducing further the low levels of alcohol drinking induced by the negative ADE.

  4. [Latent inhibition and extinction of passive avoidance in mice C57BL/6J AND DBA/2J].

    PubMed

    Dubrovina, N I; Red'kina, A V

    2012-04-01

    The study was carried out in mice C57BL/6J and DBA/2J for comparative analysis of two interference processes: latent inhibition and extinction of passive avoidance produced with an unconditioned aversive stimulus of different parameters (0.5 and 0.25 mA). With a strong training to new stimulus, impairment of extinction has been detected only in mice DBA/2J. Reduction in the strength of punishment during training was accompanied by acceleration of extinction in mice C57BL/6J and its appearance in mice DBA/2J. The learning of passive avoidance in strong and weak reinforcement was the same for both strains of mice. Interline differences were found also in the analysis of latent inhibition. With strong and weak training to conditional stimulus, lost of novelty by repeated an 8-fold pre-exposures to the experimental chamber, in DBA/2J mice, in contrast to C57BL/6J, latent inhibition was disrupted. In addition, DBA/2J mice showed impairment of extinction with weak training to non-relevant stimulus. PMID:22834338

  5. [Latent inhibition and extinction of passive avoidance in mice C57BL/6J AND DBA/2J].

    PubMed

    Dubrovina, N I; Red'kina, A V

    2012-04-01

    The study was carried out in mice C57BL/6J and DBA/2J for comparative analysis of two interference processes: latent inhibition and extinction of passive avoidance produced with an unconditioned aversive stimulus of different parameters (0.5 and 0.25 mA). With a strong training to new stimulus, impairment of extinction has been detected only in mice DBA/2J. Reduction in the strength of punishment during training was accompanied by acceleration of extinction in mice C57BL/6J and its appearance in mice DBA/2J. The learning of passive avoidance in strong and weak reinforcement was the same for both strains of mice. Interline differences were found also in the analysis of latent inhibition. With strong and weak training to conditional stimulus, lost of novelty by repeated an 8-fold pre-exposures to the experimental chamber, in DBA/2J mice, in contrast to C57BL/6J, latent inhibition was disrupted. In addition, DBA/2J mice showed impairment of extinction with weak training to non-relevant stimulus.

  6. Differential Insulin Secretion of High-Fat Diet-Fed C57BL/6NN and C57BL/6NJ Mice: Implications of Mixed Genetic Background in Metabolic Studies.

    PubMed

    Attané, Camille; Peyot, Marie-Line; Lussier, Roxane; Zhang, Dongwei; Joly, Erik; Madiraju, S R Murthy; Prentki, Marc

    2016-01-01

    Many metabolic studies employ tissue-specific gene knockout mice, which requires breeding of floxed gene mice, available mostly on C57BL/6N (NN) genetic background, with cre or Flp recombinase-expressing mice, available on C57BL/6J (JJ) background, resulting in the generation of mixed C57BL/6NJ (NJ) genetic background mice. Recent awareness of many genetic differences between NN and JJ strains including the deletion of nicotinamide nucleotide transhydrogenase (nnt), necessitates examination of the consequence of mixed NJ background on glucose tolerance, beta cell function and other metabolic parameters. Male mice with NN and NJ genetic background were fed with normal or high fat diets (HFD) for 12 weeks and glucose and insulin homeostasis were studied. Genotype had no effect on body weight and food intake in mice fed normal or high fat diets. Insulinemia in the fed and fasted states and after a glucose challenge was lower in HFD-fed NJ mice, even though their glycemia and insulin sensitivity were similar to NN mice. NJ mice showed mild glucose intolerance. Moreover, glucose- but not KCl-stimulated insulin secretion in isolated islets was decreased in HFD-fed NJ vs NN mice without changes in insulin content and beta cell mass. Under normal diet, besides reduced fed insulinemia, NN and NJ mice presented similar metabolic parameters. However, HFD-fed NJ mice displayed lower fed and fasted insulinemia and glucose-induced insulin secretion in vivo and ex vivo, as compared to NN mice. These results strongly caution against using unmatched mixed genetic background C57BL/6 mice for comparisons, particularly under HFD conditions.

  7. Differential Insulin Secretion of High-Fat Diet-Fed C57BL/6NN and C57BL/6NJ Mice: Implications of Mixed Genetic Background in Metabolic Studies.

    PubMed

    Attané, Camille; Peyot, Marie-Line; Lussier, Roxane; Zhang, Dongwei; Joly, Erik; Madiraju, S R Murthy; Prentki, Marc

    2016-01-01

    Many metabolic studies employ tissue-specific gene knockout mice, which requires breeding of floxed gene mice, available mostly on C57BL/6N (NN) genetic background, with cre or Flp recombinase-expressing mice, available on C57BL/6J (JJ) background, resulting in the generation of mixed C57BL/6NJ (NJ) genetic background mice. Recent awareness of many genetic differences between NN and JJ strains including the deletion of nicotinamide nucleotide transhydrogenase (nnt), necessitates examination of the consequence of mixed NJ background on glucose tolerance, beta cell function and other metabolic parameters. Male mice with NN and NJ genetic background were fed with normal or high fat diets (HFD) for 12 weeks and glucose and insulin homeostasis were studied. Genotype had no effect on body weight and food intake in mice fed normal or high fat diets. Insulinemia in the fed and fasted states and after a glucose challenge was lower in HFD-fed NJ mice, even though their glycemia and insulin sensitivity were similar to NN mice. NJ mice showed mild glucose intolerance. Moreover, glucose- but not KCl-stimulated insulin secretion in isolated islets was decreased in HFD-fed NJ vs NN mice without changes in insulin content and beta cell mass. Under normal diet, besides reduced fed insulinemia, NN and NJ mice presented similar metabolic parameters. However, HFD-fed NJ mice displayed lower fed and fasted insulinemia and glucose-induced insulin secretion in vivo and ex vivo, as compared to NN mice. These results strongly caution against using unmatched mixed genetic background C57BL/6 mice for comparisons, particularly under HFD conditions. PMID:27403868

  8. Differential Insulin Secretion of High-Fat Diet-Fed C57BL/6NN and C57BL/6NJ Mice: Implications of Mixed Genetic Background in Metabolic Studies

    PubMed Central

    Attané, Camille; Peyot, Marie-Line; Lussier, Roxane; Zhang, Dongwei; Joly, Erik; Madiraju, S. R. Murthy; Prentki, Marc

    2016-01-01

    Many metabolic studies employ tissue-specific gene knockout mice, which requires breeding of floxed gene mice, available mostly on C57BL/6N (NN) genetic background, with cre or Flp recombinase-expressing mice, available on C57BL/6J (JJ) background, resulting in the generation of mixed C57BL/6NJ (NJ) genetic background mice. Recent awareness of many genetic differences between NN and JJ strains including the deletion of nicotinamide nucleotide transhydrogenase (nnt), necessitates examination of the consequence of mixed NJ background on glucose tolerance, beta cell function and other metabolic parameters. Male mice with NN and NJ genetic background were fed with normal or high fat diets (HFD) for 12 weeks and glucose and insulin homeostasis were studied. Genotype had no effect on body weight and food intake in mice fed normal or high fat diets. Insulinemia in the fed and fasted states and after a glucose challenge was lower in HFD-fed NJ mice, even though their glycemia and insulin sensitivity were similar to NN mice. NJ mice showed mild glucose intolerance. Moreover, glucose- but not KCl-stimulated insulin secretion in isolated islets was decreased in HFD-fed NJ vs NN mice without changes in insulin content and beta cell mass. Under normal diet, besides reduced fed insulinemia, NN and NJ mice presented similar metabolic parameters. However, HFD-fed NJ mice displayed lower fed and fasted insulinemia and glucose-induced insulin secretion in vivo and ex vivo, as compared to NN mice. These results strongly caution against using unmatched mixed genetic background C57BL/6 mice for comparisons, particularly under HFD conditions. PMID:27403868

  9. Pregnancy reduces the genetic resistance of C57BL/6 mice to Listeria monocytogenes infection by intragastric inoculation

    PubMed Central

    Poulsen, Keith P.; Faith, Nancy G.; Steinberg, Howard; Czuprynski, Charles J.

    2011-01-01

    In this study, we compared genetically resistant C57BL/6 and susceptible A/J mice for their resistance to L. monocytogenes infection model during pregnancy. Intragastric infection with modest numbers of bacterial cells (105 CFU) caused reproducible fetal infection and abortion in both mouse strains. Bioluminescence imaging demonstrated dissemination of L. monocytogenes cells from maternal to fetal organs within 3 days of intragastric infection. Although non-pregnant C57BL/6 mice were significantly more resistant to infection than non-pregnant A/J mice, C57BL/6 and A/J mice had similar microbial loads (CFU) in maternal and fetal tissues during pregnancy. Inflammation and necrosis, however, were more severe in A/J mice as evaluated by semi-quantitative histopathology. Although the microbial load in fetal tissues was similar for all fetuses within a single uterus, inflammation and necrosis varied among individual fetuses and placentas. We also noted that the uterus is a target for L. monocytogenes infection in non-pregnant mice. PMID:21320586

  10. Sexually dimorphic characteristics of the small intestine and colon of prepubescent C57BL/6 mice

    PubMed Central

    2014-01-01

    Background There is increasing appreciation for sexually dimorphic effects, but the molecular mechanisms underlying these effects are only partially understood. In the present study, we explored transcriptomics and epigenetic differences in the small intestine and colon of prepubescent male and female mice. In addition, the microbiota composition of the colonic luminal content has been examined. Methods At postnatal day 14, male and female C57BL/6 mice were sacrificed and the small intestine, colon and content of luminal colon were isolated. Gene expression of both segments of the intestine was analysed by microarray analysis. DNA methylation of the promoter regions of selected sexually dimorphic genes was examined by pyrosequencing. Composition of the microbiota was explored by deep sequencing. Results Sexually dimorphic genes were observed in both segments of the intestine of 2-week-old mouse pups, with a stronger effect in the small intestine. Amongst the total of 349 genes displaying a sexually dimorphic effect in the small intestine and/or colon, several candidates exhibited a previously established function in the intestine (i.e. Nts, Nucb2, Alox5ap and Retnlγ). In addition, differential expression of genes linked to intestinal bowel disease (i.e. Ccr3, Ccl11 and Tnfr) and colorectal cancer development (i.e. Wt1 and Mmp25) was observed between males and females. Amongst the genes displaying significant sexually dimorphic expression, nine genes were histone-modifying enzymes, suggesting that epigenetic mechanisms might be a potential underlying regulatory mechanism. However, our results reveal no significant changes in DNA methylation of analysed CpGs within the selected differentially expressed genes. With respect to the bacterial community composition in the colon, a dominant effect of litter origin was found but no significant sex effect was detected. However, a sex effect on the dominance of specific taxa was observed. Conclusions This study reveals

  11. [The effect of NADP+ on electrophysiological properties of cardiomyocytes of C57BL/6 and mdx mice].

    PubMed

    Mikhaĭlov, V M; Mamaeva, G I

    2013-01-01

    We have studied the influence of NADP+ on routine ECG in 6 months old C57BL/6 and mdx mice. The animals were anestheized by ether before ECG recording. ECG registration was made with the speed of 100 mm per sec. The first ECG recording was made before intraperitoneal NADP+ injection in a dose of 13 or 80 mg/kg. The second ECG recording was made in 10 min after NADP+ injection. Then anesthesia was cut off. The mice were occasionally anestheized 45-60 min later and the third ECG was recorded in 1 h after injection of NADP+. ECG recording was made at a speed of 100 mm/s in the standard leads I, II and III and in the unipolar leads AvR, AvL and AvF. Values of standard ECG characteristics such as the P wave, intervals PQ, QT, RR, and QRS complex in milliseconds were measured in standard lead II. We did not observe any differences between ECG magnitudes of 2-3 months old C57BL/6 and mdx mice during trial experiments. Mice of both lines had sinus rhythm of heart rate. QRS complex in mdx mice had a tendency to be larger compared with that in C57BL/6 mice. Heart rates fluctuated between 722 ± 22 and 681 ± 23 beats per minute. NADP+ influences was studied in 6 months old mice male. The increase in the RR interval and decreased heart rate from 697 ± 2 to 461 ± 23 and 491 ± 28 beats per min for C57BL/6 mice (P < 0.01) and from 722 ± 28 beats per minute to 454 ± 31 beats per min for mdx mice were registered in 10 min after NADP+ injection in a dose of 80 mg/kg. The increase in the RR interval can be explained by an increase in the interval QT. A statistically significant reduction in the QT interval leading to a decrease in the RR interval was observed in mdx mice in 1 h after NADP+ injection. NADP+ in a dose 13 mg/kg did not change mdx mice ECG properties significantly. ECG of mdx mice were characterized by negative repolarization of T wave in 37% between all leads. A deal of leads with the negative T wave repolarization decreased up to 3% in 1 h after NADP+ injection

  12. Comparison of 3 Topical Treatments against Ulcerative Dermatitis in Mice with a C57BL/6 Background.

    PubMed

    Michaud, Carmen R; Qin, Jing; Elkins, William R; Gozalo, Alfonso S

    2016-04-01

    Ulcerative dermatitis (UD) is a common condition in C57BL/6 mice and strains with this background. The etiology of UD is unclear but appears to have a genetic component associated with the C57BL/6 strain and has been reported as secondary to a variety of conditions. Treatment is unrewarding, resulting in euthanasia in many cases. In the present study we compared 3 topical treatments against spontaneous UD in mice with a C57BL/6 background. In total, 301 mice of both sexes were included in this study, and the tested treatments comprised bacitracin-neomycin sulfate-polymixin B sulfate ointment twice daily, 10% povidone-iodine ointment plus 1% silver sulfadiazine cream once daily, and 0.005% sodium hypochlorite once daily. Lesion healing was defined as complete skin reepithelialization with or without hair regrowth. Sex, age, lesion location, and type and length of treatment were analyzed by using univariate and multivariate logistic regression. Of the 79 mice treated with triple-antibiotic ointment, 27 (34%) healed, compared with 43 of the 125 (34%) treated with povidone-iodine and sulfadiazine and 69 of the 97 (71%) treated with hypochlorite. Lesion size and treatment with 0.005% sodium hypochlorite were the only significant predictors of healing; all other variables were not statistically significant in multivariate analysis. We conclude that 0.005% sodium hypochlorite is an effective topical treatment alternative for UD in C57BL/6 mice and strains on this background, and a favorable prognosis depends on the early identification and treatment of those lesions. PMID:27053563

  13. Systematic Literature Review of Risk Factors and Treatments for Ulcerative Dermatitis in C57BL/6 Mice.

    PubMed

    Sargent, Jennifer L; Koewler, Nathan J; Diggs, Helen E

    2015-12-01

    Ulcerative dermatitis (UD) in C57BL/6 mice is poorly understood and challenging to treat. We sought to evaluate the evidence regarding commonly cited risk factors for UD and reported UD treatments. The terms 'ulcerative dermatitis' and 'C57BL/6' were used to search 3 electronic databases. The resulting 347 articles were screened to identify publications that compared the risk of spontaneous UD in wild-type C57BL/6 mice according to sex, season, diet, or age and those that compared the degree of healing or rate of lesion resolution according to the intervention used. Articles were evaluated by using published criteria for assessing methodologic quality, including study design, number of animals per study group, case definition, method of diagnosis, randomization, enrollment criteria, exclusion criteria, and outcomes. The search identified 11 publications on risk factors that met the inclusion criteria, and no publication on UD treatment met all of the criteria. Relaxing the inclusion criteria for reporting of risk factors and treatment outcomes to include both wild-type C57BL/6 mice and genetically engineered mice on a B6 background yielded 12 publications on risk factors and 3 publications on treatment. Dietary factors, particularly caloric restriction, appear to influence UD risk. Female sex was inconsistently associated with a higher risk of UD, which most often occurred in 13- to 24-mo-old mice in the studies that were reviewed. Only 1 of the 3 publications that evaluated UD treatments included an untreated group or alternative therapy control. Further research is needed to explore epidemiologic aspects of UD and to compare treatment options.

  14. Systematic Literature Review of Risk Factors and Treatments for Ulcerative Dermatitis in C57BL/6 Mice

    PubMed Central

    Sargent, Jennifer L; Koewler, Nathan J; Diggs, Helen E

    2015-01-01

    Ulcerative dermatitis (UD) in C57BL/6 mice is poorly understood and challenging to treat. We sought to evaluate the evidence regarding commonly cited risk factors for UD and reported UD treatments. The terms ‘ulcerative dermatitis’ and ‘C57BL/6’ were used to search 3 electronic databases. The resulting 347 articles were screened to identify publications that compared the risk of spontaneous UD in wild-type C57BL/6 mice according to sex, season, diet, or age and those that compared the degree of healing or rate of lesion resolution according to the intervention used. Articles were evaluated by using published criteria for assessing methodologic quality, including study design, number of animals per study group, case definition, method of diagnosis, randomization, enrollment criteria, exclusion criteria, and outcomes. The search identified 11 publications on risk factors that met the inclusion criteria, and no publication on UD treatment met all of the criteria. Relaxing the inclusion criteria for reporting of risk factors and treatment outcomes to include both wild-type C57BL/6 mice and genetically engineered mice on a B6 background yielded 12 publications on risk factors and 3 publications on treatment. Dietary factors, particularly caloric restriction, appear to influence UD risk. Female sex was inconsistently associated with a higher risk of UD, which most often occurred in 13- to 24-mo-old mice in the studies that were reviewed. Only 1 of the 3 publications that evaluated UD treatments included an untreated group or alternative therapy control. Further research is needed to explore epidemiologic aspects of UD and to compare treatment options. PMID:26678363

  15. An Efficient Chronic Unpredictable Stress Protocol to Induce Stress-Related Responses in C57BL/6 Mice

    PubMed Central

    Monteiro, Susana; Roque, Susana; de Sá-Calçada, Daniela; Sousa, Nuno; Correia-Neves, Margarida; Cerqueira, João José

    2015-01-01

    Exposure to chronic stress can have broad effects on health ranging from increased predisposition for neuropsychiatric disorders to deregulation of immune responses. The chronic unpredictable stress (CUS) protocol has been widely used to study the impact of stress exposure in several animal models and consists in the random, intermittent, and unpredictable exposure to a variety of stressors during several weeks. CUS has consistently been shown to induce behavioral and immunological alterations typical of the chronic stress-response. Unfortunately C57BL/6 mice, one of the most widely used mouse strains, due to the great variety of genetically modified lines, seem to be resistant to the commonly used 4-week-long CUS protocol. The definition of an alternative CUS protocol allowing the use of C57BL/6 mice in chronic stress experiments is a need. Here, we show that by extending the CUS protocol to 8 weeks is possible to induce a chronic stress-response in C57BL/6 mice, as revealed by abrogated body weight gain, increased adrenals weight, and an overactive hypothalamic–pituitary–adrenal axis with increased levels of serum corticosterone. Moreover, we also observed stress-associated behavioral alterations, including the potentiation of anxious-like and depressive-like behaviors and a reduction of exploratory behavior, as well as subtle stress-related changes in the cell population of the thymus and of the spleen. The present protocol for C57BL/6 mice consistently triggers the spectrum of CUS-induced changes observed in rats and, thus, will be highly useful to researchers that need to use this particular mouse strain as an animal model of neuropsychiatric disorders and/or immune deregulation related to CUS. PMID:25698978

  16. Hypocholesterolemic Properties and Prebiotic Effects of Mexican Ganoderma lucidum in C57BL/6 Mice.

    PubMed

    Meneses, María E; Martínez-Carrera, Daniel; Torres, Nimbe; Sánchez-Tapia, Mónica; Aguilar-López, Miriam; Morales, Porfirio; Sobal, Mercedes; Bernabé, Teodoro; Escudero, Helios; Granados-Portillo, Omar; Tovar, Armando R

    2016-01-01

    Edible and medicinal mushrooms contain bioactive compounds with promising effects on several cardiovascular risk biomarkers. However, strains of Ganoderma lucidum of Mexican origin have not yet been studied. Standardized extracts of G. lucidum (Gl) were given to C57BL/6 mice fed a high-cholesterol diet compared with the drug simvastatin. The effects of the extracts on serum biochemical parameters, liver lipid content, cholesterol metabolism, and the composition of gut microbiota were assessed. Acetylsalicylic acid (10 mM) added to the cultivation substrate modulated properties of Gl extracts obtained from mature basidiomata. Compared to the high-cholesterol diet group, the consumption of Gl extracts significantly reduced total serum cholesterol (by 19.2% to 27.1%), LDL-C (by 4.5% to 35.1%), triglyceride concentration (by 16.3% to 46.6%), hepatic cholesterol (by 28.7% to 52%) and hepatic triglycerides (by 43.8% to 56.6%). These effects were associated with a significant reduction in the expression of lipogenic genes (Hmgcr, Srebp1c, Fasn, and Acaca) and genes involved in reverse cholesterol transport (Abcg5 and Abcg8), as well as an increase in Ldlr gene expression in the liver. No significant changes were observed in the gene expression of Srebp2, Abca1 or Cyp7a1. In several cases, Gl-1 or Gl-2 extracts showed better effects on lipid metabolism than the drug simvastatin. A proposed mechanism of action for the reduction in cholesterol levels is mediated by α-glucans and β-glucans from Gl, which promoted decreased absorption of cholesterol in the gut, as well as greater excretion of fecal bile acids and cholesterol. The prebiotic effects of Gl-1 and Gl-2 extracts modulated the composition of gut microbiota and produced an increase in the Lactobacillaceae family and Lactobacillus genus level compared to the control group, high-cholesterol diet group and group supplemented with simvastatin. Mexican genetic resources of Gl represent a new source of bioactive compounds

  17. Hypocholesterolemic Properties and Prebiotic Effects of Mexican Ganoderma lucidum in C57BL/6 Mice

    PubMed Central

    Meneses, María E.; Martínez-Carrera, Daniel; Torres, Nimbe; Sánchez-Tapia, Mónica; Aguilar-López, Miriam; Morales, Porfirio; Sobal, Mercedes; Bernabé, Teodoro; Escudero, Helios; Granados-Portillo, Omar; Tovar, Armando R.

    2016-01-01

    Edible and medicinal mushrooms contain bioactive compounds with promising effects on several cardiovascular risk biomarkers. However, strains of Ganoderma lucidum of Mexican origin have not yet been studied. Standardized extracts of G. lucidum (Gl) were given to C57BL/6 mice fed a high-cholesterol diet compared with the drug simvastatin. The effects of the extracts on serum biochemical parameters, liver lipid content, cholesterol metabolism, and the composition of gut microbiota were assessed. Acetylsalicylic acid (10 mM) added to the cultivation substrate modulated properties of Gl extracts obtained from mature basidiomata. Compared to the high-cholesterol diet group, the consumption of Gl extracts significantly reduced total serum cholesterol (by 19.2% to 27.1%), LDL-C (by 4.5% to 35.1%), triglyceride concentration (by 16.3% to 46.6%), hepatic cholesterol (by 28.7% to 52%) and hepatic triglycerides (by 43.8% to 56.6%). These effects were associated with a significant reduction in the expression of lipogenic genes (Hmgcr, Srebp1c, Fasn, and Acaca) and genes involved in reverse cholesterol transport (Abcg5 and Abcg8), as well as an increase in Ldlr gene expression in the liver. No significant changes were observed in the gene expression of Srebp2, Abca1 or Cyp7a1. In several cases, Gl-1 or Gl-2 extracts showed better effects on lipid metabolism than the drug simvastatin. A proposed mechanism of action for the reduction in cholesterol levels is mediated by α-glucans and β-glucans from Gl, which promoted decreased absorption of cholesterol in the gut, as well as greater excretion of fecal bile acids and cholesterol. The prebiotic effects of Gl-1 and Gl-2 extracts modulated the composition of gut microbiota and produced an increase in the Lactobacillaceae family and Lactobacillus genus level compared to the control group, high-cholesterol diet group and group supplemented with simvastatin. Mexican genetic resources of Gl represent a new source of bioactive compounds

  18. Hypocholesterolemic Properties and Prebiotic Effects of Mexican Ganoderma lucidum in C57BL/6 Mice.

    PubMed

    Meneses, María E; Martínez-Carrera, Daniel; Torres, Nimbe; Sánchez-Tapia, Mónica; Aguilar-López, Miriam; Morales, Porfirio; Sobal, Mercedes; Bernabé, Teodoro; Escudero, Helios; Granados-Portillo, Omar; Tovar, Armando R

    2016-01-01

    Edible and medicinal mushrooms contain bioactive compounds with promising effects on several cardiovascular risk biomarkers. However, strains of Ganoderma lucidum of Mexican origin have not yet been studied. Standardized extracts of G. lucidum (Gl) were given to C57BL/6 mice fed a high-cholesterol diet compared with the drug simvastatin. The effects of the extracts on serum biochemical parameters, liver lipid content, cholesterol metabolism, and the composition of gut microbiota were assessed. Acetylsalicylic acid (10 mM) added to the cultivation substrate modulated properties of Gl extracts obtained from mature basidiomata. Compared to the high-cholesterol diet group, the consumption of Gl extracts significantly reduced total serum cholesterol (by 19.2% to 27.1%), LDL-C (by 4.5% to 35.1%), triglyceride concentration (by 16.3% to 46.6%), hepatic cholesterol (by 28.7% to 52%) and hepatic triglycerides (by 43.8% to 56.6%). These effects were associated with a significant reduction in the expression of lipogenic genes (Hmgcr, Srebp1c, Fasn, and Acaca) and genes involved in reverse cholesterol transport (Abcg5 and Abcg8), as well as an increase in Ldlr gene expression in the liver. No significant changes were observed in the gene expression of Srebp2, Abca1 or Cyp7a1. In several cases, Gl-1 or Gl-2 extracts showed better effects on lipid metabolism than the drug simvastatin. A proposed mechanism of action for the reduction in cholesterol levels is mediated by α-glucans and β-glucans from Gl, which promoted decreased absorption of cholesterol in the gut, as well as greater excretion of fecal bile acids and cholesterol. The prebiotic effects of Gl-1 and Gl-2 extracts modulated the composition of gut microbiota and produced an increase in the Lactobacillaceae family and Lactobacillus genus level compared to the control group, high-cholesterol diet group and group supplemented with simvastatin. Mexican genetic resources of Gl represent a new source of bioactive compounds

  19. Placental HSD2 Expression and Activity Is Unaffected by Maternal Protein Consumption or Gender in C57BL/6 Mice

    PubMed Central

    Garbrecht, Mark R.; Lamb, Fred S.

    2013-01-01

    The placenta acts as a physiological barrier, preventing the transfer of maternal glucocorticoids to the developing fetus. This is accomplished via the oxidation, and subsequent inactivation, of endogenous glucocorticoids by the 11-β hydroxysteroid dehydrogenase type 2 enzyme (HSD2). Maternal protein restriction during pregnancy has been shown to result in a decrease in placental HSD2 expression and fetal glucocorticoid overexposure, especially late in gestation, resulting in low birth weight and “fetal programming” of the offspring. This dietary intervention impairs fetal growth and cardiovascular function in adult C57BL/6 offspring, but the impact on placental HSD2 has not been defined. The goal of the current study was to examine the effects of a maternal low-protein diet (18% versus 9% protein) on placental HSD2 gene expression and enzyme activity in mice during late gestation. In contrast to previous studies in rats, a maternal low-protein diet did not affect HSD2 protein or enzyme activity levels in the placentas of C57BL/6 mice and this was irrespective of the gender of the offspring. These data suggest that the effects of maternal protein restriction on adult phenotypes in C57BL/6 mice depend upon a mechanism that may be independent of placental HSD2 or possibly occurs earlier in gestation. PMID:23781346

  20. Long-Term Artificial Sweetener Acesulfame Potassium Treatment Alters Neurometabolic Functions in C57BL/6J Mice

    PubMed Central

    Cong, Wei-na; Wang, Rui; Cai, Huan; Daimon, Caitlin M.; Scheibye-Knudsen, Morten; Bohr, Vilhelm A.; Turkin, Rebecca; Wood, William H.; Becker, Kevin G.; Moaddel, Ruin

    2013-01-01

    With the prevalence of obesity, artificial, non-nutritive sweeteners have been widely used as dietary supplements that provide sweet taste without excessive caloric load. In order to better understand the overall actions of artificial sweeteners, especially when they are chronically used, we investigated the peripheral and central nervous system effects of protracted exposure to a widely used artificial sweetener, acesulfame K (ACK). We found that extended ACK exposure (40 weeks) in normal C57BL/6J mice demonstrated a moderate and limited influence on metabolic homeostasis, including altering fasting insulin and leptin levels, pancreatic islet size and lipid levels, without affecting insulin sensitivity and bodyweight. Interestingly, impaired cognitive memory functions (evaluated by Morris Water Maze and Novel Objective Preference tests) were found in ACK-treated C57BL/6J mice, while no differences in motor function and anxiety levels were detected. The generation of an ACK-induced neurological phenotype was associated with metabolic dysregulation (glycolysis inhibition and functional ATP depletion) and neurosynaptic abnormalities (dysregulation of TrkB-mediated BDNF and Akt/Erk-mediated cell growth/survival pathway) in hippocampal neurons. Our data suggest that chronic use of ACK could affect cognitive functions, potentially via altering neuro-metabolic functions in male C57BL/6J mice. PMID:23950916

  1. Long-term artificial sweetener acesulfame potassium treatment alters neurometabolic functions in C57BL/6J mice.

    PubMed

    Cong, Wei-na; Wang, Rui; Cai, Huan; Daimon, Caitlin M; Scheibye-Knudsen, Morten; Bohr, Vilhelm A; Turkin, Rebecca; Wood, William H; Becker, Kevin G; Moaddel, Ruin; Maudsley, Stuart; Martin, Bronwen

    2013-01-01

    With the prevalence of obesity, artificial, non-nutritive sweeteners have been widely used as dietary supplements that provide sweet taste without excessive caloric load. In order to better understand the overall actions of artificial sweeteners, especially when they are chronically used, we investigated the peripheral and central nervous system effects of protracted exposure to a widely used artificial sweetener, acesulfame K (ACK). We found that extended ACK exposure (40 weeks) in normal C57BL/6J mice demonstrated a moderate and limited influence on metabolic homeostasis, including altering fasting insulin and leptin levels, pancreatic islet size and lipid levels, without affecting insulin sensitivity and bodyweight. Interestingly, impaired cognitive memory functions (evaluated by Morris Water Maze and Novel Objective Preference tests) were found in ACK-treated C57BL/6J mice, while no differences in motor function and anxiety levels were detected. The generation of an ACK-induced neurological phenotype was associated with metabolic dysregulation (glycolysis inhibition and functional ATP depletion) and neurosynaptic abnormalities (dysregulation of TrkB-mediated BDNF and Akt/Erk-mediated cell growth/survival pathway) in hippocampal neurons. Our data suggest that chronic use of ACK could affect cognitive functions, potentially via altering neuro-metabolic functions in male C57BL/6J mice. PMID:23950916

  2. Maternal Transfer of BDE-47 to Offspring and Neurobehavioral Development in C57BL/6J Mice

    PubMed Central

    Koenig, Claire M.; Lango, Jozsef; Pessah, Isaac N.; Berman, Robert F.

    2012-01-01

    Polybrominated diphenyl ethers (PBDEs) are flame retardants used worldwide in a variety of commercial goods, and are now widely found in both environmental and biological samples. BDE-47 is one of the most pervasive of these PBDE congeners and therefore is of particular concern. In this study C57BL/6J mice were exposed perinatally to 0.03, 0.1 or 1 mg/kg/day of BDE-47, a dose range chosen to encompass human exposure levels. Tissue levels of BDE-47 were measured in the blood, brain, fat and milk of dams and in whole fetal homogenate and blood and brain of pups on gestational day (GD) 15, and postnatal days (PND) 1, 10 and 21. From GD 15 to PND 1 levels of BDE-47 increased within dam tissue and then decreased from PND 1 to 21. Over the period of lactation levels in dam milk were comparatively high when compared to both brain and blood for all dose groups. Measurable levels of BDE-47 were found in the fetus on GD 15 confirming gestational exposure. From PND 1 to 21, levels of BDE-47 in pup tissue increased over the period of lactation due to the transfer of BDE-47 through milk. Behavioral tests of fine motor function and learning and memory were carried out between postnatal weeks 5–17 in order to evaluate the neurobehavioral toxicity of BDE-47. Behavioral deficits were only seen in the Barnes spatial maze where mice in the three exposure groups had longer latencies and traveled longer distances to find the escape hole when compared to vehicle control mice. These results support the conclusions that perinatal exposure to BDE-47 can have neurodevelopmental consequences, and that lactational exposure represents a significant exposure risk during development. PMID:23022914

  3. Molecular Profiles of Drinking Alcohol to Intoxication in C57BL/6J Mice

    PubMed Central

    Mulligan, Megan K.; Rhodes, Justin S.; Crabbe, John C.; Mayfield, R. Dayne; Harris, R. Adron; Ponomarev, Igor

    2011-01-01

    Background Alcohol addiction develops through a series of stages, and mechanistic studies are needed to understand the transition from initial drug use to sustained controlled alcohol consumption followed by abuse and physical dependence. The focus of this study was to examine the effects of voluntary alcohol consumption on brain gene expression profiles using a mouse model of binge drinking. The main goal was to identify alcohol-responsive genes and functional categories after a single episode of drinking to intoxication. Methods We used a modification of a “Drinking In the Dark” (DID) procedure (Rhodes et al., 2005) that allows mice to experience physiologically relevant amounts of alcohol in a non-stressful environment and also allows for detection of alcohol-sensitive molecular changes in a dose-dependent manner. C57BL/6J male mice were exposed to either 20% ethanol solution or water (single bottle) starting 3 hours after lights off for 4 hours and brains were harvested immediately after the drinking session. cDNA microarrays were used to assess the effects of voluntary drinking on global gene expression in 6 brain regions. We employed three statistical approaches to analyze microarray data. Results A commonly used approach that applies a strict statistical threshold identified the eight top statistically significant genes whose expression was significantly correlated with blood ethanol concentration (BEC) in one of the brain regions. We then used a systems network approach to examine brain region-specific transcriptomes and identify modules of co-expressed (correlated) genes. In each brain region, we identified alcohol-responsive modules, i.e., modules significantly enriched for genes whose expression was correlated with BEC. A functional overrepresentation analysis was then applied to examine the organizing principles of alcohol-responsive modules. Genes were clustered into modules according to their roles in different physiological processes, functional

  4. The effect of cage shelf on the behaviour of male C57BL/6 and BALB/c mice in the elevated plus maze test.

    PubMed

    Õkva, K; Nevalainen, T; Pokk, P

    2013-07-01

    The effect of environmental enrichment in the form of a cage shelf on the behaviour of male C57BL/6 and BALB/c mice was compared. Male C57BL/6 and BALB/c mice were randomly allocated into 12 cages per strain. The mice were kept in control conditions or exposed to a cage shelf for two, four, six or eight weeks, and thereafter assessed with the elevated plus maze. C57BL/6 mice displayed a trend of being less anxious than the BALB/c mice. A cage shelf increased the number of entries made into the open arms and the total number of entries only in the case of the C57BL/6 mice, but had no effect on the behaviour of the BALB/c mice. In conclusion, the effect of a cage shelf on the elevated plus maze behaviour of mice depends on the strain of the animals.

  5. Okra polysaccharide improves metabolic disorders in high-fat diet-induced obese C57BL/6 mice.

    PubMed

    Fan, Shengjie; Guo, Lu; Zhang, Yu; Sun, Qinhu; Yang, Baican; Huang, Cheng

    2013-11-01

    Okra is a tropical vegetable that is rich in polysaccharides. Here, we investigated the effects of okra polysaccharide (OP) on metabolic disorders in mice. We found that OP lowered body weight and glucose levels, improved glucose tolerance, and decreased serum total cholesterol levels in high-fat diet-fed C57BL/6 mice. OP regulated the gene expression of liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs) and their target genes in the liver and the adipose tissue of the mice. These results suggest that OP may have therapeutic effects on metabolic diseases via the inhibition of LXR and PPAR signaling.

  6. Okra polysaccharide improves metabolic disorders in high-fat diet-induced obese C57BL/6 mice.

    PubMed

    Fan, Shengjie; Guo, Lu; Zhang, Yu; Sun, Qinhu; Yang, Baican; Huang, Cheng

    2013-11-01

    Okra is a tropical vegetable that is rich in polysaccharides. Here, we investigated the effects of okra polysaccharide (OP) on metabolic disorders in mice. We found that OP lowered body weight and glucose levels, improved glucose tolerance, and decreased serum total cholesterol levels in high-fat diet-fed C57BL/6 mice. OP regulated the gene expression of liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs) and their target genes in the liver and the adipose tissue of the mice. These results suggest that OP may have therapeutic effects on metabolic diseases via the inhibition of LXR and PPAR signaling. PMID:23894043

  7. Functional Characteristics of the Gut Microbiome in C57BL/6 Mice Differentially Susceptible to Plasmodium yoelii

    PubMed Central

    Stough, Joshua M. A.; Dearth, Stephen P.; Denny, Joshua E.; LeCleir, Gary R.; Schmidt, Nathan W.; Campagna, Shawn R.; Wilhelm, Steven W.

    2016-01-01

    C57BL/6 mice are widely used for in vivo studies of immune function and metabolism in mammals. In a previous study, it was observed that when C57BL/6 mice purchased from different vendors were infected with Plasmodium yoelii, a causative agent of murine malaria, they exhibited both differential immune responses and significantly different parasite burdens: these patterns were reproducible when gut contents were transplanted into gnotobiotic mice. To gain insight into the mechanism of resistance, we removed whole ceca from mice purchased from two vendors, Taconic Biosciences (low parasitemia) and Charles River Laboratories (high parasitemia), to determine the combined host and microflora metabolome and metatranscriptome. With the exception of two Charles River samples, we observed ≥90% similarity in overall bacterial gene expression within vendors and ≤80% similarity between vendors. In total 33 bacterial genes were differentially expressed in Charles River mice (p-value < 0.05) relative to the mice purchased from Taconic. Included among these, fliC, ureABC, and six members of the nuo gene family were overrepresented in microbiomes susceptible to more severe malaria. Moreover, 38 mouse genes were differentially expressed in these purported genetically identical mice. Differentially expressed genes included basigin, a cell surface receptor required for P. falciparum invasion of red blood cells. Differences in metabolite pools were detected, though their relevance to malaria infection, microbial community activity, or host response is not yet understood. Our data have provided new targets that may connect gut microbial activity to malaria resistance and susceptibility phenotypes in the C57BL/6 model organism. PMID:27729904

  8. C57BL/KsJ-db/db-ApcMin/+ Mice Exhibit an Increased Incidence of Intestinal Neoplasms

    PubMed Central

    Hata, Kazuya; Kubota, Masaya; Shimizu, Masahito; Moriwaki, Hisataka; Kuno, Toshiya; Tanaka, Takuji; Hara, Akira; Hirose, Yoshinobu

    2011-01-01

    The numbers of obese people and diabetic patients are ever increasing. Obesity and diabetes are high-risk conditions for chronic diseases, including certain types of cancer, such as colorectal cancer (CRC). The aim of this study was to develop a novel animal model in order to clarify the pathobiology of CRC development in obese and diabetic patients. We developed an animal model of obesity and colorectal cancer by breeding the C57BL/KsJ-db/db (db/db) mouse, an animal model of obesity and type II diabetes, and the C57BL/6J-ApcMin/+ (Min/+) mouse, a model of familial adenomatous polyposis. At 15 weeks of age, the N9 backcross generation of C57BL/KsJ-db/db-ApcMin/+ (db/db-Min/+) mice developed an increased incidence and multiplicity of adenomas in the intestinal tract when compared to the db/m-Min/+ and m/m-Min/+ mice. Blood biochemical profile showed significant increases in insulin (8.3-fold to 11.7-fold), cholesterol (1.2-fold to 1.7-fold), and triglyceride (1.2-fold to 1.3-fold) in the db/db-Min/+ mice, when compared to those of the db/m-Min/+ and m/m-Min/+ mice. Increases (1.4-fold to 2.6-fold) in RNA levels of insulin-like growth factor (IGF)-1, IRF-1R, and IGF-2 were also observed in the db/db- Min/+ mice. These results suggested that the IGFs, as well as hyperlipidemia and hyperinsulinemia, promoted adenoma formation in the db/db-Min/+ mice. Our results thus suggested that the db/db-Min/+ mice should be invaluable for studies on the pathogenesis of CRC in obese and diabetes patients and the therapy and prevention of CRC in these patients. PMID:22174655

  9. A deficiency in the B cell response of C57BL/6 mice correlates with loss of macrophage-mediated killing of Leishmania amazonensis

    PubMed Central

    Gibson-Corley, Katherine N.; Boggiatto, Paola M.; Mukbel, Rami M.; Petersen, Christine A.; Jones, Douglas E.

    2010-01-01

    Infection of C3HeB/FeJ and C57BL/6 mice with Leishmania major stimulates a healing cell-mediated immune response, while Leishmania amazonensis infection leads to chronic disease. Here we show C3HeB/FeJ mice co-infected with both species of Leishmania heal, while co-infected C57BL/6 mice do not. Using an in vitro killing assay we determined B cells from infected C57BL/6 mice are ineffective in promoting parasite killing compared with B cells from infected C3HeB/FeJ mice. Furthermore, infected C57BL/6 mice produce less antigen-specific antibodies compared with infected C3HeB/FeJ mice. These findings suggest B cells play a required role in the cell-mediated immune response against L. amazonensis. PMID:20004204

  10. Antioxidative Activity of Blueberry Leaf Extract Prevents High-fat Diet-induced Obesity in C57BL/6 Mice

    PubMed Central

    Lee, In-Chul; Kim, Dae Yong; Choi, Bu Young

    2014-01-01

    Background: Health beneficial effects of blueberry have been well documented. Obesity is health hazard that is associated with metabolic abnormalities. We investigated the effect of blueberry leaf extract (BBLE) on high-fat diet (HFD)-induced obesity in C57BL/6J mice. Methods: C57BL/6 mice were fed HFD with or without BBLE for 10 weeks. Body weight, serum parameter, and adipose tissues morphology were assessed. The expression of mRNA associated with adipogenesis was measured using real-time polymerase chain reaction (RT-PCR) analysis. Results: Administration of BBLE to mice challenged with HFD significantly decreased the body weight gain, the levels of plasma triglyceride (TG) and liver lipid peroxidation, and reduced the adipocyte size and improved hepatic status compared with the group treated with HFD only. BBLE treatment significantly improved glucose control compared with the HFD group. Moreover, BBLE showed an inhibitory effect on adipocyte differentiation in obese mice together with significant decrease in the lipid accumulation by downregulating gene expression of adipocyte-specific transcription factors, such as peroxisome proliferation-activity receptor and acetyl coenzyme A carboxylase and upregulating the mRNA expression of adiponectin, which are critical for adipogenesis. Conclusion: BBLE suppressed the body weight gain in the HFD-fed C57BL/6 mice. Intake of BBLE reduced body weight in HFD-fed mice by 20%. Furthermore, BBLE supplementation significantly decreased the TG level in the liver and inhibited leptin secretion. BBLE supplementation also improved insulin resistance. Therefore, BBLE is a possible agent to prevent obesity. PMID:25337590

  11. Comparative hemostatic parameters in BALB/c, C57BL/6 and C3H/He mice.

    PubMed

    Barrios, Mariana; Rodríguez-Acosta, Alexis; Gil, Amparo; Salazar, Ana M; Taylor, Peter; Sánchez, Elda E; Arocha-Piñango, Carmen L; Guerrero, Belsy

    2009-07-01

    This study describes micro-methods to determine biological parameters in plasma of three strains of mice. Platelet count was significantly different among strains. C57BL/6 mice showed the highest values (988 x 10(3)/microL) and BALB/c the lowest (782 x 10(3)/microL). Fibrinogen levels were 2.55 (C57BL/6), 2.37 (BALB/c) and 2.28 g/L (C3H/He). Some inter-strain differences were observed in factor XIII (94, 118 and 114%) and plasminogen levels (142, 80 and 135%) in C57BL/6, BALB/c and C3H/He, respectively. Additionally, we observed individual mice factor XIII and plasminogen levels between 80 to 200% and 65 to 180%, respectively, in relation to pooled human plasma; and between 70 to 185% and 70 to 155%, respectively, against pooled mice plasma. To our knowledge, this is first report in the literature in diverse mice strains regarding hemostasis, mainly on factor XIII, plasminogen levels, and a very simple test that allows measurement of endogenous fibrinolytic activity present in the plasma. The different results are discussed in relationship with existing literature regarding if the animals in some studies were maintained under strict pathogen-free conditions, the collection of blood was from the heart or eye and if the analysis method was tested by counting manually or automatically. This work could contribute useful knowledge to the field of investigations regarding hemostatic disorders using mouse models, especially for laboratories that are not well equipped. PMID:19101712

  12. Comparative hemostatic parameters in BALB/c, C57BL/6 and C3H/He mice.

    PubMed

    Barrios, Mariana; Rodríguez-Acosta, Alexis; Gil, Amparo; Salazar, Ana M; Taylor, Peter; Sánchez, Elda E; Arocha-Piñango, Carmen L; Guerrero, Belsy

    2009-07-01

    This study describes micro-methods to determine biological parameters in plasma of three strains of mice. Platelet count was significantly different among strains. C57BL/6 mice showed the highest values (988 x 10(3)/microL) and BALB/c the lowest (782 x 10(3)/microL). Fibrinogen levels were 2.55 (C57BL/6), 2.37 (BALB/c) and 2.28 g/L (C3H/He). Some inter-strain differences were observed in factor XIII (94, 118 and 114%) and plasminogen levels (142, 80 and 135%) in C57BL/6, BALB/c and C3H/He, respectively. Additionally, we observed individual mice factor XIII and plasminogen levels between 80 to 200% and 65 to 180%, respectively, in relation to pooled human plasma; and between 70 to 185% and 70 to 155%, respectively, against pooled mice plasma. To our knowledge, this is first report in the literature in diverse mice strains regarding hemostasis, mainly on factor XIII, plasminogen levels, and a very simple test that allows measurement of endogenous fibrinolytic activity present in the plasma. The different results are discussed in relationship with existing literature regarding if the animals in some studies were maintained under strict pathogen-free conditions, the collection of blood was from the heart or eye and if the analysis method was tested by counting manually or automatically. This work could contribute useful knowledge to the field of investigations regarding hemostatic disorders using mouse models, especially for laboratories that are not well equipped.

  13. Heterogeneity among white adipose tissue depots in male C57BL/6J mice.

    PubMed

    Sackmann-Sala, Lucila; Berryman, Darlene E; Munn, Rachel D; Lubbers, Ellen R; Kopchick, John J

    2012-01-01

    The widespread prevalence of obesity has lead to extensive research on white adipose tissue (WAT), which frequently uses the C57BL/6J mouse strain as a model. In many studies, results obtained in one WAT depot are often extrapolated to all WAT. However, functional differences among WAT depots are now becoming apparent. Thus, to identify the molecular mechanisms responsible for WAT depot-specific differences under "normal" conditions, four C57BL/6J mouse WAT depots (inguinal, mesenteric, epididymal, and retroperitoneal) were analyzed. Depot proteomic profiles, along with weights, protein contents, adipocyte sizes and oxidative stress were determined. Mesenteric WAT had almost twice the protein content of the other depots analyzed. Mean adipocyte size was highest in epididymal and lowest in mesenteric and inguinal depots. The proteome of inguinal WAT displayed low levels of enzymes involved in ATP generation, glucose and lipid metabolism, and antioxidant proteins. Higher levels of these proteins were observed in mesenteric and epididymal WAT, with variable levels in the retroperitoneal depot. Some of these proteins showed depot-specific correlations with plasma levels of insulin, leptin, and adiponectin. In agreement with the proteomic data, levels of the antioxidant protein heat shock protein β1 (HSPβ1) also were lower in inguinal WAT when analyzed by western blotting and immunohistochemistry. Also, lipid peroxidation products showed similar trends. Our results are consistent with lower triglyceride turnover and lower oxidative stress in inguinal than mesenteric and epididymal WAT. The observed WAT depot-specific differences provide clues as to the mechanisms leading to these depots' respective diverse functions. PMID:21779095

  14. Evaluating the dose effects of a longitudinal micro-CT study on pulmonary tissue in C57BL/6 mice

    NASA Astrophysics Data System (ADS)

    Detombe, Sarah A.; Dunmore-Buyze, Joy; Petrov, Ivailo E.; Drangova, Maria

    2012-03-01

    Background: Micro-computed tomography offers numerous advantages for small animal imaging, including the ability to monitor the same animals throughout a longitudinal study. However, concerns are often raised regarding the effects of x-ray dose accumulated over the course of the experiment. In this study, we scan C57BL/6 mice multiple times per week for six weeks, to determine the effect of the cumulative dose on pulmonary tissue at the end of the study. Methods/Results: C57BL/6 male mice were split into two groups (irradiated group=10, control group=10). The irradiated group was scanned (80kVp/50mA) each week for 6 weeks; the weekly scan session had three scans. This resulted in a weekly dose of 0.84 Gy, and a total study dose of 5.04 Gy. The control group was scanned on the final week. Scans from weeks 1 and 6 were reconstructed and analyzed: overall, there was no significant difference in lung volume or lung density between the control group and the irradiated group. Similarly, there were no significant differences between the week 1 and week 6 scans in the irradiated group. Histological samples taken from excised lung tissue also showed no evidence of inflammation or fibrosis in the irradiated group. Conclusion: This study demonstrates that a 5 Gy x-ray dose accumulated over six weeks during a longitudinal micro-CT study has no significant effects on the pulmonary tissue of C57BL/6 mice. As a result, the many advantages of micro- CT imaging, including rapid acquisition of high-resolution, isotropic images in free-breathing mice, can be taken advantage of in longitudinal studies without concern for negative dose-related effects.

  15. Effects of phenazepam on the behavior of C57BL/6 and BALB/c mice in the open field test after naloxone pretreatment.

    PubMed

    Seredenin, S B; Nadorova, A V; Kolik, L G; Yarkova, M A

    2013-07-01

    We studied the effects of phenazepam (0.075 mg/kg) after pretreatment (5 minutes before) with naloxone (10 mg/kg) on open-field behavior of C57Bl/6 and BALB/c mice. In ex vivo experiments, we studied the effects of naloxone (1 and 10 mg/kg) on receptor binding of [(3)H]-flunitrazepam by membranes of brain fraction (P1+P2) of C57Bl/6 and BALB/c mice. It was shown that naloxone increased motor activity in the open field in BALB/c mice and decreased this parameter in C57Bl/6 mice. During combined treatment, naloxone potentiated the activating effects of phenazepam on the open-field behavior of BALB/c mice and slightly increased the sedative effect of this drug in C57Bl/6 mice. Naloxone stimulated reception of [(3)H]-flunitrazepam in BALB/c mice and slightly increased radioligand binding in C57Bl/6 mice. These data attest to enhanced reception in benzodiazepine site of GABAA-receptor under conditions of opioid receptor blockade, the presence of anxiolytic or sedative (depending on the phenotype of the response to emotional stress) effect of naloxone, and co-directed effects of naloxone and benzodiazepine tranquilizer on open-field behavior of C57Bl/6 and BALB/c mice.

  16. Novel pathogenic epitopes of myelin oligodendrocyte glycoprotein induce experimental autoimmune encephalomyelitis in C57BL/6 mice.

    PubMed

    Delarasse, Cecile; Smith, Paul; Baker, David; Amor, Sandra

    2013-12-01

    Myelin oligodendrocyte glycoprotein (MOG), a minor protein of the central nervous system myelin, is recognized as a potential target in multiple sclerosis and neuromyelitis optica. The extracellular domain of MOG is commonly used in a wide range of mouse strains and other animals to induce experimental autoimmune encephalomyelitis (EAE), an autoimmune animal model of multiple sclerosis, because it is a target for antibody-mediated attack. Previous studies, using selected peptides, have indicated that MOG(35-55) peptide is an encephalitogenic epitope in C57BL/6 (H-2(b)) mice. A more systematic analysis of both T-cell and B-cell responses following immunization of C57BL/6 mice with either recombinant extracellular mouse MOG protein (1-116) or with overlapping peptides spanning the whole sequence of MOG, before assessment of responses to 15 mer and 23 mer peptides was undertaken. The studies identified T-cell responses within the MOG(35-55) (extracellular domain) but also two new immunogenic and encephalitogenic T-cell epitopes within residues MOG(113-127), MOG(120-134) (localized in the transmembrane region) and MOG(183-197) (in the second hydrophobic MOG domain). In addition, residue MOG(113-127) was found to be a B-cell epitope, suggesting that this may be a useful adjunct for the induction of EAE as well as for immunological studies in C57BL/6 mice, which are increasingly being used to study immune function through the use of transgenic and gene knockout technology.

  17. Mushroom lectin enhanced immunogenicity of HBV DNA vaccine in C57BL/6 and HBsAg-transgenic mice.

    PubMed

    Gao, Wenjuan; Sun, Yuhan; Chen, Shiwen; Zhang, Jingyao; Kang, Jingjing; Wang, Yongqiang; Wang, Hexiang; Xia, Guoliang; Liu, Qinghong; Kang, Youmin

    2013-04-26

    DNA vaccination is a promising strategy for activating immune responses against hepatitis B virus (HBV) infection. However, the accumulated data have shown that DNA vaccination alone generates weak immune responses. To enhance the immunogenicity of HBV DNA vaccine, lectin purified from pleurotus ostreatus (POL) was used as adjuvant of HBV DNA vaccine for C57BL/6 and HBV surface antigen transgenic (HBVsAg-Tg) mice. Our data demonstrate that low dose of POL (1 μg/mouse) in conjunction with HBV DNA vaccine stimulated stronger HBV-specific delayed-type hypersensitivity (DTH) responses and higher HBV-specific IgG level than that in high dose of POL groups (5 μg/mouse and 10 μg/mouse). POL activated strong Th2 and Tc1 cell responses in immunized C57BL/6 and HBVsAg-Tg mice. POL as adjuvant of HBV DNA vaccine effectively enhanced HBV surface protein antibody (HBVsAb) and decreased HBVsAg level for HBV Tg mice treatment. Furthermore, POL infiltrated more lymphocytes excluding Th1, Th2 and Tc1 cell subtypes to liver of HBVsAg-Tg mice. Together, these results suggest that POL as adjuvant enhanced immunogenicity of HBV DNA vaccination and effectively stimulated immune reaponse for HBsAg-Tg mice treatment. Our findings implicate the potential of mushroom lectin as adjuvant of HBV DNA vaccine.

  18. A diet rich in OMEGA-6 polyunsaturated fat and sucrose reproduces key features of metabolic syndrome in C57BL/6 mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To determine whether a diet enriched in v-6 fatty acids and sucrose will reproduce features of metabolic syndrome in C57BL/6 mice. 4- to 7-week-old male C57BL/6 mice were randomized to chow (13% kcal fat, lard and corn oil) or high fat/high sucrose (HF/HS) diet (48% kcal fat, corn oil) for a period ...

  19. Tert-butylhydroquinone reduces lipid accumulation in C57BL/6 mice with lower body weight gain.

    PubMed

    Nam, Kung-Woo; Kim, Yong Hyun; Kwon, Hyun Jung; Rhee, Sang-Ki; Kim, Wan-Jong; Han, Man-Deuk

    2013-07-01

    tert-Butylhydroquinone (tBHQ) is a commonly used antioxidant additive that is approved for human use by both the Food and Agriculture Organization and the World Health Organization (FAO/WHO). In this study, we examined the effect of tBHQ on body weight gain and found that food supplementation with 0.001 % (w/w) tBHQ inhibited 61.4 % (P < 0.01) of body weight gain in high-fat diet (HFD)-induced C57BL/6 mice, and the oral administration of tBHQ (1.5 mg/kg) reduced 47.5 % (P < 0.05) of body weight gain in normal diet fed db/db mice. The HFD increased lipid deposit in adipocytes, but these were reduced significantly by tBHQ treatment in C57BL/6 mice. tBHQ supplementation significantly lowered the plasma triglyceride and total cholesterol, with reduced size of accumulated fat mass. The rate limiting enzyme of beta-oxidation (ACOX1) was significantly over-expressed in the liver with tBHQ treatment. These results indicate that tBHQ suppresses body weight gain in mice, possibly at least related to the up-regulation of ACOX1 gene expression.

  20. Xanthohumol improves dysfunctional glucose and lipid metabolism in diet-induced obese C57BL/6J mice.

    PubMed

    Miranda, Cristobal L; Elias, Valerie D; Hay, Joshua J; Choi, Jaewoo; Reed, Ralph L; Stevens, Jan F

    2016-06-01

    Xanthohumol (XN) is a prenylated flavonoid found in hops (Humulus lupulus) and beer. The dose-dependent effects of XN on glucose and lipid metabolism in a preclinical model of metabolic syndrome were the focus of our study. Forty-eight male C57BL/6J mice, 9 weeks of age, were randomly divided into three XN dose groups of 16 animals. The mice were fed a high-fat diet (60% kcal as fat) supplemented with XN at dose levels of 0, 30, or 60 mg/kg body weight/day, for 12 weeks. Dietary XN caused a dose-dependent decrease in body weight gain. Plasma levels of glucose, total triglycerides, total cholesterol, and MCP-1 were significantly decreased in mice on the 60 mg/kg/day treatment regimen. Treatment with XN at 60 mg/kg/day resulted in reduced plasma LDL-cholesterol (LDL-C), IL-6, insulin and leptin levels by 80%, 78%, 42%, and 41%, respectively, compared to the vehicle control group. Proprotein Convertase Subtilisin Kexin 9 (PCSK-9) levels were 44% lower in the 60 mg/kg dose group compared to the vehicle control group (p ≤ 0.05) which may account for the LDL-C lowering activity of XN. Our results show that oral administration of XN improves markers of systemic inflammation and metabolic syndrome in diet-induced obese C57BL/6J mice. PMID:26976708

  1. High-fat feeding rapidly induces obesity and lipid derangements in C57BL/6N mice.

    PubMed

    Podrini, Christine; Cambridge, Emma L; Lelliott, Christopher J; Carragher, Damian M; Estabel, Jeanne; Gerdin, Anna-Karin; Karp, Natasha A; Scudamore, Cheryl L; Ramirez-Solis, Ramiro; White, Jacqueline K

    2013-06-01

    C57BL/6N (B6N) is becoming the standard background for genetic manipulation of the mouse genome. The B6N, whose genome is very closely related to the reference C57BL/6J genome, is versatile in a wide range of phenotyping and experimental settings and large repositories of B6N ES cells have been developed. Here, we present a series of studies showing the baseline characteristics of B6N fed a high-fat diet (HFD) for up to 12 weeks. We show that HFD-fed B6N mice show increased weight gain, fat mass, and hypercholesterolemia compared to control diet-fed mice. In addition, HFD-fed B6N mice display a rapid onset of lipid accumulation in the liver with both macro- and microvacuolation, which became more severe with increasing duration of HFD. Our results suggest that the B6N mouse strain is a versatile background for studying diet-induced metabolic syndrome and may also represent a model for early nonalcoholic fatty liver disease.

  2. P7C3 Attenuates the Scopolamine-Induced Memory Impairments in C57BL/6J Mice.

    PubMed

    Jiang, Bo; Song, Lu; Huang, Chao; Zhang, Wei

    2016-05-01

    Memory impairment is the most common symptom in patients with Alzheimer's disease. The purpose of this study is to evaluate the memory enhancing effects of P7C3, a recently identified compound with robust proneurogenic and neuroprotective effects, on the cognitive impairment induced by scopolamine, a muscarinic acetylcholine receptor antagonist. Different behavior tests including the Y-maze, Morris water maze, and passive avoidance tests were performed to measure cognitive functions. Scopolamine significantly decreased the spontaneous alternation and step-through latency of C57BL/6J mice in Y-maze test and passive avoidance test, whereas increased the time of mice spent to find the hidden platform in Morris water maze test. Importantly, intraperitoneal administration of P7C3 effectively reversed those Scopolamine-induced cognitive impairments in C57BL/6J mice. Furthermore, P7C3 treatment significantly enhanced the level of brain-derived neurotrophic factor (BDNF) signaling pathway in the cortex and hippocampus, and the usage of selective BDNF signaling inhibitor fully blocked the anti-amnesic effects of P7C3. Therefore, these findings suggest that P7C3 could improve the scopolamine-induced learning and memory impairment possibly through activation of BDNF signaling pathway, thereby exhibiting a cognition-enhancing potential.

  3. 1,3-Dichloro-2-propanol induced hyperlipidemia in C57BL/6J mice via AMPK signaling pathway.

    PubMed

    Lu, Jing; Huang, Guoren; Hu, Sizhuo; Wang, Zhenning; Guan, Shuang

    2014-02-01

    1,3-Dichloro-2-propanol (1,3-DCP) is a well-known contaminant that has been detected in a wide range of foods. Dietary intake represents the greatest source of exposure to 1,3-DCP. In the study, we first found 1,3-DCP could induce hyperlipidemia in C57BL/6J mice below 1 mg/kg/day. We investigated serum lipid profile, liver total cholesterol (TC) and triglyceride (TG), histopathology of Liver and adipose tissue. The results showed 1,3-DCP dose dependently increased serum TG, TC and low-density lipoprotein cholesterol (LDL-C), decreased serum high-density lipoprotein cholesterol (HDL-C), increased relative liver weight, liver TG and TC, relative adipose tissue weight and enlarged the size of adipose cells. Because AMPK signal pathway is important in the process of lipid metabolism, we further investigated the effects of 1,3-DCP on AMPK signaling pathway in murine models. The results showed that 1,3-DCP (0.1-1 mg/kg/day) decreased p-AMPK/tAMPK ratio, p-ACC/tACC ratio, PPARα expression, but increased FAT, SREBP1, HMGCR and FAS expression. These observations indicated that 1,3-DCP induced hyperlipidemia in C57BL/6J mice at least partially through regulating AMPK signaling pathway. PMID:24333398

  4. Knockout of the TauT Gene Predisposes C57BL/6 Mice to Streptozotocin-Induced Diabetic Nephropathy

    PubMed Central

    Han, Xiaobin; Patters, Andrea B.; Ito, Takashi; Schaffer, Stephen W.; Chesney, Russell W.

    2015-01-01

    Diabetic nephropathy is the leading cause of end stage renal disease in the world. Although tremendous efforts have been made, scientists have yet to identify an ideal animal model that can reproduce the characteristics of human diabetic nephropathy. In this study, we hypothesize that taurine insufficiency is a critical risk factor for development of diabetic nephropathy associated with diabetes mellitus. This hypothesis was tested in vivo in TauT heterozygous (TauT+/-) and homozygous (TauT-/-) knockout in C57BL/6 background mice. We have shown that alteration of the TauT gene (also known as SLC6A6) has a substantial effect on the susceptibility to development of extensive diabetic kidney disease in both TauT+/- and TauT-/-mouse models of diabetes. These animals developed histological changes characteristic of human diabetic nephropathy that included glomerulosclerosis, nodular lesions, arteriosclerosis, arteriolar dilation, and tubulointerstitial fibrosis. Immunohistochemical staining of molecular markers of smooth muscle actin, CD34, Ki67 and collagen IV further confirmed these observations. Our results demonstrated that both homozygous and heterozygous TauT gene deletion predispose C57BL/6 mice to develop end-stage diabetic kidney disease, which closely replicates the pathological features of diabetic nephropathy in human diabetic patients. PMID:25629817

  5. Dermal exposure to tannery effluent causes neurobehavioral changes in C57Bl/6J and Swiss mice.

    PubMed

    da Silva, Wellington Alves Mizael; Mendes, Bruna de Oliveira; Guimarães, Abraão Tiago Batista; Rabelo, Letícia Martins; Ferreira, Raíssa de Oliveira; E Silva, Bianca Costa; de Souza, Joyce Moreira; de Menezes, Ivandilson Pessoa Pinto; Rodrigues, Aline Sueli de Lima; Malafaia, Guilherme

    2016-10-01

    Tannery effluents constitute highly polluting residues, which can cause negative impacts to people's health and the environment. However, studies that have investigated the effects of the exposure to these xenobiotics on the central nervous system of mammal experimental models are rare, the few that have been published focusing on the exposure via oral intake (ingestion of water containing tannery effluent concentrations). In this sense, and with the objective of expanding the knowledge beyond the neurotoxic effects observed when water contaminated by these xenobiotics is ingested, the neurobehavioral effects of dermal exposure of male C57Bl/6J and Swiss mice were analyzed. The animals were exposed to raw (wet blue-type) tannery effluent for two hours during five days, totalizing 15 days of exposure. Afterwards, the animals underwent the elevated plus-maze (predictive of anxiety) and the object recognition tests (identification of memory deficit). Our data show that the dermal exposure to the tannery effluent caused an anxiogenic behavior in these animals, when compared those that did not have direct contact with these xenobiotics. It was also observed that the animals exposed to the tannery effluent obtained lower novel object recognition indices, thus evidencing memory deficit and indicating a possible influence of the tannery effluent constituents in animal cognition. The present study attests the hypothesis that dermal exposure to tannery effluents containing neurotoxic substances causes behavioral disorders in C57Bl/6J and Swiss mice. PMID:27380225

  6. Hyperhomocysteinemia induced by methionine supplementation does not independently cause atherosclerosis in C57BL/6J mice

    PubMed Central

    Zhou, Ji; Werstuck, Geoff H.; Lhoták, Šárka; Shi, Yuan Y.; Tedesco, Vivienne; Trigatti, Bernardo; Dickhout, Jeffrey; Majors, Alana K.; DiBello, Patricia M.; Jacobsen, Donald W.; Austin, Richard C.

    2010-01-01

    A causal relationship between diet-induced hyperhomocysteinemia (HHcy) and accelerated atherosclerosis has been established in apolipoprotein E-deficient (apoE−/−) mice. However, it is not known whether the proatherogenic effect of HHcy in apoE−/− mice is independent of hyperlipidemia and/or deficiency of apoE. In this study, a comprehensive dietary approach using C57BL/6J mice was used to investigate whether HHcy is an independent risk factor for accelerated atherosclerosis or dependent on additional dietary factors that increase plasma lipids and/or inflammation. C57BL/6J mice at 4 wk of age were divided into 6 dietary groups: chow diet (C), chow diet + methionine (C+M), western-type diet (W), western-type diet + methionine (W+M), atherogenic diet (A), or atherogenic diet + methionine (A+M). After 2, 10, 20, or 40 wk on the diets, mice were sacrificed, and the levels of total plasma homocysteine, cysteine, and glutathione, as well as total plasma cholesterol and triglycerides were analyzed. Aortic root sections were examined for atherosclerotic lesions. HHcy was induced in all groups supplemented with methionine, compared to diet-matched control groups. Plasma total cholesterol was significantly increased in mice fed the W or A diet. However, the W diet increased LDL/IDL and HDL levels, while the A diet significantly elevated plasma VLDL and LDL/IDL levels without increasing HDL. No differences in plasma total cholesterol levels or lipid profiles were observed between methionine-supplemented groups and the diet-matched control groups. Early atherosclerotic lesions containing macrophage foam cells were only observed in mice fed the A or A + M diet. Furthermore, lesion size was significantly larger in the A + M group compared to the A group at 10 and 20 wk; however, mature lesions were never observed even after 40 wk on these diets. The presence of lymphocytes, increased hyaluronan staining, and the expression of endoplasmic reticulum (ER) stress markers

  7. Effects of Lipopolysaccharide on the response of C57BL/6J mice to whole thorax irradiation

    PubMed Central

    Zaidi, Asif; Jelveh, Salomeh; Mahmood, Javed; Hill, Richard P

    2013-01-01

    Background and Purpose Inflammatory and fibrogenic processes play a crucial role in the radiation-induced injury in the lung. The aim of the present study was to examine whether additive LPS exposure in the lung (to simulate respiratory infection) would affect pneumonitis or fibrosis associated with lung irradiation. Material and Methods Wildtype C57Bl/6J (WT-C57) and TNFα, TNFR1 and TNFR2 knockout (−/−) mice, in C57Bl/6J background, were given whole thorax irradiation (10Gy) with or without post-irradiation intratracheal administration of LPS (50μg/mice). Functional deficit was examined by measuring breathing rate at various times after treatment. Real-time Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and immunohistochemistry were used to analyse the protein expression and m-RNA of Interleukin-1 alpha (IL-1α), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumour Necrosis Factor alpha (TNFα) and Transforming Growth Factor beta (TGFβ) in the lung at various times after treatment. Inflammatory cells were detected by Mac-3 (macrophages) and Toluidine Blue (mast cells) staining. Collagen content was estimated by hydroxyproline (total collagen) and Sircol assay (soluble collagen). Levels of oxidative damage were assessed by 8-hydroxy-2-deoxyguanosine (8-OHdG) staining. Results LPS exposure significantly attenuated the breathing rate increases following irradiation of WT-C57, TNFR1−/− and TNFR2−/− mice and to a lesser extent in TNFα−/− mice. Collagen content was significantly reduced after LPS treatment in WT-C57, TNFR1−/− and TNFα−/− mice and there was a trend in TNFR2−/− mice. Similarly there were lower levels of inflammatory cells and cytokines in the LPS treated mice. Conclusions This study reveals a mitigating effect of early exposure to LPS on injury caused by irradiation on lungs of C57Bl mice. The results suggest that immediate infection post irradiation may not impact lung response negatively in radiation

  8. Alterations of pancreatic islet structure, metabolism and gene expression in diet-induced obese C57BL/6J mice.

    PubMed

    Roat, Regan; Rao, Vandana; Doliba, Nicolai M; Matschinsky, Franz M; Tobias, John W; Garcia, Eden; Ahima, Rexford S; Imai, Yumi

    2014-01-01

    The reduction of functional β cell mass is a key feature of type 2 diabetes. Here, we studied metabolic functions and islet gene expression profiles of C57BL/6J mice with naturally occurring nicotinamide nucleotide transhydrogenase (NNT) deletion mutation, a widely used model of diet-induced obesity and diabetes. On high fat diet (HF), the mice developed obesity and hyperinsulinemia, while blood glucose levels were only mildly elevated indicating a substantial capacity to compensate for insulin resistance. The basal serum insulin levels were elevated in HF mice, but insulin secretion in response to glucose load was significantly blunted. Hyperinsulinemia in HF fed mice was associated with an increase in islet mass and size along with higher BrdU incorporation to β cells. The temporal profiles of glucose-stimulated insulin secretion (GSIS) of isolated islets were comparable in HF and normal chow fed mice. Islets isolated from HF fed mice had elevated basal oxygen consumption per islet but failed to increase oxygen consumption further in response to glucose or carbonyl cyanide-4-trifluoromethoxyphenylhydrazone (FCCP). To obtain an unbiased assessment of metabolic pathways in islets, we performed microarray analysis comparing gene expression in islets from HF to normal chow-fed mice. A few genes, for example, those genes involved in the protection against oxidative stress (hypoxia upregulated protein 1) and Pgc1α were up-regulated in HF islets. In contrast, several genes in extracellular matrix and other pathways were suppressed in HF islets. These results indicate that islets from C57BL/6J mice with NNT deletion mutation develop structural, metabolic and gene expression features consistent with compensation and decompensation in response to HF diet. PMID:24505268

  9. Social defeat stress induces a depression-like phenotype in adolescent male c57BL/6 mice.

    PubMed

    Iñiguez, Sergio D; Riggs, Lace M; Nieto, Steven J; Dayrit, Genesis; Zamora, Norma N; Shawhan, Kristi L; Cruz, Bryan; Warren, Brandon L

    2014-05-01

    Abstract Exposure to stress is highly correlated with the emergence of mood-related illnesses. Because major depressive disorder often emerges in adolescence, we assessed the effects of social defeat stress on responses to depressive-like behaviors in juvenile mice. To do this, postnatal day (PD) 35 male c57BL/6 mice were exposed to 10 days of social defeat stress (PD35-44), while control mice were handled daily. Twenty-four hours after the last episode of defeat (PD45), separate groups of mice were tested in the social interaction, forced swimming, sucrose preference, and elevated plus-maze behavioral assays (n = 7-12 per group). Also, we examined body weight gain across days of social defeat and levels of blood serum corticosterone 40 min after the last episode of defeat stress. Our data indicates that defeated mice exhibited a depressive-like phenotype as inferred from increased social avoidance, increased immobility in the forced swim test, and reduced sucrose preference (a measure of anhedonia), when compared to non-defeated controls. Defeated mice also displayed an anxiogenic-like phenotype when tested on the elevated plus-maze. Lastly, stressed mice displayed lower body weight gain, along with increased blood serum corticosterone levels, when compared to non-stressed controls. Overall, we show that in adolescent male c57BL/6 mice, social defeat stress induces a depression- and anxiety-like phenotype 24 h after the last episode of stress. These data suggest that the social defeat paradigm may be used to examine the etiology of stress-induced mood-related disorders during adolescence.

  10. Brain Monoamines and Antidepressant-like Responses in MRL/MpJ Versus C57BL/6J Mice

    PubMed Central

    Balu, Darrick T.; Turner, Jill R.; Brookshire, Bethany R.; Hill-Smith, Tiffany E.; Blendy, Julie A.; Lucki, Irwin

    2013-01-01

    The MRL/MpJ mouse demonstrates enhanced wound healing and tissue regeneration and increased neurotrophic mobilization to chronic antidepressant drug treatments. This study compared brain monoamine systems between MRL/MpJ and C57BL/6J mice as a potential basis for strain differences after chronic antidepressant treatment. MRL/MpJ mice had significantly higher tissue levels of serotonin and dopamine in multiple brain regions. Microdialysis studies demonstrated that baseline levels of extracellular serotonin did not differ between strains. However, acute administration of the selective serotonin reuptake inhibitor citalopram produced an increase in extracellular serotonin in the ventral hippocampus of MRL/MpJ mice that was twice as large as achieved in C57BL/6J mice. The greater effects in MRL/MpJ mice on 5-HT levels were not maintained after local perfusion of citalopram, suggesting that mechanisms outside of the hippocampus were responsible for the greater effect of citalopram after systemic injection. The density of serotonin and norepinephrine transporters in the hippocampus was significantly higher in MRL/MpJ mice. In addition, the expression of 5-HT1A mRNA was lower in the hippocampus, 5-HT1B mRNA was higher in the hippocampus and brain stem and SERT mRNA was higher in the brain stem of MRL/MpJ mice. The exaggerated neurotransmitter release in MRL/MpJ mice was accompanied by reduced baseline immobility in the tail suspension test and a greater reduction of immobility produced by citalopram or the tricyclic antidepressant desipramine. These data suggest that differences in the response to acute and chronic antidepressant treatments between the two strains could be attributed to differences in serotonin or catecholamine transmission. PMID:23220293

  11. Rapid learning of magnetic compass direction by C57BL/6 mice in a 4-armed 'plus' water maze.

    PubMed

    Phillips, John B; Youmans, Paul W; Muheim, Rachel; Sloan, Kelly A; Landler, Lukas; Painter, Michael S; Anderson, Christopher R

    2013-01-01

    Magnetoreception has been demonstrated in all five vertebrate classes. In rodents, nest building experiments have shown the use of magnetic cues by two families of molerats, Siberian hamsters and C57BL/6 mice. However, assays widely used to study rodent spatial cognition (e.g. water maze, radial arm maze) have failed to provide evidence for the use of magnetic cues. Here we show that C57BL/6 mice can learn the magnetic direction of a submerged platform in a 4-armed (plus) water maze. Naïve mice were given two brief training trials. In each trial, a mouse was confined to one arm of the maze with the submerged platform at the outer end in a predetermined alignment relative to magnetic north. Between trials, the training arm and magnetic field were rotated by 180(°) so that the mouse had to swim in the same magnetic direction to reach the submerged platform. The directional preference of each mouse was tested once in one of four magnetic field alignments by releasing it at the center of the maze with access to all four arms. Equal numbers of responses were obtained from mice tested in the four symmetrical magnetic field alignments. Findings show that two training trials are sufficient for mice to learn the magnetic direction of the submerged platform in a plus water maze. The success of these experiments may be explained by: (1) absence of alternative directional cues (2), rotation of magnetic field alignment, and (3) electromagnetic shielding to minimize radio frequency interference that has been shown to interfere with magnetic compass orientation of birds. These findings confirm that mice have a well-developed magnetic compass, and give further impetus to the question of whether epigeic rodents (e.g., mice and rats) have a photoreceptor-based magnetic compass similar to that found in amphibians and migratory birds.

  12. Rapid learning of magnetic compass direction by C57BL/6 mice in a 4-armed 'plus' water maze.

    PubMed

    Phillips, John B; Youmans, Paul W; Muheim, Rachel; Sloan, Kelly A; Landler, Lukas; Painter, Michael S; Anderson, Christopher R

    2013-01-01

    Magnetoreception has been demonstrated in all five vertebrate classes. In rodents, nest building experiments have shown the use of magnetic cues by two families of molerats, Siberian hamsters and C57BL/6 mice. However, assays widely used to study rodent spatial cognition (e.g. water maze, radial arm maze) have failed to provide evidence for the use of magnetic cues. Here we show that C57BL/6 mice can learn the magnetic direction of a submerged platform in a 4-armed (plus) water maze. Naïve mice were given two brief training trials. In each trial, a mouse was confined to one arm of the maze with the submerged platform at the outer end in a predetermined alignment relative to magnetic north. Between trials, the training arm and magnetic field were rotated by 180(°) so that the mouse had to swim in the same magnetic direction to reach the submerged platform. The directional preference of each mouse was tested once in one of four magnetic field alignments by releasing it at the center of the maze with access to all four arms. Equal numbers of responses were obtained from mice tested in the four symmetrical magnetic field alignments. Findings show that two training trials are sufficient for mice to learn the magnetic direction of the submerged platform in a plus water maze. The success of these experiments may be explained by: (1) absence of alternative directional cues (2), rotation of magnetic field alignment, and (3) electromagnetic shielding to minimize radio frequency interference that has been shown to interfere with magnetic compass orientation of birds. These findings confirm that mice have a well-developed magnetic compass, and give further impetus to the question of whether epigeic rodents (e.g., mice and rats) have a photoreceptor-based magnetic compass similar to that found in amphibians and migratory birds. PMID:24023673

  13. Parkinsonian rotenone mouse model: reevaluation of long-term administration of rotenone in C57BL/6 mice.

    PubMed

    Inden, Masatoshi; Kitamura, Yoshihisa; Abe, Mari; Tamaki, Aya; Takata, Kazuyuki; Taniguchi, Takashi

    2011-01-01

    Chronic systemic exposure of Lewis rats to rotenone produced many features of Parkinson's disease (PD), including nigrostriatal dopamine (DA) neurodegeneration and the formation of cytoplasmic inclusions in nigral DA neurons. We also reported that chronic oral administration of rotenone at 30 mg/kg for 28 d caused specific nigrostriatal DA neurodegeneration in C57BL/6 mice. To establish a PD model more suitable for evaluating nigrostriatal DA neurodegeneration, the present study has been designed to assess the neurotoxicity of rotenone after daily oral administration at 30 or 100 mg/kg for 56 d in C57BL/6 mice. The survival rate of rotenone-treated mice at 30 mg/kg did not change from 28 to 56 d, although the survival rate of rotenone-treated mice at 30 mg/kg was decreased to about 70% within one week. The survival rate of the rotenone-treated mice at 100 mg/kg was suddenly decreased after 28 d, and finally to about 15% at 56 d. Rotenone at 30 mg/kg, but not 100 mg/kg, for 28 d caused a significant loss of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra. Rotenone at 100 mg/kg caused a highly variable loss of TH-positive neurons among individual mice. Rotenone at 30 mg/kg for 56 d caused a significant loss of TH-positive neurons and behavioral impairment. In addition, α-synuclein immunoreactivity was increased in surviving TH-positive neurons in a time-dependent manner. Thus, this protocol for chronic administration of rotenone at 30 mg/kg for 56 d is more useful for understanding the mechanism of DA neurodegeneration.

  14. Effect of N-Methyl-N-Nitrosourea on Helicobacter-induced Gastric Carcinogenesis in C57BL/6 Mice

    PubMed Central

    Lee, Ju Yup; Kim, Nayoung; Choi, Yoon Jeong; Nam, Ryoung Hee; Choi, Yoon Jin; Lee, Seonmin; Choi, Daeun; Lee, Hye Seung; Kim, Jin-Wook; Lee, Dong Ho

    2016-01-01

    Background The aim of this study was to investigate the effect of N-methyl-N-nitrosourea (MNU) treatment followed by chronic Helicobacter pylori SS1 and H. felis colonization on the stomachs of C57BL/6 mice. The role of MNU and Helicobacter species in gastric carcinogenesis was also elucidated. Methods A total of 69 C57BL/6 mice at 4 weeks of age were divided into 6 groups according to MNU treatment and H. pylori SS1 or H. felis infection. The mice were sacrificed at 21 and 50 weeks. The degree of inflammation was determined by histopathology. The levels of gastric mucosal myeloperoxidase, TNF-α, and interleukin-1β (IL-1β) were measured by ELISA. Results In the H. felis groups with or without MNU, the incidence of gastric tumors was 21.1% and 35.0% at 21 and 50 weeks, respectively. No gastric tumors were observed in all control mice. At 50 weeks, 37.5% of gastric adenoma cases were observed in the H. felis alone and MNU + H. felis groups. Furthermore, 12.5% of gastric adenocarcinoma cases were observed in the MNU alone and MNU + H. felis groups. The gastric mucosal IL-1β level was significantly higher in the MNU + H. felis group at 21 weeks and H. felis group at 50 weeks, respectively, than that for control mice (P < 0.05). However, the effect of MNU on H. pylori SS1-induced gastric carcinogenesis was low compared to that on H. felis. Conclusions Administration of MNU before H. felis infection provokes severe inflammation through IL-1β, and eventually induces gastric cancer. However, the role of MNU in H. pylori SS1-induced gastric carcinogenesis model is minor. PMID:27722144

  15. Proteomics analysis of liver tissues from C57BL/6J mice receiving low-dose 137Cs radiation.

    PubMed

    Yi, Lan; Li, Linwei; Yin, Jie; Hu, Nan; Li, Guangyue; Ding, Dexin

    2016-02-01

    Differentially expressed proteins in liver tissues of C57BL/6J mice receiving low-dose (137)Cs radiation were examined by proteomics analysis. Compared with the control group, 80 proteins were differentially expressed in the irradiated group. Among the 40 randomly selected proteins used for peptide mass fingerprinting analysis and bioinformatics, 24 were meaningful. These proteins were related to antioxidant defense, amino acid metabolism, detoxification, anti-tumor development, amino acid transport, anti-peroxidation, and composition of respiratory chain. Western blot analysis showed that catalase (CAT), glycine N-methyltransferase (GNMT), and glutathione S-transferase P1 (GSTP1) were up-regulated in the irradiated group; these results were in agreement with qPCR results. These results show that CAT, GNMT, and GSTP1 may be related to stress response induced by low-dose irradiation in mice liver. The underlying mechanism however requires further investigation. PMID:26429139

  16. Proteomics analysis of liver tissues from C57BL/6J mice receiving low-dose 137Cs radiation.

    PubMed

    Yi, Lan; Li, Linwei; Yin, Jie; Hu, Nan; Li, Guangyue; Ding, Dexin

    2016-02-01

    Differentially expressed proteins in liver tissues of C57BL/6J mice receiving low-dose (137)Cs radiation were examined by proteomics analysis. Compared with the control group, 80 proteins were differentially expressed in the irradiated group. Among the 40 randomly selected proteins used for peptide mass fingerprinting analysis and bioinformatics, 24 were meaningful. These proteins were related to antioxidant defense, amino acid metabolism, detoxification, anti-tumor development, amino acid transport, anti-peroxidation, and composition of respiratory chain. Western blot analysis showed that catalase (CAT), glycine N-methyltransferase (GNMT), and glutathione S-transferase P1 (GSTP1) were up-regulated in the irradiated group; these results were in agreement with qPCR results. These results show that CAT, GNMT, and GSTP1 may be related to stress response induced by low-dose irradiation in mice liver. The underlying mechanism however requires further investigation.

  17. Development of a Chronic Kidney Disease Model in C57BL/6 Mice with Relevance to Human Pathology

    PubMed Central

    Huang, Linghong; Scarpellini, Alessandra; Funck, Muriel; Verderio, Elisabetta A.M.; Johnson, Timothy S.

    2013-01-01

    Background Genetically modified mice are used to investigate disease and assess potential interventions. However, research into kidney fibrosis is hampered by a lack of models of chronic kidney disease (CKD) in mice. Recently, aristolochic acid nephropathy (AAN), characterised by severe tubulointerstitial fibrosis, has been identified as a cause of end stage kidney disease and proposed as a model of CKD. Published studies have used various dosing regimens, species and strains, with variable outcomes. Therefore, we aimed to develop a standardised protocol to develop tubulointerstitial fibrosis using pure aristolochic acid I (AAI) in C57BL/6 mice. Methods AAI dose optimisation was performed by intraperitoneal injection of AAI at varying dose, frequency and duration. Kidney function was assessed by serum creatinine. Fibrosis was quantified by hydroxyproline levels and Masson's Trichrome staining. Specific collagens were measured by immunofluorescent staining. Results Single doses of AAI of >10 mg/kg caused acute kidney failure and death. Lower doses of 2.5 mg/kg needed to be administrated more than weekly to cause significant fibrosis. 3 mg/kg once every 3 days for 6 weeks followed by a disease development time of 6 weeks after AAI led to reduced kidney weight and function. Substantial tubulointerstitial fibrosis occurred, with males more severely affected. Increased deposition of collagen I, III and IV contributed to fibrosis, with collagen III and IV higher in males. Conclusions AAN can be induced in C57BL/6 mice. The regimen of 3 mg/kg every 3 days for 6 weeks followed by 6 weeks of disease development time gives substantial tubulointerstitial fibrosis with lesions similar to those in humans. PMID:23610565

  18. Meroxest improves the prognosis of immunocompetent C57BL/6 mice with allografts of E0771 mouse breast tumor cells

    PubMed Central

    Carrasco, Esther; Garrido, Jose Manuel; Álvarez, Pablo Juan; Álvarez-Manzaneda, Enrique; Chahboun, Rachid; Messouri, Ibtissam; Melguizo, Consolación; Aránega, Antonia

    2016-01-01

    Introduction Recently, we have reported the antitumor properties of a new family of synthetic merosesquiterpenes, among which meroxest is highlighted, since it has high activity and specificity for ER+ breast cancer cells. In this paper, we characterize allografts of ER+ E0771 mouse breast tumor cells in immunocompetent C57BL/6 mice, and also analyze the effect of meroxest on the prognosis of the disease. Material and methods Twenty female C57BL/6 mice were injected with 106 E0771 cells. Once the tumors reached the appropriate size, the mice were divided into two groups, one control and another treated orally with 15 mg/kg of meroxest. After 20 days, tumor samples were taken for histopathological study and for determination of the expression of the prognostic markers Ki67 and vascular endothelial growth factor (VEGF) by immunofluorescence. Results In sections stained with hematoxylin-eosin, we observed that tumors have a well-defined capsule enclosing E0771 tumor cells. The central area of tumors contains necrotic regions with leukocyte infiltration. Meroxest treatment significantly reduces tumor size (68%, p < 0.05), induces changes in its structure, decreases the degree of leukocyte infiltration, and significantly reduces the expression of Ki67 (33%, p < 0.05) and VEGF (82%, p < 0.05). Conclusions Meroxest improves the prognosis of mice since it reduces leukocyte infiltration, and decreases the expression of Ki67 and VEGF markers. Consequently, the merosesquiterpene could become a useful antiangiogenic drug in the treatment of breast cancer. These results encourage us to deepen the study of meroxest, in order to find more evidence that supports the convenience of its evaluation in a clinical study or trial. PMID:27695480

  19. High frequency of transmission of murine AIDS virus in C57BL/10 mice via mother's milk.

    PubMed Central

    Okada, Y; Suzuki, K; Komuro, K; Mizuochi, T

    1992-01-01

    Maternal transmission of a murine leukemia virus (MuLV) mixture named LP-BM5 MuLV, which is knwon to induce murine AIDS (MAIDS), was investigated. Adult female C57BL/10 mice were inoculated intraperitoneally with LP-BM5 MuLV. When the virus-inoculated female mice developed splenomegaly or lymphadenopathy, they were mated with normal C57BL/10 male mice. Of 56 offspring born to MAIDS mothers, 14 appeared to develop MAIDS, as assessed by the occurrence of splenomegaly or lymphadenopathy as well as the mitogen response of spleen cells. The occurrence of MAIDS in offspring was found to be accompanied by the maternal transmission and expansion of a defective virus genome from which almost the entire pol and env regions are deleted. On the other hand, the ecotropic helper virus genome was detected in all offspring regardless of the occurrence of MAIDS. To examine the mode of maternal transmission of LP-BM5 MuLV, foster-nursing experiments were conducted. The ecotropic helper viruses were found in all normal offspring nursed by a MAIDS mother, and some of them developed MAIDS. In contrast, none of offspring born to a MAIDS mother that were nursed by an uninfected foster mother either carried the LP-BM5 MuLV or developed MAIDS. Finally, both the defective and the ecotropic helper viruses were detected in LP-BM5 MuLV-infected mother's milk. These results indicated that maternal transmission of LP-BM5 MuLV occurs with a high frequency and is mediated by mother's milk. Images PMID:1323688

  20. Dietary diallyl disulfide supplementation attenuates ethanol-mediated pulmonary vitamin D speciate depletion in C57Bl/6 mice

    PubMed Central

    McCaskill, Michael L.; Hottor, Henry T.; Sapkota, Muna; Wyatt, Todd A.

    2016-01-01

    Background Slightly more than 5 % of the United States population heavily consumes ethanol, i.e., more than 14 drinks for men and 7 drinks for women a week. Chronic ethanol consumption can result in increased liver disease, reduced recovery from burn injury, and more frequent and severe respiratory infections. Chronic ethanol over-consumption also leads to vitamin D dysmetabolism and depletion. Vitamin D is a fat-soluble pro-hormone that regulates musculoskeletal health, cellular proliferation/differentiation, and innate and adaptive immune response. Methods In this study, C57BL/6 mice were fed 20 % ethanol in their water ad libitum for 7 weeks. Some mice were fed either a standard chow or a modified diet containing 0.15 μg/day of diallyl disulfide (DADS). Whole blood, lung tissue, and bronchial alveolar lavage fluid (BALF) were collected at sacrifice and analyzed for 25(OH) D3, 1,25 (OH)2D3, vitamin D receptor VDR, CYP2E1, and CYP27B1 levels. Results Ethanol reduced 25(OH) D3 and 1,25 (OH)2D3 in lung tissue and BALF on average 31 %. The largest ethanol-mediated reduction was in the 1,25 (OH)2D3 (42 %) measured in the BALF. Dietary supplementation of DADS restored BALF and lung tissue protein of 25(OH) D3 and 1,25(OH)2D3 to control levels. Chronic ethanol consumption also resulted in tissue increases of vitamin D response (VDR) protein, Cyp2E1, and reductions in vitamin D-activating enzyme CYP27B1. All three of these effects were attenuated by dietary supplementation of DADS. Conclusions In conclusion, the pulmonary metabolic disturbances mediated by chronic ethanol consumption as measured by 1,25(OH)2D3 protein levels, epithelial lining fluid, and lung tissue can be ameliorated by dietary supplementation of DADS in C57BL/6 mice. PMID:27536382

  1. Physiological, Behavioral, and Histological Responses of Male C57BL/6N Mice to Different CO2 Chamber Replacement Rates.

    PubMed

    Boivin, Gregory P; Bottomley, Michael A; Dudley, Emily S; Schiml, Patricia A; Wyatt, Christopher N; Grobe, Nadja

    2016-01-01

    Rodent euthanasia with CO2 by using gradual displacement of 10% to 30% of the chamber volume per minute is considered acceptable by the AVMA Panel on Euthanasia. However, whether a 50% to 100% chamber replacement rate (CRR) of CO2 is more painful or distressful than 10% to 30% CRR is unclear. Therefore, we examined physiological and behavioral parameters, corticosterone and ACTH levels, and lung histology of mice euthanized at CRR of 15%, 30%, 50%, or 100%. Adult male C57BL/6N mice were euthanized at different CO2 CRR as physiological parameters were recorded telemetrically. Video recordings were reviewed to determine when the mouse first became ataxic, when it was fully recumbent (characterized by the mouse's nose resting on the cage floor), and when breathing stopped. Overall, CO2 euthanasia increased cardiovascular parameters and activity. Specific significant differences that were associated with 50% to 100% compared with 15% to 30% CO2 CRR included an increase in systolic blood pressure per second from initiation of CO2 until ataxia, a decrease in total diastolic blood pressure until ataxia, and a decrease in total heart rate until ataxia, immobility, and death. All physiological responses occurred more rapidly with higher CRR. Activity levels, behavioral responses, plasma adrenocorticotropic hormone and corticosterone levels, and lung pathology were not different between groups. We found no physiological, behavioral, or histologic evidence that 15% or 30% CO2 CRR is less painful or distressful than is 50% or 100% CO2 CRR. We conclude that 50% to 100% CO2 CRR is acceptable for euthanizing adult male C57BL/6N mice. PMID:27423153

  2. Patterns of thymocyte differentiation markers on virus and radiation induced lymphomas of C57-BL/Ka mice

    SciTech Connect

    Scott, M.L.; Feinberg, M.B.; Fry, K.E.; Percy, D.E.; Lieberman, M.

    1985-01-01

    To better understand the biology of tumorigenesis in virus and radiation lymphomas of C57Bl/Ka mice, the authors examined the cell surface phenotypes of a large series of primary tumors induced by both agents. Data derived using flow cytometry and recently available monoclonal antibodies to thymocyte differentiation antigens supports three major conclusions. First, tumor cell populations are unimodal for staining with most antibodies and are probably of clonal origin. Second, many, but not all, tumor cells show surface phenotypes similar to those of previously defined subpopulations of normal thymocytes. Third, at the cell surface level, no major differences between virus- and radiation-induced lymphomas can be discerned. Our data thus further define the relationship between thymomas induced by these two agents.

  3. Brief and long periods of maternal separation affect maternal behavior and offspring behavioral development in C57BL/6 mice.

    PubMed

    Bailoo, Jeremy D; Jordan, Richard L; Garza, Xavier J; Tyler, Amber N

    2014-05-01

    For rats, maternal mediation of brief and longer term dam-pup separations were thought to account for pup differences in adult "emotionality." In this study, early handling (EH), maternal separation (MS), and maternal peer separation (MPS) groups were compared to an animal facility reared (AFR) group for maternal behavior and offspring adult open-field behavior in C57BL/6 mice. Although MS and MPS dams displayed higher levels of maternal behavior upon reunion, these group differences did not predict offspring open-field behavior. However, when offspring behavior was analyzed as a function of specific aspects of maternal behavior, irrespective of treatment group, pups that received high levels of quiescent nursing and activity, but not licking, were less "emotional." Individual differences in maternal licking of pups predicted variability of "emotional" behavior for AFR and EH pups. Thus, for this strain of mouse, individual and not treatment differences in maternal care predict offspring "emotional" development.

  4. A behavioural comparison of acute and chronic Delta9-tetrahydrocannabinol and cannabidiol in C57BL/6JArc mice.

    PubMed

    Long, Leonora E; Chesworth, Rose; Huang, Xu-Feng; McGregor, Iain S; Arnold, Jonathon C; Karl, Tim

    2010-08-01

    Cannabis contains over 70 unique compounds and its abuse is linked to an increased risk of developing schizophrenia. The behavioural profiles of the psychotropic cannabis constituent Delta9-tetrahydrocannabinol (Delta9-THC) and the non-psychotomimetic constituent cannabidiol (CBD) were investigated with a battery of behavioural tests relevant to anxiety and positive, negative and cognitive symptoms of schizophrenia. Male adult C57BL/6JArc mice were given 21 daily intraperitoneal injections of vehicle, Delta9-THC (0.3, 1, 3 or 10 mg/kg) or CBD (1, 5, 10 or 50 mg/kg). Delta9-THC produced the classic cannabinoid CB1 receptor-mediated tetrad of hypolocomotion, analgesia, catalepsy and hypothermia while CBD had modest hyperthermic effects. While sedative at this dose, Delta9-THC (10 mg/kg) produced locomotor-independent anxiogenic effects in the open-field and light-dark tests. Chronic CBD produced moderate anxiolytic-like effects in the open-field test at 50 mg/kg and in the light-dark test at a low dose (1 mg/kg). Acute and chronic Delta9-THC (10 mg/kg) decreased the startle response while CBD had no effect. Prepulse inhibition was increased by acute treatment with Delta9-THC (0.3, 3 and 10 mg/kg) or CBD (1, 5 and 50 mg/kg) and by chronic CBD (1 mg/kg). Chronic CBD (50 mg/kg) attenuated dexamphetamine (5 mg/kg)-induced hyperlocomotion, suggesting an antipsychotic-like action for this cannabinoid. Chronic Delta9-THC decreased locomotor activity before and after dexamphetamine administration suggesting functional antagonism of the locomotor stimulant effect. These data provide the first evidence of anxiolytic- and antipsychotic-like effects of chronic but not acute CBD in C57BL/6JArc mice, extending findings from acute studies in other inbred mouse strains and rats.

  5. Mephedrone (4-methylmethcathinone) and intracranial self-stimulation in C57BL/6J mice: comparison to cocaine.

    PubMed

    Robinson, J Elliott; Agoglia, Abigail E; Fish, Eric W; Krouse, Michael C; Malanga, C J

    2012-09-01

    The recreational use of cathinone-derived synthetic stimulants, also known as "bath salts", has increased during the last five years. A commonly abused drug in this class is mephedrone (4-methylmethcathinone or "meow-meow"), which alters mood and produces euphoria in humans. Intracranial self-stimulation (ICSS) measures the behavioral effects of neuroactive compounds on brain reward circuitry. We used ICSS to investigate the ability of mephedrone and cocaine to alter responding for electrical stimulation of the medial forebrain bundle in C57BL/6J mice. Adult male C57BL/6J mice (n=6) implanted with unipolar stimulating electrodes at the level of the lateral hypothalamus responded for varying frequencies of brain stimulation reward (BSR). The frequency that supported half maximal responding (EF50), the BSR threshold (θ(0)), and the maximum response rate were determined before and after intraperitoneal administration of saline, mephedrone (1.0, 3.0, or 10.0 mg/kg), or cocaine (1.0, 3.0, or 10.0 mg/kg). Mephedrone dose-dependently decreased EF50 (max. effect=72.3% of baseline), θ(0) (max. effect=59.6% of baseline), and the maximum response rate (max. effect=67.0% of baseline) beginning 15 min after administration. Beginning immediately after administration, cocaine dose-dependently lowered EF50 (max. effect=66.4% of baseline) and θ(0) (max. effect=60.1% of baseline) but did not affect maximum response rate. These results suggest that mephedrone, like cocaine, potentiates BSR, which may indicate its potential for abuse. Given the public health concern of stimulant abuse, future studies will be necessary to determine the cellular and behavioral effects of acute and chronic mephedrone use.

  6. Prepulse inhibition predicts working memory performance whilst startle habituation predicts spatial reference memory retention in C57BL/6 mice.

    PubMed

    Singer, Philipp; Hauser, Jonas; Llano Lopez, Luis; Peleg-Raibstein, Daria; Feldon, Joram; Gargiulo, Pascual A; Yee, Benjamin K

    2013-04-01

    Prepulse inhibition (PPI) of the acoustic startle reflex refers to the attenuation of the startle response to an intense pulse stimulus when it is shortly preceded by a weak non-startling prepulse stimulus. It is a well-established high-throughput translational measure of pre-attentive sensory gating, and its impairment is detected in several neuropsychiatric diseases including schizophrenia. It has been hypothesized that PPI might be associated with, or predictive of, cognitive deficiency in such diseases, and therefore provide an efficient assay for screening drugs with potential pro-cognitive efficacy. Free from any predetermined disease model, the present study evaluated in a homogeneous cohort of inbred C57BL/6 mice the presence of a statistical link between PPI expression and cognitive performance. Performance indices in a spatial reference memory test and a working memory test conducted in the Morris water maze, and contextual fear conditioning were correlated against pre-existing baseline PPI expression. A specific correlative link between working memory and PPI induced by weak (but not strong) prepulse was revealed. In addition, a correlation between habituation of the startle reflex and reference memory was identified for the first time: a stronger overt habituation effect was associated with superior spatial search accuracy. The PPI paradigm thus provides two independent predictors of dissociable cognitive traits in normal C57BL/6 mice; and they might serve as potential markers for high-throughput evaluation of potential cognitive enhancers, especially in the context of schizophrenia where deficits in startle habituation and PPI co-exist.

  7. Efficacy of acetylsalicylic acid (aspirin) in skin B16-F0 melanoma tumor-bearing C57BL/6 mice.

    PubMed

    Vad, Nikhil M; Kudugunti, Shashi K; Wang, Hezhen; Bhat, G Jayarama; Moridani, Majid Y

    2014-05-01

    Several epidemiological studies show that aspirin can act as a chemopreventive agent and decrease the incidences of various cancers including melanoma. In this work, we investigated the in vitro and in vivo efficacy of acetylsalicylic acid (ASA) as an antimelanoma agent in B16-F0 cells and skin B16-F0 melanoma tumor mouse model. Our findings indicate that the IC50 (48 h) for ASA in B16-F0 melanoma cells was 100 μM and that ASA caused a dose- and time-dependent GSH depletion and increase in reactive oxygen species (ROS) formation in B16-F0 melanoma cells. Male C57BL/6 mice were inoculated s.c. with 1 × 10(6) B16-F0 melanoma cells. ASA (80, 100, and 150 mg/kg) was initiated on day 1 or day 7, or day 9 after cell inoculation and continued daily for 13, 7, and 5 days, respectively. Animals were weighed daily and sacrificed on day 13. The tumors were excised and weighed. The animals receiving 13 days of ASA therapy at 80, 100, and 150 mg/kg demonstrated tumor growth inhibition by 1 ± 12%, 19 ± 22%, and 50 ± 29%, respectively. Animals receiving 7 days of therapy at 80, 100, and 150 mg/kg demonstrated tumor growth inhibition by 12 ± 14%, 27 ± 14%, and 40 ± 14%, respectively. No significant tumor growth inhibition was observed with 5 days of therapy. ASA at 100 and 150 mg/kg caused significant tumor growth inhibition in C57BL/6 mice when administered for 13 and 7 days, respectively. The results obtained in this study are consistent with the recent epidemiologically based report that aspirin is associated with lower melanoma risk in humans.

  8. Individual difference in prepulse inhibition does not predict spatial learning and memory performance in C57BL/6 mice.

    PubMed

    Peleg-Raibstein, Daria; Philipp, Singer; Feldon, Joram; Yee, Benjamin K

    2015-12-01

    The startle reflex to an intense acoustic pulse stimulus is attenuated if the pulse stimulus is shortly preceded by a weak non-startling prepulse stimulus. This attenuation of the startle reflex represents a form of pre-attentional sensory gating known as prepulse inhibition (PPI). Although PPI does not require learning, its expression is regulated by higher cognitive processes. PPI deficits have been detected in several psychiatric conditions including schizophrenia where they co-exist with cognitive deficits. A potential link between PPI expression and cognitive performance has therefore been suggested such that poor PPI may predict, or may be mechanistically linked to, overt cognitive impairments. A positive relationship between PPI and strategy formation, planning efficiency, and execution speed has been observed in healthy humans. However, parallel studies in healthy animals are rare. It thus remains unclear what cognitive domains may be associated with, or orthogonal to, sensory gating in the form of PPI in healthy animals. The present study evaluated a potential link between the magnitude of PPI and spatial memory performance by comparing two subgroups of animals differing substantially in baseline PPI expression (low-PPI vs high-PPI) within a homogenous cohort of 100 male adult C57BL/6 mice. Assessment of spatial reference memory in the Morris water maze and spatial recognition memory in the Y-maze failed to reveal any difference between low-PPI and high-PPI subjects. These negative findings contrast with our previous reports that individual difference in PPI correlated with sustained attention and working memory performance in C57BL/6 mice.

  9. Superovulation Using the Combined Administration of Inhibin Antiserum and Equine Chorionic Gonadotropin Increases the Number of Ovulated Oocytes in C57BL/6 Female Mice

    PubMed Central

    Takeo, Toru; Nakagata, Naomi

    2015-01-01

    Superovulation is a reproductive technique generally used to produce genetically engineered mice. Superovulation in mice involves the administration of equine chorionic gonadotropin (eCG) to promote follicle growth and then that of human chorionic gonadotropin (hCG) to induce ovulation. Previously, some published studies reported that inhibin antiserum (IAS) increased the number of ovulated oocytes in ddY and wild-derived strains of mice. However, the effect of IAS on the C57BL/6 strain, which is the most widely used inbred strain for the production of genetically engineered mice, has not been investigated. In addition, the combined effect of IAS and eCG (IASe) on the number of ovulated oocytes in superovulation treatment has not been examined. In this study, we examined the effect of IAS and eCG on the number of ovulated oocytes in immature female mice of the C57BL/6 strain in superovulation treatment. Furthermore, we evaluated the quality of obtained oocytes produced by superovulation using IASe by in vitro fertilization (IVF) with sperm from C57BL/6 or genetically engineered mice. The developmental ability of fresh or cryopreserved embryos was examined by embryo transfer. The administration of IAS or eCG had a similar effect on the number of ovulated oocytes in C57BL/6 female mice. The number of ovulated oocytes increased to about 3-fold by the administration of IASe than by the administration of IAS or eCG alone. Oocytes derived from superovulation using IASe normally developed into 2-cell embryos by IVF using sperm from C57BL/6 mice. Fresh or cryopreserved 2-cell embryos produced by IVF between oocytes of C57BL/6 mice and sperm from genetically engineered mice normally developed into live pups following embryo transfer. In summary, a novel technique of superovulation using IASe is extremely useful for producing a great number of oocytes and offspring from genetically engineered mice. PMID:26024317

  10. DISTRIBUTION OF PCB 84 ENANTIOMERS IN C57BL/6 MICE

    EPA Science Inventory

    Nineteen of the 209 possible PCB congeners exist as pairs of stable rotational isomers that are enantiomeric to each other. A racemic mixture of PCB atropisomers is present in technical PCB mixtures, thus raising concerns about enantioselective distribution, metabolism, and dispo...

  11. MRP-1 expression levels determine strain-specific susceptibility to sodium arsenic-induced renal injury between C57BL/6 and BALB/c mice

    SciTech Connect

    Kimura, Akihiko; Ishida, Yuko; Wada, Takashi; Yokoyama, Hitoshi; Mukaida, Naofumi; Kondo, Toshikazu . E-mail: kondot@wakayama-med.ac.jp

    2005-02-15

    To clarify the pathophysiological mechanism underlying acute renal injury caused by acute exposure to arsenic, we subcutaneously injected both BALB/c and C57BL/6 mice with sodium arsenite (NaAs; 13.5 mg/kg). BALB/c mice exhibited exaggerated elevation of serum blood urea nitrogen (BUN) and creatinine (CRE) levels, compared with C57BL/6 mice. Moreover, half of BALB/c mice died by 24 h, whereas all C57BL/6 mice survived. Histopathological examination on kidney revealed severe hemorrhages, acute tubular necrosis, neutrophil infiltration, cast formation, and disappearance of PAS-positive brush borders in BALB/c mice, later than 10 h. These pathological changes were remarkably attenuated in C57BL/6 mice, accompanied with lower intrarenal arsenic concentrations, compared with BALB/c mice. Among heavy metal inducible proteins including multidrug resistance-associated protein (MRP)-1, multidrug resistance gene (MDR)-1, metallothionein (MT)-1, and arsenite inducible, cysteine- and histidine-rich RNA-associated protein (AIRAP), intrarenal MDR-1, MT-1, and AIRAP gene expression was enhanced to a similar extent in both strains, whereas NaAs challenge augmented intrarenal MRP-1 mRNA and protein expression levels in C57BL/6 but not BALB/c mice. Moreover, the administration of a specific inhibitor of MRP-1, MK-571, significantly exaggerated acute renal injury in C57BL/6 mice. Thus, MRP-1 is crucially involved in arsenic efflux and eventually prevention of acute renal injury upon acute exposure to NaAs.

  12. Amino acid and carbohydrate preferences in C57BL/6ByJ and 129P3/J mice

    PubMed Central

    Bachmanov, Alexander A.; Beauchamp, Gary K.

    2008-01-01

    Compared with mice from the 129P3/J (129) inbred strain, mice from the C57BL/6ByJ (B6) inbred strain have higher consumption of several sweet-tasting amino acids and carbohydrates. To examine the relative contribution of taste and nutritive properties in these strain differences, we measured responses of B6 and 129 mice to eight sweet and non-sweet amino acids and carbohydrates in two-bottle preference tests with water. Mice from the two strains did not differ in consumption of non-sweet L-valine and L-histidine. Compared with 129 mice, B6 mice had higher consumption and lower preference thresholds for sweet amino acids L-glutamine, L-alanine and L-threonine, monosaccharides glucose and fructose, and maltooligosaccharide. These data suggest that differences in gustatory responsiveness are an important factor underlying higher consumption of some amino acids and carbohydrates by B6 mice compared with 129 mice. It is likely that in B6 mice, higher sweet taste responsiveness results in increased consumption of sweet-tasting amino acids and sugars, and higher taste responsiveness to complex carbohydrates results in increased consumption of maltooligosaccharide. However, postingestive processes also influence nutrient consumption and may be responsible for higher intake of carbohydrates compared with sweet-tasting amino acids. Results of this study set the stage for genetic analysis of differences between B6 and 129 mice in taste responsiveness and macronutrient consumption. PMID:17764708

  13. Influence of cross-fostering on preference for calcium chloride in C57BL/6J and PWK/PhJ mice.

    PubMed

    Voznesenskaya, Anna; Tordoff, Michael G

    2013-10-01

    We investigated whether maternal influences during the suckling period alter the avidity for calcium, using as models mice from the calcium-preferring PWK/PhJ strain and the calcium-avoiding C57BL/6J strain. We found that milk collected from PWK/PhJ dams had higher calcium concentrations than did milk collected from C57BL/6J dams. Despite this, cross-strain fostering had no effect on adult calcium preferences relative to mice of the same strain that were within-strain fostered or not fostered. Our results indicate that calcium avoidance by C57BL/6J mice and acceptance by PWK/PhJ mice are unaffected by maternal environment during the suckling period.

  14. Age-Related Impairment in the 250-Millisecond Delay Eyeblink Classical Conditioning Procedure in C57BL/6 Mice

    PubMed Central

    Vogel, Richard W.; Ewers, Michael; Ross, Charlene; Gould, Thomas J.; Woodruff-Pak, Diana S.

    2002-01-01

    In this study we tested 4-, 9-, 12-, and 18-month-old C57BL/6 mice in the 250-msec delay eyeblink classical conditioning procedure to study age-related changes in a form of associative learning. The short life expectancy of mice, complete knowledge about the mouse genome, and the availability of transgenic and knock-out mouse models of age-related impairments make the mouse an excellent species for expanding knowledge on the neurobiologically and behaviorally well-characterized eyeblink classical conditioning paradigm. Based on previous research with delay eyeblink conditioning in rabbits and humans, we predicted that mice would be impaired on this cerebellar-dependent associative learning task in middle-age, at ∼9 months. To fully examine age differences in behavior in mice, we used a battery of additional behavioral measures with which to compare young and older mice. These behaviors included the acoustic startle response, prepulse inhibition, rotorod, and the Morris water maze. Mice began to show impairment in cerebellar-dependent tasks such as rotorod and eyeblink conditioning at 9 to 12 months of age. Performance in hippocampally dependent tasks was not impaired in any group, including 18-month-old mice. These results in mice support results in other species, indicating that cerebellar-dependent tasks show age-related deficits earlier in adulthood than do hippocampally dependent tasks. PMID:12359840

  15. Gynura procumbens extract improves insulin sensitivity and suppresses hepatic gluconeogenesis in C57BL/KsJ-db/db mice

    PubMed Central

    Choi, Sung-In; Lee, Hyun-Ah

    2016-01-01

    BACKGROUND/OBJECTIVES This study was designed to investigate whether Gynura procumbens extract (GPE) can improve insulin sensitivity and suppress hepatic glucose production in an animal model of type 2 diabetes. MATERIALS/METHODS C57BL/Ksj-db/db mice were divided into 3 groups, a regular diet (control), GPE, and rosiglitazone groups (0.005 g/100 g diet) and fed for 6 weeks. RESULTS Mice supplemented with GPE showed significantly lower blood levels of glucose and glycosylated hemoglobin than diabetic control mice. Glucose and insulin tolerance test also showed the positive effect of GPE on increasing insulin sensitivity. The homeostatic index of insulin resistance was significantly lower in mice supplemented with GPE than in the diabetic control mice. In the skeletal muscle, the expression of phosphorylated AMP-activated protein kinase, pAkt substrate of 160 kDa, and PM-glucose transporter type 4 increased in mice supplemented with GPE when compared to that of the diabetic control mice. GPE also decreased the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the liver. CONCLUSIONS These findings demonstrate that GPE might improve insulin sensitivity and inhibit gluconeogenesis in the liver. PMID:27698958

  16. A multi-mineral natural product from red marine algae reduces colon polyp formation in C57BL/6 mice

    PubMed Central

    Aslam, Muhammad N.; Bergin, Ingrid; Naik, Madhav; Paruchuri, Tejaswi; Hampton, Anna; Rehman, Muneeb; Dame, Michael K; Rush, Howard; Varani, James

    2013-01-01

    The goal of this study was to determine if a multi-mineral natural product derived from red marine algae, could reduce colon polyp formation in mice on a high fat diet. C57BL/6 mice were maintained for up to 18 months either on a high-fat “Western-style” diet or on a low-fat diet (AIN 76A), with or without the multi-mineral-supplement. To summarize, colon polyps were detected in 22 of 70 mice (31%) on the high-fat diet, but in only 2 of 70 mice (3%) receiving the mineral-supplemented high-fat diet (p<0.0001). Colon polyps were detected in 16 of 70 mice (23%) in the low-fat group; not significantly different from high-fat group but significantly higher than the high-fat-supplemented group (p=0.0006). This was in spite of the fact that the calcium level in the low-fat diet was comparable to the level of calcium in the high-fat diet containing the multi-mineral-product. Supplementation of the low-fat diet reduced the incidence to 8 of 70 mice (11% incidence). Taken together, these findings demonstrate that a multi-mineral natural product can protect mice on a high-fat diet against adenomatous polyp formation in the colon. These data suggest that increased calcium alone is insufficient to explain the lower incidence of colon polyps. PMID:23035966

  17. Gynura procumbens extract improves insulin sensitivity and suppresses hepatic gluconeogenesis in C57BL/KsJ-db/db mice

    PubMed Central

    Choi, Sung-In; Lee, Hyun-Ah

    2016-01-01

    BACKGROUND/OBJECTIVES This study was designed to investigate whether Gynura procumbens extract (GPE) can improve insulin sensitivity and suppress hepatic glucose production in an animal model of type 2 diabetes. MATERIALS/METHODS C57BL/Ksj-db/db mice were divided into 3 groups, a regular diet (control), GPE, and rosiglitazone groups (0.005 g/100 g diet) and fed for 6 weeks. RESULTS Mice supplemented with GPE showed significantly lower blood levels of glucose and glycosylated hemoglobin than diabetic control mice. Glucose and insulin tolerance test also showed the positive effect of GPE on increasing insulin sensitivity. The homeostatic index of insulin resistance was significantly lower in mice supplemented with GPE than in the diabetic control mice. In the skeletal muscle, the expression of phosphorylated AMP-activated protein kinase, pAkt substrate of 160 kDa, and PM-glucose transporter type 4 increased in mice supplemented with GPE when compared to that of the diabetic control mice. GPE also decreased the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the liver. CONCLUSIONS These findings demonstrate that GPE might improve insulin sensitivity and inhibit gluconeogenesis in the liver.

  18. Evaluation of social and physical enrichment in modulation of behavioural phenotype in C57BL/6J female mice.

    PubMed

    Kulesskaya, Natalia; Rauvala, Heikki; Voikar, Vootele

    2011-01-01

    Housing conditions represent an important environmental variable playing a critical role in the assessment of mouse behaviour. In the present study the effects of isolation and nesting material on the behaviour of female C57BL/6J mice were evaluated. The mice were subjected to different rearing conditions from weaning (at the age of 3 weeks). The study groups were group- and single-housed mice, divided further into groups with or without nesting material (species-specific enrichment). After 8 weeks spent in respective conditions the behavioural testing began. Both factors (social conditions and nesting material) appeared to have a significant impact on the behavioural phenotype. However, it is important to stress that the interaction between the factors was virtually absent. We established that isolation increased locomotor activity and reduced anxiety-like behaviour in several tests of exploration. In contrast, absence of nesting material increased anxiety-like behaviour. Neither factor affected rota-rod performance, nociception and prepulse inhibition. Contextual fear memory was significantly reduced in single-housed mice, and interestingly, in mice with nesting material. Cued fear memory was reduced by single-housing, but not affected by enrichment. Mice from enriched cages displayed faster and better learning and spatial search strategy in the water maze. In contrast, isolation caused significant impairment in the water maze. In conclusion, both isolation and species-specific enrichment have profound effects on mouse behaviour and should be considered in design of the experiments and in assessment of animal welfare issues.

  19. Phenotypic Changes in Diabetic Neuropathy Induced by a High-Fat Diet in Diabetic C57Bl/6 Mice

    PubMed Central

    Guilford, B. L.; Ryals, J. M.; Wright, D. E.

    2011-01-01

    Emerging evidence suggests that dyslipidemia is an independent risk factor for diabetic neuropathy (DN) (reviewed by Vincent et al. 2009). To experimentally determine how dyslipidemia alters DN, we quantified neuropathic symptoms in diabetic mice fed a high-fat diet. Streptozotocin-induced diabetic C57BL/6 mice fed a high-fat diet developed dyslipidemia and a painful neuropathy (mechanical allodynia) instead of the insensate neuropathy (mechanical insensitivity) that normally develops in this strain. Nondiabetic mice fed a high-fat diet also developed dyslipidemia and mechanical allodynia. Thermal sensitivity was significantly reduced in diabetic compared to nondiabetic mice, but was not worsened by the high-fat diet. Moreover, diabetic mice fed a high-fat diet had significantly slower sensory and motor nerve conduction velocities compared to nondiabetic mice. Overall, dyslipidemia resulting from a high-fat diet may modify DN phenotypes and/or increase risk for developing DN. These results provide new insight as to how dyslipidemia may alter the development and phenotype of diabetic neuropathy. PMID:22144990

  20. Myricetin protects against diet-induced obesity and ameliorates oxidative stress in C57BL/6 mice*

    PubMed Central

    Su, Hong-ming; Feng, Li-na; Zheng, Xiao-dong; Chen, Wei

    2016-01-01

    Background: Myricetin is a naturally occurring antioxidant commonly found in various plants. However, little information is available with respect to its direct anti-obesity effects. Objective: This study was undertaken to investigate the effect of myricetin on high-fat diet (HFD)-induced obesity in C57BL/6 mice. Results: Administration of myricetin dramatically reduced the body weight of diet-induced obese mice compared with solely HFD-induced mice. Several parameters related to obesity including serum glucose, triglyceride, and cholesterol were significantly decreased in myricetin-treated mice. Moreover, obesity-associated oxidative stress (glutathione peroxidase (GPX) activity, total antioxidant capacity (T-AOC), and malondialdehyde (MDA)) and inflammation (tumor necrosis factor-α (TNF-α)) were ameliorated in myricetin-treated mice. Further investigation revealed that the protective effect of myricetin against HFD-induced obesity in mice appeared to be partially mediated through the down-regulation of mRNA expression of adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), and lipogenic transcription factor sterol regulatory element-binding protein 1c (SREBP-1c). Conclusions: Consumption of myricetin may help to prevent obesity and obesity-related metabolic complications. PMID:27256677

  1. Ampicillin-Improved Glucose Tolerance in Diet-Induced Obese C57BL/6NTac Mice Is Age Dependent

    PubMed Central

    Rune, I.; Hansen, C. H. F.; Ellekilde, M.; Nielsen, D. S.; Skovgaard, K.; Rolin, B. C.; Lykkesfeldt, J.; Josefsen, K.; Tranberg, B.; Kihl, P.; Hansen, A. K.

    2013-01-01

    Ampicillin has been shown to improve glucose tolerance in mice. We hypothesized that this effect is present only if treatment is initiated prior to weaning and that it disappears when treatment is terminated. High-fat fed C57BL/6NTac mice were divided into groups that received Ampicillin at different ages or not at all. We found that both diet and Ampicillin significantly changed the gut microbiota composition in the animals. Furthermore, there was a significant improvement in glucose tolerance in Ampicillin-treated, five-week-old mice compared to nontreated mice in the control group. At study termination, expressions of mRNA coding for tumor necrosis factor, serum amyloid A, and lactase were upregulated, while the expression of tumor necrosis factor (ligand) superfamily member 15 was downregulated in the ileum of Ampicillin-treated mice. Higher dendritic cell percentages were found systemically in high-fat diet mice, and a lower tolerogenic dendritic cell percentage was found both in relation to high-fat diet and late Ampicillin treatment. The results support our hypothesis that a “window” exists early in life in which an alteration of the gut microbiota affects glucose tolerance as well as development of gut immunity and that this window may disappear after weaning. PMID:24369539

  2. Correction of the Crb1rd8 Allele and Retinal Phenotype in C57BL/6N Mice Via TALEN-Mediated Homology-Directed Repair

    PubMed Central

    Low, Benjamin E.; Krebs, Mark P.; Joung, J. Keith; Tsai, Shengdar Q.; Nishina, Patsy M.; Wiles, Michael V.

    2014-01-01

    Purpose. We directly corrected the mouse Crb1rd8 gene mutation, which is present in many inbred laboratory strains derived from C57BL/6N and complicates genetic studies of retinal disease in mice. Methods. Fertilized C57BL/6NJ oocytes were coinjected with mRNAs encoding a transcription activator-like effector nuclease (TALEN) targeting the Crb1rd8 allele plus single-stranded oligonucleotides to correct the allele. The oligonucleotides included additional nucleotide changes to distinguish the corrected allele (Crb1em1Mvw) from wild-type Crb1 and to minimize TALEN recutting. Oligonucleotide length, concentration of injected oligonucleotides and TALEN mRNAs were varied to optimize homology-directed repair of the locus. Following microinjection, embryos were carried to term in pseudopregnant females. Correction efficiency was assessed by PCR analysis of the Crb1em1Mvw allele. Phenotypic correction was demonstrated by fundus imaging and optical coherence tomography of live mice, and by confocal fluorescence microscopy of retinal flat mounts. Results. Under optimal conditions, homology-directed repair was observed in 27% (8/30) of live-born animals and showed minimal illegitimate recombination of donor DNA. However, extensive founder mosaicism was evident, emphasizing the need to analyze offspring of founder animals. Unlike C57BL/6NJ mice, which exhibited external limiting membrane fragmentation and regional retinal dysplasia, heterozygous Crb1em1Mvw/Crb1rd8 mice showed a normal retinal phenotype. Conclusions. The C57BL/6NJ-Crb1rd8 mutation and its associated retinal phenotypes were corrected efficiently by TALEN-mediated homology-directed repair. The C57BL/6NJ-Crb1em1Mvw mice generated by this strategy will enhance ocular phenotyping efforts based on the C57BL/6N background, such as those implemented by the International Mouse Phenotyping Consortium (IMPC) project. PMID:24346171

  3. Response, use and habituation to a mouse house in C57BL/6J and BALB/c mice.

    PubMed

    Wirz, Annarita; Mandillo, Silvia; D'Amato, Francesca R; Giuliani, Alessandro; Riviello, M Cristina

    2015-01-01

    Animal welfare depends on the possibility to express species-specific behaviours and can be strongly compromised in socially and environmentally deprived conditions. Nesting materials and refuges are very important resources to express these behaviours and should be considered as housing supplementation items. We evaluated the effects of one item of housing supplementation in standard settings in laboratory mice. C57BL/6JOlaHsd (B6) and BALB/cOlaHsd (BALB) young male and female mice, upon arrival, were housed in groups of four in standard laboratory cages and after 10 days of acclimatization, a red transparent plastic triangular-shaped Mouse House™ was introduced into half of the home cages. Animals with or without a mouse house were observed in various contexts for more than one month. Body weight gain and food intake, home cage behaviours, emotionality and response to standard cage changing procedures were evaluated. The presence of a mouse house in the home cage did not interfere with main developmental and behavioural parameters or emotionality of BALB and B6 male and female mice compared with controls. Both strains habituated to the mouse house in about a week, but made use of it differently, with BALB mice using the house more than the B6 strain. Our results suggest that mice habituated to the mouse house rather quickly without disrupting their home cage activities. Scientists can thus be encouraged to use mouse houses, also in view of the implementation of the EU Directive (2010/63/EU).

  4. Response, use and habituation to a mouse house in C57BL/6J and BALB/c mice

    PubMed Central

    WIRZ, Annarita; MANDILLO, Silvia; D’AMATO, Francesca R.; GIULIANI, Alessandro; RIVIELLO, M. Cristina

    2015-01-01

    Animal welfare depends on the possibility to express species-specific behaviours and can be strongly compromised in socially and environmentally deprived conditions. Nesting materials and refuges are very important resources to express these behaviours and should be considered as housing supplementation items. We evaluated the effects of one item of housing supplementation in standard settings in laboratory mice. C57BL/6JOlaHsd (B6) and BALB/cOlaHsd (BALB) young male and female mice, upon arrival, were housed in groups of four in standard laboratory cages and after 10 days of acclimatization, a red transparent plastic triangular-shaped Mouse House™ was introduced into half of the home cages. Animals with or without a mouse house were observed in various contexts for more than one month. Body weight gain and food intake, home cage behaviours, emotionality and response to standard cage changing procedures were evaluated. The presence of a mouse house in the home cage did not interfere with main developmental and behavioural parameters or emotionality of BALB and B6 male and female mice compared with controls. Both strains habituated to the mouse house in about a week, but made use of it differently, with BALB mice using the house more than the B6 strain. Our results suggest that mice habituated to the mouse house rather quickly without disrupting their home cage activities. Scientists can thus be encouraged to use mouse houses, also in view of the implementation of the EU Directive (2010/63/EU). PMID:25854626

  5. Effects of Buprenorphine and Meloxicam Analgesia on Induced Cerebral Ischemia in C57BL/6 Male Mice

    PubMed Central

    Jacobsen, Kirsten R; Fauerby, Natasha; Raida, Zindy; Kalliokoski, Otto; Hau, Jann; Johansen, Flemming F; Abelson, Klas SP

    2013-01-01

    Laboratory mice constitute an extensively used model to study the pathologic and functional outcomes of cerebral ischemic stroke. The middle cerebral artery occlusion (MCAO) model requires surgical intervention, which potentially can result in postsurgical pain and stress. In the present study, we investigated whether buprenorphine and meloxicam, at clinically relevant doses provided pain relief without altering infarct volume in male C57BL/6 mice. Common known side-effects of buprenorphine, including decreased food consumption, were noted after surgery in buprenorphine-treated mice, but these effects were brief and seen only during the treatment period. Fecal corticosterone metabolites did not differ significantly between the groups. In the present study, buprenorphine treatment did not alter infarction volume when compared with that of mice that did not receive analgesia. In contrast, meloxicam treatment significantly reduced infarct volume and may be a confounder if used as an analgesic during MCAO surgery. Furthermore, investigation of behavioral profiles by using an automated behavioral scoring system showed that rearing and sniffing behaviors decreased as infarct volume increased. This suggests that studies of exploratory behavior may aid in developing new markers of short-term stroke-related behavioral deficiencies in laboratory mice. PMID:23582417

  6. Attenuation coefficient of the light in skin of BALB/c and C57BL/6 mice

    NASA Astrophysics Data System (ADS)

    Silva, C. R.; Camargo, C. F. M.; Aureliano, D. P.; De Pretto, L. R.; Freitas, A. Z.; Ribeiro, M. S.

    2015-06-01

    Optical properties of the biological tissue play an important role to a correct use of optical techniques for therapy and diagnosis. The mice skin presents morphological differences due to characteristics such as gender, body mass and age. Murine models are frequently used in pre-clinical trials in optical therapy and diagnosis. Therefore, the assessment of the skin tissue in animal models is needed for a proper understanding of how light interacts with skin. Noninvasive techniques such as optical coherence tomography (OCT) have been used to obtain optical information of the tissue, as the attenuation coefficient, with the advantage of obtaining sectional images in real time. In this study, eight female BALB/c albino mice (twenty-four weeks old) and eight male C57BL/6 black mice (eight weeks old) were used to measure the attenuation coefficient of the light in the skin, utilizing the OCT technique, aiming to check for influence of the aging process. Two moments were assessed twenty-two weeks apart from each other. Our data show that the aging process significantly affects the light attenuation coefficient in mice skin. Twenty-two weeks after, statistical significant differences were observed between groups within a same strain. We conclude that light attenuation coefficient of mice skin may be influenced by factors such as disorganization of the dermis. Morphological aspects of skin should be taken into account in studies that involve optical strategies in murine models.

  7. Ocular Surface Disease and Dacryoadenitis in Aging C57BL/6 Mice

    PubMed Central

    McClellan, Andrew J.; Volpe, Eugene A.; Zhang, Xiaobo; Darlington, Gretchen J.; Li, De-Quan; Pflugfelder, Stephen C.; de Paiva, Cintia S.

    2015-01-01

    Dry eye in humans displays increased prevalence in the aged and in women. Here, we investigated the ocular surfaces and lacrimal glands of aged mice of both sexes. We surveyed three different ages [young, middle-aged (6 to 9 months), and elderly] by investigating severity markers of dry eye disease (DED). We observed an age-dependent dry eye phenotype as early as 6 to 9 months: increased corneal surface irregularity, increased corneal barrier disruption, conjunctival CD4+ T-cell infiltration, and loss of mucin-filled goblet cells. Expression of interferon-γ, IL-17 mRNA transcripts was increased in the conjunctiva and IL-17A, matrix metallopeptidase 9, and chemokine ligand 20 in the corneas of elderly mice. Elderly male mice develop more of a skewed response of type 1 T helper cell, whereas female mice have a bias toward type 17 T helper cell in the conjunctiva. In the lacrimal gland, an increase in CD4+ and CD8+ T cells and B cells and a decrease in activated dendritic cells were observed. Adoptive transfer of CD4+ T cells isolated from elderly mice transferred DED into young immunodeficient recipients, which was more pronounced from male donors. Our findings show the development of DED in aging mice. Pathogenic CD4+ T cells that develop with aging are capable of transferring DED from older mice to naive immunodeficient recipients. Taken together, our results indicate that age-related autoimmunity contributes to development of DED with aging. PMID:24389165

  8. CCR5 knockout suppresses experimental autoimmune encephalomyelitis in C57BL/6 mice.

    PubMed

    Gu, Sun Mi; Park, Mi Hee; Yun, Hyung Mun; Han, Sang Bae; Oh, Ki Wan; Son, Dong Ju; Yun, Jae Suk; Hong, Jin Tae

    2016-03-29

    Multiple sclerosis (MS) is an inflammatory disease in which myelin in the spinal cord is damaged. C-C chemokine receptor type 5 (CCR5) is implicated in immune cell migration and cytokine release in central nervous system (CNS). We investigated whether CCR5 plays a role in MS progression using a murine model, experimental autoimmune encephalomyelitis (EAE), in CCR5 deficient (CCR5-/-) mice. CCR5-/- and CCR5+/+ (wild-type) mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) followed by pertussis toxin, after which EAE paralysis was scored for 28 days. We found that clinical scoring and EAE neuropathology were lower in CCR5-/- mice than CCR5+/+ mice. Immune cells (CD3+, CD4+, CD8+, B cell, NK cell and macrophages) infiltration and astrocytes/microglial activation were attenuated in CCR5-/- mice. Moreover, levels of IL-1β, TNF-α, IFN-γ and MCP-1 cytokine levels were decreased in CCR5-/- mice spinal cord. Myelin basic protein (MBP) and CNPase were increased while NG2 and O4 were decreased in CCR5-/- mice, indicating that demyelination was suppressed by CCR5 gene deletion. These findings suggest that CCR5 is likely participating in demyelination in the spinal cord the MS development, and that it could serve as an effective therapeutic target for the treatment of MS.

  9. Chronic respiratory mycoplasmosis in C3H/HeN and C57BL/6N mice: lesion severity and antibody response.

    PubMed Central

    Cartner, S C; Simecka, J W; Lindsey, J R; Cassell, G H; Davis, J K

    1995-01-01

    Mycoplasma pneumoniae is a leading, worldwide cause of death and disability due to pneumonia. Mycoplasma pulmonis infection in mice is an invaluable model for the study of host defenses against respiratory mycoplasmas in vivo. C3H/HeN mice are much more susceptible to acute inflammatory lung disease due to M. pulmonis than C57BL/6N mice, but little is known about the chronic disease in these mouse strains. We infected C3H/HeN and C57BL/6N mice with 10(4) CFU of M. pulmonis UAB CT and evaluated them at weekly intervals by quantitative mycoplasma culture of nasal passages, trachea, and lungs, assessment of lesion severity in nasal passages, trachea, and lungs, and determination of serum immunoglobulin classes and subclasses by enzyme-linked immunosorbent assay. We found that C3H/HeN mice had 2 to 5 logs more organisms in their lungs and far more severe lung disease than C57BL/6N mice through 63 days postinfection. Although both strains of mice developed the same classes of antibody, C3H/HeN mice had much greater anti-M. pulmonis immunoglobulin G (IgG) responses in the IgG1 and IgG2a subclasses than C57BL/6N mice. These results suggest that adaptive immunity does not effect resolution of chronic mycoplasma infection and disease in the lungs. PMID:7558330

  10. Humanized TLR7/8 expression drives proliferative multisystemic histiocytosis in C57BL/6 mice.

    PubMed

    Snyder, Jessica M; Treuting, Piper M; Nagy, Lee; Yam, Cathy; Yi, Jaehun; Brasfield, Alicia; Nguyen, Lisa Phuong Anh; Hajjar, Adeline M

    2014-01-01

    A humanized TLR7/TLR8 transgenic mouse line was engineered for studies using TLR7/8 ligands as vaccine adjuvants. The mice developed a spontaneous immune-mediated phenotype prior to six months of age characterized by runting, lethargy, blepharitis, and corneal ulceration. Histological examination revealed a marked, multisystemic histiocytic infiltrate that effaced normal architecture. The histological changes were distinct from those previously reported in mouse models of systemic lupus erythematosus. When the mice were crossed with MyD88-/- mice, which prevented toll-like receptor signaling, the inflammatory phenotype resolved. Illness may be caused by constitutive activation of human TLR7 or TLR8 in the bacterial artificial chromosome positive mice as increased TLR7 and TLR8 expression or activation has previously been implicated in autoimmune disease. PMID:25229618

  11. Anti-diabetic effect of purple corn extract on C57BL/KsJ db/db mice

    PubMed Central

    Huang, Bo; Wang, Zhiqiang; Park, Jong Hyuk; Ryu, Ok Hyun; Choi, Moon Ki; Lee, Jae-Yong; Kang, Young-Hee

    2015-01-01

    BACKGROUND/OBJECTIVES Recently, anthocyanins have been reported to have various biological activities. Furthermore, anthocyanin-rich purple corn extract (PCE) ameliorated insulin resistance and reduced diabetes-associated mesanginal fibrosis and inflammation, suggesting that it may have benefits for the prevention of diabetes and diabetes complications. In this study, we determined the anthocyanins and non-anthocyanin component of PCE by HPLC-ESI-MS and investigated its anti-diabetic activity and mechanisms using C57BL/KsJ db/db mice. MATERIALS/METHODS The db/db mice were divided into four groups: diabetic control group (DC), 10 or 50 mg/kg PCE (PCE 10 or PCE 50), or 10 mg/kg pinitol (pinitol 10) and treated with drugs once per day for 8 weeks. During the experiment, body weight and blood glucose levels were measured every week. At the end of treatment, we measured several diabetic parameters. RESULTS Compared to the DC group, Fasting blood glucose levels were 68% lower in PCE 50 group and 51% lower in the pinitol 10 group. Furthermore, the PCE 50 group showed 2- fold increased C-peptide and adiponectin levels and 20% decreased HbA1c levels, than in the DC group. In pancreatic islets morphology, the PCE- or pinitol-treated mice showed significant prevention of pancreatic β-cell damage and higher insulin content. Microarray analyses results indicating that gene and protein expressions associated with glycolysis and fatty acid metabolism in liver and fat tissues. In addition, purple corn extract increased the phosphorylation of AMP-activated protein kinase (AMPK) and decreased phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6pase) genes in liver, and also increased glucose transporter 4 (GLUT4) expressions in skeletal muscle. CONCLUSIONS Our results suggested that PCE exerted anti-diabetic effects through protection of pancreatic β-cells, increase of insulin secretion and AMPK activation in the liver of C57BL/KsJ db/db mice. PMID:25671064

  12. C57BL/6J and DBA/2J mice differ in extinction and renewal of extinguished conditioned fear.

    PubMed

    Waddell, Jaylyn; Dunnett, Claire; Falls, William A

    2004-10-01

    While a number of studies have examined the acquisition and expression of conditioned fear in inbred mice, very few have examined extinction of conditioned fear in inbred mice and few attempts have been made to compare extinction learning between inbred strains. Because inbred strains differ in a number of physiological and biochemical variables, differences in extinction learning may provide insight into the genetic influence of extinction learning. The purpose of this study was to examine extinction and renewal of conditioned fear in two common inbred strains of mice. C57BL/6J and DBA/2J mice were conditioned with pairings of either a tone or light and foot shock in a single session. On the following 4 days, mice were given extinction training, consisting of tone or light alone trials (Experiment 1A). C57 mice exhibited robust spontaneous recovery between sessions, but did extinguish both within and between sessions. DBA mice extinguished more quickly relative to C57 mice, and this extinction was stable between sessions (i.e., DBA mice did not exhibit spontaneous recovery). The rapid loss of fear in DBA relative to C57 mice was extinction-dependent and not merely due to poor long-term memory (Experiment 1B). Renewal testing (Experiment 2) replicated the strain difference in extinction and also showed that DBA mice have a deficit in the context specificity of extinction. C57 mice, but not DBA mice showed renewal of extinguished fear when tested in a context different from the one in which extinction training took place. These data suggest that the nature of extinction learning is influenced by characteristics of the inbred mouse strain.

  13. Effect of age and vaccination on extent and spread of Chlamydia pneumoniae infection in C57BL/6 mice

    PubMed Central

    2012-01-01

    Background Chlamydia pneumoniae is an obligate intracellular respiratory pathogen for humans. Infection by C. pneumoniae may be linked etiologically to extra-respiratory diseases of aging, especially atherosclerosis. We have previously shown that age promotes C. pneumoniae respiratory infection and extra-respiratory spread in BALB/c mice. Findings Aged C57BL/6 mice had a greater propensity to develop chronic and/or progressive respiratory infections following experimental intranasal infection by Chlamydia pneumoniae when compared to young counterparts. A heptavalent CTL epitope minigene (CpnCTL7) vaccine conferred equal protection in the lungs of both aged and young mice. This vaccine was partially effective in protecting against C. pneumoniae spread to the cardiovascular system of young mice, but failed to provide cardiovascular protection in aged animals. Conclusions Our findings suggest that vaccine strategies that target the generation of a C. pneumoniae-specific CTL response can protect the respiratory system of both young and aged animals, but may not be adequate to prevent dissemination of C. pneumoniae to the cardiovascular system or control replication in those tissues in aged animals. PMID:22594698

  14. Simulating long-term occupational exposure to decabrominated diphenyl ether using C57BL/6 mice: biodistribution and pathology.

    PubMed

    Feng, Yan; Hu, Qingliang; Meng, Ge; Wu, Xiaomeng; Zeng, Weihong; Zhang, Xing; Yu, Yingxin; Wang, Yan

    2015-06-01

    Decabrominated biphenyl ether (BDE-209) is a fully brominated diphenyl ether compound used widely as an additive brominated flame retardant in a variety of consumer products. In recent years, BDE-209 has been reported to be abundant and persistent in the environment, and comparatively high burdens have been found in occupational environmental compartments and exposed individuals. In the present study, an animal model for simulating long-term occupational exposure to BDE-209 was set up. Female C57BL/6 mice (n=10) were intragastrically administered BDE-209 at a dose of 800 mg kg(-1) bw at 2-d intervals for 2 years with an internal blood level of approximately 200 ng mL(-1), which was comparable to the high level of BDE-209 detected in the occupational population, and the biodistribution and biological effects were evaluated systematically. The results showed that large amounts of the chemical accumulated in most tissues, and the preferential organs were the ovary and uterus, liver and lung. Decreased survival was observed in the exposed mice. The subsequent pathological analysis revealed hepatomegaly in the exposed mice, accompanied by obvious histopathological changes in the liver, lung, brain, spleen, kidney and ovary. No neoplastic lesions were observed in this lifetime exposure study. Although the number of experimental mice was limited, our observations offer a comprehensive understanding of the chronic toxicology of BDE-209 after continuous high-dose exposure. PMID:25687576

  15. Impact of social isolation and enriched environment during adolescence on voluntary ethanol intake in C57BL/6J mice

    PubMed Central

    Lopez, Marcelo F.; Laber, Kathy

    2014-01-01

    This study was designed to determine the impact of an enriched environment in a previously established stress model of isolation during early development that induces high alcohol (ethanol) self-administration. The study was conducted with male and female C57BL/6J mice housed in isolation or in groups that were either provided or withheld enrichment during adolescence. The impact of these housing conditions was assessed during adulthood by measuring weight gain, quantifying voluntary ethanol intake, measuring plasma corticosterone levels, and assessing anxiety-like behavior. Results showed that, regardless of sex, mice that were single-housed during adolescence showed a significant increase in voluntary ethanol intake, which was not observed in isolated mice that were provided with nesting material during adolescence (compared to group-housed non-enriched control group). Basal corticosterone was not affected by housing, enrichment conditions, or sex. Corticosterone levels did not relate to levels of voluntary ethanol intake. However, corticosterone levels were higher after three weeks of ethanol intake. Surprisingly, mice that were group-housed during adolescence showed higher levels of anxiety-like behavior in the light/dark test. Overall, these results indicate that housing conditions during a critical developmental period can significantly modulate voluntary ethanol intake later in life. PMID:25446196

  16. Influence of reinforcement schedule on ethanol consumption patterns in non-food restricted male C57BL/6J mice.

    PubMed

    Ford, Matthew M; Fretwell, Andrea M; Mark, Gregory P; Finn, Deborah A

    2007-02-01

    Ethanol reinforcement should ideally be evaluated in animals that are not food deprived to ensure that the motivation behind its consumption is pharmacological, and not caloric, in nature. The objective of this work was to assess the influence of reinforcement schedule on ethanol intake in nondeprived mice. Male C57BL/6J mice were trained to respond on an ethanol-reinforced lever on a fixed ratio 4 reinforcement schedule for 10% ethanol (10E). The appetitive and consummatory phases were then procedurally separated by changing the response requirement (RR), so that mice were permitted 30-min continuous 10E access after completion of either four (RR4) or eight (RR8) responses. Phase separation yielded a heightened appetitive drive to acquire 10E access (as indexed by a significant decrease in the latency to first active lever and a trend toward a decrease in the latency to first sipper contact) and an augmented level of drinking (twofold elevation in the ethanol dose consumed). Robust extinction responding on the ethanol-appropriate lever indicated that ethanol was effective as a behavioral reinforcer. These results suggest that the separation of appetitive and consummatory phases of ethanol self-administration may prove useful in future evaluations of the pharmacological and genetic bases of ethanol reinforcement in mice.

  17. Strictly co-isogenic C57BL/6J-Prnp−/− mice: A rigorous resource for prion science

    PubMed Central

    Nuvolone, Mario; Hermann, Mario; Sorce, Silvia; Russo, Giancarlo; Tiberi, Cinzia; Schwarz, Petra; Minikel, Eric; Sanoudou, Despina; Pelczar, Pawel

    2016-01-01

    Although its involvement in prion replication and neurotoxicity during transmissible spongiform encephalopathies is undisputed, the physiological role of the cellular prion protein (PrPC) remains enigmatic. A plethora of functions have been ascribed to PrPC based on phenotypes of Prnp−/− mice. However, all currently available Prnp−/− lines were generated in embryonic stem cells from the 129 strain of the laboratory mouse and mostly crossed to non-129 strains. Therefore, Prnp-linked loci polymorphic between 129 and the backcrossing strain resulted in systematic genetic confounders and led to erroneous conclusions. We used TALEN-mediated genome editing in fertilized mouse oocytes to create the Zurich-3 (ZH3) Prnp-ablated allele on a pure C57BL/6J genetic background. Genomic, transcriptional, and phenotypic characterization of PrnpZH3/ZH3 mice failed to identify phenotypes previously described in non–co-isogenic Prnp−/− mice. However, aged PrnpZH3/ZH3 mice developed a chronic demyelinating peripheral neuropathy, confirming the crucial involvement of PrPC in peripheral myelin maintenance. This new line represents a rigorous genetic resource for studying the role of PrPC in physiology and disease. PMID:26926995

  18. Adenosinergic regulation of binge-like ethanol drinking and associated locomotor effects in male C57BL/6J mice.

    PubMed

    Fritz, Brandon M; Boehm, Stephen L

    2015-08-01

    We recently observed that the addition of caffeine (a nonselective adenosine receptor antagonist) to a 20% ethanol solution significantly altered the intoxication profile of male C57BL/6J (B6) mice induced by voluntary binge-like consumption in the 'Drinking-in-the-Dark' (DID) paradigm. In the current study, the roles of A1 and A2A adenosine receptor subtypes, specifically, in binge-like ethanol consumption and associated locomotor effects were explored. Adult male B6 mice (PND 60-70) were allowed to consume 20% ethanol (v/v) or 2% sucrose (w/v) for 6days via DID. On day 7, mice received a systemic administration (i.p.) of the A1 antagonist DPCPX (1, 3, 6mg/kg), the A2A antagonist MSX-3 (1, 2, 4mg/kg), or vehicle immediately prior to fluid access in DID. Antagonism of the A1 receptor via DPCPX was found to dose-dependently decrease binge-like ethanol intake and associated blood ethanol concentrations (p's<0.05), although no effect was observed on sucrose intake. Antagonism of A2A had no effect on ethanol or sucrose consumption, however, MSX-3 elicited robust locomotor stimulation in mice consuming either solution (p's<0.05). Together, these findings suggest unique roles for the A1 and A2A adenosine receptor subtypes in binge-like ethanol intake and its associated locomotor effects. PMID:26033424

  19. Use of anesthesia dramatically alters the oral glucose tolerance and insulin secretion in C57Bl/6 mice.

    PubMed

    Windeløv, Johanne A; Pedersen, Jens; Holst, Jens J

    2016-06-01

    Evaluation of the impact of anesthesia on oral glucose tolerance in mice. Anesthesia is often used when performing OGTT in mice to avoid the stress of gavage and blood sampling, although anesthesia may influence gastrointestinal motility, blood glucose, and plasma insulin dynamics. C57Bl/6 mice were anesthetized using the following commonly used regimens: (1) hypnorm/midazolam repetitive or single injection; (2) ketamine/xylazine; (3) isoflurane; (4) pentobarbital; and (5) A saline injected, nonanesthetized group. Oral glucose was administered at time 0 min and blood glucose measured in the time frame -15 to +150 min. Plasma insulin concentration was measured at time 0 and 20 min. All four anesthetic regimens resulted in impaired glucose tolerance compared to saline/no anesthesia. (1) hypnorm/midazolam increased insulin concentrations and caused an altered glucose tolerance; (2) ketamine/xylazine lowered insulin responses and resulted in severe hyperglycemia throughout the experiment; (3) isoflurane did not only alter the insulin secretion but also resulted in severe hyperglycemia; (4) pentobarbital resulted in both increased insulin secretion and impaired glucose tolerance. All four anesthetic regimens altered the oral glucose tolerance, and we conclude that anesthesia should not be used when performing metabolic studies in mice. PMID:27255361

  20. Early chronic low-level lead exposure produces glomerular hypertrophy in young C57BL/6J mice.

    PubMed

    Basgen, John M; Sobin, Christina

    2014-02-10

    Early chronic lead exposure continues to pose serious health risks for children, particularly those living in lower socioeconomic environments. This study examined effects on developing glomeruli in young C57BL/6J mice exposed to low (30 ppm), higher (330 ppm) or no lead via dams' drinking water from birth to sacrifice on post-natal day 28. Low-level lead exposed mice [BLL mean (SD); 3.19 (0.70) μg/dL] had an increase in glomerular volume but no change in podocyte number compared to control mice [0.03 (0.01) μg/dL]. Higher-level lead exposed mice [14.68 (2.74) μg/dL] had no change in either glomerular volume or podocyte number. The increase in glomerular volume was explained by increases in glomerular capillary and mesangial volumes with no change in podocyte volume. Early chronic lead exposure yielding very low blood lead levels alters glomerular development in pre-adolescent animals. PMID:24300173

  1. Protective effect of thymol on high fat diet induced diabetic nephropathy in C57BL/6J mice.

    PubMed

    Saravanan, Settu; Pari, Leelevinothan

    2016-02-01

    Obesity is one of several factors implicated in chronic kidney disease (CKD). Thymol, a monoterpene phenolic compound found in the oils of thyme with multiple biological properties especially antidiabetic activity. The present study was undertaken to evaluate the thymol against diabetic nephropathy by high fat diet (HFD)-induced diabetic C57BL/6J mice. After 10 weeks of continuous dietary intervention, HFD (fat- 35.2%) to mice presented characteristic features of progressive nephropathy by significant increased in kidney weight, blood, and urinary parameters, glomerulosclerosis, oxidative stress, hyperlipidemia and subsequent renal injuries. After intragastric administration of thymol (40 mg/kg BW) daily for the subsequent 5 weeks significantly decreased the blood, urinary parameters and kidney weight. Thymol inhibited the activation of transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF). Also, significantly increased the antioxidants and suppresses the lipid peroxidation markers in erythrocytes and kidney tissue compared to the diabetic mice. Thymol downregulated the expression level of sterol regulatory element binding protein-1c (SREBP-1c) and reduced the lipid accumulation in renal. Histopathological study of kidney tissues showed that extracellular mesangial matrix expansion, glomerulosclerosis in diabetic mice were suppressed by thymol. Further, our results indicate that administration of thymol afforded remarkable protection against HFD-induced diabetic nephropathy. PMID:26680107

  2. Prior stress interferes with the anxiolytic effect of exercise in C57BL/6J mice.

    PubMed

    Hare, Brendan D; D'Onfro, Katherine C; Hammack, Sayamwong E; Falls, William A

    2012-12-01

    Recent reports demonstrate that the beneficial effects of voluntary exercise may be sensitive to stress prior to and during the wheel access period. Here, a variate stress procedure is used with socially isolated mice for 7 days prior to the introduction of running wheels to assess the impact of prior and concurrent stress on the anxiolytic effect of exercise. Following stress exposure, functioning or nonfunctioning running wheels were introduced into stressed and unstressed group-housed control cages. Following 3 weeks of wheel access, the anxiolytic effect of exercise was assessed using acoustic startle, stress-induced hyperthermia, and a challenge with the anxiogenic drug metachlorophenylpiperazine (mCPP). Variate stress was demonstrated to interfere with normal weight gain. Further, exercise was not anxiolytic in stressed mice. Consistent with previous reports unstressed exercising mice demonstrated reduced acoustic startle, attenuated stress induced hyperthermia, and a blunted increase in startle following mCPP administration when compared with unstressed sedentary controls. Stressed exercising mice were indistinguishable from stressed sedentary and unstressed sedentary controls on each anxiety measure. Although running distance varied between individual mice, the distance run did not predict the level of anxiety on any measure. These findings suggest that prior and ongoing stress delays or prevents the anxiolytic effect of exercise without affecting exercise itself.

  3. Differences in cocaine-induced place preference persistence, locomotion and social behaviors between C57BL/6J and BALB/cJ mice.

    PubMed

    Wang, Jian-Li; Wang, Bei; Chen, Wen

    2014-09-01

    C57BL/6J and BALB/cJ mice display significant differences in sociability and response to drugs, but the phenotypic variability of their susceptibility to cocaine is still not well known. In this study, the differences between these two mice strains in the persistence of cocaine-induced conditioned place preference (CPP), as well as the locomotion and social behaviors after the 24-hour withdrawal from a four-day cocaine (20 mg/kg/day) administration were investigated. The results showed that the cocaine-induced CPP persisted over two weeks in C57BL/6J mice, while it diminished within one week among BALB/cJ mice. After 24-hours of cocaine withdrawal, high levels of locomotion as well as low levels of social interaction and aggressive behavior were found in C57BL/6J mice, but no significant changes were found in BALB/cJ mice, indicating that cocaine-induced CPP persistence, locomotion and social behavior are not consistent between these two strains, and that overall C57BL/6J mice are more susceptible to cocaine than BALB/cJ mice at the tested doses.

  4. Ulcerative Dermatitis in C57BL/6NCrl Mice on a Low-Fat or High-Fat Diet With or Without a Mineralized Red-Algae Supplement.

    PubMed

    Hampton, Anna L; Aslam, Muhammad N; Naik, Madhav K; Bergin, Ingrid L; Allen, Ron M; Craig, Ronald A; Kunkel, Steve L; Veerapaneni, Indiradevi; Paruchuri, Tejaswi; Patterson, Kathleen A; Rothman, Edward D; Hish, Gerald A; Varani, James; Rush, Howard G

    2015-09-01

    Ulcerative dermatitis (UD) is a spontaneous idiopathic disease that often affects C57BL/6 mice or mice on a C57BL/6 background. UD is characterized by intense pruritus and lesion formation, most commonly on the head or dorsal thorax. Self-trauma likely contributes to wound severity and delayed wound healing. Histologically, changes are nonspecific, consisting of ulceration with neutrophilic and mastocytic infiltration and epithelial hyperplasia and hyperkeratosis. Diet appears to have a profound effect on the development and progression of UD lesions. We investigated the incidence and severity of UD in C57BL/6NCrl mice on a high-fat western-style diet (HFWD) compared with a standard rodent chow. In addition, we examined the protective effects of dietary supplementation with a multimineral-rich product derived from marine red algae on UD in these 2 diet groups. HFWD-fed mice had an increased incidence of UD. In addition, mice on a HFWD had significantly more severe clinical and histologic lesions. Dietary mineral supplementation in mice on a HFWD decreased the histologic severity of lesions and reduced the incidence of UD in female mice in both diets. In conclusion, a high-fat western-style diet may potentiate UD in C57BL/6NCrl mice. Insufficient mineral supply and mineral imbalance may contribute to disease development. Mineral supplementation may be beneficial in the treatment of UD.

  5. Long-term individual housing in C57BL/6J and DBA/2 mice: assessment of behavioral consequences.

    PubMed

    Võikar, V; Polus, A; Vasar, E; Rauvala, H

    2005-06-01

    The aim of the present study was to investigate the effects of individual housing on mouse behavior. The male mice of the C57BL/6J and DBA/2 strains were separated at the age of 4 weeks and kept in individual housing for 7 weeks until behavioral testing began. Their behavior was compared to the group-housed mice in a battery of tests during the following 7 weeks. The single-housed mice were hyperactive and displayed reduced habituation in the tests assessing activity and exploration. Reduced anxiety was established in the elevated plus-maze, but an opposite effect was observed in the dark-light (DL) and hyponeophagia tests. Immobility in the forced swimming test was reduced by social isolation. The DBA mice displayed higher anxiety-like behavior than the B6 mice in the plus-maze and DL exploration test, but hyponeophagia was reduced in the DBA mice. Moreover, all effects of individual housing on the exploratory and emotional behavior were more evident in the DBA than in the B6 mice. Novel object recognition and fear conditioning (FC) were significantly impaired in the single-housed mice, whereas water-maze (WM) learning was not affected. Marked strain differences were established in all three learning tests. The B6 mice performed better in the object recognition and FC tasks. Initial spatial learning in the WM was faster and memory retention slightly enhanced in the B6 mice. The DBA mice displayed lower preference to the new and enhanced preference to the old platform location than the B6 mice after reversal learning in the WM. We conclude that individual housing has strong strain- and test-specific effects on emotional behavior and impairs memory in certain tasks.

  6. The measurement of corneal thickness from center to limbus in vivo in C57BL/6 and BALB/c mice using two-photon imaging.

    PubMed

    Zhang, Hongmin; Wang, Liya; Xie, Yanting; Liu, Susu; Deng, Xianming; He, Siyu; Chen, Guoming; Liu, Hui; Yang, Biao; Zhang, Junjie; Sun, Shengtao; Li, Xiaohua; Li, Zhijie

    2013-10-01

    The mouse corneal thickness is very important for research into the fields of eye disease. However, the in vivo corneal thickness for the entire cornea from the pupil to the limbus was not determined. We measured in vivo corneal layer thicknesses in different corneal areas, from the central cornea to the limbus, in the widely used inbred C57BL/6 and BALB/c mouse strains using two-photon (2 PH) imaging. Eight corneas of the C57BL/6 or BALB/c were scanned using a 2 PH laser scanning fluorescence microscopy system. A total of 14 thicknesses of the different corneal layers, from different corneal regions, were measured using image processing software. In both C57BL/6 and BALB/c mice, the thickness of the corneal layers was inhomogeneous in different areas of the cornea, and all of the layers had their minimum thickness at the limbus. In C57BL/6 mice, the thickness of the corneal layers gradually increased from the central to the paracentral cornea, peaked at the fifth measurement point in the paracentral area, and decreased from this point to the limbus. In BALB/c mice, the thickness of the entire cornea and corneal epithelium had its maximum at the central cornea and gradually decreased from the central cornea to the peripheral cornea and to the limbus. The thickness of the corneal stroma and endothelium had its maximum at the fourth measurement point in the paracentral cornea and gradually decreased from the paracentral cornea to the limbus. The ratio of epithelial thickness to the total corneal thickness gradually decreased from the central cornea to the limbus in both C57BL/6 and BALB/c mice. The minimum ratio was observed at the fourteenth measurement point in both C57BL/6 and BALB/c mice. The ratio of stromal and endothelial to the total corneal thickness gradually increased from the central cornea to the limbus in both C57BL/6 and BALB/c mice. The maximum ratio was observed at the fourteenth measurement point in C57BL/6 mice. The ratio at the first eight

  7. Comparison of tissue concentrations in male and female C57BL/6 mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The tissue-specific response to dietary vitamin K (VK) manipulation has not been well studied in mice. This limits the use of genetically modified mouse models in VK studies. The objective of this study was to determine the sex-specific effects of dietary VK manipulation on serum, liver and extra-he...

  8. Effect of perinatally supplemented flavonoids on brain structure, circulation, cognition, and metabolism in C57BL/6J mice.

    PubMed

    Janssen, Carola I F; Zerbi, Valerio; Mutsaers, Martina P C; Jochems, Mieke; Vos, Claudia A; Vos, Julle O; Berg, Brian M; van Tol, Eric A F; Gross, Gabriele; Jouni, Zeina E; Heerschap, Arend; Kiliaan, Amanda J

    2015-10-01

    Evidence suggests that flavanol consumption can beneficially affect cognition in adults, but little is known about the effect of flavanol intake early in life. The present study aims to assess the effect of dietary flavanol intake during the gestational and postnatal period on brain structure, cerebral blood flow (CBF), cognition, and brain metabolism in C57BL/6J mice. Female wild-type C57BL/6J mice were randomly assigned to either a flavanol supplemented diet or a control diet at gestational day 0. Male offspring remained on the corresponding diets throughout life and performed cognitive and behavioral tests during puberty and adulthood assessing locomotion and exploration (Phenotyper and open field), sensorimotor integration (Rotarod and prepulse inhibition), and spatial learning and memory (Morris water maze, MWM). Magnetic resonance spectroscopy and imaging at 11.7T measured brain metabolism, CBF, and white and gray matter integrity in adult mice. Biochemical and immunohistochemical analyses evaluated inflammation, synaptic plasticity, neurogenesis, and vascular density. Cognitive and behavioral tests demonstrated increased locomotion in Phenotypers during puberty after flavanol supplementation (p = 0.041) but not in adulthood. Rotarod and prepulse inhibition demonstrated no differences in sensorimotor integration. Flavanols altered spatial learning in the MWM in adulthood (p = 0.039), while spatial memory remained unaffected. Additionally, flavanols increased diffusion coherence in the visual cortex (p = 0.014) and possibly the corpus callosum (p = 0.066) in adulthood. Mean diffusion remained unaffected, a finding that corresponds with our immunohistochemical data showing no effect on neurogenesis, synaptic plasticity, and vascular density. However, flavanols decreased CBF in the cortex (p = 0.001) and thalamus (p = 0.009) in adulthood. Brain metabolite levels and neuroinflammation remained unaffected by flavanols. These data suggest

  9. Relationship between methamphetamine-induced dopamine release, hyperthermia, self-injurious behaviour and long term dopamine depletion in BALB/c and C57BL/6 mice.

    PubMed

    Halladay, Alycia K; Kusnecov, Alexander; Michna, Lauri; Kita, Taizo; Hara, Chiaki; Wagner, George C

    2003-07-01

    Differential sensitivity to neurotoxic effects of methamphetamine on striatal dopaminergic neurones between C57BL/6 and BALB/c mice has been established. In the present studies, the interaction of methamphetamine-induced dopamine release, self-injurious behaviour, the neural immune response, and the long-term (3 day) dopamine depletion were examined in these strains after administration of 8 mg/kg methamphetamine. BALB/c mice showed increased hyperthermia compared to the C57BL/6 strain, as well as induction of interleukin-1beta. Additionally, homovanillic acid (HVA) levels, as well as HVA/DA turnover ratios were elevated in the striatum and frontal cortex of BALB/c mice, both compared to untreated mice and to the C57BL/6 strain after a single injection of methamphetamine. Pretreatment with acetaminophen eliminated the methamphetamine-induced hyperthermia in BALB/c mice and reduced body temperature in C57BL/6 mice. However, acetaminophen pretreatment did not affect any parameters of dopaminergic toxicity in the striatum or frontal cortex of the BALB/c strain following repeated methamphetamine injections. Furthermore, acetaminophen pretreatment did not alter the incidence of self-injurious behaviour in BALB/c mice. Therefore, hyperthermia and methamphetamine-induced toxicity appear to be independent phenomena while self-injurious behaviour may provide a better predictor of toxicity, which, in turn, may be related to dopamine release.

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

    PubMed

    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.

  11. Motor responses of autoimmune NZB/B1NJ and C57BL/6Nnia mice to arecoline and nicotine.

    PubMed

    Retz, K C; Trimmer, C K; Forster, M J; Lal, H

    1987-10-01

    In 11-13 month C57BL/6Nnia mice, arecoline produced a dose-dependent decrease in motor activity at doses of 0.64-2.5 mg/kg, whereas at doses of 5.0-20.0 mg/kg arecoline produced a dose-dependent increase in motor activity. In marked contrast, age-matched NZB/B1NJ (New Zealand Black) mice failed to exhibit the first phase of the response, but showed a greater dose-dependent increase in motor activity following the doses of 10 and 20 mg/kg. Nicotine, 0.64-2.5 mg/kg, produced a dose-dependent decrease in motor activity in both strains. The effects of arecoline and nicotine were antagonized by scopolamine (2.5 mg/kg) and mecamylamine (1.0 mg/kg), respectively. These findings suggest that muscarinic neurotransmission may be altered in NZB/B1NJ mice, which produce brain-reactive autoantibodies, exhibit learning/memory dysfunctions, and also exhibit a loss of neurons staining positive for choline acetyltransferase.

  12. Intracage ammonia levels in static and individually ventilated cages housing C57BL/6 mice on 4 bedding substrates.

    PubMed

    Ferrecchia, Christie E; Jensen, Kelly; Van Andel, Roger

    2014-03-01

    The relationship among ammonia levels, cage-changing frequency, and bedding types is an important and potentially controversial topic in the laboratory animal science community. Some bedding options may not provide sufficient urine absorption and bacterial regulation to minimize ammonia production during the interval between cage changes. High intracage ammonia levels can cause subclinical degeneration and inflammation of nasal passages, rhinitis and olfactory epithelial necrosis in exposed mice. Here we sought to compare the effects of 4 commonly used bedding substrates (1/4-in. irradiated corncob, reclaimed wood pulp, aspen wood chips, and recycled newspaper) on ammonia generation when housing female C57BL/6 mice in static and individually ventilated caging. Intracage ammonia levels were measured daily for 1 wk (static cage experiment) or 2 wk (IVC experiment). The results of this study suggest that the corncob, aspen wood chip, and recycled newspaper beddings that we tested are suitable for once-weekly cage changing for static cages and for changing every 2 wk for IVC. However, ammonia levels were not controlled appropriately in cages containing reclaimed wood pulp bedding, and pathologic changes occurred within 1 wk in the nares of mice housed on this bedding in static cages.

  13. Comprehensive systems biology analysis of a 7-month cigarette smoke inhalation study in C57BL/6 mice

    PubMed Central

    Ansari, Sam; Baumer, Karine; Boué, Stéphanie; Dijon, Sophie; Dulize, Remi; Ekroos, Kim; Elamin, Ashraf; Foong, Clement; Guedj, Emmanuel; Hoeng, Julia; Ivanov, Nikolai V.; Krishnan, Subash; Leroy, Patrice; Martin, Florian; Merg, Celine; Peck, Michael J.; Peitsch, Manuel C.; Phillips, Blaine; Schlage, Walter K.; Schneider, Thomas; Talikka, Marja; Titz, Bjoern; Vanscheeuwijck, Patrick; Veljkovic, Emilija; Vihervaara, Terhi; Vuillaume, Gregory; Woon, Ching Qing

    2016-01-01

    Smoking of combustible cigarettes has a major impact on human health. Using a systems toxicology approach in a model of chronic obstructive pulmonary disease (C57BL/6 mice), we assessed the health consequences in mice of an aerosol derived from a prototype modified risk tobacco product (pMRTP) as compared to conventional cigarettes. We investigated physiological and histological endpoints in parallel with transcriptomics, lipidomics, and proteomics profiles in mice exposed to a reference cigarette (3R4F) smoke or a pMRTP aerosol for up to 7 months. We also included a cessation group and a switching-to-pMRTP group (after 2 months of 3R4F exposure) in addition to the control (fresh air-exposed) group, to understand the potential risk reduction of switching to pMRTP compared with continuous 3R4F exposure and cessation. The present manuscript describes the study design, setup, and implementation, as well as the generation, processing, and quality control analysis of the toxicology and ‘omics’ datasets that are accessible in public repositories for further analyses. PMID:26731301

  14. Pharmacokinetic characterization of mangosteen (Garcinia mangostana) fruit extract standardized to α-mangostin in C57BL/6 mice.

    PubMed

    Petiwala, Sakina M; Li, Gongbo; Ramaiya, Atulkumar; Kumar, Anoop; Gill, Ravinder K; Saksena, Seema; Johnson, Jeremy J

    2014-04-01

    Previously, we have reported the pharmacokinetic (PK) properties of α-mangostin in mice. For this study, we evaluated the PK profile of α-mangostin using a standardized mangosteen extract in C57BL/6 mice. The primary objective was to determine the PK properties of α-mangostin when administered as an extract. This experiment was designed to test our primary hypothesis that α-mangostin in an extract should achieve a desirable PK profile. This is especially relevant as dietary supplements of mangosteen fruit are regularly standardized to α-mangostin. Mice received 100 mg/kg of mangosteen fruit extract orally, equivalent to 36 mg/kg of α-mangostin, and plasma samples were analyzed over a 24-hour period. Concentrations of α-mangostin were determined by liquid chromatography-tandem mass spectrometry. In addition, we evaluated the stability in the presence of phase I and phase II enzymes in liver and gastrointestinal microsomes. Furthermore, we identified evidence of phase II metabolism of α-mangostin. Further research will be required to determine if less abundant xanthones present in the mangosteen may modulate the PK parameters of α-mangostin.

  15. Changes in lymphocyte subsets and macrophage functions from high, short-term dietary ethanol in C57/BL6 mice

    SciTech Connect

    Watson, R.R.; Prabhala, R.H.; Abril, E.; Smith, T.L.

    1988-01-01

    Chronic administration of a diet containing 7% ethanol (36% of total calories) for 8 days to male C57/BL6 mice resulted in significant changes in functioning of macrophages. Peritoneal exudate macrophages from the ethanol-fed mice released more tumor cell cytotoxic materials upon culturing in vitro than cells from controls. However, peritoneal exudate cells continued to respond to exogenous beta carotene in vitro to produce additional cytotoxic materials. Phagocytosis of sheep red blood cells in vitro was suppressed in cells from ethanol treated mice. The number of splenic lymphocytes of various subsets was significantly changed by the ethanol exposure. Total T cells and T suppressor cells were lower, with a significant decrease in B cells containing IgM on their surface. The percentage of spleen cells showing markers for macrophage functions and their activation were significantly reduced. It is concluded that short-term chronic consumption of dietary ethanol, which was sufficient to produce physical dependence, results in significant alterations in lymphocyte subtypes and suppression of some macrophage functions.

  16. D-psicose, a sweet monosaccharide, ameliorate hyperglycemia, and dyslipidemia in C57BL/6J db/db mice.

    PubMed

    Baek, S H; Park, S J; Lee, H G

    2010-03-01

    D-psicose has been implicated in glycemic control in recent animal and human studies. In this study, the effects of D-psicose on glycemic responses, insulin release, and lipid profiles were compared with those of D-glucose and D-fructose in a genetic diabetes model. C57BL/6J db/db mice were orally supplemented with 200 mg/kg BW of D-psicose, D-glucose, or D-fructose, respectively, while diabetes control or wild type mice were supplemented with water instead. D-psicose sustained weight gain by about 10% compared to other groups. The initial blood glucose level maintained from 276 to 305 mg/dL during 28 d in the D-psicose group, whereas a 2-fold increase was found in other groups (P < 0.05) among diabetic mice. D-psicose significantly improved glucose tolerance and the areas under the curve (AUC) for glucose among diabetes (P < 0.05), but had no effect on serum insulin concentration. The plasma lipid profile was not changed by supplemental monosacchrides, although the ratio of LDL-cholesterol/HDL-cholesterol was ameliorated by D-psicose. The administration of D-psicose reversed hepatic concentrations of triglyceride (TG) and total cholesterol (TC) by 37.88% and 62.89%, respectively, compared to the diabetes control (P < 0.05). The current findings suggest that D-psicose shows promise as an antidiabetic and may have antidyslipidemic effects in type 2 diabetes.

  17. Development and expression of maternal behavior in naïve female C57BL/6 mice.

    PubMed

    Alsina-Llanes, Marcela; De Brun, Victoria; Olazábal, Daniel E

    2015-03-01

    Naïve female mice are usually described as spontaneously maternal. We investigated how many exposures to pups (15 min vs. 1 hr) were needed to induce full maternal behavior (FMB) in 20-22, 30-35, 60-65-days-old naïve female mice (C57BL/6), and how cohabitation with the parturient mother and newborn siblings facilitated juvenile maternal behavior (MB). Only 20% of the adults displayed FMB immediately after the first exposure to pups. Incomplete MB was present in 11%, 20%, and 30% of juveniles, adolescents and adults, respectively. Three-sixty minute exposures to pups induced FMB in all adult subjects. All naïve juveniles that were not exposed to their siblings and maternal fluids failed to show maternal behavior. In contrast, more than half of the juveniles present at their homecage during delivery of a second litter showed incomplete MB (34.5%) or FMB (21.5%) when tested individually housed in a novel cage. This study suggests that most adult female mice are not spontaneously maternal but gradually sensitized. Besides, naïve juveniles could be inhibited or not motivated to show MB, but display adult-like behavior toward pups if previously exposed to newborn siblings and maternal fluids.

  18. Differential Effect of γ-radiation-induced Heme Oxygenase-1 Activity in Female and Male C57BL/6 Mice

    PubMed Central

    Han, Youngsoo; Platonov, Alexander; Akhalaia, Medea; Yun, Yeon-Sook

    2005-01-01

    Ionizing radiation produces reactive oxygen species, which exert diverse biological effects on cells and animals. We investigated alterations of heme oxygenase (HO) and non-protein thiols (NPSH), which are known as two major anti-oxidant enzymes, in female and male C57BL/6 mice in the lung, liver, and brain after whole-body γ-irradiation with 10 Gy (1-7 days) as well as in the lung after whole-thorax γ-irradiation (WTI) with 12.5 Gy (1-26 weeks). Most significant alteration of HO activity was observed in the liver, which elevated 250% in males. NPSH level in female liver was increased on the 5th-7th days but decreased in males on the 3rd day. In the lung, the elevation of HO activity in both sexes and the pattern of NPSH change were similar to that of the liver. On the other hand, the increase of HO activity on the 16th week and the decrease of NPSH level on the 2nd week were observed only in male lung after WTI. This study shows that the liver is the most sensitive tissue to γ-irradiation-induced alterations of HO activity in both female and male mice. In addition, there exists significant differential effect of γ-irradiation on anti-oxidant system in female and male mice. PMID:16100440

  19. Scratching Responses to Epidermal Injury in C57BL/6, DBA/2, BALB/c, and CD1 Mice.

    PubMed

    Sargent, Jennifer L; Löhr, Christiane V; Diggs, Helen E

    2016-01-01

    Whereas early investigations into ulcerative dermatitis (UD) focused on the possibility of a primary dermatopathology, several recent studies have advocated scratching behavior as a primary driver for UD. The aim of this study was to assess whether B6 mice exhibit excessive scratching under resting conditions or when provoked by epidermal barrier disruption. We hypothesized that B6 mice would exhibit more spontaneous scratching behavior and that B6 mice would be more pruritic after mild epidermal barrier injury compared with the other strains and stock tested. The behavior of the retired breeder female C57BL/6J, DBA/2J, BALB/cByJ, and Crl:CD1 mice was videotaped for 60 min. Behavior filming occurred at 17:15 and at 07:00 the next morning prior to (baseline) and after tape-stripping to initiate epidermal barrier disruption. Scratching duration was recorded as brief (less than 3 s) or prolonged (3 s or longer), on the basis of observations during a pilot study. In contrast to the hypothesis, B6 mice did not scratch significantly more frequently, have more long-duration scratching events, nor have a higher median scratching duration of prolonged scratching as compared with the other types of mice tested. In fact, B6 mice showed the lowest average scratching frequency and duration under both conditions. B6 mice demonstrated increased scratching behavior after epidermal barrier disruption, but the increased scratching did not surpass the rate or duration of scratching in the other types of mice tested. These findings do not support the idea that a strain-related tendency toward exaggerated scratching behavior under resting or epidermal barrier disruption conditions predisposes B6 mice to UD. PMID:27298245

  20. Postanesthetic Effects of Isoflurane on Behavioral Phenotypes of Adult Male C57BL/6J Mice

    PubMed Central

    Asakura, Ayako; Kobayashi, Ayako; Takase, Kenkichi; Goto, Takahisa

    2015-01-01

    Isoflurane was previously the major clinical anesthetic agent but is now mainly used for veterinary anesthesia. Studies have reported widespread sites of action of isoflurane, suggesting a wide array of side effects besides sedation. In the present study, we phenotyped isoflurane-treated mice to investigate the postanesthetic behavioral effects of isoflurane. We applied comprehensive behavioral test batteries comprising sensory test battery, motor test battery, anxiety test battery, depression test battery, sociability test battery, attention test battery, and learning test battery, which were started 7 days after anesthesia with 1.8% isoflurane. In addition to the control group, we included a yoked control group that was exposed to the same stress of handling as the isoflurane-treated animals before being anesthetized. Our comprehensive behavioral test batteries revealed impaired latent inhibition in the isoflurane-treated group, but the concentration of residual isoflurane in the brain was presumably negligible. The yoked control group and isoflurane-treated group exhibited higher anxiety in the elevated plus-maze test and impaired learning function in the cued fear conditioning test. No influences were observed in sensory functions, motor functions, antidepressant behaviors, and social behaviors. A number of papers have reported an effect of isoflurane on animal behaviors, but no systematic investigation has been performed. To the best of our knowledge, this study is the first to systematically investigate the general health, neurological reflexes, sensory functions, motor functions, and higher behavioral functions of mice exposed to isoflurane as adults. Our results suggest that the postanesthetic effect of isoflurane causes attention deficit in mice. Therefore, isoflurane must be used with great care in the clinical setting and veterinary anesthesia. PMID:25806517

  1. Differential expression of brain immune genes and schizophrenia-related behavior in C57BL/6N and DBA/2J female mice.

    PubMed

    Ma, Li; Kulesskaya, Natalia; Võikar, Vootele; Tian, Li

    2015-03-30

    Mounting evidence suggests the association of immune genes with complex neuropsychiatric diseases, such as schizophrenia. However, immune gene expression in the brain and their involvement in schizophrenia-related behavior in animal models have not been well studied so far. We analyzed the social (resident-intruder) and sensorimotor gating (pre-pulse inhibition (PPI) of acoustic startle) behaviors, and expression profiles of several brain immune genes in adult C57BL/6N and DBA/2J female mice. Compared to C57BL/6N mice, DBA/2J mice exhibited less social interaction in the resident-intruder test and reduced pre-pulse inhibition. The mRNA levels of Il1b and Il6 genes were significantly higher in the cortex and hypothalamus, while the mRNA level of C1qb was lower in the cortex, hippocampus and hypothalamus of DBA/2J mice compared to C57BL/6N mice. Furthermore, Tnfsf13b was up-regulated in the cortex and hippocampus, and so did Cd47 in the hippocampus, while Cx3cl1 was down-regulated in the cortex of DBA/2J mice. Our study demonstrates the differential expression of several immune genes in C57BL/6N and DBA/2J strains and more importantly provides clues on their potential importance in regulating schizophrenia-related endophenotypes in animal models.

  2. Perinatal exposure to low-dose methoxychlor impairs testicular development in C57BL/6 mice.

    PubMed

    Du, Xiaohong; Zhang, Hua; Liu, Yuanwu; Yu, Wanpeng; Huang, Chaobin; Li, Xiangdong

    2014-01-01

    Methoxychlor (MXC), an organochlorine pesticide, has adverse effects on male reproduction at toxicological doses. Humans and wild animals are exposed to MXC mostly through contaminated dietary intake. Higher concentrations of MXC have been found in human milk, raising the demand for the risk assessment of offspring after maternal exposure to low doses of MXC. In this study, pregnant mice (F0) were given intraperitoneal daily evening injections of 1 mg/kg/d MXC during their gestational (embryonic day 0.5, E0.5) and lactational periods (postnatal day 21.5, P21.5), and the F1 males were assessed. F1 testes were collected at P0.5, P21.5 and P45.5. Maternal exposure to MXC disturbed the testicular development. Serum testosterone levels decreased, whereas estradiol levels increased. To understand the molecular mechanisms of exposure to MXC in male reproduction, the F1 testes were examined for changes in the expression of steroidogenesis- and spermatogenesis- related genes. RT-PCR analysis demonstrated that MXC significantly decreased Cyp11a1 and increased Cyp19a1; furthermore, it downregulated certain spermatogenic genes (Dazl, Boll, Rarg, Stra8 and Cyclin-a1). In summary, perinatal exposure to low-dose MXC disturbs the testicular development in mice. This animal study of exposure to low-dose MXC in F1 males suggests similar dysfunctional effects on male reproduction in humans.

  3. Differences in memory development among C57BL/6NCrl, 129S2/SvPasCrl, and FVB/NCrl mice after delay and trace fear conditioning.

    PubMed

    March, Amelia; Borchelt, David; Golde, Todd; Janus, Christopher

    2014-02-01

    Fear-conditioning testing paradigms have been used to study differences in memory formation between inbred mouse strains, including numerous mouse models of human diseases. In this study, we characterized the conditioned fear memory of 3 inbred strains: C57BL/6NCrl, 129S2/SvPasCrl, and FVB/NCrl, obtained from Charles River Laboratories. We used 2 training paradigms: delay conditioning, in which an unconditional stimulus coterminates with the presentation of a conditional stimulus, and trace conditioning, in which the conditional and unconditional stimuli are separated by a trace interval. In each paradigm, we evaluated the recent (3 d) and remote (25 d) memory of the mice by using a longitudinal design. Our results showed that both C57BL/6NCrl and 129S2/SvPasCrl mice developed strong and long-lasting context and tone memories in both paradigms, but FVB/NCrl mice showed a weaker but nevertheless consistent tone memory after delay training. Tone memory in the FVB strain was stronger in male than female mice. The remote tone memory of 129S2/SvPasCrl mice diminished after delay training but was stable and stronger than that of C57BL/6NCrl mice after trace training. In conclusion, both C57BL/6NCrl and 129S2/SvPasCrl mice showed reliable and long-lasting fear memory after delay or trace training, with 129 mice showing particularly strong tone memory after trace conditioning. The FVB/NCrl strain, especially male mice, showed reliable tone fear memory after delay training. Our findings confirm that both C57BL/6NCrl and 129S2/SvPasCrl mice develop strong context and tone memory in delay and trace fear-conditioning paradigms. PMID:24672832

  4. Oral Resveratrol Prevents Osteoarthritis Progression in C57BL/6J Mice Fed a High-Fat Diet

    PubMed Central

    Gu, Hailun; Li, Keyu; Li, Xingyao; Yu, Xiaolu; Wang, Wei; Ding, Lifeng; Liu, Li

    2016-01-01

    The effects of resveratrol on osteoarthritis (OA) pathogenesis have been demonstrated in vitro and in animal models employing intra-articular injections. However, the potential for oral resveratrol supplements to mediate protective effects on OA have not been examined. Therefore, the aim of the present study was to investigate the potential anti-OA effects of oral resveratrol on mice fed a high-fat diet (HFD). C57BL/6J male mice were fed either a standard diet or a HFD, and a subset of the latter also received varying doses of resveratrol. Twelve weeks later, all of the animals were sacrificed and knee joints were evaluated with histological, immunohistochemical, and TUNEL analyses. Mice that received a HFD had significantly greater body weights than the control mice and also exhibited features consistent with knee OA. The mice that received a HFD in combination with low, intermediate, or high doses of resveratrol were only slightly heavier than the control mice at the end of 12 weeks. Quantitative histological assessments indicated that resveratrol treatment partly recovered joint structure in the mice that received a HFD, while high doses of resveratrol prevented the degradation of type II collagen into C-telopeptide of type II collagen (CTX-II) and retained type II collagen expression in cartilage. Furthermore, TUNEL analyses revealed a reduction in chondrocyte apoptosis in the resveratrol-treated mice compared with the HFD mice. Thus, oral resveratrol appears to exert anti-OA effects in a mouse model of HFD-induced OA, thereby highlighting the potential preventive and therapeutic value of administering resveratrol for obesity-associated OA. PMID:27104565

  5. Early gestational exposure to moderate concentrations of ethanol alters adult behaviour in C57BL/6J mice.

    PubMed

    Sanchez Vega, Michelle C; Chong, Suyinn; Burne, Thomas H J

    2013-09-01

    Alcohol consumption during pregnancy has deleterious effects on the developing foetus ranging from subtle physical deficits to severe behavioural abnormalities and is encompassed under a broad umbrella term, foetal alcohol spectrum disorders (FASD). High levels of exposure show distinct effects, whereas the consequences of moderate exposures have been less well studied. The aim of this study was to examine the effects of a moderate dose ethanol exposure using an ad libitum drinking procedure during the first eight days of gestation in mice on the behavioural phenotype of adult offspring. Adult female C57Bl/6J mice were mated and exposed to either 10% (v/v) ethanol or water for the first 8 days of gestation (GD 0-8), and then offered water for the rest of gestation. Early developmental milestone achievement was assessed in offspring at postnatal days (P) 7, 14 and 21. Adult offspring underwent a comprehensive battery of behavioural tests to examine a range of behavioural domains including locomotion, exploration, anxiety, social behaviour, learned helplessness, sensorimotor gating, and nociception, as well as spatial memory in a water maze. Ethanol-exposed mice had similar postnatal developmental trajectories to water-exposed mice. However, the ethanol-exposed mice showed increased hyperlocomotion at P 14, 21 and 70 (p<0.05). Increased exploration and heightened motivation were also observed in adult mice. Furthermore, ethanol-exposed mice showed a significant improvement in memory in the water maze. The main findings were that mice had persistent and long lasting alterations in behaviour, including hyperactivity and enhanced spatial memory. These data suggest that even moderate dose ethanol exposure in early gestation has long term consequences on brain function and behaviour in mice. PMID:23756143

  6. Hydroxypropylated distarch phosphate versus unmodified tapioca starch: fat oxidation and endurance in C57BL/6J mice.

    PubMed

    Haramizu, Satoshi; Shimotoyodome, Akira; Fukuoka, Daisuke; Murase, Takatoshi; Hase, Tadashi

    2012-09-01

    An RS4-type resistant starch is a chemically modified starch that shows reduced availability in comparison to the corresponding unmodified starch. Hydroxypropylated distarch phosphate (HDP) is an RS4-type resistant starch that increases energy expenditure and prevents high-fat diet-induced obesity through increased hepatic fatty acid oxidation. The aim of this study was to clarify the acute effects of HDP from tapioca starch (HPdTSP) on physical performance in mice. Male C57BL/6J mice were used to examine the effects of a single administration of 2 mg/g body weight HPdTSP or unmodified tapioca starch (TS) on postprandial responses in serum metabolic parameters, running endurance capacity on a treadmill, whole-body energy metabolism during exercise, activity of enzymes involved in fatty acid oxidation, liver and gastrocnemius muscle glycogen content, and serum glucose, insulin, non-esterified fatty acid, lactate, and triglyceride levels after exercise. Running time to fatigue was significantly greater in HPdTSP mice than in TS mice. Furthermore, HPdTSP maintained higher fat oxidation and this was associated with a greater activity of enzymes in fatty acid oxidation in the muscle during exercise. The blood lactate and serum insulin levels after exercise was significantly lower in HPdTSP mice than in TS mice. Liver glycogen was significantly higher in HPdTSP mice than in TS mice. These results suggest that acute oral administration of the RS4-type resistant starch, HPdTSP, maintained higher fat oxidation and reduced liver glycogen consumption during exercise and increased running endurance capacity in mice. PMID:22270482

  7. Early gestational exposure to moderate concentrations of ethanol alters adult behaviour in C57BL/6J mice.

    PubMed

    Sanchez Vega, Michelle C; Chong, Suyinn; Burne, Thomas H J

    2013-09-01

    Alcohol consumption during pregnancy has deleterious effects on the developing foetus ranging from subtle physical deficits to severe behavioural abnormalities and is encompassed under a broad umbrella term, foetal alcohol spectrum disorders (FASD). High levels of exposure show distinct effects, whereas the consequences of moderate exposures have been less well studied. The aim of this study was to examine the effects of a moderate dose ethanol exposure using an ad libitum drinking procedure during the first eight days of gestation in mice on the behavioural phenotype of adult offspring. Adult female C57Bl/6J mice were mated and exposed to either 10% (v/v) ethanol or water for the first 8 days of gestation (GD 0-8), and then offered water for the rest of gestation. Early developmental milestone achievement was assessed in offspring at postnatal days (P) 7, 14 and 21. Adult offspring underwent a comprehensive battery of behavioural tests to examine a range of behavioural domains including locomotion, exploration, anxiety, social behaviour, learned helplessness, sensorimotor gating, and nociception, as well as spatial memory in a water maze. Ethanol-exposed mice had similar postnatal developmental trajectories to water-exposed mice. However, the ethanol-exposed mice showed increased hyperlocomotion at P 14, 21 and 70 (p<0.05). Increased exploration and heightened motivation were also observed in adult mice. Furthermore, ethanol-exposed mice showed a significant improvement in memory in the water maze. The main findings were that mice had persistent and long lasting alterations in behaviour, including hyperactivity and enhanced spatial memory. These data suggest that even moderate dose ethanol exposure in early gestation has long term consequences on brain function and behaviour in mice.

  8. Effects of chronic low- and high-dose nicotine on cognitive flexibility in C57BL/6J mice

    PubMed Central

    Ortega, Leonardo A.; Tracy, Brittany A.; Gould, Thomas J.; Parikh, Vinay

    2012-01-01

    The addictive nature of nicotine remains a global health problem. Despite the availability of treatments for smoking cessation, relapse to smoking after quit attempts still remains very high. Here, we evaluated the effects of chronic nicotine in male C57BL/6J mice in an operant cognitive flexibility task that required the animals to progress sequentially through multiple phases including visual discrimination, strategy shifting and response reversal. As frontostriatal circuits involving discrete regions of dorsal striatum contribute directly to decision-making processes, and BDNF modulates synaptic plasticity and learning, we also assessed the effects of nicotine on striatal BDNF expression. Osmotic minipumps containing either of the two doses of nicotine (low: 6.3 mg/kg/day; high: 18 mg/kg/day) or saline (control) were implanted for chronic delivery that lasted 4 weeks. Nicotine-treated mice exhibited greater response accuracy during visual discrimination. Neither dose of nicotine affected learning of new egocentric response strategy during set-shifting. However, higher but not lower dose of nicotine impaired reversal learning by increasing perseverative responding to the previously non-reinforced stimulus. Furthermore, this effect was associated with reduced BDNF levels in the dorsal striatum. Collectively, these findings suggest that higher relapse rates often observed in high nicotine-dependent smokers may be attributed to impairments in inhibitory control processes. Moreover, striatal BDNF may play a critical role in nicotine-induced alterations in cognitive flexibility. PMID:23103711

  9. Hepatoprotective Effect of Terminalia chebula against t-BHP-Induced Acute Liver Injury in C57/BL6 Mice

    PubMed Central

    Choi, Min-Kyung; Kim, Hyeong-Geug; Han, Jong-Min; Lee, Jin-Seok; Lee, Jong Suk; Chung, Sun Ho; Son, Chang-Gue

    2015-01-01

    We aimed to identify the hepatoprotective effects of Terminalia chebula water extract (TCW) and its corresponding pharmacological actions using C57/BL6 mice model of tert-butylhydroperoxide-(t-BHP-) induced acute liver injury. Mice were orally administered with TCW (0, 50, 100, or 200 mg/kg) or gallic acid (100 mg/kg) for 5 days before t-BHP (2.5 mM/kg) injection. Liver enzymes, histopathology, oxidative stress parameters, antioxidant components, and inflammatory cytokines were examined 18 h after t-BHP injection. t-BHP injection caused dramatic elevation of serum AST, ALT, and LDH level, while TCW pretreatment notably attenuated these elevations. Inflammatory cytokines including TNF-α, IL-1β, and IL-6 were notably increased in hepatic tissues, and then these were efficiently attenuated by TCW pretreatment. t-BHP injection notably increased malondialdehyde, total reactive oxygen species, and nitric oxide in the liver tissue, while it markedly dropped the antioxidant activities including total antioxidant capacity, total glutathione contents, glutathione peroxidase, superoxide dismutase, and catalase. TCW pretreatment remarkably ameliorated these alterations, and these effects were relevant to gene expressions. Histopathological examinations supported the above findings. Collectively, these findings well prove that TCW beneficially prevents acute and severe liver injury and clarify its corresponding mechanisms involved in the inhibition of oxidative stress and inflammatory cytokines. PMID:25691908

  10. The synthetic cathelicidin HHC-10 inhibits Mycobacterium bovis BCG in vitro and in C57BL/6 mice.

    PubMed

    Llamas-González, Yessica Yadira; Pedroza-Roldán, César; Cortés-Serna, Marissa Beatriz; Márquez-Aguirre, Ana Laura; Gálvez-Gastélum, Francisco Javier; Flores-Valdez, Mario Alberto

    2013-04-01

    Tuberculosis causes close to 1.5 million deaths in the world, with new cases exceeding 9 million in recent years. Coinfection with HIV further worsens the global situation. New molecules that overcome the limitations of currently used drugs are needed. We aimed to determine whether HHC-10 is active against the Mycobacterium tuberculosis complex bacteria Mycobacterium bovis bacille calmette guerin (BCG) in vitro and in vivo. For this, HHC-10 was tested in vitro using different peptide concentrations, and in vivo, in C57BL/6 mice infected intratracheally, at two doses (1.25 and 2.5 mg kg(-1), once a week, 4 weeks). Interferon (IFN)-γ, TNF-α, interleukin (IL)-4, and IL-10 mRNA transcript levels were compared between treated and nontreated mice. In vitro, HHC-10 decreased 69% and 88% the number of colony-forming units (CFU) per millileter recovered after 24-hr treatment at 50 and 100 μg/ml, respectively. In vivo, BCG CFUs in mouse lungs were reduced 77.8% and 95.8% at 1.25 and 2.5 mg kg(-1), respectively. IFN-γ expression was lower in the HHC-10-treated group than that of nontreated animals. Considering genomic conservation between BCG and M. tuberculosis, the in vitro and in vivo activities of HHC-10 observed in this study suggest that the use of this peptide may be useful as therapeutic agent against tuberculosis.

  11. The effect of surgical and psychological stress on learning and memory function in aged C57BL/6 mice.

    PubMed

    Zhang, C; Li, C; Xu, Z; Zhao, S; Li, P; Cao, J; Mi, W

    2016-04-21

    Postoperative cognitive dysfunction (POCD) is an important complication following major surgery and general anesthesia in older patients. However, the etiology of POCD remains largely to be determined. It is unknown how surgical stress and psychological stress affect the postoperative learning and memory function in geriatric patients. We therefore established a pre-clinical model in aged C57BL/6 mice and aimed to investigate the effects of surgical stress and psychological stress on learning and memory function and the possible roles of the protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway. The surgical stress was induced by abdominal surgery under local anesthesia, and the psychological stress was induced by a communication box. Cognitive functions and markers of the AKT/mTOR pathway were assessed at 1, 3 and 7 days following the stress. The impairments of learning and memory function existed for up to 7 days following surgical stress and surgical stress plus psychological stress, whereas the psychological stress did not affect the cognitive function alone or combined with surgical stress. Analysis of brain tissue revealed a significant involvement of the AKT/mTOR pathway in the impairment of cognition. These data suggested that surgical stress could induce cognitive impairment in aged mice and perioperative psychological stress is not a constitutive factor of POCD. The AKT/mTOR pathway is likely involved as one of the underlying mechanisms of the development of POCD.

  12. Benzene-Induced Aberrant miRNA Expression Profile in Hematopoietic Progenitor Cells in C57BL/6 Mice.

    PubMed

    Wei, Haiyan; Zhang, Juan; Tan, Kehong; Sun, Rongli; Yin, Lihong; Pu, Yuepu

    2015-11-12

    Benzene is a common environmental pollutant that causes hematological alterations. MicroRNAs (miRNAs) may play a role in benzene-induced hematotoxicity. In this study, C57BL/6 mice showed significant hematotoxicity after exposure to 150 mg/kg benzene for 4 weeks. Benzene exposure decreased not only the number of cells in peripheral blood but also hematopoietic progenitor cells in the bone marrow. Meanwhile, RNA from Lin(-) cells sorted from the bone marrow was applied to aberrant miRNA expression profile using Illumina sequencing. We found that 5 miRNAs were overexpressed and 45 miRNAs were downregulated in the benzene exposure group. Sequencing results were confirmed through qRT-PCR. Furthermore, we also identified five miRNAs which significantly altered in Lin(-)c-Kit⁺ cells obtained from benzene-exposed mice, including mmu-miR-34a-5p; mmu-miR-342-3p; mmu-miR-100-5p; mmu-miR-181a-5p; and mmu-miR-196b-5p. In summary, we successfully established a classical animal model to induce significant hematotoxicity by benzene injection. Benzene exposure may cause severe hematotoxicity not only to blood cells in peripheral circulation but also to hematopoietic cells in bone marrow. Benzene exposure also alters miRNA expression in hematopoietic progenitor cells. This study suggests that benzene induces alteration in hematopoiesis and hematopoiesis-associated miRNAs.

  13. Metformin Suppresses Diethylnitrosamine-Induced Liver Tumorigenesis in Obese and Diabetic C57BL/KsJ-+Leprdb/+Leprdb Mice

    PubMed Central

    Shirakami, Yohei; Baba, Atsushi; Kochi, Takahiro; Kubota, Masaya; Tsurumi, Hisashi; Tanaka, Takuji; Moriwaki, Hisataka

    2015-01-01

    Obesity and related metabolic disorders, such as diabetes mellitus, raise the risk of liver carcinogenesis. Metformin, which is widely used in the treatment of diabetes, ameliorates insulin sensitivity. Metformin is also thought to have antineoplastic activities and to reduce cancer risk. The present study examined the preventive effect of metformin on the development of diethylnitrosamine (DEN)-induced liver tumorigenesis in C57BL/KsJ-+Leprdb/+Leprdb (db/db) obese and diabetic mice. The mice were given a single injection of DEN at 2 weeks of age and subsequently received drinking water containing metformin for 20 weeks. Metformin administration significantly reduced the multiplicity of hepatic premalignant lesions and inhibited liver cell neoplasms. Metformin also markedly decreased serum levels of insulin and reduced insulin resistance, and inhibited phosphorylation of Akt, mammalian target of rapamycin (mTOR), and p70S6 in the liver. Furthermore, serum levels of leptin were decreased, while those of adiponectin were increased by metformin. These findings suggest that metformin prevents liver tumorigenesis by ameliorating insulin sensitivity, inhibiting the activation of Akt/mTOR/p70S6 signaling, and improving adipokine imbalance. Therefore, metformin may be a potent candidate for chemoprevention of liver tumorigenesis in patients with obesity or diabetes. PMID:25879666

  14. No Overt Deficits in Aged Tau-Deficient C57Bl/6.Mapttm1(EGFP)Kit GFP Knockin Mice

    PubMed Central

    van Hummel, Annika; Bi, Mian; Ippati, Stefania; van der Hoven, Julia; Volkerling, Alexander; Lee, Wei S.; Tan, Daniel C. S.; Bongers, Andre; Ittner, Arne; Ke, Yazi D.; Ittner, Lars M.

    2016-01-01

    Several mouse lines with knockout of the tau-encoding MAPT gene have been reported in the past; they received recent attention due to reports that tau reduction prevented Aβ-induced deficits in mouse models of Alzheimer’s disease. However, the effects of long-term depletion of tau in vivo remained controversial. Here, we used the tau-deficient GFP knockin line Mapttm1(EGFP)kit on a pure C57Bl/6 background and subjected a large cohort of males and females to a range of motor, memory and behavior tests and imaging analysis, at the advanced age of over 16 months. Neither heterozygous nor homozygous Mapttm1(EGFP)kit mice presented with deficits or abnormalities compared to wild-type littermates. Differences to reports using other tau knockout models may be due to different genetic backgrounds, respective gene targeting strategies or other confounding factors, such as nutrition. To this end, we report no functional or morphological deficits upon tau reduction or depletion in aged mice. PMID:27736877

  15. Anti-Diabetic Effect of Aster sphathulifolius in C57BL/KsJ-db/db Mice.

    PubMed

    Yin, Xingfu; Huang, Yuhua; Jung, Da-Woon; Chung, Hee Chul; Choung, Se Young; Shim, Jae-Hoon; Kang, Il-Jun

    2015-09-01

    In this study, we investigated the anti-diabetic effect of Aster sphathulifolius (AS) extract in C57BL/KsJ-db/db mice. The db/db mice were orally administered with AS 50% ethanol extract at concentrations of 50, 100, and 200 mg/kg/day (db/db-AS50, db/db-AS100, and db/db-AS200, respectively) for 10 weeks. Food and water intake, fasting blood glucose concentrations, blood glycosylated hemoglobin levels, and plasma insulin levels were significantly lower in the db/db-AS200 group than in the vehicle-treated db/db group; whereas glucose tolerance was significantly improved in the db/db-AS200 group. Moreover, AS dose dependently increased both insulin receptor substrate 1 and glucose transporter type 4 expression in skeletal muscle, significantly increased glucokinase expression, and decreased glucose 6-phosphatase and phosphoenolpyruvate carboxykinase expressions in the liver. The expressions of transcription factors, such as sterol-regulatory element-binding protein, peroxisome proliferator-activated receptor γ, and adipocyte protein 2, were upregulated in adipose tissue. Furthermore, immunohistochemical analysis showed that AS upregulated insulin production by increasing pancreatic β-cell mass. In summary, AS extract normalized hyperglycemia by multiple mechanisms: inhibition of glyconeogenesis, acceleration of glucose metabolism and lipid metabolism, and increase of glucose uptake. Using in vivo assays, this study has shown the potential of AS as a medicinal food and suggests the efficacy of AS for the use of prevention of diabetes.

  16. Comparison of West African and Congo Basin Monkeypox Viruses in BALB/c and C57BL/6 Mice

    PubMed Central

    Hutson, Christina L.; Abel, Jason A.; Carroll, Darin S.; Olson, Victoria A.; Braden, Zachary H.; Hughes, Christine M.; Dillon, Michael; Hopkins, Consuelo; Karem, Kevin L.; Damon, Inger K.; Osorio, Jorge E.

    2010-01-01

    Although monkeypox virus (MPXV) studies in wild rodents and non-human primates have generated important knowledge regarding MPXV pathogenesis and inferences about disease transmission, it might be easier to dissect the importance of virulence factors and correlates of protection to MPXV in an inbred mouse model. Herein, we compared the two clades of MPXV via two routes of infection in the BALB/c and C57BL/6 inbred mice strains. Our studies show that similar to previous animal studies, the Congo Basin strain of MPXV was more virulent than West African MPXV in both mouse strains as evidenced by clinical signs. Although animals did not develop lesions as seen in human MPX infections, localized signs were apparent with the foot pad route of inoculation, primarily in the form of edema at the site of inoculation; while the Congo Basin intranasal route of infection led to generalized symptoms, primarily weight loss. We have determined that future studies with MPXV and laboratory mice would be very beneficial in understanding the pathogenesis of MPXV, in particular if used in in vivo imaging studies. Although this mouse model may not suffice as a model of human MPX disease, with an appropriate inbred mouse model, we can unravel many unknown aspects of MPX pathogenesis, including virulence factors, disease progression in rodent hosts, and viral shedding from infected animals. In addition, such a model can be utilized to test antivirals and the next generation of orthopoxvirus vaccines for their ability to alter the course of disease. PMID:20111702

  17. Cis-urocanic acid increases immunotoxicity and lethality of dermally administered permethrin in C57BL/6N mice.

    PubMed

    Prater, M R; Gogal, R M; Blaylock, B L; Holladay, S D

    2003-01-01

    Immunomodulatory effects of a single topical permethrin exposure, 5-day exposure to cis-urocanic acid (cUCA), or a combination of the two chemicals were evaluated in 4- to 5-week-old female C57BL/6N mice. Permethrin alone decreased thymic weight and cellularity. Although cUCA alone did not affect thymic end points, coexposure to topical permethrin and cUCA exacerbated the thymolytic effects of permethrin. The single topical dose of permethrin also depressed several immune responses in isolated splenic leukocytes. This included splenic T-cell proliferative response to mitogen, splenic macrophage hydrogen peroxide production, and splenic B lymphocyte-specific antibody production. Unlike the effect of coexposure to these agents on thymic end points, cUCA did not exacerbate permethrin's adverse effect on any of the splenic end points examined. These results appear to suggest divergent mechanisms by which these compounds affect precursor and functionally mature T cells. At the doses used in this study, permethrin caused neurotoxic effects, including lethality, in a portion of the mice. For undetermined reasons, cUCA significantly increased the rate of lethality caused by permethrin. Although the permethrin doses used in this study exceed that typically used in human medicine, these results raise some concerns about the possibility that sunlight, via cUCA, may increase the risk of adverse central nervous system and immune effects caused by permethrin alone. PMID:12573947

  18. Different effect of chronic stress on learning and memory in BALB/c and C57BL/6 inbred mice: Involvement of hippocampal NO production and PKC activity.

    PubMed

    Palumbo, María Laura; Zorrilla Zubilete, María Aurelia; Cremaschi, Graciela Alicia; Genaro, Ana María

    2009-07-01

    Nitric oxide (NO) has been involved in many pathophysiological brain processes. Recently, we showed that neuronal nitric oxide synthase (nNOS)-mediated decrease in NO production is involved in memory impairment induced by chronic mild stress (CMS) in BALB/c mice. Two genetically different inbred murine strains, C57BL/6 and BALB/c, show distinct behavioral responses, neurodevelopmental and neurochemical parameters. Here, we perform a comparative study on CMS effects upon learning and memory in both strains, analyzing the role of NO production and its regulation by protein kinase C (PKC). Stressed BALB/c, but not C57Bl/6 mice, showed a poor learning performance in both the open field and passive avoidance inhibitory tasks. Also, CMS induced a diminished NO production by nNOS, associated with an increment in gamma and zeta PKC isoenzymes in BALB/c mice. In C57BL/6 mice, CMS had no effect on NO production, but increased delta and decreased betaI PKC isoforms. In vivo administration of a NOS inhibitor induced behavioral alterations in both strains. These results suggest a differential effect of stress, with BALB/c being more vulnerable to stress than C57BL/6 mice. This effect could be related to a differential regulation of NOS and PKC isoenzymes, pointing to an important role of NO in learning and memory.

  19. Vinpocetine Improves Scopolamine Induced Learning and Memory Dysfunction in C57 BL/6J Mice.

    PubMed

    Shang, Yu; Wang, Lei; Li, Yue; Gu, Pei-Fei

    2016-09-01

    Vinpocetine is an inhibitor of phosphodiesterase type 1 (PDE1), which has been used for treating stroke for over 40 years. However, according to current clinical dosage and treatment period, its direct effect on memory is unclear. In this study, we investigated whether vinpocetine could reverse the scopolamine (SCO)-induced cognitive deficits in animals. Behavioral experiments, including open field, Y-maze, and fear conditioning tests were used to determine the possible role of vinpocetine on scopolamine-induced memory dysfunction. In the open field and Y-maze tests, there were significant differences between the control (CON) group and SCO group. Vinpocetine (4 mg/kg) administration for consecutive 28 d significantly improved the scopolamine-induced memory dysfunction. In the fear conditioning test, vinpocetine (2, 4 mg/kg) administration had certain beneficial effect on emotional memory. Our results suggest that vinpocetine could improve cognitive function in memory deficient mice and high clinic dosage might be better.

  20. Erchen Decoction Prevents High-Fat Diet Induced Metabolic Disorders in C57BL/6 Mice

    PubMed Central

    Gao, Bi-Zhen; Chen, Ji-Cheng; Liao, Ling-Hong; Xu, Jia-Qi; Lin, Xiao-Feng; Ding, Shan-Shan

    2015-01-01

    Erchen decoction (ECD) is a traditional Chinese medicine prescription, which is used in the treatment of obesity, hyperlipidemia, fatty liver, diabetes, hypertension, and other diseases caused by retention of phlegm dampness. In this study we investigated the potential mechanism of ECD, using metabolism-disabled mice induced by high-fat diet. Body weight and abdominal circumference were detected. OGTT was measured by means of collecting blood samples from the tail vein. Blood lipid levels and insulin were measured using biochemical assay kit. Real-time PCR was used to measure the CDKAL1 gene expression and western blot was used to measure the protein expression. Through the research, it was found that ECD showed markedly lower body weight and abdominal circumference than those in the HFD group. Consistently, we observed that ECD significantly improved glucose tolerance, promoted the secretion of insulin and decreased the level of TG, TC level. Meanwhile, we observed significantly increased CDKAL1 mRNA and protein level in the ECD group. Therefore, we speculate that the potential molecular mechanism of ECD is to promote the CDKAL1 expression, ameliorate islet cell function, and raise insulin levels to regulate the metabolic disorder. PMID:26504476

  1. Effects of Calorie Restriction on Polymicrobial Peritonitis Induced by Cecum Ligation and Puncture in Young C57BL/6 Mice

    PubMed Central

    Sun, Dongxu; Muthukumar, Alagar Raju; Lawrence, Richard A.; Fernandes, Gabriel

    2001-01-01

    Calorie restriction (CR) is known to prolong the life span and maintain an active immune function in aged mice, but it is still not known if rodents under CR can respond optimally to bacterial infection. We report here on the influence of CR on the response of peritoneal macrophages to lipopolysaccharide, splenic NF-κB and NF–interleukin-6 (IL-6) activities, and mortality in polymicrobial sepsis induced by cecal ligation and puncture (CLP). Macrophages from 6-month-old C57BL/6 mice on a calorie-restricted diet were less responsive to lipopolysaccharide, as evidenced by lower levels of IL-12 and IL-6 protein and mRNA expression. Furthermore, in vitro lipopolysaccharide-stimulated macrophages from mice under CR also expressed decreased lipopolysaccharide receptor CD14 levels as well as Toll-like receptor 2 (TLR2) and TLR4 mRNA levels. In addition, the phagocytic capacity and class II (I-Ab) expression of macrophages were also found to be significantly lower in mice under CR. Mice under CR died earlier (P < 0.005) after sepsis induced by CLP, which appeared to be a result of increased levels in serum of the proinflammatory cytokines tumor necrosis factor alpha and IL-6 and splenic NF-κB and NF–IL-6 activation 4 h after CLP. However, mice under CR survived significantly (P < 0.005) longer than mice fed ad libitum when injected with paraquat, a free radical-inducing agent. These data suggest that young mice under CR may be protected against oxidative stress but may have delayed maturation of macrophage function and increased susceptibility to bacterial infection. PMID:11527818

  2. Estrogens, androgens and generalized behavioral arousal in gonadectomized female and male C57BL/6 mice.

    PubMed

    Chu, Xi; Gagnidze, Khatuna; Pfaff, Donald; Ågmo, Anders

    2015-08-01

    General arousal has been operationally defined as an enhanced motor activity and enhanced intensity of response to sensory stimuli. Even though the effects of gonadal hormones on mating behavior have been much studied, their potential effect on generalized arousal, as defined above, has never been evaluated. In the present study we employed a thoroughly validated assay of general arousal to determine the effects of estradiol (E) and testosterone (T) in gonadectomized female and male mice, respectively. The steroids were administered in three different ways: A fast-acting, water soluble preparation given intraperitoneally, an oil solution given subcutaneously, and an oil solution in a subcutaneous Silastic capsule. Motor activity and responses to sensory stimuli were recorded for 24h, 91h, and seven days following hormone administration, respectively. All measures of arousal varied according to the day/night cycle. The water soluble steroid preparation had no reliable effect. When the same doses of estradiol and testosterone were administered subcutaneously in an oil vehicle no effect of either treatment on arousal was observed. The subcutaneously implanted capsule containing estradiol or testosterone had a delayed effect on motor activity in females (four to seven days) but no effect in males. The long time required by the gonadal hormones for affecting arousal would be consistent with, but does not prove, a genomic action. The limited effects of E and T in our arousal assay suggest to us that the strongest actions of these hormones on arousal occur in the context of sequences of responses to sexually relevant stimuli. PMID:25936820

  3. Neurogenesis of the cholinergic medial septum in female and male C57BL/6J mice.

    PubMed

    Schaevitz, Laura R; Berger-Sweeney, Joanne

    2005-12-01

    Sex differences exist in the structure and function of the cholinergic septo-hippocampal system throughout the lifespan of mammals. How and when these sex differences originate is unclear. Because estrogen modulates sexual differentiation of several brain regions during development and influences neurogenesis in adult mammals, we hypothesized that sexual dimorphism of the cholinergic septo-hippocampal system would extend to its neurogenesis. A birthdating agent 5'-bromo-2'-deoxyuridine (BrdU) was injected into pregnant dams on one of eight gestational days, ranging from embryonic day (E)10 to E17. The offspring were euthanized at 2 months of age, and brains were processed for BrdU and choline acetyltransferase (ChAT) immunoreactivity to label cholinergic neurons that became postmitotic on a given embryonic day and survived to adulthood. Unbiased stereology was used to compare the number of double-labeled neurons in the medial septum (MS) of female and male offspring. Cholinergic neurons in the MS were generated primarily between E11 and E14, similar to other published reports. We found sex differences in the pattern of peak neurogenesis but not in the length of neurogenesis, or in total number of neurons generated in the MS. Additionally, in adult female and male mice, we estimated the total number of cholinergic neurons using unbiased stereology and found no sex differences in the number of cholinergic neurons or in the volume of the MS in adulthood. These results suggest that sex differences noted in the function of the postnatal cholinergic septo-hippocampal system may originate from its neurogenesis.

  4. Estrogens, androgens and generalized behavioral arousal in gonadectomized female and male C57BL/6 mice

    PubMed Central

    Chu, Xi; Gagnidze, Khatuna; Pfaff, Donald; Ågmo, Anders

    2015-01-01

    General arousal has been operationally defined as enhanced motor activity and enhanced intensity of response to sensory stimuli. Even though the effects of gonadal hormones on mating behavior have been much studied, their potential effect on generalized arousal, as defined above, has never been evaluated. In the present study we employed a thoroughly validated assay of general arousal to determine the effects of estradiol (E) and testosterone (T) in gonadectomized female and male mice, respectively. The steroids were administered in three different ways: A fast-acting, water soluble preparation given intraperitoneally, an oil solution given subcutaneously, and an oil solution in a subcutaneous Silastic capsule. Motor activity and responses to sensory stimuli were recorded for 24 h, 91 h, and seven days following hormone administration, respectively. All measures of arousal varied according to the day/night cycle. The water soluble steroid preparation had no reliable effect. When the same doses of estradiol and testosterone were administered subcutaneously in an oil vehicle no effect of either treatment on arousal was observed. The subcutaneously implanted capsule containing estradiol or testosterone had a delayed effect on motor activity in females (four to seven days) but no effect in males. The long time required by the gonadal hormones for affecting arousal would be consistent with, but does not prove, a genomic action. The limited effects of E and T in our arousal assay suggest to us that the strongest actions of these hormones on arousal occur in the context of sequences of responses to sexually relevant stimuli. PMID:25936820

  5. Voluntary exercise decreases ethanol preference and consumption in C57BL/6 adolescent mice: sex differences and hippocampal BDNF expression.

    PubMed

    Gallego, X; Cox, R J; Funk, E; Foster, R A; Ehringer, M A

    2015-01-01

    Adolescence is a period of high vulnerability for alcohol use and abuse. Early alcohol use has been shown to increase the risk for alcohol-related problems later in life; therefore effective preventive treatments targeted toward adolescents would be very valuable. Many epidemiological and longitudinal studies in humans have revealed the beneficial effects of exercise for prevention and treatment of alcohol addiction. Pre-clinical studies have demonstrated that access to a running wheel leads to decreased voluntary alcohol consumption in adult mice, hamsters, and rats. However, age and sex may also influence the effects of exercise on alcohol use. Herein, we studied male and female C57BL/6 adolescent mice using a 24-hour two-bottle choice paradigm to evaluate 21 days of concurrent voluntary exercise on alcohol consumption and preference. Given previously known effects of exercise in increasing the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus and its role in regulating the reward system, BDNF mRNA and protein levels were measured at the end of the behavioral experiment. Our results demonstrate sex differences in the efficacy of voluntary exercise and its effects on decreasing alcohol consumption and preference. We also report increased BDNF expression after 21 days of voluntary exercise in both male and female mice. Interestingly, the distance traveled played an important role in alcohol consumption and preference in female mice but not in male mice. Overall, this study demonstrates sex differences in the effects of voluntary exercise on alcohol consumption in adolescent mice and points out the importance of distance traveled as a limiting factor to the beneficial effects of wheel running in female mice. PMID:25447477

  6. Role of MT1 Melatonin Receptors in Methamphetamine-induced Locomotor Sensitization in C57BL/6 Mice

    PubMed Central

    Hutchinson, Anthony J.; Ma, Jason; Liu, Jiabei; Hudson, Randall L.; Dubocovich, Margarita L.

    2015-01-01

    RATIONALE Melatonin modifies physiological and behavioral responses to psychostimulants, with the MT1 and MT2 melatonin receptors specifically implicated in facilitating methamphetamine-induced sensitization in melatonin-proficient mice. OBJECTIVE To assess differences in locomotor sensitization after a single dose of methamphetamine in low melatonin-expressing C57BL/6 wild-type and MT1KO mice, and comparing with melatonin-expressing C3H/HeN mice. METHODS Mice received a vehicle or methamphetamine (1.2 mg/kg, i.p.) pretreatment (Day 1) during the light (ZT5–9) or dark (ZT 19–21) periods in novel test arenas. Locomotor sensitization was assessed by methamphetamine challenge after an eight-day (Day 9) abstinence. TH protein expression was evaluated by immunofluorescence and Western blot analysis. RESULTS Methamphetamine pretreatment induced statistically significant locomotor sensitization upon challenge after eight-day abstinence in C3H and C57 wild-type mice during the light period. The magnitude of sensitization in C57 mice was diminished in the dark period and completely abrogated in MT1 receptor knockout (MT1KO) mice. No differences were observed in tyrosine hydroxylase immunoreactivity in the mesolimbic dopamine system. Additional exposures to the test arenas after methamphetamine pretreatment (Nights 2–6) enhanced sensitization. CONCLUSIONS Deletion of the MT1 melatonin receptor abolishes sensitization induced by a single METH pretreatment. The magnitude of sensitization is also altered by time of day and contextual cues. We conclude that the MT1 melatonin receptor is emerging as a novel target of therapeutic intervention for drug abuse disorders. PMID:23934259

  7. Voluntary Exercise Decreases Ethanol Preference and Consumption in C57BL/6 Adolescent Mice: Sex Differences and Hippocampal BDNF Expression

    PubMed Central

    Gallego, X.; Cox, R.J.; Funk, E.; Foster, R.A.; Ehringer, M.A.

    2014-01-01

    Adolescence is a period of high vulnerability for alcohol use and abuse. Early alcohol use has been shown to increase the risk for alcohol-related problems later in life; therefore effective preventive treatments targeted toward adolescents would be very valuable. Many epidemiological and longitudinal studies in humans have revealed the beneficial effects of exercise for prevention and treatment of alcohol addiction. Pre-clinical studies have demonstrated that access to a running wheel leads to decreased voluntary alcohol consumption in adult mice, hamsters, and rats. However, age and sex may also influence the effects of exercise on alcohol use. Herein, we studied male and female C57BL/6 adolescent mice using a 24-h two bottle choice paradigm to evaluate 21 days of concurrent voluntary exercise on alcohol consumption and preference. Given previously known effects of exercise in increasing the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus and its role in regulating the reward system, BDNF mRNA and protein levels were measured at the end of the behavioral experiment. Our results demonstrate sex differences in the efficacy of voluntary exercise and its effects on decreasing alcohol consumption and preference. We also report increased BDNF expression after 21 days of voluntary exercise in both male and female mice. Interestingly, the distance travelled played an important role in alcohol consumption and preference in female mice but not in male mice. Overall, this study demonstrates sex differences in the effects of voluntary exercise on alcohol consumption in adolescent mice and points out the importance of distance travelled as a limiting factor to the beneficial effects of wheel running in female mice. PMID:25447477

  8. The effects of EGb761 on lipopolysaccharide-induced depressive-like behaviour in C57BL/6J mice.

    PubMed

    Zhao, Yuehan; Zhang, Yongdong; Pan, Fang

    2015-01-01

    There is an increasing body of evidence for the involvement of inflammation and brain-derived neurotrophic factor (BDNF) in depression. Ginkgo extract EGb761 possesses anti-inflammatory, anti-oxidative, anti-arteriosclerosis, and neuroprotective activities. But the effect of EGb761 on lipopolysaccharide (LPS)-induced depressive-like behaviours has not been investigated. The present study mainly aimed to examine the antidepressant-like activities of Ginkgo extract EGb761 in mice after lipopolysaccharide administration. C57BL/6J male mice were pretreated with EGb761 or vehicle for 10 days. Then, a single dose of lipopolysaccharide was intraperitoneally administrated to mice to induce depressive-like behaviour. Forced swim test (FST), tail suspension test (TST), and sucrose preference test were performed to evaluate the depressive-like behaviours of the mice. Locomotor activity was examined by open field test. Levels of brain-derived neurotrophic factor, TNF-α, IL-1β, IL-6, IL-17A, and IL-10 in hippocampus tissue homogenate were measured using ELISA kits. We found that LPS administration induced significant depressive-like behaviours, higher levels of tumour necrosis factor α (TNF-α), interleukin (IL) 1β, IL-6, and IL-17A, but lower levels of BDNF and IL-10 in hippocampus tissue homogenate of the mice from the vehicle group compared to the control mice. Pretreatment with middle dose (100 mg/kg/day) and high dose (150 mg/kg/day) of EGb761 significantly attenuated depressive-like behaviours without affecting spontaneous locomotor activity, and inhibited the changes of hippocampal cytokines and BDNF induced by LPS administration. We conclude that EGb761 has antidepressant-like activities in mice with LPS-induced depressive-like behaviours.

  9. Acute Stress Facilitates Trace Eyeblink Conditioning in C57BL/6 Male Mice and Increases the Excitability of Their CA1 Pyramidal Neurons

    ERIC Educational Resources Information Center

    Weiss, Craig; Sametsky, Evgeny; Sasse, Astrid; Spiess, Joachim; Disterhoft, John F.

    2005-01-01

    The effects of stress (restraint plus tail shock) on hippocampus-dependent trace eyeblink conditioning and hippocampal excitability were examined in C57BL/6 male mice. The results indicate that the stressor significantly increased the concentration of circulating corticosterone, the amount and rate of learning relative to nonstressed conditioned…

  10. Mouse Strain Impacts Fatty Acid Uptake and Trafficking in Liver, Heart, and Brain: A Comparison of C57BL/6 and Swiss Webster Mice.

    PubMed

    Seeger, D R; Murphy, E J

    2016-05-01

    C57BL/6 and Swiss Webster mice are used to study lipid metabolism, although differences in fatty acid uptake between these strains have not been reported. Using a steady state kinetic model, [1-(14)C]16:0, [1-(14)C]20:4n-6, or [1-(14)C]22:6n-3 was infused into awake, adult male mice and uptake into liver, heart, and brain determined. The integrated area of [1-(14)C]20:4n-6 in plasma was significantly increased in C57BL/6 mice, but [1-(14)C]16:0 and [1-(14)C]22:6n-3 were not different between groups. In heart, uptake of [1-(14)C]20:4n-6 was increased 1.7-fold in C57BL/6 mice. However, trafficking of [1-(14)C]22:6n-3 into the organic fraction of heart was significantly decreased 33 % in C57BL/6 mice. Although there were limited differences in fatty acid tracer trafficking in liver or brain, [1-(14)C]16:0 incorporation into liver neutral lipids was decreased 18 % in C57BL/6 mice. In heart, the amount of [1-(14)C]16:0 and [1-(14)C]22:6n-3 incorporated into total phospholipids were decreased 45 and 49 %, respectively, in C57BL/6 mice. This was accounted for by a 53 and 37 % decrease in [1-(14)C]16:0 and 44 and 52 % decrease in [1-(14)C]22:6n-3 entering ethanolamine glycerophospholipids and choline glycerophospholipids, respectively. In contrast, there was a significant increase in [1-(14)C]20:4n-6 esterification into all heart phospholipids of C57BL/6 mice. Although changes in uptake were limited to heart, several significant differences were found in fatty acid trafficking into heart, liver, and brain phospholipids. In summary, our data demonstrates differences in tissue fatty acid uptake and trafficking between mouse strains is an important consideration when carrying out fatty acid metabolic studies.

  11. Strain differences in activity and emotionality do not account for differences in learning and memory performance between C57BL/6 and DBA/2 mice.

    PubMed

    Podhorna, J; Brown, R E

    2002-05-01

    This study examined emotionality, activity, learning and memory, as well as the influence of emotionality and activity on learning and memory performance in C57BL/6 and DBA/2 mice using a mouse-test battery. DBA/2 mice performed more poorly than C57BL/6 mice in complex learning tasks such as the water maze and object recognition tasks. In contrast, C57BL/ 6 mice showed attenuated habituation tonovelty in the open field apparatus and poorer performance in the step-down passive avoidance task. The C57BL/6 mice were less exploratory and more anxious than the DBA/ 2 mice. The anxiety score (open arm entries in the elevated plus maze) was significantly correlated with all measures of learning and memory in the object recognition task, and some measures in the passive avoidance and water maze tasks. Analysis of covariance (with open arm entries as a covariate) revealed that some measures on trial 1 of the object recognition task, but not the memory scores on trial 2,were confounded by anxiety. No confounding factors of anxiety were found in the water maze or passive avoidance tasks. Similar results were obtained with the activity scores (line crossing and rearing in the open field). In conclusion, strain differences in activity and anxiety did not account for strain differences in learning and memory performance of C57BL/6 and DBA/2 mice. Nonetheless, the importance of using complete behavioural test batteries should be stressed to ensure that strain differences in learning and memory tasks are not confounded by non-cognitive factors.

  12. Simple generation of albino C57BL/6J mice with G291T mutation in the tyrosinase gene by the CRISPR/Cas9 system.

    PubMed

    Mizuno, Seiya; Dinh, Tra Thi Huong; Kato, Kanako; Mizuno-Iijima, Saori; Tanimoto, Yoko; Daitoku, Yoko; Hoshino, Yoshikazu; Ikawa, Masahito; Takahashi, Satoru; Sugiyama, Fumihiro; Yagami, Ken-ichi

    2014-08-01

    Single nucleotide mutations (SNMs) are associated with a variety of human diseases. The CRISPR/Cas9 genome-editing system is expected to be useful as a genetic modification method for production of SNM-induced mice. To investigate whether SNM-induced mice can be generated by zygote microinjection of CRISPR/Cas9 vector and single-stranded DNA (ssDNA) donor, we attempted to produce albino C57BL/6J mice carrying the Tyr gene SNM (G291T) from pigmented C57BL/6J zygotes. We first designed and constructed a CRISPR/Cas9 expression vector for the Tyr gene (px330-Tyr-M). DNA cleavage activity of px330-Tyr-M at the target site of the Tyr gene was confirmed by the EGxxFP system. We also designed an ssDNA donor for homology-directed repair (HDR)-mediated gene modification. The px330-Tyr-M vector and ssDNA donor were co-microinjected into the pronuclei of 224 one-cell-stage embryos derived from C57BL/6J mice. We obtained 60 neonates, 28 of which showed the ocular albinism and absence of coat pigmentation. Genomic sequencing analysis of the albino mice revealed that the target of SNM, G291T in the Tyr gene, occurred in 11 mice and one founder was homozygously mutated. The remaining albino founders without Tyr G291T mutation also possessed biallelic deletion and insertion mutants adjacent to the target site in the Tyr locus. Simple production of albino C57BL/6J mice was provided by C57BL/6J zygote microinjection with px330-Tyr-M DNA vector and mutant ssDNA (G291T in Tyr) donor. A combination of CRISPR/Cas9 vector and optional mutant ssDNA could be expected to efficiently produce novel SNM-induced mouse models for investigating human diseases. PMID:24879364

  13. Cadmium-induced microsatellite instability in the kidneys and leukocytes of C57BL/6J mice.

    PubMed

    Du, Xiaoyan; Lan, Tianfeng; Yuan, Bao; Chen, Jian; Hu, Jinping; Ren, Wenzhi; Chen, Zhenwen

    2015-01-01

    Cadmium is a cytotoxic, carcinogenic, and mutagenic industrial product or byproduct. The correlation between metal exposure and microsatellite instability (MSI) has been reported by several groups. In the present study, 50 C57BL/6J mice at 6 weeks of age were divided into five groups and intraperitoneally injected with 0, 0.25, 0.5, 1, or 2 mg/kg cadmium chloride quaque die alterna for 4 weeks. Then, the liver, kidney, testis, leukocytes, bone marrow, and small intestine were collected from the treated mice and weighed. Portions of these tissues were fixed for further histological analysis, and the remaining tissues were subjected to genomic DNA extraction for the analysis of a panel of 42 microsatellite markers. The liver and testis weight coefficients were significantly changed in the 1 and 2 mg/kg cadmium chloride-treated groups compared with the control group. Simultaneously, severe histopathologic changes in the liver and kidneys, along with a complete disorganization of testicular structure and obvious severe necrosis in the testes were observed in the cadmium-treated group. The cadmium accumulated in the liver and kidneys of the mice in all cadmium-treated groups; the tissue cadmium concentrations were significantly higher than those in the control group. After STR scanning, MSI was found at three loci (D15Mit5, D10Mit266, and DxMit172) in the kidneys and leukocytes of mice in the lower dose groups (0.25 and 0.5 mg/kg). In summary, we have successfully established a sub-chronic cadmium exposure model and confirmed that cadmium exposure can induce MSI in mice. We also identified two loci that could be regarded as "hotspots" of microsatellite mutation in mice. PMID:24391048

  14. Amphibole, but not chrysotile, asbestos induces anti-nuclear autoantibodies and IL-17 in C57BL/6 mice.

    PubMed

    Ferro, Aaron; Zebedeo, Christian Nash; Davis, Chad; Ng, Kok Whei; Pfau, Jean C

    2014-01-01

    Abstract Exposure to amphibole asbestos has been associated with production of autoantibodies in mice and humans, and increases the risk of systemic autoimmune disease. However, epidemiological studies of chrysotile exposure have not indicated a similar induction of autoimmune responses. To demonstrate this difference in controlled exposures in mice, and to explore possible mechanistic explanations for the difference, C57BL/6 mice were exposed intratracheally to amphibole or chrysotile asbestos, or to saline only. Serum antinuclear antibodies (ANA), antibodies to extractable nuclear antigens (ENA), serum cytokines, and immunoglobulin isotypes were evaluated 8 months after the final treatment. The percentages of lymphocyte sub-sets were determined in the spleen and lungs. The results show that amphibole, but not chrysotile, asbestos increases the frequency of ANA/ENA in mice. Amphibole and chrysotile both increased multiple serum cytokines, but only amphibole increased IL-17. Both fibers decreased IgG1, without significant changes in other immunoglobulin isotypes. Although there were no gross changes in overall percentages of T- and B-cells in the spleen or lung, there was a significant increase in the normally rare populations of suppressor B-cells (CD19(+), CD5(+), CD1d(+)) in both the spleen and lungs of chrysotile-exposed mice. Overall, the results suggest that, while there may be an inflammatory response to both forms of asbestos, there is an autoimmune response in only the amphibole-exposed, but not the chrysotile-exposed mice. These data have critical implications in terms of screening and health outcomes of asbestos-exposed populations.

  15. Contribution of P2X4 receptors to ethanol intake in male C57BL/6 mice.

    PubMed

    Wyatt, Letisha R; Finn, Deborah A; Khoja, Sheraz; Yardley, Megan M; Asatryan, Liana; Alkana, Ronald L; Davies, Daryl L

    2014-06-01

    P2X receptors (P2XRs) are a family of cation-permeable ligand-gated ion channels activated by synaptically released extracellular adenosine 5'-triphosphate. The P2X4 subtype is abundantly expressed in the central nervous system and is sensitive to low intoxicating ethanol concentrations. Genetic meta-analyses identified the p2rx4 gene as a candidate gene for innate alcohol intake and/or preference. The current study used mice lacking the p2rx4 gene (knockout, KO) and wildtype (WT) C57BL/6 controls to test the hypothesis that P2X4Rs contribute to ethanol intake. The early acquisition and early maintenance phases of ethanol intake were measured with three different drinking procedures. Further, we tested the effects of ivermectin (IVM), a drug previously shown to reduce ethanol's effects on P2X4Rs and to reduce ethanol intake and preference, for its ability to differentially alter stable ethanol intake in KO and WT mice. Depending on the procedure and the concentration of the ethanol solution, ethanol intake was transiently increased in P2X4R KO versus WT mice during the acquisition of 24-h and limited access ethanol intake. IVM significantly reduced ethanol intake in P2X4R KO and WT mice, but the degree of reduction was 50 % less in the P2X4R KO mice. Western blot analysis identified significant changes in γ-aminobutyric acidA receptor α1 subunit expression in brain regions associated with the regulation of ethanol behaviors in P2X4R KO mice. These findings add to evidence that P2X4Rs contribute to ethanol intake and indicate that there is a complex interaction between P2X4Rs, ethanol, and other neurotransmitter receptor systems. PMID:24671605

  16. Contribution of P2X4 receptors to ethanol intake in male C57BL/6 mice

    PubMed Central

    Wyatt, Letisha R.; Finn, Deborah A.; Khoja, Sheraz; Yardley, Megan M; Asatryan, Liana; Alkana, Ronald L.; Davies, Daryl L.

    2014-01-01

    P2X receptors (P2XRs) are a family of cation-permeable ligand-gated ion channels activated by synaptically released extracellular ATP. The P2X4 subtype is abundantly expressed in the CNS and is sensitive to low intoxicating ethanol concentrations. Genetic meta-analyses identified the p2rx4 gene as a candidate gene for innate alcohol intake and/or preference. The current study used mice lacking the p2rx4 gene (knockout, KO) and wildtype (WT) C57BL/6 controls to test the hypothesis that P2X4Rs contribute to ethanol intake. The early acquisition and early maintenance phases of ethanol intake were measured with three different drinking procedures. Further, we tested the effects of ivermectin (IVM), a drug previously shown to reduce ethanol’s effects on P2X4Rs and to reduce ethanol intake and preference, for its ability to differentially alter stable ethanol intake in KO and WT mice. Depending on the procedure and the concentration of the ethanol solution, ethanol intake was transiently increased in P2X4R KO versus WT mice during the acquisition of 24-hr and limited access ethanol intake. IVM significantly reduced ethanol intake in P2X4R KO and WT mice, but the degree of reduction was 50% less in the P2X4R KO mice. Western blot analysis identified significant changes in -γ aminobutyric acidA receptor (GABAAR) α1 subunit expression in brain regions associated with the regulation of ethanol behaviors in P2X4R KO mice. These findings add to evidence that P2X4Rs contribute to ethanol intake and indicate that there is a complex interaction between P2X4Rs, ethanol, and other neurotransmitter receptor systems. PMID:24671605

  17. Obesogen effects after perinatal exposure of 4,4'-sulfonyldiphenol (Bisphenol S) in C57BL/6 mice.

    PubMed

    Ivry Del Moral, L; Le Corre, L; Poirier, H; Niot, I; Truntzer, T; Merlin, J-F; Rouimi, P; Besnard, P; Rahmani, R; Chagnon, M C

    2016-05-16

    Bisphenol A were removed from consumer products and replaced by chemical substitutes such as Bisphenol S (BPS). Based on their structural similarity, BPS may be obesogen like Bisphenol A in mice. Our objective was to determine the impact of BPS on lipid homeostasis in C57Bl/6 mice after perinatal and chronic exposure. Pregnant mice were exposed to BPS via the drinking water (0.2; 1.5; 50μg/kg bw/d). Treatment began at gestational day 0 and continued in offspring up to 23-weeks old. Then, offspring mice were fed with a standard or high fat diet. The body weight, food consumption, fat mass and energy expenditure were measured. A lipid load test was performed to check the postprandial triglyceridemia. Plasma parameters and mRNA gene expression in adipose tissues were also analysed. BPS induced overweight in male mice offspring fed with a HFD at the two highest doses. There was no change in food intake and energy expenditure. The overweight was correlated to the fat mass, hyperinsulinemia and hyperleptinemia. The plasma triglyceride clearance was significantly increased with BPS and tyloxapol(®) (triglyceride clearance inhibitor) reversed this phenomenon. BPS induced alteration in mRNA expression of marker genes involved in adipose tissue homeostasis: hormone sensitive lipase, PPARγ, insulin receptor, SOCS3 and adiponectin. This is the first time that BPS is described as obesogenic at low doses and after perinatal and chronic exposure in male mice. BPS potentiated the obesity induced by a HFD by inducing the lipid storage linked to faster lipid plasma clearance.

  18. Biaxial Mechanical Properties of the Inferior Vena Cava in C57BL/6 and CB-17 SCID/bg Mice

    PubMed Central

    Lee, Y.U.; Naito, Y.; Kurobe, H.; Breuer, C.K.; Humphrey, J.D.

    2013-01-01

    Multiple murine models have proven useful in studying the natural history of neovessel development in the tissue engineering of vascular grafts. Nevertheless, to better understand longitudinal changes in the biomechanics of such neovessels, we must first quantify native tissue structure and properties. In this paper, we present the first biaxial mechanical data for, and nonlinear constitutive modeling of, the inferior vena cava from two models used in tissue engineering: wild-type C57BL/6 and immunodeficient CB-17 SCID/bg mice. Results show that inferior vena cava from the latter are significantly stiffer in the circumferential direction, both materially (as assessed by a stored energy function) and structurally (as assessed by the compliance), despite a lower intramural content of fibrillar collagen and similar wall thickness. Quantifying the natural history of neovessel development in different hosts could lead to increased insight into the mechanisms by which cells fashion and maintain extracellular matrix in order to match best the host stiffness while ensuring sufficient vascular integrity. PMID:23859752

  19. Evaluation of Beneficial Metabolic Effects of Berries in High-Fat Fed C57BL/6J Mice

    PubMed Central

    Blanco, Narda; Sterner, Olov; Holm, Cecilia

    2014-01-01

    Objective. The aim of the study was to screen eight species of berries for their ability to prevent obesity and metabolic abnormalities associated with type 2 diabetes. Methods. C57BL/6J mice were assigned the following diets for 13 weeks: low-fat diet, high-fat diet or high-fat diet supplemented (20%) with lingonberry, blackcurrant, bilberry, raspberry, açai, crowberry, prune or blackberry. Results. The groups receiving a high-fat diet supplemented with lingonberries, blackcurrants, raspberries or bilberries gained less weight and had lower fasting insulin levels than the control group receiving high-fat diet without berries. Lingonberries, and also blackcurrants and bilberries, significantly decreased body fat content, hepatic lipid accumulation, and plasma levels of the inflammatory marker PAI-1, as well as mediated positive effects on glucose homeostasis. The group receiving açai displayed increased weight gain and developed large, steatotic livers. Quercetin glycosides were detected in the lingonberry and the blackcurrant diets. Conclusion. Lingonberries were shown to fully or partially prevent the detrimental metabolic effects induced by high-fat diet. Blackcurrants and bilberries had similar properties, but to a lower degree. We propose that the beneficial metabolic effects of lingonberries could be useful in preventing obesity and related disorders. PMID:24669315

  20. Peculiarities of the Inflammatory Process in the Reproductive Organs of C57Bl/6 Female Mice with Experimental Tuberculosis.

    PubMed

    Sukhikh, G T; Kayukova, S I; Bocharova, I V; Donnikov, A E; Lepekha, L N; Demikhova, O V; Uvarova, E V; Berezovskii, Yu S; Smirnova, T G

    2016-04-01

    Intravenous infection of C57Bl/6 female mice with M. tuberculosis H37Rv led to involvement of the lungs and dissemination of the tuberculous infection to the abdominal and pelvic organs. M. tuberculosis were detected in the lungs and spleen in 14, 35, and 90 days and in the uterine horns in 90 days after infection. Morphological analysis of organs showed successive development of exudative necrotic tuberculosis of the lungs, acute and chronic nonspecific inflammation in the reproductive organs (vagina, uterus, and uterine horns). The inflammatory process in the reproductive organs was associated with the development of anaerobic dysbiosis, that was most pronounced in 35 days after infection. Antituberculous therapy was followed by reduction of M. tuberculosis count in the lungs and spleen in 60 and 90 days after infection, eliminatation of M. tuberculosis in the uterine horns, arrest of nonspecific inflammation in female reproductive organs, recovery of the balance between aerobic and anaerobic microflora, and development of candidiasis of the urogenital mucosa.

  1. Lactulose Differently Modulates the Composition of Luminal and Mucosal Microbiota in C57BL/6J Mice.

    PubMed

    Mao, Bingyong; Li, Dongyao; Ai, Chunqing; Zhao, Jianxin; Zhang, Hao; Chen, Wei

    2016-08-10

    In this study, C57BL/6J mice were fed diets supplemented with different proportions of lactulose (0%, 5%, and 15%) for 2 weeks to study its effects on the luminal and mucosal microbiota. The luminal and mucosal samples of cecum and colon were investigated. After high-lactulose treatment (15%), pH of the luminal contents decreased from 6.90-7.72 to 5.95-6.21 from the cecum to distal colon, and the amount of total short-chain fatty acids in the cecum was significantly increased. The luminal content was mostly dominated by Firmicutes, Actinobacteria, and Bacteroidetes, while the mucus was dominated by Firmicutes, Proteobacteria, and Bacteroidetes. The abundance of Actinobacteria was significantly increased in the content, and Proteobacteria was the most abundant phylum (∼50%) in the mucus after high-lactulose treatment. At the genus level, Bifidobacterium and Akkermansia were both significantly increased in the content, and Helicobacter was the most abundant in the mucus. PMID:27438677

  2. Jicama (Pachyrhizus erosus) extract increases insulin sensitivity and regulates hepatic glucose in C57BL/Ksj-db/db mice

    PubMed Central

    Park, Chan Joo; Lee, Hyun-Ah; Han, Ji-Sook

    2016-01-01

    This study investigated the effect of jicama extract on hyperglycemia and insulin sensitivity in an animal model of type 2 diabetes. Male C57BL/Ksj-db/db mice were divided into groups subsequently fed a regular diet (controls), or diet supplemented with jicama extract, and rosiglitazone. After 6 weeks, blood levels of glucose and glycosylated hemoglobin were significantly lower in animals administered the jicama extract than the control group. Additionally, glucose and insulin tolerance tests showed that jicama extract increased insulin sensitivity. The homeostatic index of insulin resistance was lower in the jicama extract-treated group than in the diabetic control group. Administration of jicama extract significantly enhanced the expressions of the phosphorylated AMP-activated protein kinase and Akt substrate of 160 kDa, and plasma membrane glucose transporter type 4 in skeletal muscle. Jicama extract administration also decreased the expressions of glucose 6-phosphatase and phosphoenol pyruvate carboxykinase in the liver. Jicama extract may increases insulin sensitivity and inhibites the gluconeogenesis in the liver. PMID:26798198

  3. Jicama (Pachyrhizus erosus) extract increases insulin sensitivity and regulates hepatic glucose in C57BL/Ksj-db/db mice.

    PubMed

    Park, Chan Joo; Lee, Hyun-Ah; Han, Ji-Sook

    2016-01-01

    This study investigated the effect of jicama extract on hyperglycemia and insulin sensitivity in an animal model of type 2 diabetes. Male C57BL/Ksj-db/db mice were divided into groups subsequently fed a regular diet (controls), or diet supplemented with jicama extract, and rosiglitazone. After 6 weeks, blood levels of glucose and glycosylated hemoglobin were significantly lower in animals administered the jicama extract than the control group. Additionally, glucose and insulin tolerance tests showed that jicama extract increased insulin sensitivity. The homeostatic index of insulin resistance was lower in the jicama extract-treated group than in the diabetic control group. Administration of jicama extract significantly enhanced the expressions of the phosphorylated AMP-activated protein kinase and Akt substrate of 160 kDa, and plasma membrane glucose transporter type 4 in skeletal muscle. Jicama extract administration also decreased the expressions of glucose 6-phosphatase and phosphoenol pyruvate carboxykinase in the liver. Jicama extract may increases insulin sensitivity and inhibites the gluconeogenesis in the liver. PMID:26798198

  4. Modeling Longitudinal Metabonomics and Microbiota Interactions in C57BL/6 Mice Fed a High Fat Diet.

    PubMed

    Montoliu, Ivan; Cominetti, Ornella; Boulangé, Claire L; Berger, Bernard; Siddharth, Jay; Nicholson, Jeremy; Martin, François-Pierre J

    2016-08-01

    Longitudinal studies aim typically at following populations of subjects over time and are important to understand the global evolution of biological processes. When it comes to longitudinal omics data, it will often depend on the overall objective of the study, and constraints imposed by the data, to define the appropriate modeling tools. Here, we report the use of multilevel simultaneous component analysis (MSCA), orthogonal projection on latent structures (OPLS), and regularized canonical correlation analysis (rCCA) to study associations between specific longitudinal urine metabonomics data and microbiome data in a diet-induced obesity model using C57BL/6 mice. (1)H NMR urine metabolic profiling was performed on samples collected weekly over a period of 13 weeks, and stool microbial composition was assessed using 16S rRNA gene sequencing at three specific time periods (baseline, first week response, end of study). MSCA and OPLS allowed us to explore longitudinal urine metabonomics data in relation to the dietary groups, as well as dietary effects on body weight. In addition, we report a data integration strategy based on regularized CCA and correlation analyses of urine metabonomics data and 16S rRNA gene sequencing data to investigate the functional relationships between metabolites and gut microbial composition. Thanks to this workflow enabling the breakdown of this data set complexity, the most relevant patterns could be extracted to further explore physiological processes at an anthropometric, cellular, and molecular level.

  5. Identification of Possible Candidate Biomarkers for Local or Whole Body Radiation Exposure in C57BL/6 Mice

    SciTech Connect

    Lee, Hae-June; Lee, Minyoung; Kang, Chang-Mo; Jeoung, Dooil; Bae, Sangwoo; Cho, Chul-Koo; Lee, Yun-Sil

    2007-11-15

    Purpose: Specific genes expressed as a result of whole body exposure to {gamma}-radiation have been previously identified. In this study, we examined the genes further as possible biomarkers for the blood lymphocytes of C57BL/6 mice after whole body or local irradiation of the thorax, abdomen, and left subphrenic area. Methods and Materials: We performed reverse transcriptase-polymerase chain reaction and real-time reverse transcriptase-polymerase chain reaction analysis of genes encoding platelet membrane glycoprotein IIb, protein tyrosine kinase, sialyltransferase, and Cu/ZnSOD in blood lymphocytes, lung tissue, spleen, and intestines. The protein expression in blood lymphocytes was confirmed by Western blot analysis. Results: The expression of platelet membrane glycoprotein IIb, protein tyrosine kinase, sialyltransferase, and Cu/ZnSOD was significantly greater after 3 days as a result of 1 Gy of whole body irradiation. Moreover, local irradiation to the thorax, abdomen, or left subphrenic area, which are frequently exposed to therapeutic radiation doses, showed a tendency toward radiation-induced increased expression of these genes in both the blood and the locally irradiated organs. Western blot analysis also corroborated these results. Conclusion: Platelet membrane glycoprotein IIb, protein tyrosine kinase, sialyltransferase, and Cu/ZnSOD might be candidates for biomarkers of radiation exposure. However, additional experiments are required to reveal the relationship between the expression levels and the prognostic effects after irradiation.

  6. Modeling Longitudinal Metabonomics and Microbiota Interactions in C57BL/6 Mice Fed a High Fat Diet.

    PubMed

    Montoliu, Ivan; Cominetti, Ornella; Boulangé, Claire L; Berger, Bernard; Siddharth, Jay; Nicholson, Jeremy; Martin, François-Pierre J

    2016-08-01

    Longitudinal studies aim typically at following populations of subjects over time and are important to understand the global evolution of biological processes. When it comes to longitudinal omics data, it will often depend on the overall objective of the study, and constraints imposed by the data, to define the appropriate modeling tools. Here, we report the use of multilevel simultaneous component analysis (MSCA), orthogonal projection on latent structures (OPLS), and regularized canonical correlation analysis (rCCA) to study associations between specific longitudinal urine metabonomics data and microbiome data in a diet-induced obesity model using C57BL/6 mice. (1)H NMR urine metabolic profiling was performed on samples collected weekly over a period of 13 weeks, and stool microbial composition was assessed using 16S rRNA gene sequencing at three specific time periods (baseline, first week response, end of study). MSCA and OPLS allowed us to explore longitudinal urine metabonomics data in relation to the dietary groups, as well as dietary effects on body weight. In addition, we report a data integration strategy based on regularized CCA and correlation analyses of urine metabonomics data and 16S rRNA gene sequencing data to investigate the functional relationships between metabolites and gut microbial composition. Thanks to this workflow enabling the breakdown of this data set complexity, the most relevant patterns could be extracted to further explore physiological processes at an anthropometric, cellular, and molecular level. PMID:27396289

  7. Flavokawains A and B in Kava, Not Dihydromethysticin, Potentiate Acetaminophen-Induced Hepatotoxicity in C57BL/6 Mice

    PubMed Central

    2015-01-01

    Anxiolytic kava products have been associated with rare but severe hepatotoxicity in humans. This adverse potential has never been captured in animal models, and the responsible compound(s) remains to be determined. The lack of such knowledge greatly hinders the preparation of a safer kava product and limits its beneficial applications. In this study we evaluated the toxicity of kava as a single entity or in combination with acetaminophen (APAP) in C57BL/6 mice. Kava alone revealed no adverse effects for long-term usage even at a dose of 500 mg/kg bodyweight. On the contrary a three-day kava pretreatment potentiated APAP-induced hepatotoxicity, resulted in an increase in serum ALT and AST, and increased severity of liver lesions. Chalcone-based flavokawains A (FKA) and B (FKB) in kava recapitulated its hepatotoxic synergism with APAP while dihydromethysticin (DHM, a representative kavalactone and a potential lung cancer chemopreventive agent) had no such effect. These results, for the first time, demonstrate the hepatotoxic risk of kava and its chalcone-based FKA and FKB in vivo and suggest that herb–drug interaction may account for the rare hepatotoxicity associated with anxiolytic kava usage in humans. PMID:25185080

  8. A neuropeptide FF agonist blocks the acquisition of conditioned place preference to morphine in C57Bl/6J mice.

    PubMed

    Marchand, Stéphane; Betourne, Alexandre; Marty, Virginie; Daumas, Stéphanie; Halley, Hélène; Lassalle, Jean-Michel; Zajac, Jean-Marie; Frances, Bernard

    2006-05-01

    Neuropeptide FF behaves as an opioid-modulating peptide that seems to be involved in morphine tolerance and physical dependence. Nevertheless, the effects of neuropeptide FF agonists on the rewarding properties of morphine remain unknown. C57BL6 mice were conditioned in an unbiased balanced paradigm of conditioned place preference to study the effect of i.c.v. injections of 1DMe (D-Tyr1(NMe)Phe3]NPFF), a stable agonist of the neuropeptide FF system, on the acquisition of place conditioning by morphine or alcohol (ethanol). Morphine (10 mg/kg, i.p.) or ethanol (2 g/kg, i.p.) induced a significant place preference. Injection of 1DMe (1-20 nmol), given 10 min before the i.p. injection of the reinforcing drug during conditioning, inhibited the rewarding effect of morphine but had no effect on the rewarding effect of ethanol. However, a single injection of 1DMe given just before place preference testing was unable to inhibit the rewarding effects of morphine. By itself, 1DMe was inactive but an aversive effect of this agonist could be evidenced if the experimental procedure was biased. These results suggest that neuropeptide FF, injected during conditioning, should influence the development of rewarding effects of morphine and reinforce the hypothesis of strong inhibitory interactions between neuropeptide FF and opioids.

  9. Study of Biofilm Formation in C57Bl/6J Mice by Clinical Isolates of Helicobacter pylori

    PubMed Central

    Attaran, Bahareh; Falsafi, Tahereh; Moghaddam, Ali N.

    2016-01-01

    Background/Aim: Despite the significant number of studies on H. pylori pathogenesis, not much data has been published concerning its ability to form biofilm in the host stomach. This study aims to evaluate the potential of clinical isolates of H. pylori to form biofilm in C57BL/6J mice model. Materials and Methods: Two strains of H. pylori were selected from a collection of clinical isolates; one (19B), an efficient biofilm producer and the other (4B), with weak biofilm-forming ability. Mice infected through gastric avages were examined after one and two weeks. Colonization was determined by CFU and urease activity; the anti-H. pylori IgA was measured by ELISA, and chronic infections were evaluated by histopathology. Bacterial communities within mucosal sections were studied by immunofluorescence and scanning electron microscopy (SEM). Results: Successful infection was obtained by both test strains. Strain 19B with higher ability to form biofilm in vitro also showed a higher colonization rate in the mice stomach one week after infection. Difference (P < 0.05) in IgA titers was observed between the infected mice and the controls as well as between 19B and 4B infected mice, two weeks after the last challenge. Immunofluorescence and SEM results showed tightly colonizing H. pylori in stomach mucosal sections and in squamous and glandular epithelium. Conclusion: H. pylori is able to form biofilm in the mouse stomach and induce IgA production, reflecting the same potential as in humans. Firm attachment of coccoid form bacteria to host cells suggests the importance of this state in biofilm formation by H. pylori. Occurrence of biofilm in squamous and glandular epithelium of the mouse stomach proposes that H. pylori can all parts of the upper gastrointestinal tract. PMID:26997224

  10. Differential early rearing environments can accentuate or attenuate the responses to stress in male C57BL/6 mice.

    PubMed

    Parfitt, David B; Levin, Jennifer K; Saltstein, Katherine P; Klayman, Andrea S; Greer, Laura M; Helmreich, Dana L

    2004-07-30

    This study investigated the effects of neonatal handling and maternal separation on the development of anxiety behavior and the hypothalamic-pituitary-adrenal axis of C57BL/6 mice. We hypothesized short periods of neonatal handling would diminish anxiety and secretion of corticosterone, while longer periods of maternal separation would elevate anxiety and plasma corticosterone compared to a nonhandled group. Mice were bred and reared as follows. After birth, each litter was assigned to one of four groups: mother and pups removed from the home cage for 10 min (group 1) or 180 min a day (group 2); mother only removed from home cage 180 min a day (group 3); and no handling until weaning (group 4). All separation occurred on the first 10 days of life. Juvenile males that experienced 10 min of separation/day exhibited decreased anxiety behavior compared to all other mice. A second group of litters were bred and reared according to groups 1, 2, and 4 as described above. Upon adulthood, anxiety behavior was assessed in males, and the corticosterone response to an acoustic stressor was quantified. No effect of differential rearing was observed on behavior, but there was a marked effect on plasma corticosterone secretion between the groups. Adult male mice neonatally handled for 10 min/day exhibited a blunted corticosterone response, and mice that experienced 180 min of maternal separation exhibited a prolonged corticosterone response to the acoustic stimulus compared to the nonhandled group. These results demonstrate the development of the mouse's hypothalamic-pituitary-adrenal axis can be modified by neonatal rearing conditions, and suggest that the mouse could be a viable animal model to determine the genetic-environmental interactions governing brain development.

  11. Minocycline enhances hippocampal memory, neuroplasticity and synapse-associated proteins in aged C57 BL/6 mice.

    PubMed

    Jiang, Ying; Liu, Yingying; Zhu, Cansheng; Ma, Xiaomeng; Ma, Lili; Zhou, Linli; Huang, Qiling; Cen, Lei; Pi, Rongbiao; Chen, Xiaohong

    2015-05-01

    Previous studies have suggested that minocycline can attenuate cognitive deficits in animal models of conditions such as Alzheimer's disease and cerebral ischemia through inhibiting microglia associated anti-inflammatory actions. However the pathway that minocycline targets to enhance cognitive performance is not fully defined. Here we examined the effects of minocycline on learning and memory in aged (22-month-old) C57 BL/6 mice. We treated one group of mice with minocycline (30 mg/kg/day), and another group of mice with donepezil (2 mg/kg/day) as a positive control. The Morris water maze and passive avoidance tests were used to evaluate the effects of minocycline on learning and memory deficits. We also used high-frequency stimulation-induced long-term potentiation and Golgi-Cox staining to assess the effect of minocycline on synaptic plasticity and synaptogenesis. The effects of minocycline on synapse-associated signaling proteins were determined by western blot. We found that minocycline ameliorates cognitive deficits, enhances neuroplasticity, activates brain-derived neurotrophic factor- extracellular signal-regulated kinases signaling and increases expression of Arc, EGR1 and PSD-95 in the CA1 and dentate gyrus regions of the hippocampus in aged mice. The effects of minocycline in aged mice were similar to those of donepezil. Our results suggest that minocycline could improve learning and memory through enhancing synaptic plasticity and synaptogenesis, modulating the expression of synapse-associated signaling proteins, which provide a rationale for exploring the viability of using minocycline treatment in cognitive deficits.

  12. Compared with DBA/2J mice, C57BL/6J mice demonstrate greater preference for saccharin and less avoidance of a cocaine-paired saccharin cue.

    PubMed

    Freet, Christopher S; Arndt, Amanda; Grigson, Patricia S

    2013-06-01

    Rats avoid intake of a saccharin cue when paired with a drug of abuse. While this is true for most subjects, the degree of avoidance of the drug-paired cue depends upon many factors including an individual rat's preference for rewards. That said, the direction of this effect is complex. For example, reward-preferring Lewis rats exhibit greater cocaine-induced avoidance of a saccharin cue relative to Fischer 344 rats; while reward-preferring mice that overexpress ΔFosB (NSE-tTA × TetOp-ΔFosB) exhibit less avoidance of the drug-paired taste cue compared to controls. The aim here was to use two strains of commonly used mice, C57BL/6J and DBA/2J, to determine whether known differences in sensitivity to rewards will facilitate or attenuate drug-induced suppression of intake of a drug-paired taste cue. The results of Experiment 1 demonstrate that C57BL/6J mice, compared with DBA/2J mice, exhibit attenuated suppression of saccharin intake when it is paired with cocaine. The results of Experiment 2 demonstrate that strain differences in impulsivity are not likely to account for these differences. It is proposed that, while the C57BL/6J mice typically are more responsive to drug, they also are more responsive to natural rewards (in this case saccharin), and the stronger preference for saccharin serves to militate against drug.

  13. Pathogenesis of acute arthritis due to viable Chlamydia trachomatis (mouse pneumonitis agent) in C57Bl/6 mice.

    PubMed Central

    Hough, A. J.; Rank, R. G.

    1989-01-01

    The purpose of this investigation was to determine the natural history and pathogenesis of the acute arthritis induced by inoculation of a viable Chlamydia trachomatis biovar (mouse pneumonitis agent or MoPn) in C57Bl/6 mice. Immunologically naive (previously unsensitized) mice as well as mice immunized against Chlamydia (MoPn) by vaginal infection were employed. Both intravenous and intraarticular inoculations were employed. No arthritis developed after intravenous injections of MoPn although statistically significant antibody titers and splenic enlargement ensued. Intra-articular inoculation into knee joints produced a definite arthritis of 7 to 10 days duration marked by granulocyte and mononuclear cell infiltration of the joint and vacuolated synovial macrophages that stained heavily for chlamydial antigen by immunoperoxidase technique. Statistically significant increases in articular acute and chronic inflammation (P less than 0.02 were observed in previously sensitized, but not unsensitized, female mice at 2 but not 7 days after intra-articular chlamydial challenge. Chlamydiae were isolated from injected joints up to day 5, but not at day 10, after challenge. Chlamydial antigen disappeared rapidly from knee joints between day 10 and 15 after challenge. Electron micrographs demonstrated vacuolated synovial cells of the macrophage type, many of which contained degenerating chlamydial elementary bodies. Reticulate and intermediate bodies also were seen but were far less frequent than degenerating elementary bodies. Unaltered elementary bodies were difficult to identify beyond day 2 after articular inoculation. Thus, it appears likely that intra-articular chlamydial survival is shorter than the duration of the arthropathy. This may have important implications in attempts to identify chlamydiae in human joints in Reiter's Disease. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 Figure 8 Figure 9 Figure 10 Figure 11 PMID:2705510

  14. Withdrawal from Chronic Cocaine Administration Induces Deficits in Brain Reward Function in C57BL/6J Mice

    PubMed Central

    Stoker, Astrid K.; Markou, Athina

    2011-01-01

    Anhedonia is a major symptom of cocaine withdrawal, whereas euphoria characterizes the effects of acute administration of this drug in humans. These mood states can be measured quantitatively in animals with brain reward thresholds obtained from the intracranial self-stimulation (ICSS) procedure. Studies have previously reported the reward-enhancing effects of acute cocaine administration using the ICSS procedure in mice, but the effects of chronic cocaine administration and withdrawal on brain reward thresholds have not been widely investigated in this species. Cocaine withdrawal was induced in C57BL/6J mice by removal of intraperitoneal osmotic minipumps that delivered cocaine (90 or 180 mg/kg/day, salt) for 72 h. Mice were tested in the ICSS procedure 3–100 h post-pump removal. Anxiety-like behavior was assessed in the light-dark box 24 h post-pump removal. After an 18-day washout period, tolerance and sensitization to the reward-enhancing effects of cocaine were assessed by injecting bolus cocaine intraperitoneally (0, 2.5, 5, and 10 mg/kg). The results indicated that 72 h administration of 90 and 180 mg/kg/day cocaine significantly lowered brain reward thresholds. Withdrawal from 90 and 180 mg/kg/day of cocaine administration elevated ICSS thresholds to similar extents. No anxiety-like behavior was observed in the light-dark box during withdrawal from chronic cocaine administration, although the number of transitions between compartments and locomotion in the dark compartment markedly decreased. Chronic cocaine administration did not induce tolerance or sensitization to the reward-enhancing effects of acute cocaine. In conclusion, alterations in mood states induced by cocaine administration and withdrawal in mice can be measured using the ICSS procedure. PMID:21557971

  15. Infection of C57BL/6 mice by Trypanosoma musculi modulates host immune responses during Brucella abortus cocolonization.

    PubMed

    Lowry, Jake E; Leonhardt, Jack A; Yao, Chaoqun; Belden, E Lee; Andrews, Gerard P

    2014-01-01

    Brucellosis, which results in fetal abortions in domestic and wildlife animal populations, is of major concern in the US and throughout much of the world. The disease, caused by Brucella abortus, poses an economic threat to agriculture-based communities. A moderately efficacious live attenuated vaccine (B. abortus strain RB51) exists. However, even with vaccine use, outbreaks occur. Evidence suggests that elk (Cervus canadensis), a wild host reservoir, are the source of recent outbreaks in domestic cattle herds in Wyoming, USA. Brucella abortus establishes a chronic, persistent infection in elk. The molecular mechanisms allowing the establishment of this persistent infective state are currently unknown. A potential mechanism could be that concurrent pathogen burdens contribute to persistence. In Wyoming, elk are chronically infected with Trypanosoma cervi, which may modulate host responses in a similar manner to that documented for other trypanosomes. To identify any synergistic relationship between the two pathogens, we simulated coinfection in the well-established murine brucellosis model using Trypanosoma musculi and B. abortus S19. Groups of C57BL/6 mice (Mus musculus) were infected with either B. abortus strain 19 (S19) or T. musculi or both. Sera were collected weekly; spleens from euthanized mice were tested to determine bacterial load near the end of normal brucellosis infection. Although changes in bacterial load were observed during the later stages of brucellosis in those mice coinfected with T. musculi, the most significant finding was the suppression of gamma interferon early during the infection along with an increase in interleukin-10 secretion compared with mice infected with either pathogen alone. These results suggest that immune modulatory events occur in the mouse during coinfection and that further experiments are warranted to determine if T. cervi impacts Brucella infection in elk.

  16. Ethyl Acetate Extract of Origanum vulgare L. ssp. hirtum Prevents Streptozotocin-Induced Diabetes in C57BL/6 Mice.

    PubMed

    Vujicic, Milica; Nikolic, Ivana; Kontogianni, Vassiliki G; Saksida, Tamara; Charisiadis, Pantelis; Vasic, Bobana; Stosic-Grujicic, Stanislava; Gerothanassis, Ioannis P; Tzakos, Andreas G; Stojanovic, Ivana

    2016-07-01

    Type 1 diabetes (T1D) is an autoimmune disease that develops as a consequence of pancreatic β-cell death induced by proinflammatory mediators. Because Origanum vulgare L. ssp. hirtum (Greek oregano) contains antiinflammatory molecules, we hypothesized that it might be beneficial for the treatment of T1D. An ethyl acetate extract of oregano (EAO) was prepared from the leaves by a polar extraction method. Phytochemical composition was determined by liquid chromatography-UV diode array coupled to ion-trap mass spectrometry with electrospray ionization interface (LC/DAD/ESI-MS(n) ). In vitro immunomodulatory effect of EAO was estimated by measuring proliferation (MTT) or cytokine secretion (ELISA) from immune cells. Diabetes was induced by multiple low doses of streptozotocin (MLDS) in male C57BL/6 mice and EAO was administered intraperitoneally for 10 d. Determination of cellular composition (flow cytometry) and cytokine production (ELISA) was performed on 12th d after diabetes induction. EAO suppressed the function of both macrophages and lymphocytes in vitro. In vivo, EAO treatment significantly preserved pancreatic islets and reduced diabetes incidence in MLDS-challenged mice. Besides down-modulatory effect on macrophages, EAO reduced the number of total CD4(+) and activated CD4(+) CD25(+) T cells. Furthermore, EAO affected the number of T helper 1 (Th1) and T helper 17 (Th17) cells through downregulation of their key transcription factors T-bet and RORγT. Because EAO treatment protects mice from development of hyperglycemia by reducing proinflammatory macrophage/Th1/Th17 response, this plant extract could represent a basis for future diabetes therapy. PMID:27219840

  17. Depletion of Kupffer cells modulates ethanol-induced hepatocyte DNA synthesis in C57Bl/6 mice.

    PubMed

    Owumi, Solomon E; Corthals, Stacy M; Uwaifo, Anthony O; Kamendulis, Lisa M; Klaunig, James E

    2014-08-01

    Kupffer cells (KCs) are important in hepatic homeostasis and responses to xenobiotics. KCs are activated on interaction with endotoxin, releasing cytokines, and reactive oxygen species normally associated with increased gene expression, cellular growth, or hepatic injury. Ethanol-induced endotoxemia is one means of KC activation. We propose that KC depletion attenuates the effect of EtOH-induced endotoxemia to impact the hepatic growth response. Hepatic DNA synthesis was examined in KC competent (KC+) or KC-depleted (KC-) C57BL/6 mice fed EtOH-containing diet in the presence or absence of polyphenol-60 antioxidant. KC depletion was assessed by F4/80 antigen, and DNA synthesis was assessed by 5-bromo-2'-deoxyuridine incorporation. Tumor necrosis factor alpha (TNF-α) messenger RNA released was quantified by RT-PCR/electrophoresis. ERK1/2 phosphorylation was evaluated by Western blotting, and Nrf2 and CYP2E1protein were also assayed. Apoptosis and hepatic injury were examined by the Tunnel assay and hepatic transaminases in serum, respectively. Hepatic transaminases in serum (AST and ALT) were within normal range. Over 90% of KC was depleted by clodronate treatment. KC depletion decreased TNF-α mRNA release, ERK1/2 phosphorylation, and hepatocyte DNA synthesis. KC depletion is associated with increased numbers of apoptotic cells bodies in KC- mice. Antioxidant treatment decreased DNA synthesis, Nrf2, and CYP2E1 protein expression in EtOH-consuming mice. Our data indicate that upon ethanol exposure, KC participates in hepatic DNA synthesis and growth responses. Collectively, these observations suggest that KC depletion attenuates the downstream effect of ethanol-induced endotoxemia by reduced cytokine and reactive oxygen species production with its concomitant effect on MAPK-signaling pathway on hepatocyte DNA synthesis.

  18. Quantifying Perivascular Sympathetic Innervation: Regional Differences in Male C57BL/6 Mice at 3 and 20 Months

    PubMed Central

    Long, Jennifer B.; Segal, Steven S.

    2009-01-01

    Perivascular sympathetic innervation density (PSID) is a key determinant of vasomotor responses to sympathetic nerve activity. However, total axonal length (for en passant neurotransmission) per vessel surface area has not been well defined, particularly while preserving 3-dimensional vascular structure. We developed a novel method for quantifying PSID using 3-dimensional anatomical reconstruction and compare a variety of blood vessels in Young (3 months) and Old (20 months) male C57BL/6 mice. Individual vessels were dissected and immunolabeled for tyrosine hydroxylase. The total length of fluorescent axons in defined vessel surface areas was quantified by mapping Z-stack images (magnification = 760×). For young mice, innervation densities (μm axon length/μm2 vessel surface area) in mesenteric (0.075 ± 0.002) and femoral (0.080 ± 0.003) arteries were greater (P<0.05) than mesenteric veins (0.052 ± 0.002) and gracilis muscle feed arteries (0.040 ± 0.002). Carotid arteries and gracilis muscle veins were not immunoreactive nor were there significant differences in PSID between Young and Old animals. We demonstrate a novel approach to quantify sympathetic innervation of the vasculature while preserving its 3-dimensional structure and document regional variation in PSID that persists with aging in mice. This analytical approach may used for quantifying PSID in other tissues that have superficial vessels which can be studied in situ or from which embedded vessels can be excised. With appropriate visualization of neuronal projections, it may also be applied to tissues that have other sources of superficial innervation. PMID:19651158

  19. Morphoquantitative analysis of the Ileum of C57BL/6 mice (Mus musculus) fed with a high-fat diet

    PubMed Central

    Navarrete, Javiera; Vásquez, Bélgica; del Sol, Mariano

    2015-01-01

    Due to the increase in overweight and obesity in humans, various studies have been conducted in recent years that demonstrate the detrimental effects on tissues and organs. The aim of this study was to assess the morphoquantitative changes produced in the ileum of mice, associated with high-fat diets. Fourteen male C57BL/6 mice, 5 months old, were fed two types of diets for 14 weeks. The control group (C) was fed a standard diet (10% fat, AIN-93M) and the experimental group (E) was fed a high-fat diet (42% fat, AIN-93M-AG). The assessments included: body weight, calorie consumption, food efficiency, biochemical analysis of plasma lipids, diameter, total wall thickness, thickness of the tunica mucosa and tunica muscularis, length and width of the intestinal villi, depth of the intestinal crypts and number of goblet cells per mm-2 (NA). For the statistical analysis the Student’s t-test was used, considering a P value less than 0.05. The mice in the E group presented greater weight gain (P = 0.028), higher levels of total and LDL cholesterol (P = 0.03 and P = 0.01, respectively), and length of the intestinal villi (P = 0.000). The width of the intestinal villi and the NA of PAS-positive goblet cells presented significantly lower values (P = 0.037 and P = 0.039, respectively) than the C group. The observed changes could be related to the higher demand for fat absorption and to possible alterations in the intestinal microflora and inflammation by action of high-fat diets. PMID:26823788

  20. DISTINCT EFFECTS OF CALORIE RESTRICTION AND EXERCISE ON MAMMARY GLAND GENE EXPRESSION IN C57BL/6 MICE

    PubMed Central

    Padovani, Michela; Lavigne, Jackie A.; Chandramouli, Gadisetti V.R.; Perkins, Susan N.; Barrett, J. Carl; Hursting, Stephen D.; Bennett, L. Michelle; Berrigan, David

    2009-01-01

    Energy balance, including diet, weight, adiposity, and physical activity is associated with carcinogenesis. Epidemiological studies indicate that obesity and sedentary and/or active behavior are risk factors for breast cancer in postmenopausal women and survival in both pre-and postmenopausal breast cancer patients. Thus, understanding energy balance modulation’s influence on changes in gene expression patterns in the normal mammary gland is important for understanding mechanisms linking energy balance and breast cancer. In a six week long study, female C57BL/6 mice (9 weeks old) were randomized into four groups: 1) food consumed ad libitum (AL); 2) AL with access to running wheels (AL+EX); 3) 30% Calorie Restricted (CR); and 4) 30% CR with access to running wheels (CR+EX). CR mice received 70% of calories but 100% of all other nutrients compared to AL mice. Diet and exercise treatments individually and combined, had significant effects on body composition and physical activity. Affymetrix oligo-microarrays were used to explore changes in gene expression patterns in total RNA samples from excised whole mammary glands. Contrasting AL versus CR resulted in 425 statistically significant expression changes whereas AL versus AL +EX resulted in 45 changes, with only 3 changes included the same genes, indicating that CR and EX differentially influence expression patterns in non-cancerous mammary tissue. Differential expression was observed in genes related to breast cancer stem cells, the epithelial -mesenchymal transition, and the growth and survival of breast cancer cells. Thus, CR and EX appear to exert their effects on mammary carcinogenesis through distinct pathways. PMID:19952363

  1. Ethyl Acetate Extract of Origanum vulgare L. ssp. hirtum Prevents Streptozotocin-Induced Diabetes in C57BL/6 Mice.

    PubMed

    Vujicic, Milica; Nikolic, Ivana; Kontogianni, Vassiliki G; Saksida, Tamara; Charisiadis, Pantelis; Vasic, Bobana; Stosic-Grujicic, Stanislava; Gerothanassis, Ioannis P; Tzakos, Andreas G; Stojanovic, Ivana

    2016-07-01

    Type 1 diabetes (T1D) is an autoimmune disease that develops as a consequence of pancreatic β-cell death induced by proinflammatory mediators. Because Origanum vulgare L. ssp. hirtum (Greek oregano) contains antiinflammatory molecules, we hypothesized that it might be beneficial for the treatment of T1D. An ethyl acetate extract of oregano (EAO) was prepared from the leaves by a polar extraction method. Phytochemical composition was determined by liquid chromatography-UV diode array coupled to ion-trap mass spectrometry with electrospray ionization interface (LC/DAD/ESI-MS(n) ). In vitro immunomodulatory effect of EAO was estimated by measuring proliferation (MTT) or cytokine secretion (ELISA) from immune cells. Diabetes was induced by multiple low doses of streptozotocin (MLDS) in male C57BL/6 mice and EAO was administered intraperitoneally for 10 d. Determination of cellular composition (flow cytometry) and cytokine production (ELISA) was performed on 12th d after diabetes induction. EAO suppressed the function of both macrophages and lymphocytes in vitro. In vivo, EAO treatment significantly preserved pancreatic islets and reduced diabetes incidence in MLDS-challenged mice. Besides down-modulatory effect on macrophages, EAO reduced the number of total CD4(+) and activated CD4(+) CD25(+) T cells. Furthermore, EAO affected the number of T helper 1 (Th1) and T helper 17 (Th17) cells through downregulation of their key transcription factors T-bet and RORγT. Because EAO treatment protects mice from development of hyperglycemia by reducing proinflammatory macrophage/Th1/Th17 response, this plant extract could represent a basis for future diabetes therapy.

  2. Differential effects of MK-801 on cerebrocortical neuronal injury in C57BL/6J, NSA, and ICR mice.

    PubMed

    Brosnan-Watters, G; Ogimi, T; Ford, D; Tatekawa, L; Gilliam, D; Bilsky, E J; Nash, D

    2000-08-01

    1. Antagonists of the N-methyl-D-aspartate (NMDA) glutamate (Glu) receptor, including [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate], dizocilpine maleate (MK-801), injure pyramidal neurons in the posterior cingulate/retrosplenial (PC/RS) cortex when administered systemically to adult rats and mice. 2. These results have, to our knowledge, only been reported previously in Harlan Sprague Dawley albino rats and International Cancer Research (ICR) mice, an outbred albino strain. 3. Male Non-Swiss Albino (NSA) mice, an albino outbred strain, and male C57BL/6J (B6) mice, a pigmented inbred strain, were injected systemically with 1 mg/kg of MK-801 in the first experiment. This dose of MK-801 reliably produces cytoplasmic vacuoles in neurons in layers III and IV of the PC/RS cortex in 100% of ICR mice treated 4. There was a significant difference in the number of vacuolated neurons in B6 and NSA mice, as assessed by ANOVA. The NSA were not significantly different than previously examined ICR mice, but the B6 had fewer vacuolated neurons than either of the two outbred strains. 5. In the second experiment, male NSA, ICR, and B6 mice were injected systemically with a high dose, 10 mg/kg, of MK-801. This dose has been demonstrated to result in necrosis in the same population of neurons injured by lower doses of MK-801. 6. An ANOVA indicated that there was a significant difference among the three strains of mice, and a Fisher's protected t revealed that the B6 mice were significantly different from both the NSA and ICR, but that, with our test, those two strains were indistinguishable. 7. Male ICR, NSA, and B6 mice were tested in the holeboard food search task 5 hours after 1 mg/kg of MK-801. There were significant differences between the strains in performance both pre and posttreatment. The effect of the drug was not statistically significant. 8. These results suggest that there may be a genetically mediated difference in the reaction to NMDA

  3. Generating Chimeric Mice by Using Embryos from Nonsuperovulated BALB/c Mice Compared with Superovulated BALB/c and Albino C57BL/6 Mice.

    PubMed

    Esmail, Michael Y; Qi, Peimin; Connor, Aurora Burds; Fox, James G; García, Alexis

    2016-01-01

    The reliable generation of high-percentage chimeras from gene-targeted C57BL/6 embryonic stem cells has proven challenging, despite optimization of cell culture and microinjection techniques. To improve the efficiency of this procedure, we compared the generation of chimeras by using 3 different inbred, albino host, embryo-generating protocols: BALB/cAnNTac (BALB/c) donor mice superovulated at 4 wk of age, 12-wk-old BALB/c donor mice without superovulation, and C57BL/6NTac-Tyr(tm1Arte) (albino B6) mice superovulated at 4 wk of age. Key parameters measured included the average number of injectable embryos per donor, the percentage of live pups born from the total number of embryos transferred to recipients, and the number of chimeric pups with high embryonic-stem-cell contribution by coat color. Although albino B6 donors produced significantly more injectable embryos than did BALB/c donors, 12-wk-old BALB/c donor produced high-percentage (at least 70%) chimeras more than 2.5 times as often as did albino B6 mice and 20 times more efficiently than did 4-wk-old BALB/c donors. These findings clearly suggest that 12-wk-old BALB/c mice be used as blastocyst donors to reduce the number of mice used to generate each chimera, reduce the production of low-percentage chimeras, and maximize the generation of high-percentage chimeras from C57BL/6 embryonic stem cells. PMID:27423145

  4. Fish oil improves gene targets of Down syndrome in C57BL and BALB/c mice.

    PubMed

    Zmijewski, Peter A; Gao, Linda Y; Saxena, Abhinav R; Chavannes, Nastacia K; Hushmendy, Shazaan F; Bhoiwala, Devang L; Crawford, Dana R

    2015-05-01

    We have considered a novel gene targeting approach for treating pathologies and conditions whose genetic bases are defined using diet and nutrition. One such condition is Down syndrome, which is linked to overexpression of RCAN1 on human chromosome 21 for some phenotypes. We hypothesize that a decrease in RCAN1 expression with dietary supplements in individuals with Down syndrome represents a potential treatment. Toward this, we used in vivo studies and bioinformatic analysis to identify potential healthy dietary RCAN1 expression modulators. We observed Rcan1 isoform 1 (Rcan1-1) protein reduction in mice pup hippocampus after a 4-week curcumin and fish oil supplementation, with only fish oil reduction being statistically significant. Focusing on fish oil, we observed a 17% Rcan1-1 messenger RNA (mRNA) and 19% Rcan1-1 protein reduction in BALB/c mice after 5 weeks of fish oil supplementation. Fish oil supplementation starting at conception and in a different mouse strain (C57BL) led to a 27% reduction in hippocampal Rcan1-1 mRNA and a 34% reduction in spleen Rcan1-1 mRNA at 6 weeks of age. Hippocampal protein results revealed a modest 11% reduction in RCAN1-1, suggesting translational compensation. Bioinformatic mining of human fish oil studies also revealed reduced RCAN1 mRNA expression, consistent with the above studies. These results suggest the potential use of fish oil in treating Down syndrome and support our strategy of using select healthy dietary agents to treat genetically defined pathologies, an approach that we believe is simple, healthy, and cost-effective.

  5. Gustatory neural responses to umami stimuli in the parabrachial nucleus of C57BL/6J mice

    PubMed Central

    Yamamoto, Takashi; Boughter, John D.

    2012-01-01

    Umami is considered to be the fifth basic taste quality and is elicited by glutamate. The mouse is an ideal rodent model for the study of this taste quality because of evidence that suggests that this species, like humans, may sense umami-tasting compounds as unique from other basic taste qualities. We performed single-unit recording of taste responses in the parabrachial nucleus (PbN) of anesthetized C57BL/6J mice to investigate the central representation of umami taste. A total of 52 taste-responsive neurons (22 sucrose-best, 19 NaCl-best, 5 citric acid-best, and 6 quinine-best) were recorded from stimulation period with a large panel of basic and umami-tasting stimuli. No neuron responded best to monopotassium glutamate (MPG) or inosine 5′-monophosphate (IMP), suggesting convergence of input in the central nervous system. Synergism induced by an MPG-IMP mixture was observed in all sucrose-best and some NaCl-best neurons that possessed strong sensitivity to sucrose. In more than half of sucrose-best neurons, the MPG-IMP mixture evoked stronger responses than those elicited by their best stimulus. Furthermore, hierarchical cluster analysis and multidimensional analysis indicated close similarity between sucrose and the MPG-IMP mixture. These results strongly suggest the mixture tastes sweet to mice, a conclusion consistent with previous findings that show bidirectional generalization of conditioned taste aversion between sucrose and umami mixtures, and suppression of taste responses to both sucrose and mixtures by the antisweet polypeptide gurmarin in the chorda tympani nerve. The distribution pattern of reconstructed recording sites of specific neuron types suggested chemotopic organization in the PbN. PMID:22170968

  6. A transplantable TH-MYCN transgenic tumor model in C57Bl/6 mice for preclinical immunological studies in neuroblastoma.

    PubMed

    Kroesen, Michiel; Nierkens, Stefan; Ansems, Marleen; Wassink, Melissa; Orentas, Rimas J; Boon, Louis; den Brok, Martijn H; Hoogerbrugge, Peter M; Adema, Gosse J

    2014-03-15

    Current multimodal treatments for patients with neuroblastoma (NBL), including anti-disialoganglioside (GD2) monoclonal antibody (mAb) based immunotherapy, result in a favorable outcome in around only half of the patients with advanced disease. To improve this, novel immunocombinational strategies need to be developed and tested in autologous preclinical NBL models. A genetically well-explored autologous mouse model for NBL is the TH-MYCN model. However, the immunobiology of the TH-MYCN model remains largely unexplored. We developed a mouse model using a transplantable TH-MYCN cell line in syngeneic C57Bl/6 mice and characterized the immunobiology of this model. In this report, we show the relevance and opportunities of this model to study immunotherapy for human NBL. Similar to human NBL cells, syngeneic TH-MYCN-derived 9464D cells endogenously express the tumor antigen GD2 and low levels of MHC Class I. The presence of the adaptive immune system had little or no influence on tumor growth, showing the low immunogenicity of the NBL cells. In contrast, depletion of NK1.1+ cells resulted in enhanced tumor outgrowth in both wild-type and Rag1(-/-) mice, showing an important role for NK cells in the natural anti-NBL immune response. Analysis of the tumor infiltrating leukocytes ex vivo revealed the presence of both tumor associated myeloid cells and T regulatory cells, thus mimicking human NBL tumors. Finally, anti-GD2 mAb mediated NBL therapy resulted in ADCC in vitro and delayed tumor outgrowth in vivo. We conclude that the transplantable TH-MYCN model represents a relevant model for the development of novel immunocombinatorial approaches for NBL patients.

  7. [Antitumor effect of mIFN-λ3 in C57BL/6 mice model for papilloma tumors].

    PubMed

    Choobin, H; Bamdad, T; Soleimanjahi, H; Razavinikoo, H

    2015-01-01

    Although several years have passed since the determination of the human papilloma virus (HPV) as the causative agent for cervical cancer, a definitive treatment has not yet been found. Interferon-alpha (IFN-α) immunotherapy is one of the promising methods for tumor treatment, although numerous side effects were observed in clinical trials. Recently, a new type of interferon, lambda-interferon (IFN-λ), has been discovered with fewer side effects than IFN-α since its receptor repertoire is limited. IFN-λ has a series of activities including antiviral, anti-proliferative and anti-tumor actions. In the present study, the effects of IFN-α and IFN-λ on the TC1 papilloma tumor model in C57BL/6 mice were evaluated. TC1 cells were injected into the mice subcutaneously. Upon tumor formation, murine IFN, mIFN-α and mIFN-λ, expression plasmids were injected intratumorally in combination or alone. The survival time and tumor size as well as apoptosis in tumors and NK cytoxicity were measured after three injections. As compared with the control group, the remarkable results especially in the group which received mIFN-α and mIFN-λ together were obtained for all of the measured parameters. Although IFN-λ is a new member of the interferon family and its properties should be studied in detail, the data obtained suggests that the use of IFN-λ especially in combination with IFN-α could be considered as an effective strategy for papilloma cervical cancer immunotherapy. PMID:26510595

  8. Antimicrobial peptides alter early immune response to influenza A virus infection in C57BL/6 mice.

    PubMed

    LeMessurier, Kim S; Lin, Yanyan; McCullers, Jonathan A; Samarasinghe, Amali E

    2016-09-01

    Influenza is a disease of the respiratory system caused by single stranded RNA viruses with varying genotypes. Immunopathogenesis to influenza viruses differs based on virus strain, dose, and mouse strain used in laboratory models. Although effective mucosal immune defenses are important in early host defense against influenza, information on the kinetics of these immune defense mechanisms during the course of influenza infection is limited. We investigated changes to antimicrobial peptides and primary innate immune cells at early time points after infection and compared these variables between two prominent H1N1 influenza A virus (IAV) strains, A/CA/04/2009 and A/PR/08/1934 in C57BL/6 mice. Alveolar and parenchymal macrophage ratios were altered after IAV infection and pro-inflammatory cytokine production in macrophages was induced after IAV infection. Genes encoding antimicrobial peptides, β-defensin (Defb4), bactericidal-permeability increasing protein (Bpifa1), and cathelicidin antimicrobial peptide (Camp), were differentially regulated after IAV infection and the kinetics of Defb4 expression differed in response to each virus strain. Beta-defensin reduced infectivity of A/CA/04/2009 virus but not A/PR/08/1934. Beta defensins also changed the innate immune cell profile wherein mice pre-treated with β-defensin had increased alveolar macrophages and CD103(+) dendritic cells, and reduced CD11b(+) dendritic cells and neutrophils. In addition to highlighting that immune responses may vary based on influenza virus strain used, our data suggest an important role for antimicrobial peptides in host defense against influenza virus. PMID:27531368

  9. Corticosterone exposure augments sensitivity to the behavioral and neuroplastic effects of fluoxetine in C57BL/6 mice

    PubMed Central

    Robinson, Shivon A.; Brookshire, Bethany R.; Lucki, Irwin

    2016-01-01

    Both genetic background and pre-existing stress play critical roles in the effects of antidepressant drugs. The current studies showed this principal by demonstrating that exposure to the stress hormone corticosterone (CORT) allowed behavioral and neurogenic effects to emerge following chronic treatment with fluoxetine of C57BL/6 mice, a strain ordinarily resistant to these effects. Adult male mice were implanted subcutaneously with 21-day slow-release CORT pellets (10 mg) or placebo and then co-treated with 5 mg/kg fluoxetine (b.i.d., i.p.) or saline for 14 days. Animals were then assessed for approach behavior in the novelty-induced hypophagia (NIH) test, hippocampal cell proliferation, corticosteroid receptor expression, and CORT plasma levels. Co-treatment of CORT with fluoxetine significantly reduced approach behavior in the novel environment of the NIH test and increased hippocampal cell proliferation whereas fluoxetine given alone was ineffective. CORT given alone did not alter approach behavior in the novel environment and caused a smaller increase of cell proliferation. The CORT effect was blocked by adrenalectomy and was likely due to increased adrenal feedback. Cell proliferation in CORT-treated animals was associated with reduced mineralocorticoid, but not glucocorticoid, receptor mRNA expression. Although the pellets were advertised to release CORT for 21 days, plasma CORT levels were increased at 1 day after implantation but were not sustained when measured at 7 days or longer intervals. Nevertheless, the transient CORT increase was sufficient to induce long-lasting behavioral and molecular changes when followed by fluoxetine treatment. These studies warrant further investigation into the role of glucocorticoids and environmental stress as adjunctive facilitators of the response to antidepressants, especially for treatment-resistant patients. PMID:26844246

  10. Antimicrobial peptides alter early immune response to influenza A virus infection in C57BL/6 mice.

    PubMed

    LeMessurier, Kim S; Lin, Yanyan; McCullers, Jonathan A; Samarasinghe, Amali E

    2016-09-01

    Influenza is a disease of the respiratory system caused by single stranded RNA viruses with varying genotypes. Immunopathogenesis to influenza viruses differs based on virus strain, dose, and mouse strain used in laboratory models. Although effective mucosal immune defenses are important in early host defense against influenza, information on the kinetics of these immune defense mechanisms during the course of influenza infection is limited. We investigated changes to antimicrobial peptides and primary innate immune cells at early time points after infection and compared these variables between two prominent H1N1 influenza A virus (IAV) strains, A/CA/04/2009 and A/PR/08/1934 in C57BL/6 mice. Alveolar and parenchymal macrophage ratios were altered after IAV infection and pro-inflammatory cytokine production in macrophages was induced after IAV infection. Genes encoding antimicrobial peptides, β-defensin (Defb4), bactericidal-permeability increasing protein (Bpifa1), and cathelicidin antimicrobial peptide (Camp), were differentially regulated after IAV infection and the kinetics of Defb4 expression differed in response to each virus strain. Beta-defensin reduced infectivity of A/CA/04/2009 virus but not A/PR/08/1934. Beta defensins also changed the innate immune cell profile wherein mice pre-treated with β-defensin had increased alveolar macrophages and CD103(+) dendritic cells, and reduced CD11b(+) dendritic cells and neutrophils. In addition to highlighting that immune responses may vary based on influenza virus strain used, our data suggest an important role for antimicrobial peptides in host defense against influenza virus.

  11. The neurosteroid allopregnanolone impairs object memory and contextual fear memory in male C57BL/6J mice.

    PubMed

    Rabinowitz, Akiva; Cohen, Sarah J; Finn, Deborah A; Stackman, Robert W

    2014-07-01

    Allopregnanolone (ALLO, or 3α-hydroxy-5α-pregnan-20-one) is a steroid metabolite of progesterone and a potent endogenous positive allosteric modulator of GABA-A receptors. Systemic ALLO has been reported to impair spatial, but not nonspatial learning in the Morris water maze (MWM) and contextual memory in rodents. These cognitive effects suggest an influence of ALLO on hippocampal-dependent memory, although the specific nature of the neurosteroid's effects on learning, memory or performance is unclear. The present studies aimed to determine: (i) the memory process(es) affected by systemic ALLO using a nonspatial object memory task; and (ii) whether ALLO affects object memory via an influence within the dorsal hippocampus. Male C57BL/6J mice received systemic ALLO either before or immediately after the sample session of a novel object recognition (NOR) task. Results demonstrated that systemic ALLO impaired the encoding and consolidation of object memory. A subsequent study revealed that bilateral microinfusion of ALLO into the CA1 region of dorsal hippocampus immediately following the NOR sample session also impaired object memory consolidation. In light of debate over the hippocampal-dependence of object recognition memory, we also tested systemic ALLO-treated mice on a contextual and cued fear-conditioning task. Systemic ALLO impaired the encoding of contextual memory when administered prior to the context pre-exposure session. Together, these results indicate that ALLO exhibits primary effects on memory encoding and consolidation, and extend previous findings by demonstrating a sensitivity of nonspatial memory to ALLO, likely by disrupting dorsal hippocampal function.

  12. Prototypical anxiolytics do not reduce anxiety-like behavior in the open field in C57BL/6J mice.

    PubMed

    Thompson, Trey; Grabowski-Boase, Laura; Tarantino, Lisa M

    2015-06-01

    Understanding and effectively treating anxiety disorders are a challenge for both scientists and clinicians. Despite a variety of available therapies, the efficacy of current treatments is still not optimal and adverse side effects can result in non-compliance. Animal models have been useful for studying the underlying biology of anxiety and assessing the anxiolytic properties of potential therapeutics. The open field (OF) is a commonly used assay of anxiety-like behavior. The OF was developed and validated in rats and then transferred to use in the mouse with only limited validation. The present study tests the efficacy of prototypical benzodiazepine anxiolytics, chlordiazepoxide (CDP) and diazepam (DZ), for increasing center time in the OF in C57BL/6J (B6) mice. Multiple doses of CDP and DZ did not change time spent in the center of the OF. Increasing illumination in the OF did not alter these results. The non-benzodiazepine anxiolytic, buspirone (BUSP) also failed to increase center time in the OF while the anxiogenic meta-chlorophenylpiperazine (mCPP) increased center time. Additional inbred mouse strains, BALB/cJ (BALB) and DBA/2J (D2) did not show any change in center time in response to CDP. Moreover, evaluation of CDP in B6 mice in the elevated plus maze (EPM), elevated zero maze (EZM) and light dark assay (LD) did not reveal changes in anxiety-like behavior while stress-induced hyperthermia (SIH) was decreased by DZ. Pharmacokinetic (PK) studies suggest that adequate CDP is present to induce anxiolysis. We conclude that the measure of center time in the OF does not show predictive validity for anxiolysis in these inbred mouse strains.

  13. Exercise Regulation of Marrow Fat in the Setting of PPARγ Agonist Treatment in Female C57BL/6 Mice.

    PubMed

    Styner, Maya; Pagnotti, Gabriel M; Galior, Kornelia; Wu, Xin; Thompson, William R; Uzer, Gunes; Sen, Buer; Xie, Zhihui; Horowitz, Mark C; Styner, Martin A; Rubin, Clinton; Rubin, Janet

    2015-08-01

    The contribution of marrow adipose tissue (MAT) to skeletal fragility is poorly understood. Peroxisome proliferator-activated receptor (PPAR)γ agonists, associated with increased fractures in diabetic patients, increase MAT. Here, we asked whether exercise could limit the MAT accrual and increase bone formation in the setting of PPARγ agonist treatment. Eight-week-old female C57BL/6 mice were treated with 20-mg/kg · d rosiglitazone (Rosi) and compared with control (CTL) animals. Exercise groups ran 12 km/d when provided access to running wheels (CTL exercise [CTL-E], Rosi-E). After 6 weeks, femoral MAT (volume of lipid binder osmium) and tibial bone morphology were assessed by microcomputer tomography. Rosi was associated with 40% higher femur MAT volume compared with CTL (P < .0001). Exercise suppressed MAT volume by half in CTL-E mice compared with CTL (P < .01) and 19% in Rosi-E compared with Rosi (P < .0001). Rosi treatment increased fat markers perilipin and fatty acid synthase mRNA by 4-fold (P < .01). Exercise was associated with increased uncoupling protein 1 mRNA expression in both CTL-E and Rosi-E groups (P < .05), suggestive of increased brown fat. Rosi increased cortical porosity (P < .0001) but did not significantly impact trabecular or cortical bone quantity. Importantly, exercise induction of trabecular bone volume was not prevented by Rosi (CTL-E 21% > CTL, P < .05; Rosi-E 26% > Rosi, P < .01). In summary, despite the Rosi induction of MAT extending well into the femoral diaphysis, exercise was able to significantly suppress MAT volume and induce bone formation. Our results suggest that the impact of PPARγ agonists on bone and marrow health can be partially mitigated by exercise. PMID:26052898

  14. The effect of mannan oligosaccharide supplementation on body weight gain and fat accrual in C57Bl/6J mice.

    PubMed

    Smith, Daniel L; Nagy, Tim R; Wilson, Landon S; Dong, Shengli; Barnes, Stephen; Allison, David B

    2010-05-01

    The prevalence of obesity in industrialized societies has become markedly elevated. In contrast, model organism research shows that reducing caloric intake below ad libitum levels provides many health and longevity benefits. Despite these benefits, few people are willing and able to reduce caloric intake over prolonged periods. Prior research suggests that mannooligosaccharide (MOS or mannan) supplementation can increase lifespan of some livestock and in rodents can reduce visceral fat without reducing caloric intake. Hence, we tested the effect of MOS supplementation as a possible calorie restriction (CR) mimetic (CRM) in mice. C57Bl/6J male mice were fed a high-fat "western" type diet with or without 1% MOS (by weight) supplementation (n = 24/group) from 8 to 20 weeks of age. Animals were housed individually and provided 95% of ad libitum food intake throughout the study. Body weight was measured weekly and body composition (lean and fat mass) measured noninvasively every 3 weeks. Individual fat depot weights were acquired by dissection at study completion. Supplementation of a high-fat diet with 1% MOS tended to reduce total food intake (mean +/- s.d.; control (CON): 293.69 +/- 10.53 g, MOS: 288.10 +/- 11.82 g; P = 0.09) during the study. Moreover, MOS supplementation had no significant effect on final body weight (CON: 25.21 +/- 2.31 g, MOS: 25.28 +/- 1.49 g; P = 0.91), total fat (CON: 4.72 +/- 0.90 g, MOS: 4.82 +/- 0.83 g; P = 0.69), or visceral fat (CON: 1.048 +/- 0.276 g, MOS: 1.004 +/- 0.247 g; P = 0.57). Contrary to previous research, MOS supplementation had no discernable effect on body weight gain or composition during this 12-week study, challenging the potential use of MOS as a CRM or body composition enhancer. PMID:19798073

  15. Acute alcohol exposure during neurulation: Behavioral and brain structural consequences in adolescent C57BL/6J mice.

    PubMed

    Fish, E W; Holloway, H T; Rumple, A; Baker, L K; Wieczorek, L A; Moy, S S; Paniagua, B; Parnell, S E

    2016-09-15

    Prenatal alcohol exposure (PAE) can induce physical malformations and behavioral abnormalities that depend in part on thedevelopmental timing of alcohol exposure. The current studies employed a mouse FASD model to characterize the long-term behavioral and brain structural consequences of a binge-like alcohol exposure during neurulation; a first-trimester stage when women are typically unaware that they are pregnant. Time-mated C57BL/6J female mice were administered two alcohol doses (2.8g/kg, four hours apart) or vehicle starting at gestational day 8.0. Male and female adolescent offspring (postnatal day 28-45) were then examined for motor activity (open field and elevated plus maze), coordination (rotarod), spatial learning and memory (Morris water maze), sensory motor gating (acoustic startle and prepulse inhibition), sociability (three-chambered social test), and nociceptive responses (hot plate). Regional brain volumes and shapes were determined using magnetic resonance imaging. In males, PAE increased activity on the elevated plus maze and reduced social novelty preference, while in females PAE increased exploratory behavior in the open field and transiently impaired rotarod performance. In both males and females, PAE modestly impaired Morris water maze performance and decreased the latency to respond on the hot plate. There were no brain volume differences; however, significant shape differences were found in the cerebellum, hypothalamus, striatum, and corpus callosum. These results demonstrate that alcohol exposure during neurulation can have functional consequences into adolescence, even in the absence of significant brain regional volumetric changes. However, PAE-induced regional shape changes provide evidence for persistent brain alterations and suggest alternative clinical diagnostic markers.

  16. Effects of eugenol on hepatic glucose production and AMPK signaling pathway in hepatocytes and C57BL/6J mice.

    PubMed

    Jeong, Kyong Ju; Kim, Do Yeon; Quan, Hai-Yan; Jo, Hee Kyung; Kim, Go Woon; Chung, Sung Hyun

    2014-03-01

    Eugenol is a phenylpropanoid with many pharmacological activities, but its anti-hyperglycemic activity is not yet fully explored. For in vitro study, HepG2 cells and primary rat hepatocytes were used, and glucose production was induced by adding 100 nM of glucagon in the presence of gluconeogenic substrates. In animal study, hyperglycemia was induced by high fat diet (HFD) in male C57BL/6J mice, and eugenol was orally administered at 20 or 40 mg per kg (E20, E40) for 15 weeks. Eugenol significantly inhibited glucagon-induced glucose production and phosphorylated AMPK in the HepG2 and primary rat hepatocytes, and these effects were reversed in the presence of compound C (an AMPK inhibitor) or STO-609 (a CAMKK inhibitor). In addition, the protein and gene expression levels of CREB, CRTC2·CREB complex, PGC-1α, PEPCK and G6Pase were all significantly suppressed. Moreover, inhibition of AMPK by over-expression of dominant negative AMPK prevented eugenol from suppressions of gluconeogenic gene expression and hepatic glucose production. In animal study, plasma glucose and insulin levels of the E40 group were decreased by 31% and 63%, respectively, when compared to those of HFD control. In pyruvate tolerance tests, pyruvate-induced glucose excursions were decreased, indicating that the anti-hyperglycemic activity of eugenol is primarily due to the suppression of hepatic gluconeogenesis. In summary, eugenol effectively ameliorates hyperglycemia through inhibition of hepatic gluconeogenesis via modulating CAMKK-AMPK-CREB signaling pathway. Eugenol or eugenol-containing medicinal plants could represent a promising therapeutic agent to prevent type 2 diabetes.

  17. Acute alcohol exposure during neurulation: Behavioral and brain structural consequences in adolescent C57BL/6J mice.

    PubMed

    Fish, E W; Holloway, H T; Rumple, A; Baker, L K; Wieczorek, L A; Moy, S S; Paniagua, B; Parnell, S E

    2016-09-15

    Prenatal alcohol exposure (PAE) can induce physical malformations and behavioral abnormalities that depend in part on thedevelopmental timing of alcohol exposure. The current studies employed a mouse FASD model to characterize the long-term behavioral and brain structural consequences of a binge-like alcohol exposure during neurulation; a first-trimester stage when women are typically unaware that they are pregnant. Time-mated C57BL/6J female mice were administered two alcohol doses (2.8g/kg, four hours apart) or vehicle starting at gestational day 8.0. Male and female adolescent offspring (postnatal day 28-45) were then examined for motor activity (open field and elevated plus maze), coordination (rotarod), spatial learning and memory (Morris water maze), sensory motor gating (acoustic startle and prepulse inhibition), sociability (three-chambered social test), and nociceptive responses (hot plate). Regional brain volumes and shapes were determined using magnetic resonance imaging. In males, PAE increased activity on the elevated plus maze and reduced social novelty preference, while in females PAE increased exploratory behavior in the open field and transiently impaired rotarod performance. In both males and females, PAE modestly impaired Morris water maze performance and decreased the latency to respond on the hot plate. There were no brain volume differences; however, significant shape differences were found in the cerebellum, hypothalamus, striatum, and corpus callosum. These results demonstrate that alcohol exposure during neurulation can have functional consequences into adolescence, even in the absence of significant brain regional volumetric changes. However, PAE-induced regional shape changes provide evidence for persistent brain alterations and suggest alternative clinical diagnostic markers. PMID:27185739

  18. Cirsium brevicaule A. GRAY leaf inhibits adipogenesis in 3T3-L1 cells and C57BL/6 mice

    PubMed Central

    2013-01-01

    Background Various flavonoids obtained from the genus Cirsium have been reported to exhibit beneficial effects on health. The present study evaluated the antiobesity effects of Cirsium brevicaule A. GRAY leaf (CL) by using 3T3-L1 cells and C57BL/6 mice that were fed a high-fat diet (HFD). Methods Dried CL powder was serially extracted with solvents of various polarities, and these extracts were tested for antiadipogenic activity using 3T3-L1 adipocytes. Mice were fed experimental HFD supplemented with dried CL powder for 4 wk. Lipid levels and mRNA levels of genes related to lipid metabolism were determined in 3T3-L1 adipocytes and the white adipose tissue (WAT) and liver of mice fed on a HFD. Results Treatment of 3T3-L1 adipocytes with a hexane extract of CL significantly reduced cellular lipid accumulation and expression of the fatty acid synthase (FASN) gene. Dietary CL reduced the serum levels of non-esterified fatty acids in HFD-fed mice. Significant decreases in subcutaneous WAT weight and associated FASN gene expression were observed in the mice fed the experimental CL diet. Dietary CL also reduced the hepatic lipid and serum levels of a hepatopathic indicator in the HFD-fed mice. A significant reduction in mRNA levels of FASN and HMG-CoA reductase were observed in the livers of the CL-diet group. Dietary CL, on the other hand, increased in the hepatic mRNA levels of genes related to β-oxidation, namely peroxisome proliferator-activated receptor α, calnitine palmitoyltrasferase 1A, and uncoupling protein 2. Expression of the insulin receptor gene was also significantly increased in the livers of mice-fed the CL diet. Conclusions The present study therefore demonstrated that CL suppresses lipid accumulation in the WAT and liver partly through inhibiting mRNA levels of FASN gene and enhancing the lipolysis-related gene expression. PMID:23945333

  19. Immunological and nonimmunological control of severity of Trypanosoma musculi infections in C3H and C57BL/6 inbred mice

    SciTech Connect

    Albright, J.W.; Albright, J.F.

    1989-06-01

    Studies concerned with the mechanisms responsible for relative resistance or susceptibility of strains of inbred mice to Trypanosoma musculi infections are presented. Treatment with 400 rads of ionizing radiation, silica dust, or trypan blue (reticuloendothelial blocking agents) rendered C3H mice unable to control the initial maximum level of parasite growth, and the mice died of overwhelming infections. In contrast, similarly treated C57BL/6 (relatively resistant) mice controlled initial trypanosome growth as well as controls; however, the duration of infection, preceding eventual cure, was approximately doubled. Combined treatment with trypan blue and 400 rads of radiation resulted in much higher initial levels of infection in C57BL/6 mice, and about half of the mice died; the remaining mice eventually recovered after a prolonged course of infection. These results indicate that a nonimmunological mechanism, which controls initial infection, and an immunological mechanism cooperate to limit T. musculi infections in normal mice. We present results that suggest that both mechanisms are less effective in C3H than in C57BL/6 mice. The initial control of infection presumably reflects the activity of some type(s) of phagocytic effector cell; we show, however, that the initial control of infection is not an attribute of the liver Kupffer cells. Identification and characterization of the cells capable of controlling initial infection could lead to procedures for enhancing their function and, thus, to enhanced resistance to, and elimination of, trypanosome infections.

  20. Physiological effects of housing density on C57BL/6J mice over a 9-month period1

    PubMed Central

    Paigen, B.; Svenson, K. L.; Von Smith, R.; Marion, M. A.; Stearns, T.; Peters, L. L.; Smith, A. L.

    2012-01-01

    The National Research Council has consistently recommended housing densities for animals used in science and agriculture. For mice, the recommended density is 77.4 cm2 (12 in2) for a 15–25 gm mouse. The Council noted that its recommendations were based on “best professional judgment” and encouraged alternatives that were data driven. As part of a continual effort of The Jackson Laboratory to ensure the health and well-being of production and research mice while promoting cost-effective, state-of-the-art research, several density-driven studies have been conducted by lab researchers. The objectives of this study were to determine the effect of housing density on parameters related to mouse physiology and air quality in the cages and to assess the value of specific measured parameters in such studies. The study discussed in this report monitored C57BL/6J mice in individually ventilated cages from weaning until 9 months of age. Housing densities were equivalent to 66.4 and 36.8 cm2/mouse (10.3 and 5.7 in2), representing increases in density of 17% and 110%, respectively, over the National Research Council recommendation. Clinical physiological parameters representing general health and well-being were measured. Hematological traits, plasma lipids and glucose, growth, bone mineral density and percent body fat did not differ between densities. In the more densely housed mice, however, adrenal glands were significantly smaller, heart rates were significantly lower, and food consumption was less. Cage air microenvironment was evaluated for ammonia, carbon dioxide, temperature and humidity in cages changed weekly or every 2 weeks. The cage microenvironment remained within acceptable limits at the higher density of mice at both cage-changing frequencies. The results suggest that mice housed in individually ventilated cages for up to 9 months at up to twice the density currently recommended by the National Research Council show no measurable adverse effects. Continued

  1. Generation and characterization of pilocarpine-sensitive C57BL/6 mice as a model of temporal lobe epilepsy.

    PubMed

    Bankstahl, Marion; Müller, Christine J; Wilk, Esther; Schughart, Klaus; Löscher, Wolfgang

    2012-04-21

    C57BL/6 (B6) is the most widely used inbred mouse strain, but its use in epilepsy research is compromised by low sensitivity to various convulsants, including pilocarpine. We recently identified a subline of B6NCrl mice in a barrier (#8) of a German vendor (Charles River) that was much more sensitive to status epilepticus (SE) induction than B6NCrl mice from four other barriers of the same vendor and other B6 substrains. Breeding experiments indicated that the observed differences have a genetic basis, thus offering a unique opportunity to identify the genes and pathways involved and contributing to a better understanding of the underlying molecular mechanisms of seizure susceptibility. Since the pilocarpine-sensitive B6 subline (B6NCrl#8) is not further available from the breeder, we decided to generate a new highly pilocarpine-sensitive B6NCrl subline by crossing female B6NCrl#8 mice with male F1 hybrids. Further sister-brother mating of the resulting F2 generation generated a highly susceptible F3 generation. Similar to B6NCrl#8 mice, mice from the F3 generation were significantly more susceptible to SE induction than any other B6 substrain, including B6J (JAX) mice, which were particularly insensitive to seizure induction. In contrast to the marked inter-subline differences in susceptibility to induction of SE, B6 sublines did not differ in the long-term consequences of SE, i.e., development of spontaneous seizures and neurodegeneration in the hippocampus, although hippocampal damage was much less severe than previously reported for other mouse strains. We have started to search for genetic loci underlying the high seizure susceptibility of B6NCrl#8 and filial generations obtained by cross-breeding with this B6 subline. Further characterization of the genetic variations underlying high susceptibility to convulsants such as pilocarpine will facilitate our understanding of the pathomechanisms involved in the evolution of single seizures to a self-sustained SE and

  2. Quantitative trait loci that control body weight and obesity in an F2 intercross between C57BL/6J and DDD.Cg-Ay mice.

    PubMed

    Suto, Jun-ichi

    2011-07-01

    I have developed a congenic mouse strain for the A(y) allele at the agouti locus in an inbred DDD/Sgn strain, DDD.Cg-A(y). DDD.Cg-A(y) females are extremely obese and significantly heavier than B6.Cg-A(y) females. The objectives of this study were to determine the genetic basis of obesity in DDD.Cg-A(y) mice, and to determine whether or not their high body weight was due to the presence of DDD background-specific modifiers. I performed quantitative trait locus (QTL) analyses for body weight and body mass index in two types of F(2) mice [F2 A(y) (F(2) mice carrying the A(y) allele) and F(2) non-A(y) (F2 mice without the A(y) allele)] produced by crossing C57BL/6J females and DDD.Cg-A(y) males. The results of the QTL analysis of F(2) A(y) mice were very similar to those obtained for F(2) non-A(y) mice. It was unlikely that the high body weight of DDD.Cg-A(y) mice was due to the presence of specific modifiers. When both F(2) datasets were merged and analyzed, four significant body weight QTLs were identified on chromosomes 6, 9, and 17 (2 loci) and four significant obesity QTLs were identified on chromosomes 1, 6, 9, and 17. Although the presence of DDD background-specific modifiers was not confirmed, a multifactorial basis of obesity in DDD.Cg-A(y) females was thus revealed.

  3. Long Term Metabolic Syndrome Induced by a High Fat High Fructose Diet Leads to Minimal Renal Injury in C57BL/6 Mice

    PubMed Central

    Dissard, Romain; Klein, Julie; Caubet, Cécile; Breuil, Benjamin; Siwy, Justyna; Hoffman, Janosch; Sicard, Laurent; Ducassé, Laure; Rascalou, Simon; Payre, Bruno; Buléon, Marie; Mullen, William; Mischak, Harald; Tack, Ivan; Bascands, Jean-Loup; Buffin-Meyer, Bénédicte; Schanstra, Joost P.

    2013-01-01

    Metabolic syndrome can induce chronic kidney disease in humans. Genetically engineered mice on a C57BL/6 background are highly used for mechanistic studies. Although it has been shown that metabolic syndrome induces cardiovascular lesions in C57BL/6 mice, in depth renal phenotyping has never been performed. Therefore in this study we characterized renal function and injury in C57BL/6 mice with long-term metabolic syndrome induced by a high fat and fructose diet (HFFD). C57BL/6 mice received an 8 months HFFD diet enriched with fat (45% energy from fat) and drinking water enriched with fructose (30%). Body weight, food/water consumption, energy intake, fat/lean mass ratio, plasma glucose, HDL, LDL, triglycerides and cholesterol levels were monitored. At 3, 6 and 8 months, renal function was determined by inulin clearance and measure of albuminuria. At sacrifice, kidneys and liver were collected. Metabolic syndrome in C57BL/6 mice fed a HFFD was observed as early 4 weeks with development of type 2 diabetes at 8 weeks after initiation of diet. However, detailed analysis of kidney structure and function showed only minimal renal injury after 8 months of HFFD. HFFD induced moderate glomerular hyperfiltration (436,4 µL/min vs 289,8 µL/min; p-value=0.0418) together with a 2-fold increase in albuminuria only after 8 months of HFFD. This was accompanied by a 2-fold increase in renal inflammation (p-value=0.0217) but without renal fibrosis or mesangial matrix expansion. In addition, electron microscopy did not show alterations in glomeruli such as basal membrane thickening and foot process effacement. Finally, comparison of the urinary peptidome of these mice with the urinary peptidome from humans with diabetic nephropathy also suggested absence of diabetic nephropathy in this model. This study provides evidence that the HFFD C57BL/6 model is not the optimal model to study the effects of metabolic syndrome on the development of diabetic kidney disease. PMID:24098551

  4. Long term metabolic syndrome induced by a high fat high fructose diet leads to minimal renal injury in C57BL/6 mice.

    PubMed

    Dissard, Romain; Klein, Julie; Caubet, Cécile; Breuil, Benjamin; Siwy, Justyna; Hoffman, Janosch; Sicard, Laurent; Ducassé, Laure; Rascalou, Simon; Payre, Bruno; Buléon, Marie; Mullen, William; Mischak, Harald; Tack, Ivan; Bascands, Jean-Loup; Buffin-Meyer, Bénédicte; Schanstra, Joost P

    2013-01-01

    Metabolic syndrome can induce chronic kidney disease in humans. Genetically engineered mice on a C57BL/6 background are highly used for mechanistic studies. Although it has been shown that metabolic syndrome induces cardiovascular lesions in C57BL/6 mice, in depth renal phenotyping has never been performed. Therefore in this study we characterized renal function and injury in C57BL/6 mice with long-term metabolic syndrome induced by a high fat and fructose diet (HFFD). C57BL/6 mice received an 8 months HFFD diet enriched with fat (45% energy from fat) and drinking water enriched with fructose (30%). Body weight, food/water consumption, energy intake, fat/lean mass ratio, plasma glucose, HDL, LDL, triglycerides and cholesterol levels were monitored. At 3, 6 and 8 months, renal function was determined by inulin clearance and measure of albuminuria. At sacrifice, kidneys and liver were collected. Metabolic syndrome in C57BL/6 mice fed a HFFD was observed as early 4 weeks with development of type 2 diabetes at 8 weeks after initiation of diet. However, detailed analysis of kidney structure and function showed only minimal renal injury after 8 months of HFFD. HFFD induced moderate glomerular hyperfiltration (436,4 µL/min vs 289,8 µL/min; p-value=0.0418) together with a 2-fold increase in albuminuria only after 8 months of HFFD. This was accompanied by a 2-fold increase in renal inflammation (p-value=0.0217) but without renal fibrosis or mesangial matrix expansion. In addition, electron microscopy did not show alterations in glomeruli such as basal membrane thickening and foot process effacement. Finally, comparison of the urinary peptidome of these mice with the urinary peptidome from humans with diabetic nephropathy also suggested absence of diabetic nephropathy in this model. This study provides evidence that the HFFD C57BL/6 model is not the optimal model to study the effects of metabolic syndrome on the development of diabetic kidney disease.

  5. NMDA Receptor Blockade by Ketamine Abrogates Lipopolysaccharide-Induced Depressive-Like Behavior in C57BL/6J Mice

    PubMed Central

    Walker, Adam K; Budac, David P; Bisulco, Stephanie; Lee, Anna W; Smith, Robin A; Beenders, Brent; Kelley, Keith W; Dantzer, Robert

    2013-01-01

    We have previously demonstrated that lipopolysaccharide (LPS) induces depressive-like behavior by activating indoleamine 2,3 dioxygenase (IDO; O'Connor et al, 2009c). IDO degrades tryptophan along the kynurenine pathway. Using mass-spectrometry (LC-MS) analysis of kynurenine metabolites in the brain of mice injected at the periphery with 1 mg/kg LPS, we show that LPS activates the kynurenine 3-monooxygenase pathway that ultimately degrades kynurenine into quinolinic acid. As quinolinic acid acts as an N-methyl-𝒟-aspartate (NMDA) receptor agonist, we used the NMDA receptor antagonist ketamine to assess the role of NMDA receptor activation in LPS-induced depressive-like behavior. Here, we report that a low dose of ketamine (6 mg/kg, intraperitoneally) immediately before administration of LPS (0.83 mg/kg, intraperitoneally) in C57Bl/6 J mice abrogated the development of LPS-induced depressive-like behavior, without altering LPS-induced sickness measured by body weight loss, decreased motor activity, and reduced food intake. Depressive-like behavior was measured 24 h after LPS by decreased sucrose preference and increased immobility in the forced swim test (FST). Ketamine had no effect on LPS-induced cytokine expression in the liver and brain, IDO activation, and brain-derived neurotrophic factor (BDNF) transcripts. The ability of ketamine to abrogate LPS-induced depressive-like behavior independently of a possible interference with LPS-induced inflammatory signaling was confirmed when ketamine was administered 10 h after LPS instead of immediately before LPS. In contrast, ketamine had no effect when administered 24 h before LPS. To confirm that NMDA receptor antagonism by ketamine mediates the antidepressant-like activity of this compound in LPS-treated mice, mice were pretreated with the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline-2,3-dione (NBQX) to block

  6. Direct calorimetry identifies deficiencies in respirometry for the determination of resting metabolic rate in C57Bl/6 and FVB mice.

    PubMed

    Burnett, Colin M L; Grobe, Justin L

    2013-10-01

    Substantial research efforts have been aimed at identifying novel targets to increase resting metabolic rate (RMR) as an adjunct approach to the treatment of obesity. Respirometry (one form of "indirect calorimetry") is unquestionably the dominant technique used in the obesity research field to assess RMR in vivo, although this method relies upon a lengthy list of assumptions that are likely to be violated in pharmacologically or genetically manipulated animals. A "total" calorimeter, including a gradient layer direct calorimeter coupled to a conventional respirometer, was used to test the accuracy of respirometric-based estimations of RMR in laboratory mice (Mus musculus Linnaeus) of the C57Bl/6 and FVB background strains. Using this combined calorimeter, we determined that respirometry underestimates RMR of untreated 9- to 12-wk-old male mice by ∼10-12%. Quantitative and qualitative differences resulted between methods for untreated C57Bl/6 and FVB mice, C57Bl/6 mice treated with ketamine-xylazine anesthesia, and FVB mice with genetic deletion of the angiotensin II type 2 receptor. We conclude that respirometric methods underestimate RMR in mice in a magnitude that is similar to or greater than the desired RMR effects of novel therapeutics. Sole reliance upon respirometry to assess RMR in mice may lead to false quantitative and qualitative conclusions regarding the effects of novel interventions. Increased use of direct calorimetry for the assessment of RMR and confirmation of respirometry results and the reexamination of previously discarded potential obesity therapeutics are warranted.

  7. PCB153-elicited hepatic responses in the immature, ovariectomized C57BL/6 mice: Comparative toxicogenomic effects of dioxin and non-dioxin-like ligands

    SciTech Connect

    Kopec, Anna K.; Burgoon, Lyle D.; Ibrahim-Aibo, Daher; Mets, Bryan D.; Tashiro, Colleen; Potter, Dave; Sharratt, Bonnie; Harkema, Jack R.; Zacharewski, Timothy R.

    2010-03-15

    Polychlorinated biphenyls (PCBs) are ubiquitous contaminants found as complex mixtures of coplanar and non-coplanar congeners. The hepatic temporal and dose-dependent effects of the most abundant non-dioxin-like congener, 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153), were examined in immature, ovariectomized C57BL/6 mice, and compared to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the prototypical aryl hydrocarbon receptor (AhR) ligand. Animals were gavaged once with 300 mg/kg PCB153 or sesame oil vehicle and sacrificed 4, 12, 24, 72 or 168 h post dose. In the dose-response study, mice were gavaged with 1, 3, 10, 30, 100 or 300 mg/kg PCB153 or sesame oil for 24 h. Significant increases in relative liver weights were induced with 300 mg/kg PCB153 between 24 and 168 h, accompanied by slight vacuolization and hepatocellular hypertrophy. The hepatic differential expression of 186 and 177 genes was detected using Agilent 4 x 44 K microarrays in the time course (|fold change| >= 1.5, P1(t) >= 0.999) and dose-response (|fold change| >= 1.5, P1(t) >= 0.985) studies, respectively. Comparative analysis with TCDD suggests that the differential gene expression elicited by PCB153 was not mediated by the AhR. Furthermore, constitutive androstane and pregnane X receptor (CAR/PXR) regulated genes including Cyp2b10, Cyp3a11, Ces2, Insig2 and Abcc3 were dose-dependently induced by PCB153. Collectively, these results suggest that the hepatocellular effects elicited by PCB153 are qualitatively and quantitatively different from TCDD and suggestive of CAR/PXR regulation.

  8. “PCB153-Elicited Hepatic Responses in the Immature, Ovariectomized C57BL/6 Mice: Comparative Toxicogenomic Effects of Dioxin and Non-Dioxin-Like Ligands”

    PubMed Central

    Kopec, Anna K.; Burgoon, Lyle D.; Ibrahim-Aibo, Daher; Mets, Bryan D.; Tashiro, Colleen; Potter, Dave; Sharratt, Bonnie; Harkema, Jack R.; Zacharewski, Timothy

    2010-01-01

    Polychlorinated biphenyls (PCBs) are ubiquitous contaminants found as complex mixtures of coplanar and non-coplanar congeners. The hepatic temporal and dose-dependent effects of the most abundant non-dioxin-like congener, 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153), were examined in immature, ovariectomized C57BL/6 mice, and compared to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the prototypical aryl hydrocarbon receptor (AhR) ligand. Animals were gavaged once with 300 mg/kg PCB153 or sesame oil vehicle and sacrificed 4, 12, 24, 72 or 168 h post dose. In the dose-response study, mice were gavaged with 1, 3, 10, 30, 100 or 300 mg/kg PCB153 or sesame oil for 24 h. Significant increases in relative liver weights were induced with 300 mg/kg PCB153 between 24 and 168 h, accompanied by slight vacuolization and hepatocellular hypertrophy. The hepatic differential expression of 186 and 177 genes was detected using Agilent 4 x 44 K microarrays in the time course (|fold change|≥1.5, P1(t)≥0.999) and dose-response (|fold change|≥1.5, P1(t)≥0.985) studies, respectively. Comparative analysis with TCDD suggests that the differential gene expression elicited by PCB153 was not mediated by the AhR. Furthermore, constitutive androstane and pregnane X receptor (CAR/PXR) regulated genes including Cyp2b10, Cyp3a11, Ces2, Insig2 and Abcc3 were dose-dependently induced by PCB153. Collectively, these results suggest that the hepatocellular effects elicited by PCB153 are qualitatively and quantitatively different from TCDD and suggestive of CAR/PXR regulation. PMID:20005886

  9. Developmental Neurotoxic Effects of Percutaneous Drug Delivery: Behavior and Neurochemical Studies in C57BL/6 Mice.

    PubMed

    Wu, Huali; Feng, Junyi; Lv, Wenting; Huang, Qiaoling; Fu, Mengsi; Cai, Minxuan; He, Qiangqiang; Shang, Jing

    2016-01-01

    Dermatosis often as a chronic disease requires effective long-term treatment; a comprehensive evaluation of mental health of dermatology drug does not receive enough attention. An interaction between dermatology and psychiatry has been increasingly described. Substantial evidence has accumulated that psychological stress can be associated with pigmentation, endocrine and immune systems in skin to create the optimal responses against pathogens and other physicochemical stressors to maintain or restore internal homeostasis. Additionally, given the common ectodermal origin shared by the brain and skin, we are interested in assessing how disruption of skin systems (pigmentary, endocrine and immune systems) may play a key role in brain functions. Thus, we selected three drugs (hydroquinone, isotretinoin, tacrolimus) with percutaneous excessive delivery to respectively intervene in these systems and then evaluate the potential neurotoxic effects. Firstly, C57BL/6 mice were administrated a dermal dose of hydroquinone cream, isotretinoin gel or tacrolimus ointment (2%, 0.05%, 0.1%, respectively, 5 times of the clinical dose). Behavioral testing was performed and levels of proteins were measured in the hippocampus. It was found that mice treated with isotretinoin or tacrolimus, presented a lower activity in open-field test and obvious depressive-like behavior in tail suspension test. Besides, they damaged cytoarchitecture, reduced the level of 5-HT-5-HT1A/1B system and increased the expression of apoptosis-related proteins in the hippocampus. To enable sensitive monitoring the dose-response characteristics of the consecutive neurobehavioral disorders, mice received gradient concentrations of hydroquinone (2%, 4%, 6%). Subsequently, hydroquinone induced behavioral disorders and hippocampal dysfunction in a dose-dependent response. When doses were high as 6% which was 3 times higher than 2% dose, then 100% of mice exhibited depressive-like behavior. Certainly, 6% hydroquinone

  10. Developmental Neurotoxic Effects of Percutaneous Drug Delivery: Behavior and Neurochemical Studies in C57BL/6 Mice

    PubMed Central

    Lv, Wenting; Huang, Qiaoling; Fu, Mengsi; Cai, Minxuan; He, Qiangqiang

    2016-01-01

    Dermatosis often as a chronic disease requires effective long-term treatment; a comprehensive evaluation of mental health of dermatology drug does not receive enough attention. An interaction between dermatology and psychiatry has been increasingly described. Substantial evidence has accumulated that psychological stress can be associated with pigmentation, endocrine and immune systems in skin to create the optimal responses against pathogens and other physicochemical stressors to maintain or restore internal homeostasis. Additionally, given the common ectodermal origin shared by the brain and skin, we are interested in assessing how disruption of skin systems (pigmentary, endocrine and immune systems) may play a key role in brain functions. Thus, we selected three drugs (hydroquinone, isotretinoin, tacrolimus) with percutaneous excessive delivery to respectively intervene in these systems and then evaluate the potential neurotoxic effects. Firstly, C57BL/6 mice were administrated a dermal dose of hydroquinone cream, isotretinoin gel or tacrolimus ointment (2%, 0.05%, 0.1%, respectively, 5 times of the clinical dose). Behavioral testing was performed and levels of proteins were measured in the hippocampus. It was found that mice treated with isotretinoin or tacrolimus, presented a lower activity in open-field test and obvious depressive-like behavior in tail suspension test. Besides, they damaged cytoarchitecture, reduced the level of 5-HT-5-HT1A/1B system and increased the expression of apoptosis-related proteins in the hippocampus. To enable sensitive monitoring the dose-response characteristics of the consecutive neurobehavioral disorders, mice received gradient concentrations of hydroquinone (2%, 4%, 6%). Subsequently, hydroquinone induced behavioral disorders and hippocampal dysfunction in a dose-dependent response. When doses were high as 6% which was 3 times higher than 2% dose, then 100% of mice exhibited depressive-like behavior. Certainly, 6% hydroquinone

  11. Differences in BTBR T+ tf/J and C57BL/6J mice on probabilistic reversal learning and stereotyped behaviors

    PubMed Central

    Amodeo, Dionisio A.; Jones, Joshua H.; Sweeney, John A.; Ragozzino, Michael E.

    2011-01-01

    Autism spectrum disorders (ASD) represent a class of neurodevelopmental disorders characterized by impairments in social interaction, verbal and non-verbal communication, as well as restricted interests and repetitive behavior. This latter class of symptoms often includes features such as compulsive behaviors and resistance to change. The BTBR T+tf/J mouse strain has been used as an animal model to investigate the social communication and restricted interest features in ASD. Less is known about whether this mouse strain models cognitive flexibility deficits also observed in ASD. The present experiment investigated performance of BTBR T+tf/J and C57BL/6J on two different spatial reversal learning tests (100% accurate feedback and 80/20 probabilistic feedback), as well as marble burying and grooming behavior. BTBR T+tf/J and C57BL/6J mice exhibited similar performance on acquisition and reversal learning with 100% accurate feedback. BTBR T+tf/J mice were impaired in probabilistic reversal learning compared to that of C57BL/6J mice. BTBR T+tf/J mice also displayed increased stereotyped repetitive behaviors compared to that of C57BL/6J mice as shown by increased marble burying and grooming behavior. The present findings indicate that BTBR T+tf/J mice exhibit similar features related to “insistence on sameness” in ASD that include not only stereotyped repetitive behaviors, but also alterations in behavioral flexibility. Thus, BTBR T+tf/J mice can serve as a model to understand the neural mechanisms underlying alterations in behavioral flexibility, as well as to test potential treatments in alleviating these symptoms. PMID:22056750

  12. Differential regulation of pancreatic digestive enzymes during chronic high-fat diet-induced obesity in C57BL/6J mice.

    PubMed

    Birk, Ruth Z; Rubio-Aliaga, Isabel; Boekschoten, Mark V; Danino, Hila; Müller, Michael; Daniel, Hannelore

    2014-07-28

    Exocrine pancreatic digestive enzymes are essential for the digestion of dietary components and are regulated by them. Chronic excess dietary high fat (HF) consumption is a contributing factor of diet-induced obesity (DIO) and associated chronic diseases and requires adaptation by the pancreas. The aim of the present study was to investigate the effects of chronic HF diet feeding on exocrine pancreatic digestive enzyme transcript levels in DIO C57BL/6J mice. C57BL/6J mice were fed diets containing either 10 or 45% energy (E%) derived from fat for 12 weeks (n 10 mice per diet group). Pancreatic tissue and blood samples were collected at 0, 4 and 12 weeks. The expression of a panel of exocrine pancreatic digestive enzymes was analysed using quantitative RT-PCR and Western blot analysis. The HF (45 E%) diet-fed C57BL/6J mice developed obesity, hyperleptinaemia, hyperglycaemia and hyperinsulinaemia. The transcript levels of pancreatic lipase (PL), pancreatic lipase-related protein 2 (PLRP2) and pancreatic phospholipase A2 (PLA2) were initially elevated; however, they were down-regulated to basal control levels at week 12. The transcript levels of colipase were significantly affected by diet and time. The protein levels of PL and PLRP2 responded to HF diet feeding. The transcript levels of amylase and proteases were not significantly affected by diet and time. The transcript levels of specific lipases in hyperinsulinaemic, hyperleptinaemic and hyperglycaemic DIO C57BL/6J mice are down-regulated. However, these mice compensate for this by the post-transcriptional regulation of the levels of proteins that respond to dietary fat. This suggests a complex regulatory mechanism involved in the modulation of fat digestion.

  13. Characterization of the CD8{sup +} T cell responses directed against respiratory syncytial virus during primary and secondary infection in C57BL/6 mice

    SciTech Connect

    Lukens, Michael V.; Claassen, Erwin A.W.; Graaff, Patricia M.A. de; Dijk, Mariska E.A. van; Hoogerhout, Peter; Toebes, Mireille; Schumacher, Ton N.; Most, Robbert G. van der; Kimpen, Jan L.L.; Bleek, Grada M. van . E-mail: g.vanbleek@umcutrecht.nl

    2006-08-15

    The BALB/c mouse model for human respiratory syncytial virus infection has contributed significantly to our understanding of the relative role for CD4{sup +} and CD8{sup +} T cells to immune protection and pathogenic immune responses. To enable comparison of RSV-specific T cell responses in different mouse strains and allow dissection of immune mechanisms by using transgenic and knockout mice that are mostly available on a C57BL/6 background, we characterized the specificity, level and functional capabilities of CD8{sup +} T cells during primary and secondary responses in lung parenchyma, airways and spleens of C57BL/6 mice. During the primary response, epitopes were recognized originating from the matrix, fusion, nucleo- and attachment proteins, whereas the secondary response focused predominantly on the matrix epitope. C57BL/6 mice are less permissive for hRSV infection than BALB/c mice, yet we found CD8{sup +} T cell responses in the lungs and bronchoalveolar lavage, comparable to the responses described for BALB/c mice.

  14. The expression of NLRX1 in C57BL/6 mice cochlear hair cells: Possible relation to aging- and neomycin-induced deafness.

    PubMed

    Yang, Qianqian; Sun, Gaoying; Cao, Zhixin; Yin, Haiyan; Qi, Qi; Wang, Jinghan; Liu, Wenwen; Bai, Xiaohui; Wang, Haibo; Li, Jianfeng

    2016-03-11

    Nucleotide-binding domain and leucine-rich-repeat-containing family member X1 (NLRX1) is a cytoplasmic pattern recognition receptor that is predominantly located in mitochondria, which is tightly related to mitochondrial damage, reactive oxygen species (ROS) production, inflammation and apoptosis. The present study was designed to explore whether NLRX1 expresses in C57BL/6 mice cochlear hair cells and, if so, to investigate the possible correlations between NLRX1 and hearing. The location and dynamic expression of NLRX1 were investigated by immunofluorescence, real-time PCR and Western blotting. Hearing thresholds of C57BL/6 mice were measured by auditory brainstem response (ABR). Moreover, the downstream inflammatory and apoptotic pathways regulated by NLRX1 were examined in age-related and neomycin-induced hair cell damage. Data showed that NLRX1 expressed in cytoplasm of C57BL/6 cochlear hair cells, especially in the cilia, which were essential for sound sensation. The expression of NLRX1 in hair cells increased as the mice grew up, and, decreased as they aged. Additionally, the activated apoptotic JNK pathway was detected in 9-month old mice with worse-hearing and 3-month old mice treated with neomycin. Overall, results indicate that NLRX1 may relate to hair cell maturity, hearing formation and maintenance, and promote hair cell apoptosis through JNK pathway induced by aging and neomycin.

  15. The expression of NLRX1 in C57BL/6 mice cochlear hair cells: Possible relation to aging- and neomycin-induced deafness.

    PubMed

    Yang, Qianqian; Sun, Gaoying; Cao, Zhixin; Yin, Haiyan; Qi, Qi; Wang, Jinghan; Liu, Wenwen; Bai, Xiaohui; Wang, Haibo; Li, Jianfeng

    2016-03-11

    Nucleotide-binding domain and leucine-rich-repeat-containing family member X1 (NLRX1) is a cytoplasmic pattern recognition receptor that is predominantly located in mitochondria, which is tightly related to mitochondrial damage, reactive oxygen species (ROS) production, inflammation and apoptosis. The present study was designed to explore whether NLRX1 expresses in C57BL/6 mice cochlear hair cells and, if so, to investigate the possible correlations between NLRX1 and hearing. The location and dynamic expression of NLRX1 were investigated by immunofluorescence, real-time PCR and Western blotting. Hearing thresholds of C57BL/6 mice were measured by auditory brainstem response (ABR). Moreover, the downstream inflammatory and apoptotic pathways regulated by NLRX1 were examined in age-related and neomycin-induced hair cell damage. Data showed that NLRX1 expressed in cytoplasm of C57BL/6 cochlear hair cells, especially in the cilia, which were essential for sound sensation. The expression of NLRX1 in hair cells increased as the mice grew up, and, decreased as they aged. Additionally, the activated apoptotic JNK pathway was detected in 9-month old mice with worse-hearing and 3-month old mice treated with neomycin. Overall, results indicate that NLRX1 may relate to hair cell maturity, hearing formation and maintenance, and promote hair cell apoptosis through JNK pathway induced by aging and neomycin. PMID:26836140

  16. Gene Expression Changes in C57BL/6J and DBA/2J Mice Following Prenatal Alcohol Exposure

    PubMed Central

    Downing, Chris; Flink, Stephen; Florez-McClure, Maria L.; Johnson, Thomas E.; Tabakoff, Boris; Kechris, Katerina J.

    2012-01-01

    Background Prenatal alcohol exposure can result in Fetal Alcohol Spectrum Disorder (FASD). Not all women who consume alcohol during pregnancy have children with FASD and studies have shown that genetic factors can play a role in ethanol teratogenesis. We examined gene expression in embryos and placentae from C57BL/6J (B6) and DBA/2J (D2) mice following prenatal alcohol exposure. B6 fetuses are susceptible to morphological malformations following prenatal alcohol exposure while D2 are relatively resistant. Methods Male and female B6 and D2 mice were mated for two hours in the morning, producing four embryonic genotypes: true-bred B6B6 and D2D2, and reciprocal B6D2 and D2B6. On gestational day 9dams were intubated with either 5.8 g/kg ethanol, an is caloric amount of maltose-dextrin, or nothing Four hours later dams were sacrificed and embryos and placentae were harvested. RNA was extracted, labeled and hybridized to Affymetrix Mouse Genome 430 v2 microarray chips. Data were normalized, subjected to analysis of variance and tested for enrichment of gene ontology (GO) molecular function and biological process using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Results Several gene classes were differentially expressed in B6 and D2 regardless of treatment, including genes involved in polysaccharide binding and mitosis. Prenatal alcohol exposure altered expression of a subset of genes, including genes involved in methylation, chromatin remodeling, protein synthesis and mRNA splicing. Very few genes were differentially expressed between maltose-exposed tissues and tissues that received nothing, so we combined these groups for comparisons with ethanol. While we observed many expression changes specific to B6 following prenatal alcohol exposure, none were specific for D2. Gene classes up-or down regulated in B6 following prenatal alcohol exposure included genes involved in mRNA splicing, transcription and translation. Conclusions Our study

  17. The Effect of Mannan Oligosaccharide Supplementation on Body Weight Gain and Fat Accrual in C57Bl/6J Mice

    PubMed Central

    Smith, Daniel L.; Nagy, Tim R.; Wilson, Landon S.; Dong, Shengli; Barnes, Stephen; Allison, David B.

    2010-01-01

    The prevalence of obesity in industrialized societies has become markedly elevated. In contrast, model organism research shows that reducing caloric intake below ad libitum levels provides many health and longevity benefits. Despite these benefits, few people are willing and able to reduce caloric intake over prolonged periods. Prior research suggests that mannooligosaccharide (MOS or Mannan) supplementation can increase lifespan of some livestock and in rodents can reduce visceral fat without reducing caloric intake. Hence, we tested the effect of MOS supplementation as a possible calorie restriction mimetic in mice. C57Bl/6J male mice were fed a high-fat “western” type diet with or without 1% MOS (by weight) supplementation (n=24/group) from 8 to 20 weeks of age. Animals were housed individually and provided 95% of ad libitum food intake throughout the study. Body weight was measured weekly and body composition (lean and fat mass) measured non-invasively every 3 weeks. Individual fat depot weights were acquired by dissection at study completion. Supplementation of a high-fat diet with 1% MOS tended to reduce total food intake (mean±s.d.; CON: 293.69±10.53g, MOS: 288.10±11.82g; p=0.09) during the study. Moreover, MOS supplementation had no significant effect on final body weight (CON: 25.21±2.31g, MOS: 25.28±1.49g; p=0.91), total fat (CON: 4.72±0.90g, MOS: 4.82±0.83g; p=0.69) or visceral fat (CON: 1.048±0.276g, MOS: 1.004±0.247g; p=0.57). Contrary to previous research, MOS supplementation had no discernable effect on body weight gain or composition during this 12-week study, challenging the potential use of MOS as a calorie restriction mimetic or body composition enhancer. PMID:19798073

  18. Polychlorinated Biphenyl 153 Is a Diet-dependent Obesogen Which Worsens Nonalcoholic Fatty Liver Disease In Male C57BL6/J Mice

    PubMed Central

    Wahlang, Banrida; Falkner, K. Cameron; Gregory, Bonnie; Ansert, Douglas; Young, David; Conklin, Daniel J.; Bhatnagar, Aruni; McClain, Craig J.; Cave, Matt

    2013-01-01

    Background Polychlorinated biphenyls (PCBs) are persistent environmental pollutants which are detectable in the serum of all American adults. Amongst PCB congeners, PCB 153 has the highest serum level. PCBs have been dose-dependently associated with obesity, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD) in epidemiological studies. Objective The purpose of this study is to determine mechanisms by which PCB 153 worsens diet-induced obesity and NAFLD in male mice fed a high fat diet (HFD). Methods Male C57BL6/J mice were fed either control or 42% milk fat diet for 12 weeks with or without PCB 153 co-exposure (50 mg/kg i.p. × 4). Glucose tolerance test was performed, and plasma and tissues were obtained at necropsy for measurements of adipocytokine levels, histology and gene expression. Results In control diet-fed mice, addition of PCB 153 had minimal effects on any of the measured parameters. However, PCB 153 treatment in high fat-fed mice was associated with increased visceral adiposity, hepatic steatosis and plasma adipokines including adiponectin, leptin, resistin and plasminogen activator inhibitor-1 levels. Likewise, co-exposure reduced expression of hepatic genes implicated in β-oxidation while increasing the expression of genes associated with lipid biosynthesis. Regardless of diet, PCB 153 had no effect on insulin resistance or tumor necrosis factor alpha levels. Conclusion PCB 153 is an obesogen which exacerbates hepatic steatosis; alters adipocytokines; and disrupts normal hepatic lipid metabolism when administered with HFD, but not control diet. Because all U.S. adults have been exposed to PCB 153, this particular nutrient-toxicant interaction potentially impacts human obesity/NAFLD. PMID:23618531

  19. COMPARISON OF OVERALL METABOLISM OF 1, 2, 7, 8-PECDD IN CYP1A2(-L-) KNOCKOUT AND C57BL/6N PARENTAL STRAINS OF MICE

    EPA Science Inventory

    COMPARISON OF OVERALL METABOLISM OF 1,2,3,7,8-PeCDD
    IN CYP1A2 (-/-) KNOCKOUT AND C57BL/6N PARENTAL
    STRAINS OF MICE

    Heldur Hakk1 and Janet J. Diliberto2

    1 USDA-ARS, Biosciences Research Laboratory, P.O. Box 5674, Fargo, ND, USA
    2 US EPA, ORD, National Heal...

  20. Prenatal alcohol exposure retards the migration and development of serotonin neurons in fetal C57BL mice.

    PubMed

    Zhou, F C; Sari, Y; Zhang, J K; Goodlett, C R; Li, T

    2001-02-28

    Incomplete neural tube fusion (iNTF), induced by alcohol, in midline floor and roof plates was found in our recent study. In this study, serotonin (5-HT) neurons, known to be born entirely in the midline raphe at brainstem, were examined during their development with fetal alcohol exposure. Weight-matched C57BL mice pregnant dams were divided into three groups on E8: one received ethanol via a chocolate Sustacal liquid diet providing 20% ethanol-derived calories as the sole source of nutrients (ALC); the second received an isocaloric Sustacal liquid diet and was pair-fed to individual dams in the ethanol-fed group (PF); the third was fed ad lib rat chow (Chow). Fetal brains were obtained on E15 and were processed for immunostaining of 5-HT and its trophic factor, S100 beta. The ascending 5-HT neurons, in normal development, appear bilaterally near midline on E12, and by E15, as seen in chow and PF groups, migrate from the midline germinal zone laterally and dorsally to their final position with rich fibers. In contrast, in the E15 ALC group, many 5-HT-im neurons were found remaining in the midline germinal region or had migrated, but with under-differentiated, sparse fibers. There were 20--30% fewer 5-HT-im neurons in ALC as compared to PF and Chow. In addition, the number of S100 beta cells was less in ALC as compared with PF and Chow groups. No difference was found between PF and Chow in number of 5-HT-im or S100 beta-im cells. The 5-HT neurons found compromised in migration and differentiation may, in part, stem from failure of access to floor plate or midline tissue induction and the insufficient support by S100 beta. As 5-HT neurons have been implicated for signaling brain maturation, fewer 5-HT neurons may have lasting effects on the development of brain or, if persistent in the adult, profoundly affect adult brain function.

  1. Clinically-Relevant Cutaneous Lesions by Nitrogen Mustard: Useful Biomarkers of Vesicants Skin Injury in SKH-1 Hairless and C57BL/6 Mice

    PubMed Central

    Tewari-Singh, Neera; Jain, Anil K.; Inturi, Swetha; White, Carl W.; Agarwal, Rajesh

    2013-01-01

    A paucity of clinically applicable biomarkers to screen therapies in laboratory is a limitation in the development of countermeasures against cutaneous injuries by chemical weapon, sulfur mustard (SM), and its analog nitrogen mustard (NM). Consequently, we assessed NM-caused progression of clinical cutaneous lesions; notably, skin injury with NM is comparable to SM. Exposure of SKH-1 hairless and C57BL/6 (haired) mice to NM (3.2 mg) for 12–120 h caused clinical sequelae of toxicity, including microblister formation, edema, erythema, altered pigmentation, wounding, xerosis and scaly dry skin. These toxic effects of NM were similar in both mouse strains, except that wounding and altered pigmentation at 12–24 h and appearance of dry skin at 24 and 72 h post-NM exposure were more pronounced in C57BL/6 compared to SKH-1 mice. Conversely, edema, erythema and microblister formation were more prominent in SKH-1 than C57BL/6 mice at 24–72 h after NM exposure. In addition, 40–60% mortality was observed following 120 h of NM exposure in the both mouse strains. Overall, these toxic effects of NM are comparable to those reported in humans and other animal species with SM, and thus represent clinically-relevant cutaneous injury endpoints in screening and optimization of therapies for skin injuries by vesicating agents. PMID:23826320

  2. Immunotoxic effects of cis-urocanic acid exposure in C57BL/6N and C3H/HeN mice.

    PubMed

    Prater, M Renee; Gogal, Robert M; De Fabo, Edward C; Longstreth, Janice; Holladay, Steven D

    2003-04-01

    Exposure to ultraviolet radiation results in increased levels of intradermal cis-urocanic acid (cUCA) and alters cutaneous immunity by interfering with processing and presentation of antigen by Langerhans cells. Reports on effects of systemic immunotoxicity with 30 day cUCA exposure in laboratory rodents include thymic atrophy, thymic hypocellularity and decreased T-cell-mediated immunity; however, immune effects of single exposure or 5 day cUCA administration, which may better mimic human exposures, are poorly defined. The present study initially evaluated immune effects of single, 5 day, and 4 week cUCA exposure in C57BL/6N mice. Single administration of intradermal cUCA resulted in decreased splenocyte phagocytosis that persisted for 30 days after cUCA exposure. Five day consecutive cUCA exposure decreased numbers of phenotypically mature CD4(+)CD8(-) and CD4(-)CD8(+) (single positive) thymocytes, increased CD4(+)CD8(+) (double positive) immature thymocytes and increased splenocyte proliferation. Prolonged cUCA exposure (4 weeks) caused profound thymic hypocellularity and splenic hypercellularity and increased splenic macrophage chemiluminescence. Because of this apparent sensitivity of C57BL/6N mice to cUCA, thymic hypocellularity was compared between C57BL/6N and C3H/HeN mice dosed with cUCA, and was found to be more pronounced in the C57BL/6N strain. These results are an extension of previous conclusions on immune modulation caused by cUCA in the spleen and thymus. Further, the observed variation in sensitivity between the mouse strains is consistent with known genetic susceptibility of these strains to the immunomodulatory effects of exposure to sunlight. PMID:12733650

  3. Protection of the cochlear hair cells in adult C57BL/6J mice by T-type calcium channel blockers

    PubMed Central

    YU, YA-FENG; WU, WEN-YING; XIAO, GEN-SHENG; LING, HONG-YANG; PAN, CHEN

    2016-01-01

    The aim of the present study was to investigate the protective effect of T-type calcium channel blockers against presbycusis, using a C57BL/6J mice model. The expression of three T-type calcium channel receptor subunits in the cochlea of 6–8-week-old C57BL/6J mice was evaluated using reverse transcription-quantitative polymerase chain reaction. The results confirmed that the three subunits were expressed in the cochlea. In addition, the capacity of T-type calcium channel blockers to protect the cochlear hair cells of 24–26-week-old C57BL/6J mice was investigated in mice treated with mibefradil, benidipine or saline for 4 weeks. Differences in hearing threshold were detected using auditory brainstem recording (ABR), while differences in amplitudes were measured using a distortion product otoacoustic emission (DPOAE) test. The ABR test results showed that the hearing threshold significantly decreased at 24 kHz in the mibefradil-treated and benidipine-treated groups compared with the saline-treated group. The DPOAE amplitudes in the mibefradil-treated group were increased compared with those in the saline-treated group at the F2 frequencies of 11.3 and 13.4 kHz. Furthermore, the DPOAE amplitudes in the benidipine-treated group were increased compared with those in the saline-treated group at an F2 frequency of 13.4 kHz. The loss of outer hair cells (OHCs) was not evident in the mibefradil-treated group; however, the stereocilia of the inner hair cells (IHCs) were disorganised and sparse. In summary, these results indicate that the administration of a T-type calcium channel blocker for four consecutive weeks may improve the hearing at 24 kHz of 24–26-week-old C57BL/6J mice. The function and morphology of the OHCs of the C57BL/6J mice were significantly altered by the administration of a T-type calcium channel blocker; however, the IHCs were unaffected. PMID:26998034

  4. New microsatellite polymorphisms identified between C57BL/6, C57BL/10, and C57BL/KsJ inbred mouse strains

    SciTech Connect

    Slingsby, J.H.; Hogarth, M.B.; Walport, M.J.

    1996-06-01

    The C57BL/6 (B6) and C57BL/10 (B10) inbred mouse strains are among the most commonly used in biological research and have provided the genetic background for the construction of many congenic strains. The two substrains were derived from the parental C57BL stock and were separated prior to 1937. Since then, they have been thought to possess a very close genetic relationship. By 1992, 161 loci had been tested, and only three differed between B6 and B10: the minor histocompatibility locus H9, the immunoglobulin heavy chain locus Igh 2 on chromosome 12, and the delta-aminolevulinate dehydratase Lv locus on chromosome 4. B6 and B10 have also been shown to differ over an 8 cM segment on chromosome 4. Due to the differences at the H9 locus, B6 and B10 are not histocompatible. The aim of our study was to identify novel genetic polymorphisms between B6 and B10 mice and to analyze the BKs mouse with genetic markers such that further information can be gathered on the genetic origins of this strain. 13 refs., 3 figs.

  5. Dyadic social interaction of C57BL/6 mice versus interaction with a toy mouse: conditioned place preference/aversion, substrain differences, and no development of a hierarchy

    PubMed Central

    Pinheiro, Barbara S.; Seidl, Simon S.; Habazettl, Eva; Gruber, Bernadette E.; Bregolin, Tanja

    2016-01-01

    Impaired social interaction is a hallmark symptom of many psychiatric diseases, including dependence syndromes (substance use disorders). Helping the addict reorient her/his behavior away from the drug of abuse toward social interaction would be of considerable therapeutic benefit. To study the neural basis of such a reorientation, we have developed several animal models in which the attractiveness of a dyadic (i.e. one-to-one) social interaction (DSI) can be compared directly with that of cocaine as a prototypical drug of abuse. Our models are based on the conditioned place preference (CPP) paradigm. In an ongoing effort to validate our experimental paradigms in C57BL/6 mice to make use of the plethora of transgenic models available in this genus, we found the following: (a) DSI with a live mouse produced CPP, whereas an interaction with an inanimate mouse-like object (i.e. a ‘toy mouse’; toy mouse interaction) led to conditioned place aversion – but only in the Jackson substrain (C57BL/6J). (b) In the NIH substrain (C57BL/6N), both DSI and toy mouse interaction produced individual aversion in more than 50% of the tested mice. (c) Four 15 min DSI episodes did not result in the development of an observable hierarchy, that is, dominance/subordination behavior in the overwhelming majority (i.e. 30 of 32) of the tested Jackson mouse pairs. Therefore, dominance/subordination does not seem to be a confounding variable in our paradigm, at least not in C57BL/6J mice. Respective data for NIH mice were too limited to allow any conclusion. The present findings indicate that (a) DSI with a live mouse produces CPP to a greater degree than an interaction with an inanimate object resembling a mouse and that (b) certain substrain differences with respect to CPP/aversion to DSI do exist between the Jax and NIH substrain of C57BL/6 mice. These differences have to be considered when choosing a proper mouse substrain model for investigating the neural basis of DSI reward

  6. Dyadic social interaction of C57BL/6 mice versus interaction with a toy mouse: conditioned place preference/aversion, substrain differences, and no development of a hierarchy.

    PubMed

    Pinheiro, Barbara S; Seidl, Simon S; Habazettl, Eva; Gruber, Bernadette E; Bregolin, Tanja; Zernig, Gerald

    2016-04-01

    Impaired social interaction is a hallmark symptom of many psychiatric diseases, including dependence syndromes (substance use disorders). Helping the addict reorient her/his behavior away from the drug of abuse toward social interaction would be of considerable therapeutic benefit. To study the neural basis of such a reorientation, we have developed several animal models in which the attractiveness of a dyadic (i.e. one-to-one) social interaction (DSI) can be compared directly with that of cocaine as a prototypical drug of abuse. Our models are based on the conditioned place preference (CPP) paradigm. In an ongoing effort to validate our experimental paradigms in C57BL/6 mice to make use of the plethora of transgenic models available in this genus, we found the following: (a) DSI with a live mouse produced CPP, whereas an interaction with an inanimate mouse-like object (i.e. a 'toy mouse'; toy mouse interaction) led to conditioned place aversion - but only in the Jackson substrain (C57BL/6J). (b) In the NIH substrain (C57BL/6N), both DSI and toy mouse interaction produced individual aversion in more than 50% of the tested mice. (c) Four 15 min DSI episodes did not result in the development of an observable hierarchy, that is, dominance/subordination behavior in the overwhelming majority (i.e. 30 of 32) of the tested Jackson mouse pairs. Therefore, dominance/subordination does not seem to be a confounding variable in our paradigm, at least not in C57BL/6J mice. Respective data for NIH mice were too limited to allow any conclusion. The present findings indicate that (a) DSI with a live mouse produces CPP to a greater degree than an interaction with an inanimate object resembling a mouse and that (b) certain substrain differences with respect to CPP/aversion to DSI do exist between the Jax and NIH substrain of C57BL/6 mice. These differences have to be considered when choosing a proper mouse substrain model for investigating the neural basis of DSI reward versus

  7. Interferon-γ is crucial for surviving a Brucella abortus infection in both resistant C57BL/6 and susceptible BALB/c mice

    PubMed Central

    Murphy, Erin A; Sathiyaseelan, Janaki; Parent, Michelle A; Zou, Baixiang; Baldwin, Cynthia L

    2001-01-01

    Brucella abortus is an intracellular bacterial pathogen that causes chronic infections in humans and a number of agriculturally important species of animals. It has been shown that BALB/c mice are more susceptible to infections with virulent strains of Brucella abortus than C57BL/6 or C57BL/10 strains. In experiments described here, gene knock-out mice were utilized to elucidate some of the salient components of resistance. Resistant C57BL/6 mice with gene deletions or disruptions in the interferon-γ (IFN-γ), perforin or β2-microglobulin genes had decreased abilities to control intracellular infections with B. abortus strain 2308 during the first week after infection. However, only the IFN-γ knock-out mice had a sustained inability to control infections and this resulted in death of the mice at approximately 6 weeks post-infection. These mice had a continual increase in the number of bacterial colony-forming units (CFU) in their spleens until death. When BALB/c mice with the disrupted IFN-γ gene were infected they had more splenic CFU at one week post-infection than control mice but the increase was not statistically significant and by 3 weeks they did not have more CFU than control mice. Moreover, the number of splenic bacteria did not increase in the BALB/c IFN-γ knock-out mice between 6 and 10·5 weeks, although they died at 10·5 weeks, the time by which normal BALB/c mice were clearing the infection. Death in both strains of IFN-γ gene disrupted mice coincided with symptoms of cachexia and macrophages comprised ≥75% of the splenic leucocytes. PMID:11529943

  8. Effect of Cage-Induced Stereotypies on Measures of Affective State and Recurrent Perseveration in CD-1 and C57BL/6 Mice

    PubMed Central

    Novak, Janja; Bailoo, Jeremy D.; Melotti, Luca; Würbel, Hanno

    2016-01-01

    Stereotypies are abnormal repetitive behaviour patterns that are highly prevalent in laboratory mice and are thought to reflect impaired welfare. Thus, they are associated with impaired behavioural inhibition and may also reflect negative affective states. However, in mice the relationship between stereotypies and behavioural inhibition is inconclusive, and reliable measures of affective valence are lacking. Here we used an exploration based task to assess cognitive bias as a measure of affective valence and a two-choice guessing task to assess recurrent perseveration as a measure of impaired behavioural inhibition to test mice with different forms and expression levels of stereotypic behaviour. We trained 44 CD-1 and 40 C57BL/6 female mice to discriminate between positively and negatively cued arms in a radial maze and tested their responses to previously inaccessible ambiguous arms. In CD-1 mice (i) mice with higher stereotypy levels displayed a negative cognitive bias and this was influenced by the form of stereotypy performed, (ii) negative cognitive bias was evident in back-flipping mice, and (iii) no such effect was found in mice displaying bar-mouthing or cage-top twirling. In C57BL/6 mice neither route-tracing nor bar-mouthing was associated with cognitive bias, indicating that in this strain these stereotypies may not reflect negative affective states. Conversely, while we found no relation of stereotypy to recurrent perseveration in CD-1 mice, C57BL/6 mice with higher levels of route-tracing, but not bar-mouthing, made more repetitive responses in the guessing task. Our findings confirm previous research indicating that the implications of stereotypies for animal welfare may strongly depend on the species and strain of animal as well as on the form and expression level of the stereotypy. Furthermore, they indicate that variation in stereotypic behaviour may represent an important source of variation in many animal experiments. PMID:27145080

  9. Effect of Cage-Induced Stereotypies on Measures of Affective State and Recurrent Perseveration in CD-1 and C57BL/6 Mice.

    PubMed

    Novak, Janja; Bailoo, Jeremy D; Melotti, Luca; Würbel, Hanno

    2016-01-01

    Stereotypies are abnormal repetitive behaviour patterns that are highly prevalent in laboratory mice and are thought to reflect impaired welfare. Thus, they are associated with impaired behavioural inhibition and may also reflect negative affective states. However, in mice the relationship between stereotypies and behavioural inhibition is inconclusive, and reliable measures of affective valence are lacking. Here we used an exploration based task to assess cognitive bias as a measure of affective valence and a two-choice guessing task to assess recurrent perseveration as a measure of impaired behavioural inhibition to test mice with different forms and expression levels of stereotypic behaviour. We trained 44 CD-1 and 40 C57BL/6 female mice to discriminate between positively and negatively cued arms in a radial maze and tested their responses to previously inaccessible ambiguous arms. In CD-1 mice (i) mice with higher stereotypy levels displayed a negative cognitive bias and this was influenced by the form of stereotypy performed, (ii) negative cognitive bias was evident in back-flipping mice, and (iii) no such effect was found in mice displaying bar-mouthing or cage-top twirling. In C57BL/6 mice neither route-tracing nor bar-mouthing was associated with cognitive bias, indicating that in this strain these stereotypies may not reflect negative affective states. Conversely, while we found no relation of stereotypy to recurrent perseveration in CD-1 mice, C57BL/6 mice with higher levels of route-tracing, but not bar-mouthing, made more repetitive responses in the guessing task. Our findings confirm previous research indicating that the implications of stereotypies for animal welfare may strongly depend on the species and strain of animal as well as on the form and expression level of the stereotypy. Furthermore, they indicate that variation in stereotypic behaviour may represent an important source of variation in many animal experiments. PMID:27145080

  10. Nicotine-taking and nicotine-seeking in C57Bl/6J mice without prior operant training or food restriction.

    PubMed

    Yan, Yijin; Pushparaj, Abhiram; Gamaleddin, Islam; Steiner, Rebecca C; Picciotto, Marina R; Roder, John; Le Foll, Bernard

    2012-04-21

    The ability to examine genetically engineered mice in a chronic intravenous (IV) nicotine self-administration paradigm will be a powerful tool for investigating the contribution of specific genes to nicotine reinforcement and more importantly, to relapse behavior. Here we describe a reliable model of nicotine-taking and -seeking behavior in male C57BL/6J mice without prior operant training or food restriction. Mice were allowed to self-administer either nicotine (0.03mg/kg/infusion) or saline in 2-h daily sessions under fixed ratio 1 (FR1) followed by FR2 schedules of reinforcement. In the nicotine group, a dose-response curve was measured after the nose-poke behavior stabilized. Subsequently, nose-poke behavior was extinguished and ability of cue presentations, priming injections of nicotine, or intermittent footshock to reinstate responding was assessed in both groups. C57BL/6J mice given access to nicotine exhibited high levels of nose-poke behavior and self-administered a high number of infusions as compared to mice given access to saline. After this acquisition phase, changing the unit-dose of nicotine resulted in a flat dose-response curve for nicotine-taking and subsequently reinstatement of nicotine-seeking behavior was achieved by both nicotine-associated light cue presentation and intermittent footshock. Nicotine priming injections only triggered significant reinstatement on the second consecutive day of priming. In contrast, mice previously trained to self-administer saline did not increase their responding under those conditions. These results demonstrate the ability to produce nicotine-taking and nicotine-seeking behavior in naive C57BL/6J mice without both prior operant training and food restriction. Future work will utilize these models to evaluate nicotine-taking and relapsing behavior in genetically-altered mice.

  11. Comparison of immunopathology and locomotor recovery in C57BL/6, BUB/BnJ, and NOD-SCID mice after contusion spinal cord injury.

    PubMed

    Luchetti, Sabina; Beck, Kevin D; Galvan, Manuel D; Silva, Richard; Cummings, Brian J; Anderson, Aileen J

    2010-02-01

    Studies of cell transplantation therapeutics in animal models of traumatic spinal cord injury (SCI) are often hampered by partial or complete rejection of the graft by the host. Pharmacological immunosuppression is rarely sufficient to prevent rejection. Further, the immunological niche created by both the host immune response and immunosuppressant drugs could hypothetically influence the proliferation, differentiation, and fate of transplanted progenitor/stem cells. To avoid these confounds, we have previously used the constitutively immunodeficient non-obese diabetic severe combined immunodeficient (NOD-SCID) mouse as a model for transplantation studies following SCI. In the current study, we compare behavioral and histological recovery in NOD-SCID, C57BL/6, and BUB/BnJ mice of both sexes to better facilitate interpretation of data from studies using NOD-SCID mice. Of the strains examined, NOD-SCID mice exhibited the greatest locomotor recovery in the open field; no sex differences were detected in locomotor recovery in any of the strains. Stereologic estimation of the number of infiltrated neutrophils showed more cells in C57BL/6 mice than NOD-SCID mice, with BUB/BnJ mice having an intermediate number. The volume of macrophages/microglia did not differ between strains or sexes, though more rostral-caudal spreading was observed in C57BL/6 and BUB/BnJ than NOD-SCID mice. No significant differences were detected in lesion volume. Taken together these findings demonstrate that relative to other strains, NOD-SCID mice have both similar primary lesion volume and cellular inflammatory parameters after SCI, and support the applicability of the model for neurotransplantation studies.

  12. Aerobic exercise is the critical variable in an enriched environment that increases hippocampal neurogenesis and water maze learning in male C57BL/6J mice

    PubMed Central

    Mustroph, Martina L.; Chen, Shi; Desai, Shalin C.; Cay, Edward B.; DeYoung, Erin K.; Rhodes, Justin S.

    2012-01-01

    Previous studies have shown that housing mice with toys and running wheels increases adult hippocampal neurogenesis and enhances performance on the water maze. However, the relative contribution of running versus enrichment to the neurogenic and pro-cognitive effects is not clear. Recently, it was demonstrated that enrichment devoid of running wheels does not significantly enhance adult hippocampal neurogenesis in female C57BL/6J mice. However, novel toys were not rotated into the cages, and dietary enrichment was not included, so it could be argued that the environment was not enriched enough. In addition, only females were studied, and animals were group-housed, making it impossible to record individual running behavior or to determine the time spent running versus exploring the toys. Therefore, we repeated the study in singly housed male C57BL/6J mice and enhanced enrichment by rotating novel tactile, visual, dietary, auditory, and vestibular stimuli into the cages. Mice were housed for 32 days in one of 4 groups: running-only, enrichment-only, running plus enrichment, and standard cage. The first 10 days BrdU (bromodeoxyuridine) was administered to label dividing cells. The last 5 days mice were tested on the water maze, and then euthanized to measure number of BrdU cells co-labeled with NeuN (neuronal nuclear marker) in the dentate gyrus. Mice in the running-only group ran, on average, greater distances than animals in the running plus enrichment group. The combination of enrichment and running did not significantly increase hippocampal neurogenesis any more than running alone did. Animals in the running-only condition were the only group to show enhanced acquisition on water maze relative to standard cage controls. We confirm and extend the conclusion that environmental enrichment alone does not significantly increase hippocampal neurogenesis or bestow spatial learning benefits in male C57BL/6J mice, even when the modalities of enrichment are very broad. PMID

  13. Acute Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or Paraquat on Core Temperature in C57BL/6J Mice

    PubMed Central

    Jiao, Yun; Dou, Yuchen; Lockwood, Georgina; Pani, Amar; Jay Smeyne, Richard

    2015-01-01

    Abstract Background: MPTP and paraquat are two compounds that have been used to model Parkinson’s disease in mice. Previous studies in two non-traditional strains of mice have shown that a single dose of MPTP can induce changes in body temperature, while the effects of paraquat have not been examined. Examination of body temperature is important since small fluctuations in an animal’s core temperature can significantly affect drug metabolism, and if significant enough can even culminate in an animal’s death. Objective: To determine how external heating can alter the survival of C57BL/6J mice following MPTP administration. Methods: In this study, we examine the effects of MPTP (4×20 mg/kg, 2 hours apart) and paraquat (2×10 mg/kg/week for 3 weeks) on core temperature of C57BL/6J mice. Correlations of purine and catecholamine levels were also done in mice treated with MPTP. Results: We find that MPTP induces a significant hypothermia in C57BL/6J mice that reduces their core temperature below the limit of fatal hypothermia. Unlike MPTP, paraquat did not induce a significant hypothermia. Placement of animals on heating pads significantly abrogates the loss of core temperature. In both heated and non-heated conditions, mice treated with MPTP showed a significant depletion of ATP within 2 hours of administration in both striatum and SN that started to recover 2 hours after MPTP administration was complete. Striatal DA and DOPAC are significantly reduced starting 4–6 hours after MPTP. Conclusions: The fatal hypothermic effects of MPTP can be abrogated through use of external heating. PMID:25633843

  14. Impact of dietary n-3 polyunsaturated fatty acids on cognition, motor skills and hippocampal neurogenesis in developing C57BL/6J mice.

    PubMed

    Janssen, Carola I F; Zerbi, Valerio; Mutsaers, Martina P C; de Jong, Bas S W; Wiesmann, Maximilian; Arnoldussen, Ilse A C; Geenen, Bram; Heerschap, Arend; Muskiet, Frits A J; Jouni, Zeina E; van Tol, Eric A F; Gross, Gabriele; Homberg, Judith R; Berg, Brian M; Kiliaan, Amanda J

    2015-01-01

    Maternal intake of omega-3 polyunsaturated fatty acids (n-3 PUFA) is critical during perinatal development of the brain. Docosahexaenoic acid (DHA) is the most abundant n-3 PUFA in the brain and influences neuronal membrane function and neuroprotection. The present study aims to assess the effect of dietary n-3 PUFA availability during the gestational and postnatal period on cognition, brain metabolism and neurohistology in C57BL/6J mice. Female wild-type C57BL/6J mice at day 0 of gestation were randomly assigned to either an n-3 PUFA deficient diet (0.05% of total fatty acids) or an n-3 PUFA adequate diet (3.83% of total fatty acids) containing preformed DHA and its precursor α-linolenic acid. Male offspring remained on diet and performed cognitive tests during puberty and adulthood. In adulthood, animals underwent (31)P magnetic resonance spectroscopy to assess brain energy metabolites. Thereafter, biochemical and immunohistochemical analyses were performed assessing inflammation, neurogenesis and synaptic plasticity. Compared to the n-3 PUFA deficient group, pubertal n-3 PUFA adequate fed mice demonstrated increased motor coordination. Adult n-3 PUFA adequate fed mice exhibited increased exploratory behavior, sensorimotor integration and spatial memory, while neurogenesis in the hippocampus was decreased. Selected brain regions of n-3 PUFA adequate fed mice contained significantly lower levels of arachidonic acid and higher levels of DHA and dihomo-γ-linolenic acid. Our data suggest that dietary n-3 PUFA can modify neural maturation and enhance brain functioning in healthy C57BL/6J mice. This indicates that availability of n-3 PUFA in infant diet during early development may have a significant impact on brain development.

  15. High resolution 3D laboratory x-ray tomography data of femora from young, 1-14 day old C57BL/6 mice.

    PubMed

    Bortel, Emely L; Duda, Georg N; Mundlos, Stefan; Willie, Bettina M; Fratzl, Peter; Zaslansky, Paul

    2015-09-01

    This data article contains high resolution (1.2 µm effective pixel size) lab-based micro-computed tomography (µCT) reconstructed volume data of the femoral mid-shafts from young C57BL/6 mice. This data formed the basis for the analyses of bone structural development in healthy mice, including closed and open porosity as reported in Bortel et al. [1]. The data reveals changes seen in bone material and porosity distribution observed when mouse bones transform from porous scaffolds into solid structures during normal organogenesis.

  16. [Analysis of the binding capacity of the benzodiazepine site of gabaa receptor in mice C57BL/6 and BALB/C pretreated with anxiolytics].

    PubMed

    Iarkova, M A

    2011-01-01

    The level of specific 3H-flunitrazepam binding in synaptosomal membranes of C57BL/6 and BALB/c mice brain underwent to the stress of different types has been studied. Mild stress (Elevated Plus Maze) was shown to induce the decrease of benzodiazepine binding in BALB/c mice only, while the strong one (Exposure to a predator) was revealed to cause this decrease in both strains. Behavioral effects of different non-benzodiazepine drugs possessing anxiolytic properties (Afobazol, Ladasten and Noopept) was accompanied with the normalization of the level of benzodiazepine reception, reduced by the stress of both modalities. PMID:22232906

  17. Exposure of C57BL/6J mice to long photoperiod during early life stages increases body weight and alters plasma metabolomic profiles in adulthood.

    PubMed

    Uchiwa, Tatsuhiro; Takai, Yusuke; Tashiro, Ayako; Furuse, Mitsuhiro; Yasuo, Shinobu

    2016-09-01

    Perinatal photoperiod is an important regulator of physiological phenotype in adulthood. In this study, we demonstrated that postnatal (0-4 weeks old) exposure of C57BL/6J mice to long photoperiod induced persistent increase in body weight until adulthood, compared with the mice maintained under short photoperiod. The expression of peroxisome proliferator-activated receptor δ, a gene involved in fatty acid metabolism, was decreased in 10-week-old mice exposed to long photoperiod during 0-4 or 4-8 weeks of age. Plasma metabolomic profiles of adult mice exposed to a long photoperiod during the postnatal period (0-4 LD) were compared to those in the mice exposed to short photoperiod during the same period. Cluster analysis revealed that both carbon metabolic pathway and nucleic acid pathway were altered by the postnatal photoperiod. Levels of metabolites involved in glycolysis were significantly upregulated in 0-4 LD, suggesting that the mice in 0-4 LD use the glycolytic pathway for energy expenditure rather than the fatty acid oxidation pathway. In addition, the mice in 0-4 LD exhibited high levels of purine metabolites, which have a role in neuroprotection. In conclusion, postnatal exposure of C57BL/6J mice to long photoperiod induces increase in body weight and various changes in plasma metabolic profiles during adulthood. PMID:27650252

  18. Extract of Kuding Tea Prevents High-Fat Diet-Induced Metabolic Disorders in C57BL/6 Mice via Liver X Receptor (LXR) β Antagonism

    PubMed Central

    Hu, Na; Sun, Qinhu; Ding, Xiaobo; Li, Guowen; Zheng, Bin; Gu, Ming; Huang, Feisi; Sun, Yin-Qiang; Zhou, Zhiqin; Lu, Xiong; Huang, Cheng; Ji, Guang

    2012-01-01

    Objective To investigate the effects of ilex kudingcha C. J. Tseng (kuding tea), a traditional beverage in China, on the metabolic disorders in C57BL/6 mice induced by high-fat diets. Design For the preventive experiment, the female C57BL/6 mice were fed with a standard diet (Chow), high-fat diet (HF), and high-fat diet mixed with 0.05% ethanol extract of kuding tea (EK) for 5 weeks. For the therapeutic experiment, the C57BL/6 mice were fed high-fat diet for 3 months, and then mice were split and EK was given with oral gavages for 2 weeks at 50 mg/day/kg. Body weight and daily food intake amounts were measured. At the end of treatment, the adipocyte images were assayed with a scanning electron microscope, and the fasting blood glucose, glucose tolerance test, serum lipid profile and lipids in the livers were analyzed. A reporter gene assay system was used to test the whether EK could act on nuclear receptor transcription factors, and the gene expression analysis was performed with a quantitative PCR assay. Results In the preventive treatment, EK blocked the body weight gain, reduced the size of the adipocytes, lowered serum triglyceride, cholesterol, LDL-cholesterol, fasting blood glucose levels and glucose tolerance in high-fat diet-fed C57BL/6 mice. In the therapeutic treatment, EK reduced the size of the white adipocytes, serum TG and fasting blood glucose levels in obese mice. With the reporter assay, EK inhibited LXRβ transactivity and mRNA expression of LXRβ target genes. Conclusion We observed that EK has both preventive and therapeutic roles in metabolic disorders in mice induced with high-fat diets. The effects appear to be mediated through the antagonism of LXRβ transactivity. Our data indicate that kuding tea is a useful dietary therapy and a potential source for the development of novel anti-obesity and lipid lowering drugs. PMID:23226556

  19. Strain-specific differences in cell proliferation and differentiation in the dentate gyrus of C57BL/6N and C3H/HeN mice fed a high fat diet.

    PubMed

    Hwang, In Koo; Kim, Il Yong; Kim, Dae Won; Yoo, Ki-Yeon; Kim, Yo Na; Yi, Sun Shin; Won, Moo-Ho; Lee, In Se; Yoon, Yeo Sung; Seong, Je Kyung

    2008-11-19

    The authors investigated strain-specific cell proliferation and differentiation differences in the dentate gyri of C57BL/6N (susceptible strain to obesity) and C3H/HeN (resistant strain to obesity) mice. In addition, the influences of a high fat diet (HD) on neuronal differentiation in C57BL/6N and C3H/HeN mice fed a low-fat diet (LD) or HD for 4 or 12 weeks were investigated. Body weight and body weight gains were significantly higher in HD-fed C57BL/6N and C3H/HeN mice than in LD-fed C57BL/6N and C3H/HeN mice. In particular, body weight gains were significantly higher in C57BL/6N mice than in C3H/HeN mice. In both of HD- and LD-fed C57BL/6N and C3H/HeN mice for 4 weeks, some Ki67 and many DCX immunoreactive cells were detected in the subgranular zone of the dentate gyrus. In HD-fed C57BL/6N and C3H/HeN mice, the number of Ki67 immunoreactive cells and DCX immunoreactivities in the dentate gyri were significantly lower than in LD-fed C57BL/6N and C3H/HeN mice. However, the number of Ki67 immunoreactive cells and DCX immunoreactivities in HD-fed C57BL/6N mice were significantly lower than in HD-fed C3H/HeN mice. These results suggest that C57BL/6N mice are more vulnerable to HD induced obesity than C3H/HeN mice. In addition, the feeding of HD was found to exacerbate reduced cell proliferation and differentiation in the dentate gyri of C57BL/6N mice as compared with that in C3H/HeN mice.

  20. Effects of Fortunella margarita Fruit Extract on Metabolic Disorders in High-Fat Diet-Induced Obese C57BL/6 Mice

    PubMed Central

    Ding, Xiaobo; Fan, Shengjie; Guo, Lu; Gu, Ming; Zhang, Yu; Feng, Li; Jiang, Dong; Li, Yiming; Xi, Wanpeng; Huang, Cheng; Zhou, Zhiqin

    2014-01-01

    Introduction Obesity is a nutritional disorder associated with many health problems such as dyslipidemia, type 2 diabetes and cardiovascular diseases. In the present study, we investigated the anti-metabolic disorder effects of kumquat (Fortunella margarita Swingle) fruit extract (FME) on high-fat diet-induced C57BL/6 obese mice. Methods The kumquat fruit was extracted with ethanol and the main flavonoids of this extract were analyzed by HPLC. For the preventive experiment, female C57BL/6 mice were fed with a normal diet (Chow), high-fat diet (HF), and high-fat diet with 1% (w/w) extract of kumquat (HF+FME) for 8 weeks. For the therapeutic experiment, female C57BL/6 mice were fed with high-fat diet for 3 months to induce obesity. Then the obese mice were divided into two groups randomly, and fed with HF or HF+FME for another 2 weeks. Body weight and daily food intake amounts were recorded. Fasting blood glucose, glucose tolerance test, insulin tolerance test, serum and liver lipid levels were assayed and the white adipose tissues were imaged. The gene expression in mice liver and brown adipose tissues were analyzed with a quantitative PCR assay. Results In the preventive treatment, FME controlled the body weight gain and the size of white adipocytes, lowered the fasting blood glucose, serum total cholesterol (TC), serum low density lipoprotein cholesterol (LDL-c) levels as well as liver lipid contents in high-fat diet-fed C57BL/6 mice. In the therapeutic treatment, FME decreased the serum triglyceride (TG), serum TC, serum LDL-c, fasting blood glucose levels and liver lipid contents, improved glucose tolerance and insulin tolerance. Compared with the HF group, FME significantly increased the mRNA expression of PPARα and its target genes. Conclusion Our study suggests that FME may be a potential dietary supplement for preventing and ameliorating the obesity and obesity-related metabolic disturbances. PMID:24705395

  1. Long-term colonization levels of Helicobacter hepaticus in the cecum of hepatitis-prone A/JCr mice are significantly lower than those in hepatitis-resistant C57BL/6 mice.

    PubMed

    Whary, M T; Cline, J; King, A; Ge, Z; Shen, Z; Sheppard, B; Fox, J G

    2001-10-01

    Helicobacter hepaticus infection causes hepatitis in A/JCr mice but mild or no disease in C57BL/6 mice. Colonization of H. hepaticus in the cecum of experimentally infected A/JCr and C57BL/6 mice was quantified by use of real-time polymerase chain reaction (PCR) analysis with primers for the H. hepaticus cdtB gene and mouse 18srRNA. Eight-week-old mice were experimentally (n = 48) or sham (n = 24) infected with H. hepaticus, then were necropsied 6 months after infection. Liver specimens from experimentally infected mice had negative results of PCR analysis for H. hepaticus; thus, real-time quantification was not attempted. Quantitative PCR analysis of H. hepaticus in cecal specimens indicated that C57BL/6 mice were colonized to a greater extent than were A/JCr mice (P < 0.006). Appreciable typhlitis was not observed, but was consistent with that of previous reports; A/JCr mice developed more severe parenchymal necrosis, portal inflammation, and phlebitis in the liver (P < 0.0001), with mild disease observed in infected C57BL/6 mice. Thus, hepatitis in A/JCr mice caused by H. hepaticus infection is associated with significantly lower colonization levels of H. hepaticus in the cecum, compared with those of hepatitis-resistant C57BL/6 mice. Host responses of A/JCr mice that limit cecal colonization with H. hepaticus may have important roles in the pathogenesis of hepatic lesions.

  2. The Nlrp3 inflammasome, IL-1β, and neutrophil recruitment are required for susceptibility to a nonhealing strain of Leishmania major in C57BL/6 mice.

    PubMed

    Charmoy, Melanie; Hurrell, Benjamin P; Romano, Audrey; Lee, Sang Hun; Ribeiro-Gomes, Flavia; Riteau, Nicolas; Mayer-Barber, Katrin; Tacchini-Cottier, Fabienne; Sacks, David L

    2016-04-01

    Infection of C57BL/6 mice with most Leishmania major strains results in a healing lesion and clearance of parasites from the skin. Infection of C57BL/6 mice with the L. major Seidman strain (LmSd), isolated from a patient with chronic lesions, despite eliciting a strong Th1 response, results in a nonhealing lesion, poor parasite clearance, and complete destruction of the ear dermis. We show here that in comparison to a healing strain, LmSd elicited early upregulation of IL-1β mRNA and IL-1β-producing dermal cells and prominent neutrophil recruitment to the infected skin. Mice deficient in Nlrp3, apoptosis-associated speck-like protein containing a caspase recruitment domain, or caspase-1/11, or lacking IL-1β or IL-1 receptor signaling, developed healing lesions and cleared LmSd from the infection site. Mice resistant to LmSd had a stronger antigen-specific Th1 response. The possibility that IL-1β might act through neutrophil recruitment to locally suppress immunity was supported by the healing observed in neutropenic Genista mice. Secretion of mature IL-1β by LmSd-infected macrophages in vitro was dependent on activation of the Nlrp3 inflammasome and caspase-1. These data reveal that Nlrp3 inflammasome-dependent IL-1β, associated with localized neutrophil recruitment, plays a crucial role in the development of a nonhealing form of cutaneous leishmaniasis in conventionally resistant mice.

  3. Protective effects of a polysaccharide from Spirulina platensis on dopaminergic neurons in an MPTP-induced Parkinson's disease model in C57BL/6J mice.

    PubMed

    Zhang, Fang; Lu, Jian; Zhang, Ji-Guo; Xie, Jun-Xia

    2015-02-01

    The present study aimed to determine whether a polysaccharide obtained from Spirulina platensis shows protective effects on dopaminergic neurons. A Parkinson's disease model was established through the intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57BL/6J mice. Prior to the MPTP injection, some mice were pretreated with intraperitoneal injections of a polysaccharide derived from Spirulina platensis once daily for 10 days. The results showed that the immunoreactive staining and mRNA expression of the dopamine transporter and tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, in the substantia nigra, were significantly increased in mice pretreated with 800 mg/kg of the polysaccharide compared with those in MPTP-treated mice. The activities of superoxide dismutase and glutathione peroxidase in the serum and midbrain were also increased significantly in mice injected with MPTP after pretreatment with the polysaccharide from Spirulina platensis. By contrast, the activity of monoamine oxidase B in serum and midbrain maintained unchanged. These experimental findings indicate that the polysaccharide obtained from Spirulina platensis plays a protective role against the MPTP-induced loss of dopaminergic neurons in C57BL/6J mice, and that the antioxidative properties of this polysaccharide likely underlie its neuroprotective effect. PMID:25883632

  4. Red beet (Beta vulgaris L.) leaf supplementation improves antioxidant status in C57BL/6J mice fed high fat high cholesterol diet.

    PubMed

    Lee, Jeung Hee; Son, Chan Wook; Kim, Mi Yeon; Kim, Min Hee; Kim, Hye Ran; Kwak, Eun Shil; Kim, Sena; Kim, Mee Ree

    2009-01-01

    The effect of diet supplemented with red beet (Beta vulgaris L.) leaf on antioxidant status of plasma and tissue was investigated in C57BL/6J mice. The mice were randomly divided into two groups after one-week acclimation, and fed a high fat (20%) and high cholesterol (1%) diet without (control group) or with 8% freeze-dried red beet leaf (RBL group) for 4 weeks. In RBL mice, lipid peroxidation determined as 2-thiobarbituric acid-reactive substances (TBARS value) was significantly reduced in the plasma and selected organs (liver, heart, and kidney). Levels of antioxidants (glutathione and beta-carotene) and the activities of antioxidant enzyme (glutathione peroxidase) in plasma and liver were considerably increased, suggesting that antioxidant defenses were improved by RBL diet. Comet parameters such as tail DNA (%), tail extent moment, olive tail moment and tail length were significantly reduced by 25.1%, 49.4%, 35.4%, and 23.7%, respectively, in plasma lymphocyte DNA of RBL mice compared with control mice, and indicated the increased resistance of lymphocyte DNA to oxidative damage. In addition, the RBL diet controlled body weight together with a significant reduction of fat pad (retroperitoneal, epididymal, inguinal fat, and total fat). Therefore, the present study suggested that the supplementation of 8% red beet leaf in high fat high cholesterol diet could prevent lipid peroxidation and improve antioxidant defense system in the plasma and tissue of C57BL/6J mice. PMID:20016711

  5. [Effects of nootropic drugs on behavior of BALB/c and C57BL/6 mice in the exploratory cross-maze test].

    PubMed

    Vasil'eva, E V; Salimov, R M; Kovalev, G I

    2012-01-01

    Exploratory behavior, locomotor activity, and anxiety in inbred mice of C57BL/6 and BALB/c strains subchronically treated with placebo or various types of nootropic (cognition enhancing) drugs (piracetam, phenotropil, noopept, semax, pantogam, nooglutil) have been evaluated using the exploratory cross-maze test. It was found that BALB/c mice in comparison to C57BL/6 mice are characterized by greater anxiety and lower efficiency of exploratory behavior in the previously unfamiliar environment. All tested drugs clearly improved the exploratory behavior in BALB/c mice only. In BALB/c mice, piracetam, phenotropil, noopept, and semax also reduced anxiety, while phenotropil additionally increased locomotor activity. Thus, the nootropic drugs displayed clear positive modulation of spontaneous orientation in the mice strain with initially low exploratory efficiency (BALB/c) in the cross-maze test. Some drugs (pantogam, nooglutil) exhibited only nootropic properties, while the other drugs exhibited both nootropic effects on the exploratory activity and produced modulation of the anxiety level (piracetam, fenotropil, noopept, semax) and locomotor activity (fenotropil). PMID:23025044

  6. Red beet (Beta vulgaris L.) leaf supplementation improves antioxidant status in C57BL/6J mice fed high fat high cholesterol diet

    PubMed Central

    Lee, Jeung Hee; Son, Chan Wook; Kim, Mi Yeon; Kim, Min Hee; Kim, Hye Ran; Kwak, Eun Shil; Kim, Sena

    2009-01-01

    The effect of diet supplemented with red beet (Beta vulgaris L.) leaf on antioxidant status of plasma and tissue was investigated in C57BL/6J mice. The mice were randomly divided into two groups after one-week acclimation, and fed a high fat (20%) and high cholesterol (1%) diet without (control group) or with 8% freeze-dried red beet leaf (RBL group) for 4 weeks. In RBL mice, lipid peroxidation determined as 2-thiobarbituric acid-reactive substances (TBARS value) was significantly reduced in the plasma and selected organs (liver, heart, and kidney). Levels of antioxidants (glutathione and β-carotene) and the activities of antioxidant enzyme (glutathione peroxidase) in plasma and liver were considerably increased, suggesting that antioxidant defenses were improved by RBL diet. Comet parameters such as tail DNA (%), tail extent moment, olive tail moment and tail length were significantly reduced by 25.1%, 49.4%, 35.4%, and 23.7%, respectively, in plasma lymphocyte DNA of RBL mice compared with control mice, and indicated the increased resistance of lymphocyte DNA to oxidative damage. In addition, the RBL diet controlled body weight together with a significant reduction of fat pad (retroperitoneal, epididymal, inguinal fat, and total fat). Therefore, the present study suggested that the supplementation of 8% red beet leaf in high fat high cholesterol diet could prevent lipid peroxidation and improve antioxidant defense system in the plasma and tissue of C57BL/6J mice. PMID:20016711

  7. Protective effects of a polysaccharide from Spirulina platensis on dopaminergic neurons in an MPTP-induced Parkinson's disease model in C57BL/6J mice

    PubMed Central

    Zhang, Fang; Lu, Jian; Zhang, Ji-guo; Xie, Jun-xia

    2015-01-01

    The present study aimed to determine whether a polysaccharide obtained from Spirulina platensis shows protective effects on dopaminergic neurons. A Parkinson's disease model was established through the intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57BL/6J mice. Prior to the MPTP injection, some mice were pretreated with intraperitoneal injections of a polysaccharide derived from Spirulina platensis once daily for 10 days. The results showed that the immunoreactive staining and mRNA expression of the dopamine transporter and tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, in the substantia nigra, were significantly increased in mice pretreated with 800 mg/kg of the polysaccharide compared with those in MPTP-treated mice. The activities of superoxide dismutase and glutathione peroxidase in the serum and midbrain were also increased significantly in mice injected with MPTP after pretreatment with the polysaccharide from Spirulina platensis. By contrast, the activity of monoamine oxidase B in serum and midbrain maintained unchanged. These experimental findings indicate that the polysaccharide obtained from Spirulina platensis plays a protective role against the MPTP-induced loss of dopaminergic neurons in C57BL/6J mice, and that the antioxidative properties of this polysaccharide likely underlie its neuroprotective effect. PMID:25883632

  8. A weekly alternating diet between caloric restriction and medium fat protects the liver from fatty liver development in middle-aged C57BL/6J mice

    PubMed Central

    Rusli, Fenni; Boekschoten, Mark V; Zubia, Arantza Aguirre; Lute, Carolien; Müller, Michael; Steegenga, Wilma T

    2015-01-01

    Scope We investigated whether a novel dietary intervention consisting of an every-other-week calorie-restricted diet could prevent nonalcoholic fatty liver disease (NAFLD) development induced by a medium-fat (MF) diet. Methods and results Nine-week-old male C57BL/6J mice received either a (i) control (C), (ii) 30E% calorie restricted (CR), (iii) MF (25E% fat), or (iv) intermittent (INT) diet, a diet alternating weekly between 40E% CR and an ad libitum MF diet until sacrifice at the age of 12 months. The metabolic, morphological, and molecular features of NAFLD were examined. The INT diet resulted in healthy metabolic and morphological features as displayed by the continuous CR diet: glucose tolerant, low hepatic triglyceride content, low plasma alanine aminotransferase. In contrast, the C- and MF-exposed mice with high body weight developed signs of NAFLD. However, the gene expression profiles of INT-exposed mice differed to those of CR-exposed mice and showed to be more similar with those of C- and MF-exposed mice with a comparable body weight. Conclusions Our study reveals that the INT diet maintains metabolic health and reverses the adverse effects of the MF diet, thus effectively prevents the development of NAFLD in 12-month-old male C57BL/6J mice. PMID:25504628

  9. Immunopathology of B-cell lymphomas induced in C57BL/6 mice by dualtropic murine leukemia virus (MuLV).

    PubMed Central

    Pattengale, P. K.; Taylor, C. R.; Twomey, P.; Hill, S.; Jonasson, J.; Beardsley, T.; Haas, M.

    1982-01-01

    Combined clinicopathologic and immunomorphologic evidence is presented that would indicate that a murine leukemia virus (MuLV) with the dualtropic host range is capable of producing a clinically malignant lesion composed of immunoblasts and associated plasma cells in C57BL/6 mice. This process, morphologically diagnosed as an immunoblastic lymphoma of B cells using standard histopathologic criteria, was found to be distinctly polyclonal with regard to immunoglobulin (Ig) isotype when analyzed for both surface and cytoplasmic Ig. Further studies demonstrated that this clinicopathologically malignant, dualtropic MuLV-induced, polyclonal immunoblastic lymphoma of B cells in C57BL/6 mice was normal diploid and unable to be successfully transplanted to nonimmunosuppressed syngeneic recipients. Although all serum heavy and light chain components were found to be progressively elevated as the tumor load increased, the polyclonal increase in serum immunoglobulins was most pronounced for mu heavy and kappa light chains (ie, mu greater than gamma 2A greater than alpha greater than gamma 2B greater than gamma 1; kappa greater than lamba). The dissociation of clinicopathologic and biologic criteria for malignancy in the presently described dualtropic (RadLV) MuLV-induced B-cell lesion is sharply contrasted with the thymotropic (RadLV), MuLV-induced T-cell lymphoblastic lymphoma in C57BL/6 mice. This process is also a clinicopathologically malignant lesion but, when one uses biologic criteria, is found to be distinctly monoclonal, aneuploid, and easily transplanted to nonimmunosuppressed syngeneic recipients. The close clinicopathologic and biologic similarities of the dualtropic MuLV-induced animal model to corresponding human B-cell lymphoproliferative diseases are stressed. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 7 PMID:6282131

  10. Systemic L-Kynurenine sulfate administration disrupts object recognition memory, alters open field behavior and decreases c-Fos immunopositivity in C57Bl/6 mice

    PubMed Central

    Varga, Dániel; Herédi, Judit; Kánvási, Zita; Ruszka, Marian; Kis, Zsolt; Ono, Etsuro; Iwamori, Naoki; Iwamori, Tokuko; Takakuwa, Hiroki; Vécsei, László; Toldi, József; Gellért, Levente

    2015-01-01

    L-Kynurenine (L-KYN) is a central metabolite of tryptophan degradation through the kynurenine pathway (KP). The systemic administration of L-KYN sulfate (L-KYNs) leads to a rapid elevation of the neuroactive KP metabolite kynurenic acid (KYNA). An elevated level of KYNA may have multiple effects on the synaptic transmission, resulting in complex behavioral changes, such as hypoactivity or spatial working memory deficits. These results emerged from studies that focused on rats, after low-dose L-KYNs treatment. However, in several studies neuroprotection was achieved through the administration of high-dose L-KYNs. In the present study, our aim was to investigate whether the systemic administration of a high dose of L-KYNs (300 mg/bwkg; i.p.) would produce alterations in behavioral tasks (open field or object recognition) in C57Bl/6j mice. To evaluate the changes in neuronal activity after L-KYNs treatment, in a separate group of animals we estimated c-Fos expression levels in the corresponding subcortical brain areas. The L-KYNs treatment did not affect the general ambulatory activity of C57Bl/6j mice, whereas it altered their moving patterns, elevating the movement velocity and resting time. Additionally, it seemed to increase anxiety-like behavior, as peripheral zone preference of the open field arena emerged and the rearing activity was attenuated. The treatment also completely abolished the formation of object recognition memory and resulted in decreases in the number of c-Fos-immunopositive-cells in the dorsal part of the striatum and in the CA1 pyramidal cell layer of the hippocampus. We conclude that a single exposure to L-KYNs leads to behavioral disturbances, which might be related to the altered basal c-Fos protein expression in C57Bl/6j mice. PMID:26136670

  11. The chemotherapeutic effect of essential oil of Plectranthus amboinicus (Lour) on lung metastasis developed by B16F-10 cell line in C57BL/6 mice.

    PubMed

    Manjamalai, A; Grace, V M Berlin

    2013-01-01

    Current investigation is to evaluate the anticancer activity of the essential oil of Plectranthus amboinicus (Lour) on B16F-10 melanoma cell line injected C57BL/6 mice, and it was simultaneously treated with the essential oil of P. amboinicus (Lour) (50 μg/dose) via i.p. for 21 days. The present investigation exhibited the potent chemotherapeutic/chemopreventive effect of the essential oil of P. amboinicus (Lour) over lung metastasis that developed. To our knowledge, this is the first report in evaluating the effect of essential oil of P. amboinicus (Lour) using lung cancer model. PMID:23249189

  12. Comparison of Reference Values in Whole Blood of DMDmdx/J and C57BL/6J Mice Using Neutron Activation Analysis

    NASA Astrophysics Data System (ADS)

    Metairon, S.; Zamboni, C. B.; Suzuki, M. F.; Júnior, C. R. B.; Sant'Anna, O. A.

    2011-08-01

    The Br, Ca, Cl, K, Na and S concentrations in whole blood of DMDmdx/J and C57BL/6J mice were determined using Neutron Activation Analysis technique. Reference values obtained from twenty one whole blood samples of these strains were analyzed in the IEA-R1 nuclear reactor at IPEN (São Paulo, Brasil). These data contribute for applications in veterinary medicine related to biochemistry analyses using whole blood as well as to evaluate the performance of treatments in muscular dystrophy.

  13. [The influence of piracetam on behavior and brain receptors in C57BL/6 and BALB/c mice: nootropic and anxiolytic effects].

    PubMed

    Kovalev, G I; Kondrakhin, E A; Salimov, R M; Neznamov, G G

    2013-01-01

    The influence of acute and long-term piracetam administration on the dynamics of rapid (non-specific, anxiolytic) and slow (specific, nootropic) behavioral drug effects, as well as on their interrelation with NMDA- and BDZ-receptors was studied in inbred mice strains differing in cognitive and emotional status--C57BL/6 and BALB/c. The BALB/c strain contained 17% less [3H]-flunitrazepam binding sites in frontal cortex and 22% less [3H]-MK801 binding sites in hippocampus as compared to those in C57BL/6 mice. Based on these data, BALB/c strain was used as a model of psychopathology, combining increased anxiety and cognitive deficit. Under the action of single, 7-fold, and 14-fold piracetam i.p. injections (200 mg/kg body weight, daily), a fast increase in NMDA-receptor density and slow escalation of the specific nootropic effect was observed in BALB/c mice. Non-specific anxiolytic effects in these mice increased for the first 1 - 7 days without any changes in BDZ-binding and then decreased to initial values accompanied by decrement of brain receptor concentration. Thus, in BALB/c mice, a slowly manifested specific nootropic action of piracetam develops, following an increase in NMDA receptor density, whereas the non-specific anxiolytic effect precedes the fast-paced changes in BDZ-binding site density.

  14. Fluvoxamine increased glutamate release by activating both 5-HT(3) and sigma-1 receptors in prelimbic cortex of chronic restraint stress C57BL/6 mice.

    PubMed

    Fu, Yingmei; Yu, Shunying; Guo, Xiaoyun; Li, Xia; Li, Ting; Li, Huafang; Dong, Yi

    2012-04-01

    Emerging evidence from therapeutic trials in humans and animal models suggests that in the treatment of depression, antidepressants play a role by targeting the glutamatergic system. Fluvoxamine is one of the widely used SSRIs which has been considered to target monoamine neurotransmitter reuptake mechanisms. However, whether fluvoxamine has an effect on the glutamate release is still unclear. The present experiment studied the effect of fluvoxamine on presynaptic glutamate release in prelimbic cortex, both in control C57BL/6 mice and chronic restraint stress C57BL/6 mice, and further investigated the mechanism underlying this effect by using patch clamp, on-line fluorimetry, pharmacological approaches combined with other techniques. The results showed that fluvoxamine increased the glutamate release in the depression model mice but it had no effect on the glutamate release in the control mice. The mechanism underlying these effects in depression model mice was that, fluvoxamine firstly activated presynaptic 5-HT(3) receptors, which transiently increased the Ca(2+) concentration. The increase of Ca(2+) concentration via 5-HT(3) receptors caused the activation of sigma-1 receptors, which were activated by fluvoxamine. The activation of sigma-1 receptors increased the intrasynaptosomal Ca(2+) concentration significantly through the outflow of endoplasmic reticulum calcium and finally activated PKC. These results suggested that fluvoxamine may have a selective effect and different mechanism based on the condition of animal. PMID:22306004

  15. Extract of Wax Gourd Peel Prevents High-Fat Diet-Induced Hyperlipidemia in C57BL/6 Mice via the Inhibition of the PPARγ Pathway

    PubMed Central

    Gu, Ming; Fan, Shengjie; Liu, Gaigai; Guo, Lu; Ding, Xiaobo; Lu, Yan; Zhang, Yu; Huang, Cheng

    2013-01-01

    Wax gourd is a popular vegetable in East Asia. In traditional Chinese medicine, wax gourd peel is used to prevent and treat metabolic diseases such as hyperlipidemia, hyperglycemia, obesity, and cardiovascular disease. However, there is no experimental evidence to support these applications. Here, we examined the effect of the extract of wax gourd peel (EWGP) on metabolic disorders in diet-induced C57BL/6 obese mice. In the preventive experiment, EWGP blocked body weight gain and lowered serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), liver TG and TC contents, and fasting blood glucose in mice fed with a high-fat diet. In the therapeutic study, we induced obesity in the mice and treated with EWGP for two weeks. We found that EWGP treatment reduced serum and liver triglyceride (TG) contents and fasting blood glucose and improved glucose tolerance in the mice. Reporter assay and gene expression analysis showed that EWGP could inhibit peroxisome proliferator-activated receptor γ (PPARγ) transactivities and could decrease mRNA levels of PPARγ and its target genes. We also found that HMG-CoA reductase (HMGCR) was downregulated in the mouse liver by EWGP. Our data suggest that EWGP lowers hyperlipidemia of C57BL/6 mice induced by high-fat diet via the inhibition of PPARγ and HMGCR signaling. PMID:23533476

  16. Adolescent female C57BL/6 mice with vulnerability to activity-based anorexia exhibit weak inhibitory input onto hippocampal CA1 pyramidal cells

    PubMed Central

    Chowdhury, Tara G.; Wable, Gauri S.; Sabaliauskas, Nicole A.; Aoki, Chiye

    2014-01-01

    Anorexia nervosa (AN) is an eating disorder characterized by self-imposed severe starvation and often linked with excessive exercise. Activity-based anorexia (ABA) is an animal model that reproduces some of the behavioral phenotypes of AN, including the paradoxical increase in voluntary exercise following food restriction (FR). Although certain rodents have been used successfully in this animal model, C57BL/6 mice are reported to be less susceptible to ABA. We re-examined the possibility that female C57BL/6 mice might exhibit ABA vulnerability during adolescence, the developmental stage/sex among the human population with particularly high AN vulnerability. After introducing the running wheel to the cage for three days, ABA was induced by restricting food access to 1 hour per day (ABA1, N=13) or 2 hours per day (ABA2, N=10). All 23 exhibited increased voluntary wheel running (p<0.005) and perturbed circadian rhythm within two days. Only one out of five survived ABA1 for three days, while ten out of ten survived ABA2 for three days and could subsequently restore their body weight and circadian rhythm. Exposure of recovered animals to a second ABA2 induction revealed a large range of vulnerability, even within littermates. To look for the cellular substrate of differences in vulnerability, we began by examining synaptic patterns in the hippocampus, a brain region that regulates anxiety as well as plasticity throughout life. Quantitative EM analysis revealed that CA1 pyramidal cells of animals vulnerable to the second ABA2 exhibit less GABAergic innervation on cell bodies and dendrites, relative to the animals resilient to the second ABA (p<0.001) or controls (p<0.05). These findings reveal that C57BL/6J adolescent females can be used to capture brain changes underlying ABA vulnerability, and that GABAergic innervation of hippocampal pyramidal neurons is one important cellular substrate to consider for understanding the progression of and resilience to AN. PMID

  17. Maternal Weight Gain as a Predictor of Litter Size in Swiss Webster, C57BL/6J, and BALB/cJ mice

    PubMed Central

    Finlay, James B; Liu, Xueli; Ermel, Richard W; Adamson, Trinka W

    2015-01-01

    An important task facing both researchers and animal core facilities is producing sufficient mice for a given project. The inherent biologic variability of mouse reproduction and litter size further challenges effective research planning. A lack of precision in project planning contributes to the high cost of animal research, overproduction (thus waste) of animals, and inappropriate allocation of facility resources. To examine the extent daily prepartum maternal weight gain predicts litter size in 2 commonly used mouse strains (BALB/cJ and C57BL/6J) and one mouse stock (Swiss Webster), we weighed ≥ 25 pregnant dams of each strain or stock daily from the morning on which a vaginal plug (day 0) was present. On the morning when dams delivered their pups, we recorded the weight of the dam, the weight of the litter itself, and the number of pups. Litter sizes ranged from 1 to 7 pups for BALB/cJ, 2 to 13 for Swiss Webster, and 5 to 11 for C57BL/6J mice. Linear regression models (based on weight change from day 0) demonstrated that maternal weight gain at day 9 (BALB/cJ), day 11 (Swiss Webster), or day 14 (C57BL/6J) was a significant predictor of litter size. When tested prospectively, the linear regression model for each strain or stock was found to be accurate. These data indicate that the number of pups that will be born can be estimated accurately by using maternal weight gain at specific or stock-specific time points. PMID:26632778

  18. Radiation-induced chromosomal instability in BALB/c and C57BL/6 mice: the difference is as clear as black and white

    NASA Technical Reports Server (NTRS)

    Ponnaiya, B.; Cornforth, M. N.; Ullrich, R. L.

    1997-01-01

    Genomic instability has been proposed to be the earliest step in radiation-induced tumorigenesis. It follows from this hypothesis that individuals highly susceptible to induction of tumors by radiation should exhibit enhanced radiation-induced instability. BALB/c white mice are considerably more sensitive to radiation-induced mammary cancer than C57BL/6 black mice. In this study, primary mammary epithelial cell cultures from these two strains were examined for the "delayed" appearance of chromosomal aberrations after exposure to 137Cs gamma radiation, as a measure of radiation-induced genomic instability. As expected, actively dividing cultures from both strains showed a rapid decline of initial asymmetrical aberrations with time postirradiation. However, after 16 population doublings, cells from BALB/c mice exhibited a marked increase in the frequency of chromatid-type breaks and gaps which remained elevated throughout the time course of the experiment (28 doublings). No such effect was observed for the cells of C57BL/6 mice; after the rapid clearance of initial aberrations, the frequency of chromatid-type aberrations in the irradiated population remained at or near those of nonirradiated controls. These results demonstrate a correlation between the latent expression of chromosomal damage in vitro and susceptibility for mammary tumors, and provide further support for the central role of radiation-induced instability in the process of tumorigenesis.

  19. Ceftriaxone attenuates acquisition and facilitates extinction of cocaine-induced suppression of saccharin intake in C57BL/6J mice.

    PubMed

    Freet, Christopher S; Lawrence, Antoneal L

    2015-10-01

    Growing evidence implicates glutamate homeostasis in a number of behaviors observed in addiction such as acquisition of drug taking, motivation, and reinstatement. To date, however, the role of glutamate homeostasis in the avoidance of natural rewards due to exposure to drugs of abuse has received little attention. The aim of the current study was to evaluate the beta-lactam antibiotic, ceftriaxone, which has been shown to normalize disrupted glutamate homeostasis associated with exposure to drugs of abuse, in cocaine-induced suppression of saccharin intake in C57BL/6J mice. Briefly, C57BL/6J mice received daily injections of either 200mg/kg ceftriaxone or saline. Mice were then given access to 0.15% saccharin for 1h and immediately injected intraperitoneally with either saline or 30 mg/kg cocaine; taste-drug pairings occurred every 24h for 5 trials followed by a final CS only trial. One week following taste-drug pairings, extinction was evaluated in a series of one- and two-bottle saccharin intake tests. Individual differences in cocaine-induced suppression were observed (i.e., low and high suppressors) with differential effects of ceftriaxone. Ceftriaxone delayed suppression of saccharin intake in high suppressors but prevented suppression in low suppressors. In addition, ceftriaxone history facilitated extinction in the high suppressors. These data suggest that changes in glutamate homeostasis may be involved in the formation and expression of cocaine-induced suppression of saccharin intake in mice.

  20. Mixed housing with DBA/2 mice induces stress in C57BL/6 mice: implications for interventions based on social enrichment.

    PubMed

    Kulesskaya, Natalia; Karpova, Nina N; Ma, Li; Tian, Li; Voikar, Vootele

    2014-01-01

    Several behavioral interventions, based on social enrichment and observational learning are applied in treatment of neuropsychiatric disorders. However, the mechanism of such modulatory effect and the safety of applied methods on individuals involved in social support need further investigation. We took advantage of known differences between inbred mouse strains to reveal the effect of social enrichment on behavior and neurobiology of animals with different behavioral phenotypes. C57BL/6 and DBA/2 female mice displaying multiple differences in cognitive, social, and emotional behavior were group-housed either in same-strain or in mixed-strain conditions. Comprehensive behavioral phenotyping and analysis of expression of several plasticity- and stress-related genes were done to measure the reciprocal effects of social interaction between the strains. Contrary to our expectation, mixed housing did not change the behavior of DBA/2 mice. Nevertheless, the level of serum corticosterone and the expression of glucocorticoid receptor Nr3c1 in the brain were increased in mixed housed DBA/2 as compared with those of separately housed DBA/2 mice. In contrast, socially active C57BL/6 animals were more sensitive to the mixed housing, displaying several signs of stress: alterations in learning, social, and anxiety-like behavior and anhedonia. These behavioral impairments were accompanied by the elevated serum corticosterone and the reduced expression of Nr3c1, as well as the elevated Bdnf levels in the cortex and hippocampus. Our results demonstrate the importance of social factors in modulation of both behavior and the underlying neurobiological mechanisms in stress response, and draw attention to the potential negative impact of social interventions for individuals involved in social support.

  1. Inhibition of Tumor Growth and Immunomodulatory Effects of Flavonoids and Scutebarbatines of Scutellaria barbata D. Don in Lewis-Bearing C57BL/6 Mice

    PubMed Central

    Gong, Tao; Wang, Chun-Fei; Yuan, Jia-Rui; Li, Yu; Gu, Jun-Fei; Zhao, Bing-Jie; Zhang, Li; Jia, Xiao-Bin; Feng, Liang; Liu, Shen-Lin

    2015-01-01

    Immunomodulatory effect has been found to be an important therapeutic measure for immune responses against cancer. In this study, we evaluated the inhibition of Scutellaria barbata D. Don (SB), an anti-inflammatory and an antitumor Chinese herb, including flavonoids and scutebarbatines on tumor growth and its immunomodulatory effects in vivo. HPLC and LC/MS/MS methods were conducted for the analysis of flavonoids and scutebarbatines in SB. Lewis-bearing C57BL/6 mice model was established and tumor volume was evaluated by high frequency color ultrasound experiment. ELISA and western blot analysis were performed for the determination of immunomodulatory factors. SB treatment at the dose of 10, 6.67, and 3.33 g crude drug/kg/d significantly inhibited tumor growth of Lewis-bearing C57BL/6 mice with the inhibition rates of 44.41 ± 5.44%, 33.56 ± 4.85%, and 27.57 ± 4.96%, respectively. More importantly, the spleen and thymus indexes were increased remarkably by SB treatment. SB could decrease IL-17, IL-10, FOXP3, TGF-β1, RORγt, and IL-6 levels whereas it could increase remarkably IL-2 and IFN-γ levels. Our results demonstrated that SB could inhibit tumor growth in vivo through regulating immune function in tumor-bearing mice and suggested that the immunomodulatory function of SB had a potential therapeutic effect in lung cancer. PMID:26064167

  2. [The dynamics of behavioral and neuroreceptor effects after acute and long-term noopept administration in C57BL/6 and BALB/c mice].

    PubMed

    Kovalev, G I; Kondrakhin, E A; Salimov, R M; Neznamov, G G

    2014-01-01

    The effect of acute, 7-fold and 14-fold noopept (1 mg/kg/day) administration on the dynamics of anxiolitic and nootropic behavioral effects in cross-maze, as well as their correlations with NMDA- and BDZ-receptor density was studied in inbred mice strains, differing in exploratory and emotional status--C57BL/6 and BALB/c. The dipeptide failed to affect the anxiety and exploration activity in C57BL/6 mice at each of 3 steps of experimental session. In this strain the B(max) values of [3H]-MK-801 and [3H]-Flunitrazepam binding changed only after single administration. In respect to BALB/c mice noopept induced both the anxiolitic and nootropic effects reaching their maximum on 7th day. In BALB/c strain the dynamics of hippocampal NMDA-receptor binding corresponds to the dynamics of exploratory efficacy whereas the dynamics of BDZ-receptors in prefrontal cortex was reciprocally to dynamics of anxiety level. PMID:25739185

  3. Autoantibody response and pregnancy-related pathology induced by combined LPS and tetanus toxoid hyperimmunization in BALB/c and C57BL/6 mice.

    PubMed

    Petrušić, Vladimir; Todorović, Nevena; Živković, Irena; Dimitrijević, Rajna; Muhandes, Lina; Rajnpreht, Irena; Dimitrijević, Ljiljana

    2015-03-01

    Recent data concerning antiphospholipid syndrome (APS) induction have shown that β2-glycoprotein I (β2GPI) binds lipopolysaccharide (LPS), which results in conformational changes, exposition of a cryptic epitope and possible pathological anti-β2GPI antibody production. In order to investigate the effects of LPS on the induction of APS-related pathology, we performed hyperimmunization of BALB/c and C57BL/6 mice with LPS, alone or in combination with tetanus toxoid (TTd), a protein structurally similar to β2GPI. We report that, although high affinity pathological anti-β2GPI antibodies were produced in all groups of animals, the reproductive pathology was recorded only in mice that received both LPS and TTd, implying on the important roles of both infections and molecular mimicry in APS pathogenesis. Moreover, APS-related reproductive pathology was more pronounced in BALB/c (lowered fertility and fecundity) than C57BL/6 mice (lowered fecundity), which correlated well with the disruption in natural antibody network observed in BALB/c mouse strain.

  4. Sunflower Oil Supplementation Has Proinflammatory Effects and Does Not Reverse Insulin Resistance in Obesity Induced by High-Fat Diet in C57BL/6 Mice

    PubMed Central

    Masi, Laureane Nunes; Martins, Amanda Roque; Neto, José César Rosa; do Amaral, Cátia Lira; Crisma, Amanda Rabello; Vinolo, Marco Aurélio Ramirez; de Lima Júnior, Edson Alves; Hirabara, Sandro Massao; Curi, Rui

    2012-01-01

    High consumption of polyunsaturated fatty acids, such as sunflower oil has been associated to beneficial effects in plasma lipid profile, but its role on inflammation and insulin resistance is not fully elucidated yet. We evaluated the effect of sunflower oil supplementation on inflammatory state and insulin resistance condition in HFD-induced obese mice. C57BL/6 male mice (8 weeks) were divided in four groups: (a) control diet (CD), (b) HFD, (c) CD supplemented with n-6 (CD + n-6), and (d) HFD supplemented with n-6 (HFD + n-6). CD + n-6 and HFD + n-6 were supplemented with sunflower oil by oral gavage at 2 g/Kg of body weight, three times per week. CD and HFD were supplemented with water instead at the same dose. HFD induced whole and muscle-specific insulin resistance associated with increased inflammatory markers in insulin-sensitive tissues and macrophage cells. Sunflower oil supplementation was not efficient in preventing or reducing these parameters. In addition, the supplementation increased pro-inflammatory cytokine production by macrophages and tissues. Lipid profile, on the other hand, was improved with the sunflower oil supplementation in animals fed HFD. In conclusion, sunflower oil supplementation improves lipid profile, but it does not prevent or attenuate insulin resistance and inflammation induced by HFD in C57BL/6 mice. PMID:22988427

  5. Learning deficits in C57BL/6J mice following perinatal arsenic exposure: consequence of lower corticosterone receptor levels?

    PubMed

    Martinez-Finley, Ebany J; Ali, Abdul-Mehdi S; Allan, Andrea M

    2009-12-01

    Most studies on arsenic as a drinking water contaminant have focused on its carcinogenic potential but a few suggest that arsenic can adversely affect cognitive development. One parameter of the hypothalamic-pituitary-adrenal axis, the corticosterone receptor (CR) has been shown to be altered by arsenic. These receptors are found throughout the central nervous system, particularly in the hippocampus, an area of the brain of central importance for learning and memory. We examined the impact of perinatal exposure to 50 parts per billion (ppb) sodium arsenate on CRs and learning and memory behavior in the C57BL/6J mouse. Measurements of CRs revealed that arsenic-exposed offspring have significantly lower levels of these receptors in the nucleus than controls. Exposed offspring showed longer latency to approach a novel object than controls in an object recognition task. In the 8-way radial arm maze, arsenic offspring had a significant increase in the number of entry errors compared to controls. Results suggest that moderate exposures to perinatal arsenic can significantly reduce CR levels in the hippocampus and can have adverse effects on learning and memory behavior.

  6. 1H NMR Metabolomics Study of Spleen from C57BL/6 Mice Exposed to Gamma Radiation

    PubMed Central

    Xiao, X; Hu, M; Liu, M; Hu, JZ

    2016-01-01

    Due to the potential risk of accidental exposure to gamma radiation, it’s critical to identify the biomarkers of radiation exposed creatures. In the present study, NMR based metabolomics combined with multivariate data analysis to evaluate the metabolites changed in the C57BL/6 mouse spleen after 4 days whole body exposure to 3.0 Gy and 7.8 Gy gamma radiations. Principal component analysis (PCA) and orthogonal projection to latent structures analysis (OPLS) are employed for classification and identification potential biomarkers associated with gamma irradiation. Two different strategies for NMR spectral data reduction (i.e., spectral binning and spectral deconvolution) are combined with normalize to constant sum and unit weight before multivariate data analysis, respectively. The combination of spectral deconvolution and normalization to unit weight is the best way for identifying discriminatory metabolites between the irradiation and control groups. Normalized to the constant sum may achieve some pseudo biomarkers. PCA and OPLS results shown that the exposed groups can be well separated from the control group. Leucine, 2-aminobutyrate, valine, lactate, arginine, glutathione, 2-oxoglutarate, creatine, tyrosine, phenylalanine, π-methylhistidine, taurine, myoinositol, glycerol and uracil are significantly elevated while ADP is decreased significantly. These significantly changed metabolites are associated with multiple metabolic pathways and may be potential biomarkers in the spleen exposed to gamma irradiation. PMID:27019763

  7. Differential expression of cytokines in subcutaneous and marrow fat of aging C57BL/6J mice.

    PubMed

    Gasparrini, Marco; Rivas, Daniel; Elbaz, Alexandre; Duque, Gustavo

    2009-09-01

    Increasing marrow adipogenesis plays a causative role in the pathogenesis of age-related bone loss that could be associated with high cytokine production. In this study, we characterized the age-related changes in cytokine expression by bone marrow (BM) adipocytes as compared with subcutaneous (SC) fat. BM and SC adipocytes were isolated from young (4 months) and old (24 months) male C57BL/6J. Total proteins were extracted and proteomic analysis of 96 cytokines was performed using a cytokine antibody array. Proteins showing a significant change were grouped according with their known function in bone. We found a significant age-induced difference in the expression of 53 cytokines. As compared with SC adipocytes, aging BM adipocytes showed a more pro-adipogenic, anti-osteoblastogenic and pro-apoptotic phenotype. These data suggest that, with aging, BM adipocytes become significantly more toxic than SC adipocytes. These cytokines, if secreted, could play a role in the pathogenesis of age-related bone loss by affecting other cells within the marrow milieu.

  8. Antibody response is required for protection from Theiler's virus-induced encephalitis in C57BL/6 mice in the absence of CD8{sup +} T cells

    SciTech Connect

    Kang, B.-S.; Palma, Joann P.; Lyman, Michael A.; Dal Canto, Mauro; Kim, Byung S. . E-mail: bskim@northwestern.edu

    2005-09-15

    Intracerebral infection of susceptible mice with Theiler's murine encephalomyelitis virus (TMEV) induces immune-mediated demyelinating disease and this system serves as a relevant infectious model for human multiple sclerosis. It was previously shown that {beta}{sub 2}M-deficient C57BL/6 mice lacking functional CD8{sup +} T cells display increased viral persistence and enhanced susceptibility to TMEV-induced demyelination, and yet the majority of mice are free of clinical signs. To understand the mechanisms involved in this general resistance of C57BL/6 mice in the absence of CTL responses, mice ({mu}MT) deficient in the B-cell compartment lacking membrane IgM molecules were treated with anti-CD8 antibody and then infected with TMEV. Although little difference in the proliferative responses of peripheral T cells to UV-inactivated TMEV and the resistance to demyelinating disease was observed between virus-infected {mu}MT and control B6 mice, the levels of CD4{sup +} T cells were higher in the CNS of {mu}MT mice. However, after treatment with anti-CD8 antibody, 100% of the mice displayed clinical gray matter disease and prolonged viral persistence in {mu}MT mice, while only 10% of B6 mice showed clinical symptoms and very low viral persistence. Transfusion of sera from TMEV-infected B6 mice into anti-CD8 antibody-treated {mu}MT mice partially restored resistance to virus-induced encephalitis. These results indicate that the early anti-viral antibody response is also important in the protection from TMEV-induced encephalitis particularly in the absence of CD8{sup +} T cells.

  9. Age-related deterioration of cortical responses to slow FM sounds in the auditory belt region of adult C57BL/6 mice.

    PubMed

    Tsukano, Hiroaki; Horie, Masao; Honma, Yuusuke; Ohga, Shinpei; Hishida, Ryuichi; Takebayashi, Hirohide; Takahashi, Sugata; Shibuki, Katsuei

    2013-11-27

    To compare age-related deterioration of neural responses in each subfield of the auditory cortex in C57BL/6 mice, we evaluated amplitudes of tonal responses in young (5-11 weeks old) and adult (16-23 weeks old) groups using transcranial flavoprotein fluorescence imaging. Cortical responses to 20-kHz amplitude-modulated (AM) sounds, which were mainly found in the anterior auditory field (AAF) and the primary auditory cortex (AI) of the core region, were not markedly different between the two groups. In contrast, cortical responses to direction reversal of slow frequency-modulated (FM) sounds, which were mainly found in the ultrasonic field (UF), were significantly disrupted in the adult group compared with those in the young group. To investigate the mechanisms underlying such age-related deterioration, biotinylated dextran amine (BDA) was injected into UF. The number of retrograde labeled neurons in the dorsal division of the medial geniculate body (MGd) was markedly reduced in the adult group compared with that in the young group. These results strongly suggest that cortical responses to FM direction reversal in UF of adult C57BL/6 mice are mainly deteriorated by loss of non-lemniscal thalamic inputs from MGd to UF due to aging.

  10. Successful protection against tularemia in C57BL/6 mice is correlated with expansion of Francisella tularensis-specific effector T cells.

    PubMed

    Griffin, Amanda J; Crane, Deborah D; Wehrly, Tara D; Bosio, Catharine M

    2015-01-01

    Francisella tularensis is an intracellular, Gram-negative bacterium that causes the fatal disease tularemia. Currently, there are no licensed vaccines for tularemia and the requirements for protection against infection are poorly defined. To identify correlates of vaccine-induced immunity against tularemia, we compared different strains of the live vaccine strain (LVS) for their relative levels of virulence and ability to protect C57BL/6 mice against challenge with virulent F. tularensis strain SchuS4. Successful vaccination, as defined by survival of C57BL/6 mice, was correlated with significantly greater numbers of effector T cells in the spleen and lung. Further, lung cells and splenocytes from fully protected animals were more effective than lung cells and splenocytes from vaccinated but nonimmune animals in limiting intracellular replication of SchuS4 in vitro. Together, our data provide a unique model to compare efficacious vaccines to nonefficacious vaccines, which will enable comprehensive identification of host and bacterial components required for immunization against tularemia.

  11. The Effect of Oxytocin on Social and Non-Social Behaviour and Striatal Protein Expression in C57BL/6N Mice

    PubMed Central

    Zhang, Xiaofan; Li, Qi; Zhang, Min; Lam, Sylvia; Sham, Pak Chung; Bu, Bitao; Chua, Siew Eng; Wang, Wei; McAlonan, Grainne Mary

    2015-01-01

    Oxytocin has been suggested as a promising new treatment for neurodevelopmental disorders. However, important gaps remain in our understanding of its mode of action, in particular, to what extent oxytocin modulates social and non-social behaviours and whether its effects are generalizable across both sexes. Here we investigated the effects of a range of oxytocin doses on social and non-social behaviours in C57BL/6N mice of both sexes. As the striatum modulates social and non-social behaviours, and is implicated in neurodevelopmental disorders, we also conducted a pilot exploration of changes in striatal protein expression elicited by oxytocin. Oxytocin increased prepulse inhibition of startle but attenuated the recognition memory in male C57BL/6N mice. It increased social interaction time and suppressed the amphetamine locomotor response in both sexes. The striatum proteome following oxytocin exposure could be clearly discriminated from saline controls. With the caveat that these results are preliminary, oxytocin appeared to alter individual protein expression in directions similar to conventional anti-psychotics. The proteins affected by oxytocin could be broadly categorized as those that modulate glutamatergic, GABAergic or dopaminergic signalling and those that mediate cytoskeleton dynamics. Our results here encourage further research into the clinical application of this peptide hormone, which may potentially extend treatment options across a spectrum of neurodevelopmental conditions. PMID:26716999

  12. Effects of high cholesterol diet on newly generated cells in the dentate gyrus of C57BL/6N and C3H/HeN mice.

    PubMed

    Kim, Il Yong; Hwang, In Koo; Choi, Ji Won; Yoo, Ki-Yeon; Kim, Yo Na; Yi, Sun Shin; Won, Moo-Ho; Lee, In Se; Yoon, Yeo Sung; Seong, Je Kyung

    2009-06-01

    In this study, we observed and compared the effects of a high cholesterol diet (HCD) on cell proliferation and differentiation in the subgranular zone of the dentate gyrus of C57BL/6N (B6, susceptible strain) and C3H/HeN (C3H, resistant strain) mice. Ki67 (a marker for cell proliferation) positive cells) were significantly decreased in HCD-fed B6 mice compared to those in B6 (49.7%) and C3H mice fed a low cholesterol diet (LCD). In addition, doublecortin (DCX, a marker for cell differentiation or neuroblasts)-immunoreactive cells in HCD-fed B6 mice were significantly decreased compared to those in LCD-fed B6 and C3H mice. These results suggest that B6 strains are sensitive to HCD, which impairs cell proliferation and differentiation.

  13. Characterization of learning and memory deficits in C57BL/6 mice infected with LP-BM5, a murine model of AIDS.

    PubMed

    Iida, R; Yamada, K; Mamiya, T; Saito, K; Seishima, M; Nabeshima, T

    1999-03-01

    Mice infected with an immunosuppressive murine leukemia virus mixture, LP-BM5 show a profound immunosuppression described as murine acquired immune deficiency syndrome (AIDS). In the present study, we characterized learning and memory deficits in C57BL/6 mice infected with LP-BM5. Spontaneous alternation behavior in a Y-maze and latent learning (spatial attention) in a water-finding test, as well as spatial reference and reversal learning in a water maze test, were significantly impaired in the mice infected with LP-BM5. These deficits appeared in the absence of any motoric and visual impairment as assessed by open-field, rotarod and visual water maze tests. These results suggest that cognitive functions are impaired in the mice infected with LP-BM5. Furthermore, LP-BM5-infected mice may be useful as a model for the AIDS dementia complex.

  14. Impact of PACAP and PAC1 Receptor Deficiency on the Neurochemical and Behavioral Effects of Acute and Chronic Restraint Stress in Male C57BL/6 Mice

    PubMed Central

    Mustafa, Tomris; Jiang, Sunny Zhihong; Eiden, Adrian M.; Weihe, Eberhard; Thistlethwaite, Ian; Eiden, Lee E.

    2016-01-01

    Acute restraint stress (ARS) for 3 hours causes CORT elevation in venous blood, which is accompanied by Fos up-regulation in the paraventricular nucleus (PVN) of male C57BL/6 mice. CORT elevation by ARS is attenuated in PACAP-deficient mice, but unaffected in PAC1-deficient mice. Correspondingly, Fos up-regulation by ARS is greatly attenuated in PACAP-deficient mice, but much less so in PAC1-deficient animals. We noted that both PACAP- and PAC1-deficiency greatly attenuate CORT elevation after ARS when CORT measurements are performed on trunk blood following euthanasia by abrupt cervical separation: this latter observation is of critical importance in assessing the role of PACAP neurotransmission in ARS, based on previous reports in which serum CORT was sampled from trunk blood. Seven days of chronic restraint stress (CRS) induces non-habituating CORT elevation, and weight loss consequent to hypophagia, in wild-type male C57BL/6 mice. Both CORT elevation and weight loss following seven day CRS are severely blunted in PACAP-deficient mice, but only slightly in PAC1 deficient mice. However, longer periods of daily restraint (14–21 days) resulted in sustained weight loss and elevated CORT in wild-type mice, and these effects of long-term chronic stress were attenuated or abolished in both PACAP- and PAC1-deficient mice. We conclude that while a PACAP receptor in addition to PAC1 may mediate some of the PACAP-dependent central effects of acute restraint stress and short-term (<7 days) chronic restraint stress on the HPA axis, the PAC1 receptor plays a prominent role in mediating PACAP-dependent HPA axis activation, and hypophagia, during long-term (>7 days) chronic restraint stress. PMID:25853791

  15. Impact of PACAP and PAC1 receptor deficiency on the neurochemical and behavioral effects of acute and chronic restraint stress in male C57BL/6 mice.

    PubMed

    Mustafa, Tomris; Jiang, Sunny Zhihong; Eiden, Adrian M; Weihe, Eberhard; Thistlethwaite, Ian; Eiden, Lee E

    2015-01-01

    Acute restraint stress (ARS) for 3 h causes corticosterone (CORT) elevation in venous blood, which is accompanied by Fos up-regulation in the paraventricular nucleus (PVN) of male C57BL/6 mice. CORT elevation by ARS is attenuated in PACAP-deficient mice, but unaffected in PAC1-deficient mice. Correspondingly, Fos up-regulation by ARS is greatly attenuated in PACAP-deficient mice, but much less so in PAC1-deficient animals. We noted that both PACAP- and PAC1-deficiency greatly attenuate CORT elevation after ARS when CORT measurements are performed on trunk blood following euthanasia by abrupt cervical separation: this latter observation is of critical importance in assessing the role of PACAP neurotransmission in ARS, based on previous reports in which serum CORT was sampled from trunk blood. Seven days of chronic restraint stress (CRS) induces non-habituating CORT elevation, and weight loss consequent to hypophagia, in wild-type male C57BL/6 mice. Both CORT elevation and weight loss following 7-day CRS are severely blunted in PACAP-deficient mice, but only slightly in PAC1-deficient mice. However, longer periods of daily restraint (14-21 days) resulted in sustained weight loss and elevated CORT in wild-type mice, and these effects of long-term chronic stress were attenuated or abolished in both PACAP- and PAC1-deficient mice. We conclude that while a PACAP receptor in addition to PAC1 may mediate some of the PACAP-dependent central effects of ARS and short-term (<7 days) CRS on the hypothalamo-pituitary-adrenal (HPA) axis, the PAC1 receptor plays a prominent role in mediating PACAP-dependent HPA axis activation, and hypophagia, during long-term (>7 days) CRS.

  16. [Effect of estradiol on food intake, glucose and fat metabolism in mice C57BL/6J with mutation yellow at the agouti locus].

    PubMed

    Iakovleva, T V; Makarova, E N; Kazantseva, A Iu; Bazhan, N M

    2012-05-01

    Mutation yellow at the agouti locus in mice (A(y)/a-mice) causes the increase of food intake and development of obesity and type 2 diabetes. In A(y)/a-females the disturbances of glucose and fat metabolisms occur after puberty. We have assumed that the mutation yellow violates the regulatory effect of estradiol on glucose and fat metabolism in mice. We investigated the effects of ovariectomy and estradiol treatment on body weight, food intake, glucose tolerance, plasma levels of glucose, insulin and etherified fatty acids in A(y)/a-females. C57Bl/6J females, not carrying yellow mutation at the agouti locus (a/a-mice), were used as a control. The data suggest that the yellow mutation did not affect estradiol regulation of food intake and glucose blood levels after a night of fasting, but, apparently, prevented estradiol participation in the regulation of glucose and fat metabolisms in the muscle and fat tissues.

  17. Long-Term Provision of Environmental Resources Alters Behavior but not Physiology or Neuroanatomy of Male and Female BALB/c and C57BL/6 Mice.

    PubMed

    Clipperton-Allen, Amy E; Ingrao, Joelle C; Ruggiero, Laura; Batista, Lucas; Ovari, Jelena; Hammermueller, Jutta; Armstrong, John N; Bienzle, Dorothee; Choleris, Elena; Turner, Patricia V

    2015-11-01

    Few studies have evaluated the long-term effects of providing environmental resources to mice. This consideration is important given that mice are often maintained in vivaria for months. We evaluated the effects of providing simple cage resources (wood wool, cotton nesting material, a plastic tunnel, and oat cereal) compared with standard housing (solid-bottom cage with hardwood chips) to group-housed adult male and female C57BL/6 and BALB/c mice (n = 20/sex/strain/group) over 6 mo to determine whether these resources had a lasting effect on animal physiology, anatomy, and behavior. Body weights increased in all groups over time but were proportionately higher in male and female BALB/c mice housed in resource-supplemented environments. Throughout the study, adding environmental resources had no effect on hematology and lymphocyte subsets, fecal corticoid metabolite levels, response to LPS injection, or dendritic spine length or density. Strain- or sex×environmentspecific changes occurred in dark-light activity and thermal nociceptive responses. Dominant agonistic behaviors, abnormal conspecific sexual behaviors, and social nonagonistic behaviors demonstrated sex and strain×environment interactions such that fewer maladaptive social behaviors were noted in mice that were provided with environmental resources. This association was particularly evident in male mice of both strains in resource-supplemented environments. A small but significant increase in brain weight:body weight ratios occurred in mice in resource-supplemented environments. Under the conditions evaluated here, consistent use of simple environmental resources had a positive long-term effect on the behavioral wellbeing of male and female BALB/c and C57BL/6 mice yet minimally affected other aspects of murine physiology and neuroanatomy. PMID:26632781

  18. Long-Term Provision of Environmental Resources Alters Behavior but not Physiology or Neuroanatomy of Male and Female BALB/c and C57BL/6 Mice

    PubMed Central

    Clipperton-Allen, Amy E; Ingrao, Joelle C; Ruggiero, Laura; Batista, Lucas; Ovari, Jelena; Hammermueller, Jutta; Armstrong, John N; Bienzle, Dorothee; Choleris, Elena; Turner, Patricia V

    2015-01-01

    Few studies have evaluated the long-term effects of providing environmental resources to mice. This consideration is important given that mice are often maintained in vivaria for months. We evaluated the effects of providing simple cage resources (wood wool, cotton nesting material, a plastic tunnel, and oat cereal) compared with standard housing (solid-bottom cage with hardwood chips) to group-housed adult male and female C57BL/6 and BALB/c mice (n = 20/sex/strain/group) over 6 mo to determine whether these resources had a lasting effect on animal physiology, anatomy, and behavior. Body weights increased in all groups over time but were proportionately higher in male and female BALB/c mice housed in resource-supplemented environments. Throughout the study, adding environmental resources had no effect on hematology and lymphocyte subsets, fecal corticoid metabolite levels, response to LPS injection, or dendritic spine length or density. Strain- or sex×environment-specific changes occurred in dark–light activity and thermal nociceptive responses. Dominant agonistic behaviors, abnormal conspecific sexual behaviors, and social nonagonistic behaviors demonstrated sex and strain×environment interactions such that fewer maladaptive social behaviors were noted in mice that were provided with environmental resources. This association was particularly evident in male mice of both strains in resource-supplemented environments. A small but significant increase in brain weight:body weight ratios occurred in mice in resource-supplemented environments. Under the conditions evaluated here, consistent use of simple environmental resources had a positive long-term effect on the behavioral wellbeing of male and female BALB/c and C57BL/6 mice yet minimally affected other aspects of murine physiology and neuroanatomy. PMID:26632781

  19. Rapid Learning of Magnetic Compass Direction by C57BL/6 Mice in a 4-Armed ‘Plus’ Water Maze

    PubMed Central

    Phillips, John B.; Youmans, Paul W.; Muheim, Rachel; Sloan, Kelly A.; Landler, Lukas; Painter, Michael S.; Anderson, Christopher R.

    2013-01-01

    Magnetoreception has been demonstrated in all five vertebrate classes. In rodents, nest building experiments have shown the use of magnetic cues by two families of molerats, Siberian hamsters and C57BL/6 mice. However, assays widely used to study rodent spatial cognition (e.g. water maze, radial arm maze) have failed to provide evidence for the use of magnetic cues. Here we show that C57BL/6 mice can learn the magnetic direction of a submerged platform in a 4-armed (plus) water maze. Naïve mice were given two brief training trials. In each trial, a mouse was confined to one arm of the maze with the submerged platform at the outer end in a predetermined alignment relative to magnetic north. Between trials, the training arm and magnetic field were rotated by 180° so that the mouse had to swim in the same magnetic direction to reach the submerged platform. The directional preference of each mouse was tested once in one of four magnetic field alignments by releasing it at the center of the maze with access to all four arms. Equal numbers of responses were obtained from mice tested in the four symmetrical magnetic field alignments. Findings show that two training trials are sufficient for mice to learn the magnetic direction of the submerged platform in a plus water maze. The success of these experiments may be explained by: (1) absence of alternative directional cues (2), rotation of magnetic field alignment, and (3) electromagnetic shielding to minimize radio frequency interference that has been shown to interfere with magnetic compass orientation of birds. These findings confirm that mice have a well-developed magnetic compass, and give further impetus to the question of whether epigeic rodents (e.g., mice and rats) have a photoreceptor-based magnetic compass similar to that found in amphibians and migratory birds. PMID:24023673

  20. A diet containing soybean oil heated for three hours increases adipose tissue weight but decreases body weight in C57BL/6 J mice

    PubMed Central

    2013-01-01

    Background Our previous work showed that dietary oxidized linoleic acid given, as a single fatty acid, to LDL receptor knockout mice decreased weight gain as compared to control mice. Other studies have also reported that animals fed oils heated for 24 h or greater showed reduced weight gain. These observations, while important, have limited significance since fried foods in the typical human diet do not contain the extreme levels of oxidized lipids used in these studies. The main goal of this study was to investigate the effects of a diet containing soybean oil heated for 3 h on weight gain and fat pad mass in mice. Additionally, because PPARγ and UCP-1 mediate adipocyte differentiation and thermogenesis, respectively, the effect of this diet on these proteins was also examined. Findings Four to six week old male C57BL/6 J mice were randomly divided into three groups and given either a low fat diet with heated soybean oil (HSO) or unheated soybean oil (USO) or pair fed for 16 weeks. Weight and food intake were monitored and fat pads were harvested upon the study’s termination. Mice consuming the HSO diet had significantly increased fat pad mass but gained less weight as compared to mice in the USO group despite a similar caloric intake and similar levels of PPARγ and UCP1. Conclusion This is the first study to show that a diet containing soybean oil heated for a short time increases fat mass despite a decreased weight gain in C57BL/6 J mice. The subsequent metabolic consequences of this increased fat mass merits further investigation. PMID:23510583

  1. Characterization of a Severe Parenchymal Phenotype of Experimental Autoimmune Encephalomyelitis in (C57BL6xB10.PL)F1 Mice

    PubMed Central

    Carrithers, Michael D.; Carrithers, Lisette M.; Czyzyk, Jan; Henegariu, Octavian

    2009-01-01

    We here describe a novel CD4 T cell adoptive transfer model of severe experimental autoimmune encephalomyelitis in (C57BL6xB10.PL)F1 mice. This FI cross developed severe disease characterized by extensive parenchymal spinal cord and brain periventricular white matter infiltrates. In contrast, B10.PL mice developed mild disease characterized by meningeal predominant infiltrates. As determined by cDNA microarray and quantitative real time PCR expression analysis, histologic and flow cytometry analysis of inflammatory infiltrates, and attenuation of disease in class I-deficient and CD8-depleted F1 mice; this severe disease phenotype appears to be regulated by CNS infiltration of CD8 T lymphocytes early in the disease course. PMID:17512611

  2. Dietary supplementation with purified mulberry (Morus australis Poir) anthocyanins suppresses body weight gain in high-fat diet fed C57BL/6 mice.

    PubMed

    Wu, Tao; Qi, Xueming; Liu, Yan; Guo, Jun; Zhu, Ruiyu; Chen, Wei; Zheng, Xiaodong; Yu, Ting

    2013-11-01

    We present our experiment about adding anthocyanins to the daily food of mice. Three kinds of anthocyanins (cyanidin-3-glucoside, cyanidin-3-rutinoside and pelargonidin-3-glucoside) purified from Chinese mulberry (Morus australis Poir) were evaluated for suppressing body weight gain of the male C57BL/6 mice fed with high-fat diet (HFD). The results from a 12-week experiment show that consumption of purified mulberry anthocyanins (MACN) of 40 or 200mg/kg can significantly inhibit body weight gain, reduce the resistance to insulin, lower the size of adipocytes, attenuate lipid accumulation and decrease the leptin secretion. Thus, dietary supplementation with MACN can protect against body weight gain of the diet-induced obese mice.

  3. Prediabetic changes in gene expression induced by aspartame and monosodium glutamate in Trans fat-fed C57Bl/6 J mice

    PubMed Central

    2013-01-01

    Background The human diet has altered markedly during the past four decades, with the introduction of Trans hydrogenated fat, which extended the shelf-life of dietary oils and promoted a dramatic increase in elaidic acid (Trans-18.1) consumption. Food additives such as monosodium glutamate (MSG) and aspartame (ASP) were introduced to increase food palatability and reduce caloric intake. Nutrigenomics studies in small-animal models are an established platform for analyzing the interactions between various macro- and micronutrients. We therefore investigated the effects of changes in hepatic and adipose tissue gene expression induced by the food additives ASP, MSG or a combination of both additives in C57Bl/6 J mice fed a Trans fat-enriched diet. Methods Hepatic and adipose tissue gene expression profiles, together with body characteristics, glucose parameters, serum hormone and lipid profiles were examined in C57Bl/6 J mice consuming one of the following four dietary regimens, commencing in utero via the mother’s diet: [A] Trans fat (TFA) diet; [B] MSG + TFA diet; [C] ASP + TFA diet; [D] ASP + MSG + TFA diet. Results Whilst dietary MSG significantly increased hepatic triglyceride and serum leptin levels in TFA-fed mice, the combination of ASP + MSG promoted the highest increase in visceral adipose tissue deposition, serum free fatty acids, fasting blood glucose, HOMA-IR, total cholesterol and TNFα levels. Microarray analysis of significant differentially expressed genes (DEGs) showed a reduction in hepatic and adipose tissue PPARGC1a expression concomitant with changes in PPARGC1a-related functional networks including PPARα, δ and γ. We identified 73 DEGs common to both adipose and liver which were upregulated by ASP + MSG in Trans fat-fed mice; and an additional 51 common DEGs which were downregulated. Conclusion The combination of ASP and MSG may significantly alter adiposity, glucose homeostasis, hepatic and adipose tissue gene

  4. Carbenoxolone prevents the development of fatty liver in C57BL/6-Lep ob/ob mice via the inhibition of sterol regulatory element binding protein-1c activity and apoptosis.

    PubMed

    Rhee, Sang Dal; Kim, Chi-Hyun; Park, Ji Seon; Jung, Won Hoon; Park, Sung Bum; Kim, Hee Youn; Bae, Gyu Hwan; Kim, Ta Jan; Kim, Ki Young

    2012-09-15

    Carbenoxolone is the 3-hemisuccinate of glycyrrhetinic acid, the active principal of licorice (Glycyrrhiza glabra). It was reported that carbenoxolone improved glucose tolerance with increased insulin sensitivity in mice with high fat diet-induced obesity. In the present study, we elucidated the protective effect of carbenoxolone in fatty liver animal models of C57BL/6-Lep(ob/ob) mice through inhibition of hepatic lipogenesis and apoptosis. In addition, the potential mechanisms by which carbenoxolone could exert such protection were elucidated. Carbenoxolone was daily administrated by gavage for 28 days in C57BL/6 and C57BL/6-Lep(ob/ob) mice. Carbenoxolone prevented the plasma triglyceride and free fatty acid accumulation associated with the reduction of the expression of sterol regulatory element binding protein-1c, liver X receptor, fatty acid synthase and acethyl-CoA carboxylase in the livers of C57BL/6-Lep(ob/ob) mice. Carbenoxolone also prevented hepatic injury through anti-apoptotic action in the livers of C57BL/6-Lep(ob/ob) mice, accompanied by increased Bcl-2 expression and suppressed Bax and cytochrome c expression. As a mechanism, increased inflammatory cytokine expressions were inhibited by carbenoxolone in the fatty livers of C57BL/6-Lep(ob/ob) mice. Furthermore, carbenoxolone inhibited free fatty acid (oleate/palmitate) induced reactive oxygen species formation and reversed free fatty acid induced mitochondrial membrane depolarization in HepG2 cells. Carbenoxolone prevents the development of fatty liver by inhibiting sterol regulatory element binding protein-1c expression and activity with an anti-apoptotic mechanism via the inhibition of inflammatory cytokine and reactive oxygen species formation in the livers of C57BL/6-Lep(ob/ob) mice. It is suggested that carbenoxolone prevents the development and progression of fatty liver disease in patients with insulin resistance.

  5. Alcohol-free fermented blueberry-blackberry beverage phenolic extract attenuates diet-induced obesity and blood glucose in C57BL/6J mice.

    PubMed

    Johnson, Michelle H; Wallig, Matthew; Luna Vital, Diego A; de Mejia, Elvira G

    2016-05-01

    The aim of this study was to determine the potential of phenolic compounds from a fermented blackberry-blueberry beverage to reduce diet-induced obesity and hyperglycemia in mice fed a 60% high-fat diet (HFD) for 10weeks after 1week of pretreatment. C57BL/6J mice were randomized into six groups and allowed to drink (ad libitum) an alcohol-free blackberry-blueberry beverage [alcohol-free fermented beverage (AFFB), 8.4mg anthocyanin (ANC)/kg body weight (BW)/day]; three doses of a phenolic extract [postamberlite extract (PAE)] from AFFB at 0.1×, 1× and 2× ANC concentrations; sitagliptin (hypoglycemic positive control); or water (negative control). Weight and fat mass gain were attenuated in mice receiving the highest doses of PAE (18.9mg ANC/kg BW/day, P<.05). There were also reductions (P<.05) in percent fat mass, epididymal fat pad weights, mean adipocyte diameters and plasma triglycerides and cholesterol associated with PAE treatments. By the end of the study, fasting blood glucose for mice receiving 9mg (1×) or 18.9mg (2×) ANC/kg BW/day was significantly lower than in the water and the sitagliptin groups (P<.05). Histological and histochemical analyses revealed an unexpected change in liver of mice fed ANC at 1× or 2× doses consisting of liver enlargement and increased lipid deposition. PAE also induced the most differential gene expression changes, including highly significant downstream effects at all doses to reduce d-glucose concentrations. Overall, phenolic compounds from the fermented blueberry-blackberry beverage had an impact to attenuate the development of obesity and fasting blood glucose in C57BL/6J mice. PMID:27133423

  6. Combined dermal exposure to permethrin and cis-urocanic acid suppresses the contact hypersensitivity response in C57BL/6N mice in an additive manner.

    PubMed

    Prater, M R; Blaylock, B L; Holladay, S D

    2005-01-14

    Cutaneous exposure to the pyrethroid insecticide permethrin significantly suppresses contact hypersensitivity (CH) response to oxazolone in C57BL/6N mice. Additionally, cis-urocanic acid (cUCA), an endogenous cutaneous chromophore isomerized to its active form following exposure to ultraviolet radiation, modulates cell-mediated cutaneous immune responses. This study describes cutaneous immune alterations following combined topical permethrin and intradermal cUCA exposure. Female C57BL/6N mice were administered 5, 50 or 100 microg cUCA daily for 5 consecutive days. CH was then evaluated by the mouse ear swelling test (MEST) response to oxazolone. Decreased responses of 52.3%, 76.3% and 76.3%, respectively, as compared to controls were observed. Then, mice were co-exposed to 5 microg cUCA daily for 5 days and 1.5, 5, 15, or 25 microL permethrin, on either day 1, 3 or 5 of the cUCA treatment to evaluate combined immunomodulatory effects of the two chemicals, or cUCA daily for 5 days followed by permethrin on day 3, 5, or 7 after the last cUCA injection to demonstrate prolonged immunosuppressive effects. Two days after final treatment, mice were sensitized with oxazolone and MEST was performed. Mice receiving five cUCA injections and permethrin topically on cUCA injection day 1 showed up to 93.3% suppression of MEST compared to vehicle control. CH was suppressed by 87.5%, 86.6% and 74.2% in mice treated with 25 muL permethrin on days 3, 5 and 7 after cUCA, respectively, compared to vehicle control. Taken together, these data indicate co-exposure to cUCA and permethrin profoundly suppresses cell-mediated cutaneous immunity. PMID:15629246

  7. Vaccination of adult and newborn mice of a resistant strain (C57BL/6J) against challenge with leukemias induced by Moloney murine leukemia virus

    SciTech Connect

    Reif, A.E.

    1985-01-01

    Adult or newborn C57BL/6J mice were immunized with isogenic Moloney strain MuLV-induced leukemia cells irradiated with 10,000 rads or treated with low concentrations of formalin. Groups of immunized and control mice were challenged with a range of doses of viable leukemia cells, and tumor deaths were recorded for 90 days after challenge. Then, the doses of challenge cells which produced 50% tumor deaths were calculated for immunized and control mice. The logarithm of their ratio quantified the degree of protection provided by immunization. For adult C57BL/6J mice, a single immunization with MuLV-induced leukemia cells was not effective; either cells plus Bacillus Calmette-Guerin or Corynebacterium parvum, or else two immunizations with irradiated leukemia cells were needed to produce statistically significant increases in the values of the doses of challenge cells which produced 50% tumor deaths. Cross-protection was obtained by immunization with other isogenic MuLV-induced leukemias, but not by immunization with isogenic carcinogen-induced tumors or with an isogenic spontaneous leukemia. For newborn mice, a single injection of irradiated leukemia cells provided 1.3 to 1.5 logs of protection, and admixture of B. Calmette-Guerin or C. parvum increased this protection to 2.4 to 2.7 logs. Since irradiated and frozen-thawed MuLV-induced leukemia cells contained viable MuLV, leukemia cells treated with 0.5 or 1.0% formalin were tested as an alternative. A single injection of formalin-treated isogenic leukemia cells admixed with C. parvum provided between 1.7 and 2.8 logs of protection. These results demonstrate that a single vaccination of newborn animals against a highly antigenic virally induced leukemia produces strong protection against a subsequent challenge with viable leukemia cells.

  8. Impact of High Fat Diet-induced Obesity on the Plasma Levels of Monoamine Neurotransmitters in C57BL/6 Mice

    PubMed Central

    Kim, Minjeong; Bae, SeungJin; Lim, Kyung-Min

    2013-01-01

    Obesity is one of the most serious health problems in developed countries. It negatively affects diverse aspects of human wellbeing. Of these, a relationship between obesity and depression is widely recognized but biomarkers for assessment of obesityassociated mood changes in animal obesity models are rarely known. Here we explored the link between obesity and the plasma levels of monoamine neurotransmitters involved in mood control using a sensitive UPLC/MSMS technique in high fat diet (HFD)- induced obesity model in male C57BL/6 mice to explore the potential utility of plasma tests for obesity-associated mood change. HFD (60% of total calories, 8 weeks) induced significantly higher weight gains in body (+37.8%) and fat tissue (+306%) in male C57BL/6 mice. Bioanalysis of serotonin, dopamine and norepinephrine in plasma at 8 weeks of HFD revealed that serotonin decreased significantly in the obese mice when compared to normal diet-fed mice (2.7 ± 0.6 vs 4.3 ± 2.0 ng/ml, N=8). Notably, a negative correlation was found between the levels of serotonin and body weight gains. Furthermore, principal component analysis (PCA) with the individual levels of neurotransmitters revealed that plasma levels of dopamine and serotonin could apparently differentiate the obese mice from lean ones. Our study demonstrated that blood plasma levels of neurotransmitters can be employed to evaluate the mood changes associated with obesity and more importantly, provided an important clue for understanding of the relationship between obesity and mood disorders. PMID:24404339

  9. Atipamezole reverses ketamine-dexmedetomidine anesthesia without altering the antinociceptive effects of butorphanol and buprenorphine in female C57BL/6J mice.

    PubMed

    Izer, Jenelle M; Whitcomb, Tiffany L; Wilson, Ronald P

    2014-11-01

    Butorphanol and buprenorphine are common analgesics used in laboratory mice. Inadvertent attenuation of the antinociceptive effects of these analgesics via the administration of an anesthetic reversal agent could result in postprocedural pain and distress, with subsequent negative effects on animal welfare, study outcomes, and regulatory compliance. This study was undertaken to determine whether atipamezole reverses ketamine-dexmedetomidine anesthesia and alters the antinociceptive effects of butorphanol and buprenorphine in female C57BL/6J mice. Atipamezole reliably reversed the anesthetic effects of ketamine-dexmedetomidine, and mice were ambulatory 17.4 ± 30.6 min after administration of the α2-adrenoreceptor antagonist. Atipamezole alone had no significant effect on tail-flick latency and did not alter the antinociceptive properties of butorphanol or low-dose (0.05 mg/kg) or high-dose (0.1 mg/kg) buprenorphine in female C57BL/6J mice. After reversal of ketamine-dexmedetomidine anesthesia, tail-flick latency at 30, 60, and 150 min after analgesic treatment differed significantly between mice treated with atipamezole alone and those given atipamezole followed by butorphanol or high-dose buprenorphine. These results suggest that the analgesic effects of butorphanol and buprenorphine are not affected by atipamezole. Buprenorphine (0.1 mg/kg) administered 30 min prior to or at the time of anesthesia resulted in a greater magnitude of antinociception after antagonism of anesthesia than when given at the time of reversal. Given these results, we recommend the use of ketamine-dexmedetomidine anesthesia with buprenorphine administered either preemptively or at the time of anesthetic induction to provide a defined period of surgical anesthesia that is effectively reversed by atipamezole. PMID:25650975

  10. Opposite effects of maternal separation on intermale and maternal aggression in C57BL/6 mice: link to hypothalamic vasopressin and oxytocin immunoreactivity.

    PubMed

    Veenema, Alexa H; Bredewold, Remco; Neumann, Inga D

    2007-06-01

    Early life stress, in particular child abuse and neglect, is an acknowledged risk factor for the development of pathological anxiety and aggression. In rodents, 3-h daily maternal separation (MS) during the first 2 weeks of life is an established animal model of early life stress and has repeatedly been shown to increase anxiety and stress responsiveness in adulthood. However, preclinical studies on the effects of postnatal stress on adult aggression are limited. The present study investigated whether MS affects intermale aggression and/or maternal aggression in C57BL/6 mice. In both adult male and virgin female mice, MS elevated anxiety-related behavior as tested on the elevated plus-maze, in the open field and during novel object exploration. The latency to attack an unknown male intruder, as assessed with the resident-intruder test, was significantly longer in MS male mice compared with control male mice. In contrast, the latency to attack a novel male intruder was significantly shorter in MS females compared with control females on days 3 and 5 of lactation. These opposite effects of MS can be explained by the fact that intermale and maternal aggression are two different forms of aggression, and hence, might be modulated by different neurobiological pathways. Indeed, in the paraventricular nucleus of the hypothalamus, MS was found to selectively increase vasopressin immunoreactivity in males, whereas MS selectively decreased oxytocin immunoreactivity in lactating females. In conclusion, MS has long-lasting and differential effects on adult intermale and maternal aggression in C57BL/6 mice. Alterations in hypothalamic vasopressin and oxytocin immunoreactivity may, in part, underlie the opposite effects of MS on intermale and maternal aggression. The MS paradigm represents a promising animal model to reveal underlying mechanisms of aggressive behavioral dysfunctions associated with early life stress. PMID:17433558

  11. Intestinal barrier analysis by assessment of mucins, tight junctions, and α-defensins in healthy C57BL/6J and BALB/cJ mice.

    PubMed

    Volynets, Valentina; Rings, Andreas; Bárdos, Gyöngyi; Ostaff, Maureen J; Wehkamp, Jan; Bischoff, Stephan C

    2016-01-01

    The intestinal barrier is gaining increasing attention because it is related to intestinal homeostasis and disease. Different parameters have been used in the past to assess intestinal barrier functions in experimental studies; however most of them are poorly defined in healthy mice. Here, we compared a number of barrier markers in healthy mice, established normal values and correlations. In 48 mice (24 C57BL/6J, 24 BALB/cJ background), we measured mucus thickness, and expression of mucin-2, α-defensin-1 and -4, zonula occludens-1, occludin, junctional adhesion molecule-A, claudin-1, 2 and -5. We also analyzed claudin-3 and fatty acid binding protein-2 in urine and plasma, respectively. A higher expression of mucin-2 protein was found in the colon compared to the ileum. In contrast, the α-defensins-1 and -4 were expressed almost exclusively in the ileum. The protein expression of the tight junction molecules claudin-1, occludin and zonula occludens-1 did not differ between colon and ileum, although some differences occurred at the mRNA level. No age- or gender-related differences were found. Differences between C57BL/6J and BALB/cJ mice were found for α-defensin-1 and -4 mRNA expression, and for urine and plasma marker concentrations. The α-defensin-1 mRNA correlated with claudin-5 mRNA, whereas α-defensin-4 mRNA correlated with claudin-3 concentrations in urine. In conclusion, we identified a number of murine intestinal barrier markers requiring tissue analyses or measurable in urine or plasma. We provide normal values for these markers in mice of different genetic background. Such data might be helpful for future animal studies in which the intestinal barrier is of interest. PMID:27583194

  12. Intact neurogenesis is required for benefits of exercise on spatial memory but not motor performance or contextual fear conditioning in C57BL/6J mice.

    PubMed

    Clark, P J; Brzezinska, W J; Thomas, M W; Ryzhenko, N A; Toshkov, S A; Rhodes, J S

    2008-09-01

    The mammalian hippocampus continues to generate new neurons throughout life. Experiences such as exercise, anti-depressants, and stress regulate levels of neurogenesis. Exercise increases adult hippocampal neurogenesis and enhances behavioral performance on rotarod, contextual fear and water maze in rodents. To directly test whether intact neurogenesis is required for gains in behavioral performance from exercise in C57BL/6J mice, neurogenesis was reduced using focal gamma irradiation (3 sessions of 5 Gy). Two months after treatment, mice (total n=42 males and 42 females) (Irradiated or Sham), were placed with or without running wheels (Runner or Sedentary) for 54 days. The first 10 days mice received daily injections of bromodeoxyuridine (BrdU) to label dividing cells. The last 14 days mice were tested on water maze (two trials per day for 5 days, then 1 h later probe test), rotarod (four trials per day for 3 days), and conte