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Sample records for mouse mesencephalon effects

  1. Differential effects of GDF5 on the medial and lateral rat ventral mesencephalon.

    PubMed

    Clayton, Kevin B; Sullivan, Aideen M

    2007-11-12

    Growth/differentiation factor 5 (GDF5) is a member of the transforming growth factor-beta (TGF-beta) superfamily that has potent neurotrophic and protective effects on dopaminergic neurones and is expressed in the developing rat substantia nigra (the ventral mesencephalon; VM). GDF5 has the potential to be used in the treatment of Parkinson's disease (PD), a neurodegenerative disorder characterised by the selective degeneration of nigrostriatal dopaminergic neurones. One therapy being explored for PD involves transplantation of fetal VM tissue into the striatum in order to replace lost dopaminergic neurones. The majority of transplantation studies have used transplants incorporating the whole VM. The principal location of dopaminergic neurones in the E14 rat VM is in the medial VM. In the present study, the effects of GDF5 on cultures prepared from medial, lateral and whole E14 rat VM tissue were compared. GDF5 treatment increased the number of dopaminergic neurones in whole and lateral, but not in medial, VM cultures, whereas it increased total cell number in medial, but not in whole or lateral, VM cultures. RT-PCR studies showed that the receptors for GDF5 were differentially expressed in E14 VM; the expression of BMPR-IB and Ror2 was low in medial but high in lateral VM tissue. This study suggests that GDF5 increases the number of dopaminergic neurones in whole VM cultures by acting on BMPR-IB and Ror2-expressing cells in the lateral VM. PMID:17935884

  2. The protective effect of lactoferrin on ventral mesencephalon neurons against MPP+ is not connected with its iron binding ability

    PubMed Central

    Wang, Jun; Bi, Mingxia; Liu, Huiying; Song, Ning; Xie, Junxia

    2015-01-01

    Lactoferrin (Lf) can bind to lactoferrin receptor (LfR), leading to iron transport through the plasma membrane. Besides iron transportation, Lf also has antioxidant and anti-inflammatory properties. In the brain, Lf is only synthesized by activated microglia. LfR is present in blood vessels and nigral dopaminergic neurons. Both nigral iron accumulation and microglia activation is believed to be involved in Parkinson’s disease (PD), moreover, increased Lf and LfR in dopaminergic neurons were found in PD cases and MPTP-intoxicated mice. How iron influences microglia to release Lf? Does Lf tend to transport iron to dopaminergic neurons leading to cell death or to protect dopaminergic neuron from neurotoxin? In this study, we observed that iron increased Lf synthesis in activated microglia. In ventral mesencephalon neurons, both iron-free Lf (apo-Lf) and iron-saturated Lf (holo-Lf) exerted neuroprotective effects against MPP+ by mechanisms, believed to enhance the mitochondrial transmembrane potential, improve Cu/Zn-superoxide dismutase activity, increase Bcl-2 expression. Although apo-Lf but not holo-Lf chelated cellular iron, there was no difference between the two types of Lf in the neuroprotection. Our data indicate that iron overload increases the activated microglia releasing Lf. Lf plays protective role on ventral mesencephalon neurons against MPP+, which is iron-chelating independent. PMID:26035688

  3. Dextromethorphan increases tyrosine hydroxylase mRNA in the mesencephalon of adolescent rats.

    PubMed

    Zhang, T Y; Jahng, J W; Kim, D G

    2001-08-24

    Dextromethorphan (DM), an antitussive widely available in over-the-counter, has been abused mostly in teenage groups at high doses. To examine effects of DM on the reward pathway, we injected a high dose of DM (40 mg/kg; intraperitoneally) into the adolescent rat and measured tyrosine hydroxylase (TH) mRNA by in situ hybridization in the ventral tegmental area (VTA) and the substantia nigra (SN). Remarkable increases in the level of TH mRNA were observed in the VTA and SN 2 h after DM injection. Stereotyped behavior and ataxia increased, and rearing decreased by DM administration. These results suggest that DM-induced increase in TH mRNA expression in mesencephalon contribute to the reinforcing property and the behavioral effects of DM. PMID:11502351

  4. Neuronal-enriched cultures from embryonic rat ventral mesencephalon for pharmacological studies of dopamine neurons.

    PubMed

    Pardo, B; Paíno, C L; Casarejos, M J; Mena, M A

    1997-05-01

    The method described herein provides a convenient and rapid procedure to obtain enriched neuronal cultures containing reproducible numbers of dopamine (DA) cells. These cultures allow experimental paradigms designed to study the effect of drugs on DA neurons without astroglial mediation. Neuronal-enriched cultures are prepared from the mesencephalon of rat embryos at the 14th day of gestation (E14). At that moment, DA cells of the developing substantia nigra are located ventrally at the level of the mesencephalic flexure. Because the neurons of the pars compacta are mostly born between E12 and E15, E14 corresponds to an optimal stage for obtaining a high survival of DA cells. A defined medium (EF12) allows the maturation of DA neurons and reduces drastically the number of astrocytes. After 7 days in vitro (DIV) in EF12, the cultures contain 2-5% astrocytes (GFAP+ cells) and DA neurons represent 0.5-2% of the cells, as assessed by immunostaining to tyrosine hydroxylase (TH). The function of DA neurons is assessed by [3H]DA uptake and of those non-DA neurons by the high affinity [3H]GABA uptake. Cell survival is assessed by Trypan blue dye exclusion. PMID:9385075

  5. Dopaminergic Development of Prenatal Ventral Mesencephalon and Striatum in Organotypic Co-Cultures

    PubMed Central

    Lyng, Gregory D.; Snyder-Keller, Abigail; Seegal, Richard F.

    2007-01-01

    Using organotypic co-cultures of rat embryonic day 14 (E14) ventral mesencephalon (VM and E21 striatum, we have described the developmental changes in (i) dopamine (DA) neurochemistry; (ii) numbers of DA neurons; and (iii) protein expression of tyrosine hydroxylase (TH), DA transporter (DAT), and glutamic acid decarboxylase (GAD 65/67), over 17 days in vitro (DIV). Co-cultures demonstrated changes in DA development similar to those observed in vivo. The numbers of VM DA neurons remained relatively constant, while levels of VM DA progressively increased through 10 DIV. After 3 DIV, the levels of striatal DA increased substantially, through 10 DIV. Tissue levels of DA metabolites homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) reflected changes in tissue DA concentrations, indicating that release and metabolism of DA are similar to these characteristics observed in vivo. Western blot analysis of TH protein expression revealed large increases in VM TH after only 3 DIV, followed by a decline in levels through 17 DIV; levels of striatal TH, in contrast, increased through this period. Additionally, DAT and GAD 65/67 expression increased, in both the VM and striatum, over 17 DIV. By 17 DIV, many measures of DA function had decreased from those assessed at 10 DIV, thus providing an approximate limit to the effective duration of use of this co-culture model. Our results provide a much-needed description of the neurochemical changes that occur during the maturation of VM and striatum in organotypic co-cultures. Additionally, these results provide a foundation for future studies to assess toxic challenges of the developing nigrostriatal DA system, in vitro. PMID:17196555

  6. Effects of verbenalin on prostatitis mouse model

    PubMed Central

    Miao, Mingsan; Guo, Lin; Yan, Xiaoli; Wang, Tan; Li, Zuming

    2015-01-01

    The aim of this study was to observe the treatment characteristics of verbenalin on a prostatitis mouse model. Give Xiaozhiling injection in the prostate locally to make a prostatitis mouse model. High, medium and low doses of verbenalin were each given to different mouse groups. The amount of water was determined in 14th, 28th. The number of white cells and lecithin corpuscle density in prostatic fluid were determined. Morphological changes in the prostate, testis, epididymis and kidney were detected. Compared with the model control group, the mice treated with high, medium and low doses of verbenalin had significantly increased amounts of water, and prostate white blood cell count and prostate volume density (Vv) were decreased significantly, the density of lecithin corpuscle score increased, and pathologic prostatitis changes were significantly reduced. Pathological change in the testis was significantly reduced and the change in the epididymis was obviously reduced. The thymic cortex thickness and the number of lymphocytes increased significantly and could reduce the renal pathological changes in potential. Verbenalin has a good therapeutic effect on the prostatitis mouse model. PMID:26858560

  7. Expression of lactoferrin receptors is increased in the mesencephalon of patients with Parkinson disease.

    PubMed Central

    Faucheux, B A; Nillesse, N; Damier, P; Spik, G; Mouatt-Prigent, A; Pierce, A; Leveugle, B; Kubis, N; Hauw, J J; Agid, Y

    1995-01-01

    The degeneration of nigral dopaminergic neurons in Parkinson disease is believed to be associated with oxidative stress. Since iron levels are increased in the substantia nigra of parkinsonian patients and this metal catalyzes the formation of free radicals, it may be involved in the mechanisms of nerve cell death. The cause of nigral iron increase is not understood. Iron acquisition by neurons may occur from iron-transferrin complexes with a direct interaction with specific membrane receptors, but recent results have shown a low density of transferrin receptors in the substantia nigra. To investigate whether neuronal death in Parkinson disease may be associated with changes in a pathway supplementary to that of transferrin, lactoferrin (lactotransferrin) receptor expression was studied in the mesencephalon. In this report we present evidence from immunohistochemical staining of postmortem human brain tissue that lactoferrin receptors are localized on neurons (perikarya, dendrites, axons), cerebral microvasculature, and, in some cases, glial cells. In parkinsonian patients, lactoferrin receptor immunoreactivity on neurons and microvessels was increased and more pronounced in those regions of the mesencephalon where the loss of dopaminergic neurons is severe. Moreover, in the substantia nigra, the intensity of immunoreactivity on neurons and microvessels was higher for patients with higher nigral dopaminergic loss. These data suggest that lactoferrin receptors on vulnerable neurons may increase intraneuronal iron levels and contribute to the degeneration of nigral dopaminergic neurons in Parkinson disease. Images Fig. 1 Fig. 2 PMID:7568181

  8. Directing dopaminergic fiber growth along a preformed molecular pathway from embryonic ventral mesencephalon transplants in the rat brain.

    PubMed

    Jin, Y; Zhang, C; Ziemba, K S; Goldstein, G A; Sullivan, P G; Smith, G M

    2011-05-01

    To identify guidance molecules to promote long-distance growth of dopaminergic axons from transplanted embryonic ventral mesencephalon (VM) tissue, three pathways were created by expressing green fluorescent protein (GFP), glial cell line-derived neurotrophic factor (GDNF), or a combination of GDNF/GDNF receptor α1 (GFRα1) along the corpus callosum. To generate the guidance pathway, adenovirus encoding these transcripts was injected at four positions along the corpus callosum. In all groups, GDNF adenovirus was also injected on the right side 2.5 mm from the midline at the desired transplant site. Four days later, a piece of VM tissue from embryonic day 14 rats was injected at the transplant site. All rats also received daily subcutaneous injections of N-acetyl-L-cysteinamide (NACA; 100 μg per rat) as well as chondroitinase ABC at transplant site (10 U/ml, 2 μl). Two weeks after transplantation, the rats were perfused and the brains dissected out. Coronal sections were cut and immunostained with antibody to tyrosine hydroxylase (TH) to identify and count dopaminergic fibers in the corpus callosum. In GFP-expressing pathways, TH(+) fibers grew out of the transplants for a short distance in the corpus callosum. Very few TH(+) fibers grew across the midline. However, pathways expressing GDNF supported more TH(+) fiber growth across the midline into the contralateral hemisphere. Significantly greater numbers of TH(+) fibers grew across the midline in animals expressing a combination of GDNF and GFRα1 in the corpus callosum. These data suggest that expression of GDNF or a combination of GDNF and GFRα1 can support the long-distance dopaminergic fiber growth from a VM transplant, with the combination having a superior effect. PMID:21337366

  9. Combinatorial effects of odorants on mouse behavior

    PubMed Central

    Saraiva, Luis R.; Kondoh, Kunio; Ye, Xiaolan; Yoon, Kyoung-hye; Hernandez, Marcus; Buck, Linda B.

    2016-01-01

    The mechanisms by which odors induce instinctive behaviors are largely unknown. Odor detection in the mouse nose is mediated by >1, 000 different odorant receptors (ORs) and trace amine-associated receptors (TAARs). Odor perceptions are encoded combinatorially by ORs and can be altered by slight changes in the combination of activated receptors. However, the stereotyped nature of instinctive odor responses suggests the involvement of specific receptors and genetically programmed neural circuits relatively immune to extraneous odor stimuli and receptor inputs. Here, we report that, contrary to expectation, innate odor-induced behaviors can be context-dependent. First, different ligands for a given TAAR can vary in behavioral effect. Second, when combined, some attractive and aversive odorants neutralize one another’s behavioral effects. Both a TAAR ligand and a common odorant block aversion to a predator odor, indicating that this ability is not unique to TAARs and can extend to an aversive response of potential importance to survival. In vitro testing of single receptors with binary odorant mixtures indicates that behavioral blocking can occur without receptor antagonism in the nose. Moreover, genetic ablation of a single receptor prevents its cognate ligand from blocking predator odor aversion, indicating that the blocking requires sensory input from the receptor. Together, these findings indicate that innate odor-induced behaviors can depend on context, that signals from a single receptor can block innate odor aversion, and that instinctive behavioral responses to odors can be modulated by interactions in the brain among signals derived from different receptors. PMID:27208093

  10. Combinatorial effects of odorants on mouse behavior.

    PubMed

    Saraiva, Luis R; Kondoh, Kunio; Ye, Xiaolan; Yoon, Kyoung-Hye; Hernandez, Marcus; Buck, Linda B

    2016-06-01

    The mechanisms by which odors induce instinctive behaviors are largely unknown. Odor detection in the mouse nose is mediated by >1, 000 different odorant receptors (ORs) and trace amine-associated receptors (TAARs). Odor perceptions are encoded combinatorially by ORs and can be altered by slight changes in the combination of activated receptors. However, the stereotyped nature of instinctive odor responses suggests the involvement of specific receptors and genetically programmed neural circuits relatively immune to extraneous odor stimuli and receptor inputs. Here, we report that, contrary to expectation, innate odor-induced behaviors can be context-dependent. First, different ligands for a given TAAR can vary in behavioral effect. Second, when combined, some attractive and aversive odorants neutralize one another's behavioral effects. Both a TAAR ligand and a common odorant block aversion to a predator odor, indicating that this ability is not unique to TAARs and can extend to an aversive response of potential importance to survival. In vitro testing of single receptors with binary odorant mixtures indicates that behavioral blocking can occur without receptor antagonism in the nose. Moreover, genetic ablation of a single receptor prevents its cognate ligand from blocking predator odor aversion, indicating that the blocking requires sensory input from the receptor. Together, these findings indicate that innate odor-induced behaviors can depend on context, that signals from a single receptor can block innate odor aversion, and that instinctive behavioral responses to odors can be modulated by interactions in the brain among signals derived from different receptors. PMID:27208093

  11. Spatial organization of the retinal projection to the avian lentiform nucleus of the mesencephalon.

    PubMed

    Bodnarenko, S R; Rojas, X; McKenna, O C

    1988-03-15

    Utilizing the horseradish peroxidase retrograde tracing technique and the 2-deoxy-D-glucose metabolic mapping technique, we have demonstrated in chickens the distribution of retinal ganglion cells that project to the lentiform nucleus of the mesencephalon (LM) and the retinotopic organization of the projection in the LM. Retinal ganglion cells labeled after a nearly complete injection into the LM were found in the four quadrants, distributed in a wide horizontal belt lying along both sides of the retinal equator and stretching from the temporal to the nasal retina. The HRP-labeled cells, which appeared round or oval, ranged from 25 to 840 micron 2 in size with most in the smaller size range. Results of partial HRP injections into the LM and metabolic mapping patterns in the LM produced by stimulation of half the retina with horizontal visual motion suggest that there is an orderly mapping of the retina onto the LM. The inferior temporal quadrant projects to the rostrodorsal LM; the inferior nasal quadrant projects to the caudodorsal LM. The superior temporal quadrant projects to the middle and ventral LM, extending from the rostral to the caudal pole, whereas the superior nasal quadrant projects to a small zone in the caudal LM. The mapping of the retinal quadrants in the LM is remarkably similar to that reported in the optic tectum of birds. We suggest that a common embryological anlage with the optic tectum and the arrangement of retinal axons in the optic tract are important factors in establishing the retinotopic organization of the LM. PMID:3372723

  12. Identification of dopaminergic neurons of nigral and ventral tegmental area subtypes in grafts of fetal ventral mesencephalon based on cell morphology, protein expression, and efferent projections.

    PubMed

    Thompson, Lachlan; Barraud, Perrine; Andersson, Elin; Kirik, Deniz; Björklund, Anders

    2005-07-01

    Transplants of fetal ventral mesencephalic tissue are known to contain a mixture of two major dopamine (DA) neuron types: the A9 neurons of the substantia nigra pars compacta (SNpc) and the A10 neurons of the ventral tegmental area (VTA). Previous studies have suggested that these two DA neuron types may differ in their growth characteristics, but, because of technical limitations, it has so far been difficult to identify the two subtypes in fetal ventral mesencephalon (VM) grafts and trace their axonal projections. Here, we have made use of a transgenic mouse expressing green fluorescent protein (GFP) under the tyrosine hydroxylase promoter. The expression of the GFP reporter allowed for visualization of the grafted DA neurons and their axonal projections within the host brain. We show that the SNpc and VTA neuron subtypes in VM grafts can be identified on the basis of their morphology and location within the graft, and their expression of a G-protein-gated inwardly rectifying K+ channel subunit (Girk2) and calbindin, respectively, and also that the axonal projections of the two DA neuron types are markedly different. By retrograde axonal tracing, we show that dopaminergic innervation of the striatum is derived almost exclusively from the Girk2-positive SNpc cells, whereas the calbindin-positive VTA neurons project to the frontal cortex and probably also other forebrain areas. The results suggest the presence of axon guidance and target recognition mechanisms in the DA-denervated forebrain that can guide the growing axons to their appropriate targets and indicate that cell preparations used for cell replacement in Parkinson's disease will be therapeutically useful only if they contain cells capable of generating the correct nigral DA neuron phenotype. PMID:16000637

  13. Distribution of 125I-ferrotransferrin binding sites in the mesencephalon of control subjects and patients with Parkinson's disease.

    PubMed

    Faucheux, B A; Hirsch, E C; Villares, J; Selimi, F; Mouatt-Prigent, A; Javoy-Agid, F; Hauw, J J; Agid, Y

    1993-06-01

    Iron is abnormally accumulated in the substantia nigra pars compacta of patients with Parkinson's disease (PD). Because neuronal and glial iron uptake seems to be mediated by the binding of ferrotransferrin to a specific high-affinity receptor on the cell surface, the number of transferrin receptors could be altered in this disease. The regional distribution of specific binding sites for human 125I-diferric transferrin has been studied in the mesencephalon, on cryostat-cut sections from autopsy brains of control subjects and parkinsonian patients by in vitro autoradiography. Densities of binding sites were highest in the central gray substance (approximately 10 fmol/mg of tissue equivalent), intermediate in the catecholaminergic cell group A8, superior colliculus, and ventral tegmental area, and almost nonexistent in the substantia nigra. The density of 125I-transferrin binding sites was not significantly different between parkinsonian and control brains in any region analyzed. These results show that in the mesencephalon the regional density of transferrin binding sites is lowest in the dopaminergic cell groups, which are the most vulnerable to PD, and suggest that iron does not accumulate through an increased density of transferrin receptors at the level of the substantia nigra. PMID:8492137

  14. The importance of A9 dopaminergic neurons in mediating the functional benefits of fetal ventral mesencephalon transplants and levodopa-induced dyskinesias.

    PubMed

    Kuan, Wei-Li; Lin, Rachel; Tyers, Pam; Barker, Roger A

    2007-03-01

    Intrastriatal transplantation of fetal ventral mesencephalon (VM) tissue provides the potential to alleviate motor symptoms of Parkinson's disease (PD) and levodopa-induced dyskinesia (LID). However, the degree of recovery varies among individuals with an incidence of "off-phase", graft-induced dyskinesia (GID) in some patients. We hypothesised that this variability is due to the heterogeneous nature of dopaminergic neurons in the transplant. We therefore investigated this in the unilateral 6-hydroxydopamine-lesioned rat model of PD. These animals were primed to develop LID and then transplanted with fetal VM into the caudal aspects of the striatum. No GID was observed but in a significant number of animals the transplants ameliorated LID. There was a correlation between the degree of behavioural and LID recovery with the number of A9 dopaminergic neurons in the transplant, based on their expression of a G-protein-coupled inward rectifying current potassium channel (Girk2). Furthermore, we showed that LID development is related to an abnormal expression profile of cyclin-dependent kinase 5 (Cdk5) and dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) in the striatum and that intrastriatal VM transplants normalised both Cdk5 expression and DARPP-32 phosphorylation in animals exhibiting functional improvement. These results suggest that an A9 dopaminergic neuron-enriched transplant may be the key to an effective PD cell replacement therapy through normalisation of the altered striatal expression of Cdk5/DARPP-32. PMID:17188499

  15. Dissociation between the panicolytic effect of cannabidiol microinjected into the substantia nigra, pars reticulata, and fear-induced antinociception elicited by bicuculline administration in deep layers of the superior colliculus: The role of CB1-cannabinoid receptor in the ventral mesencephalon.

    PubMed

    da Silva, Juliana Almeida; Biagioni, Audrey Francisco; Almada, Rafael Carvalho; de Souza Crippa, José Alexandre; Cecílio Hallak, Jaime Eduardo; Zuardi, Antônio Waldo; Coimbra, Norberto Cysne

    2015-07-01

    Many studies suggest that the substantia nigra, pars reticulata (SNpr), a tegmental mesencephalic structure rich in γ-aminobutyric acid (GABA)- and cannabinoid receptor-containing neurons, is involved in the complex control of defensive responses through the neostriatum-nigral disinhibitory and nigro-tectal inhibitory GABAergic pathways during imminently dangerous situations. The aim of the present work was to investigate the role played by CB1-cannabinoid receptor of GABAergic pathways terminal boutons in the SNpr or of SNpr-endocannabinoid receptor-containing interneurons on the effect of intra-nigral microinjections of cannabidiol in the activity of nigro-tectal inhibitory pathways. GABAA receptor blockade in the deep layers of the superior colliculus (dlSC) elicited vigorous defensive behaviour. This explosive escape behaviour was followed by significant antinociception. Cannabidiol microinjection into the SNpr had a clear anti-aversive effect, decreasing the duration of defensive alertness, the frequency and duration of defensive immobility, and the frequency and duration of explosive escape behaviour, expressed by running and jumps, elicited by transitory GABAergic dysfunction in dlSC. However, the innate fear induced-antinociception was not significantly changed. The blockade of CB1 endocannabinoid receptor in the SNpr decreased the anti-aversive effect of canabidiol based on the frequency and duration of defensive immobility, the frequency of escape expressed by running, and both the frequency and duration of escape expressed by jumps. These findings suggest a CB1 mediated endocannabinoid signalling in cannabidiol modulation of panic-like defensive behaviour, but not of innate fear-induced antinociception evoked by GABAA receptor blockade with bicuculline microinjection into the superior colliculus, with a putative activity in nigro-collicular GABAergic pathways. PMID:25841876

  16. EFFECTS OF PERFLUOROOCTANOIC ACID EXPOSURE DURING PREGNANCY IN THE MOUSE

    EPA Science Inventory


    Title:

    Effects Of Perfluorooctanoic Acid Exposure During Pregnancy In The Mouse

    Authors & affiliations:
    Lau, C., J.R. Thibodeaux*, R.G. Hanson* and J.M. Rogers. Reproductive Toxicology Division, NHEERL, ORD, U.S. EPA, Research Triangle Park, NC
    Abstract:<...

  17. Perinatal asphyxia leads to PARP-1 overactivity, p65 translocation, IL-1β and TNF-α overexpression, and apoptotic-like cell death in mesencephalon of neonatal rats: prevention by systemic neonatal nicotinamide administration.

    PubMed

    Neira-Peña, T; Rojas-Mancilla, E; Munoz-Vio, V; Perez, R; Gutierrez-Hernandez, M; Bustamante, D; Morales, P; Hermoso, M A; Gebicke-Haerter, P; Herrera-Marschitz, M

    2015-05-01

    Perinatal asphyxia (PA) is a leading cause of neuronal damage in newborns, resulting in long-term neurological and cognitive deficits, in part due to impairment of mesostriatal and mesolimbic neurocircuitries. The insult can be as severe as to menace the integrity of the genome, triggering the overactivation of sentinel proteins, including poly (ADP-ribose) polymerase-1 (PARP-1). PARP-1 overactivation implies increased energy demands, worsening the metabolic failure and depleting further NAD(+) availability. Using a global PA rat model, we report here evidence that hypoxia increases PARP-1 activity, triggering a signalling cascade leading to nuclear translocation of the NF-κB subunit p65, modulating the expression of IL-1β and TNF-α, pro-inflammatory molecules, increasing apoptotic-like cell death in mesencephalon of neonate rats, monitored with Western blots, qPCR, TUNEL and ELISA. PARP-1 activity increased immediately after PA, reaching a maximum 1-8 h after the insult, while activation of the NF-κB signalling pathway was observed 8 h after the insult, with a >twofold increase of p65 nuclear translocation. IL-1β and TNF-α mRNA levels were increased 24 h after the insult, together with a >twofold increase in apoptotic-like cell death. A single dose of the PARP-1 inhibitor nicotinamide (0.8 mmol/kg, i.p.), 1 h post delivery, prevented the effect of PA on PARP-1 activity, p65 translocation, pro-inflammatory cytokine expression and apoptotic-like cell death. The present study demonstrates that PA leads to PARP-1 overactivation, increasing the expression of pro-inflammatory cytokines and cell death in mesencephalon, effects prevented by systemic neonatal nicotinamide administration, supporting the idea that PARP-1 inhibition represents a therapeutic target against the effects of PA. PMID:25835215

  18. Curcumin shows excellent therapeutic effect on psoriasis in mouse model.

    PubMed

    Kang, Di; Li, Bowen; Luo, Lei; Jiang, Wenbing; Lu, Qiumin; Rong, Mingqing; Lai, Ren

    2016-04-01

    Curcumin is an active herbal ingredient possessing surprisingly wide range of beneficial properties, including anti-inflammatory, antioxidant, chemopreventive and chemotherapeutic activity. Recently, it has been reported to exhibit inhibitory activity on potassium channel subtype Kv1.3. As Kv1.3 channels are mainly expressed in T cells and play a key role in psoriasis, the effects of curcumin were investigated on inflammatory factors secretion in T cells and psoriasis developed in keratin (K) 14-vascular endothelial growth factor (VEGF) transgenic mouse model. Results showed that, 10 μM of curcumin significantly inhibited secretion of inflammatory factors including interleukin (IL)-17,IL-22, IFN-γ, IL-2, IL-8 and TNF-α in T cells by 30-60% in vitro. Notably, more than 50% of T cells proliferation was inhibited by application of 100 μM curcumin. Compared with severe psoriatic symptoms observed in the negative control mice, all psoriasis indexes including ear redness, weight, thickness and lymph node weight were significantly improved by oral application of curcumin in treatment mouse group. Histological examination indicated that curcumin had anti-inflammatory function in the experimental animals. More than 50% level of inflammatory factors including TNF-α, IFN-γ, IL-2, IL-12, IL-22 and IL-23 in mouse serum was decreased by curcumin treatment as well as cyclosporine. Compared with renal fibrosis observed in the mouse group treated by cyclosporine, no obvious side effect in mouse kidney was found after treated by curcumin. Taken together, curcumin, with high efficacy and safety, has a great potential to treat psoriasis. PMID:26826458

  19. BLEOMYCIN EFFECTS ON MOUSE MEIOTIC CHROMOSOMES

    EPA Science Inventory

    The effects of a radiomimetic chemical, bleomycin (BLM), on meiotic chromosomes was evaluated in mice. hromosome aberrations were analyzed at meiotic metaphase I, and damage to the synaptonemal complex was analyzed in meiotic prophase cells. n the metaphase aberration studies, an...

  20. Toxic effect of lithium in mouse brain

    SciTech Connect

    Dixit, P.K.; Smithberg, M.

    1988-01-01

    The effect of lithium ion on glucose oxidation in the cerebrum and cerebellum of mice was measured in vitro by the conversion of isotopic glucose into /sup 14/CO/sub 2//mg wet weight. Glucose utilization is unaffected by lowest lithium dosage but is inhibited by high lithium concentrations (197-295 mM). Chronic administration of lithium to adult mice decreased the DNA content of the cerebrum and cerebellum at concentrations of 80 and 108 mM. The DNA content of selected postnatal stages of cerebrum and cerebellum was measured starting on Day 1 or 2. This served as another parameter to evaluate glucose oxidation studies at these ages. On the basis of wet weight, both brain parts of neonates of ages 1 and 10 days were approximately one-half that of the adult counterparts. On the basis of DNA content, the cerebrum enhanced its glucose utilization twofold from Day 1 to Day 10 and tripled its utilization from Day 10 to Day 20. The glucose utilization by cerebrum at Day 20 is similar to adult values. In contrast, glucose oxidation in the cerebellum remained relatively constant throughout the postnatal growth. The relative susceptibility of the two brain parts is discussed.

  1. Host genetic and environmental effects on mouse intestinal microbiota

    PubMed Central

    Campbell, James H; Foster, Carmen M; Vishnivetskaya, Tatiana; Campbell, Alisha G; Yang, Zamin K; Wymore, Ann; Palumbo, Anthony V; Chesler, Elissa J; Podar, Mircea

    2012-01-01

    The mammalian gut harbors complex and variable microbial communities, across both host phylogenetic space and conspecific individuals. A synergy of host genetic and environmental factors shape these communities and account for their variability, but their individual contributions and the selective pressures involved are still not well understood. We employed barcoded pyrosequencing of V1-2 and V4 regions of bacterial small subunit ribosomal RNA genes to characterize the effects of host genetics and environment on cecum assemblages in 10 genetically distinct, inbred mouse strains. Eight of these strains are the foundation of the Collaborative Cross (CC), a panel of mice derived from a genetically diverse set of inbred founder strains, designed specifically for complex trait analysis. Diversity of gut microbiota was characterized by complementing phylogenetic and distance-based, sequence-clustering approaches. Significant correlations were found between the mouse strains and their gut microbiota, reflected by distinct bacterial communities. Cohabitation and litter had a reduced, although detectable effect, and the microbiota response to these factors varied by strain. We identified bacterial phylotypes that appear to be discriminative and strain-specific to each mouse line used. Cohabitation of different strains of mice revealed an interaction of host genetic and environmental factors in shaping gut bacterial consortia, in which bacterial communities became more similar but retained strain specificity. This study provides a baseline analysis of intestinal bacterial communities in the eight CC progenitor strains and will be linked to integrated host genotype, phenotype and microbiota research on the resulting CC panel. PMID:22695862

  2. Host Genetic and Environmental Effects on Mouse Cecum Microbiota

    SciTech Connect

    Campbell, James H; Foster, Carmen M; Vishnivetskaya, Tatiana A; Campbell, Alisha G; Yang, Zamin Koo; Wymore, Ann; Palumbo, Anthony Vito; Podar, Mircea

    2012-01-01

    The mammalian gut harbors complex and variable microbial communities, across both host phylogenetic space and conspecific individuals. A synergy of host genetic and environmental factors shape these communities and account for their variability, but their individual contributions and the selective pressures involved are still not well understood. We employed barcoded pyrosequencing of V1-2 and V4 regions of bacterial small subunit ribosomal RNA genes to characterize the effects of host genetics and environment on cecum assemblages in 10 genetically distinct, inbred mouse strains. Eight of these strains are the foundation of the Collaborative Cross (CC), a panel of mice derived from a genetically diverse set of inbred founder strains, designed specifically for complex trait analysis. Diversity of gut microbiota was characterized by complementing phylogenetic and distance-based, sequence-clustering approaches. Significant correlations were found between the mouse strains and their gut microbiota, reflected by distinct bacterial communities. Cohabitation and litter had a reduced, although detectable effect, and the microbiota response to these factors varied by strain. We identified bacterial phylotypes that appear to be discriminative and strain-specific to each mouse line used. Cohabitation of different strains of mice revealed an interaction of host genetic and environmental factors in shaping gut bacterial consortia, in which bacterial communities became more similar but retained strain specificity. This study provides a baseline analysis of intestinal bacterial communities in the eight CC progenitor strains and will be linked to integrated host genotype, phenotype and microbiota research on the resulting CC panel.

  3. [Cloning of gene fragment of estrogen receptor-beta and its expression in mouse embryo].

    PubMed

    Zhang, Zi-Feng; Fan, Shao-Hua; Lu, Jun; Wu, Dong-Mei; Shan, Qun; Hu, Bin; Li, Fei; Zheng, Yuan-Lin

    2008-03-01

    In order to study the expression and regulation effects of estrogen receptor-beta (ERbeta) in the development of mouse embryo, the primer of ERbeta was designed, the ERbeta fragment was first obtained by RT-PCR and subcloned into plasmids pGEM- 3Z, then the recombinant plasmids were linearized with the restriction enzymes of EcoRand Hind. Using Sp6 and T7 RNA polymerase, the digoxigenin(dig) labeled sense and anti-sense probes were transcriped in vitro, respectively. Then the expression of ERbeta in mouse embryo was examined with the probes by whole-mount in situ hybridization. The results indicated that ERbeta is expressed in the brain, spinal neural tube, genital ridge, pericardium, limb bud and mandibular arch of 10.5 dpc embryo, and is also expressed in the telencephalon, mesencephalon, medulla oblongata, spinal cord and limb bud of 13.5 dpc embryo. These results suggest that ERbeta maybe play a role of regulation in sexual differentiation, primal differentiation of neural tube, further differentiation of three primary cerebral vesicles and spinal cord, generation and differentiation of bone and cartilage of limb bud, development of pericardium and configuration differentiation of mandibular in mouse embryo. PMID:18332005

  4. Dual effects of fluoxetine on mouse early embryonic development

    SciTech Connect

    Kim, Chang-Woon; Choe, Changyong; Kim, Eun-Jin; Lee, Jae-Ik; Yoon, Sook-Young; Cho, Young-Woo; Han, Sunkyu; Tak, Hyun-Min; Han, Jaehee; Kang, Dawon

    2012-11-15

    Fluoxetine, a selective serotonin reuptake inhibitor, regulates a variety of physiological processes, such as cell proliferation and apoptosis, in mammalian cells. Little is known about the role of fluoxetine in early embryonic development. This study was undertaken to investigate the effect of fluoxetine during mouse early embryonic development. Late two-cell stage embryos (2-cells) were cultured in the presence of various concentrations of fluoxetine (1 to 50 μM) for different durations. When late 2-cells were incubated with 5 μM fluoxetine for 6 h, the percentage that developed into blastocysts increased compared to the control value. However, late 2-cells exposed to fluoxetine (5 μM) over 24 h showed a reduction in blastocyst formation. The addition of fluoxetine (5 μM) together with KN93 or KN62 (calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitors) failed to increase blastocyst formation. Fluoxetine treatment inhibited TREK-1 and TREK-2, members of the two-pore domain K{sup +} channel family expressed in mouse embryos, activities, indicating that fluoxetine-induced membrane depolarization in late 2-cells might have resulted from TREK inhibition. In addition, long-term exposure to fluoxetine altered the TREK mRNA expression levels. Furthermore, injection of siRNA targeting TREKs significantly decreased blastocyst formation by ∼ 30% compared to injection of scrambled siRNA. Long-term exposure of fluoxetine had no effect on blastocyst formation of TREK deficient embryos. These results indicate that low-dose and short-term exposures of late 2-cells to fluoxetine probably increase blastocyst formation through activation of CaMKII-dependent signal transduction pathways, whereas long-term exposure decreases mouse early embryonic development through inhibition of TREK channel gating. Highlights: ► Short-term exposure of 2-cells to fluoxetine enhances mouse blastocyst formation. ► The enhancive effect of fluoxetine is resulted from Ca

  5. The Effect of Gynostemma pentaphyllum Extract on Mouse Dermal Fibroblasts.

    PubMed

    Lobo, Sara Nadia; Qi, Yu Qing; Liu, Quan Zhong

    2014-01-01

    Background. The objective of this paper is to demonstrate the effect of Gynostemma pentaphyllum extract on mouse dermal fibroblasts. Recent studies have shown that this plant may possess great antioxidant properties, which can be very beneficial in combating oxidative stress. Methods. Gynostemma pentaphyllum extract was prepared and mouse dermal fibroblasts were obtained and cultured as per our laboratory protocols. Twelve samples of cells were cultured under the same conditions and both negative and positive controls were established. Induction of oxidative stress was carried out using ultraviolet C (UVC) light. Viable cell count was carried out, using microscopy. The analysis of the overall results was processed using SPSS version 16.0. Results. Statistical analysis showed strong positive correlation between the concentration of Gynostemma pentaphyllum and the mean duration of cell viability (rs = 1), with a high level of statistical significance (P < 0.01). Likewise, strong positive correlation existed between trials of cell viability (rs = 0.988-1), with statistical significance (P < 0.01). Conclusion. Gynostemma pentaphyllum extract prolongs viability of mouse dermal fibroblasts damaged by UVC light-induced oxidative stress. The results show the potential benefits of this extract on dermal cell aging. PMID:24729883

  6. The Effect of Gynostemma pentaphyllum Extract on Mouse Dermal Fibroblasts

    PubMed Central

    Lobo, Sara Nadia; Qi, Yu Qing; Liu, Quan Zhong

    2014-01-01

    Background. The objective of this paper is to demonstrate the effect of Gynostemma pentaphyllum extract on mouse dermal fibroblasts. Recent studies have shown that this plant may possess great antioxidant properties, which can be very beneficial in combating oxidative stress. Methods. Gynostemma pentaphyllum extract was prepared and mouse dermal fibroblasts were obtained and cultured as per our laboratory protocols. Twelve samples of cells were cultured under the same conditions and both negative and positive controls were established. Induction of oxidative stress was carried out using ultraviolet C (UVC) light. Viable cell count was carried out, using microscopy. The analysis of the overall results was processed using SPSS version 16.0. Results. Statistical analysis showed strong positive correlation between the concentration of Gynostemma pentaphyllum and the mean duration of cell viability (rs = 1), with a high level of statistical significance (P < 0.01). Likewise, strong positive correlation existed between trials of cell viability (rs = 0.988–1), with statistical significance (P < 0.01). Conclusion. Gynostemma pentaphyllum extract prolongs viability of mouse dermal fibroblasts damaged by UVC light-induced oxidative stress. The results show the potential benefits of this extract on dermal cell aging. PMID:24729883

  7. The effect of the melatonin on cryopreserved mouse testicular cells

    PubMed Central

    Saki, Ghasem; Mirhoseini, Mehri; Hemadi, Masoud; Khodadadi, Ali; Beygom Talebpour Amiri, Fereshteh

    2016-01-01

    Background: After improvements in various cancer treatments, life expectancy has been raised, but success in treatment causes loss of fertility in many of the survived young men. Cryopreservation of immature testicular tissues or cells introduced as the only way to preserve fertility. However, freezing has some harmful effects. Melatonin, a pineal gland hormone, has receptors in reproductive systems of different species. It is assumed that melatonin has free radical scavenger properties. Objective: The aim of this study was to evaluate the effects of melatonin on the cryopreserved testicular cells in mouse. Materials and Methods: Cells from 7- 10 days old NMRI mice testes were isolated using two step enzymatic digestion. The testicular cells were divided into two groups randomly and cryopreserved in two different freezing media with and without the addition of 100 µm melatonin. Finally, apoptosis of the cells was assayed by flow cytometry. Also, lactate dehydrogenase activity test was performed to assess the cytotoxicity. Results: The results of lactate dehydrogenase showed the nearly cytotoxic effect of melatonin. The results of flow cytometry showed increase in apoptosis in the cryopreserved cells in the media containing melatonin compared to the control group. Conclusion: The present study shows that melatonin has an apoptotic effect on cryopreserved mouse testicular cells. PMID:27141545

  8. Genetics of primary and timing effects in the mnd mouse

    SciTech Connect

    Messer, A.; Plummer, J.; MacMillen, M.C.

    1995-06-05

    The mnd mouse shows a spontaneous adult-onset hereditary neurological disease, with motor abnormality by 6 months of age, progressing to severe spastic paralysis and premature death. The disease is autosomal recessive, with heterozygote effects seen under stress. It maps to mouse chromosome (chr) 8. Histopathology with Nissl stains documents substantial abnormalities of upper and lower motor neurons, and there is retinal degeneration beginning in the first month, even without light exposure. Increasing levels of autofluorescent lipopigment are found in both neuronal and non-neuronal tissues as the mnd mice age. Recently, NCL-like inclusions and accumulating subunit c have also been described. When mnd is outcrossed to the AKR/J genetic background, ca. 40% of the mnd/mnd F2 progeny show early onset (onset by 4.5-5 months and death by 7 months). This accelerated timing effect seems to be strain-specific, and unlinked to the mnd gene itself. Our current working hypothesis is that the timing effect is due to 2 or 3 unlinked dominant genes with incomplete penetrance at any single locus. In a combined RFLP/PCR fragment genetic analysis, the strongest deviation from the expected ratio of AKR vs B6 alleles occurs with markers on proximal half of chr 1. Additional loci on chrs 5 and 10 may also be involved. The mechanism of interaction of these modifying genes with the primary mnd gene may offer new therapeutic avenues. 22 refs., 2 tabs.

  9. Analgesic effects of NB001 on mouse models of arthralgia.

    PubMed

    Tian, Zhen; Wang, Dong-sheng; Wang, Xin-shang; Tian, Jiao; Han, Jing; Guo, Yan-yan; Feng, Bin; Zhang, Nan; Zhao, Ming-gao; Liu, Shui-bing

    2015-01-01

    Our previous studies have demonstrated the critical roles of calcium-stimulated adenylyl cyclase 1 (AC1) in the central nervous system in chronic pain. In the present study, we examined the analgesic effects of NB001, a selective inhibitor of AC1, on animal models of ankle joint arthritis and knee joint arthritis induced by complete Freund's adjuvant injection. NB001 treatment had no effect on joint edema, stiffness, and joint destruction. Furthermore, the treatment failed to attenuate the disease progression of arthritis. However, NB001 treatment (3 mg/kg) significantly weakened joint pain-related behavior in the mouse models of ankle joint arthritis and knee joint arthritis. Results indicated that NB001 exhibited an analgesic effect on the animal models of arthritis but was not caused by anti-inflammatory activities. PMID:26452469

  10. Effects of clinostat rotation on mouse meiotic maturation in vitro

    NASA Technical Reports Server (NTRS)

    Wolgemuth, D. J.; Grills, G. S.

    1984-01-01

    The effects of microgravity on meiosis, fertilization, and early embryonic development in mammals are being examined by using a clinostat to reorient the cells with respect to the gravity vector. A clinostat capable of supporting mammalian cells in tissue culture has been developed. Initial studies have focused on examining the effects of clinostat rotation on meiotic maturation in mouse oocytes. Oocytes recovered from ovarian follicles were subjected to clinostat rotation on a horizontal or vertical axis or to static conditions for a 16 hr period. No gross morphological changes and no effects on germinal vesicle breakdown were observed under any rotation conditions (1/4, 1, 10, 30, 100 RPM). Success of meiotic progression to Metaphase II was comparable among experimental and control groups except at 100 RPM, where a slight inhibition was observed.

  11. Metabolic effect of fluvoxamine in mouse peripheral tissues.

    PubMed

    Rozenblit-Susan, Sigal; Chapnik, Nava; Froy, Oren

    2016-03-15

    Serotonin leads to reduced food intake and satiety. Disrupted circadian rhythms lead to hyperphagia and obesity. The serotonergic and circadian systems are intertwined, as the central brain clock receives direct serotonergic innervation and, in turn, makes polysynaptic output back to serotonergic nuclei. Our objective was to test the hypothesis that peripherally serotonin alters circadian rhythms leading to a shift towards fat synthesis and weight gain. We studied the effect of serotonin and fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), on the circadian clock and metabolic gene and protein expression in mouse liver, muscle and white adipose tissue (WAT) and cell culture. We found that serotonin and/or the SSRI fluvoxamine led to fat accumulation in mouse liver and hepatocytes by shifting metabolism towards fatty acid synthesis mainly through low average levels of phosphorylated acetyl CoA carboxylase (pACC) and phosphorylated protein phosphatase 2A (pPP2A). This shift towards fat synthesis was also observed in adipose tissue. Muscle cells were only slightly affected metabolically by serotonin or fluvoxamine. In conclusion, although centrally it leads to increased satiety, in peripheral tissues, such as the liver and WAT, serotonin induces fat accumulation. PMID:26797245

  12. Pleiotropic effects of 5-aminolevulinic acid in mouse brain.

    PubMed

    Lavandera, Jimena; Rodríguez, Jorge; Ruspini, Silvina; Meiss, Roberto; Zuccoli, Johanna Romina; Martínez, María Del Carmen; Gerez, Esther; Batlle, Alcira; Buzaleh, Ana María

    2016-08-01

    5-Aminolevulinic acid (ALA) seems to be responsible for the neuropsychiatric manifestations of acute intermittent porphyria (AIP). Our aim was to study the effect of ALA on the different metabolic pathways in the mouse brain to enhance our knowledge about the action of this heme precursor on the central nervous system. Heme metabolism, the cholinergic system, the defense enzyme system, and nitric oxide metabolism were evaluated in the encephalon of CF-1 mice receiving a single (40 mg/kg body mass) or multiple doses of ALA (40 mg/kg, every 48 h for 14 days). We subsequently found ALA accumulation in the encephalon of the mice. ALA also altered the brain cholinergic system. After one dose of ALA, a decrease in superoxide dismutase activity and a reduction in glutathione levels were detected, whereas malondialdehyde levels and catalase activity were increased. Heme oxygenase was also increased as an antioxidant response to protect the encephalon against injury. All nitric oxide synthase isoforms were induced by ALA, these changes were more significant for the inducible isoform in glial cells. In conclusion, ALA affected several metabolic pathways in mouse encephalon. Data indicate that a rapid response to oxidative stress was developed; however, with long-term intoxication, the redox balance was probably restored, thereby minimizing oxidative damage. PMID:27472495

  13. Conflicting effects of DMSO on mouse skin tumorigenesis

    SciTech Connect

    Jacoby, W.T.; Weiss, H.S.

    1986-03-05

    A number of solvents, including dimethylsulfoxide (DMSO), when substituted for acetone as the vehicle for the potent promoter phorbol-12-myristate-13-acetate (PMA) in the two-stage mouse skin cancer model, tend to inhibit tumorigenesis. DMSO was investigated further because the literature is ambiguous concerning its effect in both single and multi-stage carcinogenesis. As solvent for the complete carcinogen benzo(a)pyrene (BaP, 125 mg in 40 ..mu..l 2x/wk), tumor yield increased an avg of 245% (3 trials in C3H mice) compared to acetone/BaP. However, in the two-stage model (CD-1 mice initiated with 50-100 ..mu..g DMBA) DMSO as the vehicle for PMA (5 ..mu..g in 40 ..mu..l 2x/wk) reduced tumor yield to 34% of the PMA/acetone controls. To test whether the inhibition was an in vitro effect, 40 ..mu..l DMSO was applied at the initiation site, the back, up to one hr before PMA/acetone. In three trials tumor yield averaged 23% of controls. To determine whether the DMSO effect was directly on initiated cells or indirectly via the systemic circulation, 40 ..mu..l DMSO was applied prior to promotion at a site distant from initiation/promotion, the abdomen. In three trials, DMSO enhanced tumor yield by 194%. DMSO itself had no initiating or promotion effects. Thus, it appears that DMSO may either inhibit or enhance mouse skin tumorigenesis depending on its method of application.

  14. Distinct Effects of Different Phosphatidylglycerol Species on Mouse Keratinocyte Proliferation

    PubMed Central

    Xie, Ding; Seremwe, Mutsa; Edwards, John G.; Podolsky, Robert; Bollag, Wendy B.

    2014-01-01

    We have previously shown that liposomes composed of egg-derived phosphatidylglycerol (PG), with a mixed fatty acid composition (comprising mainly palmitate and oleate), inhibit the proliferation and promote the differentiation of rapidly dividing keratinocytes, and stimulate the growth of slowly proliferating epidermal cells. To determine the species of PG most effective at modulating keratinocyte proliferation, primary mouse keratinocytes were treated with different PG species, and proliferation was measured. PG species containing polyunsaturated fatty acids were effective at inhibiting rapidly proliferating keratinocytes, whereas PG species with monounsaturated fatty acids were effective at promoting proliferation in slowly dividing cells. Thus, palmitoyl-arachidonyl-PG (16∶0/20∶4), palmitoyl-linoleoyl-PG (16∶0/18∶2), dilinoleoyl-PG (18∶2/18∶2) and soy PG (a PG mixture with a large percentage of polyunsaturated fatty acids) were particularly effective at inhibiting proliferation in rapidly dividing keratinocytes. Conversely, palmitoyl-oleoyl-PG (16∶0/18∶1) and dioleoyl-PG (18∶1/18∶1) were especially effective proproliferative PG species. This result represents the first demonstration of opposite effects of different species of a single class of phospholipid and suggests that these different PG species may signal to diverse effector enzymes to differentially affect keratinocyte proliferation and normalize keratinocyte proliferation. Thus, different PG species may be useful for treating skin diseases characterized by excessive or insufficient proliferation. PMID:25233484

  15. Cocaine Causes Apoptotic Death in Rat Mesencephalon and Striatum Primary Cultures.

    PubMed

    Lepsch, Lucilia B; Planeta, Cleopatra S; Scavone, Critoforo

    2015-01-01

    To study cocaine's toxic effects in vitro, we have used primary mesencephalic and striatal cultures from rat embryonic brain. Treatment with cocaine causes a dramatic increase in DNA fragmentation in both primary cultures. The toxicity induced by cocaine was paralleled with a concomitant decrease in the microtubule associated protein 2 (MAP2) and/or neuronal nucleus protein (NeuN) staining. We also observed in both cultures that the cell death caused by cocaine was induced by an apoptotic mechanism, confirmed by TUNEL assay. Therefore, the present paper shows that cocaine causes apoptotic cell death and inhibition of the neurite prolongation in striatal and mesencephalic cell culture. These data suggest that if similar neuronal damage could be produced in the developing human brain, it could account for the qualitative or quantitative defects in neuronal pathways that cause a major handicap in brain function following prenatal exposure to cocaine. PMID:26295051

  16. Cocaine Causes Apoptotic Death in Rat Mesencephalon and Striatum Primary Cultures

    PubMed Central

    Lepsch, Lucilia B.; Planeta, Cleopatra S.; Scavone, Critoforo

    2015-01-01

    To study cocaine's toxic effects in vitro, we have used primary mesencephalic and striatal cultures from rat embryonic brain. Treatment with cocaine causes a dramatic increase in DNA fragmentation in both primary cultures. The toxicity induced by cocaine was paralleled with a concomitant decrease in the microtubule associated protein 2 (MAP2) and/or neuronal nucleus protein (NeuN) staining. We also observed in both cultures that the cell death caused by cocaine was induced by an apoptotic mechanism, confirmed by TUNEL assay. Therefore, the present paper shows that cocaine causes apoptotic cell death and inhibition of the neurite prolongation in striatal and mesencephalic cell culture. These data suggest that if similar neuronal damage could be produced in the developing human brain, it could account for the qualitative or quantitative defects in neuronal pathways that cause a major handicap in brain function following prenatal exposure to cocaine. PMID:26295051

  17. Effects of ozone on transepithelial potential of mouse trachea

    SciTech Connect

    Takahashi, M.; Kleeberger, S.R.; Croxton, T.L. )

    1993-07-01

    The effects of ozone on tracheal electrical potential were investigated in inbred strains of mice that are differentially susceptible to ozone-induced inflammation. In male mice (9-13 wk), a tracheostomy was made under pentobarbital anesthesia for spontaneous breathing and tracheal potential was measured in the cephalad portion of the bisected trachea using Hanks' salt/agar-capped KCl bridges connected to a pair of calomel half cells. The mean tracheal potentials of five different strains of mice (C3H/HeJ, DBA/2J, C57BL/6J, BALB/cJ, and 129/J) were approximately 10 mV (lumen negative) with no significant interstrain difference. Amiloride reduced mouse tracheal potentials by approximately 70% in both C3H/HeJ and C57BL/6J mice, indicating that sodium absorption is the predominant ion transport across this tissue. Relative to air-exposed controls, acute ozone exposure (2 ppm for 3 h) significantly attenuated tracheal potential of inflammation-susceptible C57BL/6J mice by approximately 50% at 6 h and 40% at 24 h postexposure but had no effect immediately after exposure. The mean tracheal potential of C3H/HeJ mice was not changed by ozone. The differential effect of acute ozone exposure on tracheal potential in C57BL/6J and C3H/HeJ mice is consistent with differential susceptibility to ozone-induced increases in epithelial permeability in these strains.

  18. Effects of 810 nm laser on mouse primary cortical neurons

    NASA Astrophysics Data System (ADS)

    Kharkwal, Gitika B.; Sharma, Sulbha K.; Huang, Ying-Ying; De Taboada, Luis; McCarthy, Thomas; Hamblin, Michael R.

    2011-03-01

    In the past four decades numerous studies have reported the efficacy of low level light (laser) therapy (LLLT) as a treatment for diverse diseases and injuries. Recent studies have shown that LLLT can biomodulate processes in the central nervous system and has been extensively studied as a stroke treatment. However there is still a lack of knowledge on the effects of LLLT at the cellular level in neurons. The present study aimed to study the effect of 810 nm laser on several cellular processes in primary cortical neurons cultured from mouse embryonic brains. Neurons were irradiated with light dose of 0.03, 0.3, 3, 10 and 30 J/cm2 and intracellular levels of reactive oxygen species, nitric oxide and calcium were measured. The changes in mitochondrial function in response to light were studied in terms of adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP). Light induced a significant increase in calcium, ATP and MMP at lower fluences and a decrease at higher fluence. ROS was induced significantly by light at all light doses. Nitric oxide levels also showed an increase on treatment with light. The results of the present study suggest that LLLT at lower fluences is capable of inducing mediators of cell signaling process which in turn may be responsible for the biomodulatory effects of the low level laser. At higher fluences beneficial mediators are reduced but potentially harmful mediators are increased thus offering an explanation for the biphasic dose response.

  19. Chondroprotective effects of Salubrinal in a mouse model of osteoarthritis

    PubMed Central

    Hamamura, K.; Nishimura, A.; Iino, T.; Takigawa, S.; Sudo, A.; Yokota, H.

    2015-01-01

    Objectives Salubrinal is a synthetic agent that elevates phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) and alleviates stress to the endoplasmic reticulum. Previously, we reported that in chondrocytes, Salubrinal attenuates expression and activity of matrix metalloproteinase 13 (MMP13) through downregulating nuclear factor kappa B (NFκB) signalling. We herein examine whether Salubrinal prevents the degradation of articular cartilage in a mouse model of osteoarthritis (OA). Methods OA was surgically induced in the left knee of female mice. Animal groups included age-matched sham control, OA placebo, and OA treated with Salubrinal or Guanabenz. Three weeks after the induction of OA, immunoblotting was performed for NFκB p65 and p-NFκB p65. At three and six weeks, the femora and tibiae were isolated and the sagittal sections were stained with Safranin O. Results Salubrinal suppressed the progression of OA by downregulating p-NFκB p65 and MMP13. Although Guanabenz elevates the phosphorylation level of eIF2α, it did not suppress the progression of OA. Conclusions Administration of Salubrinal has chondroprotective effects in arthritic joints. Salubrinal can be considered as a potential therapeutic agent for alleviating symptoms of OA. Cite this article: Bone Joint Res 2015;4:84–92 PMID:25977571

  20. Effect of radiation on mouse embryonic limb development

    SciTech Connect

    Meznarich, H.K.; Sikov, M.R. )

    1990-02-26

    Extracellular matrix and molecules on the cell surface may play a role in regulating differentiation during chondrogenesis. These regulatory mechanisms are not well understood. Perturbation of developing embryonic limb buds in organ culture may provide a system for the study of intercellular interactions and regulatory mechanism. In this study, organ cultures were used to define a range of radiation doses that would induce abnormal limb development. Histochemical stains were used to detect any cellular and molecular changes. Forelimb buds of mouse embryos were explanted at 11 and 12 days of gestation (dg). One of the limb buds was irradiated with 1, 2, or 3 Gy of gamma rays, and the contralateral bud was used as a control. Both groups were incubated for 1, 2, or 3 days in center-well dishes, using BJG6 medium with 25% fetal bovine serum. Subtle effects were detectable at 1 Gy, but irradiation with 2 or 3 Gy at 11 dg led to pyknosis of the majority of nuclei in the nonchondrocytic population. At 12 dg, there was a delay of mesenchymal differentiation, and a less-well organized arrangement of chondrocytes. The authors observations demonstrate that irradiation of such cultures with doses in the range of 1 Gy and below will provide an appropriate system for studies on the normal and abnormal regulatory mechanisms involved in prenatal limb development.

  1. The effect of radiation dose on mouse skeletal muscle remodeling

    PubMed Central

    Hardee, Justin P.; Puppa, Melissa J.; Fix, Dennis K.; Gao, Song; Hetzler, Kimbell L.; Bateman, Ted A.; Carson, James A.

    2014-01-01

    Background The purpose of this study was to determine the effect of two clinically relevant radiation doses on the susceptibility of mouse skeletal muscle to remodeling. Materials and methods. Alterations in muscle morphology and regulatory signaling were examined in tibialis anterior and gastrocnemius muscles after radiation doses that differed in total biological effective dose (BED). Female C57BL/6 (8-wk) mice were randomly assigned to non-irradiated control, four fractionated doses of 4 Gy (4x4 Gy; BED 37 Gy), or a single 16 Gy dose (16 Gy; BED 100 Gy). Mice were sacrificed 2 weeks after the initial radiation exposure. Results The 16 Gy, but not 4x4 Gy, decreased total muscle protein and RNA content. Related to muscle regeneration, both 16 Gy and 4x4 Gy increased the incidence of central nuclei containing myofibers, but only 16 Gy increased the extracellular matrix volume. However, only 4x4 Gy increased muscle 4-hydroxynonenal expression. While both 16 Gy and 4x4 Gy decreased IIB myofiber mean cross-sectional area (CSA), only 16 Gy decreased IIA myofiber CSA. 16 Gy increased the incidence of small diameter IIA and IIB myofibers, while 4x4 Gy only increased the incidence of small diameter IIB myofibers. Both treatments decreased the frequency and CSA of low succinate dehydrogenase activity (SDH) fibers. Only 16 Gy increased the incidence of small diameter myofibers having high SDH activity. Neither treatment altered muscle signaling related to protein turnover or oxidative metabolism. Conclusions Collectively, these results demonstrate that radiation dose differentially affects muscle remodeling, and these effects appear to be related to fiber type and oxidative metabolism. PMID:25177239

  2. Effect of Murine Norovirus Infection on Mouse Parvovirus Infection

    PubMed Central

    Paturzo, Frank X; Macy, James D

    2010-01-01

    Enzootic infection with mouse parvovirus (MPV) remains a common problem in laboratory colonies, and diagnosis of MPV infection is complicated by viral and host factors. The effect of an underlying viral infection on MPV infection has not previously been investigated. We assessed the effect of murine norovirus (MNV) infection, the most prevalent infectious agent in laboratory mice, on MPV shedding, tissue distribution and transmission. Fecal MPV shedding persisted longer in BALB/c mice infected with MNV 1 wk prior to MPV infection than in mice infected with MPV only, but transmission of MPV to soiled-bedding sentinels was not prolonged in coinfected mice. MPV DNA levels in coinfected BALB/c mice were higher in mesenteric lymph nodes and spleens at 1 and 2 wk after inoculation and in small intestines at 1 wk after inoculation compared with levels in mice infected with MPV only. In C57BL/6 mice, fecal shedding was prolonged, but no difference in soiled bedding transmission or MPV DNA levels in tissues was detected between singly and coinfected mice. MPV DNA levels in singly and coinfected SW mice were similar. MPV DNA levels were highest in SW, intermediate in BALB/c and lowest in C57BL/6 mice. MPV DNA levels in mesenteric lymph nodes of BALB/c and SW mice exceeded those in small intestines and feces, whereas the inverse occurred in C57BL/6 mice. In conclusion, MNV infection increased the duration of MPV shedding and increased MPV DNA levels in tissues of BALB/c mice. PMID:20122310

  3. AH RECEPTOR IN EMBRYONIC MOUSE PALATE AND EFFECTS OF TCDD ON RECEPTOR EXPRESSION

    EPA Science Inventory

    2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent and widespread environmental contaminant, has diverse biological effects which include carcinogenesis, hepatotoxicity, thymic involution, hyperkeratosis, reproductive and developmental toxicity. n C57BL/6N embryonic mouse, TCDD...

  4. EFFECTS OF PERFLUOROOCTANOIC ACID EXPOSURE DURING PREGNANCY IN THE MOUSE

    EPA Science Inventory

    Perfluorooctanoic acid (PFOA), a member of the perfluoroalkyl acids that have wide commercial applications, has recently been detected in humans and wildlife. The current study characterizes the developmental toxicity of PFOA in the mouse. Timed pregnant CD-1 mice were given 1,...

  5. Preventive effect of antihistaminics on mouse skin photosensitization with hematoporphyrin derivative

    NASA Astrophysics Data System (ADS)

    Fu, Nai-wu; Yan, Li-xue

    1993-03-01

    Beta-carotene 100 mg/kg per day or vitamin C 50 mg/kg per day was administered orally for two days and did not prevent mouse skin photosensitization caused by hematoporphyrin derivative (HpD). However, (beta) -carotene 100 mg/kg per day administered intramuscularly for two days prevented mouse skin reaction. Cimetidine and benadryl 10 mg/kg per day, P.O.X 2, effectively prevented mouse skin reaction. This suggests histamine may be involved in skin photoreaction induced by HpD.

  6. Effects of red clover extract on the activation and proliferation of mouse T lymphocytes and the NO secretion of mouse macrophages.

    PubMed

    Yang, Zhi; Huang, Xiu-yan; Zeng, Yao-ying

    2008-10-01

    The study investigated the effects of red clover extract (RCE) on mouse T macrophages and lymphocytes in vitro. The cell toxic effect of RCE was estimated by MTT assay. Multiple-fluorescence staining plus flow cytometry were used to detect the effect of RCE on CD69/CD25/CD71 expression of mouse T lymphocytes stimulated by Con A; CFDA-SE staining plus flow cytometry were used to analyze the effect of RCE on proliferation of T lymphocytes activated by Con A; The effect of RCE on nitric oxide (NO) secretion of mouse macrophages stimulated by lipopolysaccharide (LPS) for 24 h was assayed by Griess reagent system. We found that RCE had potent anti-inflammatory effects on mice. RCE had little cell toxic effect on mouse lymphocytes and macrophages. RCE strongly inhibited the excessive production of inflammatory mediators (NO, CD69, CD25, CD71), in a dose-dependent manner, like cyclosporine A injection. RCE could inhibit proliferation of CD3+ T lymphocytes. These data suggested that RCE might exhibit anti-inflammatory effect by inhibiting the activation and proliferation of mouse lymphocytes and the NO secretion of mouse macrophages. PMID:19127865

  7. Further study of trichosanthin's effect on mouse embryos with confocal laser scanning microscopy

    NASA Astrophysics Data System (ADS)

    Xu, Hui; Zhang, Chunyang; Ma, Hui; Chen, Die Yan

    2001-09-01

    Trichosanthin(TCS), a ribosome inactivating protein extracted from the root tuber of a traditional Chinese medicine herb Tian Huo Fen(THF), possessed abortifacient, anti-tumor and anti-human immunodeficiency virus(HIV) activities. For centuries in China, THF has been used as an effective folk medicine to terminate early and midtrimester pregnancies and to treat ectopic pregnancies, hydatidiform moles and trophoblastic tumor. We observed the changes in reactive oxygen species and intracellular calcium in mouse embryos induced by TCS with confocal laser scanning microscopy in combination with the fluorescene diacetate (DCFHDA) and Fluo-3-AM. The results indicated that TCS induced increase in intracellular calcium and production of reactive oxygen species in mouse embryos , and TCS inhibited the development of mouse embryos effectively. Mouse embryos of different developmental stages before implantation are used in the experiments. This provides new insight into mechanism for abortifacient activity of TCS.

  8. Effects of simulated microgravity on mouse Sertoli cells in culture

    NASA Astrophysics Data System (ADS)

    Angela, Masini Maria; Prato, Paola; Linda, Scarabelli; Lanza, Cristina; Palmero, Silvio; Pointis, Georges; Ricci, Franco; Strollo, Felice

    With the advent of space flights questions concerning the effects of microgravity (0xG) on hu-man reproduction physiology have got priority Spermatogenesis is a complex, highly ordered process of cell division and differentiation by which spermatogonial cells give rise to mature spermatozoa. Sertoli cells play a crucial role in the development of germ cells and the regulation of spermatogenesis. In this study the influence of 0xG on Sertoli cells was evaluated. A Sertoli cell line from mouse testis (42GPA9) was analyzed for cytoskeletal (using the 3D reconstruction generated from a stack of confocal images) and SHBG changes by immunohistochemistry, for antioxidant agents by RT-PCR and for culture medium lactate concentrations by wet chemistry. Cells were cultured for 6, 24 and 48 hrs on a three-dimensional Random Positioning Machine (3D-RPM); static controls (1xG) were positioned on the supporting frame. At the end of each experiment, cultured cells were either fixed in paraformaldehyde or RNA-extracted or used for culture medium lactate measurements as needed. At 0xG Sertoli cytoskeleton got disorganized, microtubules fragmented and SHBG undetectable already after 24 hrs, with alterations wors-ening further until 48 hrs; various antioxidant systems (SOD, GST, PARP, MTs) appreciably increased during the first 24 hrs but significantly decreased at 48 hrs. No changes occurred in 1xG samples. At least initially, 0xG seems to perturb antioxidant protection strategies allowing the testes to support sperm production, thus generating an aging-like state of oxidative stress. Lactate production at 0xG slightly decreased only after 24 hrs. Further experiments need to be carried out in space to investigate upon steroidogenesis and germ cell differentiation within the testis, to rule out eventually pending male infertility consequences, which would be a problem nowadays, when life expectancy increases and male fertility might become a social issue often extending into 60 years

  9. Oncogenic Radiation Abscopal Effects In Vivo: Interrogating Mouse Skin

    SciTech Connect

    Mancuso, Mariateresa; Leonardi, Simona; Giardullo, Paola; Pasquali, Emanuela; Tanori, Mirella; De Stefano, Ilaria; Casciati, Arianna; Naus, Christian C.; Pazzaglia, Simonetta; Saran, Anna

    2013-08-01

    Purpose: To investigate the tissue dependence in transmission of abscopal radiation signals and their oncogenic consequences in a radiosensitive mouse model and to explore the involvement of gap junction intercellular communication (GJIC) in mediating radiation tumorigenesis in off-target mouse skin. Methods and Materials: Patched1 heterozygous (Ptch1{sup +/−}) mice were irradiated at postnatal day 2 (P2) with 10 Gy of x-rays. Individual lead cylinders were used to protect the anterior two-thirds of the body, whereas the hindmost part was directly exposed to radiation. To test the role of GJICs and their major constituent connexin43 (Cx43), crosses between Ptch1{sup +/−} and Cx43{sup +/−} mice were similarly irradiated. These mouse groups were monitored for their lifetime, and skin basal cell carcinomas (BCCs) were counted and recorded. Early responses to DNA damage - Double Strand Breaks (DSBs) and apoptosis - were also evaluated in shielded and directly irradiated skin areas. Results: We report abscopal tumor induction in the shielded skin of Ptch1{sup +/−} mice after partial-body irradiation. Endpoints were induction of early nodular BCC-like tumors and macroscopic infiltrative BCCs. Abscopal tumorigenesis was significantly modulated by Cx43 status, namely, Cx43 reduction was associated with decreased levels of DNA damage and oncogenesis in out-of-field skin, suggesting a key role of GJIC in transmission of oncogenic radiation signals to unhit skin. Conclusions: Our results further characterize the nature of abscopal responses and the implications they have on pathologic processes in different tissues, including their possible underlying mechanistic bases.

  10. Effective protein inhibition in intact mouse oocytes through peptide nanoparticle-mediated antibody transfection

    PubMed Central

    Li, Ruichao; Jin, Zhen; Gao, Leilei; Liu, Peng

    2016-01-01

    Female meiosis is a fundamental area of study in reproductive medicine, and the mouse oocyte model of in vitro maturation (IVM) is most widely used to study female meiosis. To investigate the probable role(s) of an unknown protein in female meiosis, the method traditionally used involves microinjecting a specific antibody into mouse oocytes. Recently, in studies on somatic cells, peptide nanoparticle-mediated antibody transfection has become a popular tool because of its high efficiency, low toxicity, good stability, and strong serum compatibility. However, untill now no researchers have tried using this technique on mouse oocytes because the zona pellucida surrounding the oocyte membrane (vitelline membrane) is usually thought or proved to be a tough barrier to macromolecules such as antibodies and proteins. Therefore, we attempted to introduce an antibody into mouse oocytes using a peptide nanoparticle. Here we show for the first time that with our optimized method, an antibody can be effectively delivered into mouse oocytes and inhibit its target protein with high specificity. We obtained significant results using small GTPase Arl2 as a test subject protein. We propose peptide nanoparticle-mediated antibody transfection to be a superior alternative to antibody microinjection for preliminary functional studies of unknown proteins in mouse oocytes. PMID:27114861

  11. New Mouse Model May Aid in Developing Effective Therapies for Ovarian Cancer | Poster

    Cancer.gov

    By Frank Blanchard, Staff Writer A new genetically engineered mouse model appears promising as an effective tool for preclinical testing of novel therapies for ovarian cancer, which tends to be diagnosed in late stage. There are few effective treatments for the disease.

  12. Protective effects of black rice bran against chemically-induced inflammation of mouse skin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We investigated the inhibitory effects of black rice (cv. LK1-3-6-12-1-1) bran against 12-O-tetradecanolylphorbol-13-acetate (TPA)-induced skin edema and 2,4-dinitroflurobenzene (DNFB)-induced allergic contact dermatitis (ACD) in inflammatory mouse models. We also determined the effects of the bran...

  13. Town mouse or country mouse: identifying a town dislocation effect in Chinese urbanization.

    PubMed

    Wang, Fei; Li, Shu; Bai, Xin-Wen; Ren, Xiao-Peng; Rao, Li-Lin; Li, Jin-Zhen; Liu, Huan; Liu, Hong-Zhi; Wu, Bin; Zheng, Rui

    2015-01-01

    Understanding urbanization and evaluating its impact are vital for formulating global sustainable development. The results obtained from evaluating the impact of urbanization, however, depend on the kind of measurement used. With the goal of increasing our understanding of the impact of urbanization, we developed direct and indirect subjective indicators to measure how people assess their living situation. The survey revealed that the projected endorsements and perceived social ambiance of people toward living in different types of settlements did not improve along with the urbanization level in China. The assessment scores from the city dwellers were not significantly different from those from the country areas and, more surprisingly, both were significantly higher than the assessment scores of the town dwellers, which we had expected to fall between the assessment scores of the country and city dwellers. Instead their scores were the lowest. We dubbed this V-shaped relationship the "town dislocation effect." When searching for a potential explanation for this effect, we found additional town dislocation effects in social support, loss aversion, and receptivity toward genetically modified food. Further analysis showed that only social support mediated the relationship between the three tiers of settlements (cities, country areas, and towns) and the subjective indicator. The projected endorsements yielded significant subjective assessments that could enhance our understanding of Chinese urbanization. Towns posed specific problems that require special attention. PMID:25973960

  14. Town Mouse or Country Mouse: Identifying a Town Dislocation Effect in Chinese Urbanization

    PubMed Central

    Wang, Fei; Li, Shu; Bai, Xin-Wen; Ren, Xiao-Peng; Rao, Li-Lin; Li, Jin-Zhen; Liu, Huan; Liu, Hong-Zhi; Wu, Bin; Zheng, Rui

    2015-01-01

    Understanding urbanization and evaluating its impact are vital for formulating global sustainable development. The results obtained from evaluating the impact of urbanization, however, depend on the kind of measurement used. With the goal of increasing our understanding of the impact of urbanization, we developed direct and indirect subjective indicators to measure how people assess their living situation. The survey revealed that the projected endorsements and perceived social ambiance of people toward living in different types of settlements did not improve along with the urbanization level in China. The assessment scores from the city dwellers were not significantly different from those from the country areas and, more surprisingly, both were significantly higher than the assessment scores of the town dwellers, which we had expected to fall between the assessment scores of the country and city dwellers. Instead their scores were the lowest. We dubbed this V-shaped relationship the “town dislocation effect.” When searching for a potential explanation for this effect, we found additional town dislocation effects in social support, loss aversion, and receptivity toward genetically modified food. Further analysis showed that only social support mediated the relationship between the three tiers of settlements (cities, country areas, and towns) and the subjective indicator. The projected endorsements yielded significant subjective assessments that could enhance our understanding of Chinese urbanization. Towns posed specific problems that require special attention. PMID:25973960

  15. Genotoxic effects of acrylamide and glycidamide in mouse lymphoma cells.

    PubMed

    Mei, Nan; Hu, Jiaxiang; Churchwell, Mona I; Guo, Lei; Moore, Martha M; Doerge, Daniel R; Chen, Tao

    2008-02-01

    In addition to occupational exposures to acrylamide (AA), concerns about AA health risks for the general population have been recently raised due to the finding of AA in food. In this study, we evaluated the genotoxicity of AA and its metabolite glycidamide (GA) in L5178Y/Tk(+/-) mouse lymphoma cells. The cells were treated with 2-18 mM of AA or 0.125-4 mM of GA for 4 h without metabolic activation. The DNA adducts, mutant frequencies and the types of mutations for the treated cells were examined. Within the dose range tested, GA induced DNA adducts of adenine and guanine [N3-(2-carbamoyl-2-hydroxyethyl)-adenine and N7-(2-carbamoyl-2-hydroxyethyl)-guanine] in a linear dose-dependent manner. The levels of guanine adducts were consistently about 60-fold higher across the dose range than those of adenine. In contrast, no GA-derived DNA adducts were found in the cells treated with any concentrations of AA, consistent with a lack of metabolic conversion of AA to GA. However, the mutant frequency was significantly increased by AA at concentrations of 12 mM and higher. GA was mutagenic starting with the 2mM dose, suggesting that GA is much more mutagenic than AA. The mutant frequencies were increased with increasing concentrations of AA and GA, mainly due to an increase of proportion of small colony mutants. To elucidate the underlying mutagenic mechanism, we examined the loss of heterozygosity (LOH) at four microsatellite loci spanning the entire chromosome 11 for mutants induced by AA or GA. Compared to GA induced mutations, AA induced more mutants whose LOH extended to D11Mit22 and D11Mit74, an alteration of DNA larger than half of the chromosome. Statistical analysis of the mutational spectra revealed a significant difference between the types of mutations induced by AA and GA treatments (P=0.018). These results suggest that although both AA and GA generate mutations through a clastogenic mode of action in mouse lymphoma cells, GA induces mutations via a DNA adduct

  16. Rodent Habitat On ISS: Spaceflight Effects On Mouse Behavior

    NASA Technical Reports Server (NTRS)

    Ronca, A. E.; Moyer, E. L.; Talyansky, Y.; Padmanabhan, S.; Choi, S.; Gong, C.; Globus, R. K.

    2016-01-01

    The NASA Decadal Survey (2011), Recapturing a Future for Space Exploration: Life and Physical Sciences Research for a New Era, emphasized the importance of expanding NASA life sciences research to long duration, rodent experiments on the International Space Station (ISS). To accomplish this objective, flight hardware, operations, and science capabilities supporting mouse studies in space were developed at NASA Ames Research Center. The first flight experiment carrying mice, Rodent Research Hardware and Operations Validation (Rodent Research-1), was launched on Sept 21, 2014 in an unmanned Dragon Capsule, SpaceX4, exposing the mice to a total of 37 days in space. Ground control groups were maintained in environmental chambers at Kennedy Space Center. Mouse health and behavior were monitored for the duration of the experiment via video streaming. Here we present behavioral analysis of two groups of five C57BL/6 female adult mice viewed via fixed camera views compared with identically housed Ground Controls. Flight (Flt) and Ground Control (GC) mice exhibited the same range of behaviors, including eating, drinking, exploratory behavior, self- and allo-grooming, and social interactions at similar or greater levels of occurrence. Mice propelled themselves freely and actively throughout the Habitat using their forelimbs to push off or by floating from one cage area to another, and they quickly learned to anchor themselves using tails and/or paws. Overall activity was greater in Flt as compared to GC mice, with spontaneous ambulatory behavior including the development of organized ‘circling’ or ‘race-tracking’ behavior that emerged within the first few days of flight and encompassed the primary dark cycle activity for the remainder of the experiment. We quantified the bout frequency, duration and rate of circling with respect to characteristic behaviors observed in the varying stages of the progressive development of circling: flipping utilizing two sides of the

  17. Apoptotic effects on maturation of mouse oocytes, fertilization and fetal development by puerarin.

    PubMed

    Huang, Fu-Jen; Chan, Wen-Hsiung

    2016-10-01

    Previously we identified puerarin, an isoflavone compound, as a risk factor for normal embryonic development that triggers apoptotic processes in the inner cell mass of mouse blastocysts, leading to retardation of embryonic development and cell viability. In the current study, we investigated whether puerarin exerts deleterious effects on mouse oocyte maturation, in vitro fertilization (IVF) and subsequent pre- and post-implantation development, both in vitro and in vivo. Notably, puerarin caused significant impairment of these processes in vitro. Pre-incubation of oocytes with puerarin during in vitro maturation led to increased post-implantation embryo resorption and decreased mouse fetal weight. In an in vivo animal model, intravenous injection with or without puerarin (1, 3 and 5 mg/kg body weight/day) for 4 days caused a decrease in oocyte maturation and IVF, and led to deleterious effects on early embryonic development. Importantly, pre-incubation of oocytes with a caspase-3-specific inhibitor effectively blocked puerarin-triggered deleterious effects, clearly implying that embryonic injury induced by puerarin is mediated by a caspase-dependent apoptotic mechanism. These results clearly demonstrate that puerarin has deleterious effects on mouse oocyte maturation, fertilization and subsequent embryonic development in vitro and in vivo. PMID:26712108

  18. The A9 dopamine neuron component in grafts of ventral mesencephalon is an important determinant for recovery of motor function in a rat model of Parkinson's disease.

    PubMed

    Grealish, Shane; Jönsson, Marie E; Li, Meng; Kirik, Deniz; Björklund, Anders; Thompson, Lachlan H

    2010-02-01

    Grafts of foetal ventral mesencephalon, used in cell replacement therapy for Parkinson's disease, are known to contain a mix of dopamine neuronal subtypes including the A9 neurons of the substantia nigra and the A10 neurons of the ventral tegmental area. However, the relative importance of these subtypes for functional repair of the brain affected by Parkinson's disease has not been studied thoroughly. Here, we report results from a series of grafting experiments where the anatomical and functional properties of grafts either selectively lacking in A9 neurons, or with a typical A9/A10 composition were compared. The results show that the A9 component of intrastriatal grafts is of critical importance for recovery in tests on motor performance, in a rodent model of Parkinson's disease. Analysis at the histological level indicates that this is likely to be due to the unique ability of A9 neurons to innervate and functionally activate their target structure, the dorsolateral region of the host striatum. The findings highlight dopamine neuronal subtype composition as a potentially important parameter to monitor in order to understand the variable nature of functional outcome better in transplantation studies. Furthermore, the results have interesting implications for current efforts in this field to generate well-characterized and standardized preparations of transplantable dopamine neuronal progenitors from stem cells. PMID:20123725

  19. Peripherally administered tetrahydrobiopterin increases in vivo tryptophan hydroxylase activity in the striatum after transplantation of fetal ventral mesencephalon in six hydroxydopamine lesioned rats.

    PubMed

    Ishida, Y; Todaka, K; Kuwahara, I; Hashiguchi, H; Ishizuka, Y; Nakane, H; Mitsuyama, Y

    1998-08-28

    The intraperitoneal administration of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4), a natural cofactor for tyrosine hydroxylase and tryptophan hydroxylase (TRH), dose-dependently increased the extracellular concentration of 6R-BH4 itself in rat striatum. The concentration was investigated by in vivo microdialysis and measured simultaneously with 5-hydroxytryptophan (5-HTP), a precursor of serotonin, by high performance liquid chromatography with electrochemical detection. The 6R-BH4 (50 mg/kg, i.p.) administration increased the accumulation of 5-HTP as an index of in vivo TRH activity under the inhibition of aromatic L-amino acid decarboxylase by NSD-1015 in the striatum of both normal control and 6-hydroxydopamine lesioned rats with intrastriatal transplants of fetal ventral mesencephalon (VM). The results suggest that TRH in the striatum of both control and VM-grafted rats is activated by 6R-BH4 penetrating into the brain from the blood. PMID:9754801

  20. Radiation effect in mouse skin: Dose fractionation and wound healing

    SciTech Connect

    Gorodetsky, R.; Mou, X.D.; Fisher, D.R.; Taylor, J.M.; Withers, H.R. )

    1990-05-01

    Radiation induced dermal injury was measured by the gain in the physical strength of healing wounds in mouse skin. A sigmoid dose response for the inhibition of wound healing 14 days after surgery was found for single doses of X rays. The sparing of dermal damage from fractionation of the X-ray dose was quantified in terms of the alpha/beta ratio in the linear-quadratic (LQ) model, at a wide range of doses per fraction reaching as low as about 1 Gy. The fit and the appropriateness of the LQ model for the skin wound healing assay was examined with the use of the Fe-plot in which inverse total dose is plotted versus dose per fraction for wound strength isoeffects. The alpha/beta ratio of the skin was about 2.5 Gy (95% confidence of less than +/- 1 Gy) and was appropriate over a dose range of 1 Gy to about 8 Gy. The low alpha/beta value is typical for a late responding tissue. This assay, therefore, has the advantage of measuring and forecasting late radiation responses of the dermis within a short time after irradiation.

  1. Progesterone effects on mouse sperm kinetics in conditions of viscosity.

    PubMed

    Pérez-Cerezales, S; López-Cardona, A P; Gutiérrez-Adán, A

    2016-05-01

    The spermatozoa delivered to the female genital tract need to swim towards the oocyte through viscous secretions. Once close to the oocyte, the spermatozoa are guided by a gradient of progesterone (P4) and other unknown chemoattractants via a process known as chemotaxis. Using polyvinylpyrrolidone to establish the conditions of viscosity, we examined the response of mouse spermatozoa to P4 Herein, we show that in low-viscous media, P4 induces hyperactive-like motility whereby sperm show erratic trajectories and non-progressive movement. However, an opposite response is produced in viscous medium in that trajectories are linear and motility is more progressive and less erratic. Our observations provide a behavioural explanation for the chemotaxis of spermatozoa swimming under viscous conditions in a spatial gradient of the chemoattractant P4 They also highlight the importance of using viscous solutions to mimic in vivo conditions when analysing sperm behaviour in response to any stimulus.Reproduction (2016) 151 501-507. PMID:26908919

  2. The effect on rhino mouse skin of agents which influence keratinization and exfoliation.

    PubMed

    Kligman, L H; Kligman, A M

    1979-11-01

    The skin of the rhino mouse, an allelic variant of the hariless mouse, contains deep dermal cysts and huge numbers of hornfilled utriculi which resemble comedones. Chemicals which influence either differentiation or desquamation of horny cells were applied topically twice daily for up to 6 weeks. Except for the dermal cysts, the gross epithelial abnormalities were almost completely corrected by retinoic acid in a dose-dependent fashion. Salicylic acid caused partial emptying of the horny masses, but the utriculi did not regress. Lactic acid, propylene glycol and benzoyl peroxide had minor effects on keratinization and exfoliation. The rhino mouse is a suitable model for assessing chemicals which affect epithelial differentiation (retinoids)or which promote loss of cohesion between horny cells (descaling agents). PMID:501133

  3. The Effect of Glutamate Receptor Agonists on Mouse Retinal Astrocyte [Ca2+]i

    PubMed Central

    Blandford, Stephanie N.

    2016-01-01

    Calcium-imaging techniques were used to determine if mouse retinal astrocytes in situ respond to agonists of ionotropic (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, AMPA; N-methyl-D-aspartate, NMDA) and metabotropic (S-3,5-dihydroxyphenylglycine, DHPG; trans-1-amino-1,3-cyclopentanedicarboxylic acid, ACPD) glutamate receptors. In most cases we found no evidence that retinal astrocyte intracellular calcium ion concentration ([Ca2+]i) increased in response to these glutamate agonists. The one exception was AMPA that increased [Ca2+]i in some, but not all, mouse retinal astrocytes in situ. However, AMPA did not increase [Ca2+]i in mouse retinal astrocytes in vitro, suggesting that the effect of AMPA in situ may be indirect. PMID:27413752

  4. Therapeutic effects of mouse bone marrow-derived clonal mesenchymal stem cells in a mouse model of inflammatory bowel disease.

    PubMed

    Park, Jin Seok; Yi, Tac-Ghee; Park, Jong-Min; Han, Young Min; Kim, Jun-Hyung; Shin, Dong-Hee; Tak, Seon Ji; Lee, Kyuheon; Lee, Youn Sook; Jeon, Myung-Shin; Hahm, Ki-Baik; Song, Sun U; Park, Seok Hee

    2015-11-01

    Mouse bone marrow-derived clonal mesenchymal stem cells (mcMSCs), which were originated from a single cell by a subfractionation culturing method, are recognized as new paradigm for stem cell therapy featured with its homogenous cell population. Next to proven therapeutic effects against pancreatitis, in the current study we demonstrated that mcMSCs showed significant therapeutic effects in dextran sulfate sodium (DSS)-induced experimental colitis model supported with anti-inflammatory and restorative activities. mcMSCs significantly reduced the disease activity index (DAI) score, including weight loss, stool consistency, and intestinal bleeding and significantly increased survival rates. The pathological scores were also significantly improved with mcMSC. We have demonstrated that especial mucosal regeneration activity accompanied with significantly lowered level of apoptosis as beneficiary actions of mcMSCs in UC models. The levels of inflammatory cytokines including TNF-α, IFN-γ, IL-1β, IL-6, and IL-17 were all significantly concurrent with significantly repressed NF-κB activation compared to the control group and significantly decreased infiltrations of responsible macrophage and neutrophil. Conclusively, our findings provide the rationale that mcMSCs are applicable as a potential source of cell-based therapy in inflammatory bowel diseases, especially contributing either to prevent relapse or to accelerate healing as solution to unmet medical needs in IBD therapy. PMID:26566304

  5. EFFECT OF DOSE ON THE EXCRETION AND METABOLISM OF MONOMETHYLARSONIC ACID IN THE MOUSE

    EPA Science Inventory

    EFFECT OF DOSE ON THE EXCRETION AND METABOLISM OF MONOMETHYLARSONIC ACID IN THE MOUSE
    M F Hughes1, V Devesa2, B C Edwards1, C T Mitchell1, E M Kenyon1, and D J Thomas1. 1US EPA, ORD, NHEERL, ETD, Research Triangle Park, NC; 2UNC-CH, CEMALB, Chapel Hill, NC

    Monomethylar...

  6. Timing is Essential for Rapid Effects of Corticosterone on Synaptic Potentiation in the Mouse Hippocampus

    ERIC Educational Resources Information Center

    Joels, Marian; Krugers, Harm; Wiegert, Olof

    2006-01-01

    Stress facilitates memory formation, but only when the stressor is closely linked to the learning context. These effects are, at least in part, mediated by corticosteroid hormones. Here we demonstrate that corticosterone rapidly facilitates synaptic potentiation in the mouse hippocampal CA1 area when high levels of the hormone and high-frequency…

  7. Development of an invitro technique to use mouse embryonic stem cell in evaluating effects of xenobiotics

    EPA Science Inventory

    Our goal has been to develop a high-throughput, in vitro technique for evaluating the effects of xenobiotics using mouse embryonic stem cells (mESCs). We began with the Embryonic Stem Cell Test (EST), which is used to predict the embryotoxic potential of a test compound by combin...

  8. Protective effect of porcine placenta in a menopausal ovariectomized mouse.

    PubMed

    Han, Na-Ra; Park, Chan-Lee; Kim, Na-Rae; Kim, Hee-Yun; Yoou, Myoung-Schook; Nam, Sun-Young; Moon, Phil-Dong; Jeong, Hyun-Ja; Kim, Hyung-Min

    2015-09-01

    Menopause is a significant physiological phase that occurs as women's ovaries stop producing ovum and the production of estrogen declines. Human placenta and some amino acids are known to improve menopausal symptoms. In this study, we investigated that porcine placenta extract (PPE) and arginine (Arg), a main amino acid of PPE, would have estrogenic activities in ovariectomized (OVX) mice as a menopause mouse model, human breast cancer cell line (MCF-7) cells, and human osteoblast cell line (MG-63) cells. PPE or Arg significantly inhibited the body weight and increased the vagina weight compared to the OVX mice. PPE or Arg ameliorated the vaginal atrophy in the OVX mice. The levels of 17β-estradiol and the activities of alkaline phosphatase (ALP) were significantly increased by PPE or Arg in the serum of OVX mice. Trabecular bone parameters such as bone mineral density and porosity were also improved by PPE or Arg in the OVX mice. In the MCF-7 and MG-63 cells, PPE or Arg significantly increased the cell proliferation, estrogen receptor β mRNA expression, and estrogen-response elements luciferase activity. Finally, PPE or Arg increased the activations of ALP and extracellular signal-regulated kinase 1/2 in the MG-63 cells. These results indicate that PPE or Arg would have estrogenic and osteoblastic activity. Therefore, PPE or Arg may be useful as new pharmacological tools for treating menopausal symptoms including osteoporosis. Free Korean abstract: A Korean translation of this abstract is freely available at http://www.reproduction-online.org/content/150/3/173/suppl/DC1. PMID:26047835

  9. Effects and Responses to Spaceflight in the Mouse Retina

    NASA Technical Reports Server (NTRS)

    Zanello, Susana B.; Theriot, Corey; Westby, Christian; Boyle, Richard

    2011-01-01

    Several stress environmental factors are combined in a unique fashion during spaceflight, affecting living beings widely across their physiological systems. Recently, attention has been placed on vision changes in astronauts returning from long duration missions. Alterations include hyperoptic shift, globe flattening, choroidal folds and optic disc edema, which are probably associated with increased intracranial pressure. These observations justify a better characterization of the ocular health risks associated with spaceflight. This study investigates the impact of spaceflight on the biology of the mouse retina. Within a successful tissue sharing effort, eyes from albino Balb/cJ mice aboard STS-133 were collected for histological analysis and gene expression profiling of the retina at 1 and 7 days after landing. Both vivarium and AEM (Animal Enclosure Module) mice were used as ground controls. Oxidative stress-induced DNA damage was higher in the flight samples compared to controls on R+1, and decreased on R+7. A trend toward higher oxidative and cellular stress response gene expression was also observed on R+1 compared to AEM controls, and these levels decreased on R+7. Several genes coding for key antioxidant enzymes, namely, heme-oxygenase-1, peroxiredoxin, and catalase, were among those upregulated after flight. Likewise, NF B and TGFbeta1, were upregulated in one flight specimen that overall showed the most elevated oxidative stress markers on R+1. In addition, retinas from vivarium control mice evidenced higher oxidative stress markers, NF B and TGFbeta1, likely due to the more intense illumination in vivarium cages versus the AEM. These preliminary data suggest that spaceflight represents a source of environmental stress that translates into oxidative and cellular stress in the retina, which is partially reversible upon return to Earth. Further work is needed to dissect the contribution of the various spaceflight factors (microgravity, radiation) and to

  10. Cytotoxic effects of propiconazole and its metabolites in mouse and human hepatoma cells and primary mouse hepatocytes

    EPA Science Inventory

    Abstract: Propiconazole is a triazole-containing fungicide that is used agriculturally on grasses, fruits, grains, seeds, hardwoods, and conifers. Propiconazole is a mouse liver hepatotoxicant and a hepatocarcinogen and has adverse reproductive and developmental toxicities in exp...

  11. Effects of a thermal-insulating mouse pad on temperature of forearm and hand during computer tasks.

    PubMed

    Meijer, Eline M; Formanoy, Margriet A G; Visser, Bart; Sluiter, Judith K; Frings-Dresen, Monique H W

    2006-07-15

    This laboratory experiment studied the effects of a thermal-insulating mouse pad on arm temperature and comfort during computer work. Fourteen subjects performed two 20-min computer tasks (a mouse task and a combined task alternating keyboard and mouse use), under three conditions, namely with: 1) a thermal-insulating pad; 2) a placebo pad; 3) no pad (desktop). The temperatures of the forearm, wrist, hand and fingers were measured with four thermocouples. Comfort and discomfort were determined by two visual analogue scales. No arm temperature differences were found between the experimental conditions after performing the combination task in any location. After the mouse task, however, arm temperature decreased significantly less with the thermal-insulating mouse pad than with the placebo pad. The thermal-insulating pad was rated as more comfortable and less uncomfortable than a regular desktop during mouse tasks. A large size is recommended for the thermal-insulating pad. PMID:16801230

  12. Supraspinal antinociceptive effect of apelin-13 in a mouse visceral pain model.

    PubMed

    Lv, Shuang-Yu; Qin, Yao-Jun; Wang, Ning-Bo; Yang, Yan-Jie; Chen, Qiang

    2012-09-01

    Apelin, as the endogenous ligand of the APJ receptor, is a novel identified neuropeptide whose biological functions are not fully understood. APJ receptor mRNA was found in several brain regions related to descending control system of pain, such as amygdala, hypothalamus and dorsal raphe nucleus (DRN). The present study was designed to determine whether supraspinal apelin-13 may produce antinociceptive effect observed in the acetic acid-induced writhing test, a model of visceral pain. Apelin-13 not only significantly produced preemptive antinociception at the dose of 0.3, 0.5, 1 and 3 μg/mouse when injected intracerebroventricularly (i.c.v.) before acetic acid, but also significantly induced antinociception at a dose of 0.5, 1 and 3 μg/mouse when injected i.c.v. after acetic acid. And i.c.v. apelin-13 did not influence 30-min locomotor activity counts in mice. Intrathecal (i.t.) administration of apelin-13 (1 and 3 μg/mouse) significantly decreased the number of writhes, however, intraperitoneal (i.p.) injection of apelin-13 (10-100 μg/mouse) had no effect on the number of writhes in the writhing test. The specific APJ receptor antagonist apelin-13(F13A), no-specific opioid receptor antagonist naloxone and μ-opioid receptor antagonist β-funaltrexamine hydrochloride (β-FNA) could significantly antagonize the antinociceptive effect of i.c.v. apelin-13, suggesting APJ receptor and μ-opioid receptor are involved in this process. Central low dose of apelin-13 (0.3 μg/mouse, i.c.v.) could significantly potentiate the analgesic potencies of modest and even relatively ineffective doses of morphine administrated at supraspinal level. This enhanced antinociceptive effect was reversed by naloxone, suggesting that the potentiated analgesic response is mediated by opioid-responsive neurons. PMID:22732665

  13. Teratogenic effects of amniotic sac puncture: a mouse model.

    PubMed Central

    MacIntyre, D J; Chang, H H; Kaufman, M H

    1995-01-01

    The possibility of an association between chorionic villus sampling (cvs) and limb abnormalities has prompted a review of the relevant experimental data. Although a vascular aetiology is favoured by many at present, the possibility exists that a proportion of cases may be caused by oligohydramnios secondary to inadvertent amniotic sac puncture. A mouse model of amniotic puncture syndrome has been developed to study the craniofacial and limb abnormalities produced by this procedure. Pregnant mice were anaesthetised and a laparotomy performed. One uterine horn was exteriorised, and the amniotic sacs punctured through the wall of the uterus with either a 21 gauge or a 25 gauge needle. The conceptuses in the contralateral uterine horn acted as controls. The mice were all killed on d 19 of pregnancy (day of finding a vaginal plug = d 1 of pregnancy) by cervical dislocation, and the morphological features of the embryos examined in detail. In a preliminary study, amniotic sac puncture was carried out on d 12, 13, 14, 15 or 16 of pregnancy, with either a 21 or a 25 gauge needle. Since the highest rates of palatal defects and limb deformities were observed following amniotic sac puncture using a 21 gauge needle, when this procedure was carried out on either d 13 or 14 of pregnancy, the main study was undertaken using a 21 gauge needle on these two days of pregnancy. Of 102 embryos in which amniotic sac puncture was carried out on d 13, 53% survived to d 19. Of the latter, 35% had a cleft palate, 61% had one or more morphologically abnormal limbs, and 43% had an abnormal tail. When amniotic sac puncture was carried out on d 14 of pregnancy, of 83 embryos subjected to this procedure, 81% survived to d 19. Of the latter, 27% had a cleft palate, 39% had one or more morphologically abnormal limbs, and 19% had an abnormal tail. In the controls, of 86 and 61 embryos isolated respectively from the d 13 and 14 mice, the survival rates were 97 and 90%, respectively. Palatal, limb

  14. Anti-tumor effects of peptide analogs targeting neuropeptide hormone receptors on mouse pheochromocytoma cells.

    PubMed

    Ziegler, C G; Ullrich, M; Schally, A V; Bergmann, R; Pietzsch, J; Gebauer, L; Gondek, K; Qin, N; Pacak, K; Ehrhart-Bornstein, M; Eisenhofer, G; Bornstein, S R

    2013-05-22

    Pheochromocytoma is a rare but potentially lethal chromaffin cell tumor with currently no effective treatment. Peptide hormone receptors are frequently overexpressed on endocrine tumor cells and can be specifically targeted by various anti-tumor peptide analogs. The present study carried out on mouse pheochromocytoma cells (MPCs) and a more aggressive mouse tumor tissue-derived (MTT) cell line revealed that these cells are characterized by pronounced expression of the somatostatin receptor 2 (sst2), growth hormone-releasing hormone (GHRH) receptor and the luteinizing hormone-releasing hormone (LHRH) receptor. We further demonstrated significant anti-tumor effects mediated by cytotoxic somatostatin analogs, AN-162 and AN-238, by LHRH antagonist, Cetrorelix, by the cytotoxic LHRH analog, AN-152, and by recently developed GHRH antagonist, MIA-602, on MPC and for AN-152 and MIA-602 on MTT cells. Studies of novel anti-tumor compounds on these mouse cell lines serve as an important basis for mouse models of metastatic pheochromocytoma, which we are currently establishing. PMID:23267837

  15. Effects of Acorn (Quercus acutissima CARR.) Supplementation on Acetylcholine and Its Related Enzyme Activities in Brain of Dementia Model Mouse

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was carried out to investigate the effects of acorn (Quercus acutissima CARR.) on brain dementia in mouse. Murine dementia model was induced by scopolamin administration to abdominal cavity (30 mg/kg BW). Male ICR mouse (30 ' 2 g BW) were fed basic diet (control group), or experimental d...

  16. How do you hold your mouse? Tracking the compatibility effect between hand posture and stimulus size.

    PubMed

    Flumini, Andrea; Barca, Laura; Borghi, Anna M; Pezzulo, Giovanni

    2015-11-01

    In keeping with the idea that observing objects activates possible motor responses, several experiments revealed compatibility effects between the hand postures used to report a choice and some characteristics of the stimuli. The real-time dynamics of such compatibility effects are currently unknown. We tracked the time course of a categorization experiment requiring subjects to categorize as natural or artifact figures of big and small objects. Participants reported their choice using either a big mouse (requiring a power grip: a hand posture compatible with the grasping of big objects) or a small mouse (requiring a precision grip: a hand posture compatible with the grasping of small objects). We found a compatibility effect between the grip required by the mouse and the grip elicited by objects, even if it was irrelevant to the task. In a following experiment with the same paradigm, lexical stimuli failed to reproduce the same effect. Nevertheless, a compatibility effect mediated by the target-word category (artificial vs. natural) was observed. We discuss the results in the context of affordance effects literature and grounded theories of cognition. PMID:25349026

  17. Blockade of Extracellular ATP Effect by Oxidized ATP Effectively Mitigated Induced Mouse Experimental Autoimmune Uveitis (EAU)

    PubMed Central

    Zhao, Ronglan; Liang, Dongchun; Sun, Deming

    2016-01-01

    Various pathological conditions are accompanied by ATP release from the intracellular to the extracellular compartment. Extracellular ATP (eATP) functions as a signaling molecule by activating purinergic P2 purine receptors. The key P2 receptor involved in inflammation was identified as P2X7R. Recent studies have shown that P2X7R signaling is required to trigger the Th1/Th17 immune response, and oxidized ATP (oxATP) effectively blocks P2X7R activation. In this study we investigated the effect of oxATP on mouse experimental autoimmune uveitis (EAU). Our results demonstrated that induced EAU in B6 mice was almost completely abolished by the administration of small doses of oxATP, and the Th17 response, but not the Th1 response, was significantly weakened in the treated mice. Mechanistic studies showed that the therapeutic effects involve the functional change of a number of immune cells, including dendritic cells (DCs), T cells, and regulatory T cells. OxATP not only directly inhibits the T cell response; it also suppresses T cell activation by altering the function of DCs and Foxp3+ T cell. Our results demonstrated that inhibition of P2X7R activation effectively exempts excessive autoimmune inflammation, which may indicate a possible therapeutic use in the treatment of autoimmune diseases. PMID:27196432

  18. Chronodependent effect of interleukin-2 on mouse spleen cells in the model of cyclophosphamide immunosuppression.

    PubMed

    Shurlygina, A V; Mel'nikova, E V; Trufakin, V A

    2015-02-01

    We studied the chronodependent effect of IL-2 in the experimental model of immunodeficiency, cyclophosphamide-induced immunosuppression in mice. IL-2 in a dose of 100 U/ mouse was administered at 10.00 and 16.00 for 3 days after injection of cyclophosphamide. In contrast to the morning treatment with the cytokine, evening administration produced antiapoptotic effect on splenocytes and stimulated proliferation to a greater extent. This was accompanied by an increase in the number of CD4(+), CD25(+) and CD4(+)25(+) cells in the spleen to a level of intact mice. More pronounced effect of the evening mode of IL-2 administration on the proliferation and subpopulation composition of mouse spleen cells in the studied model can be associated with high blood level of CD25(+) cells at this time of the day. PMID:25708328

  19. Effects of several salt marsh plants on mouse spleen and thymus cell proliferation using mtt assay

    NASA Astrophysics Data System (ADS)

    Seo, Youngwan; Lee, Hee-Jung; Kim, You Ah; Youn, Hyun Joo; Lee, Burm-Jong

    2005-12-01

    In the present study, we have tested the effects of 21 salt marsh plants on cell proliferation of mouse immune cells (spleen and thymus) using MTT assay in culture. The methanolic extracts of six salt marsh plants ( Rosa rugosa, Ixeris tamagawaensis, Artemisia capillaris, Tetragonia tetragonoides, Erigeron annus, and Glehnia littoralis) showed very powerful suppressive effects of mouse immune cell death and significant activities of cell proliferation in vitro. Especially, the methanolic extract of Rosa rugosa was found to have fifteen times compared to the control treatment, demonstrating that Rosa rugosa may have a potent stimulation effect on immune cell proliferation. These results suggest that several salt marsh plants including Rosa rugosa could be useful for further study as an immunomodulating agent.

  20. Evaluation of mitochondrial divisions in mouse with type-2 diabetes and effect of glucose-oxidase on mouse islet cells RIN-m5F.

    PubMed

    Gao, Yu; Li, Fan; Zhang, Anping; Wang, Li; Tong, Weidong; Liu, Baohua

    2014-03-01

    To elucidate the relationship between dynamic variations of insular β cell mitochondria and type-2 diabetes by using a mouse model, the dynamic variation (fusion or fission) of insular β cell mitochondria present in two groups of Wistar mice with type-2 diabetes (high fat feeding and streptozotocin (STZ) adding with low dose and high frequency, high fat feeding and STZ adding with high dose and low frequency), and normal Wistar mouse were systematically compared. By analysing the insulin secretion level and other related indexes, the molecular mechanism of the fusion or fission phenomenon of insular β cell mitochondria in two different models (high fat feeding and STZ adding with low dose and high frequency, high fat feeding and STZ adding with high dose and low frequency) of mice with type-2 diabetes were initially elucidated. The phenomenon of mitochondrial fusion and fission was clearly seen. In initially determining the relationship between the change of insular β cell mitochondrial structure and its cell apoptosis generated by some factors such as treatment by glucose-oxidase (GO), the effect of GO on the mouse islet cells RIN-m5F including the effects on cell growth, reactive oxygen species (ROS), cell cycle, cell apoptosis of RIN-m5F were systematically examined. GO showed some influence on the mouse islet cells RIN-m5F cell activity, ROS and apoptosis, but its effect on the cell cycle was not significant. PMID:24375791

  1. Embryonic substantia nigra grafts in the mesencephalon send neurites to the host striatum in non-human primate after overexpression of GDNF

    PubMed Central

    Redmond, D.E.; Elsworth, J.D.; Roth, R.H.; Leranth, C.; Collier, T.J.; Blanchard, B.; Bjugstad, K.B.; Samulski, R.J.; Aebischer, P.; Sladek, J.R.

    2010-01-01

    In spite of partial success in treating Parkinson's disease using ectopically placed grafts of dopamine-producing cells, restoration of the original neuroanatomical circuits, if possible, might work better. Previous evidence of normal anatomic projections from ventral mesencephalic (VM) grafts placed in the substantia nigra (SN) has been limited to neonatal rodents and double grafting or bridging procedures. This study attempted to determine whether injection of a potent growth promoting factor, glial cell line-derived neurotrophic factor (GDNF), into the target regions or placement of fetal striatal co-grafts in the nigrostriatal pathway might elicit neuritic outgrowth to the caudate nucleus. Four adult St. Kitts green monkeys received embryonic VM grafts into the rostral mesencephalon near the host substantia nigra, and injections of AAV2/GDNF or EIAV/GDNF into the caudate. Three adult monkeys were co-grafted with fetal VM tissue near the substantia nigra and fetal striatal grafts (STR) 2.5 mm rostral in the nigrostriatal pathway. Before sacrifice, the striatal target regions were injected with the retrograde tracer fluorogold (FG). FG label was found in tyrosine hydroxylase-labeled neurons in VM grafts in the SN of only those monkeys that received AAV2/GDNF vector injections into the ipsilateral striatum. All monkeys showed FG labeling in the host substantia nigra when FG labeling was injected on the same side. These data show that grafted dopaminergic neurons can extend neurites to a distant target releasing an elevated concentration of GDNF, and suggest that grafted neurons can be placed into appropriate loci for potential tract reconstruction. PMID:19399891

  2. Bridging nigrostriatal pathway with fibroblast growth factor-primed peripheral nerves and fetal ventral mesencephalon transplant recuperates from deficits in parkinsonian rats.

    PubMed

    Chiang, Yung-Hsiao; Lin, Shinn-Zong; Zhou, Feng C

    2006-01-01

    Previous studies have indicated that the nigrostriatal dopaminergic (DA) pathway can be reconstructed in hemiparkinsonian rats with a bridge transplantation technique involving fetal ventral mesencephalic transplants and glial cell line-derived neurotrophic factor. In this study, we examined if the nigrostriatal pathway can be restored by combining peripheral nervous tissue with the fetal ventral mesencephalon transplants. Adult rats were injected with 6-hydroxydopamine into left median forebrain bundle. Those with marked rotational behavior, which has been previously shown to indicate complete DA dennervtion, were used for transplant treatments. One month after the lesion, fetal ventral mesencephalic cells were transplanted into the nigral region followed by nigral-striatal grafting of peripheral nerves as a bridge. The bridging nerves (sciatic or intercostals) were pretreated with basic fibrous growth factor (nerve+bFGF+) or Hank's saline (nerve+bFGF-). We found that (a) animals receiving transplants of VM and bFGF+ nerve had a reduction in rotational behavior; (b) animals receiving bFGF-- nerve bridge only had a partial improvement in rotation. Reinnervation of tyrosine hydroxylase (TH)-immunoreactive (ir) fibers into the striatum was found in both of the above groups with more innervation in the former than in the latter. No TH-ir fibers in lesioned striatum or reduction in rotational behavior were found in animals receiving VM only, or VM plus bFGF. Taken together, our data indicate that peripheral nerve, with the aid of bFGF, greatly facilitates the reconstitution of the TH pathway from nigra to striatum and improves motor function in hemiparkinsonian rats. PMID:17121158

  3. Effective PCR-based detection of Naegleria fowleri from cultured sample and PAM-developed mouse.

    PubMed

    Kang, Heekyoung; Seong, Gi-Sang; Sohn, Hae-Jin; Kim, Jong-Hyun; Lee, Sang-Eun; Park, Mi Yeoun; Lee, Won-Ja; Shin, Ho-Joon

    2015-10-01

    Increasing numbers of Primary Amoebic Meningoencephalitis (PAM) cases due to Naegleria fowleri are becoming a serious issue in subtropical and tropical countries as a Neglected Tropical Disease (NTD). To establish a rapid and effective diagnostic tool, a PCR-based detection technique was developed based on previous PCR methods. Four kinds of primer pairs, Nfa1, Nae3, Nf-ITS, and Naegl, were employed in the cultured amoebic trophozoites and a mouse with PAM experimentally developed by N. fowleri inoculation (PAM-mouse). For the extraction of genomic DNA from N. fowleri trophozoites (1×10(6)), simple boiling with 10μl of PBS (pH 7.4) at 100°C for 30min was found to be the most rapid and efficient procedure, allowing amplification of 2.5×10(2) trophozoites using the Nfa-1 primer. The primers Nfa1 and Nae3 amplified only N. fowleri DNA, whereas the ITS primer detected N. fowleri and N. gruberi DNA. Using the PAM-mouse brain tissue, the Nfa1 primer was able to amplify the N. fowleri DNA 4 days post infection with 1ng/μl of genomic DNA being detectable. Using the PAM-mouse CSF, amplification of the N. fowleri DNA with the Nae3 primer was possible 5 days post infection showing a better performance than the Nfa1 primer at day 6. PMID:26322498

  4. Cochlear implantation in the mouse via the round window: effects of array insertion.

    PubMed

    Mistry, N; Nolan, L S; Saeed, S R; Forge, A; Taylor, R R

    2014-06-01

    Animal models are the only means of assessing the effects of cochlear implantation (CI) at a cellular and molecular level. The range of naturally occurring and genetically-modified mouse strains which mimic human deafness provide excellent opportunities for auditory research. To date, there are very few studies of CI in mice. The main aims of this study were to develop a reproducible and viable technique to enable long term CI in the mouse and to assess the response of the mouse cochlea to implantation as a means of evaluating the success of the procedure. Electrode array implantation via the round window was performed in C57Bl/6 mice aged 3 and 6 months. The contralateral cochlea acted as a control. Auditory brainstem responses (ABR) were recorded prior to and following CI. Analysis showed greater threshold shifts in the implanted ear compared to the control ear post-implantation, but substantial preservation of hearing. There were no cases in which implantation caused a profound hearing loss across all frequencies. Cone beam computerised tomography and light microscopy confirmed correct placement of the electrode array within the scala tympani. Cochleae were prepared for histological examination. Initial analysis revealed encapsulation of the implant in tissue with morphological characteristics suggestive of fibrosis. Our results show that mouse CI via the round window offers a model for exploring tissue responses to implantation. PMID:24657211

  5. Effects of ochratoxin a on mouse oocyte maturation and fertilization, and apoptosis during fetal development.

    PubMed

    Huang, Fu-Jen; Chan, Wen-Hsiung

    2016-06-01

    We previously reported that ochratoxin A (OTA), a mycotoxin found in many foods worldwide, causes nephrotoxicity, hepatotoxicity, and immunotoxicity, and is a risk factor for abnormal embryonic development. More specifically, OTA triggers apoptotic processes in the inner cell mass of mouse blastocysts, decreasing cell viability and embryonic development. In the current study, we investigated the deleterious effects of OTA on mouse oocyte maturation, in vitro fertilization (IVF), and subsequent pre- and postimplantation development both in vitro and in vivo. Notably, OTA significantly impaired mouse oocyte maturation, decreased IVF rates, and inhibited subsequent embryonic development in vitro. Preincubation of oocytes with OTA during in vitro maturation increased postimplantation embryonic resorption and decreased mouse fetal weight. In an in vivo animal model, provision of 1-10 μM OTA in the drinking water or intravenous injection of 1 or 2 mg/kg body weight of OTA decreased oocyte maturation and IVF, and had deleterious effects on early embryonic development. Importantly, preincubation of oocytes with a caspase-3-specific inhibitor effectively blocked these OTA-triggered deleterious effects, suggesting that the embryonic injury induced by OTA is mediated via a caspase-dependent apoptotic mechanism. Furthermore, OTA upregulated the levels of p53 and p21 in blastocyst cells derived from OTA-pretreated oocytes, indicating that such cells undergo apoptosis via p53-, p21-, and caspase-3-dependent regulatory mechanisms. This could have deleterious effects on embryonic implantation and fetal survival rates, as seen in our animal models. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 724-735, 2016. PMID:25504763

  6. The effect of interferon-{beta} on mouse neural progenitor cell survival and differentiation

    SciTech Connect

    Hirsch, Marek; Knight, Julia; Tobita, Mari; Soltys, John; Panitch, Hillel; Mao-Draayer, Yang

    2009-10-16

    Interferon-{beta} (IFN-{beta}) is a mainstay therapy for relapse-remitting multiple sclerosis (MS). However, the direct effects of IFN-{beta} on the central nervous system (CNS) are not well understood. To determine whether IFN-{beta} has direct neuroprotective effects on CNS cells, we treated adult mouse neural progenitor cells (NPCs) in vitro with IFN-{beta} and examined the effects on proliferation, apoptosis, and differentiation. We found that mouse NPCs express high levels of IFN{alpha}/{beta} receptor (IFNAR). In response to IFN-{beta} treatment, no effect was observed on differentiation or proliferation. However, IFN-{beta} treated mouse NPCs demonstrated decreased apoptosis upon growth factor withdrawal. Pathway-specific polymerase chain reaction (PCR) arrays demonstrated that IFN-{beta} treatment upregulated the STAT 1 and 2 signaling pathway, as well as GFRA2, NOD1, Caspases 1 and 12, and TNFSF10. These results suggest that IFN-{beta} can directly affect NPC survival, possibly playing a neuroprotective role in the CNS by modulating neurotrophic factors.

  7. Effects of Substrate Size and Orientation on Quadrupedal Gait Kinematics in Mouse Lemurs (Microcebus murinus).

    PubMed

    Shapiro, Liza J; Kemp, Addison D; Young, Jesse W

    2016-06-01

    As the smallest living primate, the mouse lemur is a suitable model for reconstructing the locomotor mechanisms by which primate ancestors might have responded to the challenges of an arboreal environment. In this study, we tested the effects of substrate diameter and orientation on quadrupedal gait kinematics in mouse lemurs (Microcebus murinus). Mouse lemurs highly preferred asymmetrical to symmetrical gaits as they moved across a flat board and poles of three diameters (2.5, 1.0, and 0.5 cm), set at horizontal, 30° inclined, and 30° declined orientations. During symmetrical gaits, mouse lemurs used diagonal sequence walking and ambling gaits on the same substrates and at the same duty factors for which some similarly sized nonprimate mammals use lateral sequence gaits, suggesting that reliance on diagonal sequence walking in primates may not be explicitly a response to body size relative to substrate diameter. When using asymmetrical gaits, kinematic adjustments to small diameter and/or nonhorizontal substrates included a preference for transverse gallops over other gaits, the avoidance of whole-body suspensions, increases in limb contact duration, and increases in the time interval between the landing of trailing and leading limbs. All of these adjustments are consistent with increasing locomotor stability by dampening center of mass movements and reducing the forces imparted to the substrate. Like mouse lemurs, small-bodied ancestral primates likely used symmetrical gaits occasionally, but more frequently used asymmetrical gaits that were adjusted in response to challenging substrates. Therefore, asymmetrical gait dynamics should be incorporated into hypotheses addressing early primate locomotor evolution. PMID:27222465

  8. Effects of GDNF and LIF on mouse spermatogonial stem cells proliferation in vitro.

    PubMed

    Wang, Peng; Suo, Li-Juan; Wang, Yan-Feng; Shang, Hua; Li, Guang-Xuan; Hu, Jian-Hong; Li, Qing-Wang

    2014-03-01

    Spermatogonial stem cells (SSCs) are the only type of cells that transmit genes to the subsequent generations. The proliferation, cultivation and identification of SSCs in vitro are critical to understanding of male infertility, genetic resources and conservation of endangered species. To investigate the effects of glial cell-derived neurotrophic factor (GDNF) and leukemia inhibitory factor (LIF) on the proliferation of mouse SSCs in vitro, supplement of GDNF and/or LIF were designed to culture SSCs. The testes of 6-8 d mouse were harvested and digested by two-step enzyme digestion method. The SSCs and Sertoli cells were separated by differential plating. Then the SSCs were identified by alkaline phosphatase staining, RT-PCR and indirect immunofluorescence cell analysis. The cellular proliferation capacity was measured by methyl thiazolyl tetrazolium assay. The results showed that addition of 20 and 40 ng/ml of GDNF could strongly promote growth of mouse SSCs (p < 0.05). There was no significant difference between LIF treatment groups and the control group in promoting proliferation of the mouse SSCs (p > 0.05). However, the combination of 20 ng/ml GDNF and 1,000 U/ml LIF could significantly enhance the invitro proliferation of mouse SSCs (p < 0.05), and the OD490 value was 0.696 at day 5 of culture when the density of SSCs was 5-10 × 10(4) cells/ml. PMID:23896701

  9. Effects of crude garlic extract on mouse chromosomes in vivo.

    PubMed

    Das, T; Choudhury, A R; Sharma, A; Talukder, G

    1996-01-01

    Three concentrations (25, 50 and 100 mg/kg body weight) of fresh garlic (Allium sativum L.) were administered daily by gavage to Swiss albino mice for different durations up to 60 days. These concentrations had been observed to protect significantly against effects of known clastogens. The endpoints scored were frequencies of chromosomal aberrations and damaged cells induced in bone marrow preparations. These parameters were found to be directly dose dependent and after an initial enhancement at 7 days, were reduced following prolonged exposure for 30 and 60 days to the low level observed at 24 hr. Therefore, administration of a low concentration of garlic extract daily is suggested for at least 30 days to obtain the maximum benefit of the extract in protecting against the clastogenic effects of known genotoxicants. PMID:8603796

  10. Effect of soman on the cholinergic system in mouse brain

    SciTech Connect

    Tripathi, H.L.; Szakal, A.R.; Little, D.M.; Dewey, W.L.

    1986-03-05

    The effects of soman on levels of acetylcholine (ACh) and choline (Ch) and turnover rate of ACh have been studied in whole brain and brain regions (cerebellum, medulla-pons, midbrain, corpus striatum, hippocampus and cortex) of mice. Animals were injected with saline or a dose of soman up to 80..mu..g/kg, i.v. and were sacrificed by focussed microwave irradiation of the head. The tracer, /sup 3/H-Ch was injected (i.v.) 2 min prior to sacrifice and turnover rate of ACh was quantitated by using HPLC with electrochemical detection. A behaviorally effective dose of 80 ..mu..g/kg soman increased the levels of ACh significantly in whole brain (57.5%), corpus striatum (42.8%), hippocampus (24.1%) and cortex (43.1%). The levels of Ch were also increased in cerebellum (80.1%), midbrain (75.7%), corpus striatum (86.0%) and cortex (52.5%). The turnover rate of ACh was decreased in whole brain (53.8%), cerebellum (80.4%), medulla-pons (66.8%), midbrain (57.0%), corpus striatum (62.1%) and cortex (52.6%). The duration of these effects lasted more than 1 hr and the results indicate that the decrease in ACh turnover is not due necessarily to an increase in brain levels of ACh and/or Ch.

  11. Effect of Yi Gong San Decoction on Iron Homeostasis in a Mouse Model of Acute Inflammation

    PubMed Central

    Zheng, Qin; Guan, Yu; Xia, Lemin; Wang, Zhicheng; Jiang, Yiling; Zhang, Xiaofeng; Wang, Jianying; Wang, Guohua; Pu, Yiqiong; Xia, Jing; Luo, Meihong

    2016-01-01

    We investigated the effect of Yi Gong San (YGS) decoction on iron homeostasis and the possible underlying mechanisms in a mouse model of acute inflammation in this study. Our findings suggest that YGS regulates iron homeostasis by downregulating the level of HAMP mRNA, which may depend on regulation of the IL-6/STAT3 or BMP/HJV/SMAD pathway during acute inflammation. PMID:27143982

  12. Protective effects of papaverine salicylate in mouse ear dermatitis and PAF-induced rat paw oedema.

    PubMed

    de Bernardis, E; Leonardi, G; Caruso, A; Cutuli, V M; Amico-Roxas, M

    1994-08-01

    Papaverine salicylate (MR-800) has been tested as a topical antiinflammatory agent in several models of skin inflammation in rodents, such as mouse ear dermatitis induced by croton oil, cantharidin or zymosan, and rat paw oedema induced by PAF. MR-800 exerted a dose-dependent inhibitory activity in all assays, when equimolar doses of sodium salicylate or papaverine were less effective, suggesting the existence of a favourable synergism between salicylate and papaverine. PMID:7847181

  13. Effect of cyclophosphamide and electromagnetic fields on mouse bone marrow

    SciTech Connect

    Cadossi, R.; Zucchini, P.; Emilia, G.; Torelli, G. )

    1990-02-26

    The authors have previously shown that the exposure to low frequency pulsing electromagnetic fields (PEMF) of mice X-ray irradiated resulted in an increased damage to the bone marrow. The series of experiments here reported were designed to investigate the effect of PEMF exposure after intraperitoneum injection of 200mg/kg of cyclophosphamide (CY). Control mice were CY injected only; experimental mice were CY injected and then exposed to PEMF. Exposure to PEMF (24 hours/day) increased the rate of decline of white blood cells in peripheral blood. Spleen weight was statistically higher among control mice than among mice exposed to PEMF at day 6, 8 and 10 after CY injection. Spleen autoradiography proved to be higher among PEMF exposed mice than among controls at day 8 and 9 after CY injection. The grafting efficiency of the bone marrow obtained from control mice was higher than the grafting efficiency of the bone marrow recovered from mice exposed to PEMF. All these data indicate that the exposure to PEMF increases the cytotoxic effect of CY.

  14. Effects of oxaliplatin on mouse myenteric neurons and colonic motility

    PubMed Central

    Wafai, Linah; Taher, Mohammadali; Jovanovska, Valentina; Bornstein, Joel C.; Dass, Crispin R.; Nurgali, Kulmira

    2013-01-01

    Oxaliplatin, an anti-cancer chemotherapeutic agent used for the treatment of colorectal cancer, commonly causes gastrointestinal side-effects such as constipation, diarrhoea, nausea, and vomiting. Damage to enteric neurons may underlie some of these gastrointestinal side-effects, as the enteric nervous system (ENS) controls functions of the bowel. In this study, neuronal loss and changes to the structure and immunoreactivity of myenteric neuronal nitric oxide synthase (nNOS) neurons were examined in colonic segments from mice following exposure to oxaliplatin ex vivo and following repeated intraperitoneal injections of oxaliplatin over 3 weeks in vivo, using immunohistochemistry and confocal microscopy. Significant morphological alterations and increases in the proportion of NOS-immunoreactive (IR) neurons were associated with both short-term oxaliplatin exposure and long-term oxaliplatin administration, confirming that oxaliplatin causes changes to the myenteric neurons. Long-term oxaliplatin administration induced substantial neuronal loss that was correlated with a reduction in both the frequency and propagation speed of colonic migrating motor complexes (CMMCs) in vitro. Similar changes probably produce some symptoms experienced by patients undergoing oxaliplatin treatment. PMID:23486839

  15. Galactose effects on enterocyte differentiation in the mouse jejunum.

    PubMed

    Smith, M W; James, P S; Peacock, M A

    1991-07-10

    The present work investigates the ability of galactose to affect enterocyte differentiation during normal development in vivo. Energy intake has also been varied to take account of the fact that galactose is poorly metabolized in mice. Brush-border lactase, alpha-glucosidase, dipeptidylpeptidase-IV, aminopeptidase N, alkaline phosphatase and microvillus length were measured as markers of enterocyte differentiation in mice fed diets containing galactose (G diet), corn oil (E diet) or galactose + corn oil (G + E diet). Maintaining mice on a G instead of E diet reduced brush-border lactase activity and enterocyte migration rates; alpha-glucosidase, dipeptidylpeptidase-IV, aminopeptidase N and microvillus length expression increased and alkaline phosphatase activity remained unchanged. Feeding the G + E diet restored enterocyte migration rates, lactase, aminopeptidase N and dipeptidylpeptidase-IV activities to values found in mice fed the E diet. Galactose stimulation of alpha-glucosidase and microvillus length expression was, however, fully maintained in mice fed the G + E diet. Present results show that enterocyte differentiation is affected independently by varying dietary galactose and energy levels; that galactose effects always increase and energy effects usually decrease expression of enterocyte components and that energy stimulation of lactase activity is exceptional. PMID:1907492

  16. Effective suppression of acrylamide neurotoxicity by lithium in mouse.

    PubMed

    Song, Lingzhen; Wang, Jiutao; Zhang, Wei; Yan, Runchuan; Hu, Xinde; Chen, Shulin; Zhao, Shanting

    2014-11-01

    The primary objective of this investigation was to assess the neuroprotective efficacy of lithium in an acrylamide (ACR)-induced neuropathy model in mice. In this study, Kunming male mice were administered ACR (25 mg/kg bw, i.p. once a day) with or without lithium (25 mg/kg bw, i.p. once a day) for 2 weeks. All ACR-administered mice exhibited severe symptoms of neuropathy. We found that treatment with lithium effectively alleviated behavioral deficits in animals elicited by acrylamide. Interestingly, the reduction of hippocampal neurogenesis resulting from ACR injection was promoted by administration of lithium. Further, lithium treatment significantly offset ACR-induced depletion in p-GSK-3β (Ser9) levels in hippocampus. Collectively our findings suggest the propensity of lithium to attenuate ACR-induced neuropathy. Further studies are necessary to understand the precise molecular mechanism by which the lithium attenuates neuropathy. Nevertheless, our data clearly demonstrate the beneficial effects of lithium on ACR-induced neuropathy in mice and suggest its possible therapeutic application as an adjuvant in the management of other forms of neuropathy in humans. PMID:25146901

  17. Effect of amlodipine on mouse renal interstitial fibrosis.

    PubMed

    Honma, Shigeyoshi; Nakamura, Kazuki; Shinohara, Masahiro; Mitazaki, Satoru; Abe, Sumiko; Yoshida, Makoto

    2016-06-01

    Unilateral ureteral obstruction (UUO) is a well-established method to study interstitial fibrosis of the kidney. In this study, we investigated the effects of a calcium channel blocker, amlodipine, on UUO-induced renal interstitial fibrosis in mice. UUO significantly increased the fibrotic area in the obstructed kidney, but this change was inhibited by amlodipine (6.7mg/kg/day in drinking water). mRNA expression of heat shock protein (HSP) 47 and type IV collagen was increased in the kidneys of UUO mice. Amlodipine reduced the expression of both HSP47 and type IV collagen mRNAs. Phosphorylation of c-jun-N-terminal kinase (JNK) was significantly increased by UUO, but the change was inhibited by amlodipine. Collectively, these results suggest that amlodipine may inhibit the expression of HSP47 and type IV collagen by reducing phosphorylation of JNK and ameliorating the renal interstitial fibrosis induced by UUO. PMID:27029240

  18. The effects of aging on the BTBR mouse model of autism spectrum disorder

    PubMed Central

    Jasien, Joan M.; Daimon, Caitlin M.; Wang, Rui; Shapiro, Bruce K.; Martin, Bronwen; Maudsley, Stuart

    2014-01-01

    Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder characterized by alterations in social functioning, communicative abilities, and engagement in repetitive or restrictive behaviors. The process of aging in individuals with autism and related neurodevelopmental disorders is not well understood, despite the fact that the number of individuals with ASD aged 65 and older is projected to increase by over half a million individuals in the next 20 years. To elucidate the effects of aging in the context of a modified central nervous system, we investigated the effects of age on the BTBR T + tf/j mouse, a well characterized and widely used mouse model that displays an ASD-like phenotype. We found that a reduction in social behavior persists into old age in male BTBR T + tf/j mice. We employed quantitative proteomics to discover potential alterations in signaling systems that could regulate aging in the BTBR mice. Unbiased proteomic analysis of hippocampal and cortical tissue of BTBR mice compared to age-matched wild-type controls revealed a significant decrease in brain derived neurotrophic factor and significant increases in multiple synaptic markers (spinophilin, Synapsin I, PSD 95, NeuN), as well as distinct changes in functional pathways related to these proteins, including “Neural synaptic plasticity regulation” and “Neurotransmitter secretion regulation.” Taken together, these results contribute to our understanding of the effects of aging on an ASD-like mouse model in regards to both behavior and protein alterations, though additional studies are needed to fully understand the complex interplay underlying aging in mouse models displaying an ASD-like phenotype. PMID:25225482

  19. LONG-TERM EFFECTS OF TRIETHYLENEMELAMINE EXPOSURE ON MOUSE TESTIS CELLS AND SPERM CHROMATIN STRUCTURE ASSAYED BY FLOW CYTOMETRY

    EPA Science Inventory

    The toxic and potentially mutagenic actions of triethylenemelamine (TEM) on mouse body and testis weights, testicular cell kinetics, sperm production, sperm head morphology, and sperm chromatin structure were assessed in two experiments. he first experiment examined effects of fo...

  20. Stereoselective Effects of 4-Hydroxynonenal in Cultured Mouse Hepatocytes

    PubMed Central

    Dabrowski, Michael J.; Zolnerciks, Joseph K.; Balogh, Larissa M.; Greene, Robert J.; Kavanagh, Terrance J.; Atkins, William M.

    2010-01-01

    4-Hydroxynonenal (HNE) is produced from arachidonic acid or linoleic acid during oxidative stress. Although HNE is formed in tissues as a racemate, enantiospecific HNE effects have not been widely documented, nor considered. Therefore, a panel of cellular responses was compared after treatment with (R)-HNE, (S)-HNE, or racemic HNE. The phosphorylation status of Jun kinase (JNK) or Akt increased 28-fold or 2-3-fold, respectively, after treatment with 100 μM (S)-HNE and racemic HNE compared to (R)-HNE. In contrast, the increase in phosphorylation of MAPK was greatest for (R)-HNE. caspase-3-dependent cleavage of glutamate cysteine ligase (GCL) catalytic subunit and focal adhesion kinase (FAK) were greater in cells treated with (S)-HNE at 48 hrs. (S)-HNE also caused a greater number of subG1 nuclei, a hallmark of apoptosis, at 30 hours after treatment. Together, the results demonstrate different dose- and time-dependent responses to (R)-HNE and (S)-HNE. The results further suggest that HNE enantiomers could differentially contribute to the progression of different diseases or contribute by different mechanisms. PMID:20873854

  1. Prophylactic effect of administration of human gamma globulins in a mouse model of tuberculosis.

    PubMed

    Olivares, Nesty; Puig, Alina; Aguilar, Diana; Moya, Aniel; Cádiz, Armando; Otero, Oscar; Izquierdo, Luis; Falero, Gustavo; Solis, Rosa L; Orozco, Hector; Sarmiento, Maria E; Norazmi, Mohd Nor; Hernández-Pando, Rogelio; Acosta, Armando

    2009-05-01

    The protective effect of human gamma globulins on Mycobacterium tuberculosis infection was evaluated in a mouse model of intratracheal infection. Animals receiving human gamma globulins intranasally, 2h before intratracheal challenge showed a significant decrease in lung bacilli load compared to non-treated animals in different time intervals of up to 2 months after challenge. The same effect was obtained when M. tuberculosis was pre-incubated with the gamma globulin before challenge. The protective effect of the gamma-globulin formulation was abolished after pre-incubation with M. tuberculosis. These results suggest a potential role of specific antibodies in the defence against mycobacterial infections. PMID:19362883

  2. Effect of organochlorine pesticides on maturation of starfish and mouse oocytes.

    PubMed

    Picard, André; Pahlavan, Golbahar; Palavan, Golbahar; Robert, Stéphanie; Pesando, Danielle; Ciapa, Brigitte

    2003-05-01

    Methoxychlor, lindane, and dieldrin are organochlorine pesticides that have been described as altering different reproductive functions in mammals and in invertebrates. However, few data have been published concerning the effects these pesticides have on oocyte maturation and fertilization. The aim of this study was to determine whether these compounds could affect maturation of mouse and starfish oocytes. We observed that germinal vesicle breakdown (GVBD) in starfish oocytes was significantly inhibited by the pesticides. Furthermore, formation of the first meiotic spindle and extrusion of the first polar body were also altered in mouse as well as in starfish. Our results suggest that the three pesticides act on common intracellular targets in invertebrates as well as in vertebrates. PMID:12700411

  3. Effects of ovarian endometriotic fluid exposure on fertilization rate of mouse oocytes and subsequent embryo development

    PubMed Central

    2013-01-01

    Background Accidental exposure of oocyte/cumulus complex to endometriotic fluid is not uncommon during oocyte retrieval. Only two studies were available on this subject and they gave conflicting results. In this study, we used a mouse model to evaluate the effect of controlled exposure of oocytes to ovarian endometriotic fluid. Methods Mouse oocytes/cumulus complexes (n = 862) were divided into 4 groups, and were exposed to endometriotic fluid (group 1), pooled sera from subjects without endometrioma (group 2), phosphate-buffered saline (group 3), and fertilization medium (controls). After five minutes, oocytes were washed and inseminated. Embryo development was observed daily. The quality of hatching blastocysts was assessed by counting the number of inner cell mass (ICM) and trophectoderm (TE) cells. Results The fertilization, cleavage and blastocyst formation rates in the four groups were not statistically different. The proportions of hatching/hatched blastocysts from fertilized oocytes in groups 1 and 2 were significantly lower than those in group 3 and controls (P = 0.015). Hatching blastocysts from all groups showed no significant difference in the number of ICM and TE cells. Conclusions Exposure of mouse oocytes/cumulus complexes to endometriotic fluid had subtle detrimental effects on subsequent blastocyst development. However, one should be cautious in projecting the results of this study to contaminated human oocytes in a clinical setting. PMID:23332096

  4. Effect of scanning beam size on the lateral resolution of mouse retinal imaging with SLO

    PubMed Central

    Zhang, Pengfei; Goswami, Mayank; Zam, Azhar; Pugh, Edward N.; Zawadzki, Robert J.

    2016-01-01

    Scanning laser ophthalmoscopy (SLO) employs the eye’s optics as a microscope objective for retinal imaging in vivo. The mouse retina has become an increasingly important object for investigation of ocular disease and physiology with optogenetic probes. SLO imaging of the mouse eye, in principle, can achieve submicron lateral resolution thanks to a numerical aperture (NA) of ~0.5, about 2.5 times larger than that of the human eye. In the absence of adaptive optics, however, natural ocular aberrations limit the available optical resolution. The use of a contact lens, in principle, can correct many aberrations, permitting the use of a wider scanning beam and, thus, achieving greater resolution then would otherwise be possible. In this Letter, using an SLO equipped with a rigid contact lens, we report the effect of scanning beam size on the lateral resolution of mouse retinal imaging. Theory predicts that the maximum beam size full width at half-maximum (FWHM) that can be used without any deteriorating effects of aberrations is ~0.6 mm. However, increasing the beam size up to the diameter of the dilated pupil is predicted to improve lateral resolution, though not to the diffraction limit. To test these predictions, the dendrites of a retinal ganglion cell expressing YFP were imaged, and transverse scans were analyzed to quantify the SLO system resolution. The results confirmed that lateral resolution increases with the beam size as predicted. With a 1.3 mm scanning beam and no high-order aberration correction, the lateral resolution is ~1.15 μm, superior to that achievable by most human AO-SLO systems. Advantages of this approach include stabilization of the mouse eye and simplified optical design. PMID:26670523

  5. Effect of scanning beam size on the lateral resolution of mouse retinal imaging with SLO.

    PubMed

    Zhang, Pengfei; Goswami, Mayank; Zam, Azhar; Pugh, Edward N; Zawadzki, Robert J

    2015-12-15

    Scanning laser ophthalmoscopy (SLO) employs the eye's optics as a microscope objective for retinal imaging in vivo. The mouse retina has become an increasingly important object for investigation of ocular disease and physiology with optogenetic probes. SLO imaging of the mouse eye, in principle, can achieve submicron lateral resolution thanks to a numerical aperture (NA) of ∼0.5, about 2.5 times larger than that of the human eye. In the absence of adaptive optics, however, natural ocular aberrations limit the available optical resolution. The use of a contact lens, in principle, can correct many aberrations, permitting the use of a wider scanning beam and, thus, achieving greater resolution then would otherwise be possible. In this Letter, using an SLO equipped with a rigid contact lens, we report the effect of scanning beam size on the lateral resolution of mouse retinal imaging. Theory predicts that the maximum beam size full width at half-maximum (FWHM) that can be used without any deteriorating effects of aberrations is ∼0.6  mm. However, increasing the beam size up to the diameter of the dilated pupil is predicted to improve lateral resolution, though not to the diffraction limit. To test these predictions, the dendrites of a retinal ganglion cell expressing YFP were imaged, and transverse scans were analyzed to quantify the SLO system resolution. The results confirmed that lateral resolution increases with the beam size as predicted. With a 1.3 mm scanning beam and no high-order aberration correction, the lateral resolution is ∼1.15  μm, superior to that achievable by most human AO-SLO systems. Advantages of this approach include stabilization of the mouse eye and simplified optical design. PMID:26670523

  6. Evaluation of neuronal protective effects of xanthine oxidoreductase inhibitors on severe whole-brain ischemia in mouse model and analysis of xanthine oxidoreductase activity in the mouse brain.

    PubMed

    Suzuki, Go; Okamoto, Ken; Kusano, Teruo; Matsuda, Yoko; Fuse, Akira; Yokota, Hiroyuki

    2015-01-01

    Global cerebral ischemia and reperfusion (I/R) often result in high mortality. Free radicals play an important role in global cerebral I/R. Xanthine oxidoreductase (XOR) inhibitors, such as allopurinol, have been reported to protect tissues from damage caused by reactive oxygen species (ROS) by inhibiting its production through XOR inhibition. The recently introduced XOR inhibitor febuxostat, which is a more potent inhibitor than allopurinol, is expected to decrease free radical production more effectively. Here, we analyzed the effects of allopurinol and febuxostat in decreasing global severe cerebral I/R damage in mice. Mice were divided into three groups: a placebo group, an allopurinol group, and a febuxostat group. Pathological examinations, which were performed in each group in the CA1 and CA2 regions of the hippocampus 4 days after I/R surgery, revealed that there was a decrease in the number of neuronal cells in the 14-min occlusion model in both regions and that drugs that were administered to prevent this damage were not effective. The enzymatic activity was extremely low in the mouse brain, and XOR could not be detected in the nonischemic and ischemic mice brains with western blot analyses. Thus, one of the reasons for the decreased effectiveness of XOR inhibitors in controlling severe whole-brain ischemia in a mouse model was the low levels of expression of XOR in the mouse brain. PMID:25744353

  7. Immunostimulatory effect of spinach aqueous extract on mouse macrophage-like J774.1 cells and mouse primary peritoneal macrophages.

    PubMed

    Ishida, Momoko; Ose, Saya; Nishi, Kosuke; Sugahara, Takuya

    2016-07-01

    We herein report the immunostimulatory effect of spinach aqueous extract (SAE) on mouse macrophage-like J774.1 cells and mouse primary peritoneal macrophages. SAE significantly enhanced the production of interleukin (IL)-6 and tumor necrosis factor-α by both J774.1 cells and peritoneal macrophages by enhancing the expression levels of these cytokine genes. In addition, the phagocytosis activity of J774.1 cells was facilitated by SAE. Immunoblot analysis revealed that SAE activates mitogen-activated protein kinase and nuclear factor-κB cascades. It was found that SAE activates macrophages through not only TLR4, but also other receptors. The production of IL-6 was significantly enhanced by peritoneal macrophages from SAE-administered BALB/c mice, suggesting that SAE has a potential to stimulate macrophage activity in vivo. Taken together, these data indicate that SAE would be a beneficial functional food with immunostimulatory effects on macrophages. PMID:27095137

  8. Effect of different cryoprotectant agents on spermatogenesis efficiency in cryopreserved and grafted neonatal mouse testicular tissue.

    PubMed

    Yildiz, Cengiz; Mullen, Brendan; Jarvi, Keith; McKerlie, Colin; Lo, Kirk C

    2013-08-01

    Restoration of male fertility associated with use of the cryopreserved testicular tissue would be a significant advance in human and animal assisted reproductive technology. The purpose of this study was to test the effects of four different cryoprotectant agents (CPA) on spermatogenesis and steroidogenesis in cryopreserved and allotransplanted neonatal mouse testicular tissue. Hank's balanced salt solution (HBSS) with 5% fetal bovine serum including either 0.7 M dimethyl sulfoxide (DMSO), 0.7 M propylene glycol (PrOH), 0.7 M ethylene glycol (EG), or glycerol was used as the cryoprotectant solution. Donor testes were collected and dissected from neonatal pups of CD-1 mice (one day old). Freezing and seeding of the testicular whole tissues was performed using an automated controlled-rate freezer. Four fresh (non-frozen) or frozen-thawed pieces of testes were subcutaneously grafted onto the hind flank of each castrated male NCr nude recipient mouse and harvested after 3 months. Fresh neonatal testes grafts recovered from transplant sites had the most advanced rate of spermatogenesis with elongated spermatid and spermatozoa in 46.6% of seminiferous tubules and had higher levels of serum testosterone compared to all other frozen-thawed-graft groups (p<0.05). Fresh grafts and frozen-thawed grafts in the DMSO group had the highest rate of tissue survival compared to PrOH, EG, and glycerol after harvesting (p>0.05). The most effective CPA for the freezing and thawing of neonatal mouse testes was DMSO in comparison with EG (p<0.05) in both pre-grafted and post-grafted tissues based on histopathological evaluation. Likewise, the highest level of serum testosterone was obtained from the DMSO CPA group compared to all other cryoprotectants evaluated (p<0.05). The typical damage observed in the frozen-thawed grafts included disruption of the interstitial stroma, intercellular connection ruptures, and detachment of spermatogonia from the basement membrane. These findings

  9. Application of mouse model for effective evaluation of foot-and-mouth disease vaccine.

    PubMed

    Lee, Seo-Yong; Ko, Mi-Kyeong; Lee, Kwang-Nyeong; Choi, Joo-Hyung; You, Su-Hwa; Pyo, Hyun-Mi; Lee, Myoung-Heon; Kim, Byounghan; Lee, Jong-Soo; Park, Jong-Hyeon

    2016-07-19

    Efficacy evaluation of foot-and-mouth disease (FMD) vaccines has been conducted in target animals such as cows and pigs. In particular, handling FMD virus requires a high level of biosafety management and facilities to contain the virulent viruses. The lack of a laboratory animal model has resulted in inconvenience when it comes to using target animals for vaccine evaluation, bringing about increased cost, time and labor for the experiments. The FMD mouse model has been studied, but most FMD virus (FMDV) strains are not known to cause disease in adult mice. In the present study, we created a series of challenge viruses that are lethal to adult C57BL/6 mice. FMDV types O, A, and Asia1, which are related to frequent FMD outbreaks, were adapted for mice and the pathogenesis of each virus was evaluated in the mouse model. Challenge experiments after vaccination using in-house and commercial vaccines demonstrated vaccine-mediated protection in a dose-dependent manner. In conclusion, we propose that FMD vaccine evaluation should be carried out using mouse-adapted challenge viruses as a swift, effective efficacy test of experimental or commercial vaccines. PMID:27340094

  10. Effect of mycotoxin-containing diets on epigenetic modifications of mouse oocytes by fluorescence microscopy analysis.

    PubMed

    Zhu, Cheng-Cheng; Hou, Yan-Jun; Han, Jun; Liu, Hong-Lin; Cui, Xiang-Shun; Kim, Nam-Hyung; Sun, Shao-Chen

    2014-08-01

    Mycotoxins, such as aflatoxin (AF), fumonisin B1, zearalenone (ZEA), and deoxynivalenol (DON), are commonly found in many food commodities. Mycotoxins have been shown to increase DNA methylation levels in a human intestinal cell line. We previously showed that the developmental competence of oocytes was affected in mice that had been fed a mycotoxin-containing diet. In this study, we explored possible mechanisms of low mouse oocyte developmental competence after mycotoxin treatment in an epigenetic modification perspective. Mycotoxin-contaminated maize (DON at 3,875 μg/kg, ZEA at 1,897 μg/kg, and AF at 806 μg/kg) was included in diets at three different doses (mass percentage: 0, 15, and 30%) and fed to mice for 4 weeks. The fluorescence intensity analysis showed that the general DNA methylation levels increased in oocytes from high dose mycotoxin-fed mice. Mouse oocyte histone methylation was also altered. H3K9me3 and H4K20me3 level increased in oocytes from mycotoxin-fed mice, whereas H3K27me3 and H4K20me2 level decreased in oocytes from mycotoxin-fed mice. Thus, our results indicate that naturally occurring mycotoxins have effects on epigenetic modifications in mouse oocytes, which may be one of the reasons for reduced oocyte developmental competence. PMID:24810297

  11. Additive effect of Zfhx3/Atbf1 and Pten deletion on mouse prostatic tumorigenesis

    PubMed Central

    Sun, Xiaodong; Xing, Changsheng; Fu, Xiaoying; Li, Jie; Zhang, Baotong; Frierson, Henry F.; Dong, Jin-Tang

    2016-01-01

    The phosphatase and tensin homolog (PTEN) and the zinc finger homeobox 3 (ZFHX3)/AT-motif binding factor 1 (ATBF1) genes have been established as tumor suppressor genes in prostate cancer by their frequent deletions and mutations in human prostate cancer and by the formation of mouse prostatic intraepithelial neoplasia (mPIN) or tumor by their deletions in mouse prostates. However, whether ZFHX3/ATBF1 deletion together with PTEN deletion facilitates prostatic tumorigenesis is unknown. In this study, we simultaneously deleted both genes in mouse prostatic epithelia and performed histological and molecular analyses. While deletion of one Pten allele alone caused low-grade (LG) mPIN as previously reported, concurrent deletion of Zfhx3/Atbf1 promoted the progression to high-grade (HG) mPIN or early carcinoma. Zfhx3/Atbf1 and Pten deletions together increased cell proliferation, disrupted the smooth muscle layer between epithelium and stroma, and increased the number of apoptotic cells. Deletion of both genes also accelerated the activation of Akt and Erk1/2 oncoproteins. These results suggest an additive effect of ZFHX3/ATBF1 and PTEN deletions on the development and progression of prostate neoplasia. PMID:26233892

  12. Calcium channels contribute to albiflorin-mediated antinociceptive effects in mouse model.

    PubMed

    Zhang, Yizhi; Sun, Dejun; Meng, Qingjin; Guo, Wanxu; Chen, Qiuhui; Zhang, Ying

    2016-08-15

    Albiflorin (AF), one of important bioactive constituents of Paeonia lactiflora Radix, possesses neuro-protective effect. The present study aims to investigate the antinociceptive activities of AF and possible mechanisms. AF suppressed acetic acid-caused writhing, lengthened the latency period of mouse in hot plate test, and reduced the licking and biting response time of the injected mouse paw during phase I and phase II, and it suggested that AF exerted the antinociceptive activity mainly through central nervous system. Nimodipine, a commonly used calcium channels blocker, strongly lengthened AF-enhanced latency period of mouse in hot plate test. Compared with control group, AF reduced the levels of euronal nitric oxide synthase (nNOS), and enhanced the levels of serotonin (5-HT) in serum and/or hypothalamus before and after 30-s thermal stimuli. The reduced activation of calmodulin-dependent protein kinase II and c-Jun N-terminal kinase in hypothalamus was observed in AF-treated mice. Collectively, AF-mediated antinociceptive activities were, at least partially, related to calcium channels. PMID:27038516

  13. Tumour effect on arginine/ornithine metabolic relationship in hypertrophic mouse kidney.

    PubMed

    Manteuffel-Cymborowska, M; Chmurzyńska, W; Peska, M; Grzelakowska-Sztabert, B

    1997-03-01

    The presence of a tumour significantly changes nitrogen metabolism, including that of amino acids and polyamines, in host animals. In this study, we examine whether developing tumours affect the metabolic relationship of arginine and ornithine, precursors of polyamines, in the testosterone-induced hypertrophic mouse kidney model. Androgen-induced changes in the activity of enzymes involved with ornithine biosynthesis (arginase), its consumption (ornithine aminotransferase, OAT and ornithine decarboxylase, ODC) and the hypertrophy of host mouse kidney were not affected by the presence of an ascitic tumour (EAC) and only slightly by a mammary carcinoma (MaCa). The HPLC determined renal level of arginine and ornithine showed a striking homeostasis and was disturbed neither by testosterone nor EAC. The effect of MaCa and testosterone on the levels of both amino acids, although significant, was not very pronounced. Developing tumours, especially ascitic, altered the renal activity of OAT and ODC, but not of arginase, in testosterone-untreated mice. All examined tumours, EAC, L 1210 and MaCa actively metabolized arginine and ornithine. the tumour content of arginine which coincided with the activity of arginase, resulted in a marked increase of the ornithine/arginine ratio in tumours, when compared with kidneys. These results indicate that the androgen-induced anabolic response in mouse kidney is preserved, in spite of tumour requirements for essential metabolites. PMID:9062893

  14. Effect of intermittent fasting on prostate cancer tumor growth in a mouse model.

    PubMed

    Thomas, J A; Antonelli, J A; Lloyd, J C; Masko, E M; Poulton, S H; Phillips, T E; Pollak, M; Freedland, S J

    2010-12-01

    Caloric restriction (CR) has been shown to have anti-cancer properties. However, CR may be difficult to apply in humans secondary to compliance and potentially deleterious effects. An alternative is intermittent CR, or in the extreme case intermittent fasting (IF). In a previous small pilot study, we found 2 days per week of IF with ad libitum feeding on the other days resulted in trends toward prolonged survival of mice bearing prostate cancer xenografts. We sought to confirm these findings in a larger study. A total of 100 (7- to 8-week-old) male severe combined immunodeficiency mice were injected subcutaneously with 1 × 10(5) LAPC-4 prostate cancer cells. Mice were randomized to either ad libitum Western Diet (44% carbohydrates, 40% fat and 16% protein) or ad libitum Western Diet with twice-weekly 24 h fasts (IF). Tumor volumes and mouse bodyweights were measured twice weekly. Mice were killed when tumor volumes reached 1000 mm(3). Serum and tumor were collected for analysis of the insulin/insulin-like growth factor 1 (IGF-1) hormonal axis. Overall, there was no difference in mouse survival (P=0.37) or tumor volumes (P ≥ 0.10) between groups. Mouse body weights were similar between arms (P=0.84). IF mice had significantly higher serum IGF-1 levels and IGF-1/IGFBP-3 ratios at killing (P<0.001). However, no difference was observed in serum insulin, IGFBP-3 or tumor phospho-Akt levels (P ≥ 0.39). IF did not improve mouse survival nor did it delay prostate tumor growth. This may be secondary to metabolic adaptations to the 24 h fasting periods. Future studies are required to optimize CR for application in humans. PMID:20733612

  15. Primary Culture of Mouse Dopaminergic Neurons

    PubMed Central

    Gaven, Florence; Marin, Philippe; Claeysen, Sylvie

    2014-01-01

    Dopaminergic neurons represent less than 1% of the total number of neurons in the brain. This low amount of neurons regulates important brain functions such as motor control, motivation, and working memory. Nigrostriatal dopaminergic neurons selectively degenerate in Parkinson's disease (PD). This progressive neuronal loss is unequivocally associated with the motors symptoms of the pathology (bradykinesia, resting tremor, and muscular rigidity). The main agent responsible of dopaminergic neuron degeneration is still unknown. However, these neurons appear to be extremely vulnerable in diverse conditions. Primary cultures constitute one of the most relevant models to investigate properties and characteristics of dopaminergic neurons. These cultures can be submitted to various stress agents that mimic PD pathology and to neuroprotective compounds in order to stop or slow down neuronal degeneration. The numerous transgenic mouse models of PD that have been generated during the last decade further increased the interest of researchers for dopaminergic neuron cultures. Here, the video protocol focuses on the delicate dissection of embryonic mouse brains. Precise excision of ventral mesencephalon is crucial to obtain neuronal cultures sufficiently rich in dopaminergic cells to allow subsequent studies. This protocol can be realized with embryonic transgenic mice and is suitable for immunofluorescence staining, quantitative PCR, second messenger quantification, or neuronal death/survival assessment. PMID:25226064

  16. Metabolic Effects of Bariatric Surgery in Mouse Models of Circadian Disruption

    PubMed Central

    Arble, Deanna M.; Sandoval, Darleen A.; Turek, Fred W.; Woods, Stephen C.; Seeley, Randy J.

    2015-01-01

    Background/Objectives Mounting evidence supports a link between circadian disruption and metabolic disease. Humans with circadian disruption (e.g., night-shift workers) have an increased risk of obesity and cardiometabolic diseases compared to the non-disrupted population. However, it is unclear if the obesity and obesity-related disorders associated with circadian disruption respond to therapeutic treatments as well as individuals with other types of obesity. Subjects/Methods Here, we test the effectiveness of the commonly used bariatric surgical procedure, Vertical Sleeve Gastrectomy (VSG) in mouse models of genetic and environmental circadian disruption. Results VSG led to a reduction in body weight and fat mass in both ClockΔ19 mutant and constant-light mouse models (P < .05), resulting in an overall metabolic improvement independent of circadian disruption. Interestingly, the decrease in body weight occurred without altering diurnal feeding or activity patterns (P > .05). Within circadian-disrupted models, VSG also led to improved glucose tolerance and lipid handling (P < .05). Conclusions Together these data demonstrate that VSG is an effective treatment for the obesity associated with circadian disruption, and that the potent effects of bariatric surgery are orthogonal to circadian biology. However, since the effects of bariatric surgery are independent of circadian disruption, VSG cannot be considered a cure for circadian disruption. These data have important implications for circadian-disrupted obese patients. Moreover, these results reveal new information about the metabolic pathways governing the effects of bariatric surgery as well as of circadian disruption. PMID:25869599

  17. Effect of Delta-9-Tetrahydrocannabinol on Mouse Resistance to Systemic Candida albicans Infection

    PubMed Central

    Blumstein, Gideon W.; Parsa, Arya; Park, Anthony K.; McDowell, Beverly L. P.; Arroyo-Mendoza, Melissa; Girguis, Marie; Adler-Moore, Jill P.; Olson, Jon; Buckley, Nancy E.

    2014-01-01

    Delta-9-tetrahydrocannabinol (Δ9-THC), the psychoactive component of marijuana, is known to suppress the immune responses to bacterial, viral and protozoan infections, but its effects on fungal infections have not been studied. Therefore, we investigated the effects of chronic Δ9-THC treatment on mouse resistance to systemic Candida albicans (C. albicans) infection. To determine the outcome of chronic Δ9-THC treatment on primary, acute systemic candidiasis, c57BL/6 mice were given vehicle or Δ9-THC (16 mg/kg) in vehicle on days 1–4, 8–11 and 15–18. On day 19, mice were infected with 5×105 C. albicans. We also determined the effect of chronic Δ9-THC (4–64 mg/kg) treatment on mice infected with a non-lethal dose of 7.5×104 C. albicans on day 2, followed by a higher challenge with 5×105 C. albicans on day 19. Mouse resistance to the infection was assessed by survival and tissue fungal load. Serum cytokine levels were determine to evaluate the immune responses. In the acute infection, chronic Δ9-THC treatment had no effect on mouse survival or tissue fungal load when compared to vehicle treated mice. However, Δ9-THC significantly suppressed IL-12p70 and IL-12p40 as well as marginally suppressed IL-17 versus vehicle treated mice. In comparison, when mice were given a secondary yeast infection, Δ9-THC significantly decreased survival, increased tissue fungal burden and suppressed serum IFN-γ and IL-12p40 levels compared to vehicle treated mice. The data showed that chronic Δ9-THC treatment decreased the efficacy of the memory immune response to candida infection, which correlated with a decrease in IFN-γ that was only observed after the secondary candida challenge. PMID:25057822

  18. Combined effects of social stress and liver fluke infection in a mouse model.

    PubMed

    Avgustinovich, Damira F; Marenina, Mariya K; Zhanaeva, Svetlana Ya; Tenditnik, Mikhail V; Katokhin, Alexey V; Pavlov, Konstantin S; Sivkov, Anton Yu; Vishnivetskaya, Galina B; Lvova, Maria N; Tolstikova, Tatiana G; Mordvinov, Viatcheslav A

    2016-03-01

    The effects of two influences, social stress and acute opisthorchiasis, were investigated in inbred C57BL/6J male mice. In the model of social stress, mice were repeatedly attacked and defeated by aggressive outbred ICR male mice and were in continuous sensory contact with an aggressive conspecific mouse in their home cage for 20 days. Acute opisthorchiasis was provoked by invasion of Opisthorchis felineus (50 larvae per animal) on the fourth day after the social stress was induced. Simultaneous action of both factors caused the hypertrophy of adrenal glands, as well as elevated the activity of cathepsins B and L in the spleen. This effect on the activity of the cysteine proteases in the hippocampus and hypothalamus following O. felineus invasion was the predominant result of simultaneous action with social stress. Acute opisthorchiasis, social stress, and their combination caused an increase in the level of blood IL-6 in approximately 30% of the animals. Social stress induced a more pronounced effect on mouse plus-maze behavior than O. felineus invasion. Our results suggest a more severe negative effect of the simultaneous influence of both factors on most of the parameters that were investigated. PMID:26778779

  19. Experimenter effects on behavioral test scores of eight inbred mouse strains under the influence of ethanol

    PubMed Central

    Bohlen, Martin; Hayes, Erika R.; Bohlen, Benjamin; Bailoo, Jeremy; Crabbe, John C.; Wahlsten, Douglas

    2016-01-01

    Eight standard inbred mouse strains were evaluated for ethanol effects on a refined battery of behavioral tests in a study that was originally designed to assess the influence of rat odors in the colony on mouse behaviors. As part of the design of the study, two experimenters conducted the tests, and the study was carefully balanced so that equal numbers of mice in all groups and times of day were tested by each experimenter. A defect in airflow in the facility compromised the odor manipulation, and in fact the different odor exposure groups did not differ in their behaviors. The two experimenters, however, obtained markedly different results for three of the tests. Certain of the experimenter effects arose from the way they judged behaviors that were not automated and had to be rated by the experimenter, such as slips on the balance beam. Others were not evident prior to ethanol injection but had a major influence after the injection. For several measures, the experimenter effects were notably different for different inbred strains. Methods to evaluate and reduce the impact of experimenter effects in future research are discussed. PMID:24933191

  20. NMR estimation of protective effect of insulin on mouse liver with epinephrine-induced metabolic lesions.

    PubMed

    Yushmanov, V E; Khristianovich, D S; Rozantseva, T V; Sibeldina, L A

    1991-08-01

    In order to study the effects of epinephrine and insulin on liver metabolism, measurements of cellular phosphates and intracellular pH by 31PNMR, of glycogen by 13C NMR and of lactate by 1H NMR were performed in freshly dissected mouse liver at 0-4 degrees C and in ethanolic liver extracts. The injection of epinephrine hydrochloride (0.1 mL of 0.1% solution i.p. per mouse) caused remarkable changes in liver metabolic profiles which were expressed most distinctly in 15-30 min and could not be attributed solely to epinephrine-induced hyperglycemia. Among these metabolic changes are falls in the levels of ATP and uridine diphosphate sugars by 60-70%, possibly related to glycogen depletion, and intracellular acidification by 0.5 units attributed to the release of protons during hydrolysis of ATP rather than to accumulation of lactate in anaerobic glycolysis. Insulin injected prior to epinephrine (4 units i.p.) markedly suppressed epinephrine-induced metabolic alterations, although the effect of the combination of insulin and epinephrine was not the sum of the separate effects of these hormones. The maximum protective effect of insulin was reached when insulin was injected 15 min prior to epinephrine. The results obtained demonstrate the applicability of NMR for evaluating the protective activity of modifiers at various extreme exposures. PMID:1931556

  1. Short-term effects of fluoride and strontium on bone formation and resorption in the mouse.

    PubMed

    Marie, P J; Hott, M

    1986-06-01

    The early effects of sodium fluoride (0.80 mg/kg/d) and strontium chloride (0.27%) given alone, or in combination in drinking water, on bone metabolism were examined in the mouse using dynamic histomorphometric methods. Four weeks of oral strontium supplementation increased the osteoid surface and reduced the number of acid phosphatase-stained osteoclasts. However the trabecular calcified bone volume was not augmented. By contrast, short-term treatment with fluoride produced a rapid stimulatory effect on bone formation at a dose that did not affect the bone mineralization rate. Four weeks of fluoride supplementation induced a rapid 21.1% increase in the osteoblastic surface and a 26.3% stimulation of the bone matrix apposition rate evaluated by the double tritiated proline labelling method, which resulted in a 29% increase in the amount of osteoid. This rapid stimulation of the bone formation rate without detectable change in osteoclastic bone resorption led to a 12% increase in the trabecular calcified bone density. This study shows that fluoride and strontium produce distinct early effects on bone formation and resorption in the mouse and that fluoride exerts a rapid stimulatory effect on the bone matrix synthesis rate through an augmentation of the number of bone-forming cells. PMID:3713515

  2. Toxic effects of HT-2 toxin on mouse oocytes and its possible mechanisms.

    PubMed

    Zhu, Cheng-Cheng; Zhang, Yue; Duan, Xing; Han, Jun; Sun, Shao-Chen

    2016-06-01

    T-2 toxin is one of the type A trichothecene mycotoxins that is considered to be the most toxic of the trichothecenes. T-2 toxin has been shown to exert various toxic effects in farm animals and humans, as it induces lesions in the brain and in lymphoid, hematopoietic, and gastrointestinal tissues. HT-2 toxin is the major metabolite of T-2 toxin. There is little information regarding the effects of HT-2 toxin on the female reproductive system, particularly oocyte maturation. Thus, in this study, we investigated the toxic effects of HT-2 on mouse oocyte maturation and its possible mechanisms of action. HT-2 toxin exposure disrupted oocyte maturation, reduced actin expression in both the oocyte cortex and cytoplasm, and disrupted meiotic spindle morphology by reducing p-MAPK protein level. HT-2 toxin exposure also induced oxidative stress and resulted in oocyte apoptosis, as shown by ROS accumulation, increased SOD mRNA level, and the expression of the early apoptosis marker Annexin V and increased caspase-3 and bax mRNA levels. Additionally, HT-2 toxin exposure increased LC3 and ATG12 protein levels and lc3 and atg14 mRNA levels, which indicated that HT-2 toxin induced autophagy in mouse oocytes. We also examined for possible epigenetic modifications. Fluorescence intensity analysis showed that 5mC level increased after HT-2 toxin exposure, whereas H3K9me2 and H3K27me3 levels decreased after HT-2 toxin exposure, which indicated that DNA and histone methylations were altered. Thus, our results indicated that HT-2 toxin exposure reduced mouse oocyte maturation capability by affecting cytoskeletal dynamics, apoptosis/autophagy, oxidative stress, and epigenetic modifications. PMID:26138683

  3. Effect of the secretions from the IUD-bearing uterus on peri-implantation mouse embryos.

    PubMed

    Takeuchi, K; Mori, A; Yamamoto, S; Sonoda, T; Nagata, Y

    1990-06-01

    This study was performed to evaluate the effect of IUD-bearing uterine secretions on peri-implantation mouse embryo. 83% of blastocysts degenerated by 96 hr after co-culture with uterine fluids from the IUD-bearing uterus. This degeneration rate was contrasted to 78% after heat treatment (56 degrees C for 30 min) of the IUD-bearing uterine secretions. These results suggest that embryotoxic agents are present in the fluid of the IUD-bearing uterus, especially in the supernatant component and that these agents may be related to the presence of macrophage or a chemical mediator produced by macrophage. PMID:2361372

  4. Relative biological effectiveness of fast neutrons compared with X-rays: Prenatal mortality in the mouse

    NASA Technical Reports Server (NTRS)

    Friedberg, W.; Hanneman, G. D.; Faulkner, D. N.; Darden, E. B., Jr.

    1972-01-01

    The effects of fission neutrons and of X-rays on the mouse zygote are discussed. Seven-week-old virgin mice were allowed a 12-hour mating opportunity beginning at 7:00 P.M. Between 1:30 and 4:00 P.M., except where indicated otherwise, the females which had mated (vaginal plug) during the night were either irradiated or sham-irradiated. At the time of irradiation the zygotes were in a pronuclear stage. Sixteen days later the mice were killed and the uteri dissected. The number of dead embryos, live embryos, and gross anomalies were determined. Dead embryos were classified as to stage of development.

  5. Effects of mouse genotype on bone wound healing and irradiation-induced delay of healing.

    PubMed

    Glowacki, Julie; Mizuno, Shuichi; Kung, Jason; Goff, Julie; Epperly, Michael; Dixon, Tracy; Wang, Hong; Greenberger, Joel S

    2014-01-01

    We tested the effects of mouse genotype (C57BL/6NHsd, NOD/SCID, SAMR1, and SAMP6) and ionizing irradiation on bone wound healing. Unicortical wounds were made in the proximal tibiae, and the time course of spontaneous healing and effects of irradiation were monitored radiographically and histologically. There was reproducible healing beginning with intramedullary osteogenesis, subsequent bone resorption by osteoclasts, gradual bridging of the cortical wound, and re-population of medullary hematopoietic cells. The most rapid wound closure was noted in SAMR1 mice, followed by SAMP6, C57BL/6NHsd, and NOD/SCID. Ionizing irradiation (20 Gy) to the leg significantly delayed bone wound healing in mice of all four genotypes. Mice with genetically-determined predisposition to early osteopenia (SAMP6) or with immune deficiency (NOD/SCID) had impairments in bone wound healing. These mouse models should be valuable for determining the effects of irradiation on bone healing and also for the design and testing of novel bone growth-enhancing drugs and mitigators of ionizing irradiation. PMID:24632972

  6. Effects of Hemin and Nitrite on Intestinal Tumorigenesis in the A/J Min/+ Mouse Model

    PubMed Central

    Sødring, Marianne; Oostindjer, Marije; Egelandsdal, Bjørg; Paulsen, Jan Erik

    2015-01-01

    Red and processed meats are considered risk factors for colorectal cancer (CRC); however, the underlying mechanisms are still unclear. One cause for the potential link between CRC and meat is the heme iron in red meat. Two pathways by which heme and CRC promotion may be linked have been suggested: fat peroxidation and N-nitrosation. In the present work we have used the novel A/J Min/+ mouse model to test the effects of dietary hemin (a model of red meat), and hemin in combination with nitrite (a model of processed meat) on intestinal tumorigenesis. Mice were fed a low Ca2+ and vitamin D semi-synthetic diet with added hemin and/or nitrite for 8 weeks post weaning, before termination followed by excision and examination of the intestinal tract. Our results indicate that dietary hemin decreased the number of colonic lesions in the A/J Min/+ mouse. However, our results also showed that the opposite occurred in the small intestine, where dietary hemin appeared to stimulate tumor growth. Furthermore, we find that nitrite, which did not have an effect in the colon, appeared to have a suppressive effect on tumor growth in the small intestine. PMID:25836260

  7. Effect of light on global gene expression in the neuroglobin-deficient mouse retina

    PubMed Central

    ILMJÄRV, STEN; REIMETS, RIIN; HUNDAHL, CHRISTIAN ANSGAR; LUUK, HENDRIK

    2014-01-01

    Several previous studies have raised controversy over the functional role of neuroglobin (Ngb) in the retina. Certain studies indicate a significant impact of Ngb on retinal physiology, whereas others are conflicting. The present is an observational study that tested the effect of Ngb deficiency on gene expression in dark- and light-adapted mouse retinas. Large-scale gene expression profiling was performed using GeneChip® Mouse Exon 1.0 ST arrays and the results were compared to publicly available data sets. The lack of Ngb was found to have a minor effect on the light-induced retinal gene expression response. In addition, there was no increase in the expression of marker genes associated with hypoxia, endoplasmic reticulum-stress and oxidative stress in the Ngb-deficient retina. By contrast, several genes were identified that appeared to be differentially expressed between the genotypes when the effect of light was ignored. The present study indicates that Ngb deficiency does not lead to major alternations in light-dependent gene expression response, but leads to subtle systemic differences of a currently unknown functional significance. PMID:25279145

  8. In vitro inhibitory effect of aflatoxin B1 on acetylcholinesterase activity in mouse brain.

    PubMed

    Cometa, Maria Francesca; Lorenzini, Paola; Fortuna, Stefano; Volpe, Maria Teresa; Meneguz, Annarita; Palmery, Maura

    2005-01-01

    Growing concern on the problem of mycotoxins in the alimentary chain underlines the need to investigate the mechanisms explaining the cholinergic effects of aflatoxin B(1) (AFB(1)). We examined the effect of AFB(1), a mycotoxin produced by Aspergillus flavus, on mouse brain acetylcholinesterase (AChE) and specifically on its molecular isoforms (G(1) and G(4)) after in vitro exposure. AFB(1) (from 10(-9) to 10(-4)M), inhibited mouse brain AChE activity (IC(50) = 31.6 x 10(-6)M) and its G(1) and G(4) molecular isoforms in a dose-dependent manner. Michaelis-Menten parameters indicate that the K(m) value increased from 55.2 to 232.2% whereas V(max) decreased by 46.2-75.1%. The direct, the Lineweaver-Burk and the secondary plots indicated a non-competitive-mixed type antagonism, induced when the inhibitor binds to the free enzyme and to the enzyme-substrate complex. AFB(1)-inhibited AChE was partially reactivated by pyridine 2-aldoxime (2-PAM) (10(-4)M) but the AChE-inhibiting time courses of AFB(1) (10(-4)M) and diisopropylfluorophosphate (DFP) (2 x 10(-7)M) differed. Overall these data suggest that AFB(1) non-competitively inhibits mouse brain AChE by blocking access of the substrate to the active site or by inducing a defective conformational change in the enzyme through non-covalent binding interacting with the AChE peripheral binding site, or through both mechanisms. PMID:15590113

  9. Comparative late effects of X-rays and negative pimesons on the mouse kidney.

    PubMed Central

    Jordan, S. W.; Yuhas, J. M.; Key, C. R.; Hogstrom, K. R.; Butler, J. L.; Kligerman, M. M.

    1979-01-01

    A system is described for comparing various modalities and fractionation schedules of radiation by means of their long-term morphologic effects upon the mouse kidney. The comparison system utilizes a grading scale for histopathologic changes in which a given histologic grade depends upon meeting defined threshold criteria, rather than quantitation of a particular measurement. Renal tubular alterations served as the basis for comparison, since they appeared more reliably defined than glomerular changes. The radiation dose that induced a specific threshold effect in kidneys from 50% of the animals at 6 months was defined as the effective dose-50%, or ED50.ED50 was found for x-rays and negative pimesons administered in 1, 2, or 5 fractions. From these data, the relative biologic effectiveness (RBE) of negative pi-mesons with respect to x-rays was determined for each fractionation schedule. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:525675

  10. Contribution of dietary and loading changes to the effects of suspension on mouse femora

    NASA Technical Reports Server (NTRS)

    Simske, S. J.; Broz, J. J.; Fleet, M. L.; Schmeister, T. A.; Gayles, E. C.; Luttges, M. W.; Spooner, B. S. (Principal Investigator)

    1994-01-01

    The present study assessed the contributions of feeding changes and unloading to the overall measured effects of 2-wk hindlimb (Tail) suspension on the mouse femora. Feeding changes were addressed by considering the effects of matched feeding among suspended and control mice. The effects of hind limb unloading were considered by comparing suspended mice to mice equipped identically (though not suspended) and matched-fed. The feeding and unloading aspects of suspension appear to cause distinctly differing effects on the stereotypic modeling of the femora. Matched-feeding was accompanied by increased resorption surface in comparison to suspended mice, while unloading led to reduced bone formation at the mid-diaphysis of the femora. Reduced mineral content was observed in the bones of suspended mice when compared to the other mice groups, but without increased resorption surface. Thus, the unloading aspects of the antiorthostatic suspension protocol apparently causes reduced formation and mineralization in the femur.

  11. Thermoregulatory effects of intraventricular injection of noradrenaline in the mouse and the influence of ambient temperature

    PubMed Central

    Handley, Sheila L.; Spencer, P. S. J.

    1972-01-01

    1. At an ambient temperature of 20° C, intraventricular injection of noradrenaline in the mouse resulted in hypothermia accompanied by a fall in metabolic rate and by cutaneous vasodilatation. Subcutaneous injection of noradrenaline resulted in hyperthermia with raised metabolic rate and cutaneous vasodilatation. 2. The hypothermia and fall in oxygen consumption rate following intraventricular noradrenaline were prevented by pre-treatment with subcutaneous propranolol, while the cutaneous vasodilatation was un-affected. However, the effects of subcutaneously injected noradrenaline were completely abolished by subcutaneous propranolol. Intraventricular propranolol did not modify the hypothermic effect of intraventricular noradrenaline. 3. The direction of the effect on body temperature of intraventricular noradrenaline was dependent upon ambient temperature; hypothermia occurring at low (15° C) and hyperthermia at high (36° C) ambient temperatures. However, when the possibility of any peripheral action of noradrenaline escaping into the systemic circulation was prevented by prior subcutaneous injection of propranolol, significant hypothermia could be detected at temperatures as high as 32° C. 4. The possibility that the effects of intraventricular noradrenaline could be due to complete abolition of central temperature regulation was further excluded by the occurrence of thermal salivation in all animals during experiments performed at 36° C. 5. It is suggested that, in the mouse, the hypothermic actions of intraventricular noradrenaline are due to a central effect, while its hyperthermic effects at high ambient temperature are due to escape of noradrenaline into the peripheral circulation. The hypothermia could be the result of selective activation of central heat loss mechanisms. 6. Intraventricular noradrenaline was without effect on brain plasma-space although exposure to 100% oxygen caused a detectable fall. PMID:5045735

  12. Effects of Low-Dose Diethylstilbestrol Exposure on DNA Methylation in Mouse Spermatocytes

    PubMed Central

    Yin, Li; Zheng, Li-juan; Jiang, Xiao; Liu, Wen-bin; Han, Fei; Cao, Jia; Liu, Jin-yi

    2015-01-01

    Evidence from previous studies suggests that the male reproductive system can be disrupted by fetal or neonatal exposure to diethylstilbestrol (DES). However, the molecular basis for this effect remains unclear. To evaluate the effects of DES on mouse spermatocytes and to explore its potential mechanism of action, the levels of DNA methyltransferases (DNMTs) and DNA methylation induced by DES were detected. The results showed that low doses of DES inhibited cell proliferation and cell cycle progression and induced apoptosis in GC-2 cells, an immortalized mouse pachytene spermatocyte-derived cell line, which reproduces primary cells responses to E2. Furthermore, global DNA methylation levels were increased and the expression levels of DNMTs were altered in DES-treated GC-2 cells. A total of 141 differentially methylated DNA sites were detected by microarray analysis. Rxra, an important component of the retinoic acid signaling pathway, and mybph, a RhoA pathway-related protein, were found to be hypermethylated, and Prkcd, an apoptosis-related protein, was hypomethylated. These results showed that low-dose DES was toxic to spermatocytes and that DNMT expression and DNA methylation were altered in DES-exposed cells. Taken together, these data demonstrate that DNA methylation likely plays an important role in mediating DES-induced spermatocyte toxicity in vitro. PMID:26588706

  13. Effects of heavy ion to the primary culture of mouse brain cells

    NASA Technical Reports Server (NTRS)

    Nojima, Kumie; Nakadai, Taeko; Kohno, Yukio; Vazquez, Marcelo E.; Yasuda, Nakahiro; Nagaoka, Shunji

    2004-01-01

    To investigate effects of low dose heavy particle radiation to CNS system, we adopted mouse neonatal brain cells in culture being exposed to heavy ions by HIMAC at NIRS and NSRL at BNL. The applied dose varied from 0.05 Gy up to 2.0 Gy. The subsequent biological effects were evaluated by an induction of apoptosis and neuron survival focusing on the dependencies of the animal strains, SCID, B6, B6C3F1, C3H, used for brain cell culture, SCID was the most sensitive and C3H the least sensitive to particle radiation as evaluated by 10% apoptotic criterion. The LET dependency was compared with using SCID and B6 cells exposing to different ions (H, C, Ne, Si, Ar, and Fe). Although no detectable LET dependency was observed in the high LET (55-200 keV/micrometers) and low dose (<0.5 Gy) regions. The survivability profiles of the neurons were different in the mouse strains and ions. In this report, a result of memory and learning function to adult mice after whole-body and brain local irradiation at carbon ion and iron ion.

  14. Comparing the Effects of Isoflurane and Alpha Chloralose upon Mouse Physiology.

    PubMed

    Low, Lucie A; Bauer, Lucy C; Klaunberg, Brenda A

    2016-01-01

    Functional magnetic resonance imaging of mice requires that the physiology of the mouse (body temperature, respiration and heart rates, blood pH level) be maintained in order to prevent changes affecting the outcomes of functional scanning, namely blood oxygenation level dependent (BOLD) measures and cerebral blood flow (CBF). The anesthetic used to sedate mice for scanning can have major effects on physiology. While alpha chloralose has been commonly used for functional imaging of rats, its effects on physiology are not well characterized in the literature for any species. In this study, we anesthetized or sedated mice with isoflurane or alpha chloralose for up to two hours, and monitored physiological parameters and arterial blood gasses. We found that, when normal body temperature is maintained, breathing rates for both drugs decrease over the course of two hours. In addition, alpha chloralose causes a substantial drop in heart rate and blood pH with severe hypercapnia (elevated blood CO2) that is not seen in isoflurane-treated animals. We suggest that alpha chloralose does not maintain normal mouse physiology adequately for functional brain imaging outcome measures. PMID:27148970

  15. Effects of Varied Housing Density on a Hybrid Mouse Strain Followed for 20 Months.

    PubMed

    Paigen, Beverly; Currer, Joanne M; Svenson, Karen L

    2016-01-01

    To evaluate the effect of increased housing density in a hybrid mouse strain, we evaluated a panel of physiological and behavioral traits in animals that were housed in groups of 3, 5, 8, or 12, using cages that provide 78.1 in2 of floor space. Such groupings resulted in cage densities that ranged from half to almost twice the density recommended by the Guide for the Care and Use of Laboratory Animals. While previous studies have investigated physiological effects of increased housing density using inbred mouse strains, including C57BL/6J and 129S1/SvImJ, this study tested an F1 hybrid population of C57BL/6J x 129S1/SvImJ for changes resulting from either decreased or increased housing density. Mice were followed until they were 20 months old, a substantially longer duration than has been used in previous density studies. We evaluated mortality, growth, home cage behavior, blood pressure, body composition, clinical plasma chemistries, immune function, and organ weights (heart, kidney, adrenal glands, and testes) as endpoints of chronic stress that may arise from sub-optimal housing conditions. Few statistically different parameters were observed in this study, none of which describe chronic stress and all within normal physiological ranges for research mice, suggesting that this hybrid strain was not adversely affected by housing at twice the density currently recommended. PMID:26900840

  16. Modafinil Abrogates Methamphetamine-Induced Neuroinflammation and Apoptotic Effects in the Mouse Striatum

    PubMed Central

    Goitia, Belen; Garcia-Rill, Edgar; Krasnova, Irina N.; Cadet, Jean Lud; Urbano, Francisco J.; Bisagno, Veronica

    2012-01-01

    Methamphetamine is a drug of abuse that can cause neurotoxic damage in humans and animals. Modafinil, a wake-promoting compound approved for the treatment of sleeping disorders, is being prescribed off label for the treatment of methamphetamine dependence. The aim of the present study was to investigate if modafinil could counteract methamphetamine-induced neuroinflammatory processes, which occur in conjunction with degeneration of dopaminergic terminals in the mouse striatum. We evaluated the effect of a toxic methamphetamine binge in female C57BL/6 mice (4×5 mg/kg, i.p., 2 h apart) and modafinil co-administration (2×90 mg/kg, i.p., 1 h before the first and fourth methamphetamine injections) on glial cells (microglia and astroglia). We also evaluated the striatal expression of the pro-apoptotic BAX and anti-apoptotic Bcl-2 proteins, which are known to mediate methamphetamine-induced apoptotic effects. Modafinil by itself did not cause reactive gliosis and counteracted methamphetamine-induced microglial and astroglial activation. Modafinil also counteracted the decrease in tyrosine hydroxylase and dopamine transporter levels and prevented methamphetamine-induced increases in the pro-apoptotic BAX and decreases in the anti-apoptotic Bcl-2 protein expression. Our results indicate that modafinil can interfere with methamphetamine actions and provide protection against dopamine toxicity, cell death, and neuroinflammation in the mouse striatum. PMID:23056363

  17. Anticonvulsant effects of a triheptanoin diet in two mouse chronic seizure models

    PubMed Central

    Willis, Sarah; Stoll, James; Sweetman, Lawrence; Borges, Karin

    2010-01-01

    We hypothesized that in epileptic brains citric acid cycle intermediate levels may be deficient leading to hyperexcitability. Anaplerosis is the metabolic refilling of deficient metabolites. Our goal was to determine the anticonvulsant effects of feeding triheptanoin, the triglyceride of anaplerotic heptanoate. CF1 mice were fed 0-35% calories from triheptanoin. Body weights and dietary intake were similar in mice fed triheptanoin vs. standard diet. Triheptanoin feeding increased blood propionyl-carnitine levels, signifying its metabolism. 35%, but not 20%, triheptanoin delayed development of corneal kindled seizures. After pilocarpine-induced status epilepticus (SE), triheptanoin feeding increased the pentylenetetrazole tonic seizure threshold during the chronically epileptic stage. Mice in the chronically epileptic stage showed various changes in brain metabolite levels, including a reduction in malate. Triheptanoin feeding largely restored a reduction in propionyl-CoA levels and increased methylmalonyl-CoA levels in SE mice. In summary, triheptanoin was anticonvulsant in two chronic mouse models and increased levels of anaplerotic precursor metabolites in epileptic mouse brains. The mechanisms of triheptanoin's effects and its efficacy in humans suffering from epilepsy remain to be determined. PMID:20691264

  18. Decellularized liver scaffolds effectively support the proliferation and differentiation of mouse fetal hepatic progenitors

    PubMed Central

    Wang, Xiaojun; Cui, Jing; Zhang, Bing-Qiang; Zhang, Hongyu; Bi, Yang; Kang, Quan; Wang, Ning; Bie, Ping; Yang, Zhanyu; Wang, Huaizhi; Liu, Xiangde; Haydon, Rex C; Luu, Hue H; Tang, Ni; Dong, Jiahong; He, Tong-Chuan

    2014-01-01

    Decellularized whole organs represent ideal scaffolds for engineering new organs and/or cell transplantation. Here, we investigate whether decellularized liver scaffolds provide cell-friendly biocompatible three-dimensional environment to support the proliferation and differentiation of hepatic progenitor cells. Mouse liver tissues are efficiently decellularized through portal vein perfusion. Using the reversibly immortalized mouse fetal hepatic progenitor cells (iHPCs), we are able to effectively recellularize the decellularized liver scaffolds. The perfused iHPCs survive and proliferate in the three-dimensional scaffolds in vitro for 2 weeks. When the recellularized scaffolds are implanted into the kidney capsule of athymic nude mice, cell survival and proliferation of the implanted scaffolds are readily detected by whole body imaging for 10 days. Furthermore, EGF is shown to significantly promote the proliferation and differentiation of the implanted iHPCs. Histologic and immunochemical analyses indicate that iHPCs are able to proliferate and differentiate to mature hepatocytes upon EGF stimulation in the scaffolds. The recellularization of the biomaterial scaffolds is accompanied with vascularization. Taken together, these results indicate that decullarized liver scaffolds effectively support the proliferation and differentiation of iHPCs, suggesting that decellularized liver matrix may be used as ideal biocompatible scaffolds for hepatocyte transplantation. PMID:23625886

  19. The effects of cyclooxygenase isozyme inhibition on incisional wound healing in mouse skin.

    PubMed

    Müller-Decker, Karin; Hirschner, Wolfgang; Marks, Friedrich; Fürstenberger, Gerhard

    2002-11-01

    In addition to their proinflammatory activities, prostaglandins recently have been shown to be beneficial in the resolution of tissue injury and inflammation. Thus, inhibition of cyclooxygenase-2, the predominant prostaglandin endoperoxide synthase under these conditions, may not only result in attenuating the inflammatory response but also in delaying tissue regeneration and repair. To this end, we investigated cyclooxygenase isozyme expression and the effects of cyclooxygenase inhibitors on wound healing upon full-thickness incisions in mouse skin. Immunohistochemical analysis revealed prominent expression of cyclooxygenase isozymes in keratinocytes of the hyperplastic epithelium, with cyclooxygenase-1 immunosignals predominating in the suprabasal compartment and cyclooxygenase-2 immunosignals spread throughout the whole epidermis. Moreover, dendritic cells, resembling Langerhans cells, as well as endothelial cells and macrophages in the vicinity of or within the granulation tissue were found to express both isozymes. Inhibition of prostaglandin E2 synthesis by oral administration of the cyclooxygenase-1-selective inhibitor SC-560 or the cyclooxygenase-2-selective inhibitor valdecoxib did not retard wound healing in mouse skin macroscopically. Except for a slight transient retardation of epithelialization early after wounding wound-induced neoangiogenesis, collagen deposition, and the restoration of tensile strength were not delayed by these agents. Likewise, the nonselective inhibitor indomethacin had no effect on the tensile strength of incisional skin wounds. PMID:12445211

  20. Comparing the Effects of Isoflurane and Alpha Chloralose upon Mouse Physiology

    PubMed Central

    Bauer, Lucy C.; Klaunberg, Brenda A.

    2016-01-01

    Functional magnetic resonance imaging of mice requires that the physiology of the mouse (body temperature, respiration and heart rates, blood pH level) be maintained in order to prevent changes affecting the outcomes of functional scanning, namely blood oxygenation level dependent (BOLD) measures and cerebral blood flow (CBF). The anesthetic used to sedate mice for scanning can have major effects on physiology. While alpha chloralose has been commonly used for functional imaging of rats, its effects on physiology are not well characterized in the literature for any species. In this study, we anesthetized or sedated mice with isoflurane or alpha chloralose for up to two hours, and monitored physiological parameters and arterial blood gasses. We found that, when normal body temperature is maintained, breathing rates for both drugs decrease over the course of two hours. In addition, alpha chloralose causes a substantial drop in heart rate and blood pH with severe hypercapnia (elevated blood CO2) that is not seen in isoflurane-treated animals. We suggest that alpha chloralose does not maintain normal mouse physiology adequately for functional brain imaging outcome measures. PMID:27148970

  1. Computational Multiscale Toxicodynamic Modeling of Silver and Carbon Nanoparticle Effects on Mouse Lung Function

    PubMed Central

    Mukherjee, Dwaipayan; Botelho, Danielle; Gow, Andrew J.; Zhang, Junfeng; Georgopoulos, Panos G.

    2013-01-01

    A computational, multiscale toxicodynamic model has been developed to quantify and predict pulmonary effects due to uptake of engineered nanomaterials (ENMs) in mice. The model consists of a collection of coupled toxicodynamic modules, that were independently developed and tested using information obtained from the literature. The modules were developed to describe the dynamics of tissue with explicit focus on the cells and the surfactant chemicals that regulate the process of breathing, as well as the response of the pulmonary system to xenobiotics. Alveolar type I and type II cells, and alveolar macrophages were included in the model, along with surfactant phospholipids and surfactant proteins, to account for processes occurring at multiple biological scales, coupling cellular and surfactant dynamics affected by nanoparticle exposure, and linking the effects to tissue-level lung function changes. Nanoparticle properties such as size, surface chemistry, and zeta potential were explicitly considered in modeling the interactions of these particles with biological media. The model predictions were compared with in vivo lung function response measurements in mice and analysis of mice lung lavage fluid following exposures to silver and carbon nanoparticles. The predictions were found to follow the trends of observed changes in mouse surfactant composition over 7 days post dosing, and are in good agreement with the observed changes in mouse lung function over the same period of time. PMID:24312506

  2. Anticonvulsant effects of a triheptanoin diet in two mouse chronic seizure models.

    PubMed

    Willis, Sarah; Stoll, James; Sweetman, Lawrence; Borges, Karin

    2010-12-01

    We hypothesized that in epileptic brains citric acid cycle intermediate levels may be deficient leading to hyperexcitability. Anaplerosis is the metabolic refilling of deficient metabolites. Our goal was to determine the anticonvulsant effects of feeding triheptanoin, the triglyceride of anaplerotic heptanoate. CF1 mice were fed 0-35% calories from triheptanoin. Body weights and dietary intake were similar in mice fed triheptanoin vs. standard diet. Triheptanoin feeding increased blood propionyl-carnitine levels, signifying its metabolism. 35%, but not 20%, triheptanoin delayed development of corneal kindled seizures. After pilocarpine-induced status epilepticus (SE), triheptanoin feeding increased the pentylenetetrazole tonic seizure threshold during the chronically epileptic stage. Mice in the chronically epileptic stage showed various changes in brain metabolite levels, including a reduction in malate. Triheptanoin feeding largely restored a reduction in propionyl-CoA levels and increased methylmalonyl-CoA levels in SE mice. In summary, triheptanoin was anticonvulsant in two chronic mouse models and increased levels of anaplerotic precursor metabolites in epileptic mouse brains. The mechanisms of triheptanoin's effects and its efficacy in humans suffering from epilepsy remain to be determined. PMID:20691264

  3. Decellularized liver scaffolds effectively support the proliferation and differentiation of mouse fetal hepatic progenitors.

    PubMed

    Wang, Xiaojun; Cui, Jing; Zhang, Bing-Qiang; Zhang, Hongyu; Bi, Yang; Kang, Quan; Wang, Ning; Bie, Ping; Yang, Zhanyu; Wang, Huaizhi; Liu, Xiangde; Haydon, Rex C; Luu, Hue H; Tang, Ni; Dong, Jiahong; He, Tong-Chuan

    2014-04-01

    Decellularized whole organs represent ideal scaffolds for engineering new organs and/or cell transplantation. Here, we investigate whether decellularized liver scaffolds provide cell-friendly biocompatible three-dimensional (3-D) environment to support the proliferation and differentiation of hepatic progenitor cells. Mouse liver tissues are efficiently decellularized through portal vein perfusion. Using the reversibly immortalized mouse fetal hepatic progenitor cells (iHPCs), we are able to effectively recellularize the decellularized liver scaffolds. The perfused iHPCs survive and proliferate in the 3-D scaffolds in vitro for 2 weeks. When the recellularized scaffolds are implanted into the kidney capsule of athymic nude mice, cell survival and proliferation of the implanted scaffolds are readily detected by whole body imaging for 10 days. Furthermore, epidermal growth factor (EGF) is shown to significantly promote the proliferation and differentiation of the implanted iHPCs. Histologic and immunochemical analyzes indicate that iHPCs are able to proliferate and differentiate to mature hepatocytes upon EGF stimulation in the scaffolds. The recellularization of the biomaterial scaffolds is accompanied with vascularization. Taken together, these results indicate that decullarized liver scaffolds effectively support the proliferation and differentiation of iHPCs, suggesting that decellularized liver matrix may be used as ideal biocompatible scaffolds for hepatocyte transplantation. PMID:23625886

  4. Effects of baicalin cream in two mouse models: 2,4-dinitrofluorobenzene-induced contact hypersensitivity and mouse tail test for psoriasis

    PubMed Central

    Wu, Jie; Li, Hong; Li, Ming

    2015-01-01

    Background:Scutellaria baicalensis is a Chinese herbal medicine that has been used for centuries to treat psoriasis. Baicalin is one of the major flavonoids and bioactive components of S. baicalensis and is responsible for the pharmacologic actions of the plant. Objective: This study aimed to investigate the anti-inflammatory effect and keratinocyte differentiation-inducing activity of baicalin in vivo. Methods: Baicalin was formulated into topical creams at concentrations of 1%, 3%, and 5%. The anti-inflammatory effect of baicalin cream was evaluated in 2,4-dinitrofluorobenzene (DNFB)-induced contact hypersensitivity (CHS) mice, and its keratinocyte-modulating action was assessed using the mouse tail model for psoriasis. Results: During the topical application of baicalin cream, no evidence of irritant effect was observed in both tests. In the inflammation model, mice exposed to baicalin cream displayed a reduction in DNFB-induced CHS responses compared with vehicle-treated animals, showing that the topical application of baicalin cream exerted an anti-inflammatory effect. In the second model, baicalin cream dose-dependently increased the orthokeratosis of granular layers and the relative epidermal thickness of mouse tail skin, indicative of the keratinocyte differentiation-inducing activity of this topical preparation. Conclusions: Taking the in vivo findings together, the present study indicated that baicalin cream may be a promising antipsoriatic agent worthy of further investigation for psoriasis treatment. PMID:25932143

  5. Flavanone silibinin treatment attenuates nitrogen mustard-induced toxic effects in mouse skin.

    PubMed

    Jain, Anil K; Tewari-Singh, Neera; Inturi, Swetha; Kumar, Dileep; Orlicky, David J; Agarwal, Chapla; White, Carl W; Agarwal, Rajesh

    2015-05-15

    Currently, there is no effective antidote to prevent skin injuries by sulfur mustard (SM) and nitrogen mustard (NM), which are vesicating agents with potential relevance to chemical warfare, terrorist attacks, or industrial/laboratory accidents. Our earlier report has demonstrated the therapeutic efficacy of silibinin, a natural flavanone, in reversing monofunctional alkylating SM analog 2-chloroethyl ethyl sulfide-induced toxic effects in mouse skin. To translate this effect to a bifunctional alkylating vesicant, herein, efficacy studies were carried out with NM. Topical application of silibinin (1 or 2mg) 30 min after NM exposure on the dorsal skin of male SKH-1 hairless mice significantly decreased NM-induced toxic lesions at 24, 72 or 120 h post-exposure. Specifically, silibinin treatment resulted in dose-dependent reduction of NM-induced increase in epidermal thickness, dead and denuded epidermis, parakeratosis and microvesication. Higher silibinin dose also caused a 79% and 51%reversal in NM-induced increases in myeloperoxidase activity and COX-2 levels, respectively. Furthermore, silibinin completely prevented NM-induced H2A.X phosphorylation, indicating reversal of DNA damage which could be an oxidative DNA damage as evidenced by high levels of 8-oxodG in NM-exposed mouse skin that was significantly reversed by silibinin. Together, these findings suggest that attenuation of NM-induced skin injury by silibinin is due to its effects on the pathways associated with DNA damage, inflammation, vesication and oxidative stress. In conclusion, results presented here support the optimization of silibinin as an effective treatment of skin injury by vesicants. PMID:25791923

  6. Flavanone silibinin treatment attenuates nitrogen mustard-induced toxic effects in mouse skin

    SciTech Connect

    Jain, Anil K.; Tewari-Singh, Neera; Inturi, Swetha; Kumar, Dileep; Orlicky, David J.; Agarwal, Chapla; White, Carl W.; Agarwal, Rajesh

    2015-05-15

    Currently, there is no effective antidote to prevent skin injuries by sulfur mustard (SM) and nitrogen mustard (NM), which are vesicating agents with potential relevance to chemical warfare, terrorist attacks, or industrial/laboratory accidents. Our earlier report has demonstrated the therapeutic efficacy of silibinin, a natural flavanone, in reversing monofunctional alkylating SM analog 2-chloroethyl ethyl sulfide-induced toxic effects in mouse skin. To translate this effect to a bifunctional alkylating vesicant, herein, efficacy studies were carried out with NM. Topical application of silibinin (1 or 2 mg) 30 min after NM exposure on the dorsal skin of male SKH-1 hairless mice significantly decreased NM-induced toxic lesions at 24, 72 or 120 h post-exposure. Specifically, silibinin treatment resulted in dose-dependent reduction of NM-induced increase in epidermal thickness, dead and denuded epidermis, parakeratosis and microvesication. Higher silibinin dose also caused a 79% and 51%reversal in NM-induced increases in myeloperoxidase activity and COX-2 levels, respectively. Furthermore, silibinin completely prevented NM-induced H2A.X phosphorylation, indicating reversal of DNA damage which could be an oxidative DNA damage as evidenced by high levels of 8-oxodG in NM-exposed mouse skin that was significantly reversed by silibinin. Together, these findings suggest that attenuation of NM-induced skin injury by silibinin is due to its effects on the pathways associated with DNA damage, inflammation, vesication and oxidative stress. In conclusion, results presented here support the optimization of silibinin as an effective treatment of skin injury by vesicants. - Highlights: • Silibinin treatment attenuated nitrogen mustard (NM)-induced skin injury. • Silibinin affects pathways associated with DNA damage, inflammation and vesication. • The efficacy of silibinin could also be associated with oxidative stress. • These results support testing and optimization of

  7. [Effects of alkaloids from Coptidis Rhizoma on mouse peritoneal macrophages in vitro].

    PubMed

    Zhou, Xia; Peng, Yao-zong; Huang, Tao; Li, Ling; Mou, Shao-xia; Kou, Shu-ming; Li, Xue-gang

    2015-12-01

    This work was mainly studied the effects of the four alkaloids from Coptidis Rhizoma on the mouse peritoneal macrophages in vitro and preliminarily discussed the regulating mechanisms. The effect of alkaloids from Coptidis Rhizoma on the vitality of macrophages was measured by the MTT assay. The effect of alkaloids on the phagocytosis of macrophages was determined by neutral red trial and respiratory burst activity was tested by NBT. The expressions of respiratory-burst-associated genes influenced by alkaloids were detected by qRT-PCR. The conformation change of membrane protein in macrophages by the impact of alkaloids was studied by fluorospectro-photometer. Results showed that the four alkaloids from Coptidis Rhizoma could increase the phagocytosis of macrophages in different level and berberine had the best effect. Berberine, coptisine and palmatine had up-regulation effects on respiratory burst activity of mouse peritoneal macrophages stimulated by PMA and regulatory activity on the mRNA expression of PKC, p40phox or p47phox, whereas the epiberberine had no significant influence on respiratory burst. Moreover, alkaloids from Coptidis Rhizoma could change the conformation of membrane protein and the berberine showed the strongest activity. The results suggested that the four alkaloids from Coptidis Rhizoma might activate macrophages through changing the conformation of membrane protein of macrophages and then enhanced the phagocytosis and respiratory burst activity of macrophages. Furthermore, the regulatory mechanism of alkaloids on the respiratory burst activity of macrophages may be also related to the expression level of PKC, p40phox and p47phox. PMID:27141680

  8. Inhibitory effect of CGRP on osteoclast formation by mouse bone marrow cells treated with isoproterenol.

    PubMed

    Ishizuka, Kyoko; Hirukawa, Koji; Nakamura, Hiroshi; Togari, Akifumi

    2005-04-29

    The present study was designed to elucidate the mode of action of isoproterenol (Isp; adrenergic beta-agonist) and to characterize the effect of the calcitonin gene-related peptide (CGRP; sensory neuropeptide) on osteoclast formation induced by Isp in a mouse bone marrow culture system. Treatment of mouse bone marrow cells with Isp generated tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells (MNCs) capable of excavating resorptive pits on dentine slices, and caused an increase in receptor activator of NF-kappaB ligand (RANKL) and a decrease in osteoprotegerin (OPG) production by the marrow cells. The osteoclast formation was significantly inhibited by OPG, suggesting the involvement of the RANKL-RANK system. CGRP inhibited the osteoclast formation caused by Isp or soluble RANKL (s-RANKL) but had no influence on RANKL or OPG production by the bone marrow cells treated with Isp, suggesting that CGRP inhibited the osteoclast formation by interfering with the action of RANKL produced by the Isp-treated bone marrow cells without affecting RANKL or OPG production. This in vitro data suggest the physiological interaction of sympathetic and sensory nerves in osteoclastogenesis in vivo. PMID:15814197

  9. The effect of handling method on the mouse grimace scale in two strains of laboratory mice

    PubMed Central

    Leach, Matthew C

    2015-01-01

    Pain assessment in laboratory animals is an ethical and legal requirement. The mouse grimace scale (MGS) is a new method of pain assessment deemed to be both accurate and reliable, and observers can be rapidly trained to use it. In order for a new pain assessment technique to be effective, we must ensure that the score awarded by the technique is only influenced by pain and not by other husbandry or non-painful but integral aspects of research protocols. Here, we studied 16 male mice, housed under standard laboratory conditions. Eight mice were randomly assigned to tail handling and eight to tube handling on arrival at the unit. On each occasion the mice were removed from their cage for routine husbandry, they were picked up using their assigned handling method. Photographs of the mouse faces were then scored by treatment-blind observers as per the MGS manual (see Nature Methods 2010, Vol. 7, pp 447–449), and scores from the two groups were compared. There was no significant difference in MGS scores between the mice that had been handled using a tube compared with the tail. Consequently, these methods of handling did not influence the baseline grimace score given, suggesting that these handling techniques are not confounding factors when establishing baseline MGS scores, further validating this technique. PMID:26657061

  10. Effects of Low Dose Particle Radiation to Mouse Neonatal Neurons in Culture

    NASA Astrophysics Data System (ADS)

    Nojima, K.; Vazquez, M. E.; Okayasu, R.; Nagaoka, S.

    To investigate effects of low dose heavy particle radiation to CNS system, we adopted mouse neonatal brain cells in culture being exposed to heavy ions by HIMAC at NIRS and NSRL at BNL. The applied dose varied from 0.05Gy up to 2.0Gy. The subsequent biological effectswere evaluated by an induction of apoptosis and neuron survival focusing on the dependencies of the animal strains, SCID, B6, B6C3F1, C3H, used for brain cell culture, SCID was the most sensitive and C3H the least sensitive to particle radiation as evaluated by 10% apoptotic criterion. The LET dependency was compared with using SCID and B6 cells exposing to different ions (H, C, Ne, Si, Ar, and Fe). Although no detectable LET dependency was observed in the high LET (55 -200 keV/μ m) and low dose (<0.5 Gy) regions. The survivability profiles of the neurons were different in the mouse strains and ions. In this repot, a result of memory and learning function to adult mice after whole-body and brainlocal irradiation at carbon ion and iron ion.

  11. Effect of Acrylamide on Oocyte Nuclear Maturation and Cumulus Cells Apoptosis in Mouse In Vitro

    PubMed Central

    Liu, Shuzhen; Jiang, Ligang; Zhong, Tao; Kong, Shuhui; Zheng, Rongbin; Kong, Fengyun; Zhang, Cong; Zhang, Lei; An, Liguo

    2015-01-01

    Acrylamide (ACR) is a chemical compound with severe neurotoxicity, genotoxicity, carcinogenicity and reproductive toxicity. Recent studies showed that ACR impairs the function of reproductive organs, e.g., epididymis and testes. In vitro maturation of mouse oocyte is a sensitive assay to identify potential chemical hazard to female fertility. The aim of this study was to evaluate the adverse effects of ACR on the nuclear maturation and cumulus cells apoptosis of mouse oocytes in vitro. Cumulus–oocyte complexes were incubated in a maturation medium containing 0, 5, 10 and 20 μM of ACR. Chromosome alignment and spindle morphology of oocytes was determined by immunofluorescence and confocal microscopy. Our results showed that oocytes exposed to different doses of ACR in vitro were associated with a significant decrease of oocyte maturation, significant increase of chromosome misalignment rate, occurrence of abnormal spindle configurations, and the inhibition of oocyte parthenogenetic activation. Furthermore, apoptosis of cumulus cells was determined by TUNEL and CASPASE-3 assay. Results showed that apoptosis in cumulus cells was enhanced and the expression of CASPASE-3 was increased after cumulus–oocyte complexes were exposed to ACR. Therefore, ACR may affect the nuclear maturation of oocytes via the apoptosis of cumulus cells in vitro. PMID:26275143

  12. Dosimetry for a study of effects of 2. 45-GHz microwaves on mouse testis

    SciTech Connect

    Cairnie, A.B.; Hill, D.A.; Assenheim, H.M.

    1980-01-01

    In order to determine the effects of microwave radiation on the testis, it is necessary to express the physical insult in animal studies in a way that can be replicated elsewhere and ultimately used as a basis for extrapolation to man. However, there is conflict--especially in chronic experiments--between the desire for precise dosimetry and the need to minimise alteration of the normal physiological functions of the animals. The compromise arrangement used in this study was to house the mice singly, in cages with limited food and water, and to irradiate them for up to 30 days (16 h/day) in an anechoic chamber. The only measurements taken routinely were of power density in the positions normally occupied by the cages. In addition, a series of absorption measurements was made in mouse carcasses: Whole-body specific absorption rate (SAR); energy-deposition patterns (determined thermographically); and local SAR in testis (using a miniature electric (E)-field probe). It was concluded that the SAR in testis was considerably less than the whole-body SAR. Exposure for 16 h at 50 mW/cm2 elevated rectal but not testis temperature, thus demonstrating the ability of the conscious mouse to regulate the temperature of its testis.

  13. Evaluation of fractional photothermolysis effect in a mouse model using nonlinear optical microscopy

    NASA Astrophysics Data System (ADS)

    Guo, Han Wen; Tseng, Te-Yu; Dong, Chen-Yuan; Tsai, Tsung-Hua

    2014-07-01

    Fractional photothermolysis (FP) induces discrete columns of photothermal damage in skin dermis, thereby promoting collagen regeneration. This technique has been widely used for treating wrinkles, sun damage, and scar. In this study, we evaluate the potential of multiphoton microscopy as a noninvasive imaging modality for the monitoring of skin rejuvenation following FP treatment. The dorsal skin of a nude mouse underwent FP treatment in order to induce microthermal zones (MTZs). We evaluated the effect of FP on skin remodeling at 7 and 14 days after treatment. Corresponding histology was performed for comparison. After 14 days of FP treatment at 10 mJ, the second harmonic generation signal recovered faster than the skin treated with 30 mJ, indicating a more rapid regeneration of dermal collagen at 10 mJ. Our results indicate that nonlinear optical microscopy is effective in detecting the damaged areas of MTZ and monitoring collagen regeneration following FP treatment.

  14. The effect of space flight on monoclonal antibody synthesis in a hybridoma mouse cell line

    NASA Technical Reports Server (NTRS)

    Smiley, S. A.; Gillock, E. T.; Black, M. C.; Consigli, R. A.; Spooner, B. S. (Principal Investigator)

    1997-01-01

    The hybridoma cell line, 3G10G5, producing a monoclonal antibody to the major capsid protein VP1 from the avian polyomavirus budgerigar fledgling disease virus, was produced from a Balb/C mouse. This cell line was used to test the effects of microgravity on cellular processes, specifically protein synthesis. A time course study utilizing incorporation of [35S]methionine into newly synthesized monoclonal antibody was performed on STS-77. After 5.5 days, it was observed that cell counts for the samples exposed to microgravity were lower than those of ground-based samples. However, radiolabel incorporation of the synthesized monoclonal antibody was similar in both orbiter and ground control samples. Overall, microgravity does not seem to have an effect on this cell line's ability to synthesize IgG protein.

  15. Effects of (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate on mouse osteoclasts

    SciTech Connect

    Marshall, M.J.; Wilson, A.S.; Davie, M.W. )

    1990-09-01

    A group of 5-day-old mice were injected intraperitoneally with (3-amino-1-hydroxypropylidine)-1,1-bisphosphonate (APD). Morphologic changes were observed in vitally stained osteoclasts on parietal bones 3 days later, and these were judged to be degenerative. At this time significantly increased numbers of nuclei per osteoclast and total numbers of osteoclast nuclei were observed. However, at 4 days after the injection of APD, the total numbers of osteoclasts were significantly reduced relative to controls. When parietal bones were maintained in culture, APD reduced osteoclast numbers and inhibited cell-mediated 45Ca2+ release. Exposure of bones to parathyroid hormone increased the number of osteoclasts counted 1 day later. This effect was not blocked by APD. Calcitonin prevented the reduction in osteoclast numbers due to APD in vitro. We conclude that APD has a direct effect on resorbing mouse osteoclasts.

  16. Effects of Subretinal Gene Transfer at Different Time Points in a Mouse Model of Retinal Degeneration

    PubMed Central

    Dai, Xufeng; Zhang, Hua; Han, Juanjuan; He, Ying; Zhang, Yangyang; Qi, Yan; Pang, Ji-jing

    2016-01-01

    Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is necessary for photoreceptors to generate an important lipid component of their membranes. The absence of LPCAT1 results in early and rapid rod and cone degeneration. Retinal degeneration 11 (rd11) mice carry a mutation in the Lpcat1 gene, and are an excellent model of early-onset rapid retinal degeneration (RD). To date, no reports have documented gene therapy administration in the rd11 mouse model at different ages. In this study, the AAV8 (Y733F)-smCBA-Lpcat1 vector was subretinally injected at postnatal day (P) 10, 14, 18, or 22. Four months after injection, immunohistochemistry and analysis of retinal morphology showed that treatment at P10 rescued about 82% of the wild-type retinal thickness. However, the diffusion of the vector and the resulting rescue were limited to an area around the injection site that was only 31% of the total retinal area. Injection at P14 resulted in vector diffusion that covered approximately 84% of the retina, and we found that gene therapy was more effective against RD when exposure to light was limited before and after treatment. We observed long-term preservation of electroretinogram (ERG) responses, and preservation of retinal structure, indicating that early treatment followed by limited light exposure can improve gene therapy effectiveness for the eyes of rd11 mice. Importantly, delayed treatment still partially preserved M-cones, but not S-cones, and M-cones in the rd11 retina appeared to have a longer window of opportunity for effective preservation with gene therapy. These results provide important information regarding the effects of subretinal gene therapy in the mouse model of LPCAT1-deficiency. PMID:27228218

  17. Effects of the inhaled treatment of liriope radix on an asthmatic mouse model.

    PubMed

    Kim, Ki-Suk; Cho, Dong-Hyuk; Yang, Hea Jung; Choi, Eun-Kyeong; Shin, Min Hee; Kim, Kang-Hoon; Ahn, Kwang Seok; Ha, In Jin; Na, Yun-Cheol; Um, Jae Young; Chung, Won Seok; Jung, Hee-Jae; Jung, Sung-Ki; Jang, Hyeung-Jin

    2015-01-01

    As a treatment for allergic asthma, inhaled treatments such as bronchodilators that contain β2-agonists have an immediate effect, which attenuates airway obstructions and decreases airway hypersensitivity. However, bronchodilators only perform on a one off basis, but not consistently. Asthma is defined as a chronic inflammatory disease of the airways accompanying the overproduction of mucus, airway wall remodeling, bronchial hyperreactivity and airway obstruction. Liriope platyphylla radix extract (LPP), a traditional Korean medicine, has been thoroughly studied and found to be an effective anti-inflammatory medicine. Here, we demonstrate that an inhaled treatment of LPP can attenuate airway hyperresponsiveness (AHR) in an ovalbumin-induced asthmatic mouse model, compared to the saline-treated group (p < 0.01). Moreover, LPP decreases inflammatory cytokine levels, such as eotaxin (p < 0.05), IL-5 (p < 0.05), IL-13 (p < 0.001), RANTES (p < 0.01), and TNF-α (p < 0.05) in the bronchoalveolar lavage (BAL) fluid of asthmatic mice. A histopathological study was carried out to determine the effects of LPP inhalation on mice lung tissue. We performed UPLC/ESI-QTOF-MS, LC/MS, and GC/MS analyses to analyze the chemical constituents of LPP, finding that these are ophiopogonin D, spicatoside A, spicatoside B, benzyl alcohol, and 5-hydroxymethylfurfural. This study demonstrates the effect of an inhaled LPP treatment both on airway AHR and on the inflammatory response in an asthmatic mouse model. Hence, LPP holds significant promise as a nasal inhalant for the treatment of asthmatic airway disease. PMID:25967662

  18. Effect of Lactobacillus salivarius Bacteriocin Abp118 on the Mouse and Pig Intestinal Microbiota

    PubMed Central

    Riboulet-Bisson, Eliette; Sturme, Mark H. J.; Jeffery, Ian B.; O'Donnell, Michelle M.; Neville, B. Anne; Forde, Brian M.; Claesson, Marcus J.; Harris, Hugh; Gardiner, Gillian E.; Casey, Patrick G.; Lawlor, Peadar G.; O'Toole, Paul W.; Ross, R. Paul

    2012-01-01

    Lactobacilli are Gram-positive bacteria that are a subdominant element in the human gastrointestinal microbiota, and which are commonly used in the food industry. Some lactobacilli are considered probiotic, and have been associated with health benefits. However, there is very little culture-independent information on how consumed probiotic microorganisms might affect the entire intestinal microbiota. We therefore studied the impact of the administration of Lactobacillus salivarius UCC118, a microorganism well characterized for its probiotic properties, on the composition of the intestinal microbiota in two model animals. UCC118 has anti-infective activity due to production of the bacteriocin Abp118, a broad-spectrum class IIb bacteriocin, which we hypothesized could impact the microbiota. Mice and pigs were administered wild-type (WT) L. salivarius UCC118 cells, or a mutant lacking bacteriocin production. The microbiota composition was determined by pyrosequencing of 16S rRNA gene amplicons from faeces. The data show that L. salivarius UCC118 administration had no significant effect on proportions of major phyla comprising the mouse microbiota, whether the strain was producing bacteriocin or not. However, L. salivarius UCC118 WT administration led to a significant decrease in Spirochaetes levels, the third major phylum in the untreated pig microbiota. In both pigs and mice, L. salivarius UCC118 administration had an effect on Firmicutes genus members. This effect was not observed when the mutant strain was administered, and was thus associated with bacteriocin production. Surprisingly, in both models, L. salivarius UCC118 administration and production of Abp118 had an effect on Gram-negative microorganisms, even though Abp118 is normally not active in vitro against this group of microorganisms. Thus L. salivarius UCC118 administration has a significant but subtle impact on mouse and pig microbiota, by a mechanism that seems at least partially bacteriocin

  19. Effect of mouse strain as a background for Alzheimer’s disease models on the clearance of amyloid-β

    PubMed Central

    Qosa, Hisham; Kaddoumi, Amal

    2016-01-01

    Novel animal models of Alzheimer’s disease (AD) are relentlessly being developed and existing ones are being fine-tuned; however, these models face multiple challenges associated with the complexity of the disease where most of these models do not reproduce the full phenotypical disease spectrum. Moreover, different AD models express different phenotypes that could affect their validity to recapitulate disease pathogenesis and/or response to a drug. One of the most important and understudied differences between AD models is differences in the phenotypic characteristics of the background species. Here, we used the brain clearance index (BCI) method to investigate the effect of strain differences on the clearance of amyloid β (Aβ) from the brains of four mouse strains. These mouse strains, namely C57BL/6, FVB/N, BALB/c and SJL/J, are widely used as a background for the development of AD mouse models. Findings showed that while Aβ clearance across the blood-brain barrier (BBB) was comparable between the 4 strains, levels of LRP1, an Aβ clearance protein, was significantly lower in SJL/J mice compared to other mouse strains. Furthermore, these mouse strains showed a significantly different response to rifampicin treatment with regard to Aβ clearance and effect on brain level of its clearance-related proteins. Our results provide for the first time an evidence for strain differences that could affect ability of AD mouse models to recapitulate response to a drug, and opens a new research avenue that requires further investigation to successfully develop mouse models that could simulate clinically important phenotypic characteristics of AD.

  20. Maneb-induced dopaminergic neuronal death is not affected by loss of mitochondrial complex I activity: Results from primary mesencephalic dopaminergic neurons cultured from individual Ndufs4+/+ and Ndufs4-/- mouse embryos

    PubMed Central

    Choi, Won-Seok; Xia, Zhengui

    2014-01-01

    Primary cultures from embryonic mouse ventral mesencephalon are widely used for investigating the mechanisms of dopaminergic neuronal death in Parkinson's disease models. Specifically, single mouse or embryo cultures from littermates can be very useful for comparative studies involving transgenic mice when the neuron cultures are to be prepared before genotyping. However, preparing single mouse embryo culture is technically challenging because of the small number of cells present in the mesencephalon of each embryo (150,000-300,000), of which only 0.5-5% are tyrosine hydroxylase (TH) -positive, dopaminergic neurons. In this study, we optimized the procedure for preparing primary mesencephalic neuron cultures from individual mouse embryos. Mesencephalic neurons that are dissociated delicately, plated on Aclar film coverslips, and incubated in DMEM supplemented with FBS for 5 days and then N2 supplement for 1 day resulted in the best survival of dopaminergic neurons from each embryo. Using this optimized method, we prepared mesencephalic neuron cultures from single Ndufs4+/+ or Ndufs4-/- embryos, and investigated the role of mitochondrial complex I in maneb-induced dopamine neuron death. Our results suggest that maneb toxicity to dopamine neurons is not affected by loss of mitochondrial complex I activity in Ndufs4-/- cultures. PMID:25275677

  1. The effect of polymer dots on bioactivity of mouse sperm in vitro

    NASA Astrophysics Data System (ADS)

    Feng, Gang; Chen, Qiang; Zhai, Peng; Wang, Xiaomei; Lin, Guimiao; Xu, Gaixia; Chen, Danni

    2014-09-01

    Objective: In recent years, semiconducting polymer dots (Pdots)have caught considerable attention for their outstanding optical characteristics in biomedical imaging applications. Not as semiconductor quantum dots, Pdots are composed of nonmetallic material and their biological effects remain unclear. In this work, we investigated the effects of a band new polymer dots on bioactivity of mouse sperm using a computer-aided sperm analysis system(CASA) and an in vitro fertilization (IVF) model. Methods: The semiconducting polymer dots used in this study is CN-PPV Pdots, which emits in the orange wavelength range with high brightness. Epididymal mouse sperm were collected from 7-8weeks old Balb/c mouse. Firstly, CN-PPV Pdots was added into the Human Tubal Fluid (HTF) media at various concentrations (0, 1, 10, 100 nmol/L respectively ), then sperm bioactivity and vitality were evaluated every 10 minutes. Secondly, the treated sperm were co-cultured with matured oocytes in HTF media, fertilization rate and oocytes development were recorded after 24 hours co-incubation. Results: Sperm viability in the control group (0 nmol/L) and experimental group (1, 10,100 nmol/L) were 57.20+/-4.51%, 58.17+/-4.81%, 55.50+/-4.52%, 46.26%+/-3.83%, respectively. Fertilization rate in different groups showed no obvious differences, control group (0 nmol/L) and experimental group (1, 10, 100 nmol/L) were 38.75+/-1.71%, 37.01+/-4.69%, 32.75+/-1.71%, 35.24+/-2.37%, respectively. Conclusion: Our data indicated that the CN-PPV Pdots had a very high biocompatibility on sperm in both the activation and the IVF process, even in extreme high Pdots concentration,the sperm bioactivity only got slight restrained. The effect of CN-PPV Pdots seems has no or little toxicity,and the long-term embryonic development has yet to be verified.

  2. Flowers of Hibiscus rosa-sinensis, a potential source of contragestative agent. III: Interceptive effect of benzene extract in mouse.

    PubMed

    Pakrashi, A; Bhattacharya, K; Kabir, S N; Pal, A K

    1986-11-01

    In mouse, oral administration of the benzene extract of Hibiscus rosa-sinensis flowers at a dose level of 1 gm/kg body weight/day from day 5-8 of gestation led to termination of pregnancy in about 92% of the animals. The effect was associated with a significant fall in peripheral level of progesterone and increase in uterine acid phosphatase activity, as measured on day 10. The ovary exhibited signs of luteolysis, and the corpus luteal delta 5-3 beta -hydroxysteroid dehydrogenase activity decreased markedly. The interceptive effect of the extract was prevented completely by exogenous progesterone (1 mg/mouse/day) or chorionic gonadotropin (1 I.U./mouse/day) and partially (62.5%) by exogenous prolactin (500 micrograms/mouse/day). In unilaterally pregnant mouse having trauma-induced deciduomata in the sterile horn, the extract caused resorption of the fetuses, and regression of the deciduomata accompanied by reduction in weight of the ovaries. Luteolysis, may be due to interference with the luteotropic influence, and a consequent fall in plasma level of progesterone have been suggested as the plausible cause of termination of pregnancy. PMID:3816235

  3. Effects of the jimpy mutation on mouse retinal structure and function.

    PubMed

    Hovhannisyan, Anahit; Benkner, Boris; Biesemeier, Antje; Schraermeyer, Ulrich; Kukley, Maria; Münch, Thomas A

    2015-12-15

    The Jimpy mutant mouse has a point mutation in the proteolipid protein gene (plp1). The resulting misfolding of the protein leads to oligodendrocyte death, myelin destruction, and failure to produce adequately myelinated axons in the central nervous system (CNS). It is not known how the absence of normal myelination during development influences neural function. We characterized the Jimpy mouse retina to find out whether lack of myelination in the optic nerve during development has an effect on normal functioning and morphology of the retina. Optokinetic reflex measurements showed that Jimpy mice had, in general, a functional visual system. Both PLP1 antibody staining and reverse transcriptase-polymerase chain reaction for plp1 mRNA showed that plp1 is not expressed in the wild-type retina. However, in the optic nerve, plp1 is normally expressed, and consequently, in Jimpy mutant mice, myelination of axons in the optic nerve was mostly absent. Nevertheless, neither axon count nor axon ultrastructure in the optic nerve was affected. Physiological recordings of ganglion cell activity using microelectrode arrays revealed a decrease of stimulus-evoked activity at mesopic light levels. Morphological analysis of the retina did not show any significant differences in the gross morphology, such as thickness of retinal layers or cell number in the inner and outer nuclear layer. The cell bodies in the inner nuclear layer, however, were larger in the peripheral retina of Jimpy mutant mice. Antibody labeling against cell type-specific markers showed that the number of rod bipolar and horizontal cells was increased in Jimpy mice. In conclusion, whereas the Jimpy mutation has dramatic effects on the myelination of retinal ganglion cell axons, it has moderate effects on retinal morphology and function. PMID:26011242

  4. Carcinine Has 4-Hydroxynonenal Scavenging Property and Neuroprotective Effect in Mouse Retina

    PubMed Central

    Marchette, Lea D.; Wang, Huaiwen; Li, Feng; Babizhayev, Mark A.; Kasus-Jacobi, Anne

    2012-01-01

    Purpose. Oxidative stress induces retinal damage and contributes to vision loss in progressive retinopathies. Carcinine (β-alanyl-histamine) is a natural imidazole-containing peptide derivative with antioxidant activity. It is predicted to scavenge 4-hydroxynonenal (4-HNE), a toxic product of lipid oxidation. The aim of this study was to confirm the 4-HNE scavenging effect and evaluate the neuroprotective effect of carcinine in mouse retina subjected to oxidative stress. Methods. HPLC coupled with mass spectrometry was used to analyze carcinine and 4-HNE-carcinine adduct. Protection of retinal proteins from modification by 4-HNE was tested by incubating carcinine with retinal protein extract and 4-HNE. Modified retinal proteins were quantified by dot-blot analysis. Mice were treated with carcinine (intravitreal injection and gavage) and exposed to bright light to induce oxidative damage in the retina. Photoreceptor degeneration was measured by histology and electroretinography. Retinal levels of retinol dehydrogenase 12 (RDH12) were measured by immunoblot analysis, after exposure to bright light and in retinal explants after exposure to 4-HNE. Results. The ability of carcinine to form an adduct with 4-HNE, as well as to prevent and even reverse the adduction of retinal proteins by the toxic aldehyde was demonstrated in vitro. Carcinine, administered by intravitreal injection or gavage, strongly protected mouse retina against light-induced photoreceptor degeneration and had a protective effect on RHD12, a protein found specifically in photoreceptor cells. Conclusions. This study suggests that carcinine can be administered noninvasively to efficiently protect photoreceptor cells from oxidative damage. Carcinine could be administered daily to prevent vision loss in progressive retinopathies. PMID:22577078

  5. Effects of angiopoietin-1 on vascular endothelial growth factor-induced angiogenesis in the mouse brain.

    PubMed

    Zhu, Y; Shwe, Y; Du, R; Chen, Y; Shen, F X; Young, W L; Yang, G Y

    2006-01-01

    A better understanding of angiogenic factors and their effects on angiogenesis in brain is necessary to treat cerebral vascular disorders such as ischemic brain injury. Vascular endothelial growth factor (VEGF) induces angiogenesis and increases blood-brain barrier (BBB) permeability in adult mouse brain. The effect of angiopoietin-1 on BBB leakage during the angiogenesis process is unclear. We sought to identify the effects of combining VEGF with angiopoietin-1 on cerebral angiogenesis and BBB. Adult male CD-1 mice underwent AdFc (adenoviral vector control), AdAng-1, VEGF protein, VEGF protein plus AdAng-1, or saline (negative control) injection. Brain microvessels were counted using lectin staining on tissue sections after 2 weeks of adenoviral gene transfer. The presence of zonula occludens-1 (ZO-1) was determined by Western blot analysis and immunohistochemistry. Microvessel count and augmented capillary diameter increased in mice treated with either VEGF protein or AdAng-1 plus VEGF protein compared to saline, AdFc, or AdAng-1 alone (p < 0.05). Double-labeled immunostaining demonstrated that ZO-1-positive staining was more complete on the microvessel wall in the AdAng-1 and AdAng-1 plus VEGF protein treated group compared to VEGF protein group. The results of ZO-1 expression from Western blot analysis paralleled that from immunohistochemistry (p < 0.05). We conclude that focal VEGF and angiopoietin-1 hyperstimulation in mouse brain increases microvessel density while maintaining ZO-1 protein expression, suggesting that angiopoietin-1 plays a role in synergistically inducing angiogenesis and BBB integrity. PMID:16671501

  6. The effect of metals on spatial memory in a transgenic mouse model of Alzheimer's disease.

    PubMed

    Railey, Angela M; Groeber, Caitlin M; Flinn, Jane M

    2011-01-01

    The amyloid-β protein (Aβ) is a metalloprotein with affinity for the metal ions zinc (Zn), copper (Cu), and iron (Fe), which are found in high concentrations in the plaques of Alzheimer's disease (AD). Increasing attention is focused on the role of these metals in AD, and much of the evidence suggests a dyshomeostasis between these metal ions may significantly affect Aβ aggregation and deposition in the brain. While the effect of these metals on Aβ has been shown in vitro, there is less behavioral data supporting a direct role in cognitive impairment. In order to investigate the cognitive consequences of metal dyshomeostasis, we sought to directly increase metal levels in the brain by dietary means in a transgenic mouse model (Tg2576). We have now examined the effect of increased Zn (10 ppm) and Fe (10 ppm) levels in the drinking water in the Tg2576 mouse. Since increased dietary Zn can lead to Cu deficiency, a Zn group supplemented with copper was also examined (Zn (10 ppm)+Cu (0.025 ppm)). Significant increases in latency and fewer platform crossings on probe trials, which are considered measures of spatial memory impairment, were seen in both Fe and Zn supplemented transgenic mice, compared to those raised on lab water. No significant differences were seen between the Zn + Cu group and in transgenic mice raised on lab water. These data suggest that the negative consequences of Zn may be due to a reduction in copper levels and, therefore, an imbalance between these metal ions rather than a direct effect of increased Zn. PMID:21239856

  7. Effects of colistin on amino acid neurotransmitters and blood-brain barrier in the mouse brain.

    PubMed

    Wang, Jian; Yi, Meishuang; Chen, Xueping; Muhammad, Ishfaq; Liu, Fangping; Li, Rui; Li, Jian; Li, Jichang

    2016-01-01

    Neurotoxicity is one of the major potential side effects of colistin therapy. However, the mechanistic aspects of colistin-induced neurotoxicity remain largely unknown. The objective of this study was to examine the effects of colistin on the blood-brain barrier (BBB) and amino acid neurotransmitters in the cerebral cortex of mouse. Mice were divided into four groups (n=5) and were administrated intravenously with 15mg/kg/day of colistin sulfate for 1, 3 and 7days successively while the control group was administrated intravenously with saline solution. The permeability and ultrastructure of the BBB were detected using the Evans blue (EB) dye and transmission electron microscopy (TEM), and the expression of Claudin-5 were determined by real-time PCR examination and western blotting. The brain uptake of colistin was measured by high-performance liquid chromatography (HPLC). The effects of colistin on amino acid neurotransmitters and their receptors were also examined by HPLC and real-time PCR. The results of EB extravasation, TEM and expression of Claudin-5 showed that colistin treatment did not affect the BBB integrity. In addition, multiple doses of colistin could induce accumulation of this compound in the brain parenchyma although there was poor brain uptake of colistin. Moreover, colistin exposure significantly increased the contents of glutamate (Glu) and gamma aminobutyric acid (GABA), and enhanced the mRNA expression levels of gamma aminobutyric acid type A receptor (GABAAR), gamma aminobutyric acid type B receptor (GABABR), N-methyl-d-aspartate 1 receptor (NR1), N-methyl-d-aspartate 2A receptor (NR2A) and N-methyl-d-aspartate 2B receptor (NR2B) in the cerebral cortex. Our data demonstrate that colistin is able to accumulate in the mouse brain and elevate the levels of amino acid neurotransmitters. These findings may be associated with colistin-induced neurotoxicity. PMID:27018023

  8. Effects of hydroxamate metalloendoprotease inhibitors on botulinum neurotoxin A poisoned mouse neuromuscular junctions

    PubMed Central

    Thyagarajan, Baskaran; Potian, Joseph G.; Garcia, Carmen C.; Hognason, Kormakur; Čapková, Kateřina; Moe, Scott T.; Jacobson, Alan R.; Janda, Kim D.; McArdle, Joseph J.

    2010-01-01

    Summary Currently the only therapy for botulinum neurotoxin A (BoNT/A) poisoning is antitoxin. Antidotes that are effective after BoNT/A has entered the motor nerve terminals would dramatically benefit BoNT/A therapy. Inhibition of proteolytic activity of BoNT/A light chain by metalloendoprotease inhibitors (MEIs) is under development. We tested the effects of MEIs on in vitro as well as in vivo BoNT/A poisoned mouse nerve muscle preparations (NMPs). The Ki for inhibition of BoNT/A metalloendoprotease was 0.40 and 0.36 μM, respectively, for 2, 4 – dichlorocinnamic acid hydroxamate (DCH) and its methyl derivative, ABS 130. Acute treatment of nerve muscle preparations with 10 pM BoNT/A inhibited nerve evoked muscle twitches, reduced mean quantal content, and induced failures of endplate currents (EPCs). Bath application of 10 μM DCH or 5 μM ABS 130 reduced failures, increased the quantal content of EPCs, and partially restored muscle twitches after a delay of 40 to 90 min. The restorative effects of DCH and ABS 130, as well as 3,4 diaminopyridine (DAP) on twitch tension were greater at 22 °C compared to 37 °C. Unlike DAP, neither DCH nor ABS 130 increased Ca2+ levels in cholinergic Neuro 2a cells. Injection of MEIs into mouse hind limbs before or after BoNT/A injection neither prevented the toe spread reflex inhibition nor improved muscle functions. We suggest that hydroxamate MEIs partially restore neurotransmission of acutely BoNT/A poisoned nerve muscle preparations in vitro in a temperature dependent manner without increasing the Ca2+ levels within motor nerve endings. PMID:20211192

  9. The effect of epidermal growth factor on neonatal incisor differentiation in the mouse.

    PubMed

    Topham, R T; Chiego, D J; Gattone, V H; Hinton, D A; Klein, R M

    1987-12-01

    The effect of epidermal growth factor (EGF) on cellular differentiation of the neonatal mouse mandibular incisor was examined autoradiographically using tritiated thymidine ([3H]TDR) and tritiated proline ([3H]PRO). On days 0 (day of birth), 1, and 2, EGF was administered (3 micrograms/g body wt) sc to neonates. Mice were killed on Days 1, 4, 7, 10, and 13 after birth and were injected with either [3H]TDR or [3H]PRO 1 hr before death. [3H]TDR was used to analyze cell proliferation in eight cell types in the developing mouse incisor including upper (lingual) and lower (buccal) pulpal fibroblasts, preodontoblasts, inner and outer enamel epithelial cells (IEE and OEE), stratum intermedium (SI), stellate reticulum (SR), and periodontal ligament (PDL) fibroblasts. [3H]PRO was used to analyze protein synthesis in ameloblasts, and their secretion products (enamel and dentin), as well as PDL fibroblasts. The selected EGF injection scheme elicited acceleration of incisor eruption with minimal growth retardation. At Day 1, the upper and lower pulp, preodontoblasts, SI, and SR showed a significant decrease in labeling index (LI) 24 hr after a single EGF injection. After multiple injections (Days 0, 1, 2), two LI patterns were observed. In lower pulp, preodontoblasts, IEE, SI, SR, and OEE, a posteruptive change in LI was observed. In contrast, the upper pulp and PDL regions demonstrated a direct temporal relationship with eruption. Autoradiographic analysis with [3H]PRO indicated that EGF treatment caused significant increases in grain counts per unit area in ameloblast, odontoblast, and PDL regions studied. Significant differences were found in all four regions studied (ameloblasts, enamel, odontoblasts, dentin) at the 45-microns-tall ameloblast level as well as ameloblasts and odontoblasts at the 30-microns level at 13 days of age. The PDL demonstrated significant differences at all locations studied (base, 30 microns, 45 microns,) in 4-, 7-, and 13-day-old mice

  10. Psychomotor stimulant effects of cocaine in rats and 15 mouse strains

    PubMed Central

    Thomsen, Morgane; Caine, S. Barak

    2012-01-01

    Relative to intravenous drug self-administration, locomotor activity is easier to measure with high throughput, particularly in mice. Therefore its potential to predict differences in self-administration between genotypes (e.g., targeted mutations, recombinant inbred strains) is appealing, but such predictive value is unverified. The main goal of this study was to evaluate the utility of the locomotor assay for accurately predicting differences in cocaine self-administration. A second goal was to evaluate any correlation between activity in a novel environment, and cocaine-induced hyperactivity, between strains. We evaluated locomotor activity in male and female Sprague-Dawley rats and 15 mouse strains (129S1/SvImJ, 129S6/SvEvTac, 129X1/SvJ, A/J, BALB/cByJ, BALB/cJ, C3H/HeJ, C57BL/6J, CAST/EiJ, DBA/2J, FVB/NJ, SJL/J, SPRET/EiJ, and outbred Swiss Webster and CD-1/ICR), as well as cocaine self-administration in BALB substrains. All but BALB/cJ mice showed locomotor habituation and significant cocaine-induced hyperactivity. BALB/cJ mice also failed to self-administer cocaine. BALB/cByJ mice showed modest locomotor habituation, cocaine-induced locomotion, and cocaine self-administration. As previously reported, female rats showed greater cocaine-induced locomotion than males, but this was only observed in one of fifteen mouse strains (FVB/NJ), and the reverse was observed in two strains (129X1/SvJ, BALB/cByJ). The intriguing phenotype of the BALB/cJ strain may indicate some correlation between all-or-none locomotion in a novel environment, and stimulant and reinforcing effects of cocaine. However, neither novelty- nor cocaine-induced activity offered a clear prediction of relative reinforcing effects among strains. Additionally, these results should aid in selecting mouse strains for future studies in which relative locomotor responsiveness to psychostimulants is a necessary consideration. PMID:21843010

  11. Protective effect of resveratrol against caspase 3 activation in primary mouse fibroblasts

    PubMed Central

    Ulakcsai, Zsófia; Bagaméry, Fruzsina; Vincze, István; Szökő, Éva; Tábi, Tamás

    2015-01-01

    Aim To study the effect of resveratrol on survival and caspase 3 activation in non-transformed cells after serum deprivation. Methods Apoptosis was induced by serum deprivation in primary mouse embryonic fibroblasts. Caspase 3 activation and lactate dehydrogenase release were assayed as cell viability measure by using their fluorogenic substrates. The involvement of PI3K, ERK, JNK, p38, and SIRT1 signaling pathways was also examined. Results Serum deprivation of primary fibroblasts induced significant activation of caspase 3 within 3 hours and reduced cell viability after 24 hours. Resveratrol dose-dependently prevented caspase activation and improved cell viability with 50% inhibitory concentration (IC50) = 66.3 ± 13.81 µM. It also reduced the already up-regulated caspase 3 activity when it was added to the cell culture medium after 3 hour serum deprivation, suggesting its rescue effect. Among the major signaling pathways, p38 kinase was critical for the protective effect of resveratrol which was abolished completely in the presence of p38 inhibitor. Conclusion Resveratrol showed protective effect against cell death in a rather high dose. Involvement of p38 kinase in this effect suggests the role of mild stress in its cytoprotective action. Furthermore due to its rescue effect, resveratrol may be used not only for prevention, but also treatment of age-related degenerative diseases, but in the higher dose than consumed in conventional diet. PMID:25891866

  12. Telomerase inhibition effectively targets mouse and human AML stem cells and delays relapse following chemotherapy.

    PubMed

    Bruedigam, Claudia; Bagger, Frederik O; Heidel, Florian H; Paine Kuhn, Catherine; Guignes, Solene; Song, Axia; Austin, Rebecca; Vu, Therese; Lee, Erwin; Riyat, Sarbjit; Moore, Andrew S; Lock, Richard B; Bullinger, Lars; Hill, Geoffrey R; Armstrong, Scott A; Williams, David A; Lane, Steven W

    2014-12-01

    Acute myeloid leukemia (AML) is an aggressive and lethal blood cancer maintained by rare populations of leukemia stem cells (LSCs). Selective targeting of LSCs is a promising approach for treating AML and preventing relapse following chemotherapy, and developing such therapeutic modalities is a key priority. Here, we show that targeting telomerase activity eradicates AML LSCs. Genetic deletion of the telomerase subunit Terc in a retroviral mouse AML model induces cell-cycle arrest and apoptosis of LSCs, and depletion of telomerase-deficient LSCs is partially rescued by p53 knockdown. Murine Terc(-/-) LSCs express a specific gene expression signature that can be identified in human AML patient cohorts and is positively correlated with patient survival following chemotherapy. In xenografts of primary human AML, genetic or pharmacological inhibition of telomerase targets LSCs, impairs leukemia progression, and delays relapse following chemotherapy. Altogether, these results establish telomerase inhibition as an effective strategy for eliminating AML LSCs. PMID:25479751

  13. Escape from Genomic Imprinting at the Mouse T-Associated Maternal Effect (Tme) Locus

    PubMed Central

    Tsai, J. Y.; Silver, L. M.

    1991-01-01

    Genomic imprinting occurs at the paternally inherited allele of the mouse T-associated maternal effect (Tme) locus. As a consequence, maternal transmission of a functional Tme gene is normally required for viability and individuals that receive a Tme-deleted chromosome (T(hp) or t(lub2)) from their mother die late in gestation or shortly thereafter. Here we report that a rearranged paternally derived chromosome duplicated for the Tme locus can act to rescue animals that have not received a maternal copy of the Tme locus. Unexpectedly, all rescued animals display an abnormal short/kinky tail phenotype. Somatic transfer of genomic imprinting between homologs by means of a transvection-like process between paired Tme and T loci is proposed as a model to explain the results obtained. PMID:1783296

  14. Sibling effects on the behavior of infant mouse litters (Mus domesticus).

    PubMed

    Laviola, G; Alleva, E

    1995-03-01

    We investigated whether the number of same- or other-sex littermates had a graded effect on the occurrence of early solitary play and social play by mouse (Mus domesticus) family units. Sixty litters, reduced at birth to 5 different sex ratios (6 males, 5 males and 1 female, 3 males and 3 females, 1 male and 5 females, and 6 females) were scored in 15-min sessions on postnatal Days 18 and 21. An increasing trend with age was found for run, pounce, popcorn, self-groom, and explore episodes. Type of family unit influenced the occurrence of specific social interactions: One male-5 female and 6 female litters showed more social play than similar male litters. Litters with a balanced sex ratio showed higher exploration than isosexual litters. The results extend previous reports of both social and solitary play in developing laboratory mice and, in contrast with rat data, indicate a marked female primacy in playful social behavior. PMID:7705064

  15. Effects of traumatic brain injury on reactive astrogliosis and seizures in mouse models of Alexander disease

    PubMed Central

    Cotrina, Maria Luisa; Chen, Michael; Han, Xiaoning; Iliff, Jeffrey; Ren, Zeguang; Sun, Wei; Hagemann, Tracy; Goldman, James; Messing, Albee; Nedergaard, Maiken

    2014-01-01

    Alexander disease (AxD) is the only known human pathology caused by mutations in an astrocyte-specific gene, glial fibrillary acidic protein (GFAP). These mutations result in abnormal GFAP accumulations that promote seizures, motor delays and, ultimately, death. The exact contribution of increased, abnormal levels of astrocytic mutant GFAP in the development and progression of the epileptic phenotype is not clear, and we addressed this question using two mouse models of AxD. Comparison of brain seizure activity spontaneously and after traumatic brain injury (TBI), an effective way to trigger seizures, revealed that abnormal GFAP accumulation contributes to abnormal brain activity (increased interictal discharges) but is not a risk factor for the development of epilepsy after TBI. These data highlight the need to further explore the complex and heterogeneous response of astrocytes towards injury and the involvement of GFAP in the progression of AxD. PMID:25069089

  16. Effects of chlorpyrifos on the gut microbiome and urine metabolome in mouse (Mus musculus).

    PubMed

    Zhao, Yanping; Zhang, Yan; Wang, Guoxiang; Han, Ruiming; Xie, Xianchuan

    2016-06-01

    In this study, the toxic effects of clorpyrifos (CPF) on the gut microbiome and related urine metabolome in mouse (Mus musculus) were investigated. Mice were exposed to a daily dose of 1 mg kg(-1) bodyweight of CPF for 30 d. As a result, CPF significantly altered the gut microbiota composition in terms of the relative abundance of key microbes. Meanwhile, CPF exposure induced the alterations of urine metabolites related to the metabolism of amino acids, energy, short-chain fatty acids (SCFAs), phenyl derivatives and bile acids. High correlations were observed between perturbed gut microbiome and altered metabolic profiles. These perturbations finally resulted in intestinal inflammation and abnormal intestinal permeability, which were also confirm by the histologic changes in colon and remarkable increase of lipopolysaccharide (LPS) and diamine oxidase (DAO) in the serum of CPF-treated mice. Our findings will provide a new perspective to reveal the mechanism of CPF toxicity. PMID:27018521

  17. Telomerase Inhibition Effectively Targets Mouse and Human AML Stem Cells and Delays Relapse Following Chemotherapy

    PubMed Central

    Bruedigam, Claudia; Bagger, Frederik O.; Heidel, Florian H.; Kuhn, Catherine Paine; Guignes, Solene; Song, Axia; Austin, Rebecca; Vu, Therese; Lee, Erwin; Riyat, Sarbjit; Moore, Andrew S.; Lock, Richard B.; Bullinger, Lars; Hill, Geoffrey R.; Armstrong, Scott A.; Williams, David A.; Lane, Steven W.

    2014-01-01

    SUMMARY Acute myeloid leukemia (AML) is an aggressive and lethal blood cancer maintained by rare populations of leukemia stem cells (LSCs). Selective targeting of LSCs is a promising approach for treating AML and preventing relapse following chemotherapy, and developing such therapeutic modalities is a key priority. Here, we show that targeting telomerase activity eradicates AML LSCs. Genetic deletion of the telomerase subunit Terc in a retroviral mouse AML model induces cell cycle arrest and apoptosis of LSCs, and depletion of telomerase-deficient LSCs is partially rescued by p53 knockdown. Murine Terc−/− LSCs express a specific gene expression signature that can be identified in human AML patient cohorts and is positively correlated with patient survival following chemotherapy. In xenografts of primary human AML, genetic or pharmacological inhibition of telomerase targets LSCs, impairs leukemia progression, and delays relapse following chemotherapy. Together, these results establish telomerase inhibition as an effective strategy for eliminating AML LSCs. PMID:25479751

  18. Effects of combination therapy with vildagliptin and valsartan in a mouse model of type 2 diabetes

    PubMed Central

    2013-01-01

    Background Dipeptidyl peptidase-4 (DPP-4) inhibitors modulate incretin hormones and exert anti-diabetic effects in type 2 diabetes mellitus. Treatment with angiotensin II type 1 receptor blockers (ARB) is a proven successful intervention for hypertension with type 2 diabetes. The present study investigated the combined effects of the DPP-4 inhibitor vildagliptin and the ARB valsartan in a mouse model of type 2 diabetes. Methods C57BL/6 J mice fed with high-fat diet (HFD) or db/db mice were treated with placebo, phloridzin (PHZ), vildagliptin alone (ViL), valsartan alone (VaL) or ViL with VaL (ViLVaL) for 8 weeks. Results Glucose metabolism was improved in response to PHZ, ViL and ViLVaL in both HFD and db/db mice. Upon glucose challenge, ViLVaL showed the greatest suppression of blood glucose excursions, with increased insulin secretion, in db/db mice. ViLVaL treatment also showed an improvement of insulin sensitivity in db/db mice. Serum inflammatory cytokines were significantly decreased, and adiponectin was highest, in the ViLVaL group. ViLVaL improved insulin signaling and attenuated stress signaling in liver with amelioration of hepatic steatosis due to activated fatty acid oxidation in db/db mice. Furthermore, immunohistochemical analysis of the pancreas revealed that the combination treatment resulted in an increased expression of insulin and PDX-1, and increased insulin content. Conclusions The combination therapy of ViL and VaL improves both pancreatic beta-cell function and insulin sensitivity, with a reduction of the inflammatory and cell stress milieu in mouse models of T2DM. Our results suggest that this combination therapy exerts additive or even synergistic benefits to treat T2DM. PMID:24188631

  19. Effects of different forms of chitosan on intercellular junctions of mouse fibroblasts in vitro.

    PubMed

    Uslu, B; Biltekin, B; Denir, S; Özbaş-Turan, S; Arbak, S; Akbuğa, J; Bilir, A

    2016-01-01

    Chitosan is a linear polysaccharide that has many biomedical applications. We compared the effects of chitosan, in both solution and membranous form, on intercellular adhesion of Swiss 3T3 mouse fibroblasts. Cells were grown as spheroidal cell cultures. Some control cell spheroids were cultured without chitosan and two experimental groups were cultured with chitosan. Chitosan in solution was used for one experimental group and chitosan in membranous form was used for the other. For each group, intercellular adhesion was investigated on days 5 and 10 of culture. Transmission electron microscopy revealed well-defined cellular projections that were more prominent in cells exposed to either membranous or solution forms of chitosan than to the chitosan-free control. Immunocytochemical staining of ICAM-1 and e-cadherin was used to determine the development of intercellular junctions. Compared to the weakly stained control, strong reactions were observed in both chitosan exposed groups at both 5 and 10 days. Cells were treated with 5-bromo-2-deoxyuridine (BrdU) and incubated with anti-BrdU primary antibody to assess proliferation. Both the solution and membranous forms of chitosan increased proliferation at both 5 and 10 days. Cellular viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The MTT assay indicated high cell viability; maximum viability was obtained with the solution form of chitosan at day 5. Chitosan exposure increased the number of intercellular junctions and showed a significant proliferative effect on 3T3 mouse fibroblasts. PMID:26523482

  20. Immunomodulatory effects of sulfated polysaccharides of pine pollen on mouse macrophages.

    PubMed

    Geng, Yue; Xing, Li; Sun, Mengmeng; Su, Fangchen

    2016-10-01

    This study was undertaken to explore the effects of sulfated polysaccharide (SPPM60-D) from masson pine pollen on [Ca(2+)]i and immune function of RAW264.7 macrophages. SPPM60-D was obtained by subjecting Masson pine pollen to boiling water and alcohol precipitation, 60% ethanol grading precipitation, Sephacryl S-400HR purification, and chlorosulfonic acid-pyridine method sulfation. An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to measure the effect of SPPM60-D on relative activity and proliferation of RAW264.7 cells, and a fluorescence spectrophotometer was used to determine [Ca(2+)]i. Phagocytosis of neutral red was used to determine phagocytosis capacity. Adherence, scratch healing, and transwell assays were used to assess migration and adhesion abilities of macrophages. An enzyme-linked immuno sorbent assay (ELISA) assay was used to assess the secretion of cytokines and inflammatory mediators. A dexamethasone (DEX) inhibition method was used to measure the recovery of RAW264.7 immune activity by SPPM60-D. SPPM60-D significantly increased relative activity, proliferation, and [Ca(2+)]i levels of mouse RAW264.7 cells. It also significantly enhanced the immune function of macrophages from normal and immune-suppressed mouse. The results showed that SPPM60-D mainly bound to TLR4 on macrophages. This activated the TLR4-PI3K-PLC-IP3R signaling pathway, leading to the opening of calcium release-activated calcium channels (CRAC), increasing [Ca(2+)]i and activating the macrophages, and thus improving immunity. PMID:27288698

  1. Anti-arrhythmic effects of hypercalcemia in hyperkalemic, Langendorff-perfused mouse hearts

    PubMed Central

    Tse, Gary; Sun, Bing; Wong, Sheung Ting; Tse, Vivian; Yeo, Jie Ming

    2016-01-01

    The present study examined the ventricular arrhythmic and electrophysiological properties during hyperkalemia (6.3 mM [K+] vs. 4 mM in normokalemia) and anti-arrhythmic effects of hypercalcemia (2.2 mM [Ca2+]) in Langendorff-perfused mouse hearts. Monophasic action potential recordings were obtained from the left ventricle during right ventricular pacing. Hyperkalemia increased the proportion of hearts showing provoked ventricular tachycardia (VT) from 0 to 6 of 7 hearts during programmed electrical stimulation (Fisher's exact test, P<0.05). It shortened the epicardial action potential durations (APDx) at 90, 70, 50 and 30% repolarization and ventricular effective refractory periods (VERPs) (analysis of variance, P<0.05) without altering activation latencies. Endocardial APDx and VERPs were unaltered. Consequently, ∆APDx (endocardial APDx-epicardial APDx) was increased, VERP/latency ratio was decreased and critical intervals for reexcitation (APD90-VERP) were unchanged. Hypercalcemia treatment exerted anti-arrhythmic effects during hyperkalemia, reducing the proportion of hearts showing VT to 1 of 7 hearts. It increased epicardial VERPs without further altering the remaining parameters, returning VERP/latency ratio to normokalemic values and also decreased the critical intervals. In conclusion, hyperkalemia exerted pro-arrhythmic effects by shortening APDs and VERPs. Hypercalcemia exerted anti-arrhythmic effects by reversing VERP changes, which scaled the VERP/latency ratio and critical intervals. PMID:27588173

  2. Mouse tracking traces the "Camrbidge Unievrsity" effects in monolingual and bilingual minds.

    PubMed

    Lin, Yu-Cheng; Lin, Pei-Ying

    2016-06-01

    Previous monolingual studies have consistently suggested that there was flexibility of letter position encoding in different alphabetic writing systems. This robust letter transposition was named the "Cambridge University" effect. However, to date whether the orthographic neighborhood and cross-language script similarity would modulate the magnitude of the Cambridge University effect during the second-language word recognition in bilingual minds was unknown. We address this question using a mouse-tracking experimental paradigm to trace the internal lexical matching processes underlying the lexical access. Our linear mixed effects models and growth curve analyses revealed that a low orthographic neighborhood can trigger a large magnitude of the Cambridge University effect for monolinguals and bilinguals on their hand trajectories. We also found that different-script bilinguals (Chinese-English bilinguals) exhibited a greater Cambridge University effect than similar-script bilinguals (Spanish-English bilinguals) and English monolinguals. The findings offer compelling evidence that a human lexical match criterion of recognition system can be modified by neighborhood density and cross-language script similarity of readers. PMID:27107983

  3. Nutritive evaluation and effect of Moringa oleifera pod on clastogenic potential in the mouse.

    PubMed

    Promkum, Chadamas; Kupradinun, Piengchai; Tuntipopipat, Siriporn; Butryee, Chaniphun

    2010-01-01

    Moringa oleifera Lam (horseradish tree; tender pod or fruits) has been consumed as a vegetable and utilized as a major ingredient of healthy Thai cuisine. Previous studies have shown that M. oleifera pod extracts act as bifunctional inducers along with displaying antioxidant properties and also inhibiting skin papillomagenesis in mice. This study was aimed to determine the nutritive value, and clastogenic and anticlastogenic potentials of M. oleifera pod. The nutritive value was determined according to AOAC methods. The clastogenic and anticlastogenic potentials were determined using the in vivo erythrocyte micronucleus assay in the mouse. Eighty male mice were fed semi-purified diets containing 1.5%, 3.0% and 6.0% of ground freeze-dried boiled M. oleifera pod (bMO) for 2 weeks prior to administration of both direct-acting (mitomycin C, MMC) and indirect-acting (7, 12-dimethylbenz(a)anthracene, DMBA), clastogens. Blood samples were collected at 0, 24, 48 and 72 h, dropped on acridine orange-coated slides, and then counted for reticulocytes both with and without micronuclei by fluorescence microscopy. The nutritive value of 100 g bMO consisted of: moisture content, 8.2 g; protein, 19.2 g; fat, 3.9 g; carbohydrate (dietary fiber included), 60.5 g; dietary fiber, 37.5 g; ash, 8.1 g and energy, 354 kcal. Freeze-dried boiled M. oleifera had no clastogenic activity in the mouse while it possessed anticlastogenic activity against both direct and indirect-acting clastogens. Freeze-dried boiled M. oleifera pod at 1.5%, 3.0% and 6.0% in the diets decreased the number of micronucleated peripheral reticulocytes (MNRETs) induced by both MMC and DMBA. However, the effect was statistically significant in the dose dependent manner only in the MMC-treated group. In conclusion, the present study demonstrated that bMO has no clastogenicity and possesses anticlastogenic potential against clastogens, and particularly a direct-acting clastogen in the mouse. PMID:21039028

  4. Effect of urethane, dimethylnitrosamine, paraquat, and butylated hydroxytoluene on the activities of glycolytic key enzymes in mouse lung

    SciTech Connect

    Arany, I.; Rady, P.; Bojan, I.; Kertai, P.

    1981-12-01

    Effects of carcinogens and noncarcinogenic pulmonary toxicants on the activities of glycolytic key enzymes in the mouse lung were investigated. The carcinogens urethane (URTH) and dimethylnitrosamine (DMN) permanently enhanced, and the noncarcinogenic pulmonary toxicants paraquat (PAR) and butylated hydroxytoluene (BHT) temporarily, enhanced the activities of hexokinase (HK), phosphofructokinase (PFK), and pyruvate kinase (PK) in the lungs of mice.

  5. EFFECTS OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) ON FETAL MOUSE URINARY TRACT EPITHELIUM IN VITRO

    EPA Science Inventory

    2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), produces hydronephrosis by altering the differentiation and proliferation of ureteric epithelial cells in the embryonic C57BL/6N mouse urinary tract. This study examines the effects of TCDD on late gestation fetal urinary tract cells u...

  6. Effect of glucagon on digestive enzyme synthesis, transport and secretion in mouse pancreatic acinar cells.

    PubMed Central

    Singh, M

    1980-01-01

    1. Effect of glucagon on amylase secretion and lactic dehydrogenase (LDH) release from functionally intact dissociated pancreatic acinar cells and acini was studied. 2. In dissociated rat pancreatic acinar cells, the rate of amylase secretion was increased by 70% with bethanechol (maximally effective concentration, 10(-4) M) and 125% with A23187 (10(-5) M), but the response to cholecystokinin-pancreozymin (CCK-PZ) was inconsistent. In dissociated cells from mouse pancreas, the increases amounted to 78% with bethanechol (10(-4) M), 134% with A23187 (10(-5) M) and 82% with CCK-PZ (maximally effective concentration, 0 . 01 u. ml.-1). Glucagon in concentrations ranging from 10(-7) to 10(-4) M increased amylase secretion by 3, 26, 67 and 80%, whereas secretin (10(-8)--10(-5) M) increased amylase secretion by 8, 39, 88 and 138%. LDH release was increased with A23187 in concentrations greater than 10(-6) M. 3. CCK-PZ, bethanechol and A23187 used in maximal concentrations potentiated the effect of a submaximal dose of glucagon whereas secretin did not have an additive or a potentiating effect. 4. Pancreatic acini were approximately 3 times more responsive to secretagogues than cells. The dose--response curves to bethanechol, glucagon and CCK-PZ for increase in amylase secretion were similar. LDH release was not increased by these agents. Cytochalasin B (5 microgram ml.-1) which is known to disrupt the integrity of luminal membrane inhibited the amylase secretion stimulated by glucagon, bethanechol and CCK-PZ. 5. Glucagon inhibited incorporation of a mixture of fifteen 14C-labelled amino acids (algal profile, Schwarz Mann) into perchloric acid precipitable proteins in dissociated mouse pancreatic acini within 30 min. 6. In 'pulse-chase' experiments, glucagon decreased the specific activity of zymogen granules isolated by differential centrifugation, from pancreatic lobules (120 min) and increased the specific activity of radiolabelled proteins in the medium (60 and 120 min

  7. Genotoxic effects of 1 GeV/amu Fe ions in mouse kidney epithelial cells

    NASA Astrophysics Data System (ADS)

    Kronenberg, A.; Gauny, S. S.; Connolly, L.; Turker, M.

    Human exploration of space places individuals in environments where they are exposed to charged particle radiation. The goal of our studies is to assess the genotoxic and mutagenic effects of high energy Fe ions (1 GeV/amu) in kidney epithelial cells of the mouse irradiated either in vitro or in vivo. The initial study focused on establishing the toxicity of these heavy ions (LET=159 keV/micron) in two Aprt heterozygous kidney epithelial cell lines: K06 cells derived from a C57BL6/129Sv animal, and clone 4a cells derived from a C57BL6/DBA2 animal. Cells were exposed in vitro to graded doses of Fe ions (0-300 cGy) and the toxicity of the treatment was established using colony forming assays. Experiments were performed in triplicate at the NASA Space Radiation Laboratory at Brookhaven National Laboratory. The results indicate that Fe ions are toxic to mouse kidney epithelial cells and that no shoulder is observed on the survival curve for cells from either genetic background. The clone 4a cells were more sensitive to Fe ion exposures than the K06 cells. The D(37) for clone 4a cells was 92 cGy and the D(10) was 212 cGy. The more resistant K06 cells had a D(37) of 192 cGy and an estimated D(10) of 388 cGy. Parallel experiments are underway to establish the RBE's for cell killing for these two cell lines. Supported by NASA grant T-403X to A. Kronenberg

  8. A mouse model mimicking human first night effect for the evaluation of hypnotics.

    PubMed

    Xu, Qi; Xu, Xin-Hong; Qu, Wei-Min; Lazarus, Michael; Urade, Yoshihiro; Huang, Zhi-Li

    2014-01-01

    In humans, a first night effect (FNE) is characterized by increased sleep latency and decreased total sleep time in an unfamiliar environment, but the mechanism and treatment options for this universally experienced acute insomnia are unclear. We continuously recorded electroencephalography (EEG) and electromyogram (EMG) and measured plasma corticosterone levels to develop a mouse FNE model by inducing acute insomnia in mice that have been placed in unfamiliar cage environments. The sleep latency of mice 'moved to clean cages' (MCC) was longer than that for mice 'moved to dirty ones' (MDC). As compared to MDC mice, MCC mice showed stronger decreases in the amount of non-rapid eye movement (non-REM, NREM) and REM sleep, with a lower power density of NREM sleep, increased fragmentation and decreased stage transitions from NREM sleep to wake, and higher variation in plasma corticosterone levels. Treatment of MCC mice with zolpidem, diazepam, raclopride, pyrilamine, except SCH23390 shortened NREM sleep latency. In addition, zolpidem significantly increased NREM and REM sleep with the increase in slow wave activity (1.00-2.75 Hz), while raclopride significantly increased NREM and REM sleep without changing the EEG power density in MCC mice, whereas diazepam increased sleep with a drastic decrease in power density of the frequency band between 1.00 and 4.00 Hz, diazepam also increased the frequency band between 9.75 and 24.75 Hz during NREM sleep. These results indicate that a MCC mouse can mimic a FNE phenotype of humans and that zolpidem and raclopride may be useful drugs to prevent acute insomnia, including FNE. PMID:24316349

  9. Metabolic Substrates Exhibit Differential Effects on Functional Parameters of Mouse Sperm Capacitation1

    PubMed Central

    Goodson, Summer G.; Qiu, Yunping; Sutton, Keith A.; Xie, Guoxiang; Jia, Wei; O'Brien, Deborah A.

    2012-01-01

    ABSTRACT Although substantial evidence exists that sperm ATP production via glycolysis is required for mammalian sperm function and male fertility, conflicting reports involving multiple species have appeared regarding the ability of individual glycolytic or mitochondrial substrates to support the physiological changes that occur during capacitation. Several mouse models with defects in the signaling pathways required for capacitation exhibit reductions in sperm ATP levels, suggesting regulatory interactions between sperm metabolism and signal transduction cascades. To better understand these interactions, we conducted quantitative studies of mouse sperm throughout a 2-h in vitro capacitation period and compared the effects of single substrates assayed under identical conditions. Multiple glycolytic and nonglycolytic substrates maintained sperm ATP levels and comparable percentages of motility, but only glucose and mannose supported hyperactivation. These monosaccharides and fructose supported the full pattern of tyrosine phosphorylation, whereas nonglycolytic substrates supported at least partial tyrosine phosphorylation. Inhibition of glycolysis impaired motility in the presence of glucose, fructose, or pyruvate but not in the presence of hydroxybutyrate. Addition of an uncoupler of oxidative phosphorylation reduced motility with pyruvate or hydroxybutyrate as substrates but unexpectedly stimulated hyperactivation with fructose. Investigating differences between glucose and fructose in more detail, we demonstrated that hyperactivation results from the active metabolism of glucose. Differences between glucose and fructose appeared to be downstream of changes in intracellular pH, which rose to comparable levels during incubation with either substrate. Sperm redox pathways were differentially affected, with higher levels of associated metabolites and reactive oxygen species generated during incubations with fructose than during incubations with glucose. PMID

  10. Neuroprotective Effects of Voluntary Exercise in an Inherited Retinal Degeneration Mouse Model

    PubMed Central

    Hanif, Adam M.; Lawson, Eric C.; Prunty, Megan; Gogniat, Marissa; Aung, Moe H.; Chakraborty, Ranjay; Boatright, Jeffrey H.; Pardue, Machelle T.

    2015-01-01

    Purpose Our previous investigations showed that involuntary treadmill exercise is neuroprotective in a light-induced retinal degeneration mouse model, and it may act through activation of tropomyosin-related kinase B (TrkB) receptors. This study investigated whether voluntary running wheel exercise can be neuroprotective in an inheritable model of the retinal degenerative disease retinitis pigmentosa (RP), rd10 mice. Methods Breeding pairs of rd10 and C57BL/6J mice were given free-spinning (active) or locked (inactive) running wheels. Pups were weaned into separate cages with their parents' respective wheel types, and visual function was tested with ERG and a virtual optokinetic system at 4, 5, and 6 weeks of age. Offspring were killed at 6 weeks of age and retinal cross-sections were prepared for photoreceptor nuclei counting. Additionally, separate cohorts of active and inactive rd10 pups were injected daily for 14 days after eye opening with a selective TrkB receptor antagonist (ANA-12) or vehicle solution and assessed as described above. Results Mice in the rd10 active group exhibited significant preservation of visual acuity, cone nuclei, and total photoreceptor nuclei number. Injection with ANA-12 precluded the preservation of visual acuity and photoreceptor nuclei number in rd10 mice. Conclusions Voluntary running partially protected against the retinal degeneration and vision loss that otherwise occurs in the rd10 mouse model of RP. This protection was prevented by injection of ANA-12, suggesting that TrkB activation mediates exercise's preservation of the retina. Exercise may serve as an effective, clinically translational intervention against retinal degeneration. PMID:26567796

  11. Effects of Aroclor 1254 on In Vivo Oocyte Maturation in the Mouse

    PubMed Central

    Liu, ShuZhen; Jiang, LiGang; Meng, XiaoQian; Han, XiaoYing; Cheng, Dong; Zhang, TianLiang; Miao, YiLiang

    2014-01-01

    Polychlorinated biphenyls (PCBs) are stable, lipophilic compounds that accumulate in the environment and in the food chain. Though some studies provided evidence that PCBs had adverse effects on reproductive function, most of these results were from in vitro models. Therefore we investigated the effect of Aroclor 1254 (a commercial PCBs mixture) treatments on in vivo maturation and developmental potential of mouse oocytes. In the present study, female ICR mice were treated with different doses (12.5, 25 and 50 mg/kg) of Aroclor 1254 (a commercial PCB mixture) once every 72 hours by intraperitoneal injection for 9 days. After three treatments of Aroclor 1254, the mice were superovulated to collect oocytes one day after the last exposure. The effects of Aroclor 1254 on oocyte maturation, fertilization, and preimplantation embryonic development were investigated. Immunofluorescence-stained oocytes were observed under a confocal microscope to assess the effects of Aroclor 1254 on spindle morphology. Parthenogenic activation and the incidence of cumulus apoptosis in cumulus-oocyte complexes were observed as well. Oocytes exposed to different doses of Aroclor 1254 in vivo were associated with a significant decrease in outgrowth potential, abnormal spindle configurations, and the inhibition of parthenogenetic activation of ovulated oocytes. Furthermore, the incidence of apoptosis in cumulus cells was increased after exposed to Aroclor 1254. These results may provide reference for the treatment of reproductive diseases such as infertility or miscarriage caused by environmental contaminants. PMID:25013911

  12. Effects of suspension-induced osteopenia on the mechanical behaviour of mouse long bones

    NASA Technical Reports Server (NTRS)

    Simske, S. J.; Greenberg, A. R.; Luttges, M. W.; Spooner, B. S. (Principal Investigator)

    1991-01-01

    Whereas most studies of tail-suspension induced osteopenia have utilized rat femora, the present study investigated the effects of a 14 day tail-suspension on the mechanical behaviour of mice femora, tibiae and humeri. Force-deflection properties were obtained via three-point bending for long bones from suspended and control mice. Whole bone behaviour was characterized by converting the force-deflection values to stiffness, strength, ductility and energy parameters which were not normalized for specimen geometry. The effects of a systematic variation in the deflection rate over the range 0.1-10 mm min-1 were also evaluated. Statistical analysis indicated that the primary effect of the tail-suspension period was lowered bone mass which was manifested mechanically through lower values of the bone strength parameters. These effects were similar in the bones of both the fore and hind limbs. The results also demonstrated that the stiffness, ductility and energy characteristics were much less influenced by the tail-suspension. Whereas a significant dependence of the bone strength values upon deflection rate was observed for the femora and humeri, the other mechanical parameters were less sensitive. Based upon the nature of the physical and mechanical changes observed in the long bones following tail-suspension, the mouse appears to be a suitable animal model for the study of osteopenia.

  13. Effect of azelnidipine and amlodipine on single cell mechanics in mouse cardiomyocytes.

    PubMed

    Iribe, Gentaro; Kaihara, Keiko; Ito, Hiroshi; Naruse, Keiji

    2013-09-01

    Azelnidipine and amlodipine are dihydropyridine-type Ca(2+) channel blockers for the treatment of hypertension. Although these drugs have high vasoselectivity and small negative inotropic effects in vivo, little is known regarding their direct effects on cellular contractility without humoral regulation or the additive effects of these drugs with other antihypertensive drugs on myocardial contractility. To investigate the effects of Ca(2+) channel blockers on single cell mechanics, mouse cardiomyocytes were enzymatically isolated, and a pair of carbon fibers was attached to opposite cell-ends to stretch the cells. Cells were paced at 4 Hz superfused in normal Tyrode solution at 37°C. Cell length and active/passive force calculated from carbon fiber bending were recorded in 6 different preload conditions. Slopes of end-systolic force-length relation curves (maximum elastance) were measured as an index of contractility before and after drugs were administered. Azelnidipine at 10nM and 100 nM did not change maximum elastance, while amlodipine at 100 nM did decrease maximum elastance. The combination of RNH-6270 (active form of angiotensin II receptor blocker, olmesartan, 10nM) and either amlodipine (10nM) or azelnidipine (10nM) did not affect maximum elastance. Although both amlodipine and azelnidipine can be used safely at therapeutically relevant concentrations even in combination with olmesartan, the present results suggest that azelnidipine has a less negative inotropic action compared to amlodipine. PMID:23747592

  14. Limited Effect of Chronic Valproic Acid Treatment in a Mouse Model of Machado-Joseph Disease

    PubMed Central

    Esteves, Sofia; Duarte-Silva, Sara; Naia, Luana; Neves-Carvalho, Andreia; Teixeira-Castro, Andreia; Rego, Ana Cristina; Silva-Fernandes, Anabela; Maciel, Patrícia

    2015-01-01

    Machado-Joseph disease (MJD) is an inherited neurodegenerative disease, caused by a CAG repeat expansion within the coding region of ATXN3 gene, and which currently lacks effective treatment. In this work we tested the therapeutic efficacy of chronic treatment with valproic acid (VPA) (200mg/kg), a compound with known neuroprotection activity, and previously shown to be effective in cell, fly and nematode models of MJD. We show that chronic VPA treatment in the CMVMJD135 mouse model had limited effects in the motor deficits of these mice, seen mostly at late stages in the motor swimming, beam walk, rotarod and spontaneous locomotor activity tests, and did not modify the ATXN3 inclusion load and astrogliosis in affected brain regions. However, VPA chronic treatment was able to increase GRP78 protein levels at 30 weeks of age, one of its known neuroprotective effects, confirming target engagement. In spite of limited results, the use of another dosage of VPA or of VPA in a combined therapy with molecules targeting other pathways, cannot be excluded as potential strategies for MJD therapeutics. PMID:26505994

  15. Differences in the spatiotemporal expression and epistatic gene regulation of the mesodiencephalic dopaminergic precursor marker PITX3 during chicken and mouse development.

    PubMed

    Klafke, Ruth; Prem Anand, A Alwin; Wurst, Wolfgang; Prakash, Nilima; Wizenmann, Andrea

    2016-02-15

    Mesodiencephalic dopaminergic (mdDA) neurons are located in the ventral mesencephalon and caudal diencephalon of all tetrapod species studied so far. They are the most prominent DA neuronal population and are implicated in control and modulation of motor, cognitive and rewarding/affective behaviors. Their degeneration or dysfunction is intimately linked to several neurological and neuropsychiatric human diseases. To gain further insights into their generation, we studied spatiotemporal expression patterns and epistatic interactions in chick embryos of selected marker genes and signaling pathways associated with mdDA neuron development in mouse. We detected striking differences in the expression patterns of the chick orthologs of the mouse mdDA marker genes Pitx3 and Aldh1a1, which suggests important differences between the species in the generation/generating of these cells. We also discovered that the sonic hedgehog signaling pathway is both necessary and sufficient for the induction of ectopic PITX3 expression in chick mesencephalon downstream of WNT9A-induced LMX1a transcription. These aspects of early chicken development resemble the ontogeny of zebrafish diencephalic DA neuronal populations, and suggest a divergence between birds and mammals during evolution. PMID:26755703

  16. Longitudinal Effects of Ketamine on Dendritic Architecture In Vivo in the Mouse Medial Frontal Cortex123

    PubMed Central

    Phoumthipphavong, Victoria; Barthas, Florent; Hassett, Samantha

    2016-01-01

    Abstract A single subanesthetic dose of ketamine, an NMDA receptor antagonist, leads to fast-acting antidepressant effects. In rodent models, systemic ketamine is associated with higher dendritic spine density in the prefrontal cortex, reflecting structural remodeling that may underlie the behavioral changes. However, turnover of dendritic spines is a dynamic process in vivo, and the longitudinal effects of ketamine on structural plasticity remain unclear. The purpose of the current study is to use subcellular resolution optical imaging to determine the time course of dendritic alterations in vivo following systemic ketamine administration in mice. We used two-photon microscopy to visualize repeatedly the same set of dendritic branches in the mouse medial frontal cortex (MFC) before and after a single injection of ketamine or saline. Compared to controls, ketamine-injected mice had higher dendritic spine density in MFC for up to 2 weeks. This prolonged increase in spine density was driven by an elevated spine formation rate, and not by changes in the spine elimination rate. A fraction of the new spines following ketamine injection was persistent, which is indicative of functional synapses. In a few cases, we also observed retraction of distal apical tuft branches on the day immediately after ketamine administration. These results indicate that following systemic ketamine administration, certain dendritic inputs in MFC are removed immediately, while others are added gradually. These dynamic structural modifications are consistent with a model of ketamine action in which the net effect is a rebalancing of synaptic inputs received by frontal cortical neurons. PMID:27066532

  17. Effects of heat shock on survival, proliferation and differentiation of mouse neural stem cells.

    PubMed

    Omori, Hiroyuki; Otsu, Masahiro; Suzuki, Asami; Nakayama, Takashi; Akama, Kuniko; Watanabe, Masaru; Inoue, Nobuo

    2014-02-01

    Hyperthermia during pregnancy is a significant cause of reproductive problems ranging from abortion to congenital defects of the central nervous system (CNS), including neural tube defects and microcephaly. Neural stem cells (NSCs) can proliferate and differentiate into neurons and glia, playing a key role in the formation of the CNS. Here, we examined the effects of heat shock on homogeneous proliferating NSCs derived from mouse embryonic stem cells. After heat shock at 42 °C for 20 min, the proliferating NSCs continued to proliferate, although subtle changes were observed in gene expression and cell survival and proliferation. In contrast, heat shock at 43 °C caused a variety of responses: the up-regulation of genes encoding heat shock proteins (HSP), induction of apoptosis, temporal inhibition of cell proliferation and retardation of differentiation. Finally, effects of heat shock at 44 °C were severe, with almost all cells disappearing and the remaining cells losing the capacity to proliferate and differentiate. These temperature-dependent effects of heat shock on NSCs may be valuable in elucidating the mechanisms by which hyperthermia during pregnancy causes various reproductive problems. PMID:24316183

  18. Ret is essential to mediate GDNF's neuroprotective and neuroregenerative effect in a Parkinson disease mouse model.

    PubMed

    Drinkut, Anja; Tillack, Karsten; Meka, Durga P; Schulz, Jorg B; Kügler, Sebastian; Kramer, Edgar R

    2016-01-01

    Glial cell line-derived neurotrophic factor (GDNF) is a potent survival and regeneration-promoting factor for dopaminergic neurons in cell and animal models of Parkinson disease (PD). GDNF is currently tested in clinical trials on PD patients with so far inconclusive results. The receptor tyrosine kinase Ret is the canonical GDNF receptor, but several alternative GDNF receptors have been proposed, raising the question of which signaling receptor mediates here the beneficial GDNF effects. To address this question we overexpressed GDNF in the striatum of mice deficient for Ret in dopaminergic neurons and subsequently challenged these mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Strikingly, in this established PD mouse model, the absence of Ret completely abolished GDNF's neuroprotective and regenerative effect on the midbrain dopaminergic system. This establishes Ret signaling as absolutely required for GDNF's effects to prevent and compensate dopaminergic system degeneration and suggests Ret activation as the primary target of GDNF therapy in PD. PMID:27607574

  19. The effect of glucocorticoids on mouse oocyte in vitro maturation and subsequent fertilization and embryo development.

    PubMed

    González, Raquel; Ruiz-León, Yolanda; Gomendio, Montserrat; Roldan, Eduardo R S

    2010-02-01

    Increased glucocorticoid levels, due to medical therapy or stress-related, may affect reproduction via the hypothalamus-pituitary-axis or directly at the oocyte level. We examined the effects of natural (corticosterone) or synthetic (dexamethasone) glucocorticoids on mouse oocyte maturation and underlying changes in extracellular signal-regulated kinase (ERK) phosphorylation patterns. Fertilization and progression up to the blastocyst stage were also evaluated. Oocytes were exposed to corticosterone or dexamethasone (0, 0.25, 2.5, 25 or 250microM) for 17h during in vitro maturation. After maturation, ERK-1/2 activation in oocytes was assessed by SDS-PAGE and immunoblotting, and fertilization and developmental capacity were examined in vitro. Corticosterone exposure during oocyte maturation significantly decreased progression to metaphase II, fertilization and embryo development at the highest concentration. Corticosterone caused a concentration-dependent inhibition of ERK-1/2 activation, with the highest concentration resulting in considerable inhibition of oocyte ERK-1/2 phosphorylation and no blastocyst development. In contrast, dexamethasone had no effect on maturation, fertilization and cleavage, and no effect was seen on ERK-1/2 phosphorylation. Based on these in vitro findings, high glucocorticoid levels may have consequences for subsequent development, although a short exposure to physiologic or stress-related glucocorticoid levels may not represent a hazard to meiosis progression of the oocyte. PMID:19733225

  20. Therapeutic Effect of Berberine on Huntington’s Disease Transgenic Mouse Model

    PubMed Central

    Jiang, Wenxiao; Wei, Wenjie; Gaertig, Marta A.; Li, Shihua; Li, Xiao-Jiang

    2015-01-01

    Huntington disease (HD) represents a family of neurodegenerative diseases that are caused by misfolded proteins. The misfolded proteins accumulate in the affected brain regions in an age-dependent manner to cause late-onset neurodegeneration. Transgenic mouse models expressing the HD protein, huntingtin, have been widely used to identify therapeutics that may retard disease progression. Here we report that Berberine (BBR), an organic small molecule isolated from plants, has protective effects on transgenic HD (N171-82Q) mice. We found that BBR can reduce the accumulation of mutant huntingtin in cultured cells. More importantly, when given orally, BBR could effectively alleviate motor dysfunction and prolong the survival of transgenic N171-82Q HD mice. We found that BBR could promote the degradation of mutant huntingtin by enhancing autophagic function. Since BBR is an orally-taken drug that has been safely used to treat a number of diseases, our findings suggest that BBR can be tested on different HD animal models and HD patients to further evaluate its therapeutic effects. PMID:26225560

  1. Effect of oral calcium and calcium + fluoride treatments on mouse bone properties during suspension

    NASA Technical Reports Server (NTRS)

    Simske, S. J.; Luttges, M. W.; Allen, K. A.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    The bone effects of oral dosages of calcium chloride with or without supplementary sodium fluoride were assessed in antiorthostatically suspended mice. Two calcium dosages were used to replace half (3.1 mM) or all(6.3 mM) of the dietary calcium lost due to reduced food intake by the suspended mice. Two groups of 6.3 mM CaCl2-treated mice were additionally treated with 0.25 or 2.5 mM NaF. The results indicate that supplementation of the mouse drinking water with calcium salts prevents bone changes induced by short-term suspension, while calcium salts in combination with fluoride are less effective as fluoride dosage increases. However, the calcium supplements change the relationship between the femur mechanical properties and the mineral composition of the bone. Because of this, it appears that oral calcium supplements are effective through a mechanism other than simple dietary supplementation and may indicate a dependence of bone consistency on systemic and local fluid conditions.

  2. Neuroprotective effects of geniposide in the MPTP mouse model of Parkinson's disease.

    PubMed

    Chen, YiMei; Zhang, Yanfang; Li, Lin; Hölscher, Christian

    2015-12-01

    Parkinson's disease (PD) is a chronic neurodegenerative disease, and there is no cure for it at present. We tested the drug Geniposide, an active component of Gardenia jasminoides Ellis which is used in traditional Chinese medicine. Geniposide has shown neuroprotective and growth-factor like effects in several in vivo and in vitro studies. In the present study, Geniposide had been tested in an acute PD mouse model induced by four 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneal injections. Geniposide treatment (100mg/kg ip.) for 8 days after MPTP treatment (30mg/kg ip.) improved the locomotor and exploratory activity of mice (open field), and improved bradykinesia and movement balance of mice (rotarod, swim test). Geniposide treatment also restored tyrosine hydroxylase (TH) positive dopaminergic neuron numbers in the substantia nigra pars compacta. Drug treatment also increased levels of growth factor signaling molecule Bax and reduced the apoptosis signaling molecule Bcl-2. Caspase 3 activation was also reduced in the substantia nigra. We conclude that Geniposide exerted its neuroprotective effect by enhancing growth factor signaling and the reduction of apoptosis. Geniposide is an ingredient in Chinese traditional medicine with few known side effects and shows potential as a drug treatment for Parkinson's disease. PMID:26409043

  3. Effects of multimodal analgesia on the success of mouse embryo transfer surgery.

    PubMed

    Parker, John M; Austin, Jamie; Wilkerson, James; Carbone, Larry

    2011-07-01

    Multimodal analgesia is promoted as the best practice pain management for invasive animal research procedures. Universal acceptance and incorporation of multimodal analgesia requires assessing potential effects on study outcome. The focus of this study was to assess effects on embryo survival after multimodal analgesia comprising an opioid and nonsteroidal antiinflammatory drug (NSAID) compared with opioid-only analgesia during embryo transfer procedures in transgenic mouse production. Mice were assigned to receive either carprofen (5 mg/kg) with buprenorphine (0.1 mg/kg; CB) or vehicle with buprenorphine (0.1 mg/kg; VB) in a prospective, double-blinded placebo controlled clinical trial. Data were analyzed in surgical sets of 1 to 3 female mice receiving embryos chimeric for a shared targeted embryonic stem-cell clone and host blastocyst cells. A total of 99 surgical sets were analyzed, comprising 199 Crl:CD1 female mice and their 996 offspring. Neither yield (pups weaned per embryo implanted in the surgical set) nor birth rate (average number of pups weaned per dam in the set) differed significantly between the CB and VB conditions. Multimodal opioid-NSAID analgesia appears to have no significant positive or negative effect on the success of producing novel lines of transgenic mice by blastocyst transfer. PMID:21838973

  4. Neurotoxic effects of ochratoxin A on the subventricular zone of adult mouse brain.

    PubMed

    Paradells, Sara; Rocamonde, Brenda; Llinares, Cristina; Herranz-Pérez, Vicente; Jimenez, Misericordia; Garcia-Verdugo, Jose Manuel; Zipancic, Ivan; Soria, Jose Miguel; Garcia-Esparza, Ma Angeles

    2015-07-01

    Ochratoxin A (OTA), a mycotoxin that was discovered as a secondary metabolite of the fungal species Aspergillus and Penicillium, is a common contaminant in food and animal feed. This mycotoxin has been described as teratogenic, carcinogenic, genotoxic, immunotoxic and has been proven a potent neurotoxin. Other authors have previously reported the effects of OTA in different structures of the central nervous system as well as in some neurogenic regions. However, the impact of OTA exposure in the subventricular zone (SVZ) has not been assessed yet. To elucidate whether OTA affects neural precursors of the mouse SVZ we investigated, in vitro and in vivo, the effects of OTA exposure on the SVZ and on the neural precursors obtained from this neurogenic niche. In this work, we prove the cumulative effect of OTA exposure on proliferation, differentiation and depletion of neural stem cells cultured from the SVZ. In addition, we corroborated these results in vivo by immunohistochemistry and electron microscopy. As a result, we found a significant alteration in the proliferation process, which was evidenced by a decrease in the number of 5-bromo-2-deoxyuridine-positive cells and glial cells, as well as, a significant decrease in the number of neuroblasts in the SVZ. To summarize, in this study we demonstrate how OTA could be a threat to the developing and the adult SVZ through its impact in cell viability, proliferation and differentiation in a dose-dependent manner. PMID:25256750

  5. Effective chemoimmunotherapy with anti-TGFβ antibody and cyclophosphamide in a mouse model of breast cancer.

    PubMed

    Chen, Xin; Yang, Yuan; Zhou, Qiong; Weiss, Jonathan M; Howard, Olamae Zack; McPherson, John M; Wakefield, Lalage M; Oppenheim, Joost J

    2014-01-01

    TGFβ is reportedly responsible for accumulation of CD4(+)Foxp3(+) regulatory T cells (Tregs) in tumor. Thus, we treated mouse 4T1 mammary carcinoma with 1D11, a neutralizing anti-TGFβ (1,2,3) antibody. The treatment delayed tumor growth, but unexpectedly increased the proportion of Tregs in tumor. In vitro, 1D11 enhanced while TGFβ potently inhibited the proliferation of Tregs. To enhance the anti-tumor effects, 1D11 was administered with cyclophosphamide which was reported to eliminate intratumoral Tregs. This combination resulted in long term tumor-free survival of up to 80% of mice, and the tumor-free mice were more resistant to re-challenge with tumor. To examine the phenotype of tumor infiltrating immune cells, 4T1-tumor bearing mice were treated with 1D11 and a lower dose of cyclophosphamide. This treatment markedly inhibited tumor growth, and was accompanied by massive infiltration of IFNγ-producing T cells. Furthermore, this combination markedly decreased the number of splenic CD11b(+)Gr1(+) cells, and increased their expression levels of MHC II and CD80. In a spontaneous 4T1 lung metastasis model with resection of primary tumor, this combination therapy markedly increased the survival of mice, indicating it was effective in reducing lethal metastasis burden. Taken together, our data show that anti-TGFβ antibody and cyclophosphamide represents an effective chemoimmunotherapeutic combination. PMID:24416401

  6. Effects of Chung-Pae Inhalation Therapy on a Mouse Model of Chronic Obstructive Pulmonary Disease

    PubMed Central

    Hwang, Joon-Ho; Lee, Beom-Joon; Jung, Hee Jae; Kim, Kwan-Il; Choi, Jun-Yong; Joo, Myungsoo; Jung, Sung-Ki

    2015-01-01

    Chung-pae (CP) inhalation therapy is a method frequently used in Korea to treat lung disease, especially chronic obstructive pulmonary disease (COPD). This study investigated the effects of CP inhalation on a COPD animal model. C57BL/6 mice received porcine pancreatic elastase (PPE) and lipopolysaccharide (LPS) alternately three times for 3 weeks to induce COPD. Then, CP (5 or 20 mg/kg) was administered every 2 h after the final LPS administration. The effect of CP was evaluated by bronchoalveolar lavage (BAL) fluid analysis, histological analysis of lung tissue, and reverse transcription polymerase chain reaction analysis of mRNA of interleukin- (IL-) 1β, tumor necrosis factor- (TNF-) α, IL-6, and tumor growth factor- (TGF-) β. Intratracheal CP administration reduced the number of leukocytes and neutrophils in BAL fluid, inhibited the histological appearance of lung damage, and decreased the mRNA levels of the proinflammatory cytokines IL-1β, TNF-α, IL-6, and TGF-β. Intratracheal CP administration effectively decreased the chronic inflammation and pathological changes in a PPE- and LPS-induced COPD mouse model. Therefore, we suggest that CP is a promising strategy for COPD. PMID:26539225

  7. Technical note: Milk composition in mice--methodological aspects and effects of mouse strain and lactation day.

    PubMed

    Görs, S; Kucia, M; Langhammer, M; Junghans, P; Metges, C C

    2009-02-01

    Analysis in individual mouse milk samples is restricted by small sample volumes and hindered by high fat contents. Miniaturized methods were developed for the analysis of dry matter (DM), crude fat, crude protein (CP), and lactose in individual samples of mouse milk and used to compare milk from the mouse strain DU6, the largest growth-selected mouse line worldwide, with unselected mice (CON) on lactation d 3, 14, and 18. Individual milk samples were collected by means of a self-constructed milking machine. Aliquots of 10 microL of milk were used to measure DM [coefficient of variation (CV) <2.1%], which was subsequently used to analyze nitrogen for calculation of CP (CV 2.7%). Crude fat was determined in 100 microL via a miniaturized Röse-Gottlieb method (CV 2.8%). An HPLC protocol was used to analyze lactose in 20 microL of diluted whey (CV 5.3%). The miniaturized methods gave similar results compared with conventional approaches. Homogenization was the most important factor affecting milk composition and its reproducibility. Milk storage at -20 degrees C had no effect on composition. Irrespective of the mouse strain, maximum values of 45.5% DM, 29.8% fat, and 12.7% CP were observed at d 14. The greatest lactose contents were found on d 18 (2.41%). Milk lactose concentration at d 3 was lower in DU6 (1.13 +/- 0.10%) than CON (1.67 +/- 0.18%). The method provides an accurate assessment of mouse milk composition. PMID:19164675

  8. Inhibitory effects of sodium salicylate and acetylsalicylic acid on UVB-induced mouse skin carcinogenesis.

    PubMed

    Bair, Warner B; Hart, Nancy; Einspahr, Janine; Liu, Guangming; Dong, Zigang; Alberts, David; Bowden, G Tim

    2002-12-01

    We conducted an in vivo carcinogenesis experiment to determine the efficacy of topical aspirin and sodium salicylate (NAS) in preventing UVB-induced nonmelanoma skin cancer. Hairless SKH-1 mice were randomly divided into eight treatment groups. They were treated topically with either 40 or 10 micromol aspirin or NAS three times weekly before 9 kJ/m(2) UVB irradiation. The experiment was carried out over 25 weeks. Both dose levels of NAS significantly inhibited (P < 0.05) the rate of tumor formation when compared with vehicle control. The 40 micromol dose of aspirin significantly inhibited the rate of tumor formation (P < 0.05), whereas the 10 micromol dose had no inhibitory effect when compared with the vehicle control. To investigate the mechanism of this inhibition, we studied UVB-induced thymine dimer formation in the epidermis of the mouse skin. We found that NAS inhibited UVB-induced thymine dimer formation (P = 0.0001), whereas aspirin did not. Therefore, we conclude that NAS prevents UVB-induced tumor growth and formation through a sunscreen effect; whereas, the moderate inhibition of aspirin may be because of a molecular event, such as the inhibition of various UVB signaling pathways. PMID:12496056

  9. Androgen actions in mouse wound healing: Minimal in vivo effects of local antiandrogen delivery.

    PubMed

    Wang, Yiwei; Simanainen, Ulla; Cheer, Kenny; Suarez, Francia G; Gao, Yan Ru; Li, Zhe; Handelsman, David; Maitz, Peter

    2016-05-01

    The aims of this work were to define the role of androgens in female wound healing and to develop and characterize a novel wound dressing with antiandrogens. Androgens retard wound healing in males, but their role in female wound healing has not been established. To understand androgen receptor (AR)-mediated androgen actions in male and female wound healing, we utilized the global AR knockout (ARKO) mouse model, with a mutated AR deleting the second zinc finger to disrupt DNA binding and transcriptional activation. AR inactivation enhanced wound healing rate in males by increasing re-epithelialization and collagen deposition even when wound contraction was eliminated. Cell proliferation and migration in ARKO male fibroblasts was significantly increased compared with wild-type (WT) fibroblasts. However, ARKO females showed a similar healing rate compared to WT females. To exploit local antiandrogen effects in wound healing, while minimizing off-target systemic effects, we developed a novel electrospun polycaprolactone (PCL) scaffold wound dressing material for sustained local antiandrogen delivery. Using the antiandrogen hydroxyl flutamide (HF) at 1, 5, and 10 mg/mL in PCL scaffolds, controlled HF delivery over 21 days significantly enhanced in vitro cell proliferation of human dermal fibroblasts and human keratinocytes. HF-PCL scaffolds also promoted in vivo wound healing in mice compared with open wounds but not to PCL scaffolds. PMID:26873751

  10. Effect of rabies virus infection on gene expression in mouse brain

    PubMed Central

    Prosniak, Mikhail; Hooper, D. Craig; Dietzschold, Bernhard; Koprowski, Hilary

    2001-01-01

    A variety of molecular genetic approaches were used to study the effect of rabies virus (RV) infection on host gene expression in mouse brain. The down-regulation of gene expression was found to be a major effect of RV infection by using subtraction hybridization. However, a combination of techniques identified approximately 39 genes activated by infection. These included genes involved in regulation of cell metabolism, protein synthesis, synaptic activity, and cell growth and differentiation. Northern blot analysis to monitor temporal activation of several of these genes following infection revealed essentially two patterns of activation: (i) an early response with up-regulation beginning within 3 days after infection and correlating with transcription of RV nuclear protein; and (ii) a late response with enhanced expression occurring at days 6–7 after infection and associated with peak RV replication. The gene activation patterns and the known functions of their products suggest that a number of host genes may be involved in the replication and spread of RV in the brain. PMID:11226313

  11. Antinociceptive effects of vitexin in a mouse model of postoperative pain

    PubMed Central

    Zhu, Qing; Mao, Li-Na; Liu, Cheng-Peng; Sun, Yue-Hua; Jiang, Bo; Zhang, Wei; Li, Jun-Xu

    2016-01-01

    Vitexin, a C-glycosylated flavone present in several medicinal herbs, has showed various pharmacological activities including antinociception. The present study investigated the antinociceptive effects of vitexin in a mouse model of postoperative pain. This model was prepared by making a surgical incision on the right hindpaw and von Frey filament test was used to assess mechanical hyperalgesia. Isobolographical analysis method was used to examine the interaction between vitexin and acetaminophen. A reliable mechanical hyperalgesia was observed at 2 h post-surgery and lasted for 4 days. Acute vitexin administration (3–10 mg/kg, i.p.) dose-dependently relieved this hyperalgesia, which was also observed from 1 to 3 days post-surgery during repeated daily treatment. However, repeated vitexin administration prior to surgery had no preventive value. The 10 mg/kg vitexin-induced antinociception was blocked by the opioid receptor antagonist naltrexone or the GABAA receptor antagonist bicuculline. The doses of vitexin used did not significantly suppress the locomotor activity. In addition, the combination of vitexin and acetaminophen produced an infra-additive effect in postoperative pain. Together, though vitexin-acetaminophen combination may not be useful for treating postoperative pain, vitexin exerts behaviorally-specific antinociception against postoperative pain mediated through opioid receptors and GABAA receptors, suggesting that vitexin may be useful for the control of postoperative pain. PMID:26763934

  12. Hormetic Effect of Chronic Hypergravity in a Mouse Model of Allergic Asthma and Rhinitis

    PubMed Central

    Jang, Tae Young; Jung, Ah-Yeoun; Kim, Young Hyo

    2016-01-01

    We aimed to evaluate the effect of chronic hypergravity in a mouse model of allergic asthma and rhinitis. Forty BALB/c mice were divided as: group A (n = 10, control) sensitized and challenged with saline, group B (n = 10, asthma) challenged by intraperitoneal and intranasal ovalbumin (OVA) to induce allergic asthma and rhinitis, and groups C (n = 10, asthma/rotatory control) and D (n = 10, asthma/hypergravity) exposed to 4 weeks of rotation with normogravity (1G) or hypergravity (5G) during induction of asthma/rhinitis. Group D showed significantly decreased eosinophils, neutrophils, and lymphocytes in their BAL fluid compared with groups B and C (p < 0.05). In real-time polymerase chain reaction using lung homogenate, the expression of IL-1β was significantly upregulated (p < 0.001) and IL-4 and IL-10 significantly downregulated (p < 0.05) in group D. Infiltration of inflammatory cells into lung parenchyma and turbinate, and the thickness of respiratory epithelium was significantly reduced in group D (p < 0.05). The expression of Bcl-2 and heme oxygenase-1 were significantly downregulated, Bax and extracellular dismutase significantly upregulated in Group D. Therefore, chronic hypergravity could have a hormetic effect for allergic asthma and rhinitis via regulation of genes involved in antioxidative and proapoptotic pathways. It is possible that we could use hypergravity machinery for treating allergic respiratory disorders. PMID:27251783

  13. Effect of laser optoperforation of the zona pellucida on mouse embryo development in vitro.

    PubMed

    Zakharchenko, E O; Zalessky, A D; Osychenko, A A; Krivokharchenko, A S; Shakhbazyan, A K; Ryabova, A V; Nadtochenko, V A

    2015-06-01

    The effect of laser optical perforation of the zona pellucida on the viability and development of mouse embryos has been studied. Operations of zona pellucida thinning and single or double perforation were carried out on 2-cell embryo, morula, and blastocyst stages with a laser pulse (wavelength 1.48 µm, pulse duration 2 ms). Embryo development up to the blastocyst stage and hatching efficiency were statistically analyzed. It was found that 2-cell or morula stage embryo zona pellucida thinning or single perforation did not affect development to the blastocyst stage and number of hatched embryos, but it accelerated embryo hatching compared to control groups one day earlier in vitro. Double optoperforation on 2-cell embryo or morula stage did not significantly affect development to the blastocyst stage, but it strongly decreased the number of hatched embryos. Also, zona pellucida perforation at the blastocyst stage had a negative effect: hatching did not occur after this manipulation. Blastocyst cell number calculation after single zona pellucida perforation at 2-cell and morula stages showed that cell number of hatching or hatched blastocysts did not differ from the same control groups. This fact points out that the laser single optoperforation method is a useful and safe experimental tool that allows further manipulations within the zona pellucida. PMID:26531022

  14. Anti-wrinkle Effects of Water Extracts of Teas in Hairless Mouse

    PubMed Central

    Kim, Sang Nam; Kim, Young Chul

    2014-01-01

    Tea flavonoids and polyphenols are well known for their extraordinary antioxidant activity which is considered important for anti-aging processes in animals. This study evaluated the anti-wrinkle effects of three different kinds of tea (Camellia sinensis) water extracts (CSWEs) including green, white, and black teas using a photoaged hairless mouse model. Data showed that the CSWE-treatment greatly improved skin conditions of mice suffering from UVB-induced photoaging, based on the parameters including the skin erythema index, moisture capacity, and transepidermal water loss. In addition, the wrinkle measurement and image analysis of skin replicas indicated that CSWEs remarkably inhibited wrinkle formation. In histological examination, the CSWE-treated mice exhibited diminished epidermal thickness and increased collagen and elastic fiber content, key signatures for skin restoration. Furthermore, the reduced expression of MMP-3, a collagen-degradative enzyme, was observed in the skin of CSWE-treated animals. Interestingly, comparative data between green, white, and black tea indicated that the anti-wrinkle activity of white tea and black tea is equally greater than that of green tea. Taken together, these data clearly demonstrated that CSWEs could be used as an effective anti-wrinkle agent in photoaged animal skin, implying their extended uses in therapeutics. PMID:25584148

  15. RXR controlled regulatory networks identified in mouse brain counteract deleterious effects of Aβ oligomers

    PubMed Central

    Nam, Kyong Nyon; Mounier, Anais; Fitz, Nicholas F.; Wolfe, Cody; Schug, Jonathan; Lefterov, Iliya; Koldamova, Radosveta

    2016-01-01

    Bexarotene, a selective agonist for Retinoid X receptors (RXR) improves cognitive deficits and amyloid-β (Aβ) clearance in mice. Here we examine if the effect of bexarotene on RXR cistrome and transcriptomes depend on APOE isoform and Aβ deposition. We found bexarotene increased RXR binding to promoter regions in cortex of APOE3 mice. Rho family GTPases and Wnt signaling pathway were highly enriched in ChIP-seq and RNA-seq datasets and members of those pathways - Lrp1, Lrp5, Sfrp5 and Sema3f were validated. The effect of APOE isoform was compared in APOE3 and APOE4 mice and we found significant overlapping in affected pathways. ChIP-seq using mouse embryonic stem cells and enrichment levels of histone marks H3K4me3 and H3K27me3 revealed that, bexarotene induced epigenetic changes, consistent with increased neuronal differentiation and in correlation with changes in transcription. Comparison of transcriptome in APOE3 and APP/APOE3 mice revealed that amyloid deposition significantly affects the response to bexarotene. In primary neurons, bexarotene ameliorated the damaged dendrite complexity and loss of neurites caused by Aβ42. Finally, we show that the disruption of actin cytoskeleton induced by Aβ42 in vitro was inhibited by bexarotene treatment. Our results suggest a mechanism to establish RXR therapeutic targets with significance in neurodegeneration. PMID:27051978

  16. Non-thermal effects of terahertz radiation on gene expression in mouse stem cells

    PubMed Central

    Alexandrov, Boian S.; Rasmussen, Kim Ø.; Bishop, Alan R.; Usheva, Anny; Alexandrov, Ludmil B.; Chong, Shou; Dagon, Yossi; Booshehri, Layla G.; Mielke, Charles H.; Phipps, M. Lisa; Martinez, Jennifer S.; Chen, Hou-Tong; Rodriguez, George

    2011-01-01

    Abstract In recent years, terahertz radiation sources are increasingly being exploited in military and civil applications. However, only a few studies have so far been conducted to examine the biological effects associated with terahertz radiation. In this study, we evaluated the cellular response of mesenchymal mouse stem cells exposed to THz radiation. We apply low-power radiation from both a pulsed broad-band (centered at 10 THz) source and from a CW laser (2.52 THz) source. Modeling, empirical characterization, and monitoring techniques were applied to minimize the impact of radiation-induced increases in temperature. qRT-PCR was used to evaluate changes in the transcriptional activity of selected hyperthermic genes. We found that temperature increases were minimal, and that the differential expression of the investigated heat shock proteins (HSP105, HSP90, and CPR) was unaffected, while the expression of certain other genes (Adiponectin, GLUT4, and PPARG) showed clear effects of the THz irradiation after prolonged, broad-band exposure. PMID:21991556

  17. Neuroprotective effect of the endogenous neural peptide apelin in cultured mouse cortical neurons

    SciTech Connect

    Zeng, Xiang Jun; Yu, Shan Ping; Zhang, Like; Wei, Ling

    2010-07-01

    The adipocytokine apelin and its G protein-coupled APJ receptor were initially isolated from a bovine stomach and have been detected in the brain and cardiovascular system. Recent studies suggest that apelin can protect cardiomyocytes from ischemic injury. Here, we investigated the effect of apelin on apoptosis in mouse primary cultures of cortical neurons. Exposure of the cortical cultures to a serum-free medium for 24 h induced nuclear fragmentation and apoptotic death; apelin-13 (1.0-5.0 nM) markedly prevented the neuronal apoptosis. Apelin neuroprotective effects were mediated by multiple mechanisms. Apelin-13 reduced serum deprivation (SD)-induced ROS generation, mitochondria depolarization, cytochrome c release and activation of caspase-3. Apelin-13 prevented SD-induced changes in phosphorylation status of Akt and ERK1/2. In addition, apelin-13 attenuated NMDA-induced intracellular Ca{sup 2+} accumulation. These results indicate that apelin is an endogenous neuroprotective adipocytokine that may block apoptosis and excitotoxic death via cellular and molecular mechanisms. It is suggested that apelins may be further explored as a potential neuroprotective reagent for ischemia-induced brain damage.

  18. Exenatide Is an Effective Antihyperglycaemic Agent in a Mouse Model of Wolfram Syndrome 1.

    PubMed

    Sedman, Tuuli; Rünkorg, Kertu; Krass, Maarja; Luuk, Hendrik; Plaas, Mario; Vasar, Eero; Volke, Vallo

    2016-01-01

    Wolfram syndrome 1 is a very rare monogenic disease resulting in a complex of disorders including diabetes mellitus. Up to now, insulin has been used to treat these patients. Some of the monogenic forms of diabetes respond preferentially to sulphonylurea preparations. The aim of the current study was to elucidate whether exenatide, a GLP-1 receptor agonist, and glipizide, a sulphonylurea, are effective in a mouse model of Wolfram syndrome 1. Wolframin-deficient mice were used to test the effect of insulin secretagogues. Wolframin-deficient mice had nearly normal fasting glucose levels but developed hyperglycaemia after glucose challenge. Exenatide in a dose of 10 μg/kg lowered the blood glucose level in both wild-type and wolframin-deficient mice when administered during a nonfasted state and during the intraperitoneal glucose tolerance test. Glipizide (0.6 or 2 mg/kg) was not able to reduce the glucose level in wolframin-deficient animals. In contrast to other groups, wolframin-deficient mice had a lower insulin-to-glucose ratio during the intraperitoneal glucose tolerance test, indicating impaired insulin secretion. Exenatide increased the insulin-to-glucose ratio irrespective of genotype, demonstrating the ability to correct the impaired insulin secretion caused by wolframin deficiency. We conclude that GLP-1 agonists may have potential in the treatment of Wolfram syndrome-related diabetes. PMID:27069934

  19. Effect of equilibration period on the viability of frozen-thawed mouse morulae after rapid freezing.

    PubMed

    Takahashi, Y; Kanagawa, H

    1990-06-01

    Mouse morulae were frozen with 1.5-4.0 M glycerol + 0.25 M lactose solution by direct plunging into liquid nitrogen vapor 0.5-30 min after equilibration at room temperature. After thawing, embryos were cultured in vitro, and the highest survival rates were obtained after exposure for 3 min at 3.0 and 4.0 M and for 5 min at 1.5 and 2.0 M glycerol levels. Significant reductions in the survival rates (P less than 0.05) were observed when equilibration periods were extended for 3-5 min at 3.0 and 4.0 M and for 5-10 min at 1.5 and 2.0 M glycerol levels. These results clearly demonstrate that the equilibration time of embryos in glycerol-lactose mixture is one of the most important factors in the present rapid freezing conditions. To clarify the factors that lower embryo viability after prolonged equilibration, we performed further experiments on the effects of exposure to glycerol-lactose mixture on the developmental potential of embryos without freezing and on the volume changes of embryos during the exposure to glycerol solution with or without lactose. It was suggested that the detrimental effects of prolonged equilibration are due not only to the toxicity and osmotic injury of higher concentrations of cryoprotectant solution but also to the influx of water into embryonic cells caused by the hypotonic salt concentration of the extracellular (freezing) solution. PMID:2372393

  20. Hormetic Effect of Chronic Hypergravity in a Mouse Model of Allergic Asthma and Rhinitis

    NASA Astrophysics Data System (ADS)

    Jang, Tae Young; Jung, Ah-Yeoun; Kim, Young Hyo

    2016-06-01

    We aimed to evaluate the effect of chronic hypergravity in a mouse model of allergic asthma and rhinitis. Forty BALB/c mice were divided as: group A (n = 10, control) sensitized and challenged with saline, group B (n = 10, asthma) challenged by intraperitoneal and intranasal ovalbumin (OVA) to induce allergic asthma and rhinitis, and groups C (n = 10, asthma/rotatory control) and D (n = 10, asthma/hypergravity) exposed to 4 weeks of rotation with normogravity (1G) or hypergravity (5G) during induction of asthma/rhinitis. Group D showed significantly decreased eosinophils, neutrophils, and lymphocytes in their BAL fluid compared with groups B and C (p < 0.05). In real-time polymerase chain reaction using lung homogenate, the expression of IL-1β was significantly upregulated (p < 0.001) and IL-4 and IL-10 significantly downregulated (p < 0.05) in group D. Infiltration of inflammatory cells into lung parenchyma and turbinate, and the thickness of respiratory epithelium was significantly reduced in group D (p < 0.05). The expression of Bcl-2 and heme oxygenase-1 were significantly downregulated, Bax and extracellular dismutase significantly upregulated in Group D. Therefore, chronic hypergravity could have a hormetic effect for allergic asthma and rhinitis via regulation of genes involved in antioxidative and proapoptotic pathways. It is possible that we could use hypergravity machinery for treating allergic respiratory disorders.

  1. Effects of boldine on mouse diaphragm and sarcoplasmic reticulum vesicles isolated from skeletal muscle.

    PubMed

    Kang, J J; Cheng, Y W

    1998-02-01

    The effects of boldine [(S)-2,9-dihydroxy-1,10-dimethoxyaporphine], a major alkaloid in the leaves and bark of boldo (Peumus boldus Mol.), on skeletal muscle were studied using mouse diaphragm and isolated sarcoplasmic reticulum membrane vesicles. Boldine, at 10-200 microM, has little effect on the muscle-evoked twitches; however, the ryanodine-induced contracture was potentiated dose-dependently. At higher concentrations of 300 microM, boldine by itself induced muscle contracture of two phases, which were caused by the influx of extracellular Ca2+ and induction of Ca2+ release from the internal Ca2+ storage site, the sarcoplasmic reticulum, respectively. When tested with isolated sarcoplasmic reticulum membrane vesicles, boldine dose-dependently induced Ca2+ release from actively loaded sarcoplasmic reticulum vesicles isolated from skeletal muscle of rabbit or rat which was inhibited by ruthenium red, suggesting that the release was through the Ca2+ release channel, also known as the ryanodine receptor. Boldine also dose-dependently increased apparent [3H]-ryanodine binding with the EC50 value of 50 microM. In conclusion, we have shown that boldine could sensitize the ryanodine receptor and induce Ca2+ release from the internal Ca2+ storage site of skeletal muscle. PMID:9491763

  2. Differential effects of targeting Notch receptors in a mouse model of liver cancer

    PubMed Central

    Huntzicker, Erik G.; Hötzel, Kathy; Choy, Lisa; Che, Li; Ross, Jed; Pau, Gregoire; Sharma, Neeraj; Siebel, Christian W.; Chen, Xin; French, Dorothy M.

    2015-01-01

    Primary liver cancer encompasses both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). The Notch signaling pathway, known to be important for the proper development of liver architecture, is also a potential driver of primary liver cancer. However, with four known Notch receptors and several Notch ligands, it is not clear which Notch pathway members play the predominant role in liver cancer. To address this question we utilized antibodies to specifically target Notch1, Notch2, Notch3 or Jag1 in a mouse model of primary liver cancer driven by AKT and NRas. We show that inhibition of Notch2 reduces tumor burden by eliminating highly malignant hepatocellular carcinoma- and cholangiocarcinoma-like tumors. Inhibition of the Notch ligand Jag 1 had a similar effect, consistent with Jag1 acting in cooperation with Notch2. This effect was specific to Notch2, as Notch3 inhibition did not decrease tumor burden. Unexpectedly, Notch1 inhibition altered the relative proportion of tumor types, reducing HCC-like tumors but dramatically increasing CC-like tumors. Finally, we show that Notch2 and Jag1 are expressed in, and Notch2 signaling is activated in, a subset of human HCC samples. Conclusions: These findings underscore the distinct roles of different Notch receptors in the liver and suggest that inhibition of Notch2 signaling represents a novel therapeutic option in the treatment of liver cancer. PMID:25311838

  3. Effect of caffeine on induction of endogenous type C virus in mouse cells in vitro

    SciTech Connect

    Niwa, O.; Sugahara, T.

    1981-08-01

    The effect of caffeine on the expression of murine endogenous virus in mouse cells induced by radiation and chemicals was studied. Postirradiation treatment of K-BALB cells with caffeine enhanced cell killing as well as the induction of xenotropic virus after ultraviolet light irradiation. The degree of enhancement for the virus induction was comparable to that for cell killing. On the other hand, colony-forming ability and the expression of xenotropic virus of K-BALB cells after X-irradiation were unaffected by caffeine. These data suggest a linear relationship between the degree of endogenous virus expression and the amount of lethal damages after irradiation. For induction by halogenated pyrimidines, a 24-hr incubation of AKR2B cells with caffeine after 5-iodo-2'-deoxyuridine treatment resulted in marked suppression of the expression of ecotropic virus. On the contrary, in K-BALB cells, caffeine exerted only a small effect on 5-iodo-2'-deoxyuridine-induced expression of ecotropic and xenotropic viruses. These results indicate that, although using the same inducing agent, the pathway of endogenous virus induction may be different for AKR2B cells and for K-BALB cells.

  4. Antiviral effects of liposome-encapsulated PolyICLC against Dengue virus in a mouse model.

    PubMed

    Hu, Yongxin; Hu, Yanxin; Sun, Lunquan; Wong, Jonathan; Wang, Ming

    2016-09-16

    This study presents the first investigation of the antiviral effects of the liposome-encapsulated PolyICLC (LE-PolyICLC) on Dengue virus (DENV) in a mouse model. In vivo efficacy studies showed that LE-PolyICLC acted to increase antiviral mechanisms mainly through promoting cytokine expression associated with innate immunity, such as IFN-γ. In addition, the pro-inflammatory cytokine TNF-α was also increased, while IL-6 level was decreased in serum. The titers of total antibodies against DENV2 in mice were also elevated. Administration of LE-PolyICLC not only alleviated the loss of body weight, degree of morbidity, and pathological damage in brains, but also reduced the viral titers and expression of viral E protein in the brain. Notably, the effectiveness of LE-PolyICLC was better than PolyICLC on the basis of the data presented in this study. These results, therefore, set a foundation for further development of LE-PolyICLC as an attractive candidate of antiviral agents to be used in both prophylactic and therapeutic settings in DENV diseases. PMID:27524246

  5. Hormetic Effect of Chronic Hypergravity in a Mouse Model of Allergic Asthma and Rhinitis.

    PubMed

    Jang, Tae Young; Jung, Ah-Yeoun; Kim, Young Hyo

    2016-01-01

    We aimed to evaluate the effect of chronic hypergravity in a mouse model of allergic asthma and rhinitis. Forty BALB/c mice were divided as: group A (n = 10, control) sensitized and challenged with saline, group B (n = 10, asthma) challenged by intraperitoneal and intranasal ovalbumin (OVA) to induce allergic asthma and rhinitis, and groups C (n = 10, asthma/rotatory control) and D (n = 10, asthma/hypergravity) exposed to 4 weeks of rotation with normogravity (1G) or hypergravity (5G) during induction of asthma/rhinitis. Group D showed significantly decreased eosinophils, neutrophils, and lymphocytes in their BAL fluid compared with groups B and C (p < 0.05). In real-time polymerase chain reaction using lung homogenate, the expression of IL-1β was significantly upregulated (p < 0.001) and IL-4 and IL-10 significantly downregulated (p < 0.05) in group D. Infiltration of inflammatory cells into lung parenchyma and turbinate, and the thickness of respiratory epithelium was significantly reduced in group D (p < 0.05). The expression of Bcl-2 and heme oxygenase-1 were significantly downregulated, Bax and extracellular dismutase significantly upregulated in Group D. Therefore, chronic hypergravity could have a hormetic effect for allergic asthma and rhinitis via regulation of genes involved in antioxidative and proapoptotic pathways. It is possible that we could use hypergravity machinery for treating allergic respiratory disorders. PMID:27251783

  6. Exenatide Is an Effective Antihyperglycaemic Agent in a Mouse Model of Wolfram Syndrome 1

    PubMed Central

    Sedman, Tuuli; Rünkorg, Kertu; Krass, Maarja; Luuk, Hendrik; Plaas, Mario; Vasar, Eero; Volke, Vallo

    2016-01-01

    Wolfram syndrome 1 is a very rare monogenic disease resulting in a complex of disorders including diabetes mellitus. Up to now, insulin has been used to treat these patients. Some of the monogenic forms of diabetes respond preferentially to sulphonylurea preparations. The aim of the current study was to elucidate whether exenatide, a GLP-1 receptor agonist, and glipizide, a sulphonylurea, are effective in a mouse model of Wolfram syndrome 1. Wolframin-deficient mice were used to test the effect of insulin secretagogues. Wolframin-deficient mice had nearly normal fasting glucose levels but developed hyperglycaemia after glucose challenge. Exenatide in a dose of 10 μg/kg lowered the blood glucose level in both wild-type and wolframin-deficient mice when administered during a nonfasted state and during the intraperitoneal glucose tolerance test. Glipizide (0.6 or 2 mg/kg) was not able to reduce the glucose level in wolframin-deficient animals. In contrast to other groups, wolframin-deficient mice had a lower insulin-to-glucose ratio during the intraperitoneal glucose tolerance test, indicating impaired insulin secretion. Exenatide increased the insulin-to-glucose ratio irrespective of genotype, demonstrating the ability to correct the impaired insulin secretion caused by wolframin deficiency. We conclude that GLP-1 agonists may have potential in the treatment of Wolfram syndrome-related diabetes. PMID:27069934

  7. Effects of oxidized and reduced forms of methylthioninium in two transgenic mouse tauopathy models.

    PubMed

    Melis, Valeria; Magbagbeolu, Mandy; Rickard, Janet E; Horsley, David; Davidson, Kathleen; Harrington, Kathleen A; Goatman, Keith; Goatman, Elizabeth A; Deiana, Serena; Close, Steve P; Zabke, Claudia; Stamer, Karsten; Dietze, Silke; Schwab, Karima; Storey, John M D; Harrington, Charles R; Wischik, Claude M; Theuring, Franz; Riedel, Gernot

    2015-06-01

    Given the repeated failure of amyloid-based approaches in Alzheimer's disease, there is increasing interest in tau-based therapeutics. Although methylthioninium (MT) treatment was found to be beneficial in tau transgenic models, the brain concentrations required to inhibit tau aggregation in vivo are unknown. The comparative efficacy of methylthioninium chloride (MTC) and leucomethylthioninium salts (LMTX; 5-75 mg/kg; oral administration for 3-8 weeks) was assessed in two novel transgenic tau mouse lines. Behavioural (spatial water maze, RotaRod motor performance) and histopathological (tau load per brain region) proxies were applied. Both MTC and LMTX dose-dependently rescued the learning impairment and restored behavioural flexibility in a spatial problem-solving water maze task in Line 1 (minimum effective dose: 35 mg MT/kg for MTC, 9 mg MT/kg for LMTX) and corrected motor learning in Line 66 (effective doses: 4 mg MT/kg). Simultaneously, both drugs reduced the number of tau-reactive neurons, particularly in the hippocampus and entorhinal cortex in Line 1 and in a more widespread manner in Line 66. MT levels in the brain followed a sigmoidal concentration-response relationship over a 10-fold range (0.13-1.38 μmol/l). These data establish that diaminophenothiazine compounds, like MT, can reverse both spatial and motor learning deficits and reduce the underlying tau pathology, and therefore offer the potential for treatment of tauopathies. PMID:25769090

  8. Rickettsial effects on leukotriene and prostaglandin secretion by mouse polymorphonuclear leukocytes.

    PubMed Central

    Walker, T S; Hoover, C S

    1991-01-01

    Typhus rickettsiae were incubated with mouse exudative polymorphonuclear leukocytes (PMN), and supernatants were examined for leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) secretion by radioimmunoassay. PMN incubated with native rickettsiae secreted significantly more LTB4 and PGE2 than did those incubated with buffer alone. Autacoid secretion was dependent on both the time of PMN incubation with rickettsiae and the number of rickettsiae present in the incubation suspension. Rickettsial stimulation of LTB4 secretion was associated with rickettsial hemolytic activity; treatments which inactivated the rickettsial hemolysin abolished the ability of rickettsiae to stimulate PMN LTB4 secretion. Trifluoperazine, which did not alter the rate of phagocytosis of rickettsiae by PMN, stimulated rickettsial effects on secretion of both LTB4 and PGE2 but inhibited the PMN LTB4 response to A23187. This suggested that the PMN response to rickettsiae and to the calcium ionophore involved differing mechanisms of activation. Finally, rabbit antirickettsial antiserum, which inhibited rickettsial hemolysis and was opsonic, did not block the effects of rickettsiae on PMN LTB4 secretion. PMID:1846125

  9. Limited Effects of Muc1 Deficiency on Mouse Adenovirus Type 1 Respiratory Infection

    PubMed Central

    Nguyen, Y; Procario, Megan C.; Ashley, Shanna L.; O'Neal, Wanda K.; Pickles, Raymond J.; Weinberg, Jason B.

    2011-01-01

    Muc1 (MUC1 in humans) is a membrane-tethered mucin that exerts anti-inflammatory effects in the lung during bacterial infection. Muc1 and other mucins are also likely to form a protective barrier in the lung. We used mouse adenovirus type 1 (MAV-1, also known as MAdV-1) to determine the role of Muc1 in the pathogenesis of an adenovirus in its natural host. Following intranasal inoculation of wild type mice, we detected increased TNF-α, a cytokine linked to Muc1 production, but no consistent changes in the production of lung Muc1, Muc5ac or overall lung mucus production. Viral loads were modestly higher in the lungs of Muc1−/− mice compared to Muc1+/+ mice at several early time points but decreased to similar levels by 14 days post infection in both groups. However, cellular inflammation and the expression of CXCL1, CCL5, and CCL2 did not significantly differ between Muc1−/− and Muc1+/+ mice. Our data therefore suggest that Muc1 may contribute to a physical barrier that protects against MAV-1 respiratory infection. However, our data do not reveal an anti-inflammatory effect of Muc1 that contributes to MAV-1 pathogenesis.. PMID:21816184

  10. Antisenescence effect of mouse embryonic stem cell conditioned medium through a PDGF/FGF pathway.

    PubMed

    Bae, Yun-Ui; Choi, Joon-Hyuk; Nagy, Andras; Sung, Hoon-Ki; Kim, Jae-Ryong

    2016-03-01

    Cellular senescence, an irreversible state of growth arrest, underlies organismal aging and age-related diseases. Recent evidence suggests that aging intervention based on inhibition of cellular senescence might be a promising strategy for treatment of aging and age-related diseases. Embryonic stem cells (ESCs) and ESC conditioned medium (CM) have been suggested as a desirable source for regenerative medicine. However, effects of ESC-CM on cellular senescence remain to be determined. We found that treatment of senescent human dermal fibroblasts with CM from mouse ESCs (mESCs) decreases senescence phenotypes. We found that platelet-derived growth factor BB in mESC-CM plays a critical role in antisenescence effect of mESC-CM through up-regulation of fibroblast growth factor 2. We confirmed that mESC-CM treatment accelerates the wound-healing process by down-regulating senescence-associated p53 expression in in vivo models. Taken together, our results suggest that mESC-CM has the ability to suppress cellular senescence and maintain proliferative capacity. Therefore, this strategy might emerge as a novel therapeutic strategy for aging and age-related diseases. PMID:26675707

  11. Inhibitory Effects of Lanthanum Chloride on Wear Particle-Induced Osteolysis in a Mouse Calvarial Model.

    PubMed

    Shang, Jiang-Yin-Zi; Zhan, Ping; Jiang, Chuan; Zou, Yang; Liu, Hucheng; Zhang, Bin; Dai, Min

    2016-02-01

    Osteolysis is a bone disorder associated with progressive destruction of bone tissues. However, the effects of lanthanum chloride (LaCl3) on osteolysis remain unknown. Therefore, the aim of this study was to determine the effects of LaCl3 on osteolysis in vivo. In a mouse calvarial model, C57BL/6J mice were injected with wear particles with or without LaCl3. Microcomputed tomography, hematoxylin and eosin staining, and tartrate-resistant acid phosphatase staining were performed for the pathological characterization of calvariae, and eight calvariae per group were prepared for the assay of TNF-α, IL-1β, and RANKL secretion using quantitative enzyme-linked immunosorbent assay (ELISA). In mice treated with high-dose LaCl3, particle-induced osteolysis and inflammatory reaction were reduced compared with that in the vehicle-treated control. Moreover, treatment with high-dose LaCl3 suppressed the wear particle-induced decrease in bone mineral content, bone mineral density, and bone volume fraction. Bone destruction and resorption were higher in the LaCl3-treated group than in the saline-treated group but lower than those in the wear particle group. Finally, our results showed that treatment with a high dose of LaCl3 suppressed osteoclastogenesis. Thus, LaCl3 may represent a novel therapeutic agent for the treatment or prevention of wear particle-induced osteolysis and aseptic loosening. PMID:26105543

  12. RXR controlled regulatory networks identified in mouse brain counteract deleterious effects of Aβ oligomers.

    PubMed

    Nam, Kyong Nyon; Mounier, Anais; Fitz, Nicholas F; Wolfe, Cody; Schug, Jonathan; Lefterov, Iliya; Koldamova, Radosveta

    2016-01-01

    Bexarotene, a selective agonist for Retinoid X receptors (RXR) improves cognitive deficits and amyloid-β (Aβ) clearance in mice. Here we examine if the effect of bexarotene on RXR cistrome and transcriptomes depend on APOE isoform and Aβ deposition. We found bexarotene increased RXR binding to promoter regions in cortex of APOE3 mice. Rho family GTPases and Wnt signaling pathway were highly enriched in ChIP-seq and RNA-seq datasets and members of those pathways - Lrp1, Lrp5, Sfrp5 and Sema3f were validated. The effect of APOE isoform was compared in APOE3 and APOE4 mice and we found significant overlapping in affected pathways. ChIP-seq using mouse embryonic stem cells and enrichment levels of histone marks H3K4me3 and H3K27me3 revealed that, bexarotene induced epigenetic changes, consistent with increased neuronal differentiation and in correlation with changes in transcription. Comparison of transcriptome in APOE3 and APP/APOE3 mice revealed that amyloid deposition significantly affects the response to bexarotene. In primary neurons, bexarotene ameliorated the damaged dendrite complexity and loss of neurites caused by Aβ42. Finally, we show that the disruption of actin cytoskeleton induced by Aβ42 in vitro was inhibited by bexarotene treatment. Our results suggest a mechanism to establish RXR therapeutic targets with significance in neurodegeneration. PMID:27051978

  13. Sexually dimorphic effect of in vitro fertilization (IVF) on adult mouse fat and liver metabolomes.

    PubMed

    Feuer, Sky K; Donjacour, Annemarie; Simbulan, Rhodel K; Lin, Wingka; Liu, Xiaowei; Maltepe, Emin; Rinaudo, Paolo F

    2014-11-01

    The preimplantation embryo is particularly vulnerable to environmental perturbation, such that nutritional and in vitro stresses restricted exclusively to this stage may alter growth and affect long-term metabolic health. This is particularly relevant to the over 5 million children conceived by in vitro fertilization (IVF). We previously reported that even optimized IVF conditions reprogram mouse postnatal growth, fat deposition, and glucose homeostasis in a sexually dimorphic fashion. To more clearly interrogate the metabolic changes associated with IVF in adulthood, we used nontargeted mass spectrometry to globally profile adult IVF- and in vivo-conceived liver and gonadal adipose tissues. There was a sex- and tissue-specific effect of IVF on adult metabolite signatures indicative of metabolic reprogramming and oxidative stress and reflective of the observed phenotypes. Additionally, we observed a striking effect of IVF on adult sexual dimorphism. Male-female differences in metabolite concentration were exaggerated in hepatic IVF tissue and significantly reduced in IVF adipose tissue, with the majority of changes affecting amino acid and lipid metabolites. We also observed female-specific changes in markers of oxidative stress and adipogenesis, including reduced glutathione, cysteine glutathione disulfide, ophthalmate, urate, and corticosterone. In summary, embryo manipulation and early developmental experiences can affect adult patterns of sexual dimorphism and metabolic physiology. PMID:25211591

  14. Effect of mouse Sim2 gene on the cell cycle of PC12 cells.

    PubMed

    Meng, Xianfang; Shi, Jing; Peng, Bin; Zou, Xiaojing; Zhang, Chun

    2006-04-01

    Sim2 gene plays an important role in the pathogenesis of Down syndrome (DS). To observe the effect of mouse Sim2 (mSim2) on the cell cycle of PC12 cells in vitro and explore the role of Sim2 in the pathogenesis of DS, we cloned the full open reading frame of mSim2 into the pcDNA3 vector and transfected it into PC12 cells, before analysing the effect of mSim2 on the cell cycle. A eukaryotic expression vector of mSim2 (pcDNA3-mSim2) was successfully constructed. There was notable expression of mSim2 mRNA in the cells transfected with pcDNA3-Sim2. Flow cytometry showed that there were more cells in G(0)/G(1) phase in the Sim2-transfected cells than that in the controls (P < 0.01), and significantly fewer in G(2)/M phase (P < 0.01). The mRNA and protein expressions of cyclin E decreased in the Sim2-transfected cells, while p27 expression increased significantly (P < 0.01). It is concluded that Sim2 may play an important role in the pathogenesis of DS by inhibiting the cell cycle, which is related to the decreased expression of cyclin E and increased expression of p27. PMID:16530433

  15. Amylase release from dissociated mouse pancreatic acinar cells stimulated by glucagon: effect of membrane stabilizers.

    PubMed Central

    Singh, M

    1980-01-01

    1. The effect of membrane stabilizers and cytochalasin-B on amylase secretion, basal and induced by ionophore A23187, CCK-PZ, bethanechol and glucagon, was studied in dissociated mouse pancreatic acinar cells. 2. Cytochalasin-B did not affect basal or secretagogue-stimulated amylase secretion. 3. Membrane stabilizers [thymol (10(-7)-10(-4) M), chlorpromazine (10(-7)-10(-4) M) and propranolol (10(-7)-10(-5) M) did not alter basal release of amylase. At higher concentrations of thymol (10(-3) M), chlorpromazine (10(-3) M) and propranolol (10(-4) M), dissociated acinar cells were lysed as indicated by an increase in release of lactic dehydrogenase (LDH). 4. Ionophore A23187, CCK-PZ (maximal effective concentrations, 0.01 u. ml.-1), bethanechol (maximal effective concentrations, 10(-4) M) and glucagon increased amylase secretion in a dose-dependent fashion. Concentrations of CCK-PZ and bethanechol beyond optimal levels decreased amylase secretion. Concentrations of ionophore A23187 and glucagon when tested beyond 10(-6) M and 10(-4) M respectively increased the release of LDH. In concentrations that were non-toxic, membrane stabilizers blocked the stimulating effect of cholecystokinin-pancreozymin and bethanechol on amylase secretion but did not alter the response to A23187 and glucagon. 5. Unlike bethanechol, glucagon neither increased the uptake of 45Ca nor did it alter the release of 45Ca from cells previously loaded with 45CaCl2. 6. These data provide evidence that stimulus-secretion coupling in dissociated pancreatic acinar cells is basically similar to cells in situ. The effect of glucagon is consistent with the model in which hormone-dependent mobilization of Ca2+ from intra- or extracellular sources is bypassed leading to digestive enzyme secretion. PMID:6166745

  16. Pro-oxidant effects of Ecstasy and its metabolites in mouse brain synaptosomes

    PubMed Central

    Barbosa, Daniel José; Capela, João Paulo; Oliveira, Jorge MA; Silva, Renata; Ferreira, Luísa Maria; Siopa, Filipa; Branco, Paula Sério; Fernandes, Eduarda; Duarte, José Alberto; de Lourdes Bastos, Maria; Carvalho, Félix

    2012-01-01

    BACKGROUND AND PURPOSE 3,4-Methylenedioxymethamphetamine (MDMA or ‘Ecstasy’) is a worldwide major drug of abuse known to elicit neurotoxic effects. The mechanisms underlying the neurotoxic effects of MDMA are not clear at present, but the metabolism of dopamine and 5-HT by monoamine oxidase (MAO), as well as the hepatic biotransformation of MDMA into pro-oxidant reactive metabolites is thought to contribute to its adverse effects. EXPERIMENTAL APPROACH Using mouse brain synaptosomes, we evaluated the pro-oxidant effects of MDMA and its metabolites, α-methyldopamine (α-MeDA), N-methyl-α-methyldopamine (N-Me-α-MeDA) and 5-(glutathion-S-yl)-α-methyldopamine [5-(GSH)-α-MeDA], as well as those of 5-HT, dopamine, l-DOPA and 3,4-dihydroxyphenylacetic acid (DOPAC). KEY RESULTS 5-HT, dopamine, l-DOPA, DOPAC and MDMA metabolites α-MeDA, N-Me-α-MeDA and 5-(GSH)-α-MeDA, concentration- and time-dependently increased H2O2 production, which was significantly reduced by the antioxidants N-acetyl-l-cysteine (NAC), ascorbic acid and melatonin. From experiments with MAO inhibitors, it was observed that H2O2 generation induced by 5-HT was totally dependent on MAO-related metabolism, while for dopamine, it was a minor pathway. The MDMA metabolites, dopamine, l-DOPA and DOPAC concentration-dependently increased quinoproteins formation and, like 5-HT, altered the synaptosomal glutathione status. Finally, none of the compounds modified the number of polarized mitochondria in the synaptosomal preparations, and the compounds’ pro-oxidant effects were unaffected by prior mitochondrial depolarization, excluding a significant role for mitochondrial-dependent mechanisms of toxicity in this experimental model. CONCLUSIONS AND IMPLICATIONS MDMA metabolites along with high levels of monoamine neurotransmitters can be major effectors of neurotoxicity induced by Ecstasy. PMID:21506960

  17. Therapeutic and preventive effects of methylene blue on Alzheimer's disease pathology in a transgenic mouse model.

    PubMed

    Paban, V; Manrique, C; Filali, M; Maunoir-Regimbal, S; Fauvelle, F; Alescio-Lautier, B

    2014-01-01

    Methylene blue (MB) belongs to the phenothiazinium family. It has been used to treat a variety of human conditions and has beneficial effects on the central nervous system in rodents with and without brain alteration. The present study was designed to test whether chronic MB treatment taken after (therapeutic effect) or before (preventive effect) the onset of beta-amyloid pathology influences cognition in a transgenic mouse model (APP/PS1). In addition, the present study aims at revealing whether these behavioral effects might be related to brain alteration in beta-amyloid deposition. To this end, we conducted an in vivo study and compared two routes of drug administration, drinking water versus intraperitoneal injection. Results showed that transgenic mice treated with MB orally or following intraperitoneal injection were protected from cognitive impairments in a variety of social, learning, and exploratory tasks. Immunoreactive beta-amyloid deposition was significantly reduced in the hippocampus and adjacent cortex in MB-treated transgenic mice. Interestingly, these beneficial effects were observed independently of beta-amyloid load at the time of MB treatment. This suggests that MB treatment is beneficial at both therapeutic and preventive levels. Using solid-state High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (HRMAS-NMR), we showed that MB administration after the onset of amyloid pathology significantly restored the concentration of two metabolites related to mitochondrial metabolism, namely alanine and lactate. We conclude that MB might be useful for the therapy and prevention of Alzheimer's disease. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'. PMID:23891615

  18. Effect of Ames dwarfism and caloric restriction on spontaneous mutation frequency in different mouse tissues

    PubMed Central

    Garcia, Ana Maria; Busuttil, Rita; Calder, Brent; Dollé, Martijn E. T.; Diaz, Vivian; McMahan, C. Alex; Bartke, Andrzej; Nelson, James; Reddick, Robert; Vijg, Jan

    2008-01-01

    Genetic instability has been implicated as a causal factor in cancer and aging. Caloric restriction (CR) and suppression of the somatotroph axis significantly increase life span in the mouse and reduces multiple symptoms of aging, including cancer. To test if in vivo spontaneous mutation frequency is reduced by such mechanisms, we crossed long-lived Ames dwarf mice with a C57BL/6J line harboring multiple copies of the lacZ mutation reporter gene as part of a plasmid that can be recovered from tissues and organs into E. coli to measure mutant frequencies. Four cohorts were studied: (1) ad lib wild-type; (2) CR wild-type; (3) ad lib dwarf; and (4) CR dwarf. While both CR wild-type and ad lib dwarf mice lived significantly longer than the ad lib wild-type mice, under CR conditions dwarf mice did not live any longer than ad lib wild-type mice. While this may be due to an as yet unknown adverse effect of the C57Bl/6 background, it did not prevent an effect on spontaneous mutation frequencies at the lacZ locus, which were assessed in liver, kidney and small intestine of 7- and 15-month old mice of all four cohorts. A lower mutant frequency in the ad lib dwarf background was observed in liver and kidney at 7 and 15 months of age and in small intestine at 15 months of age as compared to the ad lib wild-type. CR also significantly reduced spontaneous mutant frequency in kidney and small intestine, but not in liver. In a separate cohort of lacZ-C57BL/6J mice CR was also found to significantly reduce spontaneous mutant frequency in liver and small intestine, across three age levels. These results indicate that two major pro-longevity interventions in the mouse are associated with a reduced mutation frequency. This could be responsible, at least in part, for the enhanced longevity associated with Ames dwarfism and CR. PMID:18565572

  19. Effect of fumaric acid, its dimethylester, and topical antipsoriatic drugs on epidermal differentiation in the mouse tail model.

    PubMed

    Sebök, B; Szabados, T; Kerényi, M; Schneider, I; Mahrle, G

    1996-01-01

    Fumaric acid, fumaric acid dimethylester, and the dithranol derivative C4-lactone were studied in the mouse tail test to evaluate their effects on epidermal cell differentiation compared with other topical antipsoriatic drugs, such as betamethasone, calcipotriol, and dithranol. Mouse tails were treated for 2 weeks and longitudinal histological sections prepared of the tail skin. The length of the orthokeratotic regions (stratum granulosum) was measured on 10 sequential scales per tail and expressed as percentage of the full length of the scale. In addition, epidermal thickness was measured and the efficacy of the various compounds evaluated. In comparison to 2% salicylic acid ointment, all tested compounds except fumaric acid significantly (p < or = 0.05) increased the proportion of the orthokeratotic region. C4-lactone and calcipotriol were less effective than dithranol, fumaric acid dimethylester only moderately influenced cell differentiation, and betamethasone showed the least potent effect. Dithranol was the most potent substance inducing orthokeratosis without increasing epidermal thickness. PMID:8722603

  20. Effects of growth hormone and insulin-like growth factor I on muscle in mouse models of human growth disorders.

    PubMed

    Clark, Ryan P; Schuenke, Mark; Keeton, Stephanie M; Staron, Robert S; Kopchick, John J

    2006-01-01

    The precise effects of growth hormone (GH) and insulin-like growth factor I (IGF-I) on muscle development and physiology are relatively unknown. Furthermore, there have been conflicting reports on the effects of GH/IGF-I on muscle. Distinguishing the direct effects of GH versus those of IGF-I is problematic, but animal models with altered GH/IGF-I action could help to alleviate some of the conflicting results and help to determine the independent actions of GH and IGF-I. The phenotypes of several mouse models, namely the GH receptor-gene-disrupted (GHR -/-) mouse and a variety of IGF-I -/- mice, are summarized, which ultimately will aid our understanding of this complex area. PMID:17259718

  1. Analgesic effects of adenylyl cyclase inhibitor NB001 on bone cancer pain in a mouse model

    PubMed Central

    Kang, Wen-bo; Yang, Qi; Guo, Yan-yan; Wang, Lu; Wang, Dong-sheng; Cheng, Qiang; Li, Xiao-ming; Tang, Jun; Zhao, Jian-ning; Liu, Gang; Zhuo, Min

    2016-01-01

    Background Cancer pain, especially the one caused by metastasis in bones, is a severe type of pain. Pain becomes chronic unless its causes and consequences are resolved. With improvements in cancer detection and survival among patients, pain has been considered as a great challenge because traditional therapies are partially effective in terms of providing relief. Cancer pain mechanisms are more poorly understood than neuropathic and inflammatory pain states. Chronic inflammatory pain and neuropathic pain are influenced by NB001, an adenylyl cyclase 1 (AC1)-specific inhibitor with analgesic effects. In this study, the analgesic effects of NB001 on cancer pain were evaluated. Results Pain was induced by injecting osteolytic murine sarcoma cell NCTC 2472 into the intramedullary cavity of the femur of mice. The mice injected with sarcoma cells for four weeks exhibited significant spontaneous pain behavior and mechanical allodynia. The continuous systemic application of NB001 (30 mg/kg, intraperitoneally, twice daily for three days) markedly decreased the number of spontaneous lifting but increased the mechanical paw withdrawal threshold. NB001 decreased the concentrations of cAMP and the levels of GluN2A, GluN2B, p-GluA1 (831), and p-GluA1 (845) in the anterior cingulate cortex, and inhibited the frequency of presynaptic neurotransmitter release in the anterior cingulate cortex of the mouse models. Conclusions NB001 may serve as a novel analgesic to treat bone cancer pain. Its analgesic effect is at least partially due to the inhibition of AC1 in anterior cingulate cortex. PMID:27612915

  2. Effects of perinatal exposure to a polybrominated diphenyl ether (PBDE 99) on mouse neurobehavioural development.

    PubMed

    Branchi, Igor; Alleva, Enrico; Costa, Lucio G

    2002-09-01

    Polybrominated diphenyl ethers (PBDEs), a class of widely used flame retardants, are extensively diffused in the environment as shown by several studies on sentinel animal species, as well as humans. Of particular concern are the reported high levels of PBDEs in human milk, as almost no information is available on their potential effects on developing organisms. We investigated the effects of perinatal PBDE exposure on mouse neurobehavioural development. 2,2',4,4,5-pentabromodiphenylether (PBDE 99; 0.6, 6 and 30 mg/kg per day) was administered daily to CD-1 Swiss females by gavage from gestational day (GD) 6 to postnatal day (PND) 21. Aroclor 1254 (A1254; 6 mg/ kg per day), a PCB mixture, was administered following the same schedule and served as a positive controL The PBDE 99 medium dose had an effect on litter viability. Sensori-motor development analysis (PNDs 2-20) revealed a delayed appearance of climbing response in the PBDE 99 high-dose group. On PND 11, the homing test revealed a trend for treated animals, particularly the A1254 group, to be more active than controls. This activity level alteration was strongly increased on PNDs 34 and 60 in an open-field arena. On PND 60, treated mice showed also an altered thigmotaxis, spending more time in the centre of the arena than controls. At adulthood, A1254 treated mice were still hyperactive, whereas the PBDE 99 groups tended to be hypoactive. These findings showed that perinatal exposure to PBDE 99 produces several behavioural alterations and that its effects are not always similar to those of A1254. The possibility of exposure of neonates to PBDEs warrants further studies to characterise their developmental neurotoxicity. PMID:12387364

  3. Effect of Recombinant Human Keratinocyte Growth Factor (rHuKGF, Palifermin) on Radiation-Induced Mouse Urinary Bladder Dysfunction

    SciTech Connect

    Jaal, Jana Doerr, Wolfgang

    2007-10-01

    Purpose: To determine the effect of Palifermin (rHuKGF) on acute and late radiation effects in mouse urinary bladder. Methods and Materials: Graded radiation doses were applied on day 0. Single subcutaneous injections of Palifermin (15 mg/kg) were given on day -2 or day +2. Changes in bladder function (i.e., a reduction in bladder volume by {>=}50% of the individual preirradiation value) were assessed by cystometry. Results: Early changes in mouse bladder after irradiation occur in two phases. In the first early phase, a single injection of Palifermin on day -2 increased the ED{sub 50} (dose associated with a positive bladder response in 50% of the mice) from 20.0 {+-} 3.3 Gy to 27.1 {+-} 6.9 Gy (p < .0051). Palifermin given on day +2 was not beneficial. No significant effects of Palifermin were seen in the second early phase. However, Palifermin administration before, but not after, irradiation, also modified late radiation effects, with an ED{sub 50} of 22.2 {+-} 4.8 Gy compared with 16.2 {+-} 4.9 Gy in control animals (p < .0187). Conclusions: Initial early functional changes in the mouse urinary bladder after irradiation as well as late effects can be significantly reduced by a single administration of Palifermin before irradiation.

  4. Mouse Adenovirus Type 1 Early Region 1A Effects on the Blood-Brain Barrier

    PubMed Central

    Tirumuru, Nagaraja; Pretto, Carla D.; Castro Jorge, Luiza A.

    2016-01-01

    ABSTRACT Mouse adenovirus type 1 (MAV-1) infects endothelial cells and disrupts the blood-brain barrier (BBB), causing encephalitis in inbred and outbred mice. Using a virus mutant that does not produce the early region 1A protein E1A, we investigated whether the activity of this known viral transcriptional regulator is needed for BBB disruption and other phenotypes associated with encephalitis. The wild-type (wt) virus and E1A mutant virus caused similar levels of permeability of sodium fluorescein in brains of infected mice. In an in vitro assay of BBB integrity, wt and mutant virus caused similar decreases in transendothelial electrical resistance in primary mouse brain endothelial cell monolayers. These results indicate that E1A protein does not contribute to disruption of BBB integrity in animals or cultured cells. Both wt and E1A mutant virus infection of mice led to similar increases in the activity of two matrix metalloproteinases known to correlate with BBB disruption, MMP2 and MMP9, while causing no increase in the steady-state expression of MMP2 or MMP9 mRNA. In contrast, the amount of MMP3 transcripts increased upon infection by both viruses and to a higher level in infections by the mutant virus lacking E1A protein production. There was no difference in the levels of steady-state expression of mRNA for tight junction proteins among mock virus, wt virus, and mutant virus infections. Thus, the MAV-1 E1A protein does not measurably affect BBB integrity in the parameters assayed, although it reduces the amount of MMP3 mRNA steady-state expression induced in brains upon infection. IMPORTANCE Encephalitis can be caused by viruses, and it is potentially life-threatening because of the vital nature of the brain and the lack of treatment options. MAV-1 produces viral encephalitis in its natural host, providing a model for investigating factors involved in development of encephalitis. MAV-1 infection disrupts the BBB and increases activity of matrix

  5. Mouse Adenovirus Type 1 Early Region 1A Effects on the Blood-Brain Barrier.

    PubMed

    Tirumuru, Nagaraja; Pretto, Carla D; Castro Jorge, Luiza A; Spindler, Katherine R

    2016-01-01

    Mouse adenovirus type 1 (MAV-1) infects endothelial cells and disrupts the blood-brain barrier (BBB), causing encephalitis in inbred and outbred mice. Using a virus mutant that does not produce the early region 1A protein E1A, we investigated whether the activity of this known viral transcriptional regulator is needed for BBB disruption and other phenotypes associated with encephalitis. The wild-type (wt) virus and E1A mutant virus caused similar levels of permeability of sodium fluorescein in brains of infected mice. In an in vitro assay of BBB integrity, wt and mutant virus caused similar decreases in transendothelial electrical resistance in primary mouse brain endothelial cell monolayers. These results indicate that E1A protein does not contribute to disruption of BBB integrity in animals or cultured cells. Both wt and E1A mutant virus infection of mice led to similar increases in the activity of two matrix metalloproteinases known to correlate with BBB disruption, MMP2 and MMP9, while causing no increase in the steady-state expression of MMP2 or MMP9 mRNA. In contrast, the amount of MMP3 transcripts increased upon infection by both viruses and to a higher level in infections by the mutant virus lacking E1A protein production. There was no difference in the levels of steady-state expression of mRNA for tight junction proteins among mock virus, wt virus, and mutant virus infections. Thus, the MAV-1 E1A protein does not measurably affect BBB integrity in the parameters assayed, although it reduces the amount of MMP3 mRNA steady-state expression induced in brains upon infection. IMPORTANCE Encephalitis can be caused by viruses, and it is potentially life-threatening because of the vital nature of the brain and the lack of treatment options. MAV-1 produces viral encephalitis in its natural host, providing a model for investigating factors involved in development of encephalitis. MAV-1 infection disrupts the BBB and increases activity of matrix metalloproteinases in

  6. Multifaceted strain-specific effects in a mouse model of depression and of antidepressant reversal.

    PubMed

    Ibarguen-Vargas, Yadira; Surget, Alexandre; Touma, Chadi; Palme, Rupert; Belzung, Catherine

    2008-11-01

    Etiopathogenesis of depression and the cause of insensitivity to treatment remain poorly understood, although genetic makeup has been established as a contributing factor. The isogenicity of inbred mouse strains provides a useful tool for investigating the link between genes and behavior or drug response. Hence, our aim was to identify inbred mouse strains (among A/J, BALB/c, C3H, C57BL/6, CBA, DBA and FVB) sensitive to a 9-week period of unpredictable chronic mild stress (UCMS) and, from the fifth week onward, to the reversal effect of an antidepressant (AD) (imipramine, 20mg/kg/day i.p.) on various depression-related changes: physical, behavioral and neuroendocrine states. UCMS induced a significant deterioration of the coat state (in all the strains), blunted emotional reactivity in the novelty-suppressed feeding (NSF) test (A/J, BALB/c, C57BL/6), and changes in the level of fecal corticosterone metabolites (BALB/c, C57BL/6, DBA, FVB). Imipramine treatment reversed the UCMS-induced alterations of the coat state (BALB/c, DBA), in the NSF test (A/J, BALB/c, C57BL/6) and in fecal corticosterone metabolites (BALB/c, C57BL/6). C3H, CBA and FVB mice were irresponsive to imipramine treatment. It is noteworthy that UCMS-induced physical or behavioral changes occurred without hypothalamo-pituitary-adrenal (HPA) axis alterations in some strains (A/J, C3H, CBA), although the AD-induced reversal of these changes in BALB/c and C57BL/6 was associated with HPA axis normalization. Finally, UCMS is shown to discriminate various alterations and to replicate in a strain-dependent manner diverse profiles reminiscent of human disease subtypes. UCMS may thus enable the selection of strains suitable for investigating specific depression-related features and could be an appropriate model for identifying genetic factors associated with increased vulnerability, specific symptoms of affective disorders, and AD resistance. PMID:18790573

  7. Perinatal and lifetime exposure to methylmercury in the mouse: behavioral effects.

    PubMed

    Weiss, Bernard; Stern, Sander; Cox, Christopher; Balys, Marlene

    2005-08-01

    This project was undertaken to more completely understand the consequences of lifetime exposure to methylmercury. A series of experiments examined how perinatal or lifetime exposure to methylmercury affected behavioral performances in the adult mouse at different ages. One hundred female B6C3F1/HSD mice were assigned to one of three dose groups, 0 ppm, 1 ppm, or 3 ppm methylmercury chloride administered in a 5 nM sodium carbonate drinking solution. Four weeks after initiating dosing, the females were bred with male CBA/J HSD mice to produce the trihybrid offspring B6C3F1/HSD x CBA/J HSD. The methylmercury-treated litters were split into two subgroups, one exposed throughout its lifetime to the original dose, the other exposed through postnatal day 13. Altogether, then, five groups were studied: Control, 1 ppm perinatal, 1 ppm lifetime, 3 ppm perinatal, and 3 ppm lifetime. Three neurobehavioral indices were evaluated: (1) delayed spatial alternation (a test of memory) and (2) running in a wheel to earn food pellets (schedule-controlled operant behavior) were assessed starting at 5 and 15 months of age; (3) hindlimb splay, a measure of motor function, was assessed at 5, 15, and 26 months of age. Subjects tested at one age were littermates of those tested at the other ages. MeHg altered the hindlimb splay distance; control mice differed from methylmercury-exposed mice, the 1 ppm lifetime and 3 ppm lifetime groups differed from each other, and the analysis yielded an age by dose interaction. MeHg exposure altered different measures of wheel running under the 3 ppm lifetime condition. In the delayed alternation procedure, the mouse was required to respond to one of two locations in a strictly alternating sequence. More mice from the treated groups, except for the 1 ppm perinatal group, failed to meet the criterion at longer delay values. Overall, the results show that exposure to low levels of methylmercury produces behavioral effects that depend on the test procedure

  8. The effect of low fluoride concentrations on microdamage accumulation in mouse tibias under impact loading

    NASA Astrophysics Data System (ADS)

    Luo, Qing; Chen, Nan; Zhou, Yan-Heng; Rong, Qi-Guo

    2015-12-01

    Microdamage accumulation in bone is one of the mechanisms for energy dissipation during the fracture process. Changes in the ultrastructure and composition of bone constituents due to aging or diseases could affect microdamage accumulation. Low concentration (1 mM) of sodium fluoride (NaF) has been used in this study to investigate the effect of ultrastructural changes on microdamage accumulation in mouse tibias following free-fall impact loadings. Twenty-two tibias were divided randomly into control and NaF-treated groups. Free-fall impact loading was conducted twice on each tibia to produce microdamage. The elastic modulus of NaF-treated tibias decreased significantly after the impact loadings, while there was no significant difference in the modulus of untreated samples between pre- and post-damage loadings. Microdamage morphology analysis showed that less and shorter microcracks existed in NaF-treated tibias compared with control bones. Meanwhile, more and longer microcracks were observed in tensile regions in untreated samples compared with that in compressive regions, whereas no significant difference was observed between tensile and compressive regions in NaF-treated bones. The results of this study indicate that more energy is required to generate microcracks in NaF-treated bone than in normal bone. A low concentration of fluoride treatment may increase the toughness of bone under impact loading.

  9. Biocompatibility effects of biologically synthesized graphene in primary mouse embryonic fibroblast cells

    NASA Astrophysics Data System (ADS)

    Gurunathan, Sangiliyandi; Han, Jae Woong; Eppakayala, Vasuki; Dayem, Ahmed Abdal; Kwon, Deug-Nam; Kim, Jin-Hoi

    2013-09-01

    Due to unique properties and unlimited possible applications, graphene has attracted abundant interest in the areas of nanobiotechnology. Recently, much work has focused on the synthesis and properties of graphene. Here we show that a successful reduction of graphene oxide (GO) using spinach leaf extract (SLE) as a simultaneous reducing and stabilizing agent. The as-prepared SLE-reduced graphene oxide (S-rGO) was characterized by ultraviolet-visible spectroscopy and Fourier transform infrared spectroscopy. Dynamic light scattering technique was used to determine the average size of GO and S-rGO. Scanning electron microscopy and atomic force microscopy images provide clear surface morphological evidence for the formation of graphene. The resulting S-rGO has a mostly single-layer structure, is stable, and has significant water solubility. In addition, the biocompatibility of graphene was investigated using cell viability, leakage of lactate dehydrogenase and alkaline phosphatase activity in primary mouse embryonic fibroblast (PMEFs) cells. The results suggest that the biologically synthesized graphene has significant biocompatibility with PMEF cells, even at a higher concentration of 100 μg/mL. This method uses a `green', natural reductant and is free of additional stabilizing reagents; therefore, it is an environmentally friendly, simple, and cost-effective method for the fabrication of soluble graphene. This study could open up a promising view for substitution of hydrazine by a safe, biocompatible, and powerful reduction for the efficient deoxygenation of GO, especially in large-scale production and potential biomedical applications.

  10. Drugs that reverse disease transcriptomic signatures are more effective in a mouse model of dyslipidemia.

    PubMed

    Wagner, Allon; Cohen, Noa; Kelder, Thomas; Amit, Uri; Liebman, Elad; Steinberg, David M; Radonjic, Marijana; Ruppin, Eytan

    2015-01-01

    High-throughput omics have proven invaluable in studying human disease, and yet day-to-day clinical practice still relies on physiological, non-omic markers. The metabolic syndrome, for example, is diagnosed and monitored by blood and urine indices such as blood cholesterol levels. Nevertheless, the association between the molecular and the physiological manifestations of the disease, especially in response to treatment, has not been investigated in a systematic manner. To this end, we studied a mouse model of diet-induced dyslipidemia and atherosclerosis that was subject to various drug treatments relevant to the disease in question. Both physiological data and gene expression data (from the liver and white adipose) were analyzed and compared. We find that treatments that restore gene expression patterns to their norm are associated with the successful restoration of physiological markers to their baselines. This holds in a tissue-specific manner-treatments that reverse the transcriptomic signatures of the disease in a particular tissue are associated with positive physiological effects in that tissue. Further, treatments that introduce large non-restorative gene expression alterations are associated with unfavorable physiological outcomes. These results provide a sound basis to in silico methods that rely on omic metrics for drug repurposing and drug discovery by searching for compounds that reverse a disease's omic signatures. Moreover, they highlight the need to develop drugs that restore the global cellular state to its healthy norm rather than rectify particular disease phenotypes. PMID:25735304