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Sample records for adolescent mice exhibited

  1. Adolescent female C57BL/6 mice with vulnerability to activity-based anorexia exhibit weak inhibitory input onto hippocampal CA1 pyramidal cells

    PubMed Central

    Chowdhury, Tara G.; Wable, Gauri S.; Sabaliauskas, Nicole A.; Aoki, Chiye

    2014-01-01

    Anorexia nervosa (AN) is an eating disorder characterized by self-imposed severe starvation and often linked with excessive exercise. Activity-based anorexia (ABA) is an animal model that reproduces some of the behavioral phenotypes of AN, including the paradoxical increase in voluntary exercise following food restriction (FR). Although certain rodents have been used successfully in this animal model, C57BL/6 mice are reported to be less susceptible to ABA. We re-examined the possibility that female C57BL/6 mice might exhibit ABA vulnerability during adolescence, the developmental stage/sex among the human population with particularly high AN vulnerability. After introducing the running wheel to the cage for three days, ABA was induced by restricting food access to 1 hour per day (ABA1, N=13) or 2 hours per day (ABA2, N=10). All 23 exhibited increased voluntary wheel running (p<0.005) and perturbed circadian rhythm within two days. Only one out of five survived ABA1 for three days, while ten out of ten survived ABA2 for three days and could subsequently restore their body weight and circadian rhythm. Exposure of recovered animals to a second ABA2 induction revealed a large range of vulnerability, even within littermates. To look for the cellular substrate of differences in vulnerability, we began by examining synaptic patterns in the hippocampus, a brain region that regulates anxiety as well as plasticity throughout life. Quantitative EM analysis revealed that CA1 pyramidal cells of animals vulnerable to the second ABA2 exhibit less GABAergic innervation on cell bodies and dendrites, relative to the animals resilient to the second ABA (p<0.001) or controls (p<0.05). These findings reveal that C57BL/6J adolescent females can be used to capture brain changes underlying ABA vulnerability, and that GABAergic innervation of hippocampal pyramidal neurons is one important cellular substrate to consider for understanding the progression of and resilience to AN. PMID

  2. Norepinephrine transporter heterozygous knockout mice exhibit altered transport and behavior.

    PubMed

    Fentress, H M; Klar, R; Krueger, J J; Sabb, T; Redmon, S N; Wallace, N M; Shirey-Rice, J K; Hahn, M K

    2013-11-01

    The norepinephrine (NE) transporter (NET) regulates synaptic NE availability for noradrenergic signaling in the brain and sympathetic nervous system. Although genetic variation leading to a loss of NET expression has been implicated in psychiatric and cardiovascular disorders, complete NET deficiency has not been found in people, limiting the utility of NET knockout mice as a model for genetically driven NET dysfunction. Here, we investigate NET expression in NET heterozygous knockout male mice (NET(+/-) ), demonstrating that they display an approximately 50% reduction in NET protein levels. Surprisingly, these mice display no significant deficit in NET activity assessed in hippocampal and cortical synaptosomes. We found that this compensation in NET activity was due to enhanced activity of surface-resident transporters, as opposed to surface recruitment of NET protein or compensation through other transport mechanisms, including serotonin, dopamine or organic cation transporters. We hypothesize that loss of NET protein in the NET(+/-) mouse establishes an activated state of existing surface NET proteins. The NET(+/-) mice exhibit increased anxiety in the open field and light-dark box and display deficits in reversal learning in the Morris water maze. These data suggest that recovery of near basal activity in NET(+/-) mice appears to be insufficient to limit anxiety responses or support cognitive performance that might involve noradrenergic neurotransmission. The NET(+/-) mice represent a unique model to study the loss and resultant compensatory changes in NET that may be relevant to behavior and physiology in human NET deficiency disorders.

  3. Norepinephrine Transporter Heterozygous Knockout Mice Exhibit Altered Transport and Behavior

    PubMed Central

    Fentress, HM; Klar, R; Krueger, JK; Sabb, T; Redmon, SN; Wallace, NM; Shirey-Rice, JK; Hahn, MK

    2013-01-01

    The norepinephrine (NE) transporter (NET) regulates synaptic NE availability for noradrenergic signaling in the brain and sympathetic nervous system. Although genetic variation leading to a loss of NET expression has been implicated in psychiatric and cardiovascular disorders, complete NET deficiency has not been found in people, limiting the utility of NET knockout mice as a model for genetically-driven NET dysfunction. Here, we investigate NET expression in NET heterozygous knockout male mice (NET+/−), demonstrating that they display an ~50% reduction in NET protein levels. Surprisingly, these mice display no significant deficit in NET activity, assessed in hippocampal and cortical synaptosomes. We found that this compensation in NET activity was due to enhanced activity of surface-resident transporters, as opposed to surface recruitment of NET protein or compensation through other transport mechanisms, including serotonin, dopamine or organic cation transporters. We hypothesize that loss of NET protein in the NET+/− mouse establishes an activated state of existing, surface NET proteins. NET+/− mice exhibit increased anxiety in the open field and light-dark box and display deficits in reversal learning in the Morris Water Maze. These data suggest recovery of near basal activity in NET+/− mice appears to be insufficient to limit anxiety responses or support cognitive performance that might involve noradrenergic neurotransmission. The NET+/− mice represent a unique model to study the loss and resultant compensatory changes in NET that may be relevant to behavior and physiology in human NET deficiency disorders. PMID:24102798

  4. Artificially reared mice exhibit anxiety-like behavior in adulthood.

    PubMed

    Yasuda, Hidemi; Harauma, Akiko; Kato, Maki; Ootomo, Yuki; Hatanaka, Erisa; Moriguchi, Toru

    2016-07-29

    It is important to establish experimental animal techniques that are applicable to the newborn and infant phases for nutrition and pharmacological studies. Breeding technology using the artificial suckling method without breast milk is very effective for the study of newborn nutrition. Using this method, we separated newborn mice from dams within 48 h of birth and provided them with artificial milk. We evaluated mouse anxiety levels after early postnatal maternal separation. Artificially reared mice were subjected to elevated plus-maze tests to assess emotional behavior at 9 weeks of age. Artificially reared mice showed a significantly lower frequency of entries and dipping into the open arms of the maze compared with dam-reared mice. This result indicates that the anxiety level of artificially reared mice was higher than that of dam-reared mice. Moreover, the concentration of monoamines in the brain was determined after the behavioral experiment. The hippocampal norepinephrine, serotonin, and 5-hydroxyindoleacetic acid levels in the artificially reared mice were significantly higher than those of the dam-reared mice. These results suggest that maternal-offspring interactions are extremely important for the emotional development of newborn infants during the lactation period. In future studies, it is necessary to consider the environmental factors and conditions that minimize the influence of artificial rearing on emotional behavior.

  5. Artificially reared mice exhibit anxiety-like behavior in adulthood

    PubMed Central

    Yasuda, Hidemi; Harauma, Akiko; Kato, Maki; Ootomo, Yuki; Hatanaka, Erisa; Moriguchi, Toru

    2016-01-01

    It is important to establish experimental animal techniques that are applicable to the newborn and infant phases for nutrition and pharmacological studies. Breeding technology using the artificial suckling method without breast milk is very effective for the study of newborn nutrition. Using this method, we separated newborn mice from dams within 48 h of birth and provided them with artificial milk. We evaluated mouse anxiety levels after early postnatal maternal separation. Artificially reared mice were subjected to elevated plus-maze tests to assess emotional behavior at 9 weeks of age. Artificially reared mice showed a significantly lower frequency of entries and dipping into the open arms of the maze compared with dam-reared mice. This result indicates that the anxiety level of artificially reared mice was higher than that of dam-reared mice. Moreover, the concentration of monoamines in the brain was determined after the behavioral experiment. The hippocampal norepinephrine, serotonin, and 5-hydroxyindoleacetic acid levels in the artificially reared mice were significantly higher than those of the dam-reared mice. These results suggest that maternal-offspring interactions are extremely important for the emotional development of newborn infants during the lactation period. In future studies, it is necessary to consider the environmental factors and conditions that minimize the influence of artificial rearing on emotional behavior. PMID:26948536

  6. Neuregulin 3 Knockout Mice Exhibit Behaviors Consistent with Psychotic Disorders.

    PubMed

    Hayes, Lindsay N; Shevelkin, Alexey; Zeledon, Mariela; Steel, Gary; Chen, Pei-Lung; Obie, Cassandra; Pulver, Ann; Avramopoulos, Dimitrios; Valle, David; Sawa, Akira; Pletnikov, Mikhail V

    2016-07-01

    Neuregulin 3 (NRG3) is a paralog of NRG1. Genetic studies in schizophrenia demonstrate that risk variants in NRG3 are associated with cognitive and psychotic symptom severity, and several intronic single nucleotide polymorphisms in NRG3 are associated with delusions in patients with schizophrenia. In order to gain insights into the biological function of the gene, we generated a novel Nrg3 knockout (KO) mouse model and tested for neurobehavioral phenotypes relevant to psychotic disorders. KO mice displayed novelty-induced hyperactivity, impaired prepulse inhibition of the acoustic startle response, and deficient fear conditioning. No gross cytoarchitectonic or layer abnormalities were noted in the brain of KO mice. Our findings suggest that deletion of the Nrg3 gene leads to alterations consistent with aspects of schizophrenia. We propose that KO mice will provide a valuable animal model to determine the role of the NRG3 in the molecular pathogenesis of schizophrenia and other psychotic disorders. PMID:27606322

  7. P2X6 Knockout Mice Exhibit Normal Electrolyte Homeostasis

    PubMed Central

    Viering, Daan H. H. M.; Bos, Caro; Bindels, René J. M.; Hoenderop, Joost G. J.

    2016-01-01

    ATP-mediated signaling is an important regulator of electrolyte transport in the kidney. The purinergic cation channel P2X6 has been previously localized to the distal convoluted tubule (DCT), a nephron segment important for Mg2+ and Na+ reabsorption, but its role in ion transport remains unknown. In this study, P2x6 knockout (P2x6-/-) mice were generated to investigate the role of P2X6 in renal electrolyte transport. The P2x6-/- animals displayed a normal phenotype and did not differ physiologically from wild type mice. Differences in serum concentration and 24-hrs urine excretion of Na+, K+, Mg2+ and Ca2+ were not detected between P2x6+/+, P2x6+/- and P2x6-/- mice. Quantitative PCR was applied to examine potential compensatory changes in renal expression levels of other P2x subunits and electrolyte transporters, including P2x1-5, P2x7, Trpm6, Ncc, Egf, Cldn16, Scnn1, Slc12a3, Slc41a1, Slc41a3, Cnnm2, Kcnj10 and Fxyd2. Additionally, protein levels of P2X2 and P2X4 were assessed in P2x6+/+ and P2x6-/- mouse kidneys. However, significant changes in expression were not detected. Furthermore, no compensatory changes in gene expression could be demonstrated in heart material isolated from P2x6-/- mice. Except for a significant (P<0.05) upregulation of P2x2 in the heart of P2x6-/- mice compared to the P2x6+/+ mice. Thus, our data suggests that purinergic signaling via P2X6 is not significantly involved in the regulation of renal electrolyte handling under normal physiological conditions. PMID:27254077

  8. Duck Tembusu virus exhibits neurovirulence in BALB/c mice

    PubMed Central

    2013-01-01

    Background Duck Tembusu virus is a member of the Ntaya group in the genus Flavivirus. The virus has been responsible for severe duck egg-drop syndrome in China since 2010. Its emergence and rapid spread have caused great economic loss for the poultry industry. The epidemiology of the virus infection and the potential threat to public health is of great concern because of the infective and zoonotic nature of flaviviruses. Results In this study, the pathogenicity of duck Tembusu virus in BALB/c mice was investigated. Infected mice developed clinical signs, including loss of appetite, ruffled hair, weight loss, disorientation, blindness and paralysis of hind limbs from six days post- infection following intracerebral inoculation. Morbidity was 100%, with mortality ranging from 20 to 80% in three- to eight-week-old mice. High virus titers were recovered from the brain, and the virus was distributed in several organs. Histologically, there was widespread non-suppurative encephalitis in the brain. Lymphocyte depletion in the spleen was observed, along with fatty degeneration in the liver and kidney. Conclusions Our results demonstrate, for the first time, that duck Tembusu virus is highly neurovirulent in BALB/c mice. The mouse model used in this work was able to produce Tembusu virus infection and could be useful for elucidating some of the aspects of the pathophysiology of other flavivirus infections. PMID:23941427

  9. Preadolescent drd1-EGFP mice exhibit cocaine-induced behavioral sensitization

    PubMed Central

    Tobón, Krishna E.; Kuzhikandathil, Eldo V.

    2013-01-01

    In adult mice, repeated cocaine administration induces behavioral sensitization measured as increased horizontal locomotor activity. Cocaine-induced locomotor sensitization has been well characterized in adult mice. In adult animals, the D1 dopamine receptor is important for mediating effects of cocaine. The effect of cocaine on D1 receptor expression and function in preadolescent animals is less understood. The recently described drd1-Enhanced Green Fluorescent Protein (drd1-EGFP) reporter mouse is a useful model for performing such mechanistic studies; however, preadolescent drd1-EGFP mice have not been characterized previously. Here we studied cocaine-induced locomotor sensitization in preadolescent drd1-EGFP reporter mice. We administered 15 mg/kg cocaine three times daily at one hour intervals for seven consecutive days beginning on postnatal day 23 to drd1-EGFP reporter mice and the commonly used C57BL/6 mice. Under this regimen, preadolescent mice of both strains exhibited cocaine-induced locomotor sensitization; however, by day 7 the cocaine-induced locomotor activity in the drd1-EGFP mice was maintained for a longer duration compared to the C57BL/6 mice. The preadolescent drd1-EGFP mice also exhibited elevated basal locomotor activity in a novel environment and had higher D1 and D2 dopamine receptor mRNA levels in the caudate nucleus compared to the C57BL/6 mice. The cocaine-induced locomotor sensitization was not retained when the drd1-EGFP mice were maintained cocaine-free for two weeks suggesting that in preadolescent drd1-EGFP mice the cocaine-induced changes do not persist. PMID:24095672

  10. Increased vulnerability to ethanol consumption in adolescent maternal separated mice.

    PubMed

    García-Gutiérrez, María S; Navarrete, Francisco; Aracil, Auxiliadora; Bartoll, Adrián; Martínez-Gras, Isabel; Lanciego, José L; Rubio, Gabriel; Manzanares, Jorge

    2016-07-01

    The purpose of this study was to evaluate the effects of early life stress on the vulnerability to ethanol consumption in adolescence. To this aim, mice were separated from their mothers for 12 hours/day on postnatal days 8 and 12. Emotional behavior (light-dark box, elevated plus maze and tail suspension tests) and pre-attentional deficit (pre-pulse inhibition) were evaluated in adolescent maternal separated (MS) mice. Alterations of the corticotropin-releasing factor (CRF), glucocorticoid receptor (NR3C1), tyrosine hydroxylase (TH), mu-opioid receptor (MOr), brain-derived neurotrophic factor (BDNF), neuronal nuclei (NeuN), microtubule-associated protein 2 (MAP2) and neurofilament heavy (NF200)-immunoreactive fibers were studied in the paraventricular nucleus of the hypothalamus (PVN), ventral tegmental area (VTA), nucleus accumbens (NAc) or hippocampus (HIP). The effects of maternal separation (alone or in combination with additional stressful stimuli) on ethanol consumption during adolescence were evaluated using the oral ethanol self-administration paradigm. MS mice presented mood-related alterations and pre-attentional deficit. Increased CRF, MOr and TH, and reduced BDNF, NR3C1, NeuN, MAP2 and NF200-immunoreactive fibers were observed in the PVN, NAc and HIP of adolescent MS mice. In the oral ethanol self-administration test, adolescent MS mice presented higher ethanol consumption and motivation. Exposure to additional new stressful stimuli during adolescence significantly increased the vulnerability to ethanol consumption induced by maternal separation. These results clearly demonstrated that exposure to early life stress increased the vulnerability to ethanol consumption, potentiated the effects of stressful stimuli exposure during adolescence on ethanol consumption and modified the expression of key targets involved in the response to stress, ethanol reinforcing properties and cognitive processes. PMID:25988842

  11. GPRC6A Null Mice Exhibit Osteopenia, Feminization and Metabolic Syndrome

    PubMed Central

    Pi, Min; Chen, Ling; Huang, Min-Zhao; Zhu, Wenyu; Ringhofer, Brian; Luo, Junming; Christenson, Lane; Li, Benyi; Zhang, Jianghong; Jackson, P. David; Faber, Pieter; Brunden, Kurt R.; Harrington, John J.; Quarles, L. Darryl

    2008-01-01

    Background GPRC6A is a widely expressed orphan G-protein coupled receptor that senses extracellular amino acids, osteocalcin and divalent cations in vitro. The physiological functions of GPRC6A are unknown. Methods/Principal Findings In this study, we created and characterized the phenotype of GPRC6A−/− mice. We observed complex metabolic abnormalities in GPRC6A−/− mice involving multiple organ systems that express GPRC6A, including bone, kidney, testes, and liver. GPRC6A−/− mice exhibited hepatic steatosis, hyperglycemia, glucose intolerance, and insulin resistance. In addition, we observed high expression of GPRC6A in Leydig cells in the testis. Ablation of GPRC6A resulted in feminization of male GPRC6A−/− mice in association with decreased lean body mass, increased fat mass, increased circulating levels of estradiol, and reduced levels of testosterone. GPRC6A was also highly expressed in kidney proximal and distal tubules, and GPRC6A−/− mice exhibited increments in urine Ca/Cr and PO4/Cr ratios as well as low molecular weight proteinuria. Finally, GPRC6A−/− mice exhibited a decrease in bone mineral density (BMD) in association with impaired mineralization of bone. Conclusions/Significance GPRC6A−/− mice have a metabolic syndrome characterized by defective osteoblast-mediated bone mineralization, abnormal renal handling of calcium and phosphorus, fatty liver, glucose intolerance and disordered steroidogenesis. These findings suggest the overall function of GPRC6A may be to coordinate the anabolic responses of multiple tissues through the sensing of extracellular amino acids, osteocalcin and divalent cations. PMID:19050760

  12. Trpc2-deficient lactating mice exhibit altered brain and behavioral responses to bedding stimuli.

    PubMed

    Hasen, Nina S; Gammie, Stephen C

    2011-03-01

    The trpc2 gene encodes an ion channel involved in pheromonal detection and is found in the vomeronasal organ. In tprc2(-/-) knockout (KO) mice, maternal aggression (offspring protection) is impaired and brain Fos expression in females in response to a male are reduced. Here we examine in lactating wild-type (WT) and KO mice behavioral and brain responses to different olfactory/pheromonal cues. Consistent with previous studies, KO dams exhibited decreased maternal aggression and nest building, but we also identified deficits in nighttime nursing and increases in pup weight. When exposed to the bedding tests, WT dams typically ignored clean bedding, but buried male-soiled bedding from unfamiliar males. In contrast, KO dams buried both clean and soiled bedding. Differences in brain Fos expression were found between WT and KO mice in response to either no bedding, clean bedding, or soiled bedding. In the accessory olfactory bulb, a site of pheromonal signal processing, KO mice showed suppressed Fos activation in the anterior mitral layer relative to WT mice in response to clean and soiled bedding. However, in the medial and basolateral amygdala, KO mice showed a robust Fos response to bedding, suggesting that regions of the amygdala canonically associated with pheromonal sensing can be active in the brains of KO mice, despite compromised signaling from the vomeronasal organ. Together, these results provide further insights into the complex ways by which pheromonal signaling regulates the brain and behavior of the maternal female.

  13. Weaver mutant mice exhibit long-term learning deficits under several measures of instrumental behavior.

    PubMed

    Derenne, Adam; Arsenault, Matthew L; Austin, David P; Weatherly, Jeffrey N

    2007-12-01

    Homozygous weaver mutant mice (wv/wv) exhibit symptoms that parallel Parkinson's disease, including motor deficits and the destruction of dopaminergic neurons as well as degeneration in the cerebellum and hippocampus. To develop a more complete behavioral profile of these organisms, groups of wv/wv, wv/+ mice and C57BL/6 mice were observed on a within-subjects basis under a fixed-interval schedule of reinforcement, a differential-reinforcement-of-low-rate-of-responding schedule, and a discrimination task in which a saccharin solution and tap water were concurrently available from two food cups. Under both reinforcement schedules, the wv/wv mice responded as frequently as the comparison subjects, but they responded in a manner that was inappropriate to the contingencies. Rather than respond with increasing frequency as the upcoming reinforcer became temporally proximate, wv/wv mice responded with decreasing probability as a function of the time since the previous reinforcer. Under the discrimination task, the wv/wv mice, unlike the controls, obtained saccharin over tap water at the level of chance. The findings suggest that weaver mutant mice express learning deficits similar to those found in other dopamine-deficient organisms.

  14. Socially Isolated Mice Exhibit a Blunted Homeostatic Sleep Response to Acute Sleep Deprivation Compared to Socially Paired Mice

    PubMed Central

    Kaushal, Navita; Nair, Deepti; Gozal, David; Ramesh, Vijay

    2012-01-01

    Sleep is an important physiological process underlying maintenance of physical, mental and emotional health. Consequently, sleep deprivation (SD) is associated with adverse consequences and increases the risk for anxiety, immune, and cognitive disorders. SD is characterized by increased energy expenditure responses and sleep rebound upon recovery that are regulated by homeostatic processes, which in turn are influenced by stress. Since all previous studies on SD were conducted in a setting of social isolation, the impact of the social contextual setting is unknown. Therefore, we used a relatively stress-free SD paradigm in mice to assess the impact of social isolation on sleep, wakefulness and delta electroencephalogram (EEG) power during non-rapid eye movement (NREM) sleep. Paired or isolated C57BL/6J adult chronically-implanted male mice were exposed to SD for 6 hours and telemetric polygraphic recordings were conducted, including 18 hours recovery. Recovery from SD in the paired group showed a significant decrease in wake and significant increase in NREM sleep and rapid eye movement (REM), and a similar, albeit less robust response occurred in the isolated mice. Delta power during NREM sleep was increased in both groups immediately following SD, but paired mice exhibited significantly higher delta power throughout the dark period. The increase in body temperature and gross motor activity observed during the SD procedure was decreased during the dark period. In both open field and elevated plus maze tests, socially isolated mice showed significantly higher anxiety than paired mice. The homeostatic processes altered by SD are differentially affected in paired and isolated mice, suggesting that the social context of isolation stress may adversely affect the quantity and quality of sleep in mice. PMID:22498175

  15. Mice with Dab1 or Vldlr insufficiency exhibit abnormal neonatal vocalization patterns

    PubMed Central

    Fraley, E. R.; Burkett, Z. D.; Day, N. F.; Schwartz, B. A.; Phelps, P. E.; White, S. A.

    2016-01-01

    Genetic and epigenetic changes in components of the Reelin-signaling pathway (RELN, DAB1) are associated with autism spectrum disorder (ASD) risk. Social communication deficits are a key component of the ASD diagnostic criteria, but the underlying neurogenetic mechanisms remain unknown. Reln insufficient mice exhibit ASD-like behavioral phenotypes including altered neonatal vocalization patterns. Reelin affects multiple pathways including through the receptors, Very low-density lipoprotein receptor (Vldlr), Apolipoprotein receptor 2 (Apoer2), and intracellular signaling molecule Disabled-1 (Dab1). As Vldlr was previously implicated in avian vocalization, here we investigate vocalizations of neonatal mice with a reduction or absence of these components of the Reelin-signaling pathway. Mice with low or no Dab1 expression exhibited reduced calling rates, altered call-type usage, and differential vocal development trajectories. Mice lacking Vldlr expression also had altered call repertoires, and this effect was exacerbated by deficiency in Apoer2. Together with previous findings, these observations 1) solidify a role for Reelin in vocal communication of multiple species, 2) point to the canonical Reelin-signaling pathway as critical for development of normal neonatal calling patterns in mice, and 3) suggest that mutants in this pathway could be used as murine models for Reelin-associated vocal deficits in humans. PMID:27184477

  16. Social defeat in adolescent mice increases vulnerability to alcohol consumption.

    PubMed

    Rodriguez-Arias, Marta; Navarrete, Francisco; Blanco-Gandia, Maria Carmen; Arenas, Maria Carmen; Bartoll-Andrés, Adrián; Aguilar, Maria A; Rubio, Gabriel; Miñarro, José; Manzanares, Jorge

    2016-01-01

    This study employs an oral operant conditioning paradigm to evaluate the effects of repeated social defeat during adolescence on the reinforcing and motivational actions of ethanol in adult OF1 mice. Social interaction, emotional and cognitive behavioral aspects were also analyzed, and real-time polymerase chain reaction (PCR) experiments were performed to study gene expression changes in the mesocorticolimbic and hypothalamus-hypophysis-adrenal (HHA) axis. Social defeat did not alter anxiety-like behavior in the elevated plus maze or cognitive performance in the passive avoidance and Hebb-Williams tests. A social interaction test revealed depression-like symptoms and social subordination behavior in defeated OF1 mice. Interestingly, social defeat in adolescence significantly increased the number of effective responses, ethanol consumption values and motivation to drink. Finally, real-time PCR analyses revealed that social defeat significantly increased tyrosine hydroxylase and corticotropin-releasing hormone in the ventral tegmental area and paraventricular nucleus, respectively. In contrast, mu-opioid receptor gene expression was decreased in the nucleus accumbens of socially defeated mice. In summary, these findings suggest that exposure to social defeat during adolescence increases vulnerability to the rewarding effects of ethanol without affecting emotional or cognitive performance. The gene expression alterations we have observed in the mesocorticolimbic and HHA axis systems of defeated mice could be related with their increased ethanol consumption. These results endorse future research into pharmacological strategies that modulate these systems for the treatment of social stress-related alcohol consumption problems.

  17. Mutant mice derived by ICSI of evaporatively dried spermatozoa exhibit expected phenotype.

    PubMed

    Li, Ming-Wen; Baridon, Brian; Trainor, Amanda; Djan, Esi; Koehne, Amanda; Griffey, Stephen M; Biggers, John D; Toner, Mehmet; Lloyd, K C Kent

    2012-04-01

    Apolipoprotein E (Apoe)-deficient knockout mice were used to test the hypothesis that mutant mice preserved as evaporatively dried (ED) spermatozoa, stored at -80 °C for 6 months, and then recovered by ICSI will exhibit the same phenotype as before preservation. The birth rate of mice recovered by ICSI of evaporatively dried spermatozoa was lower than that of fresh spermatozoa (17.5 vs 38.0%). Progeny of mice preserved using evaporatively dried spermatozoa were reproductively sound. From these, the second generation of mice produced by natural mating showed lesions typical of APOE deficiency, including severe hypercholesterolemia, hypertriglyceridemia, markedly increased plasma low-density lipoprotein level, and extensive and severe atherosclerotic lesions in the aorta. We conclude that the expected phenotype caused by an induced genetic mutation can be faithfully recapitulated and sustained in subsequent generations of mice preserved and stored as ED spermatozoa and recovered using ICSI. Because it is simpler, faster, and cheaper than conventional (cryopreservation) and nonconventional (freeze-drying) preservation procedures, evaporative drying is a viable, cost-effective, and efficient method for preserving and storing valuable mutant mouse strains.

  18. Selenoprotein-deficient transgenic mice exhibit enhanced exercise-induced muscle growth.

    PubMed

    Hornberger, Troy A; McLoughlin, Thomas J; Leszczynski, Jori K; Armstrong, Dustin D; Jameson, Ruth R; Bowen, Phyllis E; Hwang, Eun-Sun; Hou, Honglin; Moustafa, Mohamed E; Carlson, Bradley A; Hatfield, Dolph L; Diamond, Alan M; Esser, Karyn A

    2003-10-01

    Dietary intake of selenium has been implicated in a wide range of health issues, including aging, heart disease and cancer. Selenium deficiency, which can reduce selenoprotein levels, has been associated with several striated muscle pathologies. To investigate the role of selenoproteins in skeletal muscle biology, we used a transgenic mouse (referred to as i6A-) that has reduced levels of selenoproteins due to the introduction and expression of a dominantly acting mutant form of selenocysteine transfer RNA (tRNA[Ser]Sec). As a consequence, each organ contains reduced levels of most selenoproteins, yet these mice are normal with regard to fertility, overall health, behavior and blood chemistries. In the present study, although skeletal muscles from i6A- mice were phenotypically indistinguishable from those of wild-type mice, plantaris muscles were approximately 50% heavier after synergist ablation, a model of exercise overload. Like muscle in wild-type mice, the enhanced growth in the i6A- mice was completely blocked by inhibition of the mammalian target of rapamycin (mTOR) pathway. Muscles of transgenic mice exhibited increased site-specific phosphorylation on both Akt and p70 ribosomal S6 kinase (p70S6k) (P < 0.05) before ablation, perhaps accounting for the enhanced response to synergist ablation. Thus, a single genetic alteration resulted in enhanced skeletal muscle adaptation after exercise, and this is likely through subtle changes in the resting phosphorylation state of growth-related kinases.

  19. Gomafu lncRNA knockout mice exhibit mild hyperactivity with enhanced responsiveness to the psychostimulant methamphetamine.

    PubMed

    Ip, Joanna Y; Sone, Masamitsu; Nashiki, Chieko; Pan, Qun; Kitaichi, Kiyoyuki; Yanaka, Kaori; Abe, Takaya; Takao, Keizo; Miyakawa, Tsuyoshi; Blencowe, Benjamin J; Nakagawa, Shinichi

    2016-01-01

    The long noncoding RNA Gomafu/MIAT/Rncr2 is thought to function in retinal cell specification, stem cell differentiation and the control of alternative splicing. To further investigate physiological functions of Gomafu, we created mouse knockout (KO) model that completely lacks the Gomafu gene. The KO mice did not exhibit any developmental deficits. However, behavioral tests revealed that the KO mice are hyperactive. This hyperactive behavior was enhanced when the KO mice were treated with the psychostimulant methamphetamine, which was associated with an increase in dopamine release in the nucleus accumbens. RNA sequencing analyses identified a small number of genes affected by the deficiency of Gomafu, a subset of which are known to have important neurobiological functions. These observations suggest that Gomafu modifies mouse behavior thorough a mild modulation of gene expression and/or alternative splicing of target genes. PMID:27251103

  20. Gomafu lncRNA knockout mice exhibit mild hyperactivity with enhanced responsiveness to the psychostimulant methamphetamine

    PubMed Central

    Ip, Joanna Y.; Sone, Masamitsu; Nashiki, Chieko; Pan, Qun; Kitaichi, Kiyoyuki; Yanaka, Kaori; Abe, Takaya; Takao, Keizo; Miyakawa, Tsuyoshi; Blencowe, Benjamin J.; Nakagawa, Shinichi

    2016-01-01

    The long noncoding RNA Gomafu/MIAT/Rncr2 is thought to function in retinal cell specification, stem cell differentiation and the control of alternative splicing. To further investigate physiological functions of Gomafu, we created mouse knockout (KO) model that completely lacks the Gomafu gene. The KO mice did not exhibit any developmental deficits. However, behavioral tests revealed that the KO mice are hyperactive. This hyperactive behavior was enhanced when the KO mice were treated with the psychostimulant methamphetamine, which was associated with an increase in dopamine release in the nucleus accumbens. RNA sequencing analyses identified a small number of genes affected by the deficiency of Gomafu, a subset of which are known to have important neurobiological functions. These observations suggest that Gomafu modifies mouse behavior thorough a mild modulation of gene expression and/or alternative splicing of target genes. PMID:27251103

  1. Mice lacking selenoprotein P and selenocysteine lyase exhibit severe neurological dysfunction, neurodegeneration, and audiogenic seizures.

    PubMed

    Byrns, China N; Pitts, Matthew W; Gilman, Christy A; Hashimoto, Ann C; Berry, Marla J

    2014-04-01

    Selenoproteins are a unique family of proteins, characterized by the co-translational incorporation of selenium as selenocysteine, which play key roles in antioxidant defense. Among selenoproteins, selenoprotein P (Sepp1) is particularly distinctive due to the fact that it contains multiple selenocysteine residues and has been postulated to act in selenium transport. Within the brain, Sepp1 delivers selenium to neurons by binding to the ApoER2 receptor. Upon feeding a selenium-deficient diet, mice lacking ApoER2 or Sepp1 develop severe neurological dysfunction and exhibit widespread brainstem neurodegeneration, indicating an important role for ApoER2-mediated Sepp1 uptake in normal brain function. Selenocysteine lyase (Scly) is an enzyme that plays an important role in selenium homeostasis, in that it catalyzes the decomposition of selenocysteine and allows selenium to be recycled for additional selenoprotein synthesis. We previously reported that constitutive deletion of Scly results in neurological deficits only when mice are challenged with a low selenium diet. To gain insight into the relationship between Sepp1 and Scly in selenium metabolism, we created novel transgenic mice constitutively lacking both genes (Scly(-/-)Sepp1(-/-)) and characterized the neurobehavioral phenotype. We report that deletion of Scly in conjunction with Sepp1 further aggravates the phenotype of Sepp1(-/-) mice, as these mice needed supraphysiological selenium supplementation to survive, and surviving mice exhibited impaired motor coordination, audiogenic seizures, and brainstem neurodegeneration. These findings provide the first in vivo evidence that Scly and Sepp1 work cooperatively to maintain selenoprotein function in the mammalian brain.

  2. Mice lacking chromogranins exhibit increased aggressive and depression-like behaviour.

    PubMed

    Pereda, Daniel; Pardo, Marta R; Morales, Yezer; Dominguez, Natalia; Arnau, Maria Rosa; Borges, Ricardo

    2015-02-01

    Chromogranins are acidic proteins; both chromogranins A and B constitute the main protein component in the vesicular matrix of large dense core vesicles. Chromogranins are a natural source of peptides with different physiological activities that have been associated with vascular and neurological diseases. We have used three different genetic mutant models of mice lacking chromogranin A, chromogranin B and both all on the same C57BL/6J background, to characterize the physiological roles of these proteins using metabolic, cardiovascular and behavioural tests. In mice from 3 to 18 months of age, the lack of any chromogranin promoted age-dependent hypersensitivity to insulin, while the lack of both chromogranins provoked progressive lack of response to stress, as restriction did not promote tachycardia in old mice. Moreover, the lack of chromogranin B produced a depressive-like and aggressive phenotype, while the lack either or both chromogranins increased barbering behaviour. In addition, we observed no effects on light-dark box or RotaRod tests. Mice lacking chromogranin B exhibited lower exploratory activity. Based on this extensive phenotyping with more than 2800 mice, these findings support roles of chromogranins, or the peptides derived from them, in the control of aggressive behaviour along with changes in their metabolic profile beyond their previously described activities in the secretory pathway.

  3. Microbiota and bile acid profiles in retinoic acid-primed mice that exhibit accelerated liver regeneration

    PubMed Central

    Liu, Hui-Xin; Hu, Ying; Wan, Yu-Jui Yvonne

    2016-01-01

    Background & Aims All-trans Retinoic acid (RA) regulates hepatic lipid and bile acid homeostasis. Similar to bile acid (BA), RA accelerates partial hepatectomy (PHx)-induced liver regeneration. Because there is a bidirectional regulatory relationship between gut microbiota and BA synthesis, we examined the effect of RA in altering the gut microbial population and BA composition and established their relationship with hepatic biological processes during the active phases of liver regeneration. Methods C57BL/6 mice were treated with RA orally followed by 2/3 PHx. The roles of RA in shifting gut microbiota and BA profiles as well as hepatocyte metabolism and proliferation were studied. Results RA-primed mice exhibited accelerated hepatocyte proliferation revealed by higher numbers of Ki67-positive cells compared to untreated mice. Firmicutes and Bacteroidetes phyla dominated the gut microbial community (>85%) in both control and RA-primed mice after PHx. RA reduced the ratio of Firmicutes to Bacteroidetes, which was associated with a lean phenotype. Consistently, RA-primed mice lacked transient lipid accumulation normally found in regenerating livers. In addition, RA altered BA homeostasis and shifted BA profiles by increasing the ratio of hydrophilic to hydrophobic BAs in regenerating livers. Accordingly, metabolic regulators fibroblast growth factor 21, Sirtuin1, and their downstream targets AMPK and ERK1/2 were more robustly activated in RA-primed than unprimed regenerating livers. Conclusions Priming mice with RA resulted in a lean microbiota composition and hydrophilic BA profiles, which were associated with facilitated metabolism and enhanced cell proliferation. PMID:26701854

  4. Choline Kinase β Mutant Mice Exhibit Reduced Phosphocholine, Elevated Osteoclast Activity, and Low Bone Mass*

    PubMed Central

    Kular, Jasreen; Tickner, Jennifer C.; Pavlos, Nathan J.; Viola, Helena M.; Abel, Tamara; Lim, Bay Sie; Yang, Xiaohong; Chen, Honghui; Cook, Robert; Hool, Livia C.; Zheng, Ming Hao; Xu, Jiake

    2015-01-01

    The maintenance of bone homeostasis requires tight coupling between bone-forming osteoblasts and bone-resorbing osteoclasts. However, the precise molecular mechanism(s) underlying the differentiation and activities of these specialized cells are still largely unknown. Here, we identify choline kinase β (CHKB), a kinase involved in the biosynthesis of phosphatidylcholine, as a novel regulator of bone homeostasis. Choline kinase β mutant mice (flp/flp) exhibit a systemic low bone mass phenotype. Consistently, osteoclast numbers and activity are elevated in flp/flp mice. Interestingly, osteoclasts derived from flp/flp mice exhibit reduced sensitivity to excessive levels of extracellular calcium, which could account for the increased bone resorption. Conversely, supplementation of cytidine 5′-diphosphocholine in vivo and in vitro, a regimen that bypasses CHKB deficiency, restores osteoclast numbers to physiological levels. Finally, we demonstrate that, in addition to modulating osteoclast formation and function, loss of CHKB corresponds with a reduction in bone formation by osteoblasts. Taken together, these data posit CHKB as a new modulator of bone homeostasis. PMID:25451916

  5. Laminin α4 deficient mice exhibit decreased capacity for adipose tissue expansion and weight gain.

    PubMed

    Vaicik, Marcella K; Thyboll Kortesmaa, Jill; Movérare-Skrtic, Sofia; Kortesmaa, Jarkko; Soininen, Raija; Bergström, Göran; Ohlsson, Claes; Chong, Li Yen; Rozell, Björn; Emont, Margo; Cohen, Ronald N; Brey, Eric M; Tryggvason, Karl

    2014-01-01

    Obesity is a global epidemic that contributes to the increasing medical burdens related to type 2 diabetes, cardiovascular disease and cancer. A better understanding of the mechanisms regulating adipose tissue expansion could lead to therapeutics that eliminate or reduce obesity-associated morbidity and mortality. The extracellular matrix (ECM) has been shown to regulate the development and function of numerous tissues and organs. However, there is little understanding of its function in adipose tissue. In this manuscript we describe the role of laminin α4, a specialized ECM protein surrounding adipocytes, on weight gain and adipose tissue function. Adipose tissue accumulation, lipogenesis, and structure were examined in mice with a null mutation of the laminin α4 gene (Lama4-/-) and compared to wild-type (Lama4+/+) control animals. Lama4-/- mice exhibited reduced weight gain in response to both age and high fat diet. Interestingly, the mice had decreased adipose tissue mass and altered lipogenesis in a depot-specific manner. In particular, epididymal adipose tissue mass was specifically decreased in knock-out mice, and there was also a defect in lipogenesis in this depot as well. In contrast, no such differences were observed in subcutaneous adipose tissue at 14 weeks. The results suggest that laminin α4 influences adipose tissue structure and function in a depot-specific manner. Alterations in laminin composition offers insight into the roll the ECM potentially plays in modulating cellular behavior in adipose tissue expansion.

  6. Fibroblast Growth Factor 21-Null Mice Do Not Exhibit an Impaired Response to Fasting

    PubMed Central

    Antonellis, Patrick Joseph; Hayes, Meghan Patricia; Adams, Andrew Charles

    2016-01-01

    Fibroblast growth factor 21 (FGF21) is a pleotropic metabolic regulator, expression of which is elevated during fasting. To this end, the precise role played by FGF21 in the biology of fasting has been the subject of several recent studies, which have demonstrated contributions to the regulation of both lipid and carbohydrate metabolism. In the present study, we compared wild-type (WT) and FGF21-null (FGF21KO) mice, demonstrating that, despite the significant induction of FGF21 during fasting in the WT animals, our strain of FGF21-null mice exhibits only limited impairments in their adaptation to nutrient deprivation. Specifically, fasted FGF21KO mice display a mild attenuation of gluconeogenic transcriptional induction in the liver accompanied by partially blunted glucose production in response to a pyruvate challenge. Furthermore, FGF21KO mice displayed only minor impairments in lipid metabolism in the fasted state, limited to accumulation of hepatic triglycerides and a reduction in expression of genes associated with fatty acid oxidation. To address the possibility of compensation to germline deletion of FGF21, we further interrogated the role of endogenous FGF21 via acute pharmacological blockade of FGF21 signaling. At the transcriptional level, we show that FGF21 signaling is required for full induction of gluconeogenic and oxidative genes in the liver. However, corroborating our findings in FGF21KO mice, pharmacological blockade of the FGF21 axis did not profoundly disrupt the physiological response to fasting. Taken as a whole, these data demonstrate that, while FGF21 is partially required for appropriate gene expression during the fed to fasted transition, its absence does not significantly impact the downstream physiology of the fasted state. PMID:27445980

  7. Children and Adolescents with Autism Exhibit Reduced MEG Steady-State Gamma Responses

    PubMed Central

    Wilson, Tony W.; Rojas, Donald C.; Reite, Martin L.; Teale, Peter D.; Rogers, Sally J.

    2009-01-01

    Background Recent neuroimaging studies of autism have indicated reduced functional connectivity during both cognitive tasks and rest. These data suggest long-range connectivity may be compromised in this disorder, and current neurological theories of autism contend disrupted inter-regional interactions may be an underlying mechanism explaining behavioral symptomatology. However, it is unclear whether deficient neuronal communication is attributable to fewer long-range tracts or more of a local deficit in neural circuitry. This study examines the integrity of local circuitry by focusing on gamma band activity in auditory cortices of children and adolescents with autism. Methods Ten children and adolescents with autism and 10 matched controls participated. Both groups listened to 500 ms duration monaural click trains with a 25 ms inter-click interval, as magnetoencephalography was acquired from the contralateral hemisphere. To estimate 40 Hz spectral power density, we performed time-frequency decomposition of the single-trial magnetic steady-state response data using complex demodulation. Results Children and adolescents with autism exhibited significantly reduced left hemispheric 40 Hz power from 200–500 ms post-stimulus onset. In contrast, no significant between group differences were observed for right hemispheric cortices. Conclusions The production and/or maintenance of left hemispheric gamma oscillations appeared abnormal in participants with autism. We interpret these data as indicating that in autism, particular brain regions may be unable to generate the high-frequency activity likely necessary for binding and other forms of inter-regional interactions. These findings augment connectivity theories of autism with novel evidence that aberrations in local circuitry could underlie putative deficiencies in long-range neural communication. PMID:16950225

  8. Alk7 Depleted Mice Exhibit Prolonged Cardiac Repolarization and Are Predisposed to Ventricular Arrhythmia

    PubMed Central

    Ying, Shaozhen; Cao, Hong; Hu, He; Wang, Xin; Tang, Yanhong; Huang, Congxin

    2016-01-01

    We aimed to investigate the role of activin receptor-like kinase (ALK7) in regulating cardiac electrophysiology. Here, we showed that Alk7-/- mice exhibited prolonged QT intervals in telemetry ECG recordings. Furthermore, Langendorff-perfused Alk7-/- hearts had significantly longer action potential duration (APD) and greater incidence of ventricular arrhythmia (AV) induced by burst pacing. Using whole-cell patch clamp, we found that the densities of repolarizing K+ currents Ito and IK1 were profoundly reduced in Alk7-/- ventricular cardiomyocytes. Mechanistically, the expression of Kv4.2 (a major subunit of Ito carrying channel) and KCHIP2 (a key accessory subunit of Ito carrying channel), was markedly decreased in Alk7-/- hearts. These findings suggest that endogenous expression of ALK7 is necessary to maintain repolarizing K+ currents in ventricular cardiomyocytes, and finally prevent action potential prolongation and ventricular arrhythmia. PMID:26882027

  9. Neuropeptide FF receptors exhibit direct and anti-opioid effects on mice dorsal raphe nucleus neurons.

    PubMed

    Ding, Zhong; Zajac, Jean-Marie

    2014-10-01

    By using acutely dissociated dorsal raphe nucleus neurons (DRN) from young mice, direct and anti-opioid effects of Neuropeptide FF (NPFF) receptors were measured. The NPFF analog 1 DMe (10 µM) had no effect on resting Ca2+ channels but reduced the magnitude of Ca2+ transients induced by depolarization in 83.3% neurons tested, of which the inhibition rate is 45.4±2.9%. Pertussis toxin treatment reduced to 18.9% the number of responding neurons and attenuated by 47% the response of 1 DMe. In contrast, cholera toxin treatment had no significant effect. Eighteen minute perfusion with 1 DMe at a very low 10 nM concentration, that did not directly inhibit Ca2+ transients triggered by depolarization in every neuron, attenuated by 78% the inhibitory effect of Nociceptin/orphanin FQ (N/OFQ) on Ca2+ transients, but not that of by serotonin. These results demonstrated for the first time that NPFF receptors on mice DRN inhibit Ca2+ transients induced by depolarization via Gi/o protein and also exhibit a specific anti-opioid activity on nociceptin receptors, and that their specific anti-opioid activity is not a direct consequence of their activity on Ca2+ transients.

  10. Predicting Early Sexual Activity with Behavior Problems Exhibited at School Entry and in Early Adolescence

    ERIC Educational Resources Information Center

    Schofield, Hannah-Lise T.; Bierman, Karen L.; Heinrichs, Brenda; Nix, Robert L.

    2008-01-01

    Youth who initiate sexual intercourse in early adolescence (age 11-14) experience multiple risks, including concurrent adjustment problems and unsafe sexual practices. The current study tested two models describing the links between childhood precursors, early adolescent risk factors, and adolescent sexual activity: a cumulative model and a…

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

    PubMed

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

    2014-05-01

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

  12. Hematopoietic stem cells from NOD mice exhibit autonomous behavior and a competitive advantage in allogeneic recipients.

    PubMed

    Chilton, Paula M; Rezzoug, Francine; Ratajczak, Mariusz Z; Fugier-Vivier, Isabelle; Ratajczak, Janina; Kucia, Magda; Huang, Yiming; Tanner, Michael K; Ildstad, Suzanne T

    2005-03-01

    Type 1 diabetes is a systemic autoimmune disease that can be cured by transplantation of hematopoietic stem cells (HSCs) from disease-resistant donors. Nonobese diabetic (NOD) mice have a number of features that distinguish them as bone marrow transplant recipients that must be understood prior to the clinical application of chimerism to induce tolerance. In the present studies, we characterized NOD HSCs, comparing their engraftment characteristics to HSCs from disease-resistant strains. Strikingly, NOD HSCs are significantly enhanced in engraftment potential compared with HSCs from disease-resistant donors. Unlike HSCs from disease-resistant strains, they do not require graft-facilitating cells to engraft in allogeneic recipients. Additionally, they exhibit a competitive advantage when coadministered with increasing numbers of syngeneic HSCs, produce significantly more spleen colony-forming units (CFU-Ss) in vivo in allogeneic recipients, and more granulocyte macrophage-colony-forming units (CFU-GMs) in vitro compared with HSCs from disease-resistant controls. NOD HSCs also exhibit significantly enhanced chemotaxis to a stromal cell-derived factor 1 (SDF-1) gradient and adhere significantly better on primary stroma. This enhanced engraftment potential maps to the insulin-dependent diabetes locus 9 (Idd9) locus, and as such the tumor necrosis factor (TNF) receptor family as well as ski/sno genes may be involved in the mechanism underlying the autonomy of NOD HSCs. These findings may have important implications to understand the evolution of autoimmune disease and impact on potential strategies for cure. PMID:15522953

  13. Long-lived crowded-litter mice exhibit lasting effects on insulin sensitivity and energy homeostasis

    PubMed Central

    Landeryou, Taylor; Blandino-Rosano, Manuel; Cady, Gillian; Elghazi, Lynda; Meister, Daniel; See, Lauren; Bartke, Andrzej; Bernal-Mizrachi, Ernesto; Miller, Richard A.

    2014-01-01

    The action of nutrients on early postnatal growth can influence mammalian aging and longevity. Recent work has demonstrated that limiting nutrient availability in the first 3 wk of life [by increasing the number of pups in the crowded-litter (CL) model] leads to extension of mean and maximal lifespan in genetically normal mice. In this study, we aimed to characterize the impact of early-life nutrient intervention on glucose metabolism and energy homeostasis in CL mice. In our study, we used mice from litters supplemented to 12 or 15 pups and compared those to control litters limited to eight pups. At weaning and then throughout adult life, CL mice are significantly leaner and consume more oxygen relative to control mice. At 6 mo of age, CL mice had low fasting leptin concentrations, and low-dose leptin injections reduced body weight and food intake more in CL female mice than in controls. At 22 mo, CL female mice also have smaller adipocytes compared with controls. Glucose and insulin tolerance tests show an increase in insulin sensitivity in 6 mo old CL male mice, and females become more insulin sensitive later in life. Furthermore, β-cell mass was significantly reduced in the CL male mice and was associated with reduction in β-cell proliferation rate in these mice. Together, these data show that early-life nutrient intervention has a significant lifelong effect on metabolic characteristics that may contribute to the increased lifespan of CL mice. PMID:24735888

  14. Sirh7/Ldoc1 knockout mice exhibit placental P4 overproduction and delayed parturition.

    PubMed

    Naruse, Mie; Ono, Ryuichi; Irie, Masahito; Nakamura, Kenji; Furuse, Tamio; Hino, Toshiaki; Oda, Kanako; Kashimura, Misho; Yamada, Ikuko; Wakana, Shigeharu; Yokoyama, Minesuke; Ishino, Fumitoshi; Kaneko-Ishino, Tomoko

    2014-12-01

    Sirh7/Ldoc1 [sushi-ichi retrotransposon homolog 7/leucine zipper, downregulated in cancer 1, also called mammalian retrotransposon-derived 7 (Mart7)] is one of the newly acquired genes from LTR retrotransposons in eutherian mammals. Interestingly, Sirh7/Ldoc1 knockout (KO) mice exhibited abnormal placental cell differentiation/maturation, leading to an overproduction of placental progesterone (P4) and placental lactogen 1 (PL1) from trophoblast giant cells (TGCs). The placenta is an organ that is essential for mammalian viviparity and plays a major endocrinological role during pregnancy in addition to providing nutrients and oxygen to the fetus. P4 is an essential hormone in the preparation and maintenance of pregnancy and the determination of the timing of parturition in mammals; however, the biological significance of placental P4 in rodents is not properly recognized. Here, we demonstrate that mouse placentas do produce P4 in mid-gestation, coincident with a temporal reduction in ovarian P4, suggesting that it plays a role in the protection of the conceptuses specifically in this period. Pregnant Sirh7/Ldoc1 knockout females also displayed delayed parturition associated with a low pup weaning rate. All these results suggest that Sirh7/Ldoc1 has undergone positive selection during eutherian evolution as a eutherian-specific acquired gene because it impacts reproductive fitness via the regulation of placental endocrine function.

  15. Sirh7/Ldoc1 knockout mice exhibit placental P4 overproduction and delayed parturition.

    PubMed

    Naruse, Mie; Ono, Ryuichi; Irie, Masahito; Nakamura, Kenji; Furuse, Tamio; Hino, Toshiaki; Oda, Kanako; Kashimura, Misho; Yamada, Ikuko; Wakana, Shigeharu; Yokoyama, Minesuke; Ishino, Fumitoshi; Kaneko-Ishino, Tomoko

    2014-12-01

    Sirh7/Ldoc1 [sushi-ichi retrotransposon homolog 7/leucine zipper, downregulated in cancer 1, also called mammalian retrotransposon-derived 7 (Mart7)] is one of the newly acquired genes from LTR retrotransposons in eutherian mammals. Interestingly, Sirh7/Ldoc1 knockout (KO) mice exhibited abnormal placental cell differentiation/maturation, leading to an overproduction of placental progesterone (P4) and placental lactogen 1 (PL1) from trophoblast giant cells (TGCs). The placenta is an organ that is essential for mammalian viviparity and plays a major endocrinological role during pregnancy in addition to providing nutrients and oxygen to the fetus. P4 is an essential hormone in the preparation and maintenance of pregnancy and the determination of the timing of parturition in mammals; however, the biological significance of placental P4 in rodents is not properly recognized. Here, we demonstrate that mouse placentas do produce P4 in mid-gestation, coincident with a temporal reduction in ovarian P4, suggesting that it plays a role in the protection of the conceptuses specifically in this period. Pregnant Sirh7/Ldoc1 knockout females also displayed delayed parturition associated with a low pup weaning rate. All these results suggest that Sirh7/Ldoc1 has undergone positive selection during eutherian evolution as a eutherian-specific acquired gene because it impacts reproductive fitness via the regulation of placental endocrine function. PMID:25468940

  16. Sirh7/Ldoc1 knockout mice exhibit placental P4 overproduction and delayed parturition

    PubMed Central

    Naruse, Mie; Ono, Ryuichi; Irie, Masahito; Nakamura, Kenji; Furuse, Tamio; Hino, Toshiaki; Oda, Kanako; Kashimura, Misho; Yamada, Ikuko; Wakana, Shigeharu; Yokoyama, Minesuke; Ishino, Fumitoshi; Kaneko-Ishino, Tomoko

    2014-01-01

    Sirh7/Ldoc1 [sushi-ichi retrotransposon homolog 7/leucine zipper, downregulated in cancer 1, also called mammalian retrotransposon-derived 7 (Mart7)] is one of the newly acquired genes from LTR retrotransposons in eutherian mammals. Interestingly, Sirh7/Ldoc1 knockout (KO) mice exhibited abnormal placental cell differentiation/maturation, leading to an overproduction of placental progesterone (P4) and placental lactogen 1 (PL1) from trophoblast giant cells (TGCs). The placenta is an organ that is essential for mammalian viviparity and plays a major endocrinological role during pregnancy in addition to providing nutrients and oxygen to the fetus. P4 is an essential hormone in the preparation and maintenance of pregnancy and the determination of the timing of parturition in mammals; however, the biological significance of placental P4 in rodents is not properly recognized. Here, we demonstrate that mouse placentas do produce P4 in mid-gestation, coincident with a temporal reduction in ovarian P4, suggesting that it plays a role in the protection of the conceptuses specifically in this period. Pregnant Sirh7/Ldoc1 knockout females also displayed delayed parturition associated with a low pup weaning rate. All these results suggest that Sirh7/Ldoc1 has undergone positive selection during eutherian evolution as a eutherian-specific acquired gene because it impacts reproductive fitness via the regulation of placental endocrine function. PMID:25468940

  17. Mice expressing a mutant form of fibrinogen that cannot support fibrin formation exhibit compromised antimicrobial host defense

    PubMed Central

    Prasad, Joni M.; Gorkun, Oleg V.; Raghu, Harini; Thornton, Sherry; Mullins, Eric S.; Palumbo, Joseph S.; Ko, Ya-Ping; Höök, Magnus; David, Tovo; Coughlin, Shaun R.; Degen, Jay L.

    2015-01-01

    Fibrin(ogen) is central to hemostasis and thrombosis and also contributes to multiple physiologic and pathologic processes beyond coagulation. However, the precise contribution of soluble fibrinogen vs insoluble fibrin matrices to vascular integrity, tissue repair, inflammation, and disease has been undefined and unapproachable. To establish the means to distinguish fibrinogen- and fibrin-dependent processes in vivo, FibAEK mice were generated that carry normal levels of circulating fibrinogen but lack the capacity for fibrin polymer formation due to a germ-line mutation in the Aα chain thrombin cleavage site. Homozygous FibAEK mice developed to term and exhibited postnatal survival superior to that of fibrinogen-deficient mice. Unlike fibrinogen-deficient mice, platelet-rich plasma from FibAEK mice supported normal platelet aggregation in vitro, highlighting that fibrinogenAEK retains the functional capacity to support interactions with platelets. Thrombin failed to release fibrinopeptide-A from fibrinogenAEK and failed to induce polymer formation with FibAEK plasma or purified fibrinogenAEK in 37°C mixtures regardless of incubation time. FibAEK mice displayed both an absence of fibrin polymer formation following liver injury, as assessed by electron microscopy, and a failure to generate stable occlusive thrombi following FeCl3 injury of carotid arteries. FibAEK mice exhibited a profound impediment in Staphylococcus aureus clearance following intraperitoneal infection similar to fibrinogen-deficient mice, yet FibAEK mice displayed a significant infection dose-dependent survival advantage over fibrinogen-deficient mice following peritonitis challenge. Collectively, these findings establish for the first time that fibrin polymer is the molecular form critical for antimicrobial mechanisms while simultaneously highlighting biologically meaningful contributions and functions of the soluble molecule. PMID:26228483

  18. Mice expressing a mutant form of fibrinogen that cannot support fibrin formation exhibit compromised antimicrobial host defense.

    PubMed

    Prasad, Joni M; Gorkun, Oleg V; Raghu, Harini; Thornton, Sherry; Mullins, Eric S; Palumbo, Joseph S; Ko, Ya-Ping; Höök, Magnus; David, Tovo; Coughlin, Shaun R; Degen, Jay L; Flick, Matthew J

    2015-10-22

    Fibrin(ogen) is central to hemostasis and thrombosis and also contributes to multiple physiologic and pathologic processes beyond coagulation. However, the precise contribution of soluble fibrinogen vs insoluble fibrin matrices to vascular integrity, tissue repair, inflammation, and disease has been undefined and unapproachable. To establish the means to distinguish fibrinogen- and fibrin-dependent processes in vivo, Fib(AEK) mice were generated that carry normal levels of circulating fibrinogen but lack the capacity for fibrin polymer formation due to a germ-line mutation in the Aα chain thrombin cleavage site. Homozygous Fib(AEK) mice developed to term and exhibited postnatal survival superior to that of fibrinogen-deficient mice. Unlike fibrinogen-deficient mice, platelet-rich plasma from Fib(AEK) mice supported normal platelet aggregation in vitro, highlighting that fibrinogen(AEK) retains the functional capacity to support interactions with platelets. Thrombin failed to release fibrinopeptide-A from fibrinogen(AEK) and failed to induce polymer formation with Fib(AEK) plasma or purified fibrinogen(AEK) in 37°C mixtures regardless of incubation time. Fib(AEK) mice displayed both an absence of fibrin polymer formation following liver injury, as assessed by electron microscopy, and a failure to generate stable occlusive thrombi following FeCl3 injury of carotid arteries. Fib(AEK) mice exhibited a profound impediment in Staphylococcus aureus clearance following intraperitoneal infection similar to fibrinogen-deficient mice, yet Fib(AEK) mice displayed a significant infection dose-dependent survival advantage over fibrinogen-deficient mice following peritonitis challenge. Collectively, these findings establish for the first time that fibrin polymer is the molecular form critical for antimicrobial mechanisms while simultaneously highlighting biologically meaningful contributions and functions of the soluble molecule. PMID:26228483

  19. Effect of intermittent exposure to ethanol and MDMA during adolescence on learning and memory in adult mice

    PubMed Central

    2012-01-01

    Background Heavy binge drinking is increasingly frequent among adolescents, and consumption of 3,4-methylenedioxymethamphetamine (MDMA) is often combined with ethanol (EtOH). The long-lasting effects of intermittent exposure to EtOH and MDMA during adolescence on learning and memory were evaluated in adult mice using the Hebb-Williams maze. Methods Adolescent OF1 mice were exposed to EtOH (1.25 g/kg) on two consecutive days at 48-h intervals over a 14-day period (from PD 29 to 42). MDMA (10 or 20 mg/kg) was injected twice daily at 4-h intervals over two consecutive days, and this schedule was repeated six days later (PD 33, 34, 41 and 42), resulting in a total of eight injections. Animals were initiated in the Hebb-Williams maze on PND 64. The concentration of brain monoamines in the striatum and hippocampus was then measured. Results At the doses employed, both EtOH and MDMA, administered alone or together, impaired learning in the Hebb-Williams maze, as treated animals required more time to reach the goal than their saline-treated counterparts. The groups treated during adolescence with EtOH, alone or plus MDMA, also presented longer latency scores and needed more trials to reach the acquisition criterion score. MDMA induced a decrease in striatal DA concentration, an effect that was augmented by the co-administration of EtOH. All the treatment groups displayed an imbalance in the interaction DA/serotonin. Conclusions The present findings indicate that the developing brain is highly vulnerable to the damaging effects of EtOH and/or MDMA, since mice receiving these drugs in a binge pattern during adolescence exhibit impaired learning and memory in adulthood. PMID:22716128

  20. Mice that lack the C-terminal region of Reelin exhibit behavioral abnormalities related to neuropsychiatric disorders.

    PubMed

    Sakai, Kaori; Shoji, Hirotaka; Kohno, Takao; Miyakawa, Tsuyoshi; Hattori, Mitsuharu

    2016-01-01

    The secreted glycoprotein Reelin is believed to play critical roles in the pathogenesis of several neuropsychiatric disorders. The highly basic C-terminal region (CTR) of Reelin is necessary for efficient activation of its downstream signaling, and the brain structure of knock-in mice that lack the CTR (ΔC-KI mice) is impaired. Here, we performed a comprehensive behavioral test battery on ΔC-KI mice, in order to evaluate the effects of partial loss-of-function of Reelin on brain functions. The ΔC-KI mice were hyperactive and exhibited reduced anxiety-like and social behaviors. The working memory in ΔC-KI mice was impaired in a T-maze test. There was little difference in spatial reference memory, depression-like behavior, prepulse inhibition, or fear memory between ΔC-KI and wild-type mice. These results suggest that CTR-dependent Reelin functions are required for some specific normal brain functions and that ΔC-KI mice recapitulate some aspects of neuropsychiatric disorders, such as schizophrenia, bipolar disorder, and autism spectrum disorder. PMID:27346785

  1. Mice that lack the C-terminal region of Reelin exhibit behavioral abnormalities related to neuropsychiatric disorders

    PubMed Central

    Sakai, Kaori; Shoji, Hirotaka; Kohno, Takao; Miyakawa, Tsuyoshi; Hattori, Mitsuharu

    2016-01-01

    The secreted glycoprotein Reelin is believed to play critical roles in the pathogenesis of several neuropsychiatric disorders. The highly basic C-terminal region (CTR) of Reelin is necessary for efficient activation of its downstream signaling, and the brain structure of knock-in mice that lack the CTR (ΔC-KI mice) is impaired. Here, we performed a comprehensive behavioral test battery on ΔC-KI mice, in order to evaluate the effects of partial loss-of-function of Reelin on brain functions. The ΔC-KI mice were hyperactive and exhibited reduced anxiety-like and social behaviors. The working memory in ΔC-KI mice was impaired in a T-maze test. There was little difference in spatial reference memory, depression-like behavior, prepulse inhibition, or fear memory between ΔC-KI and wild-type mice. These results suggest that CTR-dependent Reelin functions are required for some specific normal brain functions and that ΔC-KI mice recapitulate some aspects of neuropsychiatric disorders, such as schizophrenia, bipolar disorder, and autism spectrum disorder. PMID:27346785

  2. Complexin 1 knockout mice exhibit marked deficits in social behaviours but appear to be cognitively normal.

    PubMed

    Drew, Cheney J G; Kyd, Rachel J; Morton, A Jennifer

    2007-10-01

    Complexins are presynaptic proteins that modulate neurotransmitter release. Abnormal expression of complexin 1 (Cplx1) is seen in several neurodegenerative and psychiatric disorders in which disturbed social behaviour is commonplace. These include Parkinsons's disease, Alzheimer's disease, schizophrenia, major depressive illness and bipolar disorder. We wondered whether changes in Cplx1 expression contribute to the psychiatric components of the diseases in which Cplx1 is dysregulated. To investigate this, we examined the cognitive and social behaviours of complexin 1 knockout mice (Cplx1(-/-)) mice. Cplx1(-/-) mice have a profound ataxia that limits their ability to perform co-ordinated motor tasks. Nevertheless, when we taught juvenile Cplx1(-/-) mice to swim, they showed no evidence of cognitive impairment in the two-choice swim tank. In contrast, although olfactory discrimination in Cplx1(-/-) mice was normal, Cplx1(-/-) mice failed in the social transmission of food preference task, another cognitive paradigm. This was due to abnormal social interactions rather than cognitive impairments, increased anxiety or neophobia. When we tested social behaviour directly, Cplx1(-/-) mice failed to demonstrate a preference for social novelty. Further, in a resident-intruder paradigm, male Cplx1(-/-) mice failed to show the aggressive behaviour that is typical of wild-type males towards an intruder mouse. Together our results show that in addition to the severe motor and exploratory deficits already described, Cplx1(-/-) mice have pronounced deficits in social behaviours. Abnormalities in complexin 1 levels in the brain may therefore contribute to the psycho-social aspects of human diseases in which this protein is dysregulated.

  3. Predicting Early Sexual Activity with Behavior Problems Exhibited at School Entry and in Early Adolescence

    PubMed Central

    Schofield, Hannah-Lise T.; Heinrichs, Brenda; Nix, Robert L.

    2009-01-01

    Youth who initiate sexual intercourse in early adolescence (age 11–14) experience multiple risks, including concurrent adjustment problems and unsafe sexual practices, The current study tested two models describing the links between childhood precursors, early adolescent risk factors, and adolescent sexual activity: a cumulative model and a meditational model, A longitudinal sample of 694 boys and girls from four geographical locations was utilized, with data collected from kindergarten through high school. Structural equation models revealed that, irrespective of gender or race, high rates of aggressive disruptive behaviors and attention problems at school entry increased risk for a constellation of problem behaviors in middle school (school maladjustment, antisocial activity, and substance use) which, in turn, promoted the early initiation of sexual activity. Implications are discussed for developmental models of early sexual activity and for prevention programming. PMID:18607716

  4. Fgf8-Deficient Mice Compensate for Reduced GnRH Neuronal Population and Exhibit Normal Testicular Function.

    PubMed

    Zhang, Wei; Johnson, Joshua I; Tsai, Pei-San

    2015-01-01

    Gonadotropin-releasing hormone (GnRH) is critical for the onset and maintenance of reproduction in vertebrates. The development of GnRH neurons is highly dependent on fibroblast growth factor (Fgf) signaling. Mice with a hypomorphic Fgf8 allele (Fgf8 Het) exhibited a ~50% reduction in GnRH neuron number at birth. Female Fgf8 Het mice were fertile but showed significantly delayed puberty. However, it was unclear if these mice suffered additional loss of GnRH neurons after birth, and if male Fgf8 Het mice had normal pubertal transition and testicular function. In this study, we examined postnatal GnRH neuron number and hypothalamic GnRH content in Fgf8 Het mice from birth to 120 days of age. Further, we examined seminal vesicle and testicular growth, testicular histology, and circulating luteinizing hormone (LH) around and after pubertal transition. Our results showed that GnRH neuron numbers were significantly and consistently reduced in Fgf8 Het mice of both sexes in all ages examined, suggesting these animals were born with an inherently defective GnRH system, and no further postnatal loss of GnRH neurons had occurred. Despite an innately compromised GnRH system, male and female Fgf8 mice exhibited normal levels of immunoassayable hypothalamic GnRH peptide at all ages examined except on 60 days of age, suggesting increased GnRH synthesis or reduced turnover as a compensatory mechanism. Fgf8 Het males also had normal seminal vesicle and testicular mass/body mass ratios, testicular histology, and circulating LH. Overall, our data speak to the extraordinary ability of a GnRH system permanently compromised by developmental defect to overcome pre-existing deficiencies to ensure pubertal progression and reproduction. PMID:26441841

  5. Fgf8-Deficient Mice Compensate for Reduced GnRH Neuronal Population and Exhibit Normal Testicular Function

    PubMed Central

    Zhang, Wei; Johnson, Joshua I.; Tsai, Pei-San

    2015-01-01

    Gonadotropin-releasing hormone (GnRH) is critical for the onset and maintenance of reproduction in vertebrates. The development of GnRH neurons is highly dependent on fibroblast growth factor (Fgf) signaling. Mice with a hypomorphic Fgf8 allele (Fgf8 Het) exhibited a ~50% reduction in GnRH neuron number at birth. Female Fgf8 Het mice were fertile but showed significantly delayed puberty. However, it was unclear if these mice suffered additional loss of GnRH neurons after birth, and if male Fgf8 Het mice had normal pubertal transition and testicular function. In this study, we examined postnatal GnRH neuron number and hypothalamic GnRH content in Fgf8 Het mice from birth to 120 days of age. Further, we examined seminal vesicle and testicular growth, testicular histology, and circulating luteinizing hormone (LH) around and after pubertal transition. Our results showed that GnRH neuron numbers were significantly and consistently reduced in Fgf8 Het mice of both sexes in all ages examined, suggesting these animals were born with an inherently defective GnRH system, and no further postnatal loss of GnRH neurons had occurred. Despite an innately compromised GnRH system, male and female Fgf8 mice exhibited normal levels of immunoassayable hypothalamic GnRH peptide at all ages examined except on 60 days of age, suggesting increased GnRH synthesis or reduced turnover as a compensatory mechanism. Fgf8 Het males also had normal seminal vesicle and testicular mass/body mass ratios, testicular histology, and circulating LH. Overall, our data speak to the extraordinary ability of a GnRH system permanently compromised by developmental defect to overcome pre-existing deficiencies to ensure pubertal progression and reproduction. PMID:26441841

  6. The effects of paradoxical sleep deprivation on amphetamine-induced behavioral sensitization in adult and adolescent mice.

    PubMed

    Kameda, Sonia R; Fukushiro, Daniela F; Trombin, Thaís F; Sanday, Leandro; Wuo-Silva, Raphael; Saito, Luis P; Tufik, Sergio; D'Almeida, Vânia; Frussa-Filho, Roberto

    2014-08-30

    Drug-induced behavioral sensitization (BS), paradoxical sleep deprivation (PSD) and adolescence in rodents are associated with changes in the mesolimbic dopaminergic system. We compared the effects of PSD on amphetamine-induced BS in adult and adolescent mice. Adult (90 days old) and adolescent (45 days old) Swiss mice were subjected to PSD for 48h. Immediately after PSD, mice received saline or 2.0mg/kg amphetamine intraperitoneally (i.p.), and their locomotion was quantified in activity chambers. Seven days later, all the animals were challenged with 2.0mg/kg amphetamine i.p., and their locomotion was quantified again. Acute amphetamine enhanced locomotion in both adult and adolescent mice, but BS was observed only in adolescent mice. Immediately after its termination, PSD decreased locomotion of both saline- and amphetamine-treated adolescent mice. Seven days later, previous PSD potentiated both the acute stimulatory effect of amphetamine and its sensitization in adolescent mice. In adult animals, previous PSD revealed BS. Our data suggest that adolescent mice are more vulnerable to both the immediate and long-term effects of PSD on amphetamine-induced locomotion. Because drug-induced BS in rodents shares neuroplastic changes with drug craving in humans, our findings also suggest that both adolescence and PSD could facilitate craving-related mechanisms in amphetamine abuse.

  7. Low-Income, African American Adolescent Mothers and Their Toddlers Exhibit Similar Dietary Variety Patterns

    ERIC Educational Resources Information Center

    Papas, Mia A.; Hurley, Kristen M.; Quigg, Anna M.; Oberlander, Sarah E.; Black, Maureen M.

    2009-01-01

    Objective: To examine the relationship between maternal and toddler dietary variety. Design: Longitudinal; maternal and toddler dietary data were collected at 13 months; anthropometry was collected at 13 and 24 months. Setting: Data were collected in homes. Participants: 109 primiparous, low-income, African American adolescent mothers and…

  8. Characteristics of Adolescents with Type 1 Diabetes Who Exhibit Adverse Outcomes

    PubMed Central

    Johns, Carla; Faulkner, Melissa Spezia; Quinn, Lauretta

    2008-01-01

    Purpose The primary purpose of this study was to determine differences in key characteristics between adolescents with type 1 diabetes who experienced the adverse outcomes of poor glycemic control, hypoglycemic events, and hospitalizations due to their disease versus those who do not experience such events. A secondary purpose was to examine differences in outcomes for adolescents using insulin pumps versus daily insulin injections (≥ 2). Methods Data from 108 adolescents were divided according to glycemic control (HbA1c <8% vs. ≥8%), hypoglycemic reactions and hospitalizations in the past year (0 vs. ≥ 1 episode of each), and pump versus injection delivery of insulin. The following variables were compared within each grouping: body mass index (BMI) insulin dose, caloric intake, parental educational level, marital status, annual family income, race, and gender. HbA1c was examined in relation to the number of hypoglycemic reactions and hospitalizations in the past year, as well as for any differences between those receiving insulin via pump therapy versus daily injections (≥ 2). Results Subjects receiving insulin via pump had better glucose control and were on lower insulin doses than those receiving insulin injections. Subjects with adequate versus inadequate glucose control used a lower insulin dose, checked their blood sugar more frequently, and had fathers with a higher education level. Finally, those with inadequate control were more likely to come from a single parent home, a lower income family, and from an ethnic minority. Conclusions Pump therapy for adolescents should be encouraged when appropriate. Also, certain groups of adolescents need increased supervision to manage their disease appropriately. Further research needs to explore what interventions will bring more favorable outcomes for such groups. PMID:18832292

  9. Early adolescent nicotine exposure affects later-life cocaine reward in mice.

    PubMed

    Alajaji, Mai; Lazenka, Matthew F; Kota, Dena; Wise, Laura E; Younis, Rabha M; Carroll, F Ivy; Levine, Amir; Selley, Dana E; Sim-Selley, Laura J; Damaj, M Imad

    2016-06-01

    Adolescence represents a unique developmental period associated with increased risk-taking behavior and experimentation with drugs of abuse, in particular nicotine. We hypothesized that exposure to nicotine during early adolescence might increase the risk for drug reward in adulthood. To test this hypothesis, male ICR mice were treated with a subchronic regimen of nicotine or saline during adolescence, and their preference for cocaine, morphine and amphetamine was examined using the conditioned place preference (CPP) test in adulthood. Long-term behavioral changes induced by nicotine suggested a possible role of altered gene transcription. Thus, immunoblot for ΔFosB, a member of the Fos family of transcription factors, was conducted in the nucleus accumbens of these mice. Mice treated with nicotine during early but not late adolescence showed an increase in CPP for cocaine, morphine and amphetamine later in adulthood. This effect was not seen in mice pretreated with a subchronic regimen of nicotine as adults, suggesting that exposure to nicotine specifically during early adolescence increases the rewarding effects of other drugs in adulthood. However, adolescent nicotine exposure did not alter highly palatable food conditioning in mice. The enhancement of cocaine CPP by nicotine was strain-dependent and was blocked by pretreatment with nicotinic antagonists. In addition, nicotine exposure during early adolescence induced ΔFosB expression to a greater extent than identical nicotine exposure in adulthood, and enhanced cocaine-induced locomotor sensitization later in adulthood. These results suggest that nicotine exposure during early adolescence increases drug-induced reward in adulthood through mechanisms that may involve the induction of ΔFosB. PMID:26808314

  10. Mice heterozygous for cathepsin D deficiency exhibit mania-related behavior and stress-induced depression.

    PubMed

    Zhou, Rui; Lu, Yi; Han, Yong; Li, Xia; Lou, Huifang; Zhu, Liya; Zhen, Xuechu; Duan, Shumin

    2015-12-01

    Mutations in cathepsin D (CTSD), an aspartic protease in the endosomal-lysosomal system, underlie congenital neuronal ceroid-lipofuscinosis (cNCL, also known as CLN10), a devastating neurodegenerative disease. CLN10 patients die within the first few days of life, and in the few patients who live into adulthood psychopathological symptoms have not been reported. Extensive neuropathology and altered neurotransmission have been reported in CTSD-deficient mice; however signs of neuropsychiatric behavior in these mice are not well characterized due to the severe movement disorder and premature death of the animal. In the present study, we show that heterozygous CTSD-deficient (CTSD HET) mice display an overall behavioral profile that is similar to human mania, including hyperlocomotion, d-amphetamine-induced hyperactivity, sleep-disturbance, and reduced anxiety-like behavior. However, under stressful conditions CTSD HET mice manifest depressive-like behavior, including anhedonia, behavioral despair, and enhanced learned helplessness. Chronic administration of lithium chloride or valproic acid, two clinically effective mood stabilizers, reverses the majority of these behavioral abnormalities. In addition, CTSD HET mice display stress-induced hypersecretion of corticosterone. These findings suggest an important role for CTSD in the regulation of mood stabilization.

  11. Romk1 Knockout Mice Do Not Produce Bartter Phenotype but Exhibit Impaired K Excretion.

    PubMed

    Dong, Ke; Yan, Qingshang; Lu, Ming; Wan, Laxiang; Hu, Haiyan; Guo, Junhua; Boulpaep, Emile; Wang, WenHui; Giebisch, Gerhard; Hebert, Steven C; Wang, Tong

    2016-03-01

    Romk knock-out mice show a similar phenotype to Bartter syndrome of salt wasting and dehydration due to reduced Na-K-2Cl-cotransporter activity. At least three ROMK isoforms have been identified in the kidney; however, unique functions of any of the isoforms in nephron segments are still poorly understood. We have generated a mouse deficient only in Romk1 by selective deletion of the Romk1-specific first exon using an ES cell Cre-LoxP strategy and examined the renal phenotypes, ion transporter expression, ROMK channel activity, and localization under normal and high K intake. Unlike Romk(-/-) mice, there was no Bartter phenotype with reduced NKCC2 activity and increased NCC expression in Romk1(-/-) mice. The small conductance K channel (SK) activity showed no difference of channel properties or gating in the collecting tubule between Romk1(+/+) and Romk1(-/-) mice. High K intake increased SK channel number per patch and increased the ROMK channel intensity in the apical membrane of the collecting tubule in Romk1(+/+), but such regulation by high K intake was diminished with significant hyperkalemia in Romk1(-/-) mice. We conclude that 1) animal knockouts of ROMK1 do not produce Bartter phenotype. 2) There is no functional linking of ROMK1 and NKCC2 in the TAL. 3) ROMK1 is critical in response to high K intake-stimulated K(+) secretion in the collecting tubule. PMID:26728465

  12. Skeletal muscle-specific HMG-CoA reductase knockout mice exhibit rhabdomyolysis: A model for statin-induced myopathy.

    PubMed

    Osaki, Yoshinori; Nakagawa, Yoshimi; Miyahara, Shoko; Iwasaki, Hitoshi; Ishii, Akiko; Matsuzaka, Takashi; Kobayashi, Kazuto; Yatoh, Shigeru; Takahashi, Akimitsu; Yahagi, Naoya; Suzuki, Hiroaki; Sone, Hirohito; Ohashi, Ken; Ishibashi, Shun; Yamada, Nobuhiro; Shimano, Hitoshi

    2015-10-23

    HMG-CoA reductase (HMGCR) catalyzes the conversion of HMG-CoA to mevalonic acid (MVA); this is the rate-limiting enzyme of the mevalonate pathway that synthesizes cholesterol. Statins, HMGCR inhibitors, are widely used as cholesterol-reducing drugs. However, statin-induced myopathy is the most adverse side effect of statins. To eludicate the mechanisms underlying statin the myotoxicity and HMGCR function in the skeletal muscle, we developed the skeletal muscle-specific HMGCR knockout mice. Knockout mice exhibited postnatal myopathy with elevated serum creatine kinase levels and necrosis. Myopathy in knockout mice was completely rescued by the oral administration of MVA. These results suggest that skeletal muscle toxicity caused by statins is dependent on the deficiencies of HMGCR enzyme activity and downstream metabolites of the mevalonate pathway in skeletal muscles rather than the liver or other organs.

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

    PubMed Central

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

    2016-01-01

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

  14. Mice lacking NCF1 exhibit reduced growth of implanted melanoma and carcinoma tumors.

    PubMed

    Kelkka, Tiina; Pizzolla, Angela; Laurila, Juha Petteri; Friman, Tomas; Gustafsson, Renata; Källberg, Eva; Olsson, Olof; Leanderson, Tomas; Rubin, Kristofer; Salmi, Marko; Jalkanen, Sirpa; Holmdahl, Rikard

    2013-01-01

    The NADPH oxidase 2 (NOX2) complex is a professional producer of reactive oxygen species (ROS) and is mainly expressed in phagocytes. While the activity of the NOX2 complex is essential for immunity against pathogens and protection against autoimmunity, its role in the development of malignant tumors remains unclear. We compared wild type and Ncf1 (m1J) mutated mice, which lack functional NOX2 complex, in four different tumor models. Ncf1 (m1J) mutated mice developed significantly smaller tumors in two melanoma models in which B16 melanoma cells expressing a hematopoietic growth factor FLT3L or luciferase reporter were used. Ncf1 (m1J) mutated mice developed significantly fewer Lewis Lung Carcinoma (LLC) tumors, but the tumors that did develop, grew at a pace that was similar to the wild type mice. In the spontaneously arising prostate carcinoma model (TRAMP), tumor growth was not affected. The lack of ROS-mediated protection against tumor growth was associated with increased production of immunity-associated cytokines. A significant increase in Th2 associated cytokines was observed in the LLC model. Our present data show that ROS regulate rejection of the antigenic B16-luc and LLC tumors, whereas the data do not support a role for ROS in growth of intrinsically generated tumors. PMID:24358335

  15. Adolescent Mice, Unlike Adults, Consume More Alcohol in the Presence of Peers than Alone

    PubMed Central

    Logue, Sheree; Chein, Jason; Gould, Thomas; Holliday, Erica; Steinberg, Laurence

    2013-01-01

    One hallmark of adolescent risk taking is that it typically occurs when adolescents are with peers. It has been hypothesized that the presence of peers primes a reward-sensitive motivational state that overwhelms adolescents’ immature capacity for inhibitory control. We examined this hypothesis using a rodent model. A sample of mice were raised in same-sex triads and were tested for alcohol consumption either as juveniles or as adults, with half in each age group tested alone and half tested with their cagemates. The presence of “peers” increased alcohol consumption among adolescent mice, but not adults. The peer effect on human adolescent reward-seeking may reflect a hard-wired, evolutionarily conserved process through which the presence of agemates increases individuals’ sensitivity to potential rewards in their immediate environment. PMID:24341974

  16. Obese carboxypeptidase E knockout mice exhibit multiple defects in peptide hormone processing contributing to low bone mineral density

    PubMed Central

    Cawley, Niamh X.; Yanik, Tulin; Woronowicz, Alicja; Chang, Weizhong; Marini, Joan C.

    2010-01-01

    Carboxypeptidase E (CPE) is a prohormone/proneuropeptide processing enzyme, and mice bearing CPE mutations exhibit an obese and diabetic phenotype. Studies on CPE knockout (KO) mice revealed poor prohormone processing, resulting in deficiencies in peptide hormones/neuropeptides such as insulin, gonadotropin-releasing hormone, and cocaine- and amphetamine-regulated transcript (CART). Here, we show that CPE KO mice, an obese animal model, have low bone mineral density (BMD) accompanied by elevated plasma CTX-1 (carboxy-terminal collagen crosslinks), and osteocalcin, indicators of increased bone turnover. Receptor activator for NF-κB ligand (RANKL) expression was elevated ∼2-fold relative to osteoprotegerin in the femur of KO animals, suggesting increased osteoclastic activity in the KO mice. In the hypothalamus, mature CART, a peptide involved in eating behavior and implicated in bone metabolism, was undetectable. The melanocortin and neuropeptide Y (NPY) systems in the hypothalamus have also been implicated in bone remodeling, since MC4R KO and NPY KO mice have increased BMD. However, reduction of α-MSH, the primary ligand of MC4R by up to 94% and the lack of detectable NPY in the hypothalamus of CPE KO do not recapitulate the single-gene KO phenotypes. This study highlights the complex physiological interplay between peptides involved in energy metabolism and bone formation and furthermore suggests the possibility that patients, bearing CPE and CART mutations leading to inactive forms of these molecules, may be at a higher risk of developing osteoporosis. PMID:20460579

  17. Permanent Suppression of Cortical Oscillations in Mice After Adolescent Exposure to Cannabinoids: Receptor Mechanisms

    PubMed Central

    Raver, Sylvina M.; Keller, Asaf

    2014-01-01

    Marijuana use in adolescence, but not adulthood, may permanently impair cognitive functioning and increase the risk of developing schizophrenia. Cortical oscillations are patterns of neural network activity implicated in cognitive processing, and are abnormal in patients with schizophrenia. We have recently reported that cortical oscillations are suppressed in adult mice that were treated, in adolescence but not adulthood, with the cannabinoids WIN55,212-2 (WIN) or Δ9tetrahydrocannabinol (THC). WIN and THC are cannabinoid types 1 and 2 receptor (CB1R & CB2R) agonists, and also have activity at non-cannabinoid receptor targets. However, as acute WIN and THC administration can suppress oscillations through CB1Rs, we hypothesize that a similar mechanism underlies the permanent suppression of oscillations by repeated cannabinoid exposure in adolescence. Here we test the prediction that cannabinoid exposure in adolescence permanently suppresses cortical oscillations by acting through CB1Rs, and that these suppressive effects can be antagonized by a CB1R antagonist. We treated adolescent mice with various cannabinoid compounds, and pharmacologically-evoked oscillations in vitro in adult mice. We find that WIN exposure for six days in early adolescence suppresses oscillations preferentially in adult medial prefrontal cortex (mPFC) via CB1Rs, and that a similar CB1R mechanism accounts for the suppressive effects of long-term (20 day) adolescent THC in adult somatosensory cortex (SCx). Unexpectedly, we also find that CB2Rs may be involved in the suppression of oscillations in both mPFC and SCx by long-term adolescent cannabinoid exposure, and that non-cannabinoid receptors may also contribute to oscillation suppression in adult mPFC. These findings represent a novel attempt to antagonize the effects of adolescent cannabinoid exposure on neural network activity, and reveal the contribution of non-CB1R targets to the suppression of cortical oscillations. PMID:25036610

  18. Walnut extract exhibits anti-fatigue action via improvement of exercise tolerance in mice.

    PubMed

    Kim, Dae-Ik; Kim, Kil-Soo

    2013-12-01

    This study was conducted to investigate the anti-fatigue effect of walnut extract (WE) on forced swimming capacity in mice. Twenty-eight male ICR mice were randomly divided into four groups, a vehicle control (VC) or one of three WE administered groups (300, 600 and 900 mg/kg/day). WE was orally administered to mice once a day for 4 weeks, during which time a forced swimming test was conducted once a week. The vehicle control group was given a corresponding volume of sterile distilled water. After 4 weeks, the forced swimming capacity and levels of blood lactate, glucose, glutamine, ammonia and triacylglycerol, and liver glycogen were measured. In the WE administration group (600 and 900 mg/kg) the maximum swimming time increased significantly when compared with the vehicle control group. WE (600 and 900 mg/kg) significantly decreased the levels of lactate andammonia and increased the blood glutamine levels and liver glycogen content after forced swimming relative to the vehicle control group. The results of this study demonstrated the anti-fatigue effects of WE in a dose-dependent manner. The effects of WE at 600 and 900 mg/kg were similar. Overall, these results suggest that walnut has anti-fatigue activity and could elevate exercise tolerance. PMID:24396383

  19. Transgenic Mice Overexpressing Renin Exhibit Glucose Intolerance and Diet-Genotype Interactions

    PubMed Central

    Fletcher, Sarah J.; Kalupahana, Nishan S.; Soltani-Bejnood, Morvarid; Kim, Jung Han; Saxton, Arnold M.; Wasserman, David H.; De Taeye, Bart; Voy, Brynn H.; Quignard-Boulange, Annie; Moustaid-Moussa, Naima

    2013-01-01

    Numerous animal and clinical investigations have pointed to a potential role of the renin-angiotensin system (RAS) in the development of insulin resistance and diabetes in conditions of expanded fat mass. However, the mechanisms underlying this association remain unclear. We used a transgenic mouse model overexpressing renin in the liver (RenTgMK) to examine the effects of chronic activation of RAS on adiposity and insulin sensitivity. Hepatic overexpression of renin resulted in constitutively elevated plasma angiotensin II (four- to six-fold increase vs. wild-type, WT). Surprisingly, RenTgMK mice developed glucose intolerance despite low levels of adiposity and insulinemia. The transgenics also had lower plasma triglyceride levels. Glucose intolerance in transgenic mice fed a low-fat diet was comparable to that observed in high-fat fed WT mice. These studies demonstrate that overexpression of renin and associated hyperangiotensinemia impair glucose tolerance in a diet-dependent manner and further support a consistent role of RAS in the pathogenesis of diabetes and insulin resistance, independent of changes in fat mass. PMID:23308073

  20. Escherichia coli Braun Lipoprotein (BLP) exhibits endotoxemia – like pathology in Swiss albino mice

    PubMed Central

    Lakshmikanth, Chikkamenahalli Lakshminarayana; Jacob, Shancy Petsel; Kudva, Avinash Kundadka; Latchoumycandane, Calivarathan; Yashaswini, Puttaraju Srikanta Murthy; Sumanth, Mosale Seetharam; Goncalves-de-Albuquerque, Cassiano F.; Silva, Adriana R.; Singh, Sridevi Annapurna; Castro-Faria-Neto, Hugo C.; Prabhu, Sandeep Kumble; McIntyre, Thomas M.; Marathe, Gopal Kedihithlu

    2016-01-01

    The endotoxin lipopolysaccharide (LPS) promotes sepsis, but bacterial peptides also promote inflammation leading to sepsis. We found, intraperitoneal administration of live or heat inactivated E. coli JE5505 lacking the abundant outer membrane protein, Braun lipoprotein (BLP), was less toxic than E. coli DH5α possessing BLP in Swiss albino mice. Injection of BLP free of LPS purified from E. coli DH5α induced massive infiltration of leukocytes in lungs and liver. BLP activated human polymorphonuclear cells (PMNs) ex vivo to adhere to denatured collagen in serum and polymyxin B independent fashion, a property distinct from LPS. Both LPS and BLP stimulated the synthesis of platelet activating factor (PAF), a potent lipid mediator, in human PMNs. In mouse macrophage cell line, RAW264.7, while both BLP and LPS similarly upregulated TNF-α and IL-1β mRNA; BLP was more potent in inducing cyclooxygenase-2 (COX-2) mRNA and protein expression. Peritoneal macrophages from TLR2−/− mice significantly reduced the production of TNF-α in response to BLP in contrast to macrophages from wild type mice. We conclude, BLP acting through TLR2, is a potent inducer of inflammation with a response profile both common and distinct from LPS. Hence, BLP mediated pathway may also be considered as an effective target against sepsis. PMID:27698491

  1. Growth hormone secretagogue receptor (GHS-R1a) knockout mice exhibit improved spatial memory and deficits in contextual memory.

    PubMed

    Albarran-Zeckler, Rosie G; Brantley, Alicia Faruzzi; Smith, Roy G

    2012-06-15

    Although the hormone ghrelin is best known for its stimulatory effect on appetite and regulation of growth hormone release, it is also reported to have beneficial effects on learning and memory formation in mice. Nevertheless, controversy exists about whether endogenous ghrelin acts on its receptors in extra-hypothalamic areas of the brain. The ghrelin receptor (GHS-R1a) is co-expressed in neurons that express dopamine receptor type-1 (DRD1a) and type-2 (DRD2), and we have shown that a subset of GHS-R1a, which are not occupied by the agonist (apo-GHSR1a), heterodimerize with these two receptors to regulate dopamine signaling in vitro and in vivo. To determine the consequences of ghsr ablation on brain function, congenic ghsr -/- mice on the C57BL6/J background were subjected to a battery of behavioral tests. We show that the ghsr -/- mice exhibit normal balance, movement, coordination, and pain sensation, outperform ghsr +/+ mice in the Morris water maze, but show deficits in contextual fear conditioning.

  2. Mx1-Cre mediated Rgs12 conditional knockout mice exhibit increased bone mass phenotype

    PubMed Central

    Yang, Shuying; Li, Yi-ping; Liu, Tongjun; He, Xiaoning; Yuan, Xue; Li, Chunyi; Cao, Jay; Kim, Yunjung

    2013-01-01

    Regulators of G-protein Signaling (Rgs) proteins are the members of a multigene family of GTPase-accelerating proteins (GAP) for the Galpha subunit of heterotrimeric G-proteins. Rgs proteins play critical roles in the regulation of G protein couple receptor (GPCR) signaling in normal physiology and human diseases such as cancer, heart diseases and inflammation. Rgs12 is the largest protein of the Rgs protein family. Some in vitro studies have demonstrated that Rgs12 plays a critical role in regulating cell differentiation and migration; however its function and mechanism in vivo is largely unknown. Here, we generated a floxed Rgs12 allele (Rgs12flox/flox) in which the exon 2, containing both PDZ and PTB_PID domains of Rgs12, was flanked with two loxp sites. By using the inducible Mx1-cre and Poly I:C system to specifically delete Rgs12 at postnatal 10 days in interferon-responsive cells including monocyte and macrophage cells, we found that Rgs12 mutant mice had growth retardation with the phenotype of increased bone mass. We further found that deletion of Rgs12 reduced osteoclast numbers and had no significant effect on osteoblast formation. Thus, Rgs12flox/flox conditional mice provide a valuable tool for in vivo analysis of Rgs12 function and mechanism through time- and cell-specific deletion of Rgs12. PMID:23349096

  3. Nebulin-deficient mice exhibit shorter thin filament lengths and reduced contractile function in skeletal muscle

    PubMed Central

    Bang, Marie-Louise; Li, Xiaodong; Littlefield, Ryan; Bremner, Shannon; Thor, Andrea; Knowlton, Kirk U.; Lieber, Richard L.; Chen, Ju

    2006-01-01

    Nebulin is a giant modular sarcomeric protein that has been proposed to play critical roles in myofibrillogenesis, thin filament length regulation, and muscle contraction. To investigate the functional role of nebulin in vivo, we generated nebulin-deficient mice by using a Cre knock-in strategy. Lineage studies utilizing this mouse model demonstrated that nebulin is expressed uniformly in all skeletal muscles. Nebulin-deficient mice die within 8–11 d after birth, with symptoms including decreased milk intake and muscle weakness. Although myofibrillogenesis had occurred, skeletal muscle thin filament lengths were up to 25% shorter compared with wild type, and thin filaments were uniform in length both within and between muscle types. Ultrastructural studies also demonstrated a critical role for nebulin in the maintenance of sarcomeric structure in skeletal muscle. The functional importance of nebulin in skeletal muscle function was revealed by isometric contractility assays, which demonstrated a dramatic reduction in force production in nebulin-deficient skeletal muscle. PMID:16769824

  4. Reduced behavioral response to gonadal hormones in mice shipped during the peripubertal/adolescent period.

    PubMed

    Laroche, Julie; Gasbarro, Lauren; Herman, James P; Blaustein, Jeffrey D

    2009-05-01

    Animals shipped from commercial suppliers to laboratories are exposed to a wide variety of stressors. Female C57Bl6/J mice shipped during the peripubertal/adolescent period (6 wk old) display lower levels of female sexual behavior in response to estradiol and progesterone injections after ovariectomy when tested in adulthood than female mice shipped in adulthood (12 wk old). These shipping-induced reductions in female sexual behavior appear to be limited to a vulnerable period around the time of puberty. Likewise, male mice shipped at 6 wk of age express lower levels of masculine sexual behavior in response to testosterone treatment as adults than do mice shipped when 12 wk old. RIA of corticosterone levels in response to behavior testing revealed that, upon first exposure to testing, mice shipped at 6 wk of age have reduced corticosterone levels. These results suggest that during the peripubertal/adolescent period, mice of both sexes are susceptible to the effects of stressors associated with shipping. Furthermore, they suggest that stress during this period has enduring, negative influences on behavioral responses to estradiol and progesterone in females and to testosterone in males, and it induces changes in response of the hypothalamic-pituitary-adrenal axis. These results suggest that age at shipping is a critical variable that may influence many endocrinological studies, and they suggest that the peripubertal/adolescent period is a period of vulnerability to some stressors.

  5. Social Peers Rescue Autism-Relevant Sociability Deficits in Adolescent Mice

    PubMed Central

    Yang, Mu; Perry, Kayla; Weber, Michael D.; Katz, Adam M.; Crawley, Jacqueline N.

    2010-01-01

    Lay Abstract Limited reciprocal social interactions are central to the diagnosis of autism. Behavioral intervention programs are effective in improving social and communication skills in children with autism. We are employing mouse models to understand the individual components of behavioral interventions which effectively improve social interactions. BTBR T+tf/J (BTBR) is an inbred strain of mice that exhibits multiple social deficits, unusual vocalizations, and high levels of repetitive behaviors, which are relevant to all three diagnostic symptom categories of autism. C57BL/6J (B6) is an inbred strain of mice that exhibits high sociability and low repetitive behaviors. We reasoned that these mouse strains with low versus high social interactions might be useful for evaluating social peer enrichment as a behavioral intervention during adolescence. Juvenile BTBR and B6 of the same sex were placed in a same home cage and lived together as cagemates until they reached young adulthood. The two control groups were juvenile B6 housed together, and juvenile BTBR housed together. B6 controls that lived with B6 cagemates showed their strain-typical high sociability. BTBR controls that lived with BTBR cagemates showed their strain-typical low sociability. Remarkably, BTBR that shared home cages with B6 showed high sociability as young adults. Peer rearing for either 20 days or 40 days were equally effective. These results from a robust mouse model of autism support the strategy of early behavioral intervention for treating the social domain in autism spectrum disorders, including beneficial interactions with social peers. Scientific Abstract Behavioral therapies are currently the most effective interventions for treating the diagnostic symptoms of autism. We employed a mouse model of autism to evaluate components of behavioral interventions that improve sociability in mice. BTBR T+tf/J (BTBR) is an inbred mouse strain that exhibits prominent behavioral phenotypes with face

  6. Evaluation and Treatment of Swimming Pool Avoidance Exhibited by an Adolescent Girl with Autism

    ERIC Educational Resources Information Center

    Rapp, John T.; Vollmer, Timothy R.; Hovanetz, Alyson N.

    2005-01-01

    We evaluated and treated swimming pool avoidance that was exhibited by a 14-year-old girl diagnosed with autism. In part, treatment involved blocking for flopping (dropping to the ground) and elopement (running away from the pool) and access to food for movements toward a swimming pool. Treatment also involved reinforcement for exposure to various…

  7. Enhancement of Behavioral Sensitization, Anxiety-Like Behavior, and Hippocampal and Frontal Cortical CREB Levels Following Cocaine Abstinence in Mice Exposed to Cocaine during Adolescence

    PubMed Central

    Valzachi, Maria Cristina; Teodorov, Elizabeth; Marcourakis, Tania; Bailey, Alexis; Camarini, Rosana

    2013-01-01

    Adolescence has been linked to greater risk-taking and novelty-seeking behavior and a higher prevalence of drug abuse and risk of relapse. Decreases in cyclic adenosine monophosphate response element binding protein (CREB) and phosphorylated CREB (pCREB) have been reported after repeated cocaine administration in animal models. We compared the behavioral effects of cocaine and abstinence in adolescent and adult mice and investigated possible age-related differences in CREB and pCREB levels. Adolescent and adult male Swiss mice received one daily injection of saline or cocaine (10 mg/kg, i.p.) for 8 days. On day 9, the mice received a saline injection to evaluate possible environmental conditioning. After 9 days of withdrawal, the mice were tested in the elevated plus maze to evaluate anxiety-like behavior. Twelve days after the last saline/cocaine injection, the mice received a challenge injection of either cocaine or saline, and locomotor activity was assessed. One hour after the last injection, the brains were extracted, and CREB and pCREB levels were evaluated using Western blot in the prefrontal cortex (PFC) and hippocampus. The cocaine-pretreated mice during adolescence exhibited a greater magnitude of the expression of behavioral sensitization and greater cocaine withdrawal-induced anxiety-like behavior compared with the control group. Significant increases in CREB levels in the PFC and hippocampus and pCREB in the hippocampus were observed in cocaine-abstinent animals compared with the animals treated with cocaine in adulthood. Interestingly, significant negative correlations were observed between cocaine sensitization and CREB levels in both regions. These results suggest that the behavioral and neurochemical consequences of psychoactive substances in a still-developing nervous system can be more severe than in an already mature nervous system. PMID:24205196

  8. Mice Deficient in Proglucagon-Derived Peptides Exhibit Glucose Intolerance on a High-Fat Diet but Are Resistant to Obesity.

    PubMed

    Takagi, Yusuke; Kinoshita, Keita; Ozaki, Nobuaki; Seino, Yusuke; Murata, Yoshiharu; Oshida, Yoshiharu; Hayashi, Yoshitaka

    2015-01-01

    Homozygous glucagon-GFP knock-in mice (Gcggfp/gfp) lack proglucagon derived-peptides including glucagon and GLP-1, and are normoglycemic. We have previously shown that Gcggfp/gfp show improved glucose tolerance with enhanced insulin secretion. Here, we studied glucose and energy metabolism in Gcggfp/gfp mice fed a high-fat diet (HFD). Male Gcggfp/gfp and Gcggfp/+ mice were fed either a normal chow diet (NCD) or an HFD for 15-20 weeks. Regardless of the genotype, mice on an HFD showed glucose intolerance, and Gcggfp/gfp mice on HFD exhibited impaired insulin secretion whereas Gcggfp/+ mice on HFD exhibited increased insulin secretion. A compensatory increase in β-cell mass was observed in Gcggfp/+mice on HFD, but not in Gcggfp/gfp mice on the same diet. Weight gain was significantly lower in Gcggfp/gfp mice than in Gcggfp/+mice. Oxygen consumption was enhanced in Gcggfp/gfp mice compared to Gcggfp/+ mice on an HFD. HFD feeding significantly increased uncoupling protein 1 mRNA expression in brown adipose and inguinal white adipose tissues of Gcggfp/gfp mice, but not of Gcggfp/+mice. Treatment with the glucagon-like peptide-1 receptor agonist liraglutide (200 mg/kg) improved glucose tolerance in Gcggfp/gfp mice and insulin content in Gcggfp/gfp and Gcggfp/+ mice was similar after liraglutide treatment. Our findings demonstrate that Gcggfp/gfp mice develop diabetes upon HFD-feeding in the absence of proglucagon-derived peptides, although they are resistant to diet-induced obesity.

  9. HdhQ111 Mice Exhibit Tissue Specific Metabolite Profiles that Include Striatal Lipid Accumulation

    PubMed Central

    Carroll, Jeffrey B.; Deik, Amy; Fossale, Elisa; Weston, Rory M.; Guide, Jolene R.; Arjomand, Jamshid; Kwak, Seung; Clish, Clary B.; MacDonald, Marcy E.

    2015-01-01

    The HTT CAG expansion mutation causes Huntington’s Disease and is associated with a wide range of cellular consequences, including altered metabolism. The mutant allele is expressed widely, in all tissues, but the striatum and cortex are especially vulnerable to its effects. To more fully understand this tissue-specificity, early in the disease process, we asked whether the metabolic impact of the mutant CAG expanded allele in heterozygous B6.HdhQ111/+ mice would be common across tissues, or whether tissues would have tissue-specific responses and whether such changes may be affected by diet. Specifically, we cross-sectionally examined steady state metabolite concentrations from a range of tissues (plasma, brown adipose tissue, cerebellum, striatum, liver, white adipose tissue), using an established liquid chromatography-mass spectrometry pipeline, from cohorts of 8 month old mutant and wild-type littermate mice that were fed one of two different high-fat diets. The differential response to diet highlighted a proportion of metabolites in all tissues, ranging from 3% (7/219) in the striatum to 12% (25/212) in white adipose tissue. By contrast, the mutant CAG-expanded allele primarily affected brain metabolites, with 14% (30/219) of metabolites significantly altered, compared to wild-type, in striatum and 11% (25/224) in the cerebellum. In general, diet and the CAG-expanded allele both elicited metabolite changes that were predominantly tissue-specific and non-overlapping, with evidence for mutation-by-diet interaction in peripheral tissues most affected by diet. Machine-learning approaches highlighted the accumulation of diverse lipid species as the most genotype-predictive metabolite changes in the striatum. Validation experiments in cell culture demonstrated that lipid accumulation was also a defining feature of mutant HdhQ111 striatal progenitor cells. Thus, metabolite-level responses to the CAG expansion mutation in vivo were tissue specific and most evident

  10. A novel transgenic line of mice exhibiting autosomal recessive male-specific lethality and non-alcoholic fatty liver disease.

    PubMed

    Sollars, Vincent E; McEntee, Benjamin J; Engiles, Julie B; Rothstein, Jay L; Buchberg, Arthur M

    2002-10-15

    We have isolated a Meis1a transgenic mouse line exhibiting recessive male-specific lethality and non-alcoholic fatty liver disease (NAFLD), which coincides with pubescence and is androgen-dependent. The phenotype is due to disruption of an endogenous locus, since other Meis1a transgenic lines do not exhibit these phenotypes. Necropsy analysis revealed hepatic microvesicular steatosis in pubescent male homozygous mice, which is absent in transgenic females. The transgene insertion site was localized to chromosome 1 and further refined by cloning the flanking regions. Sequence analysis shows that the integration site disrupts a putative metallo-beta-lactamase gene with a 21.3 kb deletion encompassing exons 5-7.

  11. Fucoidan Supplementation Improves Exercise Performance and Exhibits Anti-Fatigue Action in Mice

    PubMed Central

    Chen, Yi-Ming; Tsai, Yi-Hsin; Tsai, Tsung-Yu; Chiu, Yen-Shuo; Wei, Li; Chen, Wen-Chyuan; Huang, Chi-Chang

    2014-01-01

    Fucoidan (FCD) is a well-known bioactive constituent of seaweed extract that possess a wide spectrum of activities in biological systems, including anti-cancer, anti-inflammation and modulation of immune systems. However, evidence on the effects of FCD on exercise performance and physical fatigue is limited. Therefore, we investigated the potential beneficial effects of FCD on ergogenic and anti-fatigue functions following physiological challenge. Male ICR mice from three groups (n = 8 per group) were orally administered FCD for 21 days at 0, 310 and 620 mg/kg/day, which were, respectively, designated the vehicle, FCD-1X and FCD-2X groups. The results indicated that the FCD supplementations increased the grip strength (p = 0.0002) and endurance swimming time (p = 0.0195) in a dose-depend manner. FCD treatments also produced dose-dependent decreases in serum levels of lactate (p < 0.0001) and ammonia (p = 0.0025), and also an increase in glucose level (p < 0.0001) after the 15-min swimming test. In addition, FCD supplementation had few subchronic toxic effects. Therefore, we suggest that long-term supplementation with FCD can have a wide spectrum of bioactivities on health promotion, performance improvement and anti-fatigue. PMID:25558908

  12. Erythrocytes encapsulated with phenylalanine hydroxylase exhibit improved pharmacokinetics and lowered plasma phenylalanine levels in normal mice.

    PubMed

    Yew, Nelson S; Dufour, Emmanuelle; Przybylska, Malgorzata; Putelat, Julie; Crawley, Cristin; Foster, Meta; Gentry, Sarah; Reczek, David; Kloss, Alla; Meyzaud, Aurélien; Horand, Françoise; Cheng, Seng H; Godfrin, Yann

    2013-08-01

    Enzyme replacement therapy is often hampered by the rapid clearance and degradation of the administered enzyme, limiting its efficacy and requiring frequent dosing. Encapsulation of therapeutic molecules into red blood cells (RBCs) is a clinically proven approach to improve the pharmacokinetics and efficacy of biologics and small molecule drugs. Here we evaluated the ability of RBCs encapsulated with phenylalanine hydroxylase (PAH) to metabolize phenylalanine (Phe) from the blood and confer sustained enzymatic activity in the circulation. Significant quantities of PAH were successfully encapsulated within murine RBCs (PAH-RBCs) with minimal loss of endogenous hemoglobin. While intravenously administered free PAH enzyme was rapidly eliminated from the blood within a few hours, PAH-RBCs persisted in the circulation for at least 10days. A single injection of PAH-RBCs was able to decrease Phe levels by nearly 80% in normal mice. These results demonstrate the ability of enzyme-loaded RBCs to metabolize circulating amino acids and highlight the potential to treat disorders of amino acid metabolism.

  13. Humanized Tau Mice with Regionalized Amyloid Exhibit Behavioral Deficits but No Pathological Interaction.

    PubMed

    Yetman, Michael J; Fowler, Stephanie W; Jankowsky, Joanna L

    2016-01-01

    Alzheimer's disease (AD) researchers have struggled for decades to draw a causal link between extracellular Aβ aggregation and intraneuronal accumulation of microtubule-associated protein tau. The amyloid cascade hypothesis posits that Aβ deposition promotes tau hyperphosphorylation, tangle formation, cell loss, vascular damage, and dementia. While the genetics of familial AD and the pathological staging of sporadic disease support this sequence of events, attempts to examine the molecular mechanism in transgenic animal models have largely relied on models of other inherited tauopathies as the basis for testing the interaction with Aβ. In an effort to more accurately model the relationship between Aβ and wild-type tau in AD, we intercrossed mice that overproduce human Aβ with a tau substitution model in which all 6 isoforms of the human protein are expressed in animals lacking murine tau. We selected an amyloid model in which pathology was biased towards the entorhinal region so that we could further examine whether the anticipated changes in tau phosphorylation occurred at the site of Aβ deposition or in synaptically connected regions. We found that Aβ and tau had independent effects on locomotion, learning, and memory, but found no behavioral evidence for an interaction between the two transgenes. Moreover, we saw no indication of amyloid-induced changes in the phosphorylation or aggregation of human tau either within the entorhinal area or elsewhere. These findings suggest that robust amyloid pathology within the medial temporal lobe has little effect on the metabolism of wild type human tau in this model. PMID:27070146

  14. Mice lacking TrkB in parvalbumin-positive cells exhibit sexually dimorphic behavioral phenotypes.

    PubMed

    Lucas, Elizabeth K; Jegarl, Anita; Clem, Roger L

    2014-11-01

    Activity-dependent brain-derived neurotrophic factor (BDNF) signaling through receptor tyrosine kinase B (TrkB) is required for cued fear memory consolidation and extinction. Although BDNF is primarily secreted from glutamatergic neurons, TrkB is expressed by other genetically defined cells whose contributions to the behavioral effects of BDNF remain poorly understood. Parvalbumin (PV)-positive interneurons, which are highly enriched in TrkB, are emerging as key regulators of fear memory expression. We therefore hypothesized that activity-dependent BDNF signaling in PV-interneurons may modulate emotional learning. To test this hypothesis, we utilized the LoxP/Cre system for conditional deletion of TrkB in PV-positive cells to examine the impact of cell-autonomous BDNF signaling on Pavlovian fear conditioning and extinction. However, behavioral abnormalities indicative of vestibular dysfunction precluded the use of homozygous conditional knockouts in tests of higher cognitive functioning. While vestibular dysfunction was apparent in both sexes, female conditional knockouts exhibited an exacerbated phenotype, including extreme motor hyperactivity and circling behavior, compared to their male littermates. Heterozygous conditional knockouts were spared of vestibular dysfunction. While fear memory consolidation was unaffected in heterozygotes of both sexes, males exhibited impaired extinction consolidation compared to their littermate controls. Our findings complement evidence from human and rodent studies suggesting that BDNF signaling promotes consolidation of extinction and point to PV-positive neurons as a discrete population that mediates these effects in a sex-specific manner.

  15. Mice lacking TrkB in parvalbumin-positive cells exhibit sexually dimorphic behavioral phenotypes

    PubMed Central

    Lucas, Elizabeth K.; Jegarl, Anita; Clem, Roger L.

    2016-01-01

    Activity-dependent brain-derived neurotrophic factor (BDNF) signaling through receptor tyrosine kinase B (TrkB) is required for cued fear memory consolidation and extinction. Although BDNF is primarily secreted from glutamatergic neurons, TrkB is expressed by other genetically defined cells whose contributions to the behavioral effects of BDNF remain poorly understood. Parvalbumin (PV)-positive interneurons, which are highly enriched in TrkB, are emerging as key regulators of fear memory expression. We therefore hypothesized that activity-dependent BDNF signaling in PV-interneurons may modulate emotional learning. To test this hypothesis, we utilized the LoxP/Cre system for conditional deletion of TrkB in PV-positive cells to examine the impact of cell-autonomous BDNF signaling on Pavlovian fear conditioning and extinction. However, behavioral abnormalities indicative of vestibular dysfunction precluded the use of homozygous conditional knockouts in tests of higher cognitive functioning. While vestibular dysfunction was apparent in both sexes, female conditional knockouts exhibited an exacerbated phenotype, including extreme motor hyperactivity and circling behavior, compared to their male littermates. Heterozygous conditional knockouts were spared of vestibular dysfunction. While fear memory consolidation was unaffected in heterozygotes of both sexes, males exhibited impaired extinction consolidation compared to their littermate controls. Our findings complement evidence from human and rodent studies suggesting that BDNF signaling promotes consolidation of extinction and point to PV-positive neurons as a discrete population that mediates these effects in a sex-specific manner. PMID:25127683

  16. Cadmium increases the sensitivity of adolescent female mice to nicotine-related behavioral deficits.

    PubMed

    Adeniyi, Philip Adeyemi; Olatunji, Babawale Peter; Ishola, Azeez Olakunle; Ajonijebu, Duyilemi Chris; Ogundele, Olalekan Michael

    2014-01-01

    This study investigates spatial and nonspatial working memory, anxiety related behavior, and motor activities in cadmium and/or nicotine exposed female adolescent mice. P28 female adolescent mice (albino strain) were divided into four groups of five (n = 5) mice each. A set of mice (Nic) received subcutaneous nicotine (2.0 mg/kg) while a separate set (Cd) was treated with 2.0 mg/kg cadmium (subcutaneous). For the combined treatments of cadmium and nicotine, we administered 2.0 mg/kg Nicotine and 2.0 mg/kg of Cd. Subsequently, a separate group of animals (n = 5; control) received normal saline. The total duration of treatment for all groups was 28 days (P28-P56). At P56, the treatment was discontinued, after which the animals were examined in behavioural tests. Nicotine and cadmium increased the metabolism and food intake in the female adolescent mice. This also corresponded to an increase in weight when compared with the control. However, a combined nicotine-cadmium treatment induced a decline in weight of the animals versus the control. Also, nicotine administration increased the motor function, while cadmium and nicotine-cadmium treatment caused a decline in motor activity. Both nicotine and cadmium induced a reduction in memory index; however, nicotine-cadmium treatment induced the most significant decrease in nonspatial working memory.

  17. Mice lacking the transcriptional coactivator PGC-1α exhibit alterations in inhibitory synaptic transmission in the motor cortex.

    PubMed

    Dougherty, S E; Bartley, A F; Lucas, E K; Hablitz, J J; Dobrunz, L E; Cowell, R M

    2014-06-20

    Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a transcriptional coactivator known to regulate gene programs in a cell-specific manner in energy-demanding tissues, and its dysfunction has been implicated in numerous neurological and psychiatric disorders. Previous work from the Cowell laboratory indicates that PGC-1α is concentrated in inhibitory interneurons and is required for the expression of the calcium buffer parvalbumin (PV) in the cortex; however, the impact of PGC-1α deficiency on inhibitory neurotransmission in the motor cortex is not known. Here, we show that mice lacking PGC-1α exhibit increased amplitudes and decreased frequency of spontaneous inhibitory postsynaptic currents in layer V pyramidal neurons. Upon repetitive train stimulation at the gamma frequency, decreased GABA release is observed. Furthermore, PV-positive interneurons in PGC-1α -/- mice display reductions in intrinsic excitability and excitatory input without changes in gross interneuron morphology. Taken together, these data show that PGC-1α is required for normal inhibitory neurotransmission and cortical PV-positive interneuron function. Given the pronounced motor dysfunction in PGC-1α -/- mice and the essential role of PV-positive interneurons in maintenance of cortical excitatory:inhibitory balance, it is possible that deficiencies in PGC-1α expression could contribute to cortical hyperexcitability and motor abnormalities in multiple neurological disorders.

  18. Interleukin-27 exhibited anti-inflammatory activity during Plasmodium berghei infection in mice.

    PubMed

    Fazalul Rahiman, S S; Basir, R; Talib, H; Tie, T H; Chuah, Y K; Jabbarzare, M; Chong, W C; Mohd Yusoff, M A; Nordin, N; Yam, M F; Abdullah, W O; Abdul Majid, R

    2013-12-01

    Interleukin-27 (IL-27) has a pleiotropic role either as a pro-inflammatory or anti-inflammatory cytokine in inflammatory related diseases. The role and involvement of IL-27 during malaria was investigated and the effects of modulating its release on the production of major inflammatory cytokines and the histopathological consequences in major affected organs during the infection were evaluated. Results showed that IL-27 concentration was significantly elevated throughout the infection but no positive correlation with the parasitaemia development observed. Augmentation of IL-27 significantly elevated the release of anti-inflammatory cytokine, IL-10 whereas antagonising and neutralising IL-27 produced the opposite. A significant elevation of pro-inflammatory cytokines (IFN-γ and IL-6) was also observed, both during augmentation and inhibition of IL-27. Thus, it is suggested that IL-27 exerts an anti-inflammatory activity in the Th1 type response by signalling the production of IL-10 during malaria. Histopathological examination showed sequestration of PRBC in the microvasculature of major organs in malarial mice. Other significant histopathological changes include hyperplasia and hypertrophy of the Kupffer cells in the liver, hyaline membrane formation in lung tissue, enlargement of the white and red pulp followed by the disappearance of germinal centre of the spleen, and tubular vacuolation of the kidney tissues. In conclusion, it is suggested that IL-27 may possibly acts as an anti-inflammatory cytokine during the infection. Modulation of its release produced a positive impact on inflammatory cytokine production during the infection, suggesting its potential in malaria immunotherapy, in which the host may benefit from its inhibition.

  19. Humanized Tau Mice with Regionalized Amyloid Exhibit Behavioral Deficits but No Pathological Interaction

    PubMed Central

    Yetman, Michael J.; Fowler, Stephanie W.; Jankowsky, Joanna L.

    2016-01-01

    Alzheimer’s disease (AD) researchers have struggled for decades to draw a causal link between extracellular Aβ aggregation and intraneuronal accumulation of microtubule-associated protein tau. The amyloid cascade hypothesis posits that Aβ deposition promotes tau hyperphosphorylation, tangle formation, cell loss, vascular damage, and dementia. While the genetics of familial AD and the pathological staging of sporadic disease support this sequence of events, attempts to examine the molecular mechanism in transgenic animal models have largely relied on models of other inherited tauopathies as the basis for testing the interaction with Aβ. In an effort to more accurately model the relationship between Aβ and wild-type tau in AD, we intercrossed mice that overproduce human Aβ with a tau substitution model in which all 6 isoforms of the human protein are expressed in animals lacking murine tau. We selected an amyloid model in which pathology was biased towards the entorhinal region so that we could further examine whether the anticipated changes in tau phosphorylation occurred at the site of Aβ deposition or in synaptically connected regions. We found that Aβ and tau had independent effects on locomotion, learning, and memory, but found no behavioral evidence for an interaction between the two transgenes. Moreover, we saw no indication of amyloid-induced changes in the phosphorylation or aggregation of human tau either within the entorhinal area or elsewhere. These findings suggest that robust amyloid pathology within the medial temporal lobe has little effect on the metabolism of wild type human tau in this model. PMID:27070146

  20. MeCP2 R168X male and female mutant mice exhibit Rett-like behavioral deficits.

    PubMed

    Schaevitz, L R; Gómez, N B; Zhen, D P; Berger-Sweeney, J E

    2013-10-01

    Rett syndrome (RTT) is a regressive developmental disorder characterized by motor and breathing abnormalities, anxiety, cognitive dysfunction and seizures. Approximately 95% of RTT cases are caused by more than 200 different mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2). While numerous transgenic mice have been created modeling common mutations in MeCP2, the behavioral phenotype of many of these male and, especially, female mutant mice has not been well characterized. Thorough phenotyping of additional RTT mouse models will provide valuable insight into the effects of Mecp2 mutations on behavior and aid in the selection of appropriate models, ages, sexes and outcome measures for preclinical trials. In this study, we characterize the phenotype of male and female mice containing the early truncating MeCP2 R168X nonsense point mutation, one of the most common in RTT individuals, and compare the phenotypes to Mecp2 null mutants. Mecp2(R168X) mutants mirror many clinical features of RTT. Mecp2(R168X/y) males exhibit impaired motor and cognitive function and reduced anxiety. The behavioral phenotype is less severe and with later onset in Mecp2(R168X/+) females. Seizures were noted in 3.7% of Mecp2(R168X) mutant females. The phenotype in Mecp2(R168X/y) mutant males is remarkably similar to our previous characterizations of Mecp2 null males, whereas Mecp2(R168X/+) females exhibit a number of phenotypic differences from females heterozygous for a null Mecp2 mutation. This study describes a number of highly robust behavioral paradigms that can be used in preclinical drug trials and underscores the importance of including Mecp2 mutant females in preclinical studies.

  1. BDNF-Val66Met variant and adolescent stress interact to promote susceptibility to anorexic behavior in mice

    PubMed Central

    Madra, M; Zeltser, L M

    2016-01-01

    There is an urgent need to identify therapeutic targets for anorexia nervosa (AN) because current medications do not impact eating behaviors that drive AN's high mortality rate. A major obstacle to developing new treatments is the lack of animal models that recapitulate the pattern of disease onset typically observed in human populations. Here we describe a translational mouse model to study interactions between genetic, psychological and biological risk factors that promote anorexic behavior. We combined several factors that are consistently associated with increased risk of AN—adolescent females, genetic predisposition to anxiety imposed by the BDNF-Val66Met gene variant, social isolation stress and caloric restriction (CR). Approximately 40% of the mice with all of these risk factors will exhibit severe self-imposed dietary restriction, sometimes to the point of death. We systematically varied the risk factors outlined above to explore how they interact to influence anorexic behavior. We found that the Val66Met genotype markedly increases the likelihood and severity of abnormal feeding behavior triggered by CR, but only when CR is imposed in the peri-pubertal period. Incidence of anorexic behavior in our model is dependent on juvenile exposure to social stress and can be extinguished by adolescent handling, but is discordant from anxiety-like behavior. Thus, this study characterized gene × environment interactions during adolescence that could be the underlying driver of abnormal eating behavior in certain AN patients, and represents a promising system to identify possible targets for therapeutic intervention. PMID:27045846

  2. Transgenic mice expressing mutant Pinin exhibit muscular dystrophy, nebulin deficiency and elevated expression of slow-type muscle fiber genes

    SciTech Connect

    Wu, Hsu-Pin; Hsu, Shu-Yuan; Wu, Wen-Ai; Hu, Ji-Wei; Ouyang, Pin

    2014-01-03

    Highlights: •Pnn CCD domain functions as a dominant negative mutant regulating Pnn expression and function. •Pnn CCD mutant Tg mice have a muscle wasting phenotype during development and show dystrophic histological features. •Pnn mutant muscles are susceptible to slow fiber type gene transition and NEB reduction. •The Tg mouse generated by overexpression of the Pnn CCD domain displays many characteristics resembling NEB{sup +/−} mice. -- Abstract: Pinin (Pnn) is a nuclear speckle-associated SR-like protein. The N-terminal region of the Pnn protein sequence is highly conserved from mammals to insects, but the C-terminal RS domain-containing region is absent in lower species. The N-terminal coiled-coil domain (CCD) is, therefore, of interest not only from a functional point of view, but also from an evolutionarily standpoint. To explore the biological role of the Pnn CCD in a physiological context, we generated transgenic mice overexpressing Pnn mutant in skeletal muscle. We found that overexpression of the CCD reduces endogenous Pnn expression in cultured cell lines as well as in transgenic skeletal muscle fibers. Pnn mutant mice exhibited reduced body mass and impaired muscle function during development. Mutant skeletal muscles show dystrophic histological features with muscle fibers heavily loaded with centrally located myonuclei. Expression profiling and pathway analysis identified over-representation of genes in gene categories associated with muscle contraction, specifically those related to slow type fiber. In addition nebulin (NEB) expression level is repressed in Pnn mutant skeletal muscle. We conclude that Pnn downregulation in skeletal muscle causes a muscular dystrophic phenotype associated with NEB deficiency and the CCD domain is incapable of replacing full length Pnn in terms of functional capacity.

  3. Mice carrying a hypomorphic Evi1 allele are embryonic viable but exhibit severe congenital heart defects.

    PubMed

    Bard-Chapeau, Emilie A; Szumska, Dorota; Jacob, Bindya; Chua, Belinda Q L; Chatterjee, Gouri C; Zhang, Yi; Ward, Jerrold M; Urun, Fatma; Kinameri, Emi; Vincent, Stéphane D; Ahmed, Sayadi; Bhattacharya, Shoumo; Osato, Motomi; Perkins, Archibald S; Moore, Adrian W; Jenkins, Nancy A; Copeland, Neal G

    2014-01-01

    The ecotropic viral integration site 1 (Evi1) oncogenic transcription factor is one of a number of alternative transcripts encoded by the Mds1 and Evi1 complex locus (Mecom). Overexpression of Evi1 has been observed in a number of myeloid disorders and is associated with poor patient survival. It is also amplified and/or overexpressed in many epithelial cancers including nasopharyngeal carcinoma, ovarian carcinoma, ependymomas, and lung and colorectal cancers. Two murine knockout models have also demonstrated Evi1's critical role in the maintenance of hematopoietic stem cell renewal with its absence resulting in the death of mutant embryos due to hematopoietic failure. Here we characterize a novel mouse model (designated Evi1(fl3)) in which Evi1 exon 3, which carries the ATG start, is flanked by loxP sites. Unexpectedly, we found that germline deletion of exon3 produces a hypomorphic allele due to the use of an alternative ATG start site located in exon 4, resulting in a minor Evi1 N-terminal truncation and a block in expression of the Mds1-Evi1 fusion transcript. Evi1(δex3/δex3) mutant embryos showed only a mild non-lethal hematopoietic phenotype and bone marrow failure was only observed in adult Vav-iCre/+, Evi1(fl3/fl3) mice in which exon 3 was specifically deleted in the hematopoietic system. Evi1(δex3/δex3) knockout pups are born in normal numbers but die during the perinatal period from congenital heart defects. Database searches identified 143 genes with similar mutant heart phenotypes as those observed in Evi1(δex3/δex3) mutant pups. Interestingly, 42 of these congenital heart defect genes contain known Evi1-binding sites, and expression of 18 of these genes are also effected by Evi1 siRNA knockdown. These results show a potential functional involvement of Evi1 target genes in heart development and indicate that Evi1 is part of a transcriptional program that regulates cardiac development in addition to the development of blood. PMID:24586749

  4. CLIC5 mutant mice are resistant to diet-induced obesity and exhibit gastric hemorrhaging and increased susceptibility to torpor

    PubMed Central

    Bradford, Emily M.; Miller, Marian L.; Prasad, Vikram; Nieman, Michelle L.; Gawenis, Lara R.; Berryman, Mark; Lorenz, John N.; Tso, Patrick

    2010-01-01

    Chloride intracellular channel 5 (CLIC5) and other CLIC isoforms have been implicated in a number of biological processes, but their specific functions are poorly understood. The association of CLIC5 with ezrin and the actin cytoskeleton led us to test its possible involvement in gastric acid secretion. Clic5 mutant mice exhibited only a minor reduction in acid secretion, Clic5 mRNA was expressed at only low levels in stomach, and Clic5 mutant parietal cells were ultrastructurally normal, negating the hypothesis that CLIC5 plays a major role in acid secretion. However, the mutants exhibited gastric hemorrhaging in response to fasting, reduced monocytes and granulocytes suggestive of immune dysfunction, behavioral and social disorders suggestive of neurological dysfunction, and evidence of a previously unidentified metabolic defect. Wild-type and mutant mice were maintained on normal and high-fat diets; plasma levels of various hormones, glucose, and lipids were determined; and body composition was studied by quantitative magnetic resonance imaging. Clic5 mutants were lean, hyperphagic, and highly resistant to diet-induced obesity. Plasma insulin and glucose levels were reduced, and leptin levels were very low; however, plasma triglycerides, cholesterol, phospholipids, and fatty acids were normal. Indirect calorimetry revealed increased peripheral metabolism and greater reliance on carbohydrate metabolism. Because Clic5 mutants were unable to maintain energy reserves, they also exhibited increased susceptibility to fasting-induced torpor, as indicated by telemetric measurements showing episodes of reduced body temperature and heart rate. These data reveal a requirement for CLIC5 in the maintenance of normal systemic energy metabolism. PMID:20357015

  5. Senescence marker protein-30/superoxide dismutase 1 double knockout mice exhibit increased oxidative stress and hepatic steatosis.

    PubMed

    Kondo, Yoshitaka; Masutomi, Hirofumi; Noda, Yoshihiro; Ozawa, Yusuke; Takahashi, Keita; Handa, Setsuko; Maruyama, Naoki; Shimizu, Takahiko; Ishigami, Akihito

    2014-01-01

    Superoxide dismutase 1 (SOD1) is an antioxidant enzyme that converts superoxide anion radicals into hydrogen peroxide and molecular oxygen. The senescence marker protein-30 (SMP30) is a gluconolactonase that functions as an antioxidant protein in mammals due to its involvement in ascorbic acid (AA) biosynthesis. SMP30 also participates in Ca(2+) efflux by activating the calmodulin-dependent Ca(2+)-pump. To reveal the role of oxidative stress in lipid metabolism defects occurring in non-alcoholic fatty liver disease pathogenesis, we generated SMP30/SOD1-double knockout (SMP30/SOD1-DKO) mice and investigated their survival curves, plasma and hepatic lipid profiles, amounts of hepatic oxidative stress, and hepatic protein levels expressed by genes related to lipid metabolism. While SMP30/SOD1-DKO pups had no growth retardation by 14 days of age, they did have low plasma and hepatic AA levels. Thereafter, 39% and 53% of male and female pups died by 15-24 and 89 days of age, respectively. Compared to wild type, SMP30-KO and SOD1-KO mice, by 14 days SMP30/SOD1-DKO mice exhibited: (1) higher plasma levels of triglyceride and aspartate aminotransferase; (2) severe accumulation of hepatic triglyceride and total cholesterol; (3) higher levels of superoxide anion radicals and thiobarbituric acid reactive substances in livers; and (4) decreased mRNA and protein levels of Apolipoprotein B (ApoB) in livers - ApoB is an essential component of VLDL secretion. These results suggest that high levels of oxidative stress due to concomitant deficiency of SMP30 and/or AA, and SOD1 cause abnormal plasma lipid metabolism, hepatic lipid accumulation and premature death resulting from impaired VLDL secretion. PMID:25003023

  6. Recombinant Factor IX Fc Fusion Protein Maintains Full Procoagulant Properties and Exhibits Prolonged Efficacy in Hemophilia B Mice

    PubMed Central

    Toby, Garabet G.; Liu, Tongyao; Buyue, Yang; Zhang, Xin; Bitonti, Alan J.; Pierce, Glenn F.; Sommer, Jurg M.; Jiang, Haiyan; Peters, Robert T.

    2016-01-01

    Introduction Hemophilia B is an inherited X chromosome–linked disorder characterized by impaired blood clotting owing to the absence of functional coagulation factor IX. Due to the relatively short half-life of factor IX, patients with hemophilia B require frequent factor IX infusions to maintain prophylaxis. We have developed a recombinant factor IX (rFIX) fused to the Fc region of IgG (rFIXFc) with an extended half-life in animals and humans. Materials and Methods Procoagulant properties of rFIXFc and rFIX (BENEFIX®) were compared to determine the effect of the Fc region on rFIXFc hemostatic function. Specifically, we assessed rFIXFc activation, intermolecular interactions within the Xase complex, inactivation by antithrombin III (AT) and thrombin generation potential compared with rFIX. We also assessed the acute and prophylactic efficacy profiles of rFIXFc and rFIX in vivo in hemophilia B mouse bleeding models. Results and Conclusions The activation by factor XIa or factor VIIa/tissue factor, inhibition by AT, interaction profiles with phospholipids, affinities for factor VIIIa within the context of the Xase complex, and thrombin generation profiles were similar for rFIXFc and rFIX. Xase complexes formed with either molecule exhibited similar kinetic profiles for factor Xa generation. In acute efficacy models, mice infused with rFIXFc or rFIX were equally protected from bleeding. However, in prophylactic efficacy models, protection from bleeding was maintained approximately three times longer in rFIXFc-dosed mice than in those given rFIX; this prolonged efficacy correlates with the previously observed half-life extension. We conclude that rFIXFc retains critical FIX procoagulant attributes and that the extension in rFIXFc half-life translates into prolonged efficacy in hemophilia B mice. PMID:26840952

  7. Mice transgenic for HTLV-I LTR-tax exhibit tax expression in bone, skeletal alterations, and high bone turnover.

    PubMed

    Ruddle, N H; Li, C B; Horne, W C; Santiago, P; Troiano, N; Jay, G; Horowitz, M; Baron, R

    1993-11-01

    HTLV-I infection can result in adult T cell leukemia with accompanying hypercalcemia and increased bone resorption. A viral etiology has also been invoked for Paget's disease, a disease of high bone turnover. Delineation of pathogenetic mechanisms of viral-associated bone diseases has been impeded by the complexity of viral and host factors. In order to consider the relationship of HTLV-I infection to skeletal changes we have evaluated the role of a single viral gene in mice transgenic for HTLV-I tax under the control of the viral promoter. Tax mice exhibited severe skeletal abnormalities characterized by high bone turnover, increases in osteoblast and osteoclast numbers and activity, and myelofibrosis. These changes were apparent as early as two months of age. Tax mRNA and protein were highly expressed in bone but not in bone marrow nor in any other tissues except, as previously reported, salivary gland and neurofibromas when they did develop. Within bone, tax protein was detected in only two cell types, mature osteoclasts and spindle-shaped cells within the endosteal myelofibrosis. These observations suggest that local expression of the tax gene, which encodes a viral regulatory protein known to influence host gene expression, can induce within the bone environment marked changes in bone cell activity, resulting in profound skeletal alterations.

  8. Social crowding in the night-time reduces an anxiety-like behavior and increases social interaction in adolescent mice.

    PubMed

    Ago, Yukio; Tanaka, Tatsunori; Ota, Yuki; Kitamoto, Mari; Imoto, Emina; Takuma, Kazuhiro; Matsuda, Toshio

    2014-08-15

    Rearing in crowded conditions is a psychosocial stressor that affects biological functions. The effects of continuous crowding for many days have been studied, but those of crowding over a limited time have not. In this study, we examined the effects of night-time or daytime crowding over 2 weeks on behavior in adolescent and adult mice. Crowding (20 mice/cage) in either the night-time or daytime did not affect locomotor activity in the open field test or cognitive function in the fear conditioning test. In contrast, night-time crowding, but not daytime crowding, had an anxiolytic effect in the elevated plus-maze test and increased social interaction in adolescent mice, but not in adult mice. The first night-time, but not daytime, crowding increased plasma corticosterone levels in adolescent mice, although night-time crowding over 2 weeks did not affect the corticosterone levels. Furthermore, no significant effects of the first crowding were observed in adult mice. In a second crowding condition (six mice/small cage), the anxiolytic-like effects of night-time crowding and the change in plasma corticosterone levels were not observed, suggesting that the density of mice is not important for the behavioral consequences of crowding. Night-time crowding did not affect neurotrophic/growth factor levels and hippocampal neurogenesis in adolescent mice. These findings suggest that night-time crowding leads to anxiolytic-like behaviors in adolescent mice, and imply that night-time crowding stress in adolescence may be beneficial to brain functions.

  9. Chronic social stress during adolescence induces cognitive impairment in aged mice.

    PubMed

    Sterlemann, Vera; Rammes, Gerhard; Wolf, Miriam; Liebl, Claudia; Ganea, Karin; Müller, Marianne B; Schmidt, Mathias V

    2010-04-01

    Age-related cognitive decline is one of the major aspects that impede successful aging in humans. Environmental factors, such as chronic stress, can accelerate or aggravate cognitive deficits during aging. While there is abundant evidence that chronic stress directly affects cognitive performance, the lasting consequences of stress exposures during vulnerable developmental time windows are largely unknown. This is especially true for the adolescent period, which is critical in terms of physical, sexual, and behavioral maturation. Here we used chronic social stress during adolescence in male mice and investigated the consequences of this treatment on cognitive performance during aging. We observed a substantial impairment of spatial memory, but not other memory domains, 12 months after the end of the stress period. This hippocampus-dependent cognitive dysfunction was supported by concomitant impairment in LTP induction in CA1 neurons in 15-month-old animals. Further, we observed a decrease of hippocampal BDNF mRNA and synaptophysin immunoreactivity, suggesting plasticity and structural alterations in formerly stressed mice. Finally, we identified expression changes of specific neurotransmitter subunits critically involved in learning and memory, specifically the NMDA receptor subunit NR2B. Taken together, our results identify possible molecular mechanisms underlying cognitive impairment during aging, demonstrating the detrimental impact of stress during adolescence on hippocampus-dependent cognitive function in aged mice. PMID:19489003

  10. Adolescent Social Defeat Induced Alterations in Social Behavior and Cognitive Flexibility in Adult Mice: Effects of Developmental Stage and Social Condition.

    PubMed

    Zhang, Fan; Yuan, Sanna; Shao, Feng; Wang, Weiwen

    2016-01-01

    Negative social experiences during adolescence increase the risk of psychiatric disorders in adulthood. Using "resident-intruder" stress, the present study aimed to investigate the effects of adolescent social defeat on emotional and cognitive symptoms associated with psychiatric disorders during adulthood and the effects of the developmental stage and social condition on this process. In Experiment 1, animals were exposed to social defeat or manipulation for 10 days during early adolescence (EA, postnatal days [PND] 28-37), late adolescence (LA, PND 38-47), and adulthood (ADULT, PND 70-79) and then singly housed until the behavioral tests. Behaviors, including social avoidance of the defeat context and cortically mediated cognitive flexibility in an attentional set-shifting task (AST), were assessed during the week following stress or after 6 weeks during adulthood. We determined that social defeat induced significant and continuous social avoidance across age groups at both time points. The mice that experienced social defeat during adulthood exhibited short-term impairments in reversal learning (RL) on the AST that dissipated after 6 weeks. In contrast, social defeat during EA but not LA induced a delayed deficit in extra-dimensional set-shifting (EDS) in adulthood but not during adolescence. In Experiment 2, we further examined the effects of social condition (isolation or social housing after stress) on the alterations induced by social defeat during EA in adult mice. The adult mice that had experienced stress during EA exhibited social avoidance similar to the avoidance identified in Experiment 1 regardless of the isolation or social housing after the stress. However, social housing after the stress ameliorated the cognitive flexibility deficits induced by early adolescent social defeat in the adult mice, and the social condition had no effect on cognitive function. These findings suggest that the effects of social defeat on emotion and cognitive function are

  11. Adolescent Social Defeat Induced Alterations in Social Behavior and Cognitive Flexibility in Adult Mice: Effects of Developmental Stage and Social Condition

    PubMed Central

    Zhang, Fan; Yuan, Sanna; Shao, Feng; Wang, Weiwen

    2016-01-01

    Negative social experiences during adolescence increase the risk of psychiatric disorders in adulthood. Using “resident-intruder” stress, the present study aimed to investigate the effects of adolescent social defeat on emotional and cognitive symptoms associated with psychiatric disorders during adulthood and the effects of the developmental stage and social condition on this process. In Experiment 1, animals were exposed to social defeat or manipulation for 10 days during early adolescence (EA, postnatal days [PND] 28–37), late adolescence (LA, PND 38–47), and adulthood (ADULT, PND 70–79) and then singly housed until the behavioral tests. Behaviors, including social avoidance of the defeat context and cortically mediated cognitive flexibility in an attentional set-shifting task (AST), were assessed during the week following stress or after 6 weeks during adulthood. We determined that social defeat induced significant and continuous social avoidance across age groups at both time points. The mice that experienced social defeat during adulthood exhibited short-term impairments in reversal learning (RL) on the AST that dissipated after 6 weeks. In contrast, social defeat during EA but not LA induced a delayed deficit in extra-dimensional set-shifting (EDS) in adulthood but not during adolescence. In Experiment 2, we further examined the effects of social condition (isolation or social housing after stress) on the alterations induced by social defeat during EA in adult mice. The adult mice that had experienced stress during EA exhibited social avoidance similar to the avoidance identified in Experiment 1 regardless of the isolation or social housing after the stress. However, social housing after the stress ameliorated the cognitive flexibility deficits induced by early adolescent social defeat in the adult mice, and the social condition had no effect on cognitive function. These findings suggest that the effects of social defeat on emotion and cognitive

  12. Adult mice maintained on a high-fat diet exhibit object location memory deficits and reduced hippocampal SIRT1 gene expression.

    PubMed

    Heyward, Frankie D; Walton, R Grace; Carle, Matthew S; Coleman, Mark A; Garvey, W Timothy; Sweatt, J David

    2012-07-01

    Mounting evidence has established that diet-induced obesity (DIO) is associated with deficits in hippocampus-dependent memory. The bulk of research studies dealing with this topic have utilized rats fed a high-fat diet as an experimental model. To date, there has been a paucity of research studies that have established whether the memory deficits exhibited in DIO rats can be recapitulated in mice. Moreover, the majority of experiments that have evaluated memory performance in rodent models of DIO have utilized memory tests that are essentially aversive in nature (i.e., Morris water maze). The current study sought to fill an empirical void by determining if mice maintained on a high-fat diet exhibit deficits in two non-aversive memory paradigms: novel object recognition (NOR) and object location memory (OLM). Here we report that mice fed a high-fat diet over 23 weeks exhibit intact NOR, albeit a marked impairment in hippocampus-dependent OLM. We also determined the existence of corresponding aberrations in gene expression within the hippocampus of DIO mice. DIO mice exhibited significant reductions in both SIRT1 and PP1 mRNA within the hippocampus. Our data suggest that mice maintained on a high-fat diet present with impaired hippocampus-dependent spatial memory and a corresponding alteration in the expression of genes that have been implicated in memory consolidation.

  13. Gli3Xt−J/Xt−J mice exhibit lambdoid suture craniosynostosis which results from altered osteoprogenitor proliferation and differentiation

    PubMed Central

    Rice, David P.C.; Connor, Elaine C.; Veltmaat, Jacqueline M.; Lana-Elola, Eva; Veistinen, Lotta; Tanimoto, Yukiho; Bellusci, Saverio; Rice, Ritva

    2010-01-01

    Gli3 is a zinc-finger transcription factor whose activity is dependent on the level of hedgehog (Hh) ligand. Hh signaling has key roles during endochondral ossification; however, its role in intramembranous ossification is still unclear. In this study, we show that Gli3 performs a dual role in regulating both osteoprogenitor proliferation and osteoblast differentiation during intramembranous ossification. We discovered that Gli3Xt−J/Xt−J mice, which represent a Gli3-null allele, exhibit craniosynostosis of the lambdoid sutures and that this is accompanied by increased osteoprogenitor proliferation and differentiation. These cellular changes are preceded by ectopic expression of the Hh receptor Patched1 and reduced expression of the transcription factor Twist1 in the sutural mesenchyme. Twist1 is known to delay osteogenesis by binding to and inhibiting the transcription factor Runx2. We found that Runx2 expression in the lambdoid suture was altered in a pattern complimentary to that of Twist1. We therefore propose that loss of Gli3 results in a Twist1-, Runx2-dependent expansion of the sutural osteoprogenitor population as well as enhanced osteoblastic differentiation which results in a bony bridge forming between the parietal and interparietal bones. We show that FGF2 will induce Twist1, normalize osteoprogenitor proliferation and differentiation and rescue the lambdoid suture synostosis in Gli3Xt−J/Xt−J mice. Taken together, we define a novel role for Gli3 in osteoblast development; we describe the first mouse model of lambdoid suture craniosynostosis and show how craniosynostosis can be rescued in this model. PMID:20570969

  14. RasGRF1 regulates the hypothalamic-pituitary-adrenal axis specifically in early-adolescent female mice.

    PubMed

    Uzturk, Belkis Gizem; Jin, Shan-Xue; Rubin, Beverly; Bartolome, Christopher; Feig, Larry A

    2015-10-01

    Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the induction and prolongation of a variety of psychiatric disorders. As such, much effort has been made to understand the molecular mechanisms involved in its control. However, the vast majority of the studies on the HPA axis have used adult animals, and among these the majority has used males. Here we show that in knockout mice lacking the guanine nucleotide exchange factor, RasGRF1, habituation to 30 min/day of restraint stress is markedly accelerated, such that these mice do not display elevated corticosterone levels or enhanced locomotion after 7 days of stress exposure, like WT mice do. Strikingly, this phenotype is present in early-adolescent female RasGRF1 knockout mice, but not in their early-adolescent male, mid-adolescent female, adult female or adult male counterparts. Moreover, not only is there a clear response to restraint stress in early-adolescent female RasGRF1 knockout mice, their response after one, three and five exposures is magnified approximately threefold compared to WT mice. These findings imply that distinct mechanisms exist to regulate the HPA axis in early-adolescent females that involves RasGRF1. A full understanding of how RasGRF1 controls the HPA axis response to stress may be required to design effective strategies to combat stress-associated psychiatric disorders initiated in young females.

  15. RasGRF1 Regulates the Hypothalamic-Pituitary-Adrenal Axis Specifically in Early-Adolescent Female Mice

    PubMed Central

    Uzturk, Belkis Gizem; Jin, Shan-xue; Rubin, Beverly; Bartolome, Christopher; Feig, Larry A.

    2015-01-01

    Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the induction and prolongation of a variety of psychiatric disorders. As such, much effort has been made to understand the molecular mechanisms involved in its control. However, the vast majority of the studies on the HPA axis have used adult animals, and among these the majority has used males. Here we show that in knockout mice lacking the guanine nucleotide exchange factor, RasGRF1, habituation to 30 minutes a day of restraint stress is markedly accelerated, such that these mice do not display elevated corticosterone levels or enhanced locomotion after 7 days of stress exposure, like WT mice do. Strikingly, this phenotype is present in early-adolescent female RasGRF1 knockout mice, but not in their early-adolescent male, mid-adolescent female, adult female or adult male counterparts. Moreover, not only is there a clear response to restraint stress in early-adolescent female RasGRF1 knockout mice, their response after 1, 3, and 5 exposures is magnified ~3-fold compared to WT mice. These findings imply that distinct mechanisms exist to regulate the HPA axis in early-adolescent females that involves RasGRF1. A full understanding of how RasGRF1 controls the HPA axis response to stress may be required to design effective strategies to combat stress-associated psychiatric disorders initiated in young females. PMID:26246084

  16. Mice overexpressing murine oncostatin M (OSM) exhibit changes in hematopoietic and other organs that are distinct from those of mice overexpressing human OSM or bovine OSM.

    PubMed

    Juan, T S-C; Bolon, B; Lindberg, R A; Sun, Y; Van, G; Fletcher, F A

    2009-01-01

    Oncostatin M (OSM) and leukemia inhibitory factor (LIF) belong to the interleukin-6 family of cytokines. The authors' previous in vitro work demonstrated that in mouse cells mouse OSM (mOSM) signals through a heterodimeric receptor complex incorporating the mOSM-specific receptor mOSMRbeta while human OSM (hOSM) and bovine OSM (bOSM) use the mouse LIF receptor mLIFRbeta rather than mOSMRbeta. These in vitro data suggest that prior studies in mouse systems with hOSM or bOSM (the usual molecules used in early studies) reflect LIF rather than OSM biology. The current work assessed whether or not this divergence in actions among these three OSMs also occurs in vivo in mouse models. Adult female (C57BL/6J x DBA/2J) F(1) mice were engineered to stably overexpress mOSM, hOSM, or bOSM by retrovirus-mediated gene transfer (n = 10 or more per group). After 4 weeks, molecular and hematologic profiles and anatomic phenotypes in multiple organs were assessed by standard techniques. Animals overexpressing either hOSM or bOSM had an identical phenotype resembling that associated with LIF activation, including significant hematologic abnormalities (anemia, neutrophilia, lymphopenia, eosinopenia, and thrombocytosis); weight loss; profound enlargement (lymph node, spleen) and/or structural reorganization (lymph node, spleen, thymus) of lymphoid organs; and severe osteosclerosis. In contrast, mice overexpressing mOSM did not develop hematologic changes, weight loss, or osteosclerosis and exhibited more modest and anatomically distinct restructuring of lymphoid organs. These data indicate that activities imputed to OSM and the mOSMRbeta signaling pathway using in vitro and in vivo mouse experimental systems are unique to mOSM.

  17. Kharon1 Null Mutants of Leishmania mexicana Are Avirulent in Mice and Exhibit a Cytokinesis Defect within Macrophages

    PubMed Central

    Sanchez, Marco A.; Valli, Jessica; Gluenz, Eva; Landfear, Scott M.

    2015-01-01

    In a variety of eukaryotes, flagella play important roles both in motility and as sensory organelles that monitor the extracellular environment. In the parasitic protozoan Leishmania mexicana, one glucose transporter isoform, LmxGT1, is targeted selectively to the flagellar membrane where it appears to play a role in glucose sensing. Trafficking of LmxGT1 to the flagellar membrane is dependent upon interaction with the KHARON1 protein that is located at the base of the flagellar axoneme. Remarkably, while Δkharon1 null mutants are viable as insect stage promastigotes, they are unable to survive as amastigotes inside host macrophages. Although Δkharon1 promastigotes enter macrophages and transform into amastigotes, these intracellular parasites are unable to execute cytokinesis and form multinucleate cells before dying. Notably, extracellular axenic amastigotes of Δkharon1 mutants replicate and divide normally, indicating a defect in the mutants that is only exhibited in the intra-macrophage environment. Although the flagella of Δkharon1 amastigotes adhere to the phagolysomal membrane of host macrophages, the morphology of the mutant flagella is often distorted. Additionally, these null mutants are completely avirulent following injection into BALB/c mice, underscoring the critical role of the KHARON1 protein for viability of intracellular amastigotes and disease in the animal model of leishmaniasis. PMID:26266938

  18. B cells from aged mice exhibit reduced apoptosis upon B-cell antigen receptor stimulation and differential ability to up-regulate survival signals.

    PubMed

    Montes, C L; Maletto, B A; Acosta Rodriguez, E V; Gruppi, A; Pistoresi-Palencia, M C

    2006-01-01

    During ageing, autoimmune disorders and the higher susceptibility to infectious have been associated with alterations in the humoral immune response. We report that splenic B lymphocytes from aged mice exhibit lower level of apoptosis induced by B-cell antigen receptor (BCR) ligation in vitro. Respect to B cells from young mice the anti-mu stimulated aged B cells show similar Bcl-2 and Bcl-xL expression but differential kinetic of A1 degradation and a higher level of cFLIP and FAIM. Even though B cells from aged mice show minor Fas expression they exhibit the same susceptibility to anti-Fas induced apoptosis. Aged B cells also present upon BCR stimulation, a higher proliferative response and similar level of activation markers expression than B cells from young mice. These data agree with the observation that aged mice exhibit an increment of T2 and mature B cell subset which rapidly enters cell cycle upon BCR engagement. The diminished apoptosis after activation in aged mice could compromise homeostatic mechanism allowing the persistence of self and non-self antigen specific B cells.

  19. The recovery trajectory of adolescent social defeat stress-induced behavioral, 1H-MRS metabolites and myelin changes in Balb/c mice

    PubMed Central

    Zhang, Handi; Yan, Gen; Xu, Haiyun; Fang, Zeman; Zhang, Jinling; Zhang, Jie; Wu, Renhua; Kong, Jiming; Huang, Qingjun

    2016-01-01

    Adolescent exposure to social stress precipitates emotion-related disorders and affects the development and function of medial prefrontal cortex (mPFC). However, this adversity-induced behavioral and neurological changes remain not fully explored. Adolescent Balb/c mice were subjected to intermittent social defeat stress during postnatal days 28 to 42. Proton magnetic resonance spectroscopy (1H-MRS) measurements, behavioral tests and immunohistochemistry were performed one day or 3 weeks after the last stress episode. Defeated mice exhibited hypoactivity and social avoidance with the latter lasting into the early adulthood, while the anxiety level was unchanged. Social defeat experience lead to temporary decreases in the levels of total creatines (Cr + pCr) and Glx (Glu + Gln), but a delayed increase of N- acetylaspartate (NAA) levels. These alternations were accompanied with a persistent reduction of myelin basic protein expression although the number of mature oligodendrocyte did not change. These findings provide evidence that adolescent adverse social experience permanently impairs the emotion-related behavioral performance and induces biochemical and molecular changes in the brain which at least lasts into early adulthood, thus enhancing our understanding of the neurobiology of social defeat stress. Our finding also implicates that NAA signals on MRS may reflect myelin status. PMID:27283029

  20. A combination of glucosyl hesperidin and caffeine exhibits an anti-obesity effect by inhibition of hepatic lipogenesis in mice.

    PubMed

    Ohara, Tatsuya; Muroyama, Koutarou; Yamamoto, Yoshihiro; Murosaki, Shinji

    2015-02-01

    To develop an anti-obesity agent, we examined the combination effect of glucosyl hesperidin (G-hesperidin) and caffeine on obesity in mice. High-fat diet-induced obese KK mice were fed a low-fat diet with or without G-hesperidin, caffeine, or their combination for 2 weeks. Decreases in body weight and significantly lower adipose tissue weight were observed in the combination-fed mice but not in the G-hesperidin-fed or caffeine-fed mice. DNA microarray analysis of mouse liver suggested that the feeding of G-hesperidin + caffeine was associated with lower lipogenesis. Therefore, we examined the anti-lipogenic effect of G-hesperidin + caffeine in fasted-refed KK mice. Hepatic triglyceride levels were significantly lower in the mice fed G-hesperidin + caffeine during the refeeding period but not in the mice fed each alone. In addition, hepatic expressions of genes related to lipogenesis, such as sterol regulatory element-binding protein-1c or fatty acid synthase, were significantly lower in the mice fed G-hesperidin + caffeine compared with that in the control mice. These results suggested that G-hesperidin + caffeine is effective for controlling obesity partly by the inhibition of hepatic lipogenesis. PMID:25409936

  1. A combination of glucosyl hesperidin and caffeine exhibits an anti-obesity effect by inhibition of hepatic lipogenesis in mice.

    PubMed

    Ohara, Tatsuya; Muroyama, Koutarou; Yamamoto, Yoshihiro; Murosaki, Shinji

    2015-02-01

    To develop an anti-obesity agent, we examined the combination effect of glucosyl hesperidin (G-hesperidin) and caffeine on obesity in mice. High-fat diet-induced obese KK mice were fed a low-fat diet with or without G-hesperidin, caffeine, or their combination for 2 weeks. Decreases in body weight and significantly lower adipose tissue weight were observed in the combination-fed mice but not in the G-hesperidin-fed or caffeine-fed mice. DNA microarray analysis of mouse liver suggested that the feeding of G-hesperidin + caffeine was associated with lower lipogenesis. Therefore, we examined the anti-lipogenic effect of G-hesperidin + caffeine in fasted-refed KK mice. Hepatic triglyceride levels were significantly lower in the mice fed G-hesperidin + caffeine during the refeeding period but not in the mice fed each alone. In addition, hepatic expressions of genes related to lipogenesis, such as sterol regulatory element-binding protein-1c or fatty acid synthase, were significantly lower in the mice fed G-hesperidin + caffeine compared with that in the control mice. These results suggested that G-hesperidin + caffeine is effective for controlling obesity partly by the inhibition of hepatic lipogenesis.

  2. Caspr3-Deficient Mice Exhibit Low Motor Learning during the Early Phase of the Accelerated Rotarod Task

    PubMed Central

    Hirata, Haruna; Takahashi, Aki; Shimoda, Yasushi; Koide, Tsuyoshi

    2016-01-01

    Caspr3 (Contactin-associated protein-like 3, Cntnap3) is a neural cell adhesion molecule belonging to the Caspr family. We have recently shown that Caspr3 is expressed abundantly between the first and second postnatal weeks in the mouse basal ganglia, including the striatum, external segment of the globus pallidus, subthalamic nucleus, and substantia nigra. However, its physiological role remains largely unknown. In this study, we conducted a series of behavioral analyses on Capsr3-knockout (KO) mice and equivalent wild-type (WT) mice to investigate the role of Caspr3 in brain function. No significant differences were observed in most behavioral traits between Caspr3-KO and WT mice, but we found that Caspr3-KO mice performed poorly during the early phase of the accelerated rotarod task in which latency to falling off a rod rotating with increasing velocity was examined. In the late phase, the performance of the Caspr3-KO mice caught up to the level of WT mice, suggesting that the deletion of Caspr3 caused a delay in motor learning. We then examined changes in neural activity after training on the accelerated rotarod by conducting immunohistochemistry using antibody to c-Fos, an indirect marker for neuronal activity. Experience of the accelerated rotarod task caused increases in the number of c-Fos-positive cells in the dorsal striatum, cerebellum, and motor cortex in both Caspr3-KO and WT mice, but the number of c-Fos-positive cells was significantly lower in the dorsal striatum of Caspr3-KO mice than in that of WT mice. The expression of c-Fos in the ventral striatum of Caspr3-KO and WT mice was not altered by the training. Our findings suggest that reduced activation of neural cells in the dorsal striatum in Caspr3-KO mice leads to a decline in motor learning in the accelerated rotarod task. PMID:26807827

  3. TASK-3 knockout mice exhibit exaggerated nocturnal activity, impairments in cognitive functions, and reduced sensitivity to inhalation anesthetics.

    PubMed

    Linden, Anni-Maija; Sandu, Cristina; Aller, M Isabel; Vekovischeva, Olga Y; Rosenberg, Per H; Wisden, William; Korpi, Esa R

    2007-12-01

    The TASK-3 channel is an acid-sensitive two-pore-domain K+ channel, widely expressed in the brain and probably involved in regulating numerous neuronal populations. Here, we characterized the behavioral and pharmacological phenotypes of TASK-3 knockout (KO) mice. Circadian locomotor activity measurements revealed that the nocturnal activity of the TASK-3 KO mice was increased by 38% (P < 0.01) compared with wild-type littermate controls, light phase activity being similar. Although TASK-3 channels are abundant in cerebellar granule cells, the KO mice performed as well as the wild-type mice in walking on a rotating rod or along a 1.2-cm-diameter beam. However, they fell more frequently from a narrower 0.8-cm beam. The KO mice showed impaired working memory in the spontaneous alternation task, with the alternation percentage being 62 +/- 3% for the wild-type mice and 48 +/- 4% (P < 0.05) for the KO mice. Likewise, during training for the Morris water-maze spatial memory task, the KO mice were slower to find the hidden platform, and in the probe trial, the female KO mice visited fewer times the platform quadrant than the male KO and wild-type mice. In pharmacological tests, the TASK-3 KO mice showed reduced sensitivity to the inhalation anesthetic halothane and the cannabinoid receptor agonist WIN55212-2 mesylate [(R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate] but unaltered responses to the alpha2 adrenoceptor agonist dexmedetomidine, the i.v. anesthetic propofol, the opioid receptor agonist morphine, and the local anesthetic lidocaine. Overall, our results suggest important contributions of TASK-3 channels in the neuronal circuits regulating circadian rhythms, cognitive functions, and mediating specific pharmacological effects.

  4. TASK-3 knockout mice exhibit exaggerated nocturnal activity, impairments in cognitive functions, and reduced sensitivity to inhalation anesthetics.

    PubMed

    Linden, Anni-Maija; Sandu, Cristina; Aller, M Isabel; Vekovischeva, Olga Y; Rosenberg, Per H; Wisden, William; Korpi, Esa R

    2007-12-01

    The TASK-3 channel is an acid-sensitive two-pore-domain K+ channel, widely expressed in the brain and probably involved in regulating numerous neuronal populations. Here, we characterized the behavioral and pharmacological phenotypes of TASK-3 knockout (KO) mice. Circadian locomotor activity measurements revealed that the nocturnal activity of the TASK-3 KO mice was increased by 38% (P < 0.01) compared with wild-type littermate controls, light phase activity being similar. Although TASK-3 channels are abundant in cerebellar granule cells, the KO mice performed as well as the wild-type mice in walking on a rotating rod or along a 1.2-cm-diameter beam. However, they fell more frequently from a narrower 0.8-cm beam. The KO mice showed impaired working memory in the spontaneous alternation task, with the alternation percentage being 62 +/- 3% for the wild-type mice and 48 +/- 4% (P < 0.05) for the KO mice. Likewise, during training for the Morris water-maze spatial memory task, the KO mice were slower to find the hidden platform, and in the probe trial, the female KO mice visited fewer times the platform quadrant than the male KO and wild-type mice. In pharmacological tests, the TASK-3 KO mice showed reduced sensitivity to the inhalation anesthetic halothane and the cannabinoid receptor agonist WIN55212-2 mesylate [(R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate] but unaltered responses to the alpha2 adrenoceptor agonist dexmedetomidine, the i.v. anesthetic propofol, the opioid receptor agonist morphine, and the local anesthetic lidocaine. Overall, our results suggest important contributions of TASK-3 channels in the neuronal circuits regulating circadian rhythms, cognitive functions, and mediating specific pharmacological effects. PMID:17875609

  5. Anxiolytic-like effects of restraint during the dark cycle in adolescent mice.

    PubMed

    Ota, Yuki; Ago, Yukio; Tanaka, Tatsunori; Hasebe, Shigeru; Toratani, Yui; Onaka, Yusuke; Hashimoto, Hitoshi; Takuma, Kazuhiro; Matsuda, Toshio

    2015-05-01

    Stress during developmental stage may cause psychological morbidities, and then the studies on stress are important in adolescent rodents. Restraint is used as a common stressor in rodents and the effects of restraint during the light cycle have been studied, but those of restraint during the dark cycle have not. The present study examined the effects of restraint during the light and dark cycles on anxiety behaviors in adolescent mice. Restraint for 3h during either the light or dark cycle impaired memory function in the fear conditioning test, but did not affect locomotor activity. In the elevated plus-maze test, restraint during the dark cycle reduced anxiety-like behaviors in mice. Repeated exposure to a 3-h period dark cycle restraint for 2 weeks had a similar anxiolytic-like effect. In contrast, restraint for 3h during the light cycle produced anxiety behavior in adolescent, but not adult, mice. The light cycle stress increased plasma corticosterone levels, and elevated c-Fos expression in the prefrontal cortex, paraventricular hypothalamic nucleus, basolateral amygdala and dentate gyrus, and enhanced serotonin turnover in the hippocampus and striatum, while the dark cycle stress did not. There was no difference in the stress-mediated reduction in pentobarbital-induced sleeping time between dark and light cycle restraint. These findings suggest that the anxiolytic effect of dark cycle restraint is mediated by corticosterone, serotonin or γ-aminobutyric acid-independent mechanisms, although the anxiogenic effect of light cycle restraint is associated with changes in plasma corticosterone levels and serotonin turnover in specific brain regions. PMID:25687845

  6. Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury

    SciTech Connect

    Cheng, Kang; Rai, Partab; Lan, Xiqian; Plagov, Andrei; Malhotra, Ashwani; Gupta, Sanjeev; Singhal, Pravin C.

    2013-08-15

    Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic mice and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection. -- Highlights: •MSCs isolated from HIV mice displayed HIV genes. •MSCs isolated from HIV mice exhibited attenuated growth and paracrine functions. •AKI mice with transplanted HIV-MSC displayed poor outcome. •HIV-1 MSC secreted multiple cytokines but at a lower level.

  7. Mice expressing markedly reduced striatal dopamine transporters exhibit increased locomotor activity, dopamine uptake turnover rate, and cocaine responsiveness.

    PubMed

    Rao, Anjali; Sorkin, Alexander; Zahniser, Nancy R

    2013-10-01

    Variations in the expression levels of the dopamine transporter (DAT) can influence responsiveness to psychostimulant drugs like cocaine. To better understand this relationship, we studied a new DAT-low expresser (DAT-LE) mouse model and performed behavioral and biochemical studies with it. Immunoblotting and [(3) H]WIN 35,428 binding analyses revealed that these mice express ∼35% of wildtype (WT) mouse striatal DAT levels. Compared to WT mice, DAT-LE mice were hyperactive in a novel open-field environment. Despite their higher basal locomotor activity, cocaine (10 or 20 mg/kg, i.p.) induced greater locomotor activation in DAT-LE mice than in WT mice. The maximal velocity (Vmax ) of DAT-mediated [(3) H]DA uptake into striatal synaptosomes was reduced by 46% in DAT-LE mice, as compared to WT. Overall, considering the reduced number of DAT binding sites (Bmax ) along with the reduced Vmax in DAT-LE mice, a 2-fold increase in DA uptake turnover rate (Vmax /Bmax ) was found, relative to WT mice. This suggests that neuroadaptive changes have occurred in the DAT-LE mice that would help to compensate for their low DAT numbers. Interestingly, these changes do not include a reduction in tyrosine hydroxylase levels, as was previously reported in DAT knockout homozygous and heterozygous animals. Further, these changes are not sufficient to prevent elevated novelty- and cocaine-induced locomotor activity. Hence, these mice represent a unique model for studying changes of in vivo DAT function and regulation that result from markedly reduced levels of DAT expression. PMID:23564231

  8. Mice expressing markedly reduced striatal dopamine transporters exhibit increased locomotor activity, dopamine uptake turnover rate, and cocaine responsiveness.

    PubMed

    Rao, Anjali; Sorkin, Alexander; Zahniser, Nancy R

    2013-10-01

    Variations in the expression levels of the dopamine transporter (DAT) can influence responsiveness to psychostimulant drugs like cocaine. To better understand this relationship, we studied a new DAT-low expresser (DAT-LE) mouse model and performed behavioral and biochemical studies with it. Immunoblotting and [(3) H]WIN 35,428 binding analyses revealed that these mice express ∼35% of wildtype (WT) mouse striatal DAT levels. Compared to WT mice, DAT-LE mice were hyperactive in a novel open-field environment. Despite their higher basal locomotor activity, cocaine (10 or 20 mg/kg, i.p.) induced greater locomotor activation in DAT-LE mice than in WT mice. The maximal velocity (Vmax ) of DAT-mediated [(3) H]DA uptake into striatal synaptosomes was reduced by 46% in DAT-LE mice, as compared to WT. Overall, considering the reduced number of DAT binding sites (Bmax ) along with the reduced Vmax in DAT-LE mice, a 2-fold increase in DA uptake turnover rate (Vmax /Bmax ) was found, relative to WT mice. This suggests that neuroadaptive changes have occurred in the DAT-LE mice that would help to compensate for their low DAT numbers. Interestingly, these changes do not include a reduction in tyrosine hydroxylase levels, as was previously reported in DAT knockout homozygous and heterozygous animals. Further, these changes are not sufficient to prevent elevated novelty- and cocaine-induced locomotor activity. Hence, these mice represent a unique model for studying changes of in vivo DAT function and regulation that result from markedly reduced levels of DAT expression.

  9. Acute social defeat stress increases the conditioned rewarding effects of cocaine in adult but not in adolescent mice.

    PubMed

    Montagud-Romero, S; Aguilar, M A; Maldonado, C; Manzanedo, C; Miñarro, J; Rodríguez-Arias, M

    2015-08-01

    Stressful experiences modify activity in areas of the brain involved in the rewarding effects of psychostimulants. In the present study we evaluated the influence of acute social defeat (ASD) on the conditioned rewarding effects of cocaine in adolescent (PND 29-32) and adult (PND 50-53) male mice in the conditioned place preference (CPP) paradigm. Experimental mice were exposed to social defeat in an agonistic encounter before each session of conditioning with 1mg/kg or 25mg/kg of cocaine. The effects of social defeat on corticosterone levels were also evaluated. Adult mice exposed to ASD showed an increase in the conditioned reinforcing effects of cocaine. Only these mice developed cocaine-induced CPP with the subthreshold dose of cocaine, and they needed a higher number of extinction sessions for the 25mg/kg cocaine-induced CPP to be extinguished. In adolescent mice, on the other hand, ASD reduced the conditioned reinforcing effects of cocaine, since CPP was not produced with the lower dose of cocaine and was extinguished faster when they were conditioned with 25mg/kg. Adult mice exposed to social defeat displayed higher levels of corticosterone than their controls and adolescent mice. Our results confirm that the effect of social defeat stress on the acquisition and reinstatement of the CPP induced by cocaine varies depending on the age at which this stress is experienced.

  10. Effects of acute social stress on the conditioned place preference induced by MDMA in adolescent and adult mice.

    PubMed

    García-Pardo, Maria P; Rodríguez-Arias, Marta; Maldonado, Concepcion; Manzanedo, Carmen; Miñarro, Jose; Aguilar, Maria A

    2014-09-01

    Exposure to social defeat stress increases the rewarding effects of psychostimulants in animal models, but its effect on 3,4-methylenedioxymethylamphetamine (MDMA) reward has received little attention. In the present study, we evaluated the influence of social defeat on the rewarding effects of MDMA in adolescent [postnatal day (PND) 29-40] and adult (PND 50-61) male mice using the conditioned place preference paradigm. Experimental mice were exposed to social defeat in an agonistic encounter before each session of conditioning with 1.25 or 10 mg/kg of MDMA. The effects of social defeat on corticosterone levels and the motor or the anxiogenic effects of MDMA were also evaluated. Mice exposed to social defeat during adulthood did not show conditioned place preference after conditioning with either dose of MDMA. Conversely, social defeat did not affect the anxiogenic and motor effects of MDMA. Adult mice exposed to social defeat showed higher levels of corticosterone than their controls and adolescent mice. Social stress did not induce behavioural effects in adolescent mice. Our results show that stress induced by social defeat decreases the sensitivity of adult mice to the rewarding effects of MDMA.

  11. Effects of Intoxicating Free-Choice Alcohol Consumption During Adolescence on Drinking and Impulsivity During Adulthood in Selectively Bred High Alcohol Preferring Mice

    PubMed Central

    O’Tousa, David Scott; Matson, Liana Marie; Grahame, Nicholas Joseph

    2014-01-01

    Background Abuse of alcohol during adolescence continues to be a problem, and it has been shown that earlier onset of drinking predicts increased alcohol abuse problems later in life. High levels of impulsivity have been demonstrated to be characteristic of alcoholics, and impulsivity has also been shown to predict later alcohol use in teenage subjects, showing that impulsivity may precede the development of alcohol use disorders. These experiments examined adolescent drinking in a high-drinking, relatively impulsive mouse population, and assessed its effects on adult drinking and adult impulsivity. Methods Experiment 1: Selectively bred High-Alcohol Preferring (HAPII) mice were given either alcohol (free choice access) or water only for two weeks during middle adolescence or adulthood. All mice were given free choice access to alcohol 30 days later, in adulthood. Experiment 2: Adolescent HAPII mice drank alcohol and water, or water alone, for two weeks, and were then trained to perform a delay discounting task as adults to measure impulsivity. In each experiment, effects of volitional ethanol consumption on later behavior were assessed. We expected adolescent alcohol exposure to increase subsequent drinking and impulsivity. Results Mice consumed significant quantities of ethanol, reaching average blood ethanol concentrations (BECs) of 142 mg/dl (adolescent) or 154 mg/dl (adult) in Experiment 1. Adolescent mice in experiment 2 reached an average of 108 mg/dl. Mice exposed to alcohol in either adolescence or adulthood showed a transient increase in ethanol consumption, but we observed no differences in impulsivity in adult mice as a function of whether mice drank alcohol during adolescence. Conclusions These findings indicate that HAPII mice drink intoxicating levels of alcohol during both adolescence and adulthood, and that this volitional intake has long-term effects on subsequent drinking behavior. Nonetheless, this profound exposure to alcohol during adolescence

  12. 3xTgAD mice exhibit altered behavior and elevated Aβ after chronic mild social stress

    PubMed Central

    Rothman, Sarah M.; Herdener, Nathan; Camandola, Simonetta; Texel, Sarah J.; Mughal, Mohamed R.; Cong, Wei-Na; Martin, Bronwen; Mattson, Mark P

    2014-01-01

    Chronic stress may be a risk factor for developing Alzheimer’s disease (AD), but most studies of the effects of stress in models of AD utilize acute adverse stressors of questionable clinical relevance. The goal of this work was to determine how chronic psychosocial stress affects behavioral and pathological outcomes in an animal model of AD, and to elucidate underlying mechanisms. A triple-transgenic mouse model of AD (3xTgAD mice) and nontransgenic control mice were used to test for an affect of chronic mild social stress on blood glucose, plasma glucocorticoids, plasma insulin, anxiety and hippocampal Aβ, ptau and BDNF levels. Despite the fact that both control and 3xTgAD mice experienced rises in corticosterone during episodes of mild social stress, at the end of the 6 week stress period 3xTgAD mice displayed increased anxiety, elevated levels of Aβ oligomers and intraneuronal Aβ, and decreased BDNF levels, whereas control mice did not. Findings suggest 3xTgAD mice are more vulnerable than control mice to chronic psychosocial stress, and that such chronic stress exacerbates Aβ accumulation and impairs neurotrophic signaling. PMID:21855175

  13. Chronic alcohol consumption from adolescence to adulthood in mice--hypothalamic gene expression changes in insulin-signaling pathway.

    PubMed

    Wang, Ke; Song, Huaiguang; Jin, Meilei; Xiao, Huasheng; Zhao, Guoping; Zou, Hong; Yu, Lei

    2014-09-01

    Adolescence is a developmental stage vulnerable to alcohol drinking-related problems, and alcohol exposure during adolescence may lead to long-lasting consequences. The hypothalamus is a key brain region for food and water intake regulation as well as weight control, and is one of the alcohol-sensitive brain regions. However, it is not known what the alcohol effect is on the hypothalamus following adolescent alcohol intake, chronically over adolescent development, at moderate levels. We employed a model of chronic moderate alcohol intake from adolescence to adulthood in mice, and analyzed the effect of alcohol on growth and weight gain, as well as hypothalamic gene expression patterns. The results indicated that chronic alcohol consumption during adolescence, even at moderate levels, led to both a reduction in weight gain in mice, and considerable gene expression changes in the hypothalamus. Pathway analysis and real-time PCR identified the type II diabetes mellitus and the insulin-signaling pathways as being the hypothalamic pathways affected by chronic alcohol. Our findings from the mouse alcohol consumption study therefore serve as a potential warning against alcohol consumption during adolescence, such as in teens and college students.

  14. Cardiac Adipose-Derived Stem Cells Exhibit High Differentiation Potential to Cardiovascular Cells in C57BL/6 Mice.

    PubMed

    Nagata, Hiroki; Ii, Masaaki; Kohbayashi, Eiko; Hoshiga, Masaaki; Hanafusa, Toshiaki; Asahi, Michio

    2016-02-01

    Adipose-derived stem cells (AdSCs) have recently been shown to differentiate into cardiovascular lineage cells. However, little is known about the fat tissue origin-dependent differences in AdSC function and differentiation potential. AdSC-rich cells were isolated from subcutaneous, visceral, cardiac (CA), and subscapular adipose tissue from mice and their characteristics analyzed. After four different AdSC types were cultured with specific differentiation medium, immunocytochemical analysis was performed for the assessment of differentiation into cardiovascular cells. We then examined the in vitro differentiation capacity and therapeutic potential of AdSCs in ischemic myocardium using a mouse myocardial infarction model. The cell density and proliferation activity of CA-derived AdSCs were significantly increased compared with the other adipose tissue-derived AdSCs. Immunocytochemistry showed that CA-derived AdSCs had the highest appearance rates of markers for endothelial cells, vascular smooth muscle cells, and cardiomyocytes among the AdSCs. Systemic transfusion of CA-derived AdSCs exhibited the highest cardiac functional recovery after myocardial infarction and the high frequency of the recruitment to ischemic myocardium. Moreover, long-term follow-up of the recruited CA-derived AdSCs frequently expressed cardiovascular cell markers compared with the other adipose tissue-derived AdSCs. Cardiac adipose tissue could be an ideal source for isolation of therapeutically effective AdSCs for cardiac regeneration in ischemic heart diseases. Significance: The present study found that cardiac adipose-derived stem cells have a high potential to differentiate into cardiovascular lineage cells (i.e., cardiomyocytes, endothelial cells, and vascular smooth muscle cells) compared with stem cells derived from other adipose tissue such as subcutaneous, visceral, and subscapular adipose tissue. Notably, only a small number of supracardiac adipose-derived stem cells that were

  15. Corticotropin-releasing factor-overexpressing mice exhibit reduced neuronal activation in the arcuate nucleus and food intake in response to fasting.

    PubMed

    Stengel, Andreas; Goebel, Miriam; Million, Mulugeta; Stenzel-Poore, Mary P; Kobelt, Peter; Mönnikes, Hubert; Taché, Yvette; Wang, Lixin

    2009-01-01

    Corticotropin-releasing factor (CRF) overexpressing (OE) mice are a genetic model that exhibits features of chronic stress. We investigated whether the adaptive feeding response to a hypocaloric challenge induced by food deprivation is impaired under conditions of chronic CRF overproduction. Food intake response to a 16-h overnight fast and ip injection of gut hormones regulating food intake were compared in CRF-OE and wild type (WT) littermate mice along with brain Fos expression, circulating ghrelin levels, and gastric emptying of a nonnutrient meal. CRF-OE mice injected ip with saline showed a 47 and 44% reduction of 30-min and 4-h cumulative food intake response to an overnight fast, respectively, compared with WT. However, the 30-min food intake decrease induced by ip cholecystokinin (3 microg/kg) and increase by ghrelin (300 microg/kg) were similar in CRF-OE and WT mice. Overnight fasting increased the plasma total ghrelin to similar levels in CRF-OE and WT mice, although CRF-OE mice had a 2-fold reduction of nonfasting ghrelin levels. The number of Fos-immunoreactive cells induced by fasting in the arcuate nucleus was reduced by 5.9-fold in CRF-OE compared with WT mice whereas no significant changes were observed in other hypothalamic nuclei. In contrast, fasted CRF-OE mice displayed a 5.6-fold increase in Fos-immunoreactive cell number in the dorsal motor nucleus of the vagus nerve and a 34% increase in 20-min gastric emptying. These findings indicate that sustained overproduction of hypothalamic CRF in mice interferes with fasting-induced activation of arcuate nucleus neurons and the related hyperphagic response.

  16. Psychological stress in adolescent and adult mice increases neuroinflammation and attenuates the response to LPS challenge

    PubMed Central

    2012-01-01

    Background There is ample evidence that psychological stress adversely affects many diseases. Recent evidence has shown that intense stressors can increase inflammation within the brain, a known mediator of many diseases. However, long-term outcomes of chronic psychological stressors that elicit a neuroinflammatory response remain unknown. Methods To address this, we have modified previously described models of rat/mouse predatory stress (PS) to increase the intensity of the interaction. We postulated that these modifications would enhance the predator-prey experience and increase neuroinflammation and behavioral dysfunction in prey animals. In addition, another group of mice were subjected to a modified version of chronic unpredictable stress (CUS), an often-used model of chronic stress that utilizes a combination of stressors that include physical, psychological, chemical, and other. The CUS model has been shown to exacerbate a number of inflammatory-related diseases via an unknown mechanism. Using these two models we sought to determine: 1) whether chronic PS or CUS modulated the inflammatory response as a proposed mechanism by which behavioral deficits might be mediated, and 2) whether chronic exposure to a pure psychological stressor (PS) leads to deficits similar to those produced by a CUS model containing psychological and physical stressors. Finally, to determine whether acute PS has neuroinflammatory consequences, adult mice were examined at various time-points after PS for changes in inflammation. Results Adolescent mice subjected to chronic PS had increased basal expression of inflammation within the midbrain. CUS and chronic PS mice also had an impaired inflammatory response to a subsequent lipopolysaccharide challenge and PS mice displayed increased anxiety- and depressive-like behaviors following chronic stress. Finally, adult mice subjected to acute predatory stress had increased gene expression of inflammatory factors. Conclusion Our results

  17. Mutant mice deficient in NOS-1 exhibit attenuated long-term facilitation and short-term potentiation in breathing

    PubMed Central

    Kline, David D; Overholt, Jeffery L; Prabhakar, Nanduri R

    2002-01-01

    The objective of the present study is to examine the potential role of nitric oxide (NO) in short-term potentiation (STP) and long-term facilitation (LTF) of breathing. Experiments were performed in wild-type (WT) and mutant mice deficient in nitric oxide synthase-1 (NOS-1), as well as in WT mice administered the NOS-1 inhibitor 7-nitroindazole (7-NI; 50 mg kg−1; i.p.). Respiratory responses following either single or recurrent episodes of hypoxia (7 % O2, balance N2) were analysed in unanaesthetised animals by body plethysmography along with rate of O2 consumption (V̇O2) and CO2 production (V̇CO2). After a single hypoxic challenge, respiration in WT mice remained elevated for 5 min, suggesting STP in ventilation. Following termination of three consecutive hypoxic challenges, respiration remained elevated during normoxia for as long as 30 min, indicating LTF in breathing under awake conditions. STP and LTF were significantly attenuated or absent in WT mice after 7-NI. A similar attenuation or absence of STP and LTF was also seen in NOS-1 mutant mice. Changes in V̇O2 and V̇CO2 were comparable among mice during the post-hypoxic period, suggesting that the absence of STP and LTF was not due to alterations in body metabolism. These results suggest endogenous NO is an important physiological modulator of ventilatory STP and LTF. PMID:11850522

  18. Effect of high-fat diets on mood and learning performance in adolescent mice.

    PubMed

    Del Rio, Danila; Morales, Lidia; Ruiz-Gayo, Mariano; Del Olmo, Nuria

    2016-09-15

    Recent studies point to dietary factors as important effectors in the brain and epidemiological studies suggest a direct relationship between mood and anxiety disorders, cognitive impairment and obesity. Nevertheless the link between the consumption of high-fat diets (HFD) and emotional disorders still remains unclear. This issue is of particular interest during adolescence, which is an important period for shaping learning and memory acquisition that can be particularly sensitive to the detrimental effects of HFD. Otherwise, major depressive disorder and anxiety crisis often emerge in adolescence. In the current study we have characterized in adolescent mice i) the onset of HFD-induced memory impairment using the novel location recognition (NLR) paradigm, and ii) the effect of HFD on depression- and anxiety-related behaviors by using the forced swimming and the elevated plus maze tests, respectively. Here we report that memory impairments induced by HFD were already perceptible after 4-weeks HFD whereas HFD induced already antidepressant-like effects after 48-h, that remained after long-term treatment (8 weeks). No effects in anxiety were found. These data indicate that the antidepressant-like effect of HFD is independent of memory deficits as it was already present after 48-h HFD, while no effects in memory were still observed at this time. PMID:27212119

  19. Cocaine enhances the conditioned rewarding effects of MDMA in adolescent mice.

    PubMed

    Aguilar, M A; Roger-Sánchez, C; Rodríguez-Arias, M; Miñarro, J

    2015-04-01

    Although the consumption of cocaine is frequent in young users of MDMA (3,4-methylenedioxymethamphetamine), the influence of exposure to cocaine on the rewarding effects of MDMA in adolescents has not been studied. The purpose of the present work was to evaluate the effect of co-administration of cocaine (1 and 10 mg/kg) and a sub-threshold dose of MDMA (1.25 mg/kg) on the acquisition of conditioned place preference (CPP) (experiment 1). In addition, the effect of pre-treatment with cocaine on MDMA-induced CPP was evaluated (experiment 2). Levels of monoamines in striatum, hippocampus and cortex were measured in both experiments. Our hypotheses were that cocaine co-administration or pre-treatment would increase the rewarding effects of MDMA, and that these effects would be related with changes in brain monoamine levels. Our results showed that cocaine potentiated the rewarding effects of MDMA, since a sub-threshold dose of MDMA, which did not induce CPP by itself, induced a significant CPP in adolescent mice when administered along with cocaine during conditioning (experiment 1). Moreover, pre-treatment with cocaine several days before conditioning also increased the rewarding effects of MDMA (experiment 2). No significant changes in the levels of biogenic amines, which correlated with these behavioural effects, were observed. Our results confirm the involvement of the dopaminergic system in MDMA-induced CPP in adolescent mice and suggest that combined consumption with or pre-exposure to cocaine increases the conditioned rewarding effects of MDMA, which may enhance the capacity of MDMA to induce dependence.

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

    Lopez, Marcelo F.; Laber, Kathy

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  4. ENU-mutagenesis mice with a non-synonymous mutation in Grin1 exhibit abnormal anxiety-like behaviors, impaired fear memory, and decreased acoustic startle response

    PubMed Central

    2013-01-01

    Background The Grin1 (glutamate receptor, ionotropic, NMDA1) gene expresses a subunit of N-methyl-D-aspartate (NMDA) receptors that is considered to play an important role in excitatory neurotransmission, synaptic plasticity, and brain development. Grin1 is a candidate susceptibility gene for neuropsychiatric disorders, including schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder (ADHD). In our previous study, we examined an N-ethyl-N-nitrosourea (ENU)-generated mutant mouse strain (Grin1Rgsc174/Grin1+) that has a non-synonymous mutation in Grin1. These mutant mice showed hyperactivity, increased novelty-seeking to objects, and abnormal social interactions. Therefore, Grin1Rgsc174/Grin1+ mice may serve as a potential animal model of neuropsychiatric disorders. However, other behavioral characteristics related to these disorders, such as working memory function and sensorimotor gating, have not been fully explored in these mutant mice. In this study, to further investigate the behavioral phenotypes of Grin1Rgsc174/Grin1+ mice, we subjected them to a comprehensive battery of behavioral tests. Results There was no significant difference in nociception between Grin1Rgsc174/Grin1+ and wild-type mice. The mutants did not display any abnormalities in the Porsolt forced swim and tail suspension tests. We confirmed the previous observations that the locomotor activity of these mutant mice increased in the open field and home cage activity tests. They displayed abnormal anxiety-like behaviors in the light/dark transition and the elevated plus maze tests. Both contextual and cued fear memory were severely deficient in the fear conditioning test. The mutant mice exhibited slightly impaired working memory in the eight-arm radial maze test. The startle amplitude was markedly decreased in Grin1Rgsc174/Grin1+ mice, whereas no significant differences between genotypes were detected in the prepulse inhibition (PPI) test. The mutant mice showed no obvious

  5. Tight skin 2 mice exhibit a novel time line of events leading to increased extracellular matrix deposition and dermal fibrosis.

    PubMed

    Long, Kristen B; Artlett, Carol M; Blankenhorn, Elizabeth P

    2014-09-01

    The tight skin 2 (Tsk2) mouse model of systemic sclerosis (SSc) has many features of the human disease including tight skin, fibrosis, extracellular matrix abnormalities, and reported antinuclear antibodies (ANA). Here we report that Tsk2/+ mice develop excess dermal fibrosis with age, as skin is not significantly fibrotic until 10 weeks, a full eight weeks after the development of the physical tight skin phenotype. Concomitantly with the tight skin phenotype at two weeks of age, Tsk2/+ mice demonstrate increased levels of total transforming growth factor beta 1 (TGF-β1) and excessive accumulation of dermal elastic fibers. The increase in elastic fibers is not responsible for tight skin, however, because Tsk2/+ mice genetically engineered to lack skin elastic fibers nevertheless have tight skin and fibrosis. Finally, about two months after the first measurable increases of total collagen, a portion of Tsk2/+ mice produce ANAs, but at a similar level to wild-type littermates. The timeline of disease development in the Tsk2/+ mouse shows that fibrosis is progressive, with elastic fiber alterations and TGF-β1 over-production occurring at least two months before bona fide fibrosis, that is not dependent on ANA production.

  6. Tg-SwDI Transgenic Mice Exhibit Novel Alterations in AβPP Processing, Aβ Degradation, and Resilient Amyloid Angiopathy

    PubMed Central

    Van Vickle, Gregory D.; Esh, Chera L.; Daugs, Ian D.; Kokjohn, Tyler A.; Kalback, Walter M.; Patton, R. Lyle; Luehrs, Dean C.; Walker, Douglas G.; Lue, Lih-Fen; Beach, Thomas G.; Davis, Judianne; Van Nostrand, William E.; Castaño, Eduardo M.; Roher, Alex E.

    2008-01-01

    Alzheimer’s disease (AD) is characterized by the accumulation of extracellular insoluble amyloid, primarily derived from polymerized amyloid-β (Aβ) peptides. We characterized the chemical composition of the Aβ peptides deposited in the brain parenchyma and cerebrovascular walls of triple transgenic Tg-SwDI mice that produce a rapid and profuse Aβ accumulation. The processing of the N- and C-terminal regions of mutant AβPP differs substantially from humans because the brain parenchyma accumulates numerous, diffuse, nonfibrillar plaques, whereas the thalamic microvessels harbor overwhelming amounts of compact, fibrillar, thioflavine-S- and apolipoprotein E-positive amyloid deposits. The abundant accretion of vascular amyloid, despite low AβPP transgene expression levels, suggests that inefficient Aβ proteolysis because of conformational changes and dimerization may be key pathogenic factors in this animal model. The disruption of amyloid plaque cores by immunotherapy is accompanied by increased perivascular deposition in both humans and transgenic mice. This analogous susceptibility and response to the disruption of amyloid deposits suggests that Tg-SwDI mice provide an excellent model in which to study the functional aftermath of immunotherapeutic interventions. These mice might also reveal new avenues to promote amyloidogenic AβPP processing and fundamental insights into the faulty degradation and clearance of Aβ in AD, pivotal issues in understanding AD pathophysiology and the assessment of new therapeutic agents. PMID:18599612

  7. Pseudouridine synthase 1 deficient mice, a model for Mitochondrial Myopathy with Sideroblastic Anemia, exhibit muscle morphology and physiology alterations.

    PubMed

    Mangum, Joshua E; Hardee, Justin P; Fix, Dennis K; Puppa, Melissa J; Elkes, Johnathon; Altomare, Diego; Bykhovskaya, Yelena; Campagna, Dean R; Schmidt, Paul J; Sendamarai, Anoop K; Lidov, Hart G W; Barlow, Shayne C; Fischel-Ghodsian, Nathan; Fleming, Mark D; Carson, James A; Patton, Jeffrey R

    2016-01-01

    Mitochondrial myopathy with lactic acidosis and sideroblastic anemia (MLASA) is an oxidative phosphorylation disorder, with primary clinical manifestations of myopathic exercise intolerance and a macrocytic sideroblastic anemia. One cause of MLASA is recessive mutations in PUS1, which encodes pseudouridine (Ψ) synthase 1 (Pus1p). Here we describe a mouse model of MLASA due to mutations in PUS1. As expected, certain Ψ modifications were missing in cytoplasmic and mitochondrial tRNAs from Pus1(-/-) animals. Pus1(-/-) mice were born at the expected Mendelian frequency and were non-dysmorphic. At 14 weeks the mutants displayed reduced exercise capacity. Examination of tibialis anterior (TA) muscle morphology and histochemistry demonstrated an increase in the cross sectional area and proportion of myosin heavy chain (MHC) IIB and low succinate dehydrogenase (SDH) expressing myofibers, without a change in the size of MHC IIA positive or high SDH myofibers. Cytochrome c oxidase activity was significantly reduced in extracts from red gastrocnemius muscle from Pus1(-/-) mice. Transmission electron microscopy on red gastrocnemius muscle demonstrated that Pus1(-/-) mice also had lower intermyofibrillar mitochondrial density and smaller mitochondria. Collectively, these results suggest that alterations in muscle metabolism related to mitochondrial content and oxidative capacity may account for the reduced exercise capacity in Pus1(-/-) mice. PMID:27197761

  8. Pseudouridine synthase 1 deficient mice, a model for Mitochondrial Myopathy with Sideroblastic Anemia, exhibit muscle morphology and physiology alterations

    PubMed Central

    Mangum, Joshua E.; Hardee, Justin P.; Fix, Dennis K.; Puppa, Melissa J.; Elkes, Johnathon; Altomare, Diego; Bykhovskaya, Yelena; Campagna, Dean R.; Schmidt, Paul J.; Sendamarai, Anoop K.; Lidov, Hart G. W.; Barlow, Shayne C.; Fischel-Ghodsian, Nathan; Fleming, Mark D.; Carson, James A.; Patton, Jeffrey R.

    2016-01-01

    Mitochondrial myopathy with lactic acidosis and sideroblastic anemia (MLASA) is an oxidative phosphorylation disorder, with primary clinical manifestations of myopathic exercise intolerance and a macrocytic sideroblastic anemia. One cause of MLASA is recessive mutations in PUS1, which encodes pseudouridine (Ψ) synthase 1 (Pus1p). Here we describe a mouse model of MLASA due to mutations in PUS1. As expected, certain Ψ modifications were missing in cytoplasmic and mitochondrial tRNAs from Pus1−/− animals. Pus1−/− mice were born at the expected Mendelian frequency and were non-dysmorphic. At 14 weeks the mutants displayed reduced exercise capacity. Examination of tibialis anterior (TA) muscle morphology and histochemistry demonstrated an increase in the cross sectional area and proportion of myosin heavy chain (MHC) IIB and low succinate dehydrogenase (SDH) expressing myofibers, without a change in the size of MHC IIA positive or high SDH myofibers. Cytochrome c oxidase activity was significantly reduced in extracts from red gastrocnemius muscle from Pus1−/− mice. Transmission electron microscopy on red gastrocnemius muscle demonstrated that Pus1−/− mice also had lower intermyofibrillar mitochondrial density and smaller mitochondria. Collectively, these results suggest that alterations in muscle metabolism related to mitochondrial content and oxidative capacity may account for the reduced exercise capacity in Pus1−/− mice. PMID:27197761

  9. Prion protein-deficient mice exhibit decreased CD4 T and LTi cell numbers and impaired spleen structure.

    PubMed

    Kim, Soochan; Han, Sinsuk; Lee, Ye Eun; Jung, Woong-Jae; Lee, Hyung Soo; Kim, Yong-Sun; Choi, Eun-Kyoung; Kim, Mi-Yeon

    2016-01-01

    The cellular prion protein is expressed in almost all tissues, including the central nervous system and lymphoid tissues. To investigate the effects of the prion protein in lymphoid cells and spleen structure formation, we used prion protein-deficient (Prnp(0/0)) Zürich I mice generated by inactivation of the Prnp gene. Prnp(0/0) mice had decreased lymphocytes, in particular, CD4 T cells and lymphoid tissue inducer (LTi) cells. Decreased CD4 T cells resulted from impaired expression of CCL19 and CCL21 in the spleen rather than altered chemokine receptor CCR7 expression. Importantly, some of the white pulp regions in spleens from Prnp(0/0) mice displayed impaired T zone structure as a result of decreased LTi cell numbers and altered expression of the lymphoid tissue-organizing genes lymphotoxin-α and CXCR5, although expression of the lymphatic marker podoplanin and CXCL13 by stromal cells was not affected. In addition, CD3(-)CD4(+)IL-7Rα(+) LTi cells were rarely detected in impaired white pulp in spleens of these mice. These data suggest that the prion protein is required to form the splenic white pulp structure and for development of normal levels of CD4 T and LTi cells.

  10. Basigin null mutant male mice are sterile and exhibit impaired interactions between germ cells and Sertoli cells

    PubMed Central

    Bi, Jiajia; Li, Yanfen; Sun, Fengyun; Saalbach, Anja; Klein, Claudia; Miller, David J.; Hess, Rex; Nowak, Romana A.

    2013-01-01

    Basigin (BSG) is a multifunctional glycoprotein that plays an important role in male reproduction since male knockout (KO) mice are sterile. The Bsg KO testis lacks elongated spermatids and mature spermatozoa, a phenotype similar to that of alpha-mannosidase IIx (MX) KO mice. MX regulates formation of N-acetylglucosamine (GlcNAc) terminated N-glycans that participate in germ cell-Sertoli cell adhesion. Results showed that Bsg KO spermatocytes displayed normal homologous chromosome synapsis and progression through meiosis. However, only punctate expression of the round spermatid marker SP-10 in the acrosomal granule of germ cells of Bsg KO mice was detected indicating that spermatogenesis in Bsg KO mice was arrested at the early round spermatid stages. We observed a large increase in the number of germ cells undergoing apoptosis in Bsg KO testes. Using lectin blotting, we determined that GlcNAc terminated N-glycans are linked to BSG. GlcNAc terminated N-glycans were significantly reduced in Bsg KO testes. These observations indicate that BSG may act as a germ cell-Sertoli cell attachment molecule. Loss of BSG significantly reduced adhesion between GC-2 and SF7 cells. Moreover, wild type testes showed strong expression of N-cadherin (CDH2) while expression was greatly reduced in the testes of Bsg KO mice. In addition, the integrity of the blood-testis barrier (BTB) was compromised in Bsg KO testes. In conclusion, although some Bsg KO spermatogonia can undergo normal progression to the spermatocyte stage, BSG-mediated germ cell-Sertoli cell interactions appear to be necessary for integrity of the BTB and spermatocyte progression to mature spermatozoa. PMID:23727514

  11. Female Mucopolysaccharidosis IIIA Mice Exhibit Hyperactivity and a Reduced Sense of Danger in the Open Field Test

    PubMed Central

    Langford-Smith, Alex; Langford-Smith, Kia J.; Jones, Simon A.; Wynn, Robert F.; Wraith, J. E.; Wilkinson, Fiona L.; Bigger, Brian W.

    2011-01-01

    Reliable behavioural tests in animal models of neurodegenerative diseases allow us to study the natural history of disease and evaluate the efficacy of novel therapies. Mucopolysaccharidosis IIIA (MPS IIIA or Sanfilippo A), is a severe, neurodegenerative lysosomal storage disorder caused by a deficiency in the heparan sulphate catabolising enzyme, sulfamidase. Undegraded heparan sulphate accumulates, resulting in lysosomal enlargement and cellular dysfunction. Patients suffer a progressive loss of motor and cognitive function with severe behavioural manifestations and premature death. There is currently no treatment. A spontaneously occurring mouse model of the disease has been described, that has approximately 3% of normal enzyme activity levels. Behavioural phenotyping of the MPS IIIA mouse has been previously reported, but the results are conflicting and variable, even after full backcrossing to the C57BL/6 background. Therefore we have independently backcrossed the MPS IIIA model onto the C57BL/6J background and evaluated the behaviour of male and female MPS IIIA mice at 4, 6 and 8 months of age using the open field test, elevated plus maze, inverted screen and horizontal bar crossing at the same circadian time point. Using a 60 minute open field, we have demonstrated that female MPS IIIA mice are hyperactive, have a longer path length, display rapid exploratory behaviour and spend less time immobile than WT mice. Female MPS IIIA mice also display a reduced sense of danger and spend more time in the centre of the open field. There were no significant differences found between male WT and MPS IIIA mice and no differences in neuromuscular strength were seen with either sex. The altered natural history of behaviour that we observe in the MPS IIIA mouse will allow more accurate evaluation of novel therapeutics for MPS IIIA and potentially other neurodegenerative disorders. PMID:22028789

  12. Secretin receptor-knockout mice are resistant to high-fat diet-induced obesity and exhibit impaired intestinal lipid absorption.

    PubMed

    Sekar, Revathi; Chow, Billy K C

    2014-08-01

    Secretin, a classical gastrointestinal hormone released from S cells in response to acid and dietary lipid, regulates pleiotropic physiological functions, such as exocrine pancreatic secretion and gastric motility. Subsequent to recently proposed revisit on secretin's metabolic effects, we have confirmed lipolytic actions of secretin during starvation and discovered a hormone-sensitive lipase-mediated mechanistic pathway behind. In this study, a 12 wk high-fat diet (HFD) feeding to secretin receptor-knockout (SCTR(-/-)) mice and their wild-type (SCTR(+/+)) littermates revealed that, despite similar food intake, SCTR(-/-) mice gained significantly less weight (SCTR(+/+): 49.6±0.9 g; SCTR(-/-): 44.7±1.4 g; P<0.05) and exhibited lower body fat content. These SCTR(-/-) mice have corresponding alleviated HFD-associated hyperleptinemia and improved glucose/insulin tolerance. Further analyses indicate that SCTR(-/-) have impaired intestinal fatty acid absorption while having similar energy expenditure and locomotor activity. Reduced fat absorption in the intestine is further supported by lowered postprandial triglyceride concentrations in circulation in SCTR(-/-) mice. In jejunal cells, transcript and protein levels of a key fat absorption regulator, cluster of differentiation 36 (CD36), was reduced in knockout mice, while transcript of Cd36 and fatty-acid uptake in isolated enterocytes was stimulated by secretin. Based on our findings, a novel positive feedback pathway involving secretin and CD36 to enhance intestinal lipid absorption is being proposed.

  13. Mice expressing T4826I-RYR1 are viable but exhibit sex- and genotype-dependent susceptibility to malignant hyperthermia and muscle damage.

    PubMed

    Yuen, Benjamin; Boncompagni, Simona; Feng, Wei; Yang, Tianzhong; Lopez, Jose R; Matthaei, Klaus I; Goth, Samuel R; Protasi, Feliciano; Franzini-Armstrong, Clara; Allen, Paul D; Pessah, Isaac N

    2012-03-01

    Mutation T4825I in the type 1 ryanodine receptor (RYR1(T4825I/+)) confers human malignant hyperthermia susceptibility (MHS). We report a knock-in mouse line that expresses the isogenetic mutation T4826I. Heterozygous RYR1(T4826I/+) (Het) or homozygous RYR1(T4826I/T4826I) (Hom) mice are fully viable under typical rearing conditions but exhibit genotype- and sex-dependent susceptibility to environmental conditions that trigger MH. Hom mice maintain higher core temperatures than WT in the home cage, have chronically elevated myoplasmic[Ca(2+)](rest), and present muscle damage in soleus with a strong sex bias. Mice subjected to heat stress in an enclosed 37°C chamber fail to trigger MH regardless of genotype, whereas heat stress at 41°C invariably triggers fulminant MH in Hom, but not Het, mice within 20 min. WT and Het female mice fail to maintain euthermic body temperature when placed atop a bed whose surface is 37°C during halothane anesthesia (1.75%) and have no hyperthermic response, whereas 100% Hom mice of either sex and 17% of the Het males develop fulminant MH. WT mice placed on a 41°C bed maintain body temperature while being administered halothane, and 40% of the Het females and 100% of the Het males develop fulminant MH within 40 min. Myopathic alterations in soleus were apparent by 12 mo, including abnormally distributed and enlarged mitochondria, deeply infolded sarcolemma, and frequent Z-line streaming regions, which were more severe in males. These data demonstrate that an MHS mutation within the S4-S5 cytoplasmic linker of RYR1 confers genotype- and sex-dependent susceptibility to pharmacological and environmental stressors that trigger fulminant MH and promote myopathy. PMID:22131268

  14. Comparison of the deleterious effects of binge drinking-like alcohol exposure in adolescent and adult mice.

    PubMed

    Lacaille, Hélène; Duterte-Boucher, Dominique; Liot, Donovan; Vaudry, Hubert; Naassila, Mickael; Vaudry, David

    2015-03-01

    A major cause of alcohol toxicity is the production of reactive oxygen species generated during ethanol metabolism. The aim of this study was to compare the effect of binge drinking-like alcohol exposure on a panel of genes implicated in oxidative mechanisms in adolescent and adult mice. In adolescent animals, alcohol decreased the expression of genes involved in the repair and protection of oxidative DNA damage such as atr, gpx7, or nudt15 and increased the expression of proapoptotic genes such as casp3. In contrast, in the adult brain, genes activated by alcohol were mainly associated with protective mechanisms that prevent cells from oxidative damage. Whatever the age, iterative binge-like episodes provoked the same deleterious effects as those observed after a single binge episode. In adolescent mice, multiple binge ethanol exposure substantially reduced neurogenesis in the dentate gyrus and impaired short-term memory in the novel object and passive avoidance tests. Taken together, our results indicate that alcohol causes deleterious effects in the adolescent brain which are distinct from those observed in adults. These data contribute to explain the greater sensitivity of the adolescent brain to alcohol toxicity. The effects of alcohol exposure were investigated on genes involved in oxidative mechanisms. In adolescent animals, alcohol decreased the expression of genes involved in DNA repair, a potential cause of the observed decrease of neurogenesis. In contrast, in the adult brain, alcohol increased the expression of genes associated with antioxidant mechanisms. Apoptosis was increase in all groups and converged with other biochemical alterations to enhance short-term memory impairment in the adolescent brain. These data contribute to explain the greater sensitivity of the adolescent brain to alcohol toxicity. PMID:25556946

  15. N-palmitoylethanolamide, an endocannabinoid, exhibits antidepressant effects in the forced swim test and the tail suspension test in mice.

    PubMed

    Yu, Hai-Ling; Deng, Xian-Qing; Li, Ying-Jun; Li, Ying-Chun; Quan, Zhe-Shan; Sun, Xian-Yu

    2011-01-01

    The antidepressant-like effects of N-palmitoylethanolamide (PEA), a putative endocannabinoid, was investigated in mice using the tail suspension test (TST) and the forced swimming test (FST). In TST, PEA (10, 20, and 40 mg/kg) produced a statistically significant reduction in immobility (50, 32, and 34%, respectively, vs. the control group), whereas fluoxetine (20 mg/kg) reduced immobility by 38%. In FST, PEA (5, 10, and 20 mg/kg) produced a statistically significant reduction in immobility (15, 21, and 36%, respectively), whereas fluoxetine (20 mg/kg) reduced immobility by 18%. Moreover, PEA (20 mg/kg) did not significantly change motor activity in a spontaneous behavioral test. In conclusion, PEA (dose range of 5-40 mg/kg) administered orally reduced immobility in TST and FST, comparable to the antidepressant effect of fluoxetine, and had no effect on spontaneous activity in mice. PMID:21857095

  16. Biofilm-Forming Methicillin-Resistant Staphylococcus aureus Survive in Kupffer Cells and Exhibit High Virulence in Mice

    PubMed Central

    Oyama, Takuto; Miyazaki, Motoyasu; Yoshimura, Michinobu; Takata, Tohru; Ohjimi, Hiroyuki; Jimi, Shiro

    2016-01-01

    Although Staphylococcus aureus is part of the normal body flora, heavy usage of antibiotics has resulted in the emergence of methicillin-resistant strains (MRSA). MRSA can form biofilms and cause indwelling foreign body infections, bacteremia, soft tissue infections, endocarditis, and osteomyelitis. Using an in vitro assay, we screened 173 clinical blood isolates of MRSA and selected 20 high-biofilm formers (H-BF) and low-biofilm formers (L-BF). These were intravenously administered to mice and the general condition of mice, the distribution of bacteria, and biofilm in the liver, lung, spleen, and kidney were investigated. MRSA count was the highest in the liver, especially within Kupffer cells, which were positive for acid polysaccharides that are associated with intracellular biofilm. After 24 h, the general condition of the mice worsened significantly in the H-BF group. In the liver, bacterial deposition and aggregation and the biofilm-forming spot number were all significantly greater for H-BF group than for L-BF. CFU analysis revealed that bacteria in the H-BF group survived for long periods in the liver. These results indicate that the biofilm-forming ability of MRSA is a crucial factor for intracellular persistence, which could lead to chronic infections. PMID:27376326

  17. Model mice for 15q11-13 duplication syndrome exhibit late-onset obesity and altered lipid metabolism.

    PubMed

    Kishimoto, Rui; Tamada, Kota; Liu, Xiaoxi; Okubo, Hiroko; Ise, Satoko; Ohta, Hisashi; Ruf, Sandra; Nakatani, Jin; Kohno, Nobuoki; Spitz, François; Takumi, Toru

    2015-08-15

    Copy number variations on human chromosome 15q11-q13 have been implicated in several neurodevelopmental disorders. A paternal loss or duplication of the Prader-Willi syndrome/Angelman syndrome (PWS/AS) region confers a risk of obesity, although the mechanism remains a mystery due to a lack of an animal model that accurately recreates the obesity phenotype. We performed detailed analyses of mice with duplication of PWS/AS locus (6 Mb) generated by chromosome engineering and found that animals with a paternal duplication of this region (patDp/+) show late-onset obesity, high sensitivity for high-fat diet, high levels of blood leptin and insulin without an increase in food intake. We show that prior to becoming obese, young patDp/+ mice already had enlarged white adipocytes. Transcriptome analysis of adipose tissue revealed an up-regulation of Secreted frizzled-related protein 5 (Sfrp5), known to promote adipogenesis. We additionally generated a new mouse model of paternal duplication focusing on a 3 Mb region (3 Mb patDp/+) within the PWS/AS locus. These mice recapitulate the obese phenotypes including expansion of visceral adipose tissue. Our results suggest paternally expressed genes in PWS/AS locus play a significant role for the obesity and identify new potential targets for future research and treatment of obesity. PMID:26002101

  18. Sphingosine kinase 2 deficient mice exhibit reduced experimental autoimmune encephalomyelitis: Resistance to FTY720 but not ST-968 treatments.

    PubMed

    Imeri, Faik; Schwalm, Stephanie; Lyck, Ruth; Zivkovic, Aleksandra; Stark, Holger; Engelhardt, Britta; Pfeilschifter, Josef; Huwiler, Andrea

    2016-06-01

    The immunomodulatory drug FTY720 is presently approved for the treatment of relapsing-remitting multiple sclerosis. It is a prodrug that requires activation by sphingosine kinase 2 (SK-2) to induce T cell homing to secondary lymphoid tissue. In this study, we have investigated the role of SK-2 in experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. We show that SK-2 deficiency reduced clinical symptoms of EAE. Furthermore, in SK-2-deficient mice, the protective effect of FTY720 on EAE was abolished, while the non-prodrug FTY720-derivative ST-968 was still fully active. Protection was paralleled by reduced numbers of T-lymphocytes in blood and a reduced blood-brain-barrier leakage. This correlated with reduced mRNA expression of ICAM-1, VCAM-1, but enhanced expression of PECAM-1. A similar regulation of permeability and of PECAM-1 was seen in primary cultures of isolated mouse brain vascular endothelial cells and in a human immortalized cell line upon SK-2 knockdown. In summary, these data demonstrated that deletion of SK-2 exerts a protective effect on the pathogenesis of EAE in C57BL/6 mice and that SK-2 is essential for the protective effect of FTY720 but not of ST-968. Thus, ST-968 is a promising novel immunomodulatory compound that may be a valuable alternative to FTY720 under conditions where SK-2 activity is limited. PMID:26808312

  19. Locomotor response to acute nicotine in adolescent mice is altered by maternal undernutrition during lactation.

    PubMed

    Dutra-Tavares, Ana C; Manhães, Alex C; Silva, Juliana O; Nunes-Freitas, André L; Conceição, Ellen P S; Moura, Egberto G; Lisboa, Patrícia C; Filgueiras, Cláudio C; Abreu-Villaça, Yael; Ribeiro-Carvalho, Anderson

    2015-12-01

    Undernutrition during brain development causes long lasting alterations in different neurotransmitter systems that may alter responses to psychoactive drugs. Despite the recognized effects of early undernutrition on the cholinergic system, no evidence that demonstrates the influence of this insult on nicotine susceptibility has been reported. We investigated the effects of protein/calorie restriction during lactation on the susceptibility to nicotine in adolescent mice. Dams were randomly assigned to one of the following groups: Control (C, 20 litters)--free access to standard laboratory diet (23% protein); Protein Restricted (PR, 12 litters)--free access to a isoenergetic, 8% protein diet; Calorie Restricted (CR, 12 litters)--access to standard laboratory diet in restricted quantities (mean ingestion of PR: pair-fed group). Undernutrition extended from postnatal day 2 (PN2) to weaning (PN21). At PN30, animals either received an i.p. injection of nicotine (0.5mg/Kg) or saline and were immediately placed in open field (OF). After the OF, adrenal glands and serum were collected for the analyses of stress-related endocrine parameters and leptin concentration. PR and CR offspring showed less body mass gain and visceral fat mass. PR offspring presented reduced serum leptin concentration. In the OF, nicotine increased locomotor activity of C and PR, but not of CR. CR and PR offspring showed decreased adrenal catecholamine content, which was not dependent on nicotine exposure. Our results indicate that early undernutrition interferes with nicotine-elicited locomotor effects in adolescent mice and suggest that endocrine parameters alterations in malnourished animals do not influence the behavioral response to nicotine.

  20. Long-term effects of methamphetamine exposure in adolescent mice on the future ovarian reserve in adulthood.

    PubMed

    Wang, Lan; Qu, Guoqiang; Dong, Xiyuan; Huang, Kai; Kumar, Molly; Ji, Licheng; Wang, Ya; Yao, Junning; Yang, Shulin; Wu, Ruxing; Zhang, Hanwang

    2016-02-01

    Currently, there is an increasing prevalence of adolescent exposure to methamphetamine (MA). However, there is a paucity of information concerning the long-term impact of early exposure to MA upon female fertility and ovarian reserve. The aim of this study was to investigate the effect of long-term MA exposure in adolescents on their ovarian reserve in adulthood. Adolescent mice received intraperitoneal injections of MA (5mg/kg, three times per week) or saline from the 21st postnatal day for an 8 week period. Morphological, histological, biochemical, hormonal and ethological parameters were evaluated. An impaired ovarian reserve and vitality was found in the group treated with MA, manifesting in morphological-apparent mitochondrial damage, an activated apoptosis pathway in the ovarian tissue, a downward expression of ovarian anti-Mullerian hormone (AMH), a decreased number of primordial and growing follicles, an increased number of atretic follicles, and a depressed secretion of AMH, estradiol and progesterone from granulosa cells. However, no significant difference was noticed regarding the estrous cycle, the mating ability and the fertility outcome in the reproductive age of the mice after a period of non-medication. The present results confirmed that a long term exposure to methamphetamine in adolescent mice does have an adverse impact on their ovarian reserve, which indicates that such an early abuse of MA might influence the fertility lifespan of the female mouse.

  1. Transgenic mice overexpressing amyloid precursor protein exhibit early metabolic deficits and a pathologically low leptin state associated with hypothalamic dysfunction in arcuate neuropeptide Y neurons.

    PubMed

    Ishii, Makoto; Wang, Gang; Racchumi, Gianfranco; Dyke, Jonathan P; Iadecola, Costantino

    2014-07-01

    Weight loss is a prominent early feature of Alzheimer's disease (AD) that often precedes the cognitive decline and clinical diagnosis. While the exact pathogenesis of AD remains unclear, accumulation of amyloid-β (Aβ) derived from the amyloid precursor protein (APP) in the brain is thought to lead to the neuronal dysfunction and death underlying the dementia. In this study, we examined whether transgenic mice overexpressing the Swedish mutation of APP (Tg2576), recapitulating selected features of AD, have hypothalamic leptin signaling dysfunction leading to early body weight deficits. We found that 3-month-old Tg2576 mice, before amyloid plaque formation, exhibit decreased weight with markedly decreased adiposity, low plasma leptin levels, and increased energy expenditure without alterations in feeding behavior. The expression of the orexigenic neuropeptide Y (NPY) in the hypothalamus to the low leptin state was abnormal at basal and fasting conditions. In addition, arcuate NPY neurons exhibited abnormal electrophysiological responses to leptin in Tg2576 hypothalamic slices or wild-type slices treated with Aβ. Finally, the metabolic deficits worsened as Tg2576 mice aged and amyloid burden increased in the brain. These results indicate that excess Aβ can potentially disrupt hypothalamic arcuate NPY neurons leading to weight loss and a pathologically low leptin state early in the disease process that progressively worsens as the amyloid burden increases. Collectively, these findings suggest that weight loss is an intrinsic pathological feature of Aβ accumulation and identify hypothalamic leptin signaling as a previously unrecognized pathogenic site of action for Aβ.

  2. Transgenic Mice Overexpressing Amyloid Precursor Protein Exhibit Early Metabolic Deficits and a Pathologically Low Leptin State Associated with Hypothalamic Dysfunction in Arcuate Neuropeptide Y Neurons

    PubMed Central

    Ishii, Makoto; Wang, Gang; Racchumi, Gianfranco; Dyke, Jonathan P.

    2014-01-01

    Weight loss is a prominent early feature of Alzheimer's disease (AD) that often precedes the cognitive decline and clinical diagnosis. While the exact pathogenesis of AD remains unclear, accumulation of amyloid-β (Aβ) derived from the amyloid precursor protein (APP) in the brain is thought to lead to the neuronal dysfunction and death underlying the dementia. In this study, we examined whether transgenic mice overexpressing the Swedish mutation of APP (Tg2576), recapitulating selected features of AD, have hypothalamic leptin signaling dysfunction leading to early body weight deficits. We found that 3-month-old Tg2576 mice, before amyloid plaque formation, exhibit decreased weight with markedly decreased adiposity, low plasma leptin levels, and increased energy expenditure without alterations in feeding behavior. The expression of the orexigenic neuropeptide Y (NPY) in the hypothalamus to the low leptin state was abnormal at basal and fasting conditions. In addition, arcuate NPY neurons exhibited abnormal electrophysiological responses to leptin in Tg2576 hypothalamic slices or wild-type slices treated with Aβ. Finally, the metabolic deficits worsened as Tg2576 mice aged and amyloid burden increased in the brain. These results indicate that excess Aβ can potentially disrupt hypothalamic arcuate NPY neurons leading to weight loss and a pathologically low leptin state early in the disease process that progressively worsens as the amyloid burden increases. Collectively, these findings suggest that weight loss is an intrinsic pathological feature of Aβ accumulation and identify hypothalamic leptin signaling as a previously unrecognized pathogenic site of action for Aβ. PMID:24990930

  3. A history of chronic morphine exposure during adolescence increases despair-like behaviour and strain-dependently promotes sociability in abstinent adult mice

    PubMed Central

    Lutz, PE; Reiss, D; Ouagazzal, AM; Kieffer, BL

    2013-01-01

    A crucial issue in treating opiate addiction, a chronic relapsing disorder, is to maintain a drug-free abstinent state. Prolonged abstinence associates with mood disorders, strongly contributing to relapse. In particular, substance use disorders occurring during adolescence predispose to depression later in adulthood. Using our established mouse model of opiate abstinence, we characterized emotional consequences into adulthood of morphine exposure during adolescence. Our results indicate that morphine treatment in adolescent mice has no effect on anxiety-like behaviours in adult mice, after abstinence. In contrast, morphine treatment during adolescence increases behavioural despair in adult mice. We also show that morphine exposure strain-dependently enhances sociability in adult mice. Additional research will be required to understand where and how morphine acts during brain maturation to affect emotional and social behaviours into adulthood. PMID:23295400

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2012-06-01

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

  6. Pyrrolidine dithiocarbamate inhibits UVB-induced skin inflammation and oxidative stress in hairless mice and exhibits antioxidant activity in vitro.

    PubMed

    Ivan, Ana L M; Campanini, Marcela Z; Martinez, Renata M; Ferreira, Vitor S; Steffen, Vinicius S; Vicentini, Fabiana T M C; Vilela, Fernanda M P; Martins, Frederico S; Zarpelon, Ana C; Cunha, Thiago M; Fonseca, Maria J V; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rúbia

    2014-09-01

    Ultraviolet B (UVB) irradiation may cause oxidative stress- and inflammation-dependent skin cancer and premature aging. Pyrrolidine dithiocarbamate (PDTC) is an antioxidant and inhibits nuclear factor-κB (NF-κB) activation. In the present study, the mechanisms of PDTC were investigated in cell free oxidant/antioxidant assays, in vivo UVB irradiation in hairless mice and UVB-induced NFκB activation in keratinocytes. PDTC presented the ability to scavenge 2,2'-azinobis-(3-ethyl benzothiazoline-6-sulfonic acid) radical (ABTS), 2,2-diphenyl-1-picryl-hydrazyl radical (DPPH) and hydroxyl radical (OH); and also efficiently inhibited iron-dependent and -independent lipid peroxidation as well as chelated iron. In vivo, PDTC treatment significantly decreased UVB-induced skin edema, myeloperoxidase (MPO) activity, production of the proinflammatory cytokine interleukin-1β (IL-1β), matrix metalloproteinase-9 (MMP-9), increase of reduced glutathione (GSH) levels and antioxidant capacity of the skin tested by the ferric reducing antioxidant power (FRAP) and ABTS assays. PDTC also reduced UVB-induced IκB degradation in keratinocytes. These results demonstrate that PDTC presents antioxidant and anti-inflammatory effects in vitro, which line up well with the PDTC inhibition of UVB irradiation-induced skin inflammation and oxidative stress in mice. These data suggest that treatment with PDTC may be a promising approach to reduce UVB irradiation-induced skin damages and merits further pre-clinical and clinical studies.

  7. Anxiety is correlated with running in adolescent female mice undergoing activity-based anorexia

    PubMed Central

    Wable, Gauri S.; Min, Jung-Yun; Chen, Yi-Wen; Aoki, Chiye

    2015-01-01

    Activity-based anorexia (ABA) is a widely used animal model for identifying the biological basis of excessive exercise and starvation, two hallmarks of anorexia nervosa (AN). Anxiety is correlated with exercise in AN. Yet the anxiety level of animals in ABA has not been reported. We asked: Does food restriction as part of ABA induction change the anxiety level of animals? If so, is the degree of anxiety correlated with degree of hyperactivity? We used the open field test before food restriction and the elevated plus maze test (EPM) during food restriction to quantify anxiety among singly housed adolescent female mice and determined whether food restriction alone or combined with exercise (i.e., ABA induction) abates or increases anxiety. We show that food restriction, with or without exercise, reduced anxiety significantly, as measured by the proportion of entries into the open arms of EPM (35.73 %, p= .04). Moreover, ABA-induced individuals varied in their open arm time measure of anxiety and this value was highly and negatively correlated to the individual’s food restriction-evoked wheel activity during the 24 hours following the anxiety test (R = − .75, p= .004, N = 12). This correlation was absent among the exercise-only controls. Additionally, mice with higher increase in anxiety ran more following food restriction. Our data suggest that food restriction-evoked wheel running hyperactivity can be used as a reliable and continuous measure of anxiety in ABA. The parallel relationship between anxiety level and activity in AN and ABA-induced female mice strengthens the animal model. PMID:25730124

  8. Mice with neuropathic pain exhibit morphine tolerance due to a decrease in the morphine concentration in the brain.

    PubMed

    Ochiai, Wataru; Kaneta, Mitsumasa; Nagae, Marina; Yuzuhara, Ami; Li, Xin; Suzuki, Haruka; Hanagata, Mika; Kitaoka, Satoshi; Suto, Wataru; Kusunoki, Yoshiki; Kon, Risako; Miyashita, Kazuhiko; Masukawa, Daiki; Ikarashi, Nobutomo; Narita, Minoru; Suzuki, Tsutomu; Sugiyama, Kiyoshi

    2016-09-20

    The chronic administration of morphine to patients with neuropathic pain results in the development of a gradual tolerance to morphine. Although the detailed mechanism of this effect has not yet been elucidated, one of the known causes is a decrease in μ-opioid receptor function with regard to the active metabolite of morphine, M-6-G(morphine-6-glucuronide), in the ventrotegmental area of the midbrain. In this study, the relationship between the concentration of morphine in the brain and its analgesic effect was examined after the administration of morphine in the presence of neuropathic pain. Morphine was orally administered to mice with neuropathic pain, and the relationship between morphine's analgesic effect and its concentration in the brain was analysed. In addition, the expression levels of the conjugation enzyme, UGT2B (uridine diphosphate glucuronosyltransferase), which has morphine as its substrate, and P-gp, which is a transporter involved in morphine excretion, were examined. In mice with neuropathic pain, the concentration of morphine in the brain was significantly decreased, and a correlation was found between this decrease and the decrease in the analgesic effect. It was considered possible that this decrease in the brain morphine concentration may be due to an increase in the expression level of P-gp in the small intestine and to an increase in the expression level and binding activity of UGT2B in the liver. The results of this study suggest the possibility that a sufficient analgesic effect may not be obtained when morphine is administered in the presence of neuropathic pain due to a decrease in the total amount of morphine and M-6-G that reach the brain. PMID:27102159

  9. FTO-dependent function of N6-methyladenosine is involved in the hepatoprotective effects of betaine on adolescent mice.

    PubMed

    Chen, Jingqing; Zhou, Xihong; Wu, Weiche; Wang, Xinxia; Wang, Yizhen

    2015-09-01

    Nonalcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease among children and adolescents in the developed world. Betaine, as a methyl donor, recently has been demonstrated to exert its hepatoprotective effects through rectifying the genomic DNA hypomethylation state. However, whether betaine supplementation affects N6-methyladenosine (m(6)A) mRNA methylation in NAFLD is still unknown. We conducted the current study to investigate the effects of betaine supplementation during adolescence on high-fat diet-induced pathological changes in liver of mice, and we further identified the effects of betaine supplementation on expression of the fat mass and obesity-associated gene (FTO) and hepatic m(6)A mRNA methylation. Our results showed that betaine supplementation across adolescence significantly alleviated high-fat-induced impairment of liver function and morphology as well as ectopic fat accumulation. Surprisingly, no significant effects on serum TG and NEFA level, as well as fat mass, were observed in mice supplemented with betaine. We also found that high-fat diet upregulated ACC1 and FAS gene expression and downregulated HSL and ATGL gene expression. However, these alterations were rectified by betaine supplementation. Moreover, an m(6)A hypomethylation state and increased FTO expression were detected in mice fed with high-fat diet, while betaine supplementation prevented these changes. Our results suggested that betaine supplementation during adolescence could protect mice from high-fat-induced NAFLD by decreasing de novo lipogenesis and increasing lipolysis. Furthermore, a novel FTO-dependent function of m(6)A may involve in the hepatoprotective effects of betaine.

  10. Microbiota from the distal guts of lean and obese adolescents exhibit partial functional redundancy besides clear differences in community structure.

    PubMed

    Ferrer, Manuel; Ruiz, Alicia; Lanza, Francesca; Haange, Sven-Bastiaan; Oberbach, Andreas; Till, Holger; Bargiela, Rafael; Campoy, Cristina; Segura, Maria Teresa; Richter, Michael; von Bergen, Martin; Seifert, Jana; Suarez, Antonio

    2013-01-01

    Recent research has disclosed a tight connection between obesity, metabolic gut microbial activities and host health. Obtaining a complete understanding of this relationship remains a major goal. Here, we conducted a comparative metagenomic and metaproteomic investigation of gut microbial communities in faecal samples taken from an obese and a lean adolescent. By analysing the diversity of 16S rDNA amplicons (10% operational phylogenetic units being common), 22 Mbp of consensus metagenome sequences (~70% common) and the expression profiles of 613 distinct proteins (82% common), we found that in the obese gut, the total microbiota was more abundant on the phylum Firmicutes (94.6%) as compared with Bacteroidetes (3.2%), although the metabolically active microbiota clearly behaves in a more homogeneous manner with both contributing equally. The lean gut showed a remarkable shift towards Bacteroidetes (18.9% total 16S rDNA), which become the most active fraction (81% proteins). Although the two gut communities maintained largely similar gene repertoires and functional profiles, improved pili- and flagella-mediated host colonization and improved capacity for both complementary aerobic and anaerobic de novo B(12) synthesis, 1,2-propanediol catabolism (most likely participating in de novo B(12) synthesis) and butyrate production were observed in the obese gut, whereas bacteria from lean gut seem to be more engaged in vitamin B(6) synthesis. Furthermore, this study provides functional evidence that variable combinations of species from different phyla could 'presumptively' fulfil overlapping and/or complementary functional roles required by the host, a scenario where minor bacterial taxa seem to be significant active contributors.

  11. Fucoidan from sea cucumber Cucumaria frondosa exhibits anti-hyperglycemic effects in insulin resistant mice via activating the PI3K/PKB pathway and GLUT4.

    PubMed

    Wang, Yiming; Wang, Jingfeng; Zhao, Yanlei; Hu, Shiwei; Shi, Di; Xue, Changhu

    2016-01-01

    The present study investigated the anti-hyperglycemic properties and mechanisms of fucoidan, isolated from Cucumaria frondosa (Cf-FUC), in insulin resistant mice. Male C57BL/6J mice were fed regular diet or high-fat/high-sucrose diet for 19 weeks. Model animals were dietary administrated either rosiglitazone (RSG, 1 mg/kg·bw), fucoidan (Cf-FUC, 80 mg/kg·bw) or their combinations. Results showed that Cf-FUC significantly reduced fasting blood glucose and insulin levels, and enhanced glucose tolerance and insulin tolerance in insulin-resistant mice. Quantitative real-time PCR analysis showed that Cf-FUC increased the mRNA expressions of insulin receptors (IR), insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3 kinase (PI3K), protein kinase B (PKB), and glucose transporter 4 (GLUT4). Western blot assays demonstrated that Cf-FUC showed no effect on total protein expression but nevertheless enhanced the phosphorylation of proteins listed above and increased translocation of GLUT4 to the cell membrane. Furthermore, Cf-FUC enhanced the effects of RSG. These results indicated that Cf-FUC exhibited significant anti-hyperglycemic effects via activating PI3K/PKB pathway and GLUT4 in skeletal muscle and adipose tissue.

  12. Morc3 mutant mice exhibit reduced cortical area and thickness, accompanied by altered haematopoietic stem cells niche and bone cell differentiation

    PubMed Central

    Jadhav, Gaurav; Teguh, Dian; Kenny, Jacob; Tickner, Jennifer; Xu, Jiake

    2016-01-01

    Morc3, a member of a highly conserved nuclear matrix protein super-family plays an important part in chromatin remodeling, DNA repair, epigenetic regulation and cellular senescence. However, its role in bone homeostasis is not known. In the present study, a phenotype-driven ENU mouse mutagenesis screen revealed that Morc3mut +/− mice exhibit reduced cortical area and thickness with increased cortical porosity. Morc3mut +/− mice displayed reduced osteoclast numbers and surface per bone surface as well as osteocyte numbers, concomitant with altered gene expressions such as Rankl/Opg and Sost in ex vivo long bones. In vitro experiments revealed a significant increase in the number of Sca-1+/c-kit+ haematopoietic stem cells (HSCs), and a significant reduction in senescence associated β-galactosidase activity in bone marrow macrophages (BMMs). In addition, we observed a decrease in osteoclastogenesis and bone resorption accompanied by upregulation of STAT1 expression in osteoclast lineage cells. Strikingly, Morc3 protein localization within the nuclear membrane was shifted to the cytoplasm in Morc3mut +/− osteoclasts. Further, Morc3mut +/− mice displayed increased osteoblast differentiation and altered gene expression. Collectively, our data show that Morc3 is a previously unreported regulator of cortical bone homeostasis and haematopoietic stem cells niche, accompanied by altered bone cell differentiation. PMID:27188231

  13. Effects of chronic social defeat stress on behaviour, endoplasmic reticulum proteins and choline acetyltransferase in adolescent mice.

    PubMed

    Huang, Guang-Biao; Zhao, Tong; Muna, Sushma Shrestha; Bagalkot, Tarique Rajasaheb; Jin, Hong-Mei; Chae, Han-Jung; Chung, Young-Chul

    2013-08-01

    The present study investigated the effects of social defeat stress on the behaviours and expressions of 78-kDa glucose-regulated protein (Grp78), CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) and choline acetyltransferase (Chat) in the brains of adolescent mice. Adolescent male C57BL/6J mice were divided into two groups (susceptible and unsusceptible) after 10 d social defeat stress. In expt 1, behavioural tests were conducted and brains were processed for Western blotting on day 21 after stress. In expt 2, social avoidance tests were conducted and brains were subsequently processed for Western blotting on day 12 after stress. Chronic social defeat stress produced more pronounced depression-like behaviours such as decreased locomotion and social interaction, increased anxiety-like behaviours and immobility, and impaired memory performance in susceptible mice. Moreover, susceptible mice showed greater expression of Grp78 and CHOP in the amygdala (Amyg) on days 12 and 21 compared with the other groups. Susceptible and unsusceptible groups showed significant increases in Grp78 and CHOP expression in the prefrontal cortex (PFC) and hippocampus (Hipp) on day 12 compared with the control group; this persisted until day 21. The levels of Chat measured on days 12 and 21 were significantly lower in the PFC, Amyg and Hipp of all defeated mice compared with controls. The findings of the behavioural tests indicate that chronic social defeat in adolescents produces anxiety-like behaviours, social withdrawal, despair-like behaviours and cognitive impairment. The Grp78, CHOP and Chat results suggest that the selective response of endoplasmic reticulum stress proteins in the Amyg plays an important role in the vulnerability-stress model of depression.

  14. Exposure to nicotine increases nicotinic acetylcholine receptor density in the reward pathway and binge ethanol consumption in C57BL/6J adolescent female mice.

    PubMed

    Locker, Alicia R; Marks, Michael J; Kamens, Helen M; Klein, Laura Cousino

    2016-05-01

    Nearly 80% of adult smokers begin smoking during adolescence. Binge alcohol consumption is also common during adolescence. Past studies report that nicotine and ethanol activate dopamine neurons in the reward pathway and may increase synaptic levels of dopamine in the nucleus accumbens through nicotinic acetylcholine receptor (nAChR) stimulation. Activation of the reward pathway during adolescence through drug use may produce neural alterations affecting subsequent drug consumption. Consequently, the effect of nicotine exposure on binge alcohol consumption was examined along with an assessment of the neurobiological underpinnings that drive adolescent use of these drugs. Adolescent C57BL/6J mice (postnatal days 35-44) were exposed to either water or nicotine (200μg/ml) for ten days. On the final four days, ethanol intake was examined using the drinking-in-the-dark paradigm. Nicotine-exposed mice consumed significantly more ethanol and displayed higher blood ethanol concentrations than did control mice. Autoradiographic analysis of nAChR density revealed higher epibatidine binding in frontal cortical regions in mice exposed to nicotine and ethanol compared to mice exposed to ethanol only. These data show that nicotine exposure during adolescence increases subsequent binge ethanol consumption, and may affect the number of nAChRs in regions of the brain reward pathway, specifically the frontal cortex.

  15. Dorsal root ganglia isolated from Nf1+/- mice exhibit increased levels of mRNA expression of voltage-dependent sodium channels.

    PubMed

    Hodgdon, K E; Hingtgen, C M; Nicol, G D

    2012-03-29

    We reported previously that sensory neurons isolated from mice with a heterozygous mutation of the Nf1 gene (Nf1+/-) exhibited greater excitability and increased sodium current densities compared with wildtype mice. This raises the question as to whether the increased current density resulted from post-translational modifications or increased expression of sodium channels. Quantitative real-time polymerase chain reaction was used to measure expression levels of the nine different voltage-gated sodium channel α subunits and the four associated auxiliary β subunits in the dorsal root ganglia (DRG) obtained from wildtype and Nf1+/- mice. The Relative Expression Software Tool indicated that Nav1.1, Nav1.3, Nav1.7, and Nav1.8 were significantly elevated in DRG isolated from Nf1+/- mice. Expression of Nav1.2, Nav1.5, Nav1.6, and Nav1.9 were not significantly altered. The gene transcript for Nav1.4 was not detected. There were no significant changes in the relative expression levels of β subunits. The Nav1.9 subtype was the most abundant with Nav1.7 and Nav1.8 being the next most abundant subtypes, whereas Nav1.3 was relatively less abundant. For the β subunits, β1 was by far the most abundant subtype. These results demonstrate that the increased expression levels of Nav1.7, Nav1.8, and perhaps Nav1.1 in the Nf1+/- DRG make the largest contribution to the increased sodium current density and thus give rise to the enhanced excitability. Though the mechanisms by which many people with NF1 experience increased pain have not been elucidated, these abnormal painful states may involve elevated expression of specific sodium channel subtypes in small diameter nociceptive sensory neurons. PMID:22260870

  16. Chronic cocaine exposure in adolescence: Effects on spatial discrimination reversal, delay discounting, and performance on fixed-ratio schedules in mice.

    PubMed

    Pope, Derek A; Boomhower, Steven R; Hutsell, Blake A; Teixeira, Kathryn M; Newland, M Christopher

    2016-04-01

    Adolescence is marked by the continued development of the neural pathways that support choice and decision-making, particularly those involving dopamine signaling. Cocaine exposure during adolescence may interfere with this development and manifest as increased perseveration and delay discounting in adulthood, behavioral processes that are related to drug addiction. Adolescent mice were exposed to 30mg/kg/day of cocaine (n=11) or saline vehicle (n=10) for 14days and behavior was assessed in adulthood. In Experiment 1, performance on a spatial-discrimination-reversal procedure was evaluated. In the first two sessions following the first reversal, cocaine-exposed mice produced more preservative errors relative to controls. In Experiment 2, cocaine-exposed mice displayed steeper delay discounting than saline-exposed mice, effects that were reversed by acute cocaine administration. Experiment 3 examined responding maintained by a range of fixed-ratio schedules of reinforcement. An analysis based on a theoretical framework called Mathematical Principles of Reinforcement (MPR) was applied to response-rate functions of individual mice. According to MPR, differences in response-rate functions in adulthood were due to a steepening of the delay-of-reinforcement gradient, disrupted motoric capacity (lower maximum response rates), and enhanced reinforcer efficacy for the adolescent cocaine- compared with saline-exposed mice. Overall, these experiments suggest that chronic exposure to cocaine during adolescence may impair different features of 'executive functions' in adulthood, and these may be related to distortions in the impact of reinforcing events.

  17. Developmental Trajectories of Auditory Cortex Synaptic Structures and Gap-Prepulse Inhibition of Acoustic Startle Between Early Adolescence and Young Adulthood in Mice.

    PubMed

    Moyer, Caitlin E; Erickson, Susan L; Fish, Kenneth N; Thiels, Edda; Penzes, Peter; Sweet, Robert A

    2016-05-01

    Cortical excitatory and inhibitory synapses are disrupted in schizophrenia, the symptoms of which often emerge during adolescence, when cortical excitatory synapses undergo pruning. In auditory cortex, a brain region implicated in schizophrenia, little is known about the development of excitatory and inhibitory synapses between early adolescence and young adulthood, and how these changes impact auditory cortex function. We used immunohistochemistry and quantitative fluorescence microscopy to quantify dendritic spines and GAD65-expressing inhibitory boutons in auditory cortex of early adolescent, late adolescent, and young adult mice. Numbers of spines decreased between early adolescence and young adulthood, during which time responses increased in an auditory cortex-dependent sensory task, silent gap-prepulse inhibition of the acoustic startle reflex (gap-PPI). Within-bouton GAD65 protein and GAD65-expressing bouton numbers decreased between late adolescence and young adulthood, a delay in onset relative to spine and gap-PPI changes. In mice lacking the spine protein kalirin, there were no significant changes in spine number, within-bouton GAD65 protein, or gap-PPI between adolescence and young adulthood. These results illustrate developmental changes in auditory cortex spines, inhibitory boutons, and auditory cortex function between adolescence and young adulthood, and provide insights into how disrupted adolescent neurodevelopment could contribute to auditory cortex synapse pathology and auditory impairments.

  18. A ten fold reduction of nicotine yield in tobacco smoke does not spare the central cholinergic system in adolescent mice.

    PubMed

    Abreu-Villaça, Yael; Correa-Santos, Monique; Dutra-Tavares, Ana C; Paes-Branco, Danielle; Nunes-Freitas, Andre; Manhães, Alex C; Filgueiras, Cláudio C; Ribeiro-Carvalho, Anderson

    2016-08-01

    The tobacco industry has gradually decreased nicotine content in cigarette smoke but the impact of this reduction on health is still controversial. Since the central cholinergic system is the primary site of action of nicotine, here, we investigated the effects of exposure of adolescent mice to tobacco smoke containing either high or low levels of nicotine on the central cholinergic system and the effects associated with cessation of exposure. From postnatal day (PN) 30 to 45, male and female Swiss mice were exposed to tobacco smoke (whole body exposure, 8h/day, 7 days/week) generated from 2R1F (HighNic group: 1.74mg nicotine/cigarette) or 4A1 (LowNic group: 0.14mg nicotine/cigarette) research cigarettes, whereas control mice were exposed to ambient air. Cholinergic biomarkers were assessed in the cerebral cortex and midbrain by the end of exposure (PN45), at short- (PN50) and long-term (PN75) deprivation. In the cortex, nicotinic cholinergic receptor upregulation was observed with either type of cigarette. In the midbrain, upregulation was detected only in HighNic mice and remained significant in females at short-term deprivation. The high-affinity choline transporter was reduced in the cortex: of HighNic mice by the end of exposure; of both HighNic and LowNic females at short-term deprivation; of LowNic mice at long-term deprivation. These decrements were separable from effects on choline acetyltransferase and acetylcholinesterase activities, suggesting cholinergic synaptic impairment. Here, we demonstrated central cholinergic alterations in an animal model of tobacco smoke exposure during adolescence. This system was sensitive even to tobacco smoke with very low nicotine content.

  19. A ten fold reduction of nicotine yield in tobacco smoke does not spare the central cholinergic system in adolescent mice.

    PubMed

    Abreu-Villaça, Yael; Correa-Santos, Monique; Dutra-Tavares, Ana C; Paes-Branco, Danielle; Nunes-Freitas, Andre; Manhães, Alex C; Filgueiras, Cláudio C; Ribeiro-Carvalho, Anderson

    2016-08-01

    The tobacco industry has gradually decreased nicotine content in cigarette smoke but the impact of this reduction on health is still controversial. Since the central cholinergic system is the primary site of action of nicotine, here, we investigated the effects of exposure of adolescent mice to tobacco smoke containing either high or low levels of nicotine on the central cholinergic system and the effects associated with cessation of exposure. From postnatal day (PN) 30 to 45, male and female Swiss mice were exposed to tobacco smoke (whole body exposure, 8h/day, 7 days/week) generated from 2R1F (HighNic group: 1.74mg nicotine/cigarette) or 4A1 (LowNic group: 0.14mg nicotine/cigarette) research cigarettes, whereas control mice were exposed to ambient air. Cholinergic biomarkers were assessed in the cerebral cortex and midbrain by the end of exposure (PN45), at short- (PN50) and long-term (PN75) deprivation. In the cortex, nicotinic cholinergic receptor upregulation was observed with either type of cigarette. In the midbrain, upregulation was detected only in HighNic mice and remained significant in females at short-term deprivation. The high-affinity choline transporter was reduced in the cortex: of HighNic mice by the end of exposure; of both HighNic and LowNic females at short-term deprivation; of LowNic mice at long-term deprivation. These decrements were separable from effects on choline acetyltransferase and acetylcholinesterase activities, suggesting cholinergic synaptic impairment. Here, we demonstrated central cholinergic alterations in an animal model of tobacco smoke exposure during adolescence. This system was sensitive even to tobacco smoke with very low nicotine content. PMID:27287270

  20. Sevoflurane Inhalation Accelerates the Long-Term Memory Consolidation via Small GTPase Overexpression in the Hippocampus of Mice in Adolescence.

    PubMed

    Nakamura, Emi; Kinoshita, Hiroyuki; Feng, Guo-Gang; Hayashi, Hisaki; Satomoto, Maiko; Sato, Motohiko; Fujiwara, Yoshihiro

    2016-01-01

    Sevoflurane exposure impairs the long-term memory in neonates. Whether the exposure to animals in adolescence affects the memory, however, has been unclear. A small hydrolase enzyme of guanosine triphosphate (GTPase) rac1 plays a role in the F-actin dynamics related to the synaptic plasticity, as well as superoxide production via reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation. The current study was designed to examine whether sevoflurane exposure to mice in early adolescence modifies the long-term learning ability concomitantly with the changes in F-actin constitution as well as superoxide production in the hippocampus according to the levels of rac1 protein expression. Four-week-old mice were subjected to the evaluation of long-term learning ability for three days. On day one, each mouse was allowed to enter a dark chamber for five min to acclimatization. On day two, the procedure was repeated with the addition of an electric shock as soon as a mouse entered the dark chamber. All mice subsequently inhaled 2 L/min air with (Sevoflurane group) and without (Control group) 2.5% sevoflurane for three hours. On day three, each mouse was placed on the platform and retention time, which is the latency to enter the dark chamber, was examined. The brain removed after the behavior test, was used for analyses of immunofluorescence, Western immunoblotting and intracellular levels of superoxide. Sevoflurane exposure significantly prolonged retention time, indicating the enhanced long-term memory. Sevoflurane inhalation augmented F-actin constitution coexisting with the rac1 protein overexpression in the hippocampus whereas it did not alter the levels of superoxide. Sevoflurane exposure to 4-week-old mice accelerates the long-term memory concomitantly with the enhanced F-actin constitution coexisting with the small GTPase rac1 overexpression in the hippocampus. These results suggest that sevoflurane inhalation may amplify long-term memory

  1. cGMP-dependent protein kinase type II knockout mice exhibit working memory impairments, decreased repetitive behavior, and increased anxiety-like traits.

    PubMed

    Wincott, Charlotte M; Abera, Sinedu; Vunck, Sarah A; Tirko, Natasha; Choi, Yoon; Titcombe, Roseann F; Antoine, Shannon O; Tukey, David S; DeVito, Loren M; Hofmann, Franz; Hoeffer, Charles A; Ziff, Edward B

    2014-10-01

    Neuronal activity regulates AMPA receptor trafficking, a process that mediates changes in synaptic strength, a key component of learning and memory. This form of plasticity may be induced by stimulation of the NMDA receptor which, among its activities, increases cyclic guanosine monophosphate (cGMP) through the nitric oxide synthase pathway. cGMP-dependent protein kinase type II (cGKII) is ultimately activated via this mechanism and AMPA receptor subunit GluA1 is phosphorylated at serine 845. This phosphorylation contributes to the delivery of GluA1 to the synapse, a step that increases synaptic strength. Previous studies have shown that cGKII-deficient mice display striking spatial learning deficits in the Morris Water Maze compared to wild-type littermates as well as lowered GluA1 phosphorylation in the postsynaptic density of the prefrontal cortex (Serulle et al., 2007; Wincott et al., 2013). In the current study, we show that cGKII knockout mice exhibit impaired working memory as determined using the prefrontal cortex-dependent Radial Arm Maze (RAM). Additionally, we report reduced repetitive behavior in the Marble Burying task (MB), and heightened anxiety-like traits in the Novelty Suppressed Feeding Test (NSFT). These data suggest that cGKII may play a role in the integration of information that conveys both anxiety-provoking stimuli as well as the spatial and environmental cues that facilitate functional memory processes and appropriate behavioral response. PMID:24752151

  2. Cinnamic Acid Bornyl Ester Derivatives from Valeriana wallichii Exhibit Antileishmanial In Vivo Activity in Leishmania major-Infected BALB/c Mice

    PubMed Central

    Hazra, Sudipta; Glaser, Jan; Holzgrabe, Ulrike; Hazra, Banasri; Schurigt, Uta

    2015-01-01

    Human leishmaniasis covers a broad spectrum of clinical manifestations ranging from self-healing cutaneous leishmaniasis to severe and lethal visceral leishmaniasis caused among other species by Leishmania major or Leishmania donovani, respectively. Some drug candidates are in clinical trials to substitute current therapies, which are facing emerging drug-resistance accompanied with serious side effects. Here, two cinnamic acid bornyl ester derivatives (1 and 2) were assessed for their antileishmanial activity. Good selectivity and antileishmanial activity of bornyl 3-phenylpropanoate (2) in vitro prompted the antileishmanial assessment in vivo. For this purpose, BALB/c mice were infected with Leishmania major promastigotes and treated with three doses of 50 mg/kg/day of compound 2. The treatment prevented the characteristic swelling at the site of infection and correlated with reduced parasite burden. Transmitted light microscopy and transmission electron microscopy of Leishmania major promastigotes revealed that compounds 1 and 2 induce mitochondrial swelling. Subsequent studies on Leishmania major promastigotes showed the loss of mitochondrial transmembrane potential (ΔΨm) as a putative mode of action. As the cinnamic acid bornyl ester derivatives 1 and 2 had exhibited antileishmanial activity in vitro, and compound 2 in Leishmania major-infected BALB/c mice in vivo, they can be regarded as possible lead structures for the development of new antileishmanial therapeutic approaches. PMID:26554591

  3. Cinnamic Acid Bornyl Ester Derivatives from Valeriana wallichii Exhibit Antileishmanial In Vivo Activity in Leishmania major-Infected BALB/c Mice.

    PubMed

    Masic, Anita; Valencia Hernandez, Ana Maria; Hazra, Sudipta; Glaser, Jan; Holzgrabe, Ulrike; Hazra, Banasri; Schurigt, Uta

    2015-01-01

    Human leishmaniasis covers a broad spectrum of clinical manifestations ranging from self-healing cutaneous leishmaniasis to severe and lethal visceral leishmaniasis caused among other species by Leishmania major or Leishmania donovani, respectively. Some drug candidates are in clinical trials to substitute current therapies, which are facing emerging drug-resistance accompanied with serious side effects. Here, two cinnamic acid bornyl ester derivatives (1 and 2) were assessed for their antileishmanial activity. Good selectivity and antileishmanial activity of bornyl 3-phenylpropanoate (2) in vitro prompted the antileishmanial assessment in vivo. For this purpose, BALB/c mice were infected with Leishmania major promastigotes and treated with three doses of 50 mg/kg/day of compound 2. The treatment prevented the characteristic swelling at the site of infection and correlated with reduced parasite burden. Transmitted light microscopy and transmission electron microscopy of Leishmania major promastigotes revealed that compounds 1 and 2 induce mitochondrial swelling. Subsequent studies on Leishmania major promastigotes showed the loss of mitochondrial transmembrane potential (ΔΨm) as a putative mode of action. As the cinnamic acid bornyl ester derivatives 1 and 2 had exhibited antileishmanial activity in vitro, and compound 2 in Leishmania major-infected BALB/c mice in vivo, they can be regarded as possible lead structures for the development of new antileishmanial therapeutic approaches. PMID:26554591

  4. Cinnamic Acid Bornyl Ester Derivatives from Valeriana wallichii Exhibit Antileishmanial In Vivo Activity in Leishmania major-Infected BALB/c Mice.

    PubMed

    Masic, Anita; Valencia Hernandez, Ana Maria; Hazra, Sudipta; Glaser, Jan; Holzgrabe, Ulrike; Hazra, Banasri; Schurigt, Uta

    2015-01-01

    Human leishmaniasis covers a broad spectrum of clinical manifestations ranging from self-healing cutaneous leishmaniasis to severe and lethal visceral leishmaniasis caused among other species by Leishmania major or Leishmania donovani, respectively. Some drug candidates are in clinical trials to substitute current therapies, which are facing emerging drug-resistance accompanied with serious side effects. Here, two cinnamic acid bornyl ester derivatives (1 and 2) were assessed for their antileishmanial activity. Good selectivity and antileishmanial activity of bornyl 3-phenylpropanoate (2) in vitro prompted the antileishmanial assessment in vivo. For this purpose, BALB/c mice were infected with Leishmania major promastigotes and treated with three doses of 50 mg/kg/day of compound 2. The treatment prevented the characteristic swelling at the site of infection and correlated with reduced parasite burden. Transmitted light microscopy and transmission electron microscopy of Leishmania major promastigotes revealed that compounds 1 and 2 induce mitochondrial swelling. Subsequent studies on Leishmania major promastigotes showed the loss of mitochondrial transmembrane potential (ΔΨm) as a putative mode of action. As the cinnamic acid bornyl ester derivatives 1 and 2 had exhibited antileishmanial activity in vitro, and compound 2 in Leishmania major-infected BALB/c mice in vivo, they can be regarded as possible lead structures for the development of new antileishmanial therapeutic approaches.

  5. Effects of Cannabinoid Exposure during Adolescence on the Conditioned Rewarding Effects of WIN 55212-2 and Cocaine in Mice: Influence of the Novelty-Seeking Trait.

    PubMed

    Rodríguez-Arias, M; Roger-Sánchez, C; Vilanova, I; Revert, N; Manzanedo, C; Miñarro, J; Aguilar, M A

    2016-01-01

    Adolescent exposure to cannabinoids enhances the behavioural effects of cocaine, and high novelty-seeking trait predicts greater sensitivity to the conditioned place preference (CPP) induced by this drug. Our aim was to evaluate the influence of novelty-seeking on the effects of adolescent cannabinoid exposure. Adolescent male mice were classified as high or low novelty seekers (HNS and LNS) in the hole-board test. First, we evaluated the CPP induced by the cannabinoid agonist WIN 55212-2 (0.05 and 0.075 mg/kg, i.p.) in HNS and LNS mice. Then, HNS and LNS mice were pretreated i.p. with vehicle, WIN 55212-2 (0.1 mg/kg), or cannabinoid antagonist rimonabant (1 mg/kg) and were subsequently conditioned with WIN 55212-2 (0.05 mg/kg, i.p.) or cocaine (1 or 6 mg/kg, i.p.). Only HNS mice conditioned with the 0.075 mg/kg dose acquired CPP with WIN 55212-2. Adolescent exposure to this cannabinoid agonist increased the rewarding effects of 1 mg/kg of cocaine in both HNS and LNS mice, and in HNS mice it also increased the reinstating effect of a low dose of cocaine. Our results endorse a role for individual differences such as a higher propensity for sensation-seeking in the development of addiction.

  6. Effects of Cannabinoid Exposure during Adolescence on the Conditioned Rewarding Effects of WIN 55212-2 and Cocaine in Mice: Influence of the Novelty-Seeking Trait

    PubMed Central

    Rodríguez-Arias, M.; Roger-Sánchez, C.; Vilanova, I.; Revert, N.; Manzanedo, C.; Miñarro, J.; Aguilar, M. A.

    2016-01-01

    Adolescent exposure to cannabinoids enhances the behavioural effects of cocaine, and high novelty-seeking trait predicts greater sensitivity to the conditioned place preference (CPP) induced by this drug. Our aim was to evaluate the influence of novelty-seeking on the effects of adolescent cannabinoid exposure. Adolescent male mice were classified as high or low novelty seekers (HNS and LNS) in the hole-board test. First, we evaluated the CPP induced by the cannabinoid agonist WIN 55212-2 (0.05 and 0.075 mg/kg, i.p.) in HNS and LNS mice. Then, HNS and LNS mice were pretreated i.p. with vehicle, WIN 55212-2 (0.1 mg/kg), or cannabinoid antagonist rimonabant (1 mg/kg) and were subsequently conditioned with WIN 55212-2 (0.05 mg/kg, i.p.) or cocaine (1 or 6 mg/kg, i.p.). Only HNS mice conditioned with the 0.075 mg/kg dose acquired CPP with WIN 55212-2. Adolescent exposure to this cannabinoid agonist increased the rewarding effects of 1 mg/kg of cocaine in both HNS and LNS mice, and in HNS mice it also increased the reinstating effect of a low dose of cocaine. Our results endorse a role for individual differences such as a higher propensity for sensation-seeking in the development of addiction. PMID:26881125

  7. The effect of the anabolic steroid, nandrolone, in conditioned place preference and D1 dopamine receptor expression in adolescent and adult mice

    PubMed Central

    Martínez-Rivera, Freddyson J.; Natal-Albelo, Eduardo J.; Martínez, Namyr A.; Orozco-Vega, Roberto A.; Muñiz-Seda, Oscar A.; Barreto-Estrada, Jennifer L.

    2015-01-01

    Adolescents and adults engage in anabolic-androgenic steroid (AAS) misuse seeking their anabolic effects, even though later on, many could develop neuropsychological dependence. Previously, we have shown that nandrolone induces conditioned place preference (CPP) in adult male mice. However, whether nandrolone induces CPP during adolescence remains unknown. In this study, the CPP test was used to determine the rewarding properties of nandrolone (7.5 mg/kg) in adolescent mice. In addition, since D1 dopamine receptors (D1DR) are critical for reward-related processes, the effect of nandrolone on the expression of D1DR in the nucleus accumbens (NAc) was investigated by Western blot analysis. Similar to our previous results, nandrolone induced CPP in adults. However, in adolescents, nandrolone failed to produce place preference. At the molecular level, nandrolone decreased D1DR expression in the NAc only in adult mice. Our data suggest that nandrolone may not be rewarding in adolescents at least during short-term use. The lack of nandrolone rewarding effects in adolescents may be due, in part to differences in D1DR expression during development. PMID:25612844

  8. The effect of the anabolic steroid, nandrolone, in conditioned place preference and D1 dopamine receptor expression in adolescent and adult mice.

    PubMed

    Martínez-Rivera, Freddyson J; Natal-Albelo, Eduardo J; Martínez, Namyr A; Orozco-Vega, Roberto A; Muñiz-Seda, Oscar A; Barreto-Estrada, Jennifer L

    2015-04-01

    Adolescents and adults engage in anabolic-androgenic steroid (AAS) misuse seeking their anabolic effects, even though later on, many could develop neuropsychological dependence. Previously, we have shown that nandrolone induces conditioned place preference (CPP) in adult male mice. However, whether nandrolone induces CPP during adolescence remains unknown. In this study, the CPP test was used to determine the rewarding properties of nandrolone (7.5 mg/kg) in adolescent mice. In addition, since D1 dopamine receptors (D1DR) are critical for reward-related processes, the effect of nandrolone on the expression of D1DR in the nucleus accumbens (NAc) was investigated by Western blot analysis. Similar to our previous results, nandrolone induced CPP in adults. However, in adolescents, nandrolone failed to produce place preference. At the molecular level, nandrolone decreased D1DR expression in the NAc only in adult mice. Our data suggest that nandrolone may not be rewarding in adolescents at least during short-term use. The lack of nandrolone rewarding effects in adolescents may be due, in part to differences in D1DR expression during development.

  9. Combination of neonatal PolyI:C and adolescent phencyclidine treatments is required to induce behavioral abnormalities with overexpression of GLAST in adult mice.

    PubMed

    Hida, Hirotake; Mouri, Akihiro; Ando, Yu; Mori, Kentaro; Mamiya, Takayoshi; Iwamoto, Kunihiro; Ozaki, Norio; Yamada, Kiyofumi; Nabeshima, Toshitaka; Noda, Yukihiro

    2014-01-01

    Cumulative incidences of multiple risk factors are related to pathology of psychiatric disorders. The present study was designed to examine combinative effects of a neonatal immune challenge with adolescent abused substance treatment on the psychological behaviors and molecular expressions in the adult. C57BL/6J mice were neonatally treated, with polyriboinosinic-polyribocytidylic acid (PolyI:C: 5mg/kg) during postnatal days (PD) 2-6, then with phencyclidine (PCP: 10mg/kg) during adolescence (PD35-41). Locomotor activity was analyzed to evaluate sensitivity to PCP on PD35 and PD41. Emotional and cognitive tests were carried out on PD42-48. Neonatal PolyI:C treatment markedly enhanced sensitivity to PCP- and methamphetamine-induced hyperactivity in the adolescent. Mice treated with both neonatal PolyI:C and adolescent PCP (PolyI:C/PCP) showed social deficit and object recognition memory impairment. The expression of glutamate/aspartate transporter (GLAST) in the prefrontal cortex (PFC) was significantly increased in the (PolyI:C/PCP)-treated mice. Infusion of glutamate transporter inhibitor (DL-TBOA: 1 nmol/bilaterally) into the PFC reversed the object recognition impairment in the (PolyI:C/PCP)-treated mice. These results indicate that the combined treatment of neonatal PolyI:C with adolescent PCP leads to behavioral abnormalities, which were associated with increase of GLAST expression in the adult PFC.

  10. A Novel Bufalin Derivative Exhibited Stronger Apoptosis-Inducing Effect than Bufalin in A549 Lung Cancer Cells and Lower Acute Toxicity in Mice

    PubMed Central

    Liu, Miao; Feng, Li-Xing; Sun, Peng; Liu, Wang; Wu, Wan-Ying; Jiang, Bao-Hong; Yang, Min; Hu, Li-Hong; Guo, De-An; Liu, Xuan

    2016-01-01

    BF211 is a synthetic molecule derived from bufalin (BF). The apoptosis-inducing effect of BF211 was stronger than that of BF while the acute toxicity of BF211 was much lower than that of BF. BF211 exhibited promising concentration-dependent anti-cancer effects in nude mice inoculated with A549 cells in vivo. The growth of A549 tumor xenografts was almost totally blocked by treatment with BF211 at 6 mg/kg. Notably, BF and BF211 exhibited differences in their binding affinity and kinetics to recombinant proteins of the α subunits of Na+/K+-ATPase. Furthermore, there was a difference in the effects of BF or BF211 on inhibiting the activity of porcine cortex Na+/K+-ATPase and in their time-dependent effects on intracellular Ca2+ levels in A549 cells. The time-dependent effects of BF or BF211 on the activation of Src, which was mediated by the Na+/K+-ATPase signalosome, in A549 cells were also different. Both BF and BF211 could induce apoptosis-related cascades, such as activation of caspase-3 and the cleavage of PARP (poly ADP-ribose polymerase) in A549 cells, in a concentration-dependent manner; however, the effects of BF211 on apoptosis-related cascades was stronger than that of BF. The results of the present study supported the importance of binding to the Na+/K+-ATPase α subunits in the mechanism of cardiac steroids and also suggested the possibility of developing new cardiac steroids with a stronger anti-cancer activity and lower toxicity as new anti-cancer agents. PMID:27459387

  11. Effects of prenatal stress and exercise on dentate granule cells maturation and spatial memory in adolescent mice.

    PubMed

    Bustamante, Carlos; Bilbao, Pamela; Contreras, William; Martínez, Mauricio; Mendoza, Antonio; Reyes, Alvaro; Pascual, Rodrigo

    2010-11-01

    Exposure to prenatal stress (PS) increases the risk of developing neurobehavioral disturbances later in life. Previous work has shown that exercise can exert beneficial effects on brain damage; however, it is unknown whether voluntary wheel running (VWR) can ameliorate the neurobehavioral impairments induced by PS in adolescent offspring. Pregnant CF-1 mice were randomly assigned to control (n=5) or stressed (n=5) groups. Pregnant dams were subjected to restraint stress between gestational days 14 and 21 (G14-21), whereas controls remained undisturbed in their home cages. On postnatal day 21 (P21), male pups were randomly assigned to the following experimental groups: control (n=5), stressed (n=5), and stressed mice+daily submitted to VWR (n=4). At P52, all groups were behaviorally evaluated in the Morris water maze. Animals were then sacrificed, and Golgi-impregnated granule cells were morphometrically analyzed. The results indicate that PS produced significant behavioral and neuronal impairments in adolescent offspring and that VWR significantly offset these deleterious effects.

  12. Blocking glucocorticoid receptors at adolescent age prevents enhanced freezing between repeated cue-exposures after conditioned fear in adult mice raised under chronic early life stress.

    PubMed

    Arp, J Marit; Ter Horst, Judith P; Loi, Manila; den Blaauwen, Jan; Bangert, Eline; Fernández, Guillén; Joëls, Marian; Oitzl, Melly S; Krugers, Harm J

    2016-09-01

    Early life adversity can have long-lasting impact on learning and memory processes and increase the risk to develop stress-related psychopathologies later in life. In this study we investigated (i) how chronic early life stress (ELS) - elicited by limited nesting and bedding material from postnatal day 2 to 9 - affects conditioned fear in adult mice and (ii) whether these effects can be prevented by blocking glucocorticoid receptors (GRs) at adolescent age. In adult male and female mice, ELS did not affect freezing behavior to the first tone 24h after training in an auditory fear-conditioning paradigm. Exposure to repeated tones 24h after training also resulted in comparable freezing behavior in ELS and control mice, both in males and females. However, male (but not female) ELS compared to control mice showed significantly more freezing behavior between the tone-exposures, i.e. during the cue-off periods. Intraperitoneal administration of the GR antagonist RU38486 during adolescence (on postnatal days 28-30) fully prevented enhanced freezing behavior during the cue-off period in adult ELS males. Western blot analysis revealed no effects of ELS on hippocampal expression of glucocorticoid receptors, neither at postnatal day 28 nor at adult age, when mice were behaviorally tested. We conclude that ELS enhances freezing behavior in adult mice in a potentially safe context after cue-exposure, which can be normalized by brief blockade of glucocorticoid receptors during the critical developmental window of adolescence. PMID:27246249

  13. Exposure to enriched environments during adolescence prevents abnormal behaviours associated with histone deacetylation in phencyclidine-treated mice.

    PubMed

    Koseki, Takenao; Mouri, Akihiro; Mamiya, Takayoshi; Aoyama, Yuki; Toriumi, Kazuya; Suzuki, Shizuka; Nakajima, Azusa; Yamada, Takuma; Nagai, Taku; Nabeshima, Toshitaka

    2012-11-01

    Enriched environments (EEs) during development have been shown to influence adult behaviour. Environmental conditions during childhood may contribute to the onset and/or pathology of schizophrenia; however, it remains unclear whether EE might prevent the development of schizophrenia. Herein, we investigated the effects of EE during adolescence on phencyclidine (PCP)-induced abnormal behaviour, a proposed schizophrenic endophenotype. Male ICR mice (3 wk old) were exposed to an EE for 4 wk and then treated with PCP for 2 wk. The EE potentiated the acute PCP treatment-induced hyperlocomotion in the locomotor test and prevented chronic PCP treatment-induced impairments of social behaviour and recognition memory in the social interaction and novel object recognition tests. It also prevented the PCP-induced decrease of acetylated Lys9 in histone H3-positive cells and increase of the histone deacetylase (HDAC)5 level in the prefrontal cortex. To investigate whether the histone modification during adolescence might be critical for the effect of EE, 3-wk-old mice were first treated with sodium butyrate (SB; an HDAC inhibitor) for 4 wk and then treated with PCP for 2 wk. Chronic SB treatment during adolescence mimicked the effects of EE, including potentiation of hyperlocomotion induced by acute PCP treatment and prevention of social and cognitive impairments, decrease of acetylated Lys9 in histone H3-positive cells and increase of the HDAC5 level in the prefrontal cortex associated with chronic PCP treatment. Our results suggest that EEs prevent PCP-induced abnormal behaviour associated with histone deacetylation. EEs during childhood might prove to be a novel strategy for prophylaxis against schizophrenia.

  14. Sevoflurane Inhalation Accelerates the Long-Term Memory Consolidation via Small GTPase Overexpression in the Hippocampus of Mice in Adolescence.

    PubMed

    Nakamura, Emi; Kinoshita, Hiroyuki; Feng, Guo-Gang; Hayashi, Hisaki; Satomoto, Maiko; Sato, Motohiko; Fujiwara, Yoshihiro

    2016-01-01

    Sevoflurane exposure impairs the long-term memory in neonates. Whether the exposure to animals in adolescence affects the memory, however, has been unclear. A small hydrolase enzyme of guanosine triphosphate (GTPase) rac1 plays a role in the F-actin dynamics related to the synaptic plasticity, as well as superoxide production via reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation. The current study was designed to examine whether sevoflurane exposure to mice in early adolescence modifies the long-term learning ability concomitantly with the changes in F-actin constitution as well as superoxide production in the hippocampus according to the levels of rac1 protein expression. Four-week-old mice were subjected to the evaluation of long-term learning ability for three days. On day one, each mouse was allowed to enter a dark chamber for five min to acclimatization. On day two, the procedure was repeated with the addition of an electric shock as soon as a mouse entered the dark chamber. All mice subsequently inhaled 2 L/min air with (Sevoflurane group) and without (Control group) 2.5% sevoflurane for three hours. On day three, each mouse was placed on the platform and retention time, which is the latency to enter the dark chamber, was examined. The brain removed after the behavior test, was used for analyses of immunofluorescence, Western immunoblotting and intracellular levels of superoxide. Sevoflurane exposure significantly prolonged retention time, indicating the enhanced long-term memory. Sevoflurane inhalation augmented F-actin constitution coexisting with the rac1 protein overexpression in the hippocampus whereas it did not alter the levels of superoxide. Sevoflurane exposure to 4-week-old mice accelerates the long-term memory concomitantly with the enhanced F-actin constitution coexisting with the small GTPase rac1 overexpression in the hippocampus. These results suggest that sevoflurane inhalation may amplify long-term memory

  15. Sevoflurane Inhalation Accelerates the Long-Term Memory Consolidation via Small GTPase Overexpression in the Hippocampus of Mice in Adolescence

    PubMed Central

    Nakamura, Emi; Feng, Guo-Gang; Hayashi, Hisaki; Satomoto, Maiko; Sato, Motohiko; Fujiwara, Yoshihiro

    2016-01-01

    Sevoflurane exposure impairs the long-term memory in neonates. Whether the exposure to animals in adolescence affects the memory, however, has been unclear. A small hydrolase enzyme of guanosine triphosphate (GTPase) rac1 plays a role in the F-actin dynamics related to the synaptic plasticity, as well as superoxide production via reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation. The current study was designed to examine whether sevoflurane exposure to mice in early adolescence modifies the long-term learning ability concomitantly with the changes in F-actin constitution as well as superoxide production in the hippocampus according to the levels of rac1 protein expression. Four-week-old mice were subjected to the evaluation of long-term learning ability for three days. On day one, each mouse was allowed to enter a dark chamber for five min to acclimatization. On day two, the procedure was repeated with the addition of an electric shock as soon as a mouse entered the dark chamber. All mice subsequently inhaled 2 L/min air with (Sevoflurane group) and without (Control group) 2.5% sevoflurane for three hours. On day three, each mouse was placed on the platform and retention time, which is the latency to enter the dark chamber, was examined. The brain removed after the behavior test, was used for analyses of immunofluorescence, Western immunoblotting and intracellular levels of superoxide. Sevoflurane exposure significantly prolonged retention time, indicating the enhanced long-term memory. Sevoflurane inhalation augmented F-actin constitution coexisting with the rac1 protein overexpression in the hippocampus whereas it did not alter the levels of superoxide. Sevoflurane exposure to 4-week-old mice accelerates the long-term memory concomitantly with the enhanced F-actin constitution coexisting with the small GTPase rac1 overexpression in the hippocampus. These results suggest that sevoflurane inhalation may amplify long-term memory

  16. TLR4 elimination prevents synaptic and myelin alterations and long-term cognitive dysfunctions in adolescent mice with intermittent ethanol treatment.

    PubMed

    Montesinos, Jorge; Pascual, María; Pla, Antoni; Maldonado, Concepción; Rodríguez-Arias, Marta; Miñarro, Jose; Guerri, Consuelo

    2015-03-01

    The adolescent brain undergoes important dynamic and plastic cell changes, including overproduction of axons and synapses, followed by rapid pruning along with ongoing axon myelination. These developmental changes make the adolescent brain particularly vulnerable to neurotoxic and behavioral effects of alcohol. Although the mechanisms of these effects are largely unknown, we demonstrated that ethanol by activating innate immune receptors toll-like receptor 4 (TLR4), induces neuroinflammation and brain damage in adult mice. The present study aims to evaluate whether intermittent ethanol treatment in adolescence promotes TLR4-dependent pro-inflammatory processes, leading to myelin and synaptic dysfunctions, and long-term cognitive impairments. Using wild-type (WT) and TLR4-deficient (TLR4-KO) adolescent mice treated intermittently with ethanol (3.0g/kg) for 2weeks, we show that binge-like ethanol treatment activates TLR4 signaling pathways (MAPK, NFκB) leading to the up-regulation of cytokines and pro-inflammatory mediators (COX-2, iNOS, HMGB1), impairing synaptic and myelin protein levels and causing ultrastructural alterations. These changes were associated with long-lasting cognitive dysfunctions in young adult mice, as demonstrated with the object recognition, passive avoidance and olfactory behavior tests. Notably, elimination of TLR4 receptors prevented neuroinflammation along with synaptic and myelin derangements, as well as long-term cognitive alterations. These results support the role of the neuroimmune response and TLR4 signaling in the neurotoxic and behavioral effects of ethanol in adolescence.

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

    PubMed

    Lopez, Marcelo F; Laber, Kathy

    2015-09-01

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

  18. Altered gene expression and spine density in nucleus accumbens of adolescent and adult male mice exposed to emotional and physical stress

    PubMed Central

    Warren, Brandon L; Sial, Omar K.; Alcantara, Lyonna F.; Greenwood, Maria A.; Brewer, Jacob S.; Rozofsky, John P.; Parise, Eric M.; Bolaños-Guzmán, Carlos A.

    2014-01-01

    Stressful early life experiences are implicated in lifelong health. However, little is known about the consequences of emotional or physical stress on neurobiology. Therefore, the following set of experiments was designed to assess changes in transcription and translation of key proteins within the nucleus accumbens (NAc). Male adolescent (postnatal day [PD] 35) or adult (eight-week old) mice were exposed to emotional (ES) or physical stress (PS) using a vicarious social defeat paradigm. Twenty-four hours after the last stress session, we measured levels of specific mRNAs and proteins within the NAc. Spine density was also assessed in separate groups of mice. Exposure to ES or PS disrupted ERK2, reduced transcription of ΔFosB, and had no effect on CREB mRNA. Western blots revealed that exposure to ES or PS decreased ERK2 phosphorylation in adolescents, whereas the same stress regimen increased ERK2 phosphorylation in adults. Exposure to ES or PS had no effect on ΔFosB or CREB phosphorylation. ES and PS increased spine density in the NAc of adolescent-exposed mice, but only exposure to PS increased spine density in adults. Together, these findings demonstrate that exposure to ES or PS is a potent stressor in adolescent and adult mice, and can disturb the integrity of the NAc by altering transcription and translation of important signaling molecules in an age-dependent manner. Furthermore, exposure to ES and PS induces substantial synaptic plasticity of the NAc. PMID:24943326

  19. Effects of adolescent fluoxetine treatment on fear-, anxiety- or stress-related behaviors in C57BL/6J or BALB/cJ mice

    PubMed Central

    Norcross, Maxine; Poonam, Mathur; Enoch, Abigail J.; Karlsson, Rose-Marie; Brigman, Jonathan L.; Cameron, Heather A.; Harvey-White, Judith

    2008-01-01

    Rationale 5-Hydroxytryptamine (5-HT, serotonin) plays a major role in brain ontogeny. Disruption of 5-HT during early postnatal development produces lasting changes in rodent ‘emotion-related’ behaviors. Adverse effects of treatment with serotonin reuptake inhibitor (SRI) antidepressants have been reported in human adolescents. However, the long-term effects of chronic SRI treatment during adolescence in rodents remain unclear. Objectives The objectives of the study are to assess the effects of fluoxetine treatment throughout the adolescent period in measures of fear-, anxiety- and stress-related endpoints in drug-free adults and to examine these effects in two genetic strains of mice differing in baseline stress-and anxiety-related behaviors and sensitivity to SRIs. Materials and methods C57BL/6J and BALB/cJ mice received one of two fluoxetine doses for 4 weeks during adolescence (3–7 weeks old). A separate group of C57BL/6J and BALB/cJ mice received fluoxetine for 4 weeks during adulthood (8–12 weeks old). After a 3-week washout period, mice were tested for anxiety-like behaviors (novel open field, elevated plus-maze), fear conditioning and extinction, and stress-related responses to forced swim, as well as serotonin brain levels. Results Adolescent fluoxetine treatment did not increase adult measures of anxiety-, fear- or stress-related behaviors, or brain serotonin levels. The same duration of treatment in adulthood also had no effects on these measures when tested after a 3-week washout period. Conclusions In clear contrast with emotion-related abnormalities caused by preadolescent fluoxetine treatment or genetic inactivation of fluoxetine’s pharmacological target, the 5-HT transporter, fluoxetine treatment throughout mouse adolescence did not produce detectable, lasting abnormalities in either “high” or “low anxiety” inbred mouse strains. PMID:18594797

  20. Adolescent intake of caffeinated energy drinks does not affect adult alcohol consumption in C57BL/6 and BALB/c mice.

    PubMed

    Robins, Meridith T; DeFriel, Julia N; van Rijn, Richard M

    2016-08-01

    The rise in marketing and mass consumption of energy drink products by adolescents poses a largely unknown risk on adolescent development and drug reward. Yet, with increasing reports of acute health issues present in young adults who ingest large quantities of energy drinks alone or in combination with alcohol, the need to elucidate these potential risks is pressing. Energy drinks contain high levels of caffeine and sucrose; therefore, exposure to energy drinks may lead to changes in drug-related behaviors since caffeine and sucrose consumption activates similar brain pathways engaged by substances of abuse. With a recent study observing that adolescent caffeine consumption increased cocaine sensitivity, we sought to investigate how prolonged energy drink exposure in adolescence alters alcohol use and preference in adulthood. To do so, we utilized three different energy drink exposure paradigms and two strains of male mice (C57BL/6 and BALB/c) to monitor the effect of caffeine exposure via energy drinks in adolescence on adult alcohol intake. These paradigms included two models of volitional consumption of energy drinks or energy drink-like substances and one model of forced consumption of sucrose solutions with different caffeine concentrations. Following adolescent exposure to these solutions, alcohol intake was monitored in a limited-access, two-bottle choice between water and increasing concentrations of alcohol during adulthood. In none of the three models or two strains of mice did we observe that adolescent 'energy drink' consumption or exposure was correlated with changes in adult alcohol intake or preference. While our current preclinical results suggest that exposure to large amounts of caffeine does not alter future alcohol intake, differences in caffeine metabolism between mice and humans need to be considered before translating these results to humans. PMID:27565749

  1. Adolescent intake of caffeinated energy drinks does not affect adult alcohol consumption in C57BL/6 and BALB/c mice.

    PubMed

    Robins, Meridith T; DeFriel, Julia N; van Rijn, Richard M

    2016-08-01

    The rise in marketing and mass consumption of energy drink products by adolescents poses a largely unknown risk on adolescent development and drug reward. Yet, with increasing reports of acute health issues present in young adults who ingest large quantities of energy drinks alone or in combination with alcohol, the need to elucidate these potential risks is pressing. Energy drinks contain high levels of caffeine and sucrose; therefore, exposure to energy drinks may lead to changes in drug-related behaviors since caffeine and sucrose consumption activates similar brain pathways engaged by substances of abuse. With a recent study observing that adolescent caffeine consumption increased cocaine sensitivity, we sought to investigate how prolonged energy drink exposure in adolescence alters alcohol use and preference in adulthood. To do so, we utilized three different energy drink exposure paradigms and two strains of male mice (C57BL/6 and BALB/c) to monitor the effect of caffeine exposure via energy drinks in adolescence on adult alcohol intake. These paradigms included two models of volitional consumption of energy drinks or energy drink-like substances and one model of forced consumption of sucrose solutions with different caffeine concentrations. Following adolescent exposure to these solutions, alcohol intake was monitored in a limited-access, two-bottle choice between water and increasing concentrations of alcohol during adulthood. In none of the three models or two strains of mice did we observe that adolescent 'energy drink' consumption or exposure was correlated with changes in adult alcohol intake or preference. While our current preclinical results suggest that exposure to large amounts of caffeine does not alter future alcohol intake, differences in caffeine metabolism between mice and humans need to be considered before translating these results to humans.

  2. The nuclear receptor Tlx regulates motor, cognitive and anxiety-related behaviours during adolescence and adulthood.

    PubMed

    O'Leary, James D; Kozareva, Danka A; Hueston, Cara M; O'Leary, Olivia F; Cryan, John F; Nolan, Yvonne M

    2016-06-01

    The nuclear receptor Tlx is a key regulator of embryonic and adult hippocampal neurogenesis and has been genetically linked to bipolar disorder. Mice lacking Tlx (Nr2e1(-/-)) display deficits in adult hippocampal neurogenesis and behavioural abnormalities. However, whether Tlx regulates behaviour during adolescence or in a sex-dependent manner remains unexplored. Therefore, we investigated the role of Tlx in a series of behavioural tasks in adolescent male and female mice with a spontaneous deletion of Tlx (Nr2e1(-/-) mice). Testing commenced at adolescence (postnatal day 28) and continued until adulthood (postnatal day 67). Adolescent male and female Nr2e1(-/-) mice were hyperactive in an open field, an effect that persisted in adulthood. Male but not female Nr2e1(-/-) mice exhibited reduced thigmotaxis during adolescence and adulthood. Impairments in rotarod motor performance developed in male and female Nr2e1(-/-) mice at the onset of adulthood. Spontaneous alternation in the Y-maze, a hippocampus-dependent task, was impaired in adolescent but not adult male and female Nr2e1(-/-) mice. Contextual fear conditioning was impaired in adolescent male Nr2e1(-/-) mice only, but both male and female adolescent Nr2e1(-/-) mice showed impaired cued fear conditioning, a hippocampal-amygdala dependent cognitive process. These deficits persisted into adulthood in males but not females. In conclusion, deletion of Tlx impairs motor, cognitive and anxiety-related behaviours during adolescence and adulthood in male and female mice with most effects occurring during adolescence rather than adulthood, independent of housing conditions. This suggests that Tlx has functions beyond regulation of adult hippocampal neurogenesis, and may be an important target in understanding neurobiological disorders.

  3. Face-to-Face Sharing with Strangers and Altruistic Punishment of Acquaintances for Strangers: Young Adolescents Exhibit Greater Altruism than Adults

    PubMed Central

    Hao, Jian; Yang, Yue; Wang, Zhiwen

    2016-01-01

    Young adolescents are generally considered to be self-absorbed. Studies indicate that they lack relevant general cognitive abilities, such as impulse control, that mature in early adulthood. However, their idealism may cause them to be more intolerant of unfair treatment to others and thus result in their engaging in more altruistic behavior. The present study aimed to clarify whether young adolescents are more altruistic than adults and thus indicate whether altruistic competence is domain-specific. One hundred 22 young adolescents and adults participated in a face-to-face, two-round, third-party punishment experiment. In each interaction group, a participant served as an allocator who could share money units with a stranger; another participant who knew the allocator could punish the acquaintance for the stranger. Participants reported their emotions after the first round, and at the end of the experiment, the participants justified their behavior in each round. The results indicated that the young adolescents both shared more and punished more than did the adults. Sharing was associated with a reference to fairness in the justifications, but altruistic punishment was associated with subsequent positive emotion. In sum, greater altruism in young adolescents compared to adults with mature cognitive abilities provides evidence of domain-specificity of altruistic competence. Moreover, sharing and altruistic punishment are related to specific cognitive and emotional mechanisms, respectively. PMID:27752246

  4. Mice Deficient in Glutathione Transferase Zeta/Maleylacetoacetate Isomerase Exhibit a Range of Pathological Changes and Elevated Expression of Alpha, Mu, and Pi Class Glutathione Transferases

    PubMed Central

    Lim, Cindy E.L.; Matthaei, Klaus I.; Blackburn, Anneke C.; Davis, Richard P.; Dahlstrom, Jane E.; Koina, Mark E.; Anders, M.W.; Board, Philip G.

    2004-01-01

    Glutathione transferase zeta (GSTZ1-1) is the major enzyme that catalyzes the metabolism of α-halo acids such as dichloroacetic acid, a carcinogenic contaminant of chlorinated water. GSTZ1-1 is identical with maleylacetoacetate isomerase, which catalyzes the penultimate step in the catabolic pathways for phenylalanine and tyrosine. In this study we have deleted the Gstz1 gene in BALB/c mice and characterized their phenotype. Gstz1−/− mice do not have demonstrable activity with maleylacetone and α-halo acid substrates, and other GSTs do not compensate for the loss of this enzyme. When fed a standard diet, the GSTZ1-1-deficient mice showed enlarged liver and kidneys as well as splenic atrophy. Light and electron microscopic examination revealed multifocal hepatitis and ultrastructural changes in the kidney. The addition of 3% (w/v) phenylalanine to the drinking water was lethal for young mice (<28 days old) and caused liver necrosis, macrovesicular steatosis, splenic atrophy, and a significant loss of circulating leukocytes in older surviving mice. GSTZ1-1-deficient mice showed constitutive induction of alpha, mu, and pi class GSTs as well as NAD(P)H:quinone oxidoreductase 1. The overall response is consistent with the chronic accumulation of a toxic metabolite(s). We detected the accumulation of succinylacetone in the serum of deficient mice but cannot exclude the possibility that maleylacetoacetate and maleylacetone may also accumulate. PMID:15277241

  5. Mice Expressing the A53T Mutant Form of Human Alpha-Synuclein Exhibit Hyperactivity and Reduced Anxiety-Like Behavior

    PubMed Central

    Graham, Dianca R.; Sidhu, Anita

    2010-01-01

    Genetic mutations associated with α-synuclein (α-Syn) are implicated in the pathogenesis of Parkinson’s disease (PD). PD is primarily a movement disorder, but patients are known to experience anxiety and other mood disorders. In this study, we examined the effect of the hA53T mutation during development by analyzing the protein expression of norepinephrine (NET), serotonin (SERT), and dopamine (DAT) transporters in addition to assessing locomotor and anxiety-like behavior. We observed significant decreases in DAT expression at 8 months in transgenic animals compared with normal and younger mice. We used the elevated plus maze, open-field test, and rotarod apparatus to evaluate wild-type and hA53T hemizygous mice at 2, 8, and 12 months of age. Our results showed that 12-month-old transgenic mice spend more time in the open arms and display a greater number of open entries of the elevated plus maze compared with wild-type controls and younger mice. Open-field test results showed that 12-month-old mice travel a greater distance overall and travel more in the inner zone than either wild-type or younger mice. Rotarod testing showed that 8- and 12-month-old transgenic mice perform better than either wild-type controls or younger mice. Overall, 8–12-month-old transgenic mice showed a trend toward reduced anxiety-like behavior and increased hyperactivity. These results indicate a possible role of the A53T α-Syn mutation in anxiety-like and hyperactive behaviors in a PD mouse model, suggesting that these behaviors might be comorbid with this disease. PMID:20077428

  6. Mice expressing the A53T mutant form of human alpha-synuclein exhibit hyperactivity and reduced anxiety-like behavior.

    PubMed

    Graham, Dianca R; Sidhu, Anita

    2010-06-01

    Genetic mutations associated with alpha-synuclein (alpha-Syn) are implicated in the pathogenesis of Parkinson's disease (PD). PD is primarily a movement disorder, but patients are known to experience anxiety and other mood disorders. In this study, we examined the effect of the hA53T mutation during development by analyzing the protein expression of norepinephrine (NET), serotonin (SERT), and dopamine (DAT) transporters in addition to assessing locomotor and anxiety-like behavior. We observed significant decreases in DAT expression at 8 months in transgenic animals compared with normal and younger mice. We used the elevated plus maze, open-field test, and rotarod apparatus to evaluate wild-type and hA53T hemizygous mice at 2, 8, and 12 months of age. Our results showed that 12-month-old transgenic mice spend more time in the open arms and display a greater number of open entries of the elevated plus maze compared with wild-type controls and younger mice. Open-field test results showed that 12-month-old mice travel a greater distance overall and travel more in the inner zone than either wild-type or younger mice. Rotarod testing showed that 8- and 12-month-old transgenic mice perform better than either wild-type controls or younger mice. Overall, 8-12-month-old transgenic mice showed a trend toward reduced anxiety-like behavior and increased hyperactivity. These results indicate a possible role of the A53T alpha-Syn mutation in anxiety-like and hyperactive behaviors in a PD mouse model, suggesting that these behaviors might be comorbid with this disease. PMID:20077428

  7. Orally active opioid μ/δ dual agonist MGM-16, a derivative of the indole alkaloid mitragynine, exhibits potent antiallodynic effect on neuropathic pain in mice.

    PubMed

    Matsumoto, Kenjiro; Narita, Minoru; Muramatsu, Naotaka; Nakayama, Terumi; Misawa, Kaori; Kitajima, Mariko; Tashima, Kimihito; Devi, Lakshmi A; Suzuki, Tsutomu; Takayama, Hiromitsu; Horie, Syunji

    2014-03-01

    (E)-Methyl 2-((2S,3S,7aS,12bS)-3-ethyl-7a-hydroxy-8-methoxy-1,2,3,4,6,7,7a,12b-octahydroindolo[2,3-a]quinolizin-2-yl)-3-methoxyacrylate (7-hydroxymitragynine), a main active constituent of the traditional herbal medicine Mitragyna speciosa, is an indole alkaloid that is structurally different from morphine. 7-Hydroxymitragynine induces a potent antinociceptive effect on mouse acute pain through μ-opioid receptors. In this study, we developed dual-acting μ- and δ-opioid agonists MGM-15 and MGM-16 from 7-hydroxymitragynine for the treatment of acute and chronic pain. MGM-16 showed a higher potency than that of 7-hydroxymitragynine and MGM-15 in in vitro and in vivo assays. MGM-16 exhibited a high affinity for μ- and δ-opioid receptors, with K(i) values of 2.1 and 7.0 nM, respectively. MGM-16 showed μ- and δ-opioid full agonistic effects in a guanosine 5'-O-(3-[(35)S]thiotriphosphate) binding assay and in a functional test using electrically elicited guinea pig ileum and mouse vas deferens contractions. Systemic administration of MGM-16 produced antinociceptive effects in a mouse acute pain model and antiallodynic effects in a chronic pain model. The antinociceptive effect of MGM-16 was approximately 240 times more potent than that of morphine in a mouse tail-flick test, and its antiallodynic effect was approximately 100 times more potent than that of gabapentin in partial sciatic nerve-ligated mice, especially with oral administration. The antinociceptive effect of MGM-16 was completely and partially blocked by the μ-selective antagonist β-funaltrexamine hydrochloride (β-FNA) and by the δ-selective antagonist naltrindole, respectively, in a tail-flick test. The antiallodynic effect of MGM-16 was completely blocked by β-FNA and naltrindole in a neuropathic pain model. These findings suggest that MGM-16 could become a class of a compound with potential therapeutic utility for treating neuropathic pain. PMID:24345467

  8. Phasic dopamine neuron activity elicits unique mesofrontal plasticity in adolescence.

    PubMed

    Mastwal, Surjeet; Ye, Yizhou; Ren, Ming; Jimenez, Dennisse V; Martinowich, Keri; Gerfen, Charles R; Wang, Kuan Hong

    2014-07-16

    The mesofrontal dopaminergic circuit, which connects the midbrain motivation center to the cortical executive center, is engaged in control of motivated behaviors. In addition, deficiencies in this circuit are associated with adolescent-onset psychiatric disorders in humans. Developmental studies suggest that the mesofrontal circuit exhibits a protracted maturation through adolescence. However, whether the structure and function of this circuit are modifiable by activity in dopaminergic neurons during adolescence remains unknown. Using optogenetic stimulation and in vivo two-photon imaging in adolescent mice, we found that phasic, but not tonic, dopamine neuron activity induces the formation of mesofrontal axonal boutons. In contrast, in adult mice, the effect of phasic activity diminishes. Furthermore, our results showed that dopaminergic and glutamatergic transmission regulate this axonal plasticity in adolescence and inhibition of dopamine D2-type receptors restores this plasticity in adulthood. Finally, we found that phasic activation of dopamine neurons also induces greater changes in mesofrontal circuit activity and psychomotor response in adolescent mice than in adult mice. Together, our findings demonstrate that the structure and function of the mesofrontal circuit are modifiable by phasic activity in dopaminergic neurons during adolescence and suggest that the greater plasticity in adolescence may facilitate activity-dependent strengthening of dopaminergic input and improvement in behavioral control.

  9. IL-12p40 gene-deficient BALB/c mice exhibit lower weight loss, reduced lung pathology and decreased sensitization to allergen in response to infection with pneumonia virus of mice.

    PubMed

    Shrivastava, Pratima; Sarkar, Indranil; Atanley, Ethel; Gomis, Susantha; van Drunen Littel-van den Hurk, Sylvia

    2016-10-01

    Respiratory syncytial virus (RSV) is a major cause of bronchiolitis and pneumonia in infants and pneumonia virus of mice (PVM) causes similar disease. BALB/c mice are highly susceptible, while C57BL/6 mice are more resistant to PVM. IL-12 was significantly more up-regulated in response to PVM infection in BALB/c than in C57BL/6 mice. IL-12p40-deficient neonatal and adult BALB/c mice showed significantly less weight loss than wild-type mice after PVM challenge. The percentage of regulatory T cells, as well as IFN-β and IL-18 expression, was higher in the lungs of both neonatal and adult IL-12p40-/- mice. Adult IL-12p40-/- mice also showed enhanced TGF-β and IL-10 expression and reduced inflammatory responses. Furthermore, IL-12p40-/- mice showed decreased sensitization to inhaled cockroach antigen after PVM infection when compared to wild-type mice. In conclusion, these data suggest that a depressed regulatory capacity in BALB/c mice to PVM infection results in enhanced immunopathology and sensitization to allergen. PMID:27400340

  10. Unique Behavioral and Neurochemical Effects Induced by Repeated Adolescent Consumption of Caffeine-Mixed Alcohol in C57BL/6 Mice

    PubMed Central

    Robins, Meridith T.; Lu, Julie

    2016-01-01

    The number of highly caffeinated products has increased dramatically in the past few years. Among these products, highly caffeinated energy drinks are the most heavily advertised and purchased, which has resulted in increased incidences of co-consumption of energy drinks with alcohol. Despite the growing number of adolescents and young adults reporting caffeine-mixed alcohol use, knowledge of the potential consequences associated with co-consumption has been limited to survey-based results and in-laboratory human behavioral testing. Here, we investigate the effect of repeated adolescent (post-natal days P35-61) exposure to caffeine-mixed alcohol in C57BL/6 mice on common drug-related behaviors such as locomotor sensitivity, drug reward and cross-sensitivity, and natural reward. To determine changes in neurological activity resulting from adolescent exposure, we monitored changes in expression of the transcription factor ΔFosB in the dopaminergic reward pathway as a sign of long-term increases in neuronal activity. Repeated adolescent exposure to caffeine-mixed alcohol exposure induced significant locomotor sensitization, desensitized cocaine conditioned place preference, decreased cocaine locomotor cross-sensitivity, and increased natural reward consumption. We also observed increased accumulation of ΔFosB in the nucleus accumbens following repeated adolescent caffeine-mixed alcohol exposure compared to alcohol or caffeine alone. Using our exposure model, we found that repeated exposure to caffeine-mixed alcohol during adolescence causes unique behavioral and neurochemical effects not observed in mice exposed to caffeine or alcohol alone. Based on similar findings for different substances of abuse, it is possible that repeated exposure to caffeine-mixed alcohol during adolescence could potentially alter or escalate future substance abuse as means to compensate for these behavioral and neurochemical alterations. PMID:27380261

  11. Unique Behavioral and Neurochemical Effects Induced by Repeated Adolescent Consumption of Caffeine-Mixed Alcohol in C57BL/6 Mice.

    PubMed

    Robins, Meridith T; Lu, Julie; van Rijn, Richard M

    2016-01-01

    The number of highly caffeinated products has increased dramatically in the past few years. Among these products, highly caffeinated energy drinks are the most heavily advertised and purchased, which has resulted in increased incidences of co-consumption of energy drinks with alcohol. Despite the growing number of adolescents and young adults reporting caffeine-mixed alcohol use, knowledge of the potential consequences associated with co-consumption has been limited to survey-based results and in-laboratory human behavioral testing. Here, we investigate the effect of repeated adolescent (post-natal days P35-61) exposure to caffeine-mixed alcohol in C57BL/6 mice on common drug-related behaviors such as locomotor sensitivity, drug reward and cross-sensitivity, and natural reward. To determine changes in neurological activity resulting from adolescent exposure, we monitored changes in expression of the transcription factor ΔFosB in the dopaminergic reward pathway as a sign of long-term increases in neuronal activity. Repeated adolescent exposure to caffeine-mixed alcohol exposure induced significant locomotor sensitization, desensitized cocaine conditioned place preference, decreased cocaine locomotor cross-sensitivity, and increased natural reward consumption. We also observed increased accumulation of ΔFosB in the nucleus accumbens following repeated adolescent caffeine-mixed alcohol exposure compared to alcohol or caffeine alone. Using our exposure model, we found that repeated exposure to caffeine-mixed alcohol during adolescence causes unique behavioral and neurochemical effects not observed in mice exposed to caffeine or alcohol alone. Based on similar findings for different substances of abuse, it is possible that repeated exposure to caffeine-mixed alcohol during adolescence could potentially alter or escalate future substance abuse as means to compensate for these behavioral and neurochemical alterations. PMID:27380261

  12. Disabled-2 heterozygous mice are predisposed to endometrial and ovarian tumorigenesis and exhibit sex-biased embryonic lethality in a p53-null background.

    PubMed

    Yang, Dong-Hua; Fazili, Zia; Smith, Elizabeth R; Cai, Kathy Qi; Klein-Szanto, Andres; Cohen, Cynthia; Horowitz, Ira R; Xu, Xiang-Xi

    2006-07-01

    Disabled-2 (Dab2) is a phosphoprotein involved in cellular signal transduction and endocytic trafficking. The expression of Dab2 is frequently lost or suppressed in several epithelial tumors, and studies of its cellular function and growth suppressive activity when re-expressed in cancer cells led to the suggestion that Dab2 is a tumor suppressor. A role for Dab2 in epithelial cell positioning organization was derived from study of knockout mice: homozygous deletion of dab2 results in early embryonic lethality due to the disorganization of the primitive endoderm, the first epithelium in early embryos. We now report that dab2 heterozygous mice develop uterine hyperplasia and ovarian preneoplastic morphological changes at a high frequency. Crossing into a p53(-/-) background unexpectedly produced few female dab2(+/-):p53(-/-) mice, while the male dab2(+/-):p53(-/-) were born at the expected Mendelian frequency. The tumor-prone phenotype of dab2(+/-) mice provides additional support for a role of human Dab2 as a tumor suppressor, and the sex-biased embryonic lethality suggests a genetic interaction between p53 and dab2 genes in female mice. PMID:16816378

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

    PubMed

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

    2011-11-01

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

  14. Tankyrase 2 Poly(ADP-Ribose) Polymerase Domain-Deleted Mice Exhibit Growth Defects but Have Normal Telomere Length and Capping

    SciTech Connect

    Hsiao, Susan J; Poitras, Marc; Cook, Brandoch; Liu, Yie; Smith, Susan

    2006-03-01

    Regulation of telomere length maintenance and capping are a critical cell functions in both normal and tumor cells. Tankyrase 2 (Tnks2) is a poly(ADP-ribose) polymerase (PARP) that has been shown to modify itself and TRF1, a telomere-binding protein. We show here by overexpression studies that tankyrase 2, like its closely related homolog tankyrase 1, can function as a positive regulator of telomere length in human cells, dependent on its catalytic PARP activity. To study the role of Tnks2 in vivo, we generated mice with the Tnks2 PARP domain deleted. These mice are viable and fertile but display a growth retardation phenotype. Telomere analysis by quantitative fluorescence in situ hybridization (FISH), flow-FISH, and restriction fragment analysis showed no change in telomere length or telomere capping in these mice. To determine the requirement foTnks2 in long-term maintenance of telomeres, we generated embryonic stem cells with the Tnks2 PARP domain deleted and observed no change, even upon prolonged growth, in telomere length or telomere capping. Together these results suggest that Tnkjs2 has a role in normal growth and development but is not essential for telomere length maintenance or telomere capping in mice.

  15. Transgenic Mice Expressing a Truncated Form of CREB-Binding Protein (CBP) Exhibit Deficits in Hippocampal Synaptic Plasticity and Memory Storage

    ERIC Educational Resources Information Center

    Wood, Marcelo A.; Kaplan, Michael P.; Park, Alice; Blanchard, Edward J.; Oliveira, Ana M. M.; Lombardi, Thomas L.; Abel, Ted

    2005-01-01

    Deletions, translocations, or point mutations in the CREB-binding protein (CBP) gene have been associated with Rubinstein-Taybi Syndrome; a human developmental disorder characterized by retarded growth and reduced mental function. To examine the role of CBP in memory, transgenic mice were generated in which the CaMKII[alpha] promoter drives…

  16. Brain-Derived Neurotrophic Factor Transgenic Mice Exhibit Passive Avoidance Deficits, Increased Seizure Severity and In Vitro Hyperexcitability in the Hippocampus and Entorhinal Cortex

    PubMed Central

    Croll, S. D.; Suri, C.; Compton, D. L.; Simmons, M. V.; Yancopoulos, G. D.; Lindsay, R. M.; Wiegand, S. J.; Rudge, J. S.; Scharfman, H. E.

    2008-01-01

    Transgenic mice overexpressing brain-derived neurotrophic factor from the β-actin promoter were tested for behavioral, gross anatomical and physiological abnormalities. Brain-derived neurotrophic factor messenger RNA overexpression was widespread throughout brain. Overexpression declined with age, such that levels of overexpression decreased sharply by nine months. Brain-derived neurotrophic factor transgenic mice had no gross deformities or behavioral abnormalities. However, they showed a significant passive avoidance deficit. This deficit was dependent on continued overexpression, and resolved with age as brain-derived neurotrophic factor transcripts decreased. In addition, the brain-derived neurotrophic factor transgenic mice showed increased seizure severity in response to kainic acid. Hippocampal slices from brain-derived neurotrophic factor transgenic mice showed hyperexcitability in area CA3 and entorhinal cortex, but not in dentate gyrus. Finally, area CA1 long-term potentiation was disrupted, indicating abnormal plasticity. Our data suggest that overexpression of brain-derived neurotrophic factor in the brain can interfere with normal brain function by causing learning impairments and increased excitability. The results also support the hypothesis that excess brain-derived neurotrophic factor could be pro-convulsant in the limbic system. PMID:10501474

  17. Young APOE[subscript 4] Targeted Replacement Mice Exhibit Poor Spatial Learning and Memory, with Reduced Dendritic Spine Density in the Medial Entorhinal Cortex

    ERIC Educational Resources Information Center

    Rodriguez, Gustavo A.; Burns, Mark P.; Weeber, Edwin J.; Rebeck, G. William

    2013-01-01

    The apolipoprotein E4 ("APOE-[epsilon]4") allele is the strongest genetic risk factor for developing late-onset Alzheimer's disease, and may predispose individuals to Alzheimer's-related cognitive decline by affecting normal brain function early in life. To investigate the impact of human APOE alleles on cognitive performance in mice, we trained…

  18. Platycarya strobilacea S. et Z. Extract Has a High Antioxidant Capacity and Exhibits Hair Growth-promoting Effects in Male C57BL/6 Mice.

    PubMed

    Kim, Eun Jin; Choi, Joo Yeon; Park, Byung Cheol; Lee, Bog-Hieu

    2014-09-01

    This study was conducted to evaluate the effects of Platycarya strobilacea S. et Z. (PSE) extract on mouse hair growth and to determine the mechanism of action of PSE. PSE was purchased and its antioxidant activities, such as electron donating ability, total polyphenol content, and flavonoid content were tested. Toxicity during topical treatment was determined by the CCK-8 assay, a cell viability test. Fifteen 4-week-old male C57BL/6 mice were assigned to receive one of three treatments: dimethyl sulfoxide (negative control), minoxidil (positive control) or PSE. Test materials were topically applied to the shaved dorsal skin of each mouse daily for 3 weeks. After 21 days, we observed skin tissue hair follicle morphology and length, mast cell number, and stem cell factor (SCF) expression using hematoxylin and eosin (H&E), toluidine blue, and immunohistochemical staining, respectively. Furthermore, the expression of cytokines involved in hair growth [i.e., insulin-like growth factor (IGF)-1, keratinocyte growth factor (KGF), and transforming growth factor (TGF)-β1] was determined by PCR. PSE was found to have very high antioxidant activity. The cell viability rate of PSE-treated mice was markedly higher than that of mice in the control group. We also observed an increase in hair follicle length, strong SCF staining, and a decrease in mast cell number in the PSE group. In addition, PSE-treated mice had higher IGF-1 and KGF expression and lower TGF-β1 expression than mice in the minoxidil-treated group. These results suggest that topical application of PSE promotes hair growth by intensifying SCF, suppressing mast cell production, and increasing hair growth-promoting cytokine expression. PMID:25320710

  19. Platycarya strobilacea S. et Z. Extract Has a High Antioxidant Capacity and Exhibits Hair Growth-promoting Effects in Male C57BL/6 Mice

    PubMed Central

    Kim, Eun Jin; Choi, Joo Yeon; Park, Byung Cheol; Lee, Bog-Hieu

    2014-01-01

    This study was conducted to evaluate the effects of Platycarya strobilacea S. et Z. (PSE) extract on mouse hair growth and to determine the mechanism of action of PSE. PSE was purchased and its antioxidant activities, such as electron donating ability, total polyphenol content, and flavonoid content were tested. Toxicity during topical treatment was determined by the CCK-8 assay, a cell viability test. Fifteen 4-week-old male C57BL/6 mice were assigned to receive one of three treatments: dimethyl sulfoxide (negative control), minoxidil (positive control) or PSE. Test materials were topically applied to the shaved dorsal skin of each mouse daily for 3 weeks. After 21 days, we observed skin tissue hair follicle morphology and length, mast cell number, and stem cell factor (SCF) expression using hematoxylin and eosin (H&E), toluidine blue, and immunohistochemical staining, respectively. Furthermore, the expression of cytokines involved in hair growth [i.e., insulin-like growth factor (IGF)-1, keratinocyte growth factor (KGF), and transforming growth factor (TGF)-β1] was determined by PCR. PSE was found to have very high antioxidant activity. The cell viability rate of PSE-treated mice was markedly higher than that of mice in the control group. We also observed an increase in hair follicle length, strong SCF staining, and a decrease in mast cell number in the PSE group. In addition, PSE-treated mice had higher IGF-1 and KGF expression and lower TGF-β1 expression than mice in the minoxidil-treated group. These results suggest that topical application of PSE promotes hair growth by intensifying SCF, suppressing mast cell production, and increasing hair growth-promoting cytokine expression. PMID:25320710

  20. Outdoor Exhibits

    NASA Technical Reports Server (NTRS)

    1996-01-01

    The National Data Buoy Center (NDBC) at the John C. Stennis Space Center has exhibits located in front of the Visitors Center. These boat-shaped buoys are moored in areas of the ocean that experience hostile environmental conditions. The instruments installed gather information and relay it to the National Weather Service by satellite. Nomad buoys are 20 feet long and weigh 13,900 pounds. They provide information on wind speed and direction, humidity levels, air and sea surface temperature and air pressure. U.S. Coast Guard ships transport buoys to their mooring sites.

  1. Adolescent mice show anxiety- and aggressive-like behavior and the reduction of long-term potentiation in mossy fiber-CA3 synapses after neonatal maternal separation.

    PubMed

    Shin, S Y; Han, S H; Woo, R-S; Jang, S H; Min, S S

    2016-03-01

    Exposure to maternal separation (MS) during early life is an identified risk factor for emotional disorders such as anxiety and depression later in life. This study investigated the effects of neonatal MS on the behavior and long-term potentiation (LTP) as well as basic synaptic transmission at hippocampal CA3-CA1 and mossy fiber (MF)-CA3 synapses in adolescent mice for 19days. When mice were adolescents, we measured depression, learning, memory, anxious and aggressive behavior using the forced swimming test (FST), Y-maze, Morris water maze (MWM), elevated plus maze (EPM), three consecutive days of the open field test, the social interaction test, the tube-dominance test and the resident-intruder test. The results showed that there was no difference in FST, Y-maze, and MWM performance. However, MS mice showed more anxiety-like behavior in the EPM test and aggressive-like behavior in the tube-dominance and resident-intruder tests. In addition, the magnitude of LTP and release probability in the MF-CA3 synapses was reduced in the MS group but not in the CA3-CA1 synapse. Our results indicate that early life stress due to MS may induce anxiety- and aggressive-like behavior during adolescence, and these effects are associated with synaptic plasticity at the hippocampal MF-CA3 synapses.

  2. Acute alcohol exposure during neurulation: Behavioral and brain structural consequences in adolescent C57BL/6J mice.

    PubMed

    Fish, E W; Holloway, H T; Rumple, A; Baker, L K; Wieczorek, L A; Moy, S S; Paniagua, B; Parnell, S E

    2016-09-15

    Prenatal alcohol exposure (PAE) can induce physical malformations and behavioral abnormalities that depend in part on thedevelopmental timing of alcohol exposure. The current studies employed a mouse FASD model to characterize the long-term behavioral and brain structural consequences of a binge-like alcohol exposure during neurulation; a first-trimester stage when women are typically unaware that they are pregnant. Time-mated C57BL/6J female mice were administered two alcohol doses (2.8g/kg, four hours apart) or vehicle starting at gestational day 8.0. Male and female adolescent offspring (postnatal day 28-45) were then examined for motor activity (open field and elevated plus maze), coordination (rotarod), spatial learning and memory (Morris water maze), sensory motor gating (acoustic startle and prepulse inhibition), sociability (three-chambered social test), and nociceptive responses (hot plate). Regional brain volumes and shapes were determined using magnetic resonance imaging. In males, PAE increased activity on the elevated plus maze and reduced social novelty preference, while in females PAE increased exploratory behavior in the open field and transiently impaired rotarod performance. In both males and females, PAE modestly impaired Morris water maze performance and decreased the latency to respond on the hot plate. There were no brain volume differences; however, significant shape differences were found in the cerebellum, hypothalamus, striatum, and corpus callosum. These results demonstrate that alcohol exposure during neurulation can have functional consequences into adolescence, even in the absence of significant brain regional volumetric changes. However, PAE-induced regional shape changes provide evidence for persistent brain alterations and suggest alternative clinical diagnostic markers.

  3. Acute alcohol exposure during neurulation: Behavioral and brain structural consequences in adolescent C57BL/6J mice.

    PubMed

    Fish, E W; Holloway, H T; Rumple, A; Baker, L K; Wieczorek, L A; Moy, S S; Paniagua, B; Parnell, S E

    2016-09-15

    Prenatal alcohol exposure (PAE) can induce physical malformations and behavioral abnormalities that depend in part on thedevelopmental timing of alcohol exposure. The current studies employed a mouse FASD model to characterize the long-term behavioral and brain structural consequences of a binge-like alcohol exposure during neurulation; a first-trimester stage when women are typically unaware that they are pregnant. Time-mated C57BL/6J female mice were administered two alcohol doses (2.8g/kg, four hours apart) or vehicle starting at gestational day 8.0. Male and female adolescent offspring (postnatal day 28-45) were then examined for motor activity (open field and elevated plus maze), coordination (rotarod), spatial learning and memory (Morris water maze), sensory motor gating (acoustic startle and prepulse inhibition), sociability (three-chambered social test), and nociceptive responses (hot plate). Regional brain volumes and shapes were determined using magnetic resonance imaging. In males, PAE increased activity on the elevated plus maze and reduced social novelty preference, while in females PAE increased exploratory behavior in the open field and transiently impaired rotarod performance. In both males and females, PAE modestly impaired Morris water maze performance and decreased the latency to respond on the hot plate. There were no brain volume differences; however, significant shape differences were found in the cerebellum, hypothalamus, striatum, and corpus callosum. These results demonstrate that alcohol exposure during neurulation can have functional consequences into adolescence, even in the absence of significant brain regional volumetric changes. However, PAE-induced regional shape changes provide evidence for persistent brain alterations and suggest alternative clinical diagnostic markers. PMID:27185739

  4. Synthesized Peptides from Yam Dioscorin Hydrolysis in Silico Exhibit Dipeptidyl Peptidase-IV Inhibitory Activities and Oral Glucose Tolerance Improvements in Normal Mice.

    PubMed

    Lin, Yin-Shiou; Han, Chuan-Hsiao; Lin, Shyr-Yi; Hou, Wen-Chi

    2016-08-24

    RRDY, RL, and DPF were the top 3 of 21 peptides for inhibitions against dipeptidyl peptidase-IV (DPP-IV) from the pepsin hydrolysis of yam dioscorin in silico and were further investigated in a proof-of-concept study in normal ICR mice for regulating glucose metabolism by the oral glucose tolerance test (OGTT). The sample or sitagliptin (positive control) was orally administered by a feeding gauge; 30 min later, the glucose loads (2.5 g/kg) were performed. RRDY, yam dioscorin, or sitagliptin preload, but not DPF, lowered the area under the curve (AUC0-120) of blood glucose and DPP-IV activity and elevated the AUC0-120 of blood insulin, which showed significant differences compared to control (P < 0.05 or 0.001). These results suggested that RRDY and yam dioscorin might be beneficial in glycemic control in normal mice and need further investigations in diabetic animal models. PMID:27499387

  5. Mice Deficient in Cryptochrome 1 (Cry1−/−) Exhibit Resistance to Obesity Induced by a High-Fat Diet

    PubMed Central

    Griebel, Guy; Ravinet-Trillou, Christine; Beeské, Sandra; Avenet, Patrick; Pichat, Philippe

    2014-01-01

    Disruption of circadian clock enhances the risk of metabolic syndrome, obesity, and type 2 diabetes. Circadian clocks rely on a highly regulated network of transcriptional and translational loops that drive clock-controlled gene expression. Among these transcribed clock genes are cryptochrome (CRY) family members, which comprise Cry1 and Cry2. While the metabolic effects of deletion of several core components of the clock gene machinery have been well characterized, those of selective inactivation of Cry1 or Cry2 genes have not been described. In this study, we demonstrate that ablation of Cry1, but not Cry2, prevents high-fat diet (HFD)-induced obesity in mice. Despite similar caloric intake, Cry1−/− mice on HFD gained markedly less weight (−18%) at the end of the 16-week experiment and displayed reduced fat accumulation compared to wild-type (WT) littermates (−61%), suggesting increased energy expenditure. Analysis of serum lipid and glucose profiles showed no difference between Cry1−/− and WT mice. Both Cry1−/− and Cry2−/− mice are indistinguishable from WT controls in body weight, fat and protein contents, and food consumption when they are allowed unlimited access to a standard rodent diet. We conclude that although CRY signaling may not be essential for the maintenance of energy homeostasis under steady-state nutritional conditions, Cry1 may play a role in readjusting energy balance under changing nutritional circumstances. These studies reinforce the important role of circadian clock genes in energy homeostasis and suggest that Cry1 is a plausible target for anti-obesity therapy. PMID:24782829

  6. Arabidopsis thaliana plants expressing Rift Valley fever virus antigens: Mice exhibit systemic immune responses as the result of oral administration of the transgenic plants.

    PubMed

    Kalbina, Irina; Lagerqvist, Nina; Moiane, Bélisario; Ahlm, Clas; Andersson, Sören; Strid, Åke; Falk, Kerstin I

    2016-11-01

    The zoonotic Rift Valley fever virus affects livestock and humans in Africa and on the Arabian Peninsula. The economic impact of this pathogen due to livestock losses, as well as its relevance to public health, underscores the importance of developing effective and easily distributed vaccines. Vaccines that can be delivered orally are of particular interest. Here, we report the expression in transformed plants (Arabidopsis thaliana) of Rift Valley fever virus antigens. The antigens used in this study were the N protein and a deletion mutant of the Gn glycoprotein. Transformed lines were analysed for specific mRNA and protein content by RT-PCR and Western blotting, respectively. Furthermore, the plant-expressed antigens were evaluated for their immunogenicity in mice fed the transgenic plants. After oral intake of fresh transgenic plant material, a proportion of the mice elicited specific IgG antibody responses, as compared to the control animals that were fed wild-type plants and of which none sero-converted. Thus, we show that transgenic plants can be readily used to express and produce Rift Valley Fever virus proteins, and that the plants are immunogenic when given orally to mice. These are promising findings and provide a basis for further studies on edible plant vaccines against the Rift Valley fever virus.

  7. Reduced Excitatory Neurotransmission and Mild Autism-Relevant Phenotypes in Adolescent Shank3 Null Mutant Mice

    PubMed Central

    Yang, Mu; Bozdagi, Ozlem; Scattoni, Maria Luisa; Wöhr, Markus; Roullet, Florence I.; Katz, Adam M.; Abrams, Danielle N.; Kalikhman, David; Simon, Harrison; Woldeyohannes, Leuk; Zhang, James Y.; Harris, Mark J.; Saxena, Roheeni; Silverman, Jill L.; Buxbaum, Joseph D.; Crawley, Jacqueline N.

    2012-01-01

    Mutations in the synaptic scaffolding protein gene SHANK3 are strongly implicated in autism and Phelan-McDermid 22q13 deletion syndrome. The precise location of the mutation within the Shank3 gene is key to its phenotypic outcomes. Here we report the physiological and behavioral consequences of null and heterozygous mutations in the ankyrin repeat domain in Shank3 mice. Both homozygous and heterozygous mice showed reduced glutamatergic transmission and long-term potentiation in the hippocampus with more severe deficits detected in the homozygous mice. Three independent cohorts were evaluated for magnitude and replicability of behavioral endophenotypes relevant to autism and Phelan-McDermid syndrome. Mild social impairments were detected, primarily in juveniles during reciprocal interactions, while all genotypes displayed normal adult sociability on the three-chambered task. Impaired novel object recognition and rotarod performance were consistent across cohorts of null mutants. Repetitive self-grooming, reduced ultrasonic vocalizations, and deficits in reversal of water maze learning were detected only in some cohorts, emphasizing the importance of replication analyses. These results demonstrate the exquisite specificity of deletions in discrete domains within the Shank3 gene in determining severity of symptoms. PMID:22573675

  8. Beta 2-microglobulin-, CD8+ T-cell-deficient mice survive inoculation with high doses of vaccinia virus and exhibit altered IgG responses.

    PubMed Central

    Spriggs, M K; Koller, B H; Sato, T; Morrissey, P J; Fanslow, W C; Smithies, O; Voice, R F; Widmer, M B; Maliszewski, C R

    1992-01-01

    Transgenic mice lacking an intact beta 2-microglobulin (beta 2m) gene fail to express major histocompatibility complex (MHC) class I proteins on the cell surface and, as a result, are virtually devoid of CD4- CD8+ lymphocytes. These animals provide a unique model system for directly assessing the role of CD8+ lymphocytes in the modulation of viral infection in vivo. beta 2m- CD8- mice and their normal littermates were inoculated at the base of the tail with the WR strain of vaccinia virus and monitored for serum antibody and lesion formation. Both groups developed similar lesions in response to a broad virus dose range, and all animals had completely recovered by day 28 after inoculation. Isotype-specific immunoglobulin levels were determined for each animal on day 7 and day 14 after primary inoculation, and again 7 days after a virus challenge. The virus-specific IgG1, IgG2a, and IgG2b levels were significantly different in the beta 2m-/- group (20-, 9-, and 30-fold lower, respectively, on day 7 after challenge) compared with the beta 2m+/- group. Virus-specific serum IgM levels for both groups remained similar throughout the experiment. In a separate experiment, beta 2m-/- mice were immunized with a nonviral antigen, 2,4,6-trinitrophenyl-conjugated keyhole limpet hemocyanin, and both total and antigen-specific isotype-specific immunoglobulin titers were determined. Total IgG1, IgG2a, IgG2b, and IgG3 tended to be lower overall in the beta 2m-/- mice compared with beta 2m+/- littermates. In contrast, total and antigen-specific IgE titers were similar in the two groups. These data indicate that CD8+ lymphocytes are not required to clear high doses of vaccinia virus, and they suggest that beta 2m-/- mice are less efficient at antigen-specific IgG production than their beta 2m+/- littermates. PMID:1631092

  9. Long-term, low-level adolescent nicotine exposure produces dose-dependent changes in cocaine sensitivity and reward in adult mice.

    PubMed

    Kelley, Brian M; Rowan, James D

    2004-01-01

    Cigarette smoking by adolescents is a strong predictor of future drug use, abuse, and dependence. While this "gateway drug effect" is assumed to be related to psychosocial factors, data from our laboratory suggests that adolescent nicotine use may permanently disrupt reward systems through changes in dopamine receptor function. Behavioral pharmacological methods known to be indirectly (motor activity) and directly (conditioned-place-preference) related to drug reinforcement were used to examine changes in cocaine sensitivity. Testing was performed on adult mice that were exposed to nicotine (0.3, 1.0, and 3.0 mg/kg, SC, M-F, b.i.d.) or saline during adolescence (postnatal days 25-57). Prior to testing, subjects had a 28 day drug-free, time-off period. After acclimation to the testing apparatus, the locomotor effects (30 min, 30 cm traveled) of cocaine (5, 10, and 20 mg/kg, IP) were measured daily; cocaine tests were preceded and followed by saline control tests. Following the acute dose-response curve, mice received saline followed by 5 days of 20.0 mg/kg cocaine. Thereafter, mice underwent condition-place-preference testing. A pre-test was performed to determine compartment preference (i.e., no injection, 20 min test). Cocaine (10 mg/kg, IP) was paired with the subjects non-preferred side and saline with the other. Conditioning sessions were conducted for 8 days with the order of drug/saline injections counter-balanced across subjects. A drug-free, post-test occurred on the day following the final conditioning session. A dose-dependent relationship between adolescent nicotine exposure and cocaine reward was noted in the adult mice across both test conditions. Subjects exposed to nicotine showed an increased response to cocaine's motor activating effects and a decreased response to cocaine's rewarding effects. A follow-up study was undertaken to evaluate dopamine D1, D2, and D3 receptor function in adult mice exposed to the highest dose of nicotine from the first

  10. Effects of one- and three-day binge alcohol exposure in neonatal C57BL/6 mice on spatial learning and memory in adolescence and adulthood.

    PubMed

    Wagner, Jennifer L; Zhou, Feng C; Goodlett, Charles R

    2014-03-01

    Binge-like alcohol exposure during the early postnatal period in rats and mice causes deficits in spatial learning and memory that persist into adulthood. Wozniak et al. (2004) reported that heavy binge alcohol exposure on postnatal day 7 (PD 7) in C57BL/6 (B6) mice produced profound spatial learning deficits in the Morris water maze when tested in adolescence (P30-39); when tested in adulthood, however, the deficits were greatly attenuated. Using a similar PD 7 binge alcohol exposure paradigm in B6 mice, we tested whether a single-day (PD 7 only) alcohol treatment produced place learning deficits in both adolescence and in adulthood, and further tested whether a more extended (3-day, PD 7-9) alcohol exposure would induce more severe and enduring deficits. B6 mice were given either 2 subcutaneous injections of alcohol (2.5 g/kg each) 2 h apart on PD 7 or on PD 7-9, and compared with controls that received saline vehicle injections and controls that received no injections. The alcohol injections on PD 7 produced average peak blood alcohol concentrations of 472 mg/dL and evoked typical patterns of activated caspase-3-positive neurons in the cortex, hippocampal formation, and striatum 6 h after the last injection. Mice were given standard place training or random location training in the Morris water maze either as adolescents (PD 30-39) or adults (PD 70-79). The adolescents acquired the place learning more slowly than adults, and the alcohol treatments produced only modest place acquisition deficits. In contrast, both the PD7 and the PD 7-9 alcohol treatments resulted in large and significant spatial learning impairments in adults. In contrast to the previous findings of Wozniak et al. (2004), these results indicate that binge alcohol exposure in the 3rd trimester equivalent produces significant and enduring deficits in spatial learning in B6 mice.

  11. Methylphenidate and MDMA adolescent exposure in mice: long-lasting consequences on cocaine-induced reward and psychomotor stimulation in adulthood.

    PubMed

    Achat-Mendes, C; Anderson, K L; Itzhak, Y

    2003-07-01

    Pre-exposure to psychostimulants enhances the rewarding and psychomotor stimulating effects of subsequent drug exposure. Currently, there is a prevalence of adolescent exposure to the psychostimulants methylphenidate (MPD) and 3,4-methylenedioxymethamphetamine (MDMA). However, there is a paucity of investigation concerning the long-term behavioral consequences of exposure to these stimulants during adolescence. The aim of the present study was to investigate the effect of MPD and MDMA exposure in adolescence on cocaine-induced reward and psychomotor stimulation in adulthood. Adolescent Swiss-Webster mice received intraperitoneal injections of saline, MPD (10 mg/kg) or MDMA (10 mg/kg) from PD 26 to PD 32. Animal weights were monitored during and after drug administration. One month later, cocaine-induced conditioned place preference (CPP) and locomotor activity (LMA) were investigated. MPD and MDMA inhibited weight increase from PD 28 to PD 39 compared to the saline group, but weights amongst the three groups equalized by PD 46. MDMA exposure resulted in the same magnitude of cocaine (20 mg/kg)-induced CPP as saline exposure; however, MPD exposure caused significantly less CPP. Two weeks following extinction of CPP and withdrawal from cocaine, a priming injection of cocaine (5 mg/kg) reinstated significantly higher CPP in the MPD and MDMA groups than in the saline group. In the LMA experiments, cocaine (15 mg/kg) was administered for 5 consecutive days. On days 1 and 5, cocaine-induced hyperlocomotion in the MPD group was significantly higher than in the saline and MDMA groups. After a 2-week withdrawal period, cocaine (5 mg/kg) evoked significantly higher LMA responses in the MPD and MDMA groups compared to the saline group. Results suggest that exposure of mice to both MPD and MDMA during adolescence involves long-lasting neural adaptations, manifested as sensitized responses to cocaine-induced reward and psychomotor stimulation following cocaine withdrawal.

  12. Modulatory effects of sex steroid hormones on brain-derived neurotrophic factor-tyrosine kinase B expression during adolescent development in C57Bl/6 mice.

    PubMed

    Hill, R A; Wu, Y W C; Kwek, P; van den Buuse, M

    2012-05-01

    Sex steroid hormones and neurotrophic factors are involved in pruning and shaping the adolescent brain and have been implicated in the pathogenesis of neurodevelopmental disorders, including mental illness. We aimed to determine the association between altered levels of sex steroid hormones during adolescent development and neurotrophic signalling in the C57Bl/6 mouse. We first performed a week by week analysis from pre-pubescence to adulthood in male and female C57Bl/6 mice, measuring serum levels of testosterone and oestradiol in conjunction with western blot analysis of neurotrophin expression in the forebrain and hippocampal regions. Second, we manipulated adolescent sex steroid hormone levels by gonadectomy and hormone replacement at the pre-pubescent age of 5 weeks. Young-adult forebrain and hippocampal neurotrophin expression was then determined. Male mice showed significant changes in brain-derived neurotrophic factor (BDNF) expression in the forebrain regions during weeks 7-10, which corresponded significantly with a surge in serum testosterone. Castration and testosterone or di-hydrotestosterone replacement experiments revealed an androgen receptor-dependent effect on BDNF-tyrosine kinase (Trk) B signalling in the forebrain and hippocampal regions during adolescence. Female mice showed changes in BDNF-TrkB signalling at a much earlier time point (weeks 4-8) in the forebrain and hippocampal regions and these did not correspond with changes in serum oestradiol. Ovariectomy actually increased BDNF expression but decreased TrkB phosphorylation in the forebrain regions. 17β-Oestradiol replacement had no effect, suggesting a role for other ovarian hormones in regulating BDNF-TrkB signalling in the adolescent female mouse brain. These results suggest the differential actions of sex steroid hormones in modulating BDNF-TrkB signalling during adolescence. These data provide insight into how the male and female brain changes in response to altered levels of

  13. Contemporary Pharyngeal and Invasive emm1 and Invasive emm12 Group A Streptococcus Isolates Exhibit Similar In Vivo Selection for CovRS Mutants in Mice

    PubMed Central

    Feng, Wenchao; Liu, Mengyao; Chen, Daniel G.; Yiu, Rossana; Fang, Ferric C.; Lei, Benfang

    2016-01-01

    Group A Streptococcus (GAS) causes diverse infections ranging from common pharyngitis to rare severe invasive infections. Invasive GAS isolates can have natural mutations in the virulence regulator CovRS, which result in enhanced expression of multiple virulence genes, suppressed the expression of the protease SpeB, and increased virulence. It is believed that CovRS mutations arise during human infections with GAS carrying wild-type CovRS and are not transmissible. CovRS mutants of invasive GAS of the emm1 genotype arise readily during experimental infection in mice. It is possible that invasive GAS arises from pharyngeal GAS through rare genetic mutations that confer the capacity of mutated GAS to acquire covRS mutations during infection. The objective of this study was to determine whether contemporary pharyngeal emm1 GAS isolates have a reduced propensity to acquire CovRS mutations in vivo compared with invasive emm1 GAS and whether emm3, emm12, and emm28 GAS acquire CovRS mutants in mouse infection. The propensity of invasive and pharyngeal emm1 and invasive emm3, emm12, and emm28 SpeBA+ isolates to acquire variants with the SpeBA- phenotype was determined during subcutaneous infection of mice. The majority of both invasive and pharyngeal emm1 SpeBA+ isolates and two of three emm12 isolates, but not emm3 and emm28 isolates, were found to acquire SpeBA- variants during skin infection in mice. All analyzed SpeBA- variants of emm1 and emm12 GAS from the mouse infection acquired covRS mutations and produced more platelet-activating factor acetylhydrolase SsE. Thus, contemporary invasive and pharyngeal emm1 GAS isolates and emm12 GAS have a similar capacity to acquire covRS mutations in vivo. The rarity of severe invasive infections caused by GAS does not appear to be attributable to a reduced ability of pharyngeal isolates to acquire CovRS mutations. PMID:27611332

  14. Contemporary Pharyngeal and Invasive emm1 and Invasive emm12 Group A Streptococcus Isolates Exhibit Similar In Vivo Selection for CovRS Mutants in Mice.

    PubMed

    Feng, Wenchao; Liu, Mengyao; Chen, Daniel G; Yiu, Rossana; Fang, Ferric C; Lei, Benfang

    2016-01-01

    Group A Streptococcus (GAS) causes diverse infections ranging from common pharyngitis to rare severe invasive infections. Invasive GAS isolates can have natural mutations in the virulence regulator CovRS, which result in enhanced expression of multiple virulence genes, suppressed the expression of the protease SpeB, and increased virulence. It is believed that CovRS mutations arise during human infections with GAS carrying wild-type CovRS and are not transmissible. CovRS mutants of invasive GAS of the emm1 genotype arise readily during experimental infection in mice. It is possible that invasive GAS arises from pharyngeal GAS through rare genetic mutations that confer the capacity of mutated GAS to acquire covRS mutations during infection. The objective of this study was to determine whether contemporary pharyngeal emm1 GAS isolates have a reduced propensity to acquire CovRS mutations in vivo compared with invasive emm1 GAS and whether emm3, emm12, and emm28 GAS acquire CovRS mutants in mouse infection. The propensity of invasive and pharyngeal emm1 and invasive emm3, emm12, and emm28 SpeBA+ isolates to acquire variants with the SpeBA- phenotype was determined during subcutaneous infection of mice. The majority of both invasive and pharyngeal emm1 SpeBA+ isolates and two of three emm12 isolates, but not emm3 and emm28 isolates, were found to acquire SpeBA- variants during skin infection in mice. All analyzed SpeBA- variants of emm1 and emm12 GAS from the mouse infection acquired covRS mutations and produced more platelet-activating factor acetylhydrolase SsE. Thus, contemporary invasive and pharyngeal emm1 GAS isolates and emm12 GAS have a similar capacity to acquire covRS mutations in vivo. The rarity of severe invasive infections caused by GAS does not appear to be attributable to a reduced ability of pharyngeal isolates to acquire CovRS mutations. PMID:27611332

  15. Bupropion induced changes in exploratory and anxiety-like behaviour in NMRI male mice depends on the age.

    PubMed

    Carrasco, M Carmen; Vidal, Jose; Redolat, Rosa

    2013-09-01

    The aim of this study was to assess the effects of the antidepressant bupropion on anxiety and novelty-seeking in adolescent mice of different ages and adults. Behavioural differences between early adolescent, late adolescent and adult NMRI mice were measured both in the elevated plus-maze and the hole-board tasks following acute administration of bupropion (5, 10, 15, 20mg/kg) or saline. In the plus maze test, early and late adolescent mice treated with bupropion (10, 15mg/kg, respectively) had lower percentages of entries in the open-arms compared to their vehicle controls. Adult mice treated with bupropion did not differ from their vehicle controls. These results suggest that the effect of this drug on anxiety-like behaviour in mice depends on the age, showing adolescents an anxiogenic-like profile. In the hole-board, adolescents showed more elevated levels of novelty-seeking than adults, exhibiting shorter latency to the first head-dip (HD) and a higher number of HD's. Bupropion increases the latency to the first HD and decreases the number of HD's in all age-groups, indicating a decline in exploratory tendency. Findings reveal that the age can modulate the behaviour displayed by mice in both animal models, and that adolescents are more sensitive to bupropion's anxiogenic effects.

  16. FT-Raman study of deferoxamine and deferiprone exhibits potent amelioration of structural changes in the liver tissues of mice due to aluminum exposure

    NASA Astrophysics Data System (ADS)

    Sivakumar, S.; Khatiwada, Chandra Prasad; Sivasubramanian, J.; Raja, B.

    2014-01-01

    The present study inform the alterations on major biochemical constituents such as lipids, proteins, nucleic acids and glycogen along with phosphodiester linkages, tryptophan bands, tyrosine doublet, disulfide bridge conformations, aliphatic hydrophobic residue, and salt bridges in liver tissues of mice using Fourier transform Raman spectroscopy. In amide I, amide II and amide III, the area value significant decrease due structural alteration in the protein, glycogen and triglycerides levels but chelating agents DFP and DFO upturned it. Morphology changes by aluminium induced alterations and recovery by chelating agents within liver tissues known by histopathological examination. Concentrations of trace elements were found by ICP-OES. FT-Raman study was revealed to be in agreement with biochemical studies and demonstrate that it can successfully specify the molecular alteration in liver tissues. The tyrosyl doublet ratio I899/I831 decreases more in aluminum intoxicated tissues but treatment with DFP and DFO + DFP brings back to nearer control value. This indicates more variation in the hydrogen bonding of the phenolic hydroxyl group due to aluminum poisoning. The decreased Raman intensity ratio (I3220/I3400) observed in the aluminum induced tissues suggests a decreased water domain size, which could be interpreted in terms of weaker hydrogen-bonded molecular species of water in the aluminum intoxicated liver tissues. Finally, FT-Raman spectroscopy might be a useful tool for obtained successfully to indicate the molecular level changes.

  17. L1 Cell Adhesion Molecule-Specific Chimeric Antigen Receptor-Redirected Human T Cells Exhibit Specific and Efficient Antitumor Activity against Human Ovarian Cancer in Mice.

    PubMed

    Hong, Hao; Brown, Christine E; Ostberg, Julie R; Priceman, Saul J; Chang, Wen-Chung; Weng, Lihong; Lin, Paul; Wakabayashi, Mark T; Jensen, Michael C; Forman, Stephen J

    2016-01-01

    New therapeutic modalities are needed for ovarian cancer, the most lethal gynecologic malignancy. Recent clinical trials have demonstrated the impressive therapeutic potential of adoptive therapy using chimeric antigen receptor (CAR)-redirected T cells to target hematological cancers, and emerging studies suggest a similar impact may be achieved for solid cancers. We sought determine whether genetically-modified T cells targeting the CE7-epitope of L1-CAM, a cell adhesion molecule aberrantly expressed in several cancers, have promise as an immunotherapy for ovarian cancer, first demonstrating that L1-CAM was highly over-expressed on a panel of ovarian cancer cell lines, primary ovarian tumor tissue specimens, and ascites-derived primary cancer cells. Human central memory derived T cells (TCM) were then genetically modified to express an anti-L1-CAM CAR (CE7R), which directed effector function upon tumor antigen stimulation as assessed by in vitro cytokine secretion and cytotoxicity assays. We also found that CE7R+ T cells were able to target primary ovarian cancer cells. Intraperitoneal (i.p.) administration of CE7R+ TCM induced a significant regression of i.p. established SK-OV-3 xenograft tumors in mice, inhibited ascites formation, and conferred a significant survival advantage compared with control-treated animals. Taken together, these studies indicate that adoptive transfer of L1-CAM-specific CE7R+ T cells may offer a novel and effective immunotherapy strategy for advanced ovarian cancer. PMID:26761817

  18. Self-recognition specificity expressed by T cells from nude mice. Absence of detectable Ia-restricted T cells in nude mice that do exhibit self-K/D-restricted T cell responses

    SciTech Connect

    Kruisbeek, A.M.; Davis, M.L.; Matis, L.A.; Longo, D.L.

    1984-09-01

    The presence in athymic nude mice of precursor T cells with self-recognition specificity for either H-2 K/D or H-2 I region determinants was investigated. Chimeras were constructed of lethally irradiated parental mice receiving a mixture of F1 nude mouse (6-8 wk old) spleen and bone marrow cells. The donor inoculum was deliberately not subjected to any T cell depletion procedure, so that any potential major histocompatibility complex-committed precursor T cells were allowed to differentiate and expand in the normal parental recipients. 3 mo after reconstitution, the chimeras were immunized with several protein antigens in complete Freund's adjuvant in the footpads and their purified draining lymph node T cells tested 10 d later for ability to recognize antigen on antigen-presenting cells of either parental haplotype. Also, their spleen and lymph node cells were tested for ability to generate a cytotoxic T lymphocyte (CTL) response to trinitrophenyl (TNP)-modified stimulator cells of either parental haplotype. It was demonstrated that T cell proliferative responses of these F1(nude)----parent chimeras were restricted solely to recognizing parental host I region determinants as self and expressed the Ir gene phenotype of the host. In contrast, CTL responses could be generated (in the presence of interleukin 2) to TNP-modified stimulator cells of either parental haplotype. Thus these results indicate that nude mice which do have CTL with self-specificity for K/D region determinants lack proliferating T cells with self-specificity for I region determinants. These results provide evidence for the concepts that development of the I region-restricted T cell repertoire is strictly an intrathymically determined event and that young nude mice lack the unique thymic elements responsible for edu

  19. Carboxy-terminally truncated dengue virus envelope glycoproteins expressed on the cell surface and secreted extracellularly exhibit increased immunogenicity in mice.

    PubMed

    Men, R H; Bray, M; Lai, C J

    1991-03-01

    Recombinant vaccinia viruses expressing C-terminally truncated E's that ranged in length from 9 to 99% of the N-terminal sequence were constructed. The overall antigenicity of the E products was analyzed by radioimmunoprecipitation, using dengue virus hyperimmune mouse ascitic fluid (HMAF) or an anti-E peptide serum. Truncated E that was 79% or less in length did not bind HMAF efficiently, whereas E constructs greater than 79% were able to bind HMAF with high efficiency. The first 392 amino acids of the dengue type 4 virus E sequence, including the Arg-392 following the 79% E C terminus, appeared to be critical for proper antigenic structure required for efficient binding by HMAF. Truncated E's ranging from 59 to 81% in length were secreted extracellularly, whereas smaller or larger E's were retained intracellularly. Secreted E's contained carbohydrate side chains that were resistant to endoglycosidase H digestion, suggesting that the transport of E occurs via a pathway from the rough endoplasmic reticulum through the Golgi complex. 79% E-RKG (which possessed the three additional amino acids immediately downstream of 79% E) was expressed at a high concentration on the surface of recombinant virus-infected cells presumably being inserted into the plasma membrane by a hydrophobic C-terminal membrane anchor. Evaluation in mice of the protective efficacy of the various vaccinia virus E recombinants indicated that only truncated E's that were recognized efficiently by HMAF induced a high level of resistance to dengue virus encephalitis. 79% E-RKG which is expressed at a high concentration on the surface of infected cells was highly immunogenic when tested for induction of an E antibody response. This suggests that cell surface expression of 79% E-RKG was responsible for its enhanced immunogenicity. Finally, passive immunization studies indicated that serum antibodies to E played a major role in the complete or nearly complete resistance to dengue virus challenge induced

  20. Affinity-tuned ErbB2 or EGFR chimeric antigen receptor T cells exhibit an increased therapeutic index against tumors in mice

    PubMed Central

    Liu, Xiaojun; Jiang, Shuguang; Fang, Chongyun; Yang, Shiyu; Olalere, Devvora; Pequignot, Edward C.; Cogdill, Alexandria P.; Li, Na; Ramones, Melissa; Granda, Brian; Zhou, Li; Loew, Andreas; Young, Regina M.; June, Carl H.; Zhao, Yangbing

    2015-01-01

    Target-mediated toxicity is a major limitation in the development of chimeric antigen T cell receptors (CAR) for adoptive cell therapy of solid tumors. In this study, we developed a strategy to adjust the affinities of the scFv component of CAR to discriminate tumors overexpressing the target from normal tissues which express it at physiologic levels. A CAR-expressing T cell panel was generated with target antigen affinities varying over three orders of magnitude. High-affinity cells recognized target expressed at any level, including at levels in normal cells that were undetectable by flow cytometry. Affinity-tuned cells exhibited robust antitumor efficacy similar to high-affinity cells, but spared normal cells expressing physiologic target levels. The use of affinity-tuned scFvs offers a strategy to empower wider use of CAR T cells against validated targets widely overexpressed on solid tumors, including those considered undruggable by this approach. PMID:26330166

  1. Effects of repeated exposure to morphine in adolescent and adult male C57BL/6J mice: age-dependent differences in locomotor stimulation, sensitization, and body weight loss

    PubMed Central

    Koek, Wouter

    2013-01-01

    Rationale Given evidence for age-related differences in the effects of drugs of abuse, surprisingly few preclinical studies have explored effects of opioids in adolescents (versus adults). Objectives This study compared the motor stimulating and ataxic effects of repeatedly-administered morphine in adolescent, late-adolescent, and adult mice. Methods Mice were treated with saline or morphine (10–100 mg/kg, i.p.) once per day for 4 days, and morphine (3.2–56 mg/kg)-induced locomotion was assessed 3 days or 5 weeks later. Different mice were treated repeatedly with morphine and ataxia was measured. Results Acute administration of morphine increased locomotion more in adolescents than in adults. Repeated morphine enhanced morphine-induced locomotion, assessed 3 days later, to a similar extent in each age group (minimum effective dose: 17.8 mg/kg). This sensitization was still evident 5 weeks later when the adolescents had become adult, but was smaller and occurred at a higher dose (56 mg/kg). In animals treated repeatedly with morphine as adults, sensitization was no longer apparent 5 weeks later. Intermittent morphine was at least 10-fold less potent to produce body weight loss in adolescents than in adults. Repeated morphine did not alter morphine-induced ataxia at any age. Conclusions Compared with adults, adolescents were more sensitive to the acute locomotor stimulating effects of morphine and to its long-lasting locomotor sensitizing effects, consistent with overactivity of dopamine systems during adolescence. In contrast, adolescents were less sensitive than adults to body weight loss induced by intermittent morphine, an effect indicative of morphine withdrawal in adult rodents. PMID:24096538

  2. Acquisition and reinstatement of MDMA-induced conditioned place preference in mice pre-treated with MDMA or cocaine during adolescence.

    PubMed

    Daza-Losada, Manuel; Rodríguez-Arias, Marta; Aguilar, María A; Miñarro, José

    2009-09-01

    Those who take ecstasy are more likely to consume other drugs than non-users with cocaine abuse being reported by 75.5% of high school student MDMA (+/- 3,4-methylenedioxymetamphetamine hydrochloride) users. The aim of this work was to evaluate the effects of exposure during adolescence to MDMA, cocaine or to both drugs on the MDMA-induced conditioned place preference (CPP) in adult mice. Animals received two daily administrations of saline, 10 mg/kg of MDMA, 25 mg/kg of cocaine or 10 mg/kg of MDMA plus 25 mg/kg of cocaine over 3 days (from PD28 to 30). Three weeks after pre-treatment, the MDMA-induced CPP procedure was initiated (PD52). Acquisition of CPP was induced with a sub-threshold dose of MDMA (1.25 mg/kg) only in animals treated during adolescence with MDMA alone. Preference was established in all the groups after conditioning with 10 mg/kg of MDMA, while the time required to achieve extinction was longer in those pre-treated with cocaine or MDMA alone (46 and 28 sessions, respectively). Moreover, preference was reinstated with progressively lower priming doses of MDMA in mice pre-treated with MDMA or cocaine alone. These results demonstrate that early exposure to MDMA or cocaine induces long-lasting changes that last until adulthood and modify the response of animals to MDMA.

  3. Effects of Early Chemotherapeutic Treatment on Learning in Adolescent Mice: Implications for Cognitive Impairment and Remediation in Childhood Cancer Survivors

    PubMed Central

    Bisen-Hersh, Emily B.; Hineline, Philip N.; Walker, Ellen A.

    2013-01-01

    Purpose Among children diagnosed with acute lymphoblastic leukemia (ALL) and given chemotherapy-only treatment, 40-70% of survivors experience neurocognitive impairment. The present study used a preclinical mouse model to investigate the effects of early exposure to common ALL chemotherapeutics methotrexate (MTX) and cytarabine (Ara-C) on learning and memory. Experimental Design Pre-weanling mouse pups were treated on postnatal day (PND) 14, 15, and 16 with saline, MTX, Ara-C, or a combination of MTX and Ara-C. Nineteen days following treatment (PND 35), behavioral tasks measuring different aspects of learning and memory were administered. Results Significant impairment in acquisition and retention over both short (1h) and long (24h) intervals, as measured by autoshaping and novel object recognition tasks, were found following treatment with MTX and Ara-C. Similarly, a novel conditional discrimination task revealed impairment in acquisition for chemotherapy-treated mice. No significant group differences were found following the extensive training component of this task, with impairment following the rapid training component occurring only for the highest MTX and Ara-C combination group. Conclusions Findings are consistent with clinical studies suggesting that childhood cancer survivors are slower at learning new information and primarily exhibit deficits in memory years after successful completion of chemotherapy treatment. The occurrence of mild deficits on a novel conditional discrimination task suggests that chemotherapy-induced cognitive impairment may be ameliorated through extensive training or practice. PMID:23596103

  4. Adolescent social isolation enhances the plasmalemmal density of NMDA NR1 subunits in dendritic spines of principal neurons in the basolateral amygdala of adult mice.

    PubMed

    Gan, J O; Bowline, E; Lourenco, F S; Pickel, V M

    2014-01-31

    Social isolation during the vulnerable period of adolescence produces emotional dysregulation manifested by abnormalities in adult behaviors that require emotional processing. The affected brain regions may include the basolateral amygdala (BLA), where plasticity of glutamatergic synapses in principal neurons plays a role in conditioned emotional responses. This plasticity is dependent on NMDA receptor trafficking denoted by intracellular mobilization of the obligatory NR1 NMDA subunit. We tested the hypothesis that the psychosocial stress of adolescent social isolation (ASI) produces a lasting change in NMDA receptor distribution in principal neurons in the BLA of adults that express maladaptive emotional responses to sensory cues. For this, we used behavioral testing and dual electron microscopic immunolabeling of NR1 and calcium calmodulin-dependent protein kinase II (CaMKII), a protein predominantly expressed in principal neurons of the BLA in adult C57Bl/6 mice housed in isolation or in social groups from post-weaning day 22 until adulthood (∼3 months of age). The isolates showed persistent deficits in sensorimotor gating evidenced by altered prepulse inhibition (PPI) of acoustic startle and hyperlocomotor activity in a novel environment. Immunogold-silver labeling for NR1 alone or together with CaMKII was seen in many somatodendritic profiles in the BLA of all mice irrespective of rearing conditions. However, isolates compared with group-reared mice had a significantly lower cytoplasmic (4.72 ± 0.517 vs 6.31 ± 0.517) and higher plasmalemmal (0.397 ± 0.0779 vs 0.216 ± 0.026) density of NR1 immunogold particles in CaMKII-containing dendritic spines. There was no rearing-dependent difference in the size or number of these spines or those of other dendritic profiles within the neuropil, which also failed to show an impact of ASI on NR1 immunogold labeling. These results provide the first evidence that ASI enhances the surface trafficking of NMDA receptors

  5. Adolescent social isolation enhances the plasmalemmal density of NMDA NR1 subunits in dendritic spines of principal neurons in the basolateral amygdala of adult mice

    PubMed Central

    Gan, Jerylin O.; Bowline, Everett; Lourenco, Frederico S.; Pickel, Virginia M.

    2014-01-01

    Social isolation during the vulnerable period of adolescence produces emotional dysregulation manifested by abnormalities in adult behaviors that require emotional processing. The affected brain regions may include the basolateral amygdala (BLA), where plasticity of glutamatergic synapses in principal neurons plays a role in conditioned emotional responses. This plasticity is dependent on NMDA receptor trafficking denoted by intracellular mobilization of the obligatory NR1 NMDA subunit. We tested the hypothesis that the psychosocial stress of adolescent social isolation (ASI) produces a lasting change in NMDA receptor distribution in principal neurons in the BLA of adults that express maladaptive emotional responses to sensory cues. For this, we used behavioral testing and dual electron microscopic immunolabeling of NR1 and CaMKII, a protein predominantly expressed in principal neurons of the BLA in adult C57Bl/6 mice housed in isolation or in social groups from post-weaning day 22 until adulthood (~3 months of age). The isolates showed persistent deficits in sensorimotor gating evidenced by altered prepulse inhibition (PPI) of acoustic startle and hyperlocomotor activity in a novel environment. Immunogold-silver labeling for NR1 alone or together with CaMKII was seen in many somatodendritic profiles in the BLA of all mice irrespective of rearing conditions. However, isolates compared with group-reared mice had a significantly lower cytoplasmic (4.72±0.517 vs 6.31 ± 0.517) and higher plasmalemmal (0.397±0.0779 vs 0.216±0.026) density of NR1 immunogold particles in CaMKII-containing dendritic spines. There were no rearing-dependent difference is the size or number of these spines or those of other dendritic profiles within the neuropil, which also failed to show an impact of ASI on NR1 immunogold labeling. These results provide the first evidence that ASI enhances the surface trafficking of NMDA receptors in dendritic spines of principal neurons in the BLA of

  6. Changes in cannabinoid receptors, aquaporin 4 and vimentin expression after traumatic brain injury in adolescent male mice. Association with edema and neurological deficit.

    PubMed

    Lopez-Rodriguez, Ana Belen; Acaz-Fonseca, Estefania; Viveros, Maria-Paz; Garcia-Segura, Luis M

    2015-01-01

    Traumatic brain injury (TBI) incidence rises during adolescence because during this critical neurodevelopmental period some risky behaviors increase. The purpose of this study was to assess the contribution of cannabinoid receptors (CB1 and CB2), blood brain barrier proteins (AQP4) and astrogliosis markers (vimentin) to neurological deficit and brain edema formation in a TBI weight drop model in adolescent male mice. These molecules were selected since they are known to change shortly after lesion. Here we extended their study in three different timepoints after TBI, including short (24h), early mid-term (72h) and late mid-term (two weeks). Our results showed that TBI induced an increase in brain edema up to 72 h after lesion that was directly associated with neurological deficit. Neurological deficit appeared 24 h after TBI and was completely recovered two weeks after trauma. CB1 receptor expression decreased after TBI and was negatively correlated with edema formation and behavioral impairments. CB2 receptor increased after injury and was associated with high neurological deficit whereas no correlation with edema was found. AQP4 increased after TBI and was positively correlated with edema and neurological impairments as occurred with vimentin expression in the same manner. The results suggest that CB1 and CB2 differ in the mechanisms to resolve TBI and also that some of their neuroprotective effects related to the control of reactive astrogliosis may be due to the regulation of AQP4 expression on the end-feet of astrocytes.

  7. Changes in Cannabinoid Receptors, Aquaporin 4 and Vimentin Expression after Traumatic Brain Injury in Adolescent Male Mice. Association with Edema and Neurological Deficit

    PubMed Central

    Lopez-Rodriguez, Ana Belen; Acaz-Fonseca, Estefania; Viveros, Maria-Paz; Garcia-Segura, Luis M.

    2015-01-01

    Traumatic brain injury (TBI) incidence rises during adolescence because during this critical neurodevelopmental period some risky behaviors increase. The purpose of this study was to assess the contribution of cannabinoid receptors (CB1 and CB2), blood brain barrier proteins (AQP4) and astrogliosis markers (vimentin) to neurological deficit and brain edema formation in a TBI weight drop model in adolescent male mice. These molecules were selected since they are known to change shortly after lesion. Here we extended their study in three different timepoints after TBI, including short (24h), early mid-term (72h) and late mid-term (two weeks). Our results showed that TBI induced an increase in brain edema up to 72 h after lesion that was directly associated with neurological deficit. Neurological deficit appeared 24 h after TBI and was completely recovered two weeks after trauma. CB1 receptor expression decreased after TBI and was negatively correlated with edema formation and behavioral impairments. CB2 receptor increased after injury and was associated with high neurological deficit whereas no correlation with edema was found. AQP4 increased after TBI and was positively correlated with edema and neurological impairments as occurred with vimentin expression in the same manner. The results suggest that CB1 and CB2 differ in the mechanisms to resolve TBI and also that some of their neuroprotective effects related to the control of reactive astrogliosis may be due to the regulation of AQP4 expression on the end-feet of astrocytes. PMID:26039099

  8. A Novel Adeno-Associated Virus–Based Genetic Vaccine Encoding the Hepatitis C Virus NS3/4 Protein Exhibits Immunogenic Properties in Mice Superior to Those of an NS3-Protein-Based Vaccine

    PubMed Central

    Zhu, Fengqin; Chen, Tian; Zhang, Yeqiong; Sun, Haixia; Cao, Hong; Lu, Jianxi; Zhao, Linshan; Li, Gang

    2015-01-01

    More than 170 million individuals worldwide are infected with hepatitis C virus (HCV), and up to an estimated 30% of chronically infected individuals will go on to develop progressive liver disease. Despite the recent advances in antiviral treatment of HCV infection, it remains a major public health problem. Thus, development of an effective vaccine is urgently required. In this study, we constructed novel adeno-associated virus (AAV) vectors expressing the full-length NS3 or NS3/4 protein of HCV genotype 1b. The expression of the NS3 or NS3/4 protein in HepG2 cells was confirmed by western blotting. C57BL/6 mice were intramuscularly immunised with a single injection of AAV vectors, and the resultant immune response was investigated. The AAV2/rh32.33.NS3/4 vaccine induced stronger humoral and cellular responses than did the AAV2/rh32.33.NS3 vaccine. Our results demonstrate that AAV-based vaccines exhibit considerable potential for the development of an effective anti-HCV vaccine. PMID:26556235

  9. Isolation Rearing Reduces Neuronal Excitability in Dentate Gyrus Granule Cells of Adolescent C57BL/6J Mice: Role of GABAergic Tonic Currents and Neurosteroids.

    PubMed

    Talani, Giuseppe; Biggio, Francesca; Licheri, Valentina; Locci, Valentina; Biggio, Giovanni; Sanna, Enrico

    2016-01-01

    Early-life exposure to stress, by impacting on a brain still under development, is considered a critical factor for the increased vulnerability to psychiatric disorders and abuse of psychotropic substances during adulthood. As previously reported, rearing C57BL/6J weanling mice in social isolation (SI) from their peers for several weeks, a model of prolonged stress, is associated with a decreased plasma and brain levels of neuroactive steroids such as 3α,5α-THP, with a parallel up-regulation of extrasynaptic GABAA receptors (GABAAR) in dentate gyrus (DG) granule cells compared to group-housed (GH) mice. In the present study, together with the SI-induced decrease in plasma concentration of both progesterone and 3α,5α-THP, and an increase in THIP-stimulated GABAergic tonic currents, patch-clamp analysis of DG granule cells revealed a significant decrease in membrane input resistance and action potential (AP) firing rate, in SI compared to GH mice, suggesting that SI exerts an inhibitory action on neuronal excitability of these neurons. Voltage-clamp recordings of glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs) revealed a SI-associated decrease in frequency as well as a shift from paired-pulse (PP) depression to PP facilitation (PPF) of evoked EPSCs, indicative of a reduced probability of glutamate release. Daily administration of progesterone during isolation reverted the changes in plasma 3α,5α-THP as well as in GABAergic tonic currents and neuronal excitability caused by SI, but it had only a limited effect on the changes in the probability of presynaptic glutamate release. Overall, the results obtained in this work, together with those previously published, indicate that exposure of mice to SI during adolescence reduces neuronal excitability of DG granule cells, an effect that may be linked to the increased GABAergic tonic currents as a consequence of the sustained decrease in plasma and hippocampal levels of neurosteroids. All these

  10. Isolation Rearing Reduces Neuronal Excitability in Dentate Gyrus Granule Cells of Adolescent C57BL/6J Mice: Role of GABAergic Tonic Currents and Neurosteroids

    PubMed Central

    Talani, Giuseppe; Biggio, Francesca; Licheri, Valentina; Locci, Valentina; Biggio, Giovanni; Sanna, Enrico

    2016-01-01

    Early-life exposure to stress, by impacting on a brain still under development, is considered a critical factor for the increased vulnerability to psychiatric disorders and abuse of psychotropic substances during adulthood. As previously reported, rearing C57BL/6J weanling mice in social isolation (SI) from their peers for several weeks, a model of prolonged stress, is associated with a decreased plasma and brain levels of neuroactive steroids such as 3α,5α-THP, with a parallel up-regulation of extrasynaptic GABAA receptors (GABAAR) in dentate gyrus (DG) granule cells compared to group-housed (GH) mice. In the present study, together with the SI-induced decrease in plasma concentration of both progesterone and 3α,5α-THP, and an increase in THIP-stimulated GABAergic tonic currents, patch-clamp analysis of DG granule cells revealed a significant decrease in membrane input resistance and action potential (AP) firing rate, in SI compared to GH mice, suggesting that SI exerts an inhibitory action on neuronal excitability of these neurons. Voltage-clamp recordings of glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs) revealed a SI-associated decrease in frequency as well as a shift from paired-pulse (PP) depression to PP facilitation (PPF) of evoked EPSCs, indicative of a reduced probability of glutamate release. Daily administration of progesterone during isolation reverted the changes in plasma 3α,5α-THP as well as in GABAergic tonic currents and neuronal excitability caused by SI, but it had only a limited effect on the changes in the probability of presynaptic glutamate release. Overall, the results obtained in this work, together with those previously published, indicate that exposure of mice to SI during adolescence reduces neuronal excitability of DG granule cells, an effect that may be linked to the increased GABAergic tonic currents as a consequence of the sustained decrease in plasma and hippocampal levels of neurosteroids. All these

  11. Isolation Rearing Reduces Neuronal Excitability in Dentate Gyrus Granule Cells of Adolescent C57BL/6J Mice: Role of GABAergic Tonic Currents and Neurosteroids.

    PubMed

    Talani, Giuseppe; Biggio, Francesca; Licheri, Valentina; Locci, Valentina; Biggio, Giovanni; Sanna, Enrico

    2016-01-01

    Early-life exposure to stress, by impacting on a brain still under development, is considered a critical factor for the increased vulnerability to psychiatric disorders and abuse of psychotropic substances during adulthood. As previously reported, rearing C57BL/6J weanling mice in social isolation (SI) from their peers for several weeks, a model of prolonged stress, is associated with a decreased plasma and brain levels of neuroactive steroids such as 3α,5α-THP, with a parallel up-regulation of extrasynaptic GABAA receptors (GABAAR) in dentate gyrus (DG) granule cells compared to group-housed (GH) mice. In the present study, together with the SI-induced decrease in plasma concentration of both progesterone and 3α,5α-THP, and an increase in THIP-stimulated GABAergic tonic currents, patch-clamp analysis of DG granule cells revealed a significant decrease in membrane input resistance and action potential (AP) firing rate, in SI compared to GH mice, suggesting that SI exerts an inhibitory action on neuronal excitability of these neurons. Voltage-clamp recordings of glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs) revealed a SI-associated decrease in frequency as well as a shift from paired-pulse (PP) depression to PP facilitation (PPF) of evoked EPSCs, indicative of a reduced probability of glutamate release. Daily administration of progesterone during isolation reverted the changes in plasma 3α,5α-THP as well as in GABAergic tonic currents and neuronal excitability caused by SI, but it had only a limited effect on the changes in the probability of presynaptic glutamate release. Overall, the results obtained in this work, together with those previously published, indicate that exposure of mice to SI during adolescence reduces neuronal excitability of DG granule cells, an effect that may be linked to the increased GABAergic tonic currents as a consequence of the sustained decrease in plasma and hippocampal levels of neurosteroids. All these

  12. The combination of ethanol with mephedrone increases the signs of neurotoxicity and impairs neurogenesis and learning in adolescent CD-1 mice.

    PubMed

    Ciudad-Roberts, Andrés; Duart-Castells, Leticia; Camarasa, Jorge; Pubill, David; Escubedo, Elena

    2016-02-15

    A new family of psychostimulants, under the name of cathinones, has broken into the market in the last decade. In light of the fact that around 95% of cathinone consumers have been reported to combine them with alcoholic drinks, we sought to study the consequences of the concomitant administration of ethanol on mephedrone -induced neurotoxicity. Adolescent male Swiss-CD1 mice were administered four times in one day, every 2h, with saline, mephedrone (25mg/kg), ethanol (2; 1.5; 1.5; 1g/kg) and their combination at a room temperature of 26±2°C. The combination with ethanol impaired mephedrone-induced decreases in dopamine transporter and tyrosine hydroxylase in the frontal cortex; and in serotonin transporter and tryptophan hydroxylase in the hippocampus by approximately 2-fold, 7days post-treatment. Furthermore, these decreases correlated with a 2-fold increase in lipid peroxidation, measured as concentration of malondialdehyde (MDA), 24h post-treatment, and were accompanied by changes in oxidative stress-related enzymes. Ethanol also notably potentiated mephedrone-induced negative effects on learning and memory, as well as hippocampal neurogenesis, measured through the Morris water maze (MWM) and 5-bromo-2'-deoxyuridine staining, respectively. These results are of special significance, since alcohol is widely co-abused with amphetamine derivatives such as mephedrone, especially during adolescence, a crucial stage in brain maturation. Given that the hippocampus is greatly involved in learning and memory processes, normal brain development in young adults could be affected with permanent behavioral consequences after this type of drug co-abuse. PMID:26747301

  13. The combination of ethanol with mephedrone increases the signs of neurotoxicity and impairs neurogenesis and learning in adolescent CD-1 mice.

    PubMed

    Ciudad-Roberts, Andrés; Duart-Castells, Leticia; Camarasa, Jorge; Pubill, David; Escubedo, Elena

    2016-02-15

    A new family of psychostimulants, under the name of cathinones, has broken into the market in the last decade. In light of the fact that around 95% of cathinone consumers have been reported to combine them with alcoholic drinks, we sought to study the consequences of the concomitant administration of ethanol on mephedrone -induced neurotoxicity. Adolescent male Swiss-CD1 mice were administered four times in one day, every 2h, with saline, mephedrone (25mg/kg), ethanol (2; 1.5; 1.5; 1g/kg) and their combination at a room temperature of 26±2°C. The combination with ethanol impaired mephedrone-induced decreases in dopamine transporter and tyrosine hydroxylase in the frontal cortex; and in serotonin transporter and tryptophan hydroxylase in the hippocampus by approximately 2-fold, 7days post-treatment. Furthermore, these decreases correlated with a 2-fold increase in lipid peroxidation, measured as concentration of malondialdehyde (MDA), 24h post-treatment, and were accompanied by changes in oxidative stress-related enzymes. Ethanol also notably potentiated mephedrone-induced negative effects on learning and memory, as well as hippocampal neurogenesis, measured through the Morris water maze (MWM) and 5-bromo-2'-deoxyuridine staining, respectively. These results are of special significance, since alcohol is widely co-abused with amphetamine derivatives such as mephedrone, especially during adolescence, a crucial stage in brain maturation. Given that the hippocampus is greatly involved in learning and memory processes, normal brain development in young adults could be affected with permanent behavioral consequences after this type of drug co-abuse.

  14. Childhood and adolescent obesity and long-term cognitive consequences during aging.

    PubMed

    Wang, Jun; Freire, Daniel; Knable, Lindsay; Zhao, Wei; Gong, Bing; Mazzola, Paolo; Ho, Lap; Levine, Samara; Pasinetti, Giulio M

    2015-04-01

    The prevalence of childhood/adolescent obesity and insulin resistance has reached an epidemic level. Obesity's immediate clinical impacts have been extensively studied; however, current clinical evidence underscores the long-term implications. The current study explored the impacts of brief childhood/adolescent obesity and insulin resistance on cognitive function in later life. To mimic childhood/adolescent obesity and insulin resistance, we exposed 9-week-old C57BL/6J mice to a high-fat diet for 15 weeks, after which the mice exhibited diet-induced obesity and insulin resistance. We then put these mice back on a normal low-fat diet, after which the mice exhibited normal body weight and glucose tolerance. However, a spatial memory test in the forms of the Morris water maze (MWM) and contextual fear conditioning at 85 weeks of age showed that these mice had severe deficits in learning and long-term memory consolidation. Mechanistic investigations identified increased expression of histone deacetylases 5, accompanied by reduced expression of brain-derived neurotrophic factor, in the brains 61 weeks after the mice had been off the high-fat diet. Electrophysiology studies showed that hippocampal slices isolated from these mice are more susceptible to synaptic impairments compared with slices isolated from the control mice. We demonstrated that a 15-week occurrence of obesity and insulin resistance during childhood/adolescence induces irreversible epigenetic modifications in the brain that persist following restoration of normal metabolic homeostasis, leading to brain synaptic dysfunction during aging. Our study provides experimental evidence that limited early-life exposure to obesity and insulin resistance may have long-term deleterious consequences in the brain, contributing to the onset/progression of cognitive dysfunction during aging.

  15. Exogenous progesterone exacerbates running response of adolescent female mice to repeated food restriction stress by changing α4-GABAA receptor activity of hippocampal pyramidal cells.

    PubMed

    Wable, G S; Chen, Y-W; Rashid, S; Aoki, C

    2015-12-01

    Adolescent females are particularly vulnerable to mental illnesses with co-morbidity of anxiety, such as anorexia nervosa (AN). We used an animal model of AN, called activity-based anorexia (ABA), to investigate the neurobiological basis of vulnerability to repeated, food restriction (FR) stress-evoked anxiety. Twenty-one of 23 adolescent female mice responded to the 1st FR with increased wheel-running activity (WRA), even during the limited period of food access, thereby capturing AN's symptoms of voluntary FR and over-exercise. Baseline WRA was an excellent predictor of FR-elicited WRA (severity of ABA, SOA), with high baseline runners responding to FR with minimal SOA (i.e., negative correlation). Nine gained resistance to ABA following the 1st FR. Even though allopregnanolone (3α-OH-5α-pregnan-20-one, THP), the metabolite of progesterone (P4), is a well-recognized anxiolytic agent, subcutaneous P4 to these ABA-resistant animals during the 2nd FR was exacerbative, evoking greater WRA than the counterpart resistant group that received oil vehicle, only. Moreover, P4 had no WRA-reducing effect on animals that remained ABA-vulnerable. To explain the sensitizing effect of P4 upon the resistant mice, we examined the relationship between P4 treatment and levels of the α4 subunit of GABAARs at spines of pyramidal cells of the hippocampal CA1, a parameter previously shown to correlate with resistance to ABA. α4 levels at spine membrane correlated strongly and negatively with SOA during the 1st ABA (prior to P4 injection), confirming previous findings. α4 levels were greater among P4-treated animals that had gained resistance than of vehicle-treated resistant animals or of the vulnerable animals with or without P4. We propose that α4-GABAARs play a protective role by counterbalancing the ABA-induced increase in excitability of CA1 pyramidal neurons, and although exogenous P4's metabolite, THP, enhances α4 expression, especially among those that can gain resistance

  16. Motor Deficits on a Ladder Rung Task in Male and Female Adolescent and Adult CGG Knock-in Mice

    PubMed Central

    Hunsaker, Michael R.; von Leden, Ramona E.; Ta, Binh T.; Goodrich-Hunsaker, Naomi J.; Arque, Gloria; Kim, Kyoungmi; Willemsen, Rob; Berman, Robert F.

    2011-01-01

    The fragile X premutation is a tandem CGG trinucleotide repeat expansion on the FMR1 gene between 55 and 200 repeats in length. A CGG knock-in (CGG KI) mouse with CGG trinucleotide repeat lengths between 70 and 350 has been developed and used to model the histopathology and cognitive deficits reported in carriers of the fragile X premutation. Previous studies have shown that CGG KI mice show progressive deficits in processing spatial and temporal information. To characterize the motor deficits associated with the fragile X premutation, male and female CGG KI mice ranging from 2–16 months of age with trinucleotide repeats ranging from 72–240 CGG in length were tested for their ability to perform a skilled ladder rung walking test. The results demonstrate that both male and female CGG KI mice showed a greater number of foot slips as a function of increased CGG repeat length, independent of the age of the animal or general activity level. PMID:21440572

  17. MicroRNA-33b knock-in mice for an intron of sterol regulatory element-binding factor 1 (Srebf1) exhibit reduced HDL-C in vivo.

    PubMed

    Horie, Takahiro; Nishino, Tomohiro; Baba, Osamu; Kuwabara, Yasuhide; Nakao, Tetsushi; Nishiga, Masataka; Usami, Shunsuke; Izuhara, Masayasu; Nakazeki, Fumiko; Ide, Yuya; Koyama, Satoshi; Sowa, Naoya; Yahagi, Naoya; Shimano, Hitoshi; Nakamura, Tomoyuki; Hasegawa, Koji; Kume, Noriaki; Yokode, Masayuki; Kita, Toru; Kimura, Takeshi; Ono, Koh

    2014-01-01

    MicroRNAs (miRs) are small non-protein-coding RNAs that bind to specific mRNAs and inhibit translation or promote mRNA degradation. Recent reports, including ours, indicated that miR-33a located within the intron of sterol regulatory element-binding protein (SREBP) 2 controls cholesterol homeostasis and can be a possible therapeutic target for treating atherosclerosis. Primates, but not rodents, express miR-33b from an intron of SREBF1. Therefore, humanized mice, in which a miR-33b transgene is inserted within a Srebf1 intron, are required to address its function in vivo. We successfully established miR-33b knock-in (KI) mice and found that protein levels of known miR-33a target genes, such as ABCA1, ABCG1, and SREBP-1, were reduced compared with those in wild-type mice. As a consequence, macrophages from the miR-33b KI mice had a reduced cholesterol efflux capacity via apoA-I and HDL-C. Moreover, HDL-C levels were reduced by almost 35% even in miR-33b KI hetero mice compared with the control mice. These results indicate that miR-33b may account for lower HDL-C levels in humans than those in mice and that miR-33b is possibly utilized for a feedback mechanism to regulate its host gene SREBF1. Our mice will also aid in elucidating the roles of miR-33a/b in different genetic disease models. PMID:24931346

  18. Ethics on Exhibit

    ERIC Educational Resources Information Center

    Vick, Randy M.

    2011-01-01

    This article discusses ethical questions raised by an exhibition of work by an artist with a history of mental illness and the exhibition's relevance to art therapy and “outsider art” discourse on the subject. Considerations for how such an exhibit could be handled had the circumstances included an art therapist and art therapy client are…

  19. Paradoxical effects of D-amphetamine in infant and adolescent mice: role of gender and environmental risk factors.

    PubMed

    Cirulli, F; Laviola, G

    2000-01-01

    The psychostimulant D-amphetamine (AMPH) increases generalised activity in adult subjects, while exerting a paradoxical "calming effect" in children with Attention-deficit Hyperactivity Disorder (AD/HD). A number of animal models have been developed to characterise the neurobiological basis of this AMPH action. In this line, the present review summarises recent work on the effects of AMPH on behavioural and physiological parameters in developing mice with a special emphasis on the role of gender and environmental risk factors. Behavioural and neuroendocrine responses to AMPH administration (0, 1, or 3 mg/kg, IP) and their relation to changes in the environment, represented by social stimuli, were studied in infant CD-1 mouse pups of both sexes at three different developmental ages (3, 8, or 18 postnatal (pnd) days). Mouse pups were assessed either in baseline condition or following 24 h maternal deprivation. AMPH exerted a paradoxical effect on CORT secretion only in maternally deprived subjects while affecting behaviour mainly in deprived female subjects, which showed a generalised shift to the left in the dose-response curve to this drug. Unwanted perseverative motor effects and possible dependence states represent side effects of AMPH administration. Further knowledge on these aspects comes from another set of studies where a shortened conditioned place preference (CPP) paradigm was employed to assess the reinforcing properties of AMPH (0, 1, 3.3, or 10 mg/kg) in developing mice on 14-17, 21-24, and 28-31 pnd. Data indicate that AMPH-CPP develops early, mice being able, already at two weeks of age, to acquire a place preference that relies on adult-like sensory, motor, and associative capacities. AMPH-CPP appears earlier in females, compared to males. A detailed analysis of acute D-amphetamine effects evidenced that the drug produces a dose-dependent increase in locomotor activity and in several responses (including stereotypes). These effects appear much larger

  20. A Teaching Aids Exhibition.

    ERIC Educational Resources Information Center

    Mahanja, Salah

    1985-01-01

    Describes an exhibition for the benefit of teachers of English in Arab Primary Schools, which was prepared by third-year students at the Teachers College for Arab Teachers. The exhibition included games, songs, audiovisual aids, crossword puzzles, vocabulary, spelling booklets, preposition aids, and worksheet and lesson planning aids. (SED)

  1. Communicating Science through Exhibitions

    NASA Astrophysics Data System (ADS)

    Dusenbery, P.; Harold, J.; Morrow, C.

    It is critically important for the public to better understand the scientific process. Museum exhibitions are an important part of informal science education that can effectively reach public audiences as well as school groups. They provide an important gateway for the public to learn about compelling scientific endeavors. There are many ways for scientists to help develop science exhibitions. The Space Science Institute (SSI) is a national leader in producing traveling science exhibitions and their associated educational programming (i.e. interactive websites, educator workshops, public talks, instructional materials). Two of its exhibitions, Space Weather Center and MarsQuest, are currently on tour. Another exhibition, Alien Earths, is in development. The Space Weather Center was developed in partnership with various research missions at NASA's Goddard Space Flight Center. MarsQuest is a 5000 square-foot traveling exhibition. The exhibit's second 3-year tour began this January at the Detroit Science Center. It is enabling millions of Americans to share in the excitement of the scientific exploration of Mars and to learn more about their own planet in the process. The 3,000 square-foot traveling exhibition, called Alien Earths, will bring origins-related research and discoveries to students and the American public. Alien Earths has four interrelated exhibit areas: Our Place in Space, Star Birth, PlanetQuest, and Search for Life. Exhibit visitors will explore the awesome events surrounding the birth of stars and planets; they will join scientists in the hunt for planets outside our solar system including those that may be in ``habitable zones'' around other stars; and finally they will be able to learn about how scientists are looking for signs of life beyond Earth. Besides the exhibits, SSI is also developing interactive web sites based on exhibit themes. New technologies are transforming the Web from a static medium to an interactive environment with tremendous

  2. New Hurricane Exhibit

    NASA Technical Reports Server (NTRS)

    2007-01-01

    A new exhibit in StenniSphere depicting NASA's role in hurricane prediction and research and SSC's role in helping the region recover from Hurricane Katrina. The cyclone-shaped exhibit focuses on the effects of the Aug. 29, 2005 storm and outlines how NASA is working to improve weather forecasting. Through photos, 3-D models and digital animations, the exhibit tells the story of what happened inside the storm and how NASA's scientific research can increase the accuracy of hurricane tracking and modeling.

  3. Gallic Acid, an active constituent of grape seed extract, exhibits anti-proliferative, pro-apoptotic and anti-tumorigenic effects against prostate carcinoma xenograft growth in nude mice

    PubMed Central

    Kaur, Manjinder; Velmurugan, Balaiya; Rajamanickam, Subapriya; Agarwal, Rajesh; Agarwal, Chapla

    2009-01-01

    Purpose Gallic acid, a natural agent present wide-range of fruits and vegetables, has been of potential interest as anti-cancer agent; herein, we evaluated its efficacy in androgen-independent DU145 and androgen-dependent-22Rv1 human prostate cancer (PCa) cells Materials and Methods Cell viability was determined by MTT and apoptosis by Annexin V-PI assays. In vivo anti-cancer efficacy was assessed by DU145 and 22Rv1 xenograft growth in nude mice given normal drinking water or one supplemented with 0.3% or 1% (w/v) gallic acid. PCNA, TUNEL and CD31 immunostaining was performed in tumor tissues for in vivo anti-proliferative, apoptotic and anti-angiogenic effects of gallic acid. Results Gallic acid decreased cell viability in a dose-dependent manner in both DU145 and 22Rv1 cells largely via apoptosis induction. In tumor studies, gallic acid feeding inhibited the growth of DU145 and 22Rv1 PCa xenografts in nude mice. Immunohistochemical analysis revealed significant inhibition of tumor cell proliferation, induction of apoptosis, and reduction of microvessel density in tumor xenografts from gallic acid-fed mice as compared to controls in both DU145 and 22Rv1 models Conclusion Taken together, our findings show the anti-PCa efficacy of gallic acid providing a rationale for additional studies with this naturally-occurring agent for its efficacy against PCa. PMID:19543955

  4. Test Control Center exhibit

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Have you ever wondered how the engineers at John C. Stennis Space Center in Hancock County, Miss., test fire a Space Shuttle Main Engine? The Test Control Center exhibit at StenniSphere can answer your questions by simulating the test firing of a Space Shuttle Main Engine. A recreation of one of NASA's test control centers, the exhibit explains and portrays the 'shake, rattle and roar' that happens during a real test firing.

  5. Communicating Science through Exhibitions

    NASA Astrophysics Data System (ADS)

    Dusenbery, Paul

    2005-04-01

    It is critically important for the public to better understand the scientific process. Museum exhibitions are an important part of informal science education that can effectively reach public audiences as well as school groups. They provide an important gateway for the public to learn about compelling scientific endeavors. Science exhibitions also provide a marvelous opportunity for scientists to become engaged in the exhibit development process. The Space Science Institute (SSI) is a national leader in producing traveling science exhibitions and their associated educational programming (i.e. interactive websites, educator workshops, public talks, instructional materials). The focus of this presentation will be on two of its exhibit projects: MarsQuest (on tour for four years) and Alien Earths (its tour began early in 2005). MarsQuest is enabling millions of Americans to share in the excitement of the scientific exploration of Mars and to learn more about their own planet in the process. Alien Earths will bring origins-related research and discoveries to students and the American public. It has four interrelated exhibit areas: Our Place in Space, Star Birth, Planet Quest, and Search for Life. Exhibit visitors will explore the awesome events surrounding the birth of stars and planets; they will join scientists in the hunt for planets outside our solar system including those that may be in ``habitable zones'' around other stars; and finally they will be able to learn about how scientists are looking for signs of life beyond Earth. SSI is also developing interactive web sites based on exhibit themes. New technologies are transforming the Web from a static medium to an interactive environment with tremendous potential for informal education and inquiry-based investigations. This talk will focus on the role informal science projects play in effectively communicating science to a broad, public audience.

  6. Adolescent development

    MedlinePlus

    Development - adolescent; Growth and development - adolescent ... During adolescence, children develop the ability to: Understand abstract ideas. These include grasping higher math concepts, and developing moral ...

  7. Swamp to Space exhibit

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The menacing-looking alligator is really harmless. It is one of the realistic props to help convince visitors that the feel of the swamp is real in StenniSphere's Swamp to Space exhibit at John C. Stennis Space Center in Hancock County, Miss. The historical section of the Swamp to Space exhibit tells the story of why and how Stennis Space Center came to be. It also pays tribute to the families who moved their homes to make way for the space age in Mississippi.

  8. Exhibition in Sight

    ERIC Educational Resources Information Center

    Wasserman, Burton

    1978-01-01

    Ludwig Mies van der Rohe is known primarily as an architect. However, he also designed chairs and tables. Discusses an exhibit held in New York City a few months ago which showed how well the famous architect achieved his goals in the area of furniture design. (Author/RK)

  9. Exhibition in Sight

    ERIC Educational Resources Information Center

    Wasserman, Burton

    1978-01-01

    One of the most offbeat exhibitions presented in the last several years was the widely celebrated Warhol-Wyeth duo show, "Portraits of Each Other", held at the Brandywine River Museum in Chadds Ford, Pennsylvania. Discusses their paintings and their diametrically different personalities. (Author/RK)

  10. Adolescent exposure to MDMA induces dopaminergic toxicity in substantia nigra and potentiates the amyloid plaque deposition in the striatum of APPswe/PS1dE9 mice.

    PubMed

    Abad, Sonia; Ramon, Carla; Pubill, David; Camarasa, Jorge; Camins, Antonio; Escubedo, Elena

    2016-09-01

    MDMA is one of the most used drugs by adolescents and its consumption has been associated with many psychobiological problems, among them psychomotor problems. Moreover, some authors described that early exposure to MDMA may render the dopaminergic neurons more vulnerable to the effects of future neurotoxic insults. Alzheimer disease (AD) is the main cause of dementia in the elderly and a percentage of the patients have predisposition to suffer nigrostriatal alterations, developing extrapyramidal signs. Nigrostriatal dysfunction in the brain of aged APPswe/PS1dE9 (APP/PS1), a mouse model of familiar AD (FAD), has also been described. The aim of the present study was to investigate the consequences of adolescent exposure to MDMA in APP/PS1 mice, on nigrostriatal function on early adulthood. We used a MDMA schedule simulating weekend binge abuse of this substance. Our MDMA schedule produced a genotype-independent decrease in dopaminergic neurons in the substantia nigra that remained at least 3months. Shortly after the injury, wild-type animals showed a decrease in the locomotor activity and apparent DA depletion in striatum, however in the APP/PS1 mice neither the locomotor activity nor the DA levels were modified, but a reduction in dopamine transporter (DAT) expression and a higher levels of oxidative stress were observed. We found that these disturbances are age-related characteristics that this APP/PS1 mice develops spontaneously much later. Therefore, MDMA administration seems to anticipate the striatal dopaminergic dysfunction in this FAD model. The most important outcome lies in a potentiation, by MDMA, of the amyloid beta deposition in the striatum. PMID:27344237

  11. Starship 2040 Exhibit

    NASA Technical Reports Server (NTRS)

    2002-01-01

    This photograph shows onlookers viewing displays within the Starship 2040 exhibit on display at Joe Davis Stadium in Huntsville, Alabama. Developed by the Space Transportation Directorate at Marshall Space Flight Center (MSFC), the Starship 2040 exhibit is housed in a 48-ft (14.6-m) tractor and trailer rig, permitting it to travel around the Nation, demonstrating NASA's vision of what commercial spaceflight might be like 40 years from now. All the irnovations suggested aboard the exhibit (automated vehicle health monitoring systems, high-energy propulsion drive, navigational aids, and emergency and safety systems) are based on concepts and technologies now being studied at NASA Centers and partner institutions around the Nation. NASA is the Nation's premier agency for development of the space transportation system, including future-generation reusable launch vehicles. Such systems, the keys to a 'real' Starship 2040, require revolutionary advances in critical aerospace technologies, from thermal, magnetic, chemical, and propellantless propulsion systems to new energy sources such as space solar power or antimatter propulsion. These and other advances are now being studied, developed, and tested at NASA field centers and partner institutions all over the Nation.

  12. Starship 2040 Exhibit

    NASA Technical Reports Server (NTRS)

    2002-01-01

    This photograph shows Justin Varnadore, son of a Marshall TV employee, at the controls of one of the many displays within the Starship 2040 exhibit on display at Joe Davis Stadium in Huntsville, Alabama. Developed by the Space Transportation Directorate at Marshall Space Flight Center (MSFC), the Starship 2040 exhibit is housed in a 48-ft (14.6-m) tractor and trailer rig, permitting it to travel around the Nation, demonstrating NASA's vision of what commercial spaceflight might be like 40 years from now. All the irnovations suggested aboard the exhibit (automated vehicle health monitoring systems, high-energy propulsion drive, navigational aids, and emergency and safety systems) are based on concepts and technologies now being studied at NASA Centers and partner institutions around the Nation. NASA is the Nation's premier agency for development of the space transportation system, including future-generation reusable launch vehicles. Such systems, the keys to a 'real' Starship 2040, require revolutionary advances in critical aerospace technologies, from thermal, magnetic, chemical, and propellantless propulsion systems to new energy sources such as space solar power or antimatter propulsion. These and other advances are now being studied, developed, and tested at NASA field centers and partner institutions all over the Nation.

  13. Starship 2040 Exhibit

    NASA Technical Reports Server (NTRS)

    2001-01-01

    This photograph shows the Starship 2040 leaving the Marshall Space Flight Center (MSFC) for the exhibit site. Developed by the Space Transportation Directorate at MSFC, the Starship 2040 exhibit is housed in a 48-ft (14.6-m) tractor and trailer rig, permitting it to travel around the Nation, demonstrating NASA's vision of what commercial spaceflight might be like 40 years from now. All the irnovations suggested aboard the exhibit, automated vehicle health monitoring systems, high-energy propulsion drive, navigational aids and emergency and safety systems, are based on concepts and technologies now being studied at NASA Centers and partner institutions around the Nation. NASA is the nation's premier agency for development of the space transportation system, including future-generation reusable launch vehicles. Such systems, the keys to a 'real' Starship 2040, require revolutionary advances in critical aerospace technologies, from thermal, magnetic, chemical, and propellantless propulsion systems to new energy sources such as space solar power or antimatter propulsion. These and other advances are now being studied, developed, and tested at NASA field centers and partner institutions all over the Nation.

  14. Online Exhibits & Concept Maps

    NASA Astrophysics Data System (ADS)

    Douma, M.

    2009-12-01

    Presenting the complexity of geosciences to the public via the Internet poses a number of challenges. For example, utilizing various - and sometimes redundant - Web 2.0 tools can quickly devour limited time. Do you tweet? Do you write press releases? Do you create an exhibit or concept map? The presentation will provide participants with a context for utilizing Web 2.0 tools by briefly highlighting methods of online scientific communication across several dimensions. It will address issues of: * breadth and depth (e.g. from narrow topics to well-rounded views), * presentation methods (e.g. from text to multimedia, from momentary to enduring), * sources and audiences (e.g. for experts or for the public, content developed by producers to that developed by users), * content display (e.g. from linear to non-linear, from instructive to entertaining), * barriers to entry (e.g. from an incumbent advantage to neophyte accessible, from amateur to professional), * cost and reach (e.g. from cheap to expensive), and * impact (e.g. the amount learned, from anonymity to brand awareness). Against this backdrop, the presentation will provide an overview of two methods of online information dissemination, exhibits and concept maps, using the WebExhibits online museum (www.webexhibits.org) and SpicyNodes information visualization tool (www.spicynodes.org) as examples, with tips on how geoscientists can use either to communicate their science. Richly interactive online exhibits can serve to engage a large audience, appeal to visitors with multiple learning styles, prompt exploration and discovery, and present a topic’s breadth and depth. WebExhibits, which was among the first online museums, delivers interactive information, virtual experiments, and hands-on activities to the public. While large, multidisciplinary exhibits on topics like “Color Vision and Art” or “Calendars Through the Ages” require teams of scholars, user interface experts, professional writers and editors

  15. Space Shuttle Cockpit exhibit

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Want to sit in the cockpit of the Space Shuttle and watch astronauts work in outer space? At StenniSphere, you can do that and much more. StenniSphere, the visitor center at John C. Stennis Space Center in Hancock County, Miss., presents 14,000-square-feet of interactive exhibits that depict America's race for space as well as a glimpse of the future. StenniSphere is open free of charge from 9 a.m. to 5 p.m. daily.

  16. Smithsonian climate change exhibits

    NASA Astrophysics Data System (ADS)

    Kumar, Mohi

    2006-05-01

    Two new museum exhibits, ``Arctic: A Friend Acting Strangely'' and ``Atmosphere: Change is in the Air'' opened 15 April at the Smithsonian Institution's National Museum of Natural History in Washington, D.C., in partnership with the U.S. National Oceanic and Atmospheric Administration, NASA, and the U.S. National Science Foundation. In ``Arctic: A Friend Acting Strangely,'' anecdotes from indigenous polar people reveal how climate changes have affected life within the last 50 years. For example, as permafrost melts and sea ice shrinks, plant distributions and animal migration patterns are changing, severely affecting culture.

  17. Starship 2040 Exhibit

    NASA Technical Reports Server (NTRS)

    2002-01-01

    This photograph shows the Starship 2040 on display at Joe Davis Stadium in Huntsville, Alabama. Developed by the Space Transportation Directorate at Marshall Space Flight Center (MSFC), the Starship 2040 exhibit is housed in a 48-ft (14.6-m) tractor and trailer rig, permitting it to travel around the Nation, demonstrating NASA's vision of what commercial spaceflight might be like 40 years from now. All the irnovations suggested aboard the exhibit (automated vehicle health monitoring systems, high-energy propulsion drive, navigational aids, and emergency and safety systems) are based on concepts and technologies now being studied at NASA Centers and partner institutions around the Nation. NASA is the Nation's premier agency for development of the space transportation system, including future-generation reusable launch vehicles. Such systems, the keys to a 'real' Starship 2040, require revolutionary advances in critical aerospace technologies, from thermal, magnetic, chemical, and propellantless propulsion systems to new energy sources such as space solar power or antimatter propulsion. These and other advances are now being studied, developed, and tested at NASA field centers and partner institutions all over the Nation.

  18. Establishment of mesenchymal stem cell lines derived from the bone marrow of green fluorescent protein-transgenic mice exhibiting a diversity in intracellular transforming growth factor-β and bone morphogenetic protein signaling.

    PubMed

    Sawada, Shunsuke; Chosa, Naoyuki; Takizawa, Naoki; Yokota, Jun; Igarashi, Yasuyuki; Tomoda, Koichi; Kondo, Hisatomo; Yaegashi, Takashi; Ishisaki, Akira

    2016-03-01

    Cytokines and their intercellular signals regulate the multipotency of mesenchymal stem cells (MSCs). The present study established the MSC lines SG‑2, ‑3, and ‑5 from the bone marrow of green fluorescent protein (GFP)‑transgenic mice. These cell lines clearly expressed mouse MSC markers Sca‑1 and CD44, and SG‑2 and ‑5 cells retained the potential for osteogenic and adipogenic differentiation in the absence of members of the transforming growth factor (TGF)‑β superfamily. By contrast, SG‑3 cells only retained adipogenic differentiation potential. Analysis of cytokine and cytokine receptor expression in these SG cell lines showed that bone morphogenetic protein (BMP) receptor 1B was most highly expressed in the SG‑3 cells, which underwent osteogenesis in response to BMP, while TGF‑β receptor II was most highly expressed in SG‑3 and ‑5 cells. However, it was unexpectedly noted that phosphorylation of Smad 2, a major transcription factor, was induced by TGF‑β1 in SG‑2 cells but not in SG‑3 or ‑5 cells. Furthermore, TGF‑β1 clearly induced the expression of Smad‑interacting transcription factor CCAAT/enhancer binding protein‑β in SG‑2 but not in SG‑3 or ‑5 cells. These results demonstrated the establishment of TGF‑β‑responsive SG‑2 MSCs, BMP‑responsive SG‑3 MSCs and TGF‑β/BMP‑unresponsive SG‑5 MSCs, each of which was able to be traced by GFP fluorescence after transplantation into in vivo experimental models. In conclusion, the present study suggested that these cell lines may be used to explore how the TGF‑β superfamily affects the proliferation and differentiation status of MSCs in vivo. PMID:26781600

  19. 18F9 (4-(3,6-bis (ethoxycarbonyl)-4,5,6,7-tetrahydrothieno (2,3-c) pyridin-2-ylamino)-4-oxobutanoic acid) enhances insulin-mediated glucose uptake in vitro and exhibits antidiabetic activity in vivo in db/db mice.

    PubMed

    Anandharajan, Rathinasabapathy; Sayyed, Sufyan G; Doshi, Lalit S; Dixit, Pooja; Chandak, Prakash G; Dixit, Amol V; Brahma, Manoja K; Deshmukh, Nitin J; Gupte, Ravindra; Damre, Anagha; Suthar, Jaspreet; Padigaru, Muralidhara; Sharma, Somesh D; Nemmani, Kumar V S

    2009-10-01

    Insulin resistance is central to the pathogenesis of type 2 diabetes mellitus. Previous studies have demonstrated that compounds that cause adipogenesis and improve glucose uptake in 3T3-L1 cells are potential insulin sensitizers. Therefore, we evaluated one such compound, 18F9, for (1) adipogenesis in human subcutaneous preadipocyte (SQ) cells, (2) glucose uptake in human skeletal muscle myotubes and SQ cells, and (3) antidiabetic activity in db/db mice. We also investigated its effect on ex vivo glucose uptake in soleus muscle isolated from continuously treated db/db mice. Gene expression profiling in soleus muscle and epididymal fat of db/db mice was performed to understand its effect on glucose metabolism, lipid metabolism, and thermogenesis. 18F9 enhanced adipogenesis in SQ cells and increased glucose uptake in SQ and human skeletal muscle myotubes cells. In db/db mice, 18F9 exhibited dose-dependent reduction in plasma glucose and insulin level. Interestingly, 18F9 was as efficacious as rosiglitazone but did not cause body weight gain and hepatic adverse effects. In addition, 18F9 demonstrated no change in plasma volume in Wistar rats. Furthermore, it enhanced ex vivo glucose uptake in soleus muscles in these mice, which substantiates our in vitro findings. Human peroxisome proliferator activated receptor-gamma transactivation assay revealed a weak peroxisome proliferator activated receptor-gamma transactivation potential (44% of rosiglitazone at 10 mumol/L) of 18F9. Gene expression profiling indicated that 18F9 increased insulin sensitivity mainly through a phosphoinositide 3-kinase-dependent mechanism. 18F9 also up-regulated genes involved in lipid transport and synthesis at par with rosiglitazone. Unlike rosiglitazone, 18F9 elevated the expression of Pdk4. In addition, 18F9 elevated the expression of glycogen synthase and adiponectin significantly higher than rosiglitazone. Taken together, these observations suggest that 18F9 is a safer and potent insulin

  20. Delayed emergence of behavioral and electrophysiological effects following juvenile ketamine exposure in mice.

    PubMed

    Nagy, L R; Featherstone, R E; Hahn, C G; Siegel, S J

    2015-09-15

    Frequent ketamine abuse in adulthood correlates with increased risk of psychosis, as well as cognitive deficits, including disruption of higher-order executive function and memory formation. Although the primary abusers of ketamine are adolescents and young adults, few studies have evaluated its effects on juvenile cognition. Therefore, the current study analyzes the effect of adolescent ketamine exposure on cognitive development. Juvenile mice (4 weeks of age) were exposed to chronic ketamine (20 mg kg(-1), i.p. daily) for 14 days. Mice were tested immediately after exposure in the juvenile period (7 weeks of age) and again as adults (12 weeks of age). Measures included electroencephalography (EEG) in response to auditory stimulation, the social choice test, and a 6-arm radial water maze task. Outcome measures include low-frequency EEG responses, event-related potential (ERP) amplitudes, indices of social behavior and indices of spatial working memory. Juvenile exposure to ketamine was associated with electrophysiological abnormalities in adulthood, particularly in induced theta power and the P80 ERP. The social choice test revealed that ketamine-exposed mice failed to exhibit the same age-related decrease in social interaction time as controls. Ketamine-exposed mice outperformed control mice as juveniles on the radial water maze task, but did not show the same age-related improvement as adult controls. These data support the hypothesis that juvenile exposure to ketamine produces long-lasting changes in brain function that are characterized by a failure to progress along normal developmental trajectories.

  1. Homozygous mutation of VPS16 gene is responsible for an autosomal recessive adolescent-onset primary dystonia

    PubMed Central

    Cai, Xiaodong; Chen, Xin; Wu, Song; Liu, Wenlan; Zhang, Xiejun; Zhang, Doudou; He, Sijie; Wang, Bo; Zhang, Mali; Zhang, Yuan; Li, Zongyang; Luo, Kun; Cai, Zhiming; Li, Weiping

    2016-01-01

    Dystonia is a neurological movement disorder that is clinically and genetically heterogeneous. Herein, we report the identification a novel homozygous missense mutation, c.156 C > A in VPS16, co-segregating with disease status in a Chinese consanguineous family with adolescent-onset primary dystonia by whole exome sequencing and homozygosity mapping. To assess the biological role of c.156 C > A homozygous mutation of VPS16, we generated mice with targeted mutation site of Vps16 through CRISPR-Cas9 genome-editing approach. Vps16 c.156 C > A homozygous mutant mice exhibited significantly impaired motor function, suggesting that VPS16 is a new causative gene for adolescent-onset primary dystonia. PMID:27174565

  2. Adolescent images of adolescence.

    PubMed

    Falchikov, N

    1989-06-01

    This study examines the extent to which a group of Scottish adolescents are influenced by negative images of adolescence present in our culture, and investigates their self-image by means of a Q sort. Forty 15- and 16-year-old school students took part in the study, half of whom were female. Half of the sample were staying on at school to take higher examinations, the other half being school leavers. Eleven factors emerged from the analysis, the first six of which met the criterion that distinguishes common factors. Participants defining common factors were re-interviewed, and their responses to factor interpretations noted. Little evidence was found to suggest that adolescents are influenced by newspaper images. Some descriptions hint at conflict, while others do not. If the results of the present study were to be replicated, a more pluralistic view of adolescence may be required.

  3. Paradoxical anxiogenic response of juvenile mice to fluoxetine.

    PubMed

    Oh, Ji-eun; Zupan, Bojana; Gross, Steven; Toth, Miklos

    2009-09-01

    Depression, anxiety, and conduct disorders are common in children and adolescents, and selective serotonin reuptake inhibitors (SSRIs) are often used to treat these conditions. Fluoxetine (Prozac) is the first approved SSRI for the treatment of depression in this population. Although it is believed that overall, fluoxetine is effective in child and adolescent psychiatry, there have been reports of specific adverse drug effects, most prominently, suicidality and psychiatric symptoms such as agitation, worsening of depression, and anxiety. Chronic fluoxetine substantially increases brain extracellular 5-HT concentrations, and the juvenile developing brain may respond to supraphysiological 5-HT levels with specific adverse effects not seen or less prominent in adult brain. Using novelty-induced hypophagia, as well as open-field and elevated plus maze tests, we show that both Swiss Webster and C57Bl/6 mice, receiving fluoxetine in a clinically relevant dose and during their juvenile age corresponding to child-adolescent periods in humans, exhibit a paradoxical anxiogenic response. The adverse effects of juvenile fluoxetine disappeared upon drug discontinuation and no long-term behavioral consequences were apparent. No adverse effect to chronic fluoxetine was seen in adult mice and a dose-dependent anxiolytic effect developed. These data show that the age of the mice, independently of the strains and tests used in this study, is the determining factor of whether the response to chronic fluoxetine is anxiolytic or anxiogenic. Taken together, the response of the juvenile and adult brain to fluoxetine could be fundamentally different and the juvenile fluoxetine administration mouse model described here may help to identify the mechanism underlying this difference.

  4. The Effect of mGluR5 Antagonism During Binge Drinkingon Subsequent Ethanol Intake in C57BL/6J Mice: Sex- and Age-Induced Differences

    PubMed Central

    Cozzoli, Debra K.; Strong-Kaufman, Moriah N.; Tanchuck, Michelle A.; Hashimoto, Joel G.; Wiren, Kristine M.; Finn, Deborah A.

    2016-01-01

    Background Binge ethanol (EtOH) intake during adolescence leads to an array of behavioral and cognitive consequences including elevated intake of EtOH during adulthood, with female mice showing greater susceptibility than males. Administration of the metabotropic glutamate receptor 5 (mGluR5) antagonist 3-((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) has been shown to reduce EtOH self-administration in adult male mice, but little is known about its effect on female and adolescent mice. Methods MTEP (0, 10, 20 mg/kg, i.p.) was repeatedly administered to female and male, adult and adolescent C57BL/6J mice during binge sessions using the scheduled high alcohol consumption paradigm. Next, we assessed whether MTEP administration during binge altered the subsequent 24-hour EtOH intake following a period of abstinence. Finally, we investigated whether MTEP administration during binge followed by an abstinence period altered mRNA of glutamatergic genes within the nucleus accumbens of female mice. Results MTEP significantly decreased binge EtOH intake in all mice, but only female mice exhibited altered subsequent 24-hour EtOH intake. Interestingly, the alteration in subsequent EtOH intake in female animals was age dependent, with adolescent exposure to MTEP during binge decreasing 24-hour intake and adult exposure to MTEP during binge increasing 24-hour intake. Finally, while there were no effects of MTEP pretreatment on the genes examined, there was a robust age effect found during analysis of mGluR1 (Grm1), mGluR5 (Grm5), the NR2A subunit of the NMDA receptor (Grin2a), phosphatidylinositol 3-kinase (Pik3r1), mammalian target of rapamycin (Mtor), and extracellular signal-regulated kinase (Mapk1) mRNA, with adolescent female animals having lower expression than their adult counterparts. Conclusions Collectively, the present findings add to existing evidence implicating the contribution of long-term effects of adolescent binge drinking to enhance alcohol abuse in

  5. Exhibitions: Facing Outward, Pointing Inward

    ERIC Educational Resources Information Center

    McDonald, Joseph P.

    2007-01-01

    The Coalition of Essential Schools (CES) Exhibitions Project of the early 1990s produced a range of work that continues to inform the practice of using exhibitions as a "360 degree" method of transforming teaching and learning, community connections, school design, and assessment. Among that work was this paper coupling the origins of exhibitions…

  6. Disruption of the ErbB signaling in adolescence increases striatal dopamine levels and affects learning and hedonic-like behavior in the adult mouse.

    PubMed

    Golani, Idit; Tadmor, Hagar; Buonanno, Andres; Kremer, Ilana; Shamir, Alon

    2014-11-01

    The ErbB signaling pathway has been genetically and functionally implicated in schizophrenia. Numerous findings support the dysregulation of Neuregulin (NRG) and epidermal growth factor (EGF) signaling in schizophrenia. However, it is unclear whether alterations of these pathways in the adult brain or during development are involved in the pathophysiology of schizophrenia. Herein we characterized the behavioral profile and molecular changes resulting from pharmacologically blocking the ErbB signaling pathway during a critical period in the development of decision making, planning, judgments, emotions, social cognition and cognitive skills, namely adolescence. We demonstrate that chronic administration of the pan-ErbB kinase inhibitor JNJ-28871063 (JNJ) to adolescent mice elevated striatal dopamine levels and reduced preference for sucrose without affecting locomotor activity and exploratory behavior. In adulthood, adolescent JNJ-treated mice continue to consume less sucrose and needed significantly more correct-response trials to reach the learning criterion during the discrimination phase of the T-maze reversal learning task than their saline-injected controls. In addition, JNJ mice exhibited deficit in reference memory but not in working memory as measured in the radial arm maze. Inhibition of the pathway during adolescence did not affect exploratory behavior and locomotor activity in the open field, social interaction, social memory, and reversal learning in adult mice. Our data suggest that alteration of ErbB signaling during adolescence resulted in changes in the dopaminergic systems that emerge in pathological learning and hedonic behavior in adulthood, and pinpoints the possible role of the pathway in the development of cognitive skills and motivated behavior. PMID:25451700

  7. Against the Odds Exhibition Opens

    MedlinePlus

    ... LA and Vox Populi organizations. Photo courtesy of Bill Branson At the exhibition, HIV and AIDS were topics addressed by Dr. Victoria Cargill (right), Director of Clinical Studies and Director of Minority ...

  8. Greenhouse Earth: A Traveling Exhibition

    SciTech Connect

    Booth, W.H.; Caesar, S.

    1992-09-01

    The Franklin Institute Science Museum provided an exhibit entitled the Greenhouse Earth: A Traveling Exhibition. This 3500 square-foot exhibit on global climate change was developed in collaboration with the Association of Science-Technology Centers. The exhibit opened at The Franklin Institute on February 14, 1992, welcoming 291,000 visitors over its three-month stay. During its three-year tour, Greenhouse Earth will travel to ten US cities, reaching two million visitors. Greenhouse Earth aims to deepen public understanding of the scientific issues of global warming and the conservation measures that can be taken to slow its effects. The exhibit features hands-on exhibitry, interactive computer programs and videos, a theater production, a demonstration cart,'' guided tours, and lectures. supplemental educational programs at the Institute included a teachers preview, a symposium on climate change, and a satellite field trip.'' The development of Greenhouse Earth included front-end and formative evaluation procedures. Evaluation includes interviews with visitors, prototypes, and summative surveys for participating museums. During its stay in Philadelphia, Greenhouse Earth was covered by the local and national press, with reviews in print and broadcast media. Greenhouse Earth is the first large-scale museum exhibit to address global climate change.

  9. Early postnatal nicotine exposure causes hippocampus-dependent memory impairments in adolescent mice: association with altered nicotinic cholinergic modulation of LTP, but not impaired LTP

    PubMed Central

    Nakauchi, Sakura; Malvaez, Melissa; Su, Hailing; Kleeman, Elise; Dang, Richard; Wood, Marcelo A.; Sumikawa, Katumi

    2014-01-01

    Fetal nicotine exposure from smoking during pregnancy causes long-lasting cognitive impairments in offspring, yet little is known about the mechanisms that underlie this effect. Here we demonstrate that early postnatal exposure of mouse pups to nicotine via maternal milk impairs long-term, but not short-term, hippocampus-dependent memory during adolescence. At the Schaffer collateral (SC) pathway, the most widely studied synapses for a cellular correlate of hippocampus-dependent memory, the induction of N-methyl-d-aspartate receptor-dependent transient long-term potentiation (LTP) and protein synthesis-dependent long-lasting LTP are not diminished by nicotine exposure, but rather unexpectedly the threshold for LTP induction becomes lower after nicotine treatment. Using voltage sensitive dye to visualize hippocampal activity, we found that early postnatal nicotine exposure also results in enhanced CA1 depolarization and hyperpolarization after SC stimulation. Furthermore, we show that postnatal nicotine exposure induces pervasive changes to the nicotinic modulation of CA1 activity: activation of nicotinic receptors no longer increases CA1 network depolarization, acute nicotine inhibits rather than facilitates the induction of LTP at the SC pathway by recruiting an additional nicotinic receptor subtype, and acute nicotine no longer blocks LTP induction at the temporoammonic pathway. These findings reflect the pervasive impact of nicotine exposure during hippocampal development, and demonstrate an association of hippocampal memory impairments with altered nicotinic cholinergic modulation of LTP, but not impaired LTP. The implication of our results is that nicotinic cholinergic-dependent plasticity is required for long-term memory formation and that postnatal nicotine exposure disrupts this form of plasticity. PMID:25545599

  10. Considering High-Tech Exhibits?

    ERIC Educational Resources Information Center

    Routman, Emily

    1994-01-01

    Discusses a variety of high-tech exhibit media used in The Living World, an educational facility operated by The Saint Louis Zoo. Considers the strengths and weaknesses of holograms, video, animatronics, video-equipped microscopes, and computer interactives. Computer interactives are treated with special attention. (LZ)

  11. Balamuthia mandrillaris exhibits metalloprotease activities.

    PubMed

    Matin, Abdul; Stins, Monique; Kim, Kwang Sik; Khan, Naveed Ahmed

    2006-06-01

    Balamuthia mandrillaris is a recently identified protozoan pathogen that can cause fatal granulomatous encephalitis. However, the pathogenesis and pathophysiology of B. mandrillaris encephalitis remain unclear. Because proteases may play a role in the central nervous system (CNS) pathology, we used spectrophotometric, cytopathic and zymographic assays to assess protease activities of B. mandrillaris. Using two clinical isolates of B. mandrillaris (from human and baboon), we observed that B. mandrillaris exhibits protease activities. Zymographic assays revealed major protease bands of approximate molecular weights in the region of 40-50 kDa on sodium dodecyl sulfate-polyacrylamide gels using gelatin as substrate. The protease bands were inhibited with 1,10-phenanthroline, suggesting metallo-type proteases. The proteolytic activities were observed over a pH range of 5-11 with maximum activity at neutral pH and at 42 degrees C. Balamuthia mandrillaris proteases exhibit properties to degrade extracellular matrix (ECM), which provide structural and functional support to the brain tissue. This is shown by degradation of collagen I and III (major components of collagenous ECM), elastin (elastic fibrils of ECM), plasminogen (involved in proteolytic degradation of ECM), as well as other substrates such as casein and gelatin but not haemoglobin. However, these proteases exhibited a minimal role in B. mandrillaris-mediated host cell death in vitro using human brain microvascular endothelial cells (HBMECs). This was shown using broad-spectrum matrix metalloprotease inhibitors, GM 6001 and GM 1489, which had no effect on B. mandrillaris-mediated HBMEC cytotoxicity. This is the first demonstration that B. mandrillaris exhibits metalloproteases, which may play important role(s) in the ECM degradation and thus in CNS pathology. PMID:16706791

  12. Delayed emergence of behavioral and electrophysiological effects following juvenile ketamine exposure in mice

    PubMed Central

    Nagy, L R; Featherstone, R E; Hahn, C G; Siegel, S J

    2015-01-01

    Frequent ketamine abuse in adulthood correlates with increased risk of psychosis, as well as cognitive deficits, including disruption of higher-order executive function and memory formation. Although the primary abusers of ketamine are adolescents and young adults, few studies have evaluated its effects on juvenile cognition. Therefore, the current study analyzes the effect of adolescent ketamine exposure on cognitive development. Juvenile mice (4 weeks of age) were exposed to chronic ketamine (20 mg kg−1, i.p. daily) for 14 days. Mice were tested immediately after exposure in the juvenile period (7 weeks of age) and again as adults (12 weeks of age). Measures included electroencephalography (EEG) in response to auditory stimulation, the social choice test, and a 6-arm radial water maze task. Outcome measures include low-frequency EEG responses, event-related potential (ERP) amplitudes, indices of social behavior and indices of spatial working memory. Juvenile exposure to ketamine was associated with electrophysiological abnormalities in adulthood, particularly in induced theta power and the P80 ERP. The social choice test revealed that ketamine-exposed mice failed to exhibit the same age-related decrease in social interaction time as controls. Ketamine-exposed mice outperformed control mice as juveniles on the radial water maze task, but did not show the same age-related improvement as adult controls. These data support the hypothesis that juvenile exposure to ketamine produces long-lasting changes in brain function that are characterized by a failure to progress along normal developmental trajectories. PMID:26371763

  13. Mouse embryonic fibroblasts exhibit extensive developmental and phenotypic diversity.

    PubMed

    Singhal, Prabhat K; Sassi, Slim; Lan, Lan; Au, Patrick; Halvorsen, Stefan C; Fukumura, Dai; Jain, Rakesh K; Seed, Brian

    2016-01-01

    Analysis of embryonic fibroblasts from GFP reporter mice indicates that the fibroblast cell type harbors a large collection of developmentally and phenotypically heterogeneous subtypes. Some of these cells exhibit multipotency, whereas others do not. Multiparameter flow cytometry analysis shows that a large number of distinct populations of fibroblast-like cells can be found in cultures initiated from different embryonic organs, and cells sorted according to their surface phenotype typically retain their characteristics on continued propagation in culture. Similarly, surface phenotypes of individual cloned fibroblast-like cells exhibit significant variation. The fibroblast cell class appears to contain a very large number of denumerable subtypes. PMID:26699463

  14. Mother-Adolescent Language Proficiency and Adolescent Academic and Emotional Adjustment among Chinese American Families

    ERIC Educational Resources Information Center

    Liu, Lisa L.; Benner, Aprile D.; Lau, Anna S.; Kim, Su Yeong

    2009-01-01

    This study examined the role of adolescents' and mothers' self-reports of English and heritage language proficiency in youth's academic and emotional adjustment among 444 Chinese American families. Adolescents who were proficient in English tended to exhibit higher reading achievement scores, math achievement scores, and overall GPA. Mothers who…

  15. Adolescent Literacy

    ERIC Educational Resources Information Center

    Ippolito, Jacy, Ed.; Steele, Jennifer L., Ed.; Samson, Jennifer F., Ed.

    2012-01-01

    "Adolescent Literacy" initially appeared as a special issue of the "Harvard Educational Review". It explores key issues and debates in the adolescent literacy crisis, the popular use of cognitive strategies, and disciplinary and content-area literacy. Also examined are alternative forms of literacy, afterschool interventions, new instruction…

  16. Adolescent Neurodevelopment

    PubMed Central

    Spear, Linda Patia

    2012-01-01

    Purpose The purpose of this paper is to outline notable alterations occurring in the adolescent brain, and consider potential ramifications of these developmental transformations for public policy and programs involving adolescents. Methods Developmental changes in the adolescent brain obtained from human imaging work are reviewed, along with results of basic science studies. Results Adolescent brain transformations include both progressive and regressive changes that are regionally specific and serve to refine brain functional connectivity. Along with still maturing inhibitory control systems that can be overcome under emotional circumstances, the adolescent brain is associated with sometimes elevated activation of reward-relevant brain regions, whereas sensitivity to aversive stimuli may be attenuated. At this time, the developmental shift from greater brain plasticity early in life to the relative stability of the mature brain is still tilted more towards plasticity than seen in adulthood, perhaps providing an opportunity for some experience-influenced sculpting of the adolescent brain. Conclusions Normal developmental transformations in brain reward/aversive systems, areas critical for inhibitory control, and regions activated by emotional, exciting and stressful stimuli may promote some normative degree of adolescent risk-taking. These findings have a number of potential implications for public policies and programs focused on adolescent health and well-being. PMID:23332574

  17. Positively Adolescent!

    ERIC Educational Resources Information Center

    Williamson, Sue

    2000-01-01

    Believes that music teachers should reassess their views toward adolescent behavior in the music classroom by learning to see their behavior in a positive light. Describes teaching strategies that build on four adolescent behaviors: (1) desire for peer acceptance; (2) abundant energy; (3) love of fun; and (4) limited time-managing skills. (CMK)

  18. Crows spontaneously exhibit analogical reasoning.

    PubMed

    Smirnova, Anna; Zorina, Zoya; Obozova, Tanya; Wasserman, Edward

    2015-01-19

    Analogical reasoning is vital to advanced cognition and behavioral adaptation. Many theorists deem analogical thinking to be uniquely human and to be foundational to categorization, creative problem solving, and scientific discovery. Comparative psychologists have long been interested in the species generality of analogical reasoning, but they initially found it difficult to obtain empirical support for such thinking in nonhuman animals (for pioneering efforts, see [2, 3]). Researchers have since mustered considerable evidence and argument that relational matching-to-sample (RMTS) effectively captures the essence of analogy, in which the relevant logical arguments are presented visually. In RMTS, choice of test pair BB would be correct if the sample pair were AA, whereas choice of test pair EF would be correct if the sample pair were CD. Critically, no items in the correct test pair physically match items in the sample pair, thus demanding that only relational sameness or differentness is available to support accurate choice responding. Initial evidence suggested that only humans and apes can successfully learn RMTS with pairs of sample and test items; however, monkeys have subsequently done so. Here, we report that crows too exhibit relational matching behavior. Even more importantly, crows spontaneously display relational responding without ever having been trained on RMTS; they had only been trained on identity matching-to-sample (IMTS). Such robust and uninstructed relational matching behavior represents the most convincing evidence yet of analogical reasoning in a nonprimate species, as apes alone have spontaneously exhibited RMTS behavior after only IMTS training.

  19. Collaborative virtual environments art exhibition

    NASA Astrophysics Data System (ADS)

    Dolinsky, Margaret; Anstey, Josephine; Pape, Dave E.; Aguilera, Julieta C.; Kostis, Helen-Nicole; Tsoupikova, Daria

    2005-03-01

    This panel presentation will exhibit artwork developed in CAVEs and discuss how art methodologies enhance the science of VR through collaboration, interaction and aesthetics. Artists and scientists work alongside one another to expand scientific research and artistic expression and are motivated by exhibiting collaborative virtual environments. Looking towards the arts, such as painting and sculpture, computer graphics captures a visual tradition. Virtual reality expands this tradition to not only what we face, but to what surrounds us and even what responds to our body and its gestures. Art making that once was isolated to the static frame and an optimal point of view is now out and about, in fully immersive mode within CAVEs. Art knowledge is a guide to how the aesthetics of 2D and 3D worlds affect, transform, and influence the social, intellectual and physical condition of the human body through attention to psychology, spiritual thinking, education, and cognition. The psychological interacts with the physical in the virtual in such a way that each facilitates, enhances and extends the other, culminating in a "go together" world. Attention to sharing art experience across high-speed networks introduces a dimension of liveliness and aliveness when we "become virtual" in real time with others.

  20. Crows spontaneously exhibit analogical reasoning.

    PubMed

    Smirnova, Anna; Zorina, Zoya; Obozova, Tanya; Wasserman, Edward

    2015-01-19

    Analogical reasoning is vital to advanced cognition and behavioral adaptation. Many theorists deem analogical thinking to be uniquely human and to be foundational to categorization, creative problem solving, and scientific discovery. Comparative psychologists have long been interested in the species generality of analogical reasoning, but they initially found it difficult to obtain empirical support for such thinking in nonhuman animals (for pioneering efforts, see [2, 3]). Researchers have since mustered considerable evidence and argument that relational matching-to-sample (RMTS) effectively captures the essence of analogy, in which the relevant logical arguments are presented visually. In RMTS, choice of test pair BB would be correct if the sample pair were AA, whereas choice of test pair EF would be correct if the sample pair were CD. Critically, no items in the correct test pair physically match items in the sample pair, thus demanding that only relational sameness or differentness is available to support accurate choice responding. Initial evidence suggested that only humans and apes can successfully learn RMTS with pairs of sample and test items; however, monkeys have subsequently done so. Here, we report that crows too exhibit relational matching behavior. Even more importantly, crows spontaneously display relational responding without ever having been trained on RMTS; they had only been trained on identity matching-to-sample (IMTS). Such robust and uninstructed relational matching behavior represents the most convincing evidence yet of analogical reasoning in a nonprimate species, as apes alone have spontaneously exhibited RMTS behavior after only IMTS training. PMID:25532894

  1. Stages of Adolescence

    MedlinePlus

    ... Español Text Size Email Print Share Stages of Adolescence Page Content Article Body Adolescence, these years from puberty to adulthood, may be roughly divided into three stages: early adolescence, generally ages eleven to fourteen; middle adolescence, ages ...

  2. Stability and Change in Adjustment Profiles Among Chinese American Adolescents: The Role of Parenting.

    PubMed

    Kim, Su Yeong; Wang, Yijie; Shen, Yishan; Hou, Yang

    2015-09-01

    Asian American adolescents are often depicted as academically successful but psychologically distressed, a pattern known as the achievement/adjustment paradox. In a sample of 444 Chinese American adolescents (54 % females), we identified three distinct patterns of adjustment in early adolescence, middle adolescence, and emerging adulthood: the well-adjusted group, which was the largest, exhibited high achievement and low psychological distress; the poorly-adjusted group exhibited poor achievement and moderate distress; and the paradox group exhibited relatively high achievement and high distress. More than half of the adolescents remained in the same profile over time. Adolescents with supportive parents were more likely to stay well-adjusted, and those with "tiger" parents were more likely to stay in the paradox group over time. The present study focused on the critical role of parenting in early adolescence, highlighting variations in Chinese American adolescents' adjustment in multiple domains over time. PMID:26022414

  3. Wanting to See People Like Me? Racial and Gender Diversity in Popular Adolescent Television.

    PubMed

    Ellithorpe, Morgan E; Bleakley, Amy

    2016-07-01

    Media are one source for adolescent identity development and social identity gratifications. Nielsen viewing data across the 2014-2015 television season for adolescents ages 14-17 was used to examine racial and gender diversity in adolescent television exposure. Compared to US Census data, mainstream shows under represent women, but the proportion of Black characters is roughly representative. Black adolescents watch more television than non-Black adolescents and, after taking this into account, shows popular with Black adolescents are more likely than shows popular with non-Black adolescents to exhibit racial diversity. In addition, shows popular with female adolescents are more likely than shows popular with males to exhibit gender diversity. These results support the idea that adolescents seek out media messages with characters that are members of their identity groups, possibly because the characters serve as tools for identity development and social identity gratifications.

  4. Impairment of Oligodendroglia Maturation Leads to Aberrantly Increased Cortical Glutamate and Anxiety-Like Behaviors in Juvenile Mice

    PubMed Central

    Chen, Xianjun; Zhang, Weiguo; Li, Tao; Guo, Yu; Tian, Yanping; Wang, Fei; Liu, Shubao; Shen, Hai-Ying; Feng, Yue; Xiao, Lan

    2015-01-01

    Adolescence is the critical time for developing proper oligodendrocyte (OL)-neuron interaction and the peak of onset for many cognitive diseases, among which anxiety disorders display the highest prevalence. However, whether impairment of de novo OL development causes neuronal abnormalities and contributes to the early onset of anxiety phenotype in childhood still remains unexplored. In this study, we tested the hypothesis that defects in OL maturation manifests cortical neuron function and leads to anxiety-like behaviors in juvenile mice. We report here that conditional knockout of the Olig2 gene (Olig2 cKO) specifically in differentiating OLs in the mouse brain preferentially impaired OL maturation in the gray matter of cerebral cortex. Interestingly, localized proton magnetic resonance spectroscopy revealed that Olig2 cKO mice displayed abnormally elevated cortical glutamate levels. In addition, transmission electron microscopy demonstrated increased vesicle density in excitatory glutamatergic synapses in the cortex of the Olig2 cKO mice. Moreover, juvenile Olig2 cKO mice exhibited anxiety-like behaviors and impairment in behavioral inhibition. Taken together, our results suggest that impaired OL development affects glutamatergic neuron function in the cortex and causes anxiety-related behaviors in juvenile mice. These discoveries raise an intriguing possibility that OL defects may be a contributing mechanism for the onset of anxiety in childhood. PMID:26696827

  5. Adolescent immunization.

    PubMed

    Handal, G A

    2000-06-01

    The dramatic improvements achieved in the control of vaccine-preventable diseases in children have only been shared partially by adolescents and young adults, as today several million adolescents are not receiving the full complement of vaccines recommended by the Advisory Committee on Immunization Practices (ACIP). This article discusses the reasons for this problem and the tools to bridge this gap. In particular, medical societies and the Centers for Disease Control and Prevention (CDC) recommend a close assessment of the adolescentís immunization status between 11 and 12 years of age, inclusion of school immunization, and providing missing immunizations at any opportunity. The article also addresses other vaccines recommended for groups of adolescents with special needs, reporting information, and provides an update on the vaccines of the future.

  6. 17 CFR 232.102 - Exhibits.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Regulation S-T (17 CFR 232.311(b)). (b) Amendments to all exhibits shall be filed in electronic format... designation “CE” (confirming electronic) should be placed next to the listed exhibit in the exhibit index....

  7. Adolescent sexuality.

    PubMed

    Grant, L M; Demetriou, E

    1988-12-01

    The consequences of adolescent sexual behavior are an enormous burden both for the adolescent and society. The problem is not that teens are sexually active but rather that they have little preparation and guidance in developing responsible sexual behavior. Developmentally, adolescents reach physical maturity before they are cognitively able to appreciate the consequences of their behavior. A teenager's primary source of information regarding sexuality is his or her peer group, all of whom are experiencing and reinforcing the same behaviors. The family, the major socializer of other behaviors, is not as powerful a force in shaping responsible sexual behavior because of parental discomfort with sex education and sexual discussions. This is the result of a social milieu in which sex is frequently portrayed but rarely linked with responsible behavior or accurate, nonjudgmental information. The pediatric practitioner is in an ideal position to intervene in these dynamics. In the office, the practitioner can provide accurate sexual information to both parents and adolescents, support parental-child communication on sexual issues, and provide appropriate services or referral. In the community, the practitioner can advocate for school-based sex education as well as act as an information resource. Finally, the practitioner can advocate for the health care needs for adolescents on a national level, supporting legislation that provides adolescents with information and access to services necessary to make responsible sexual decisions.

  8. Differentiating Adolescent Self-Injury from Adolescent Depression: Possible Implications for Borderline Personality Development

    PubMed Central

    Crowell, Sheila E.; Beauchaine, Theodore P.; Hsiao, Ray C.; Vasilev, Christina A.; Yaptangco, Mona; Linehan, Marsha M.; McCauley, Elizabeth

    2011-01-01

    Self-inflicted injury (SII) in adolescence marks heightened risk for suicide attempts, completed suicide, and adult psychopathology. Although several studies have revealed elevated rates of depression among adolescents who self injure, no one has compared adolescent self injury with adolescent depression on biological, self-, and informant-report markers of vulnerability and risk. Such a comparison may have important implications for treatment, prevention, and developmental models of self injury and borderline personality disorder. We used a multi-method, multi-informant approach to examine how adolescent SII differs from adolescent depression. Self-injuring, depressed, and typical adolescent females (n = 25 per group) and their mothers completed measures of psychopathology and emotion regulation, among others. In addition, we assessed electrodermal responding (EDR), a peripheral biomarker of trait impulsivity. Participants in the SII group (a) scored higher than depressed adolescents on measures of both externalizing psychopathology and emotion dysregulation, and (b) exhibited attenuated EDR, similar to patterns observed among impulsive, externalizing males. Self-injuring adolescents also scored higher on measures of borderline pathology. These findings reveal a coherent pattern of differences between self-injuring and depressed adolescent girls, consistent with theories that SII differs from depression in etiology and developmental course. PMID:22016199

  9. Early life stress dampens stress responsiveness in adolescence: Evaluation of neuroendocrine reactivity and coping behavior.

    PubMed

    Hsiao, Young-Ming; Tsai, Tsung-Chih; Lin, Yu-Ting; Chen, Chien-Chung; Huang, Chiung-Chun; Hsu, Kuei-Sen

    2016-05-01

    Stressful experiences during early life (ELS) can affect brain development, thereby exerting a profound and long-lasting influence on mental development and psychological health. The stress inoculation hypothesis presupposes that individuals who have early experienced an attenuated form of stressors may gain immunity to its more virulent forms later in life. Increasing evidence demonstrates that ELS may promote the development of subsequent stress resistance, but the mechanisms underlying such adaptive changes are not fully understood. The present study evaluated the impact of fragmented dam-pup interactions by limiting the bedding and nesting material in the cage during postnatal days 2-9, a naturalistic animal model of chronic ELS, on the physiological and behavioral responses to different stressors in adolescent mice and characterized the possible underlying mechanisms. We found that ELS mice showed less social interaction deficits after chronic social defeat stress and acute restraint-tailshock stress-induced impaired long-term potentiation (LTP) and enhanced long-term depression (LTD) in hippocampal CA1 region compared with control mice. The effects of ELS on LTP and LTD were rescued by adrenalectomy. While ELS did not cause alterations in basal emotional behaviors, it significantly enhanced stress coping behaviors in both the tail suspension and the forced swimming tests. ELS mice exhibited a significant decrease in corticosterone response and trafficking of glucocorticoid receptors to the nucleus in response to acute restraint stress. Altogether, our data support the hypothesis that stress inoculation training, via early exposure to manageable stress, may enhance resistance to other unrelated extreme stressors in adolescence. PMID:26881834

  10. Exhibits Enhanced by Stand-Alone Computers.

    ERIC Educational Resources Information Center

    Van Rennes, Eve C.

    Both the development and evaluation of one of a set of computer programs designed for use by visitors as adjuncts to museum exhibits are described. Museum displays used were (1) a static, behind-glass exhibit on evolution; (2) a hands-on primitive stone age tools exhibit; and (3) a Foucault pendulum. A computer placed next to each exhibit served…

  11. A unique amyloidogenic apolipoprotein serum amyloid A (apoSAA) isoform expressed by the amyloid resistant CE/J mouse strain exhibits higher affinity for macrophages than apoSAA1 and apoSAA2 expressed by amyloid susceptible CBA/J mice.

    PubMed

    Liang, J; Elliott-Bryant, R; Hajri, T; Sipe, J D; Cathcart, E S

    1998-10-01

    CBA/J and other inbred strains of mice that express the amyloidogenic apolipoprotein serum amyloid A (apoSAA) apoSAA2, together with apoSAA1, are susceptible to amyloid A (AA) amyloidosis, whereas CE/J mice that express a single unique isoform, apoSAACEJ, are resistant. Studies indicate that CBA/JxCE/J hybrid mice that express apoSAA2 in the presence of apoSAACEJ are protected from amyloidogenesis. To define a mechanism by which expression of apoSAACEJ may protect from AA formation in the presence of apoSAA2, binding of recombinant apoSAA (r-apoSAA) isoforms, validated by N-terminal sequencing, to a murine macrophage cell line was investigated. Maximal specific binding occurred after incubation of radiolabeled apoSAA with IC-21 macrophages (1x105 cells/ml) for 30 min at 4 degreesC. The binding of 125I-r-apoSAA1, 125I-r-apoSAA2 and 125I-r-apoSAACEJ was specific and saturable, with an affinity (Kd) of about 2.8, 3.2 and 1.3 nM, respectively, and approximately 2-4x106 sites per cell. Competitive binding experiments indicate apoSAACEJ binds with higher affinity to macrophages than does either apoSAA1 or apoSAA2. We suggest that greater cellular affinity of apoSAACEJ compared to apoSAA2 may contribute to protection from AA amyloid in certain CBA/JxCE/J hybrid mice by interfering with interaction of apoSAA2 by macrophages and hence either membrane associated or intracellular degradation. PMID:9767146

  12. Sporadic fatal insomnia in an adolescent.

    PubMed

    Blase, Jennifer L; Cracco, Laura; Schonberger, Lawrence B; Maddox, Ryan A; Cohen, Yvonne; Cali, Ignazio; Belay, Ermias D

    2014-03-01

    The occurrence of sporadic prion disease among adolescents is extremely rare. A prion disease was confirmed in an adolescent with disease onset at 13 years of age. Genetic, neuropathologic, and biochemical analyses of the patient's autopsy brain tissue were consistent with sporadic fatal insomnia, a type of sporadic prion disease. There was no evidence of an environmental source of infection, and this patient represents the youngest documented case of sporadic prion disease. Although rare, a prion disease diagnosis should not be discounted in adolescents exhibiting neurologic signs. Brain tissue testing is necessary for disease confirmation and is particularly beneficial in cases with an unusual clinical presentation.

  13. Adolescent loneliness.

    PubMed

    Williams, E G

    1983-01-01

    The purpose of this study was to investigate the phenomenon of loneliness in delinquent adolescents with regard to types of delinquency offenses committed, demographic characteristics, and personality characteristics in the areas of interpersonal needs for inclusion, control, and affection. The types of delinquency offenses were categorized as burglary, runaway, drugs, assault, and incorrigible. The demographic variables examined were age, sex, race, family rank or birth order, family structure in terms of parental presence, family income level, religion, and geographic locale. A sample of 98 adolescents was obtained from juvenile detention facilities in three metropolitan areas in the United States. Subjects ranged in age from 12 to 18. Subjects were asked to complete the Loneliness Questionnaire as a self-reported measure of loneliness. Subjects also provided information about themselves relative to demographic characteristics and completed the FIRO-B Questionnaire, which measured interpersonal needs for inclusion, control, and affection. The results revealed no significant differences with regard to any of the demographic variables when the effect of each was considered alone. However, there was a significant effect on loneliness by income when considered jointly with other demographic variables. Adolescents from the middle income group expressed more loneliness than those from the upper and lower income groups. No significant differences were observed with regard to personality characteristics related to interpersonal needs for inclusion and affection, but delinquent adolescents with medium to high needs for control indicated significantly more feelings of loneliness than delinquent adolescents with low needs for control.

  14. Concentration- and age-dependent effects of chronic caffeine on contextual fear conditioning in C57BL/6J mice.

    PubMed

    Poole, Rachel L; Braak, David; Gould, Thomas J

    2016-02-01

    Chronic caffeine exerts negligible effects on learning and memory in normal adults, but it is unknown whether this is also true for children and adolescents. The hippocampus, a brain region important for learning and memory, undergoes extensive structural and functional modifications during pre-adolescence and adolescence. As a result, chronic caffeine may have differential effects on hippocampus-dependent learning in pre-adolescents and adolescents compared with adults. Here, we characterized the effects of chronic caffeine and withdrawal from chronic caffeine on hippocampus-dependent (contextual) and hippocampus-independent (cued) fear conditioning in pre-adolescent, adolescent, and adult mice. The results indicate that chronic exposure to caffeine during pre-adolescence and adolescence enhances or impairs contextual conditioning depending on concentration, yet has no effect on cued conditioning. In contrast, withdrawal from chronic caffeine impairs contextual conditioning in pre-adolescent mice only. No changes in learning were seen for adult mice for either the chronic caffeine or withdrawal conditions. These findings support the hypothesis that chronic exposure to caffeine during pre-adolescence and adolescence can alter learning and memory and as changes were only seen in hippocampus-dependent learning, which suggests that the developing hippocampus may be sensitive to the effects of caffeine.

  15. Sex Differences in the Forms of Aggression among Adolescent Students in Ghana

    ERIC Educational Resources Information Center

    Amedahe, Francis K.; Owusu-Banahene, Nana Opoku

    2007-01-01

    A number of studies have investigated sex differences in the forms of aggression exhibited by adolescent students, particularly in the Western world. No such study has been done among sub-Saharan Africa students. The aim was to examine the sex differences in forms of aggression among adolescent students in Ghana. A total of 800 adolescent students…

  16. Evaluating the Link between Self-Esteem and Temperament in Mexican Origin Early Adolescents

    ERIC Educational Resources Information Center

    Robins, Richard W.; Donnellan, M. Brent; Widaman, Keith F.; Conger, Rand D.

    2010-01-01

    The present study examined the relation between self-esteem and temperament in a sample of 646 Mexican-American early adolescents (mean age = 10.4). Findings show that (a) early adolescents with high self-esteem exhibit higher levels of Effortful Control but, contrary to findings in adult samples, do not differ from low self-esteem adolescents in…

  17. Contraceptive counseling for adolescents.

    PubMed

    Potter, Julia; Santelli, John S

    2015-11-01

    The majority of adolescents become sexually active during their teenage years, making contraceptive counseling an important aspect of routine adolescent healthcare. However, many healthcare providers express discomfort when it comes to counseling adolescents about contraceptive options. This Special Report highlights the evidence supporting age-appropriate contraceptive counseling for adolescents and focuses on best practices for addressing adolescents' questions and concerns about contraceptive methods.

  18. [Current concepts of depression during adolescence].

    PubMed

    Greszta, Elzbieta

    2004-01-01

    Until the 1960-ties, there was considerable debate on whether or not depression exists before adulthood. Next, there were popular concepts, which emphasized that depression during adolescence is "normal" for that particular stage of development. From 1980-ties, adolescent depression is seen as the same problem as with adults. The diagnosis of depression in adolescents is based on adult diagnostic criteria. Today, there is a more generally accepted standard that adolescence depression is essentially the same phenomenon as adult depression but with some development specific modifications. As compared with adults, adolescents with depression demonstrate a more variable course. The adolescent with depression may exhibit somatic complaints, school difficulties and deconcentration rather than depressed mood. Three conceptualizations of depressive phenomena during adolescence have been presented in the literature: (1) depressed mood alone, (2) depressive syndrome, and (3) depressive disorders. Compas, Ey and Grant have compared and integrated different approaches to a synthesis that reflected a comprehensive model of depressive phenomena during adolescence. Depressed mood, syndromes, and disorders are integrated as 3 levels of depressive phenomena in a hierarchical and sequential model.

  19. Early Childhood Television Viewing and Adolescent Behavior: The Recontact Study.

    ERIC Educational Resources Information Center

    Anderson, Daniel R.; Huston, Aletha C.; Schmitt, Kelly L.; Linebarger, Deborah L.; Wright, John C.

    2001-01-01

    Followed up on 570 adolescents studied as preschoolers. Found that preschoolers' viewing of educational television programs was associated with achieving higher grades, reading more books, placing more value on achievement, exhibiting greater creativity, and behaving less aggressively as adolescents more consistently for boys than girls. Found…

  20. Lingual deficits in neurotrophin double knockout mice.

    PubMed

    Nosrat, Irina V; Agerman, Karin; Marinescu, Andrea; Ernfors, Patrik; Nosrat, Christopher A

    2004-12-01

    Brain-derived neurotrophic factor (BDNF) and Neurotrophin 3 (NT-3) are members of the neurotrophin family and are expressed in the developing and adult tongue papillae. BDNF null-mutated mice exhibit specific impairments related to innervation and development of the gustatory system while NT-3 null mice have deficits in their lingual somatosensory innervation. To further evaluate the functional specificity of these neurotrophins in the peripheral gustatory system, we generated double BDNF/NT-3 knockout mice and compared the phenotype to BDNF(-/-) and wild-type mice. Taste papillae morphology was severely distorted in BDNF(-/-) xNT-3(-/-) mice compared to single BDNF(-/-) and wild-type mice. The deficits were found throughout the tongue and all gustatory papillae. There was a significant loss of fungiform papillae and the papillae were smaller in size compared to BDNF(-/-) and wild-type mice. Circumvallate papillae in the double knockouts were smaller and did not contain any intraepithelial nerve fibers. BDNF(-/-) xNT-3(-/-) mice exhibited additive losses in both somatosensory and gustatory innervation indicating that BDNF and NT-3 exert specific roles in the innervation of the tongue. However, the additional loss of fungiform papillae and taste buds in BDNF(-/-) xNT-3(-/-) mice compared to single BDNF knockout mice indicate a synergistic functional role for both BDNF-dependent gustatory and NT-3-dependent somatosensory innervations in taste bud and taste papillae innervation and development. PMID:16217617

  1. Science Education Through a Museum Exhibit

    ERIC Educational Resources Information Center

    Chaparian, Azad; And Others

    1973-01-01

    Describes the polywater exhibit at the Worcester Science Center in Massachusetts. Curiosity and interest are stimulated in young people by allowing them to handle the materials in the exhibit and by providing them with instructions for making polywater. (JR)

  2. Learning by Doing, Creating a Museum Exhibit.

    ERIC Educational Resources Information Center

    Main, Sarah; Kallquist, Dierdre

    2000-01-01

    Describes an exhibit called Kid's Kitchen, built within a major exhibit called Biodiversity: Life Supporting Life, in order to discuss environmental prompts hidden within the kitchen designed to surprise students and get them thinking. (ASK)

  3. Treating Children and Adolescents

    MedlinePlus

    ... Children and Adolescents Go Back Treating Children and Adolescents Email Print + Share For the most part, the ... tailored, based upon the child's weight. Children and adolescents are moving through a period of physical and ...

  4. [Adolescent sexuality].

    PubMed

    Calero, Juan del Rey

    2010-01-01

    The social Adolescent features are insecurity, narcissism, eroticism, more impetuosity than reason. 1/3 of adolescents have risk behaviour for health. The pregnancy rate in adolescent are 9/1,000 (11,720, the abort about 50 %). The total abort (2009) were 114,480. Increase the rate of 8,4 (1990) to 14,6/ 1,000 (2009). The sexual education fails. The consulting about contraceptives get pregnancy of the OR 3,2, condom OR 2,7. The adolescent are influenced in his matter: oeer have 70-75 % of influence, mother 30-40 %, father 15 %, for yhe environment and education Cyberspace access to information: 33 % exposed to unwanted sexual materials, 1 in 7 solicited sexual online. The argument have 4 central topic: Morality and Responsibility, Desire (responsibility vs gratification), Danger (fear related to pregnancy and STD/VIH), and Victimization. The prevention of STD: so called safe sex, delayed, and abstinence, Prevention HPV vaccine. The information is not enough, are necessary personal integral formation in values as self control, abstinence, mutual respect, responsibility, reasonable decisions. PMID:21877398

  5. Black Adolescents.

    ERIC Educational Resources Information Center

    Jones, Reginald L., Ed.

    This volume presents an overview of contemporary black adolescents from social, psychological, economic, educational, medical, historical, and comparative perspectives, with most emphasizing the roles that race, socioeconomic status, and environmental forces play in this critical period. The volume includes 19 chapters by various authors arranged…

  6. 32 CFR 705.24 - Exhibits.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... shopping centers, malls, etc.) provided it is clearly established that such areas are places the general... exhibits may be forwarded to the Navy Recruiting Exhibit Center via the local Navy recruiter with an information copy to the Chief of Information. The primary mission of the Navy Recruiting Exhibit Center is...

  7. 32 CFR 705.24 - Exhibits.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... shopping centers, malls, etc.) provided it is clearly established that such areas are places the general... exhibits may be forwarded to the Navy Recruiting Exhibit Center via the local Navy recruiter with an information copy to the Chief of Information. The primary mission of the Navy Recruiting Exhibit Center is...

  8. 32 CFR 705.24 - Exhibits.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... shopping centers, malls, etc.) provided it is clearly established that such areas are places the general... exhibits may be forwarded to the Navy Recruiting Exhibit Center via the local Navy recruiter with an information copy to the Chief of Information. The primary mission of the Navy Recruiting Exhibit Center is...

  9. 32 CFR 705.24 - Exhibits.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... shopping centers, malls, etc.) provided it is clearly established that such areas are places the general... exhibits may be forwarded to the Navy Recruiting Exhibit Center via the local Navy recruiter with an information copy to the Chief of Information. The primary mission of the Navy Recruiting Exhibit Center is...

  10. 29 CFR 2200.70 - Exhibits.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH REVIEW COMMISSION RULES OF PROCEDURE Hearings... separate file designated for rejected exhibits. (e) Return of physical exhibits. A party may on motion request the return of a physical exhibit within 30 days after expiration of the time for filing a...

  11. 29 CFR 2200.70 - Exhibits.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH REVIEW COMMISSION RULES OF PROCEDURE Hearings... separate file designated for rejected exhibits. (e) Return of physical exhibits. A party may on motion request the return of a physical exhibit within 30 days after expiration of the time for filing a...

  12. 29 CFR 2200.70 - Exhibits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH REVIEW COMMISSION RULES OF PROCEDURE Hearings... separate file designated for rejected exhibits. (e) Return of physical exhibits. A party may on motion request the return of a physical exhibit within 30 days after expiration of the time for filing a...

  13. Variability in empathic fear response among 11 inbred strains of mice.

    PubMed

    Keum, S; Park, J; Kim, A; Park, J; Kim, K K; Jeong, J; Shin, H-S

    2016-02-01

    Empathy is an important emotional process that involves the ability to recognize and share emotions with others. We have previously developed an observational fear learning (OFL) behavioral assay to measure empathic fear in mice. In the OFL task, a mouse is conditioned for context-dependent fear when it observes a conspecific demonstrator receiving aversive stimuli. In the present study, by comparing 11 different inbred mouse strains that are commonly used in the laboratory, we found that empathic fear response was highly variable between different strains. Five strains--C57BL/6J, C57BL/6NTac, 129S1/SvImJ, 129S4/SvJae and BTBR T(+) Itpr3(tf) /J--showed observational fear (OF) responses, whereas AKR/J, BALB/cByJ, C3H/HeJ, DBA/2J, FVB/NJ and NOD/ShiLtJ mice exhibited low empathic fear response. Importantly, day 2 OF memory was significantly correlated with contextual memory in the classical fear conditioning among the 11 strains. Innate differences in anxiety, locomotor activity, sociability and preference for social novelty were not significantly correlated with OFL. Interestingly, early adolescent C57BL/6J mice exhibited an increase in acquisition of OF. The level of OFL in C57BL/6J strain was not affected by sex or strains of the demonstrator. Taken together, these data strongly suggest that there are naturally occurring OFL-specific genetic variations modulating empathic fear behaviors in mice. The identification of causal genes may uncover novel genetic pathways and underlying neural mechanisms that modulate empathic fear and, ultimately, provide new targets for therapeutic intervention in human mental disorders associated with impaired empathy. PMID:26690560

  14. Independence of uniphasic and biphasic audiogenic seizure progressions in mice.

    PubMed

    Reid, H M; Collins, R L

    1989-11-01

    DBA/2J mice were monaurally or binaurally tested for susceptibility to sound-induced seizure. Two seconds following the beginning of running, one group of binaurally tested mice had acoustic stimulation interrupted for 15 s. These mice later seized when the stimulation was readministered. Their seizure progression closely resembled the behavior exhibited by noninterrupted binaurally stimulated mice and did not shift to the biphasic motor pattern of monaurally stimulated subjects. We conclude that the single burst of running of a binaurally tested mouse is qualitatively different from either of the two bursts of running exhibited by monaurally tested mice.

  15. Behavioral Disorder amongst Adolescents Attending Secondary School in Southeast Nigeria

    PubMed Central

    Chinawa, J. M.; Manyike, P. C.; Obu, H. A.; Odetunde, O. I.; Aniwada, E. C.; Ndu, I. K.; Chinawa, A. T.

    2014-01-01

    Background. Adolescents are prone to various forms of behavioral problems. These behavioral issues in adolescents can have serious consequences for the adolescents. Objectives. The objectives of the study are to determine the causative factors of adolescent problems and specific manifestations. Methods. Behavioral problems were investigated using a random sampling of adolescents from secondary schools in southeast Nigeria from February to April, 2014. A self-administered questionnaire was developed from Health Kids Colorado Questionnaire. Results. A total of 763 subjects completed the questionnaire. Adolescents who reported to have used tobacco 3 to 5 and 6 to 9 times during the last 30 days are just 3.14% and 3.4%, respectively. Nineteen (2.49%) adolescents claimed that they have had sex before but not in the last 3 months. Adolescents who attempted suicide are from 15 years and peaked at 18. Eighty-three (11%) adolescents who are 15 years old attempted suicide in a year; this peaks at 17 years where 235 (30.8%) committed suicide. Majority of adolescents with behavioral disorder are from the upper class family. Conclusion. This study revealed that adolescents exhibit several forms of behavioral problems. PMID:25276048

  16. Parental emotion socialization in clinically depressed adolescents: Enhancing, and dampening positive affect

    PubMed Central

    Katz, Lynn Fainsilber; Shortt, Joann Wu; Allen, Nicholas B.; Davis, Betsy; Hunter, Erin; Leve, Craig; Sheeber, Lisa

    2013-01-01

    This study compared parental socialization of adolescent positive affect in families of depressed and healthy adolescents. Participants were 107 adolescents (42 boys) aged 14 - 18 years and their parents. Half of the participants met criteria for major depressive disorder and the others were demographically matched adolescents without emotional or behavioral disorders. Results based on multi-source questionnaire and interview data indicated that mothers and fathers of depressed adolescents were less accepting of adolescents’ positive affect and more likely to use strategies that dampen adolescents’ positive affect than were parents of healthy adolescents. Additionally, fathers of depressed adolescents exhibited fewer responses likely to enhance the adolescents’ positive affect than were fathers of healthy adolescents. These findings build on those of previous work in examining parental responses to adolescent emotions, focusing on positive emotions and including both mothers and fathers. PMID:23942826

  17. Preventing suicide in adolescents with alcohol use disorders.

    PubMed

    Makhija, Nita J; Sher, Leo

    2007-01-01

    Adolescent suicide is an escalating crisis that needs to be addressed by clinicians and researchers. Alcohol use has consistently been implicated in adolescent suicide and it is generally assumed that alcohol use leads to an increased risk in suicidality, suicide attempts and completed suicides. It can lead to adolescent suicidality through alcohol myopia, disinhibition, and impaired judgment. Multiple genetically related intermediate phenotypes might contribute to the risk of alcohol misuse and suicidal behavior in adolescents. Genetic variations that enhance the risk for mood and anxiety symptoms or susceptibility to stress might increase risk through different mechanisms. Comorbid disorders such as depression are frequently exhibited in adolescents who misuse alcohol, therefore any adolescent who appears to be at risk for alcoholism or depression should always be screened for all other psychiatric disorders and for suicidality; some signs suicidal adolescents may exhibit include withdrawal, personality change, and a loss of interest in pleasurable activities. While assessment is important, prevention is crucial in any attempt to decrease the incidence of adolescent suicide. The US Center for Disease Control and Prevention (CDC) has established a set of seven guidelines that can be implemented from kindergarten through high school in order to establish alcohol prevention efforts in schools. Through beginning prevention efforts at a young age, it is hopeful that both alcohol misuse and adolescent suicide can be reduced. PMID:17458324

  18. EEG theta and beta power spectra in adolescents with ADHD versus adolescents with ASD + ADHD.

    PubMed

    Bink, M; van Boxtel, G J M; Popma, A; Bongers, I L; Denissen, A J M; van Nieuwenhuizen, Ch

    2015-08-01

    Attention problems are common in youngsters with attention deficit hyperactivity disorder (ADHD) as well as in adolescents with combined autism spectrum disorder (ASD) and ADHD. However, it is unknown whether there is psychophysiological overlap and/or a difference in electroencephalogram (EEG) power spectra between ADHD and comorbid ASD and ADHD (ASD + ADHD), on and off stimulant medication. To explore potential differences and overlap, measures of theta and beta power in adolescents diagnosed with ADHD (n = 33) versus adolescents with combined ASD + ADHD (n = 20), categorized by stimulant medication use (57 % of the total sample), were compared. EEG measures were acquired in three conditions: (1) resting state, eyes closed (2) resting state, eyes open and (3) during an oddball task. In addition, performance on the d2 attention test was analyzed. Adolescents with ADHD displayed more absolute theta activity than adolescents with ASD + ADHD during the eyes open and task conditions, independent of stimulant medication use. In addition, only the adolescents with ADHD showed an association between diminished attention test performance and increased theta in the eyes open condition. Results of the current study suggest that although there is behavioral overlap between ADHD characteristics in adolescents with ADHD and adolescents with combined ASD + ADHD, the underlying psychophysiological mechanisms may be different. Adolescents with ASD + ADHD exhibited fewer of the EEG physiological signs usually associated with ADHD, although there was an overlap in attentional problems between the groups. This may indicate that treatments developed for ADHD work differently in some adolescents with ASD + ADHD and adolescents with ADHD only.

  19. Superconductive microstrip exhibiting negative differential resistivity

    DOEpatents

    Huebener, R.P.; Gallus, D.E.

    1975-10-28

    A device capable of exhibiting negative differential electrical resistivity over a range of values of current and voltage is formed by vapor- depositing a thin layer of a material capable of exhibiting superconductivity on an insulating substrate, establishing electrical connections at opposite ends of the deposited strip, and cooling the alloy into its superconducting range. The device will exhibit negative differential resistivity when biased in the current- induced resistive state.

  20. Adolescent Development: Workshop II.

    ERIC Educational Resources Information Center

    Keng, Chiam Heng; And Others

    Workshops concerning adolescent development explored problems of adolescents, schooling and adolescence, preparation for adulthood, leisure and recreation, as well as values, culture, and change in relation to the development of youth. The discussion of adolescents' problems identified major problem areas, (emphasizing problems of communicating…

  1. Encountering Nanotechnology in an Interactive Exhibition

    ERIC Educational Resources Information Center

    Murriello, Sandra E.; Knobel, Marcelo

    2008-01-01

    This article offers findings from a learning sciences-informed evaluation of a nanoscience and nanotechnology exhibition called Nano-Aventura (NanoAdventure), based on four interactive-collaborative games and two narrated videos. This traveling exhibition was developed in Brazil by the Museu Exploratorio de Ciencias for children and teenagers…

  2. Strategies for Determining Exhibit Effectiveness. Final Report.

    ERIC Educational Resources Information Center

    Shettel, Harris H.; And Others

    This project was designed to develop research strategies and hypotheses for evaluating the effectiveness of exhibits. An exhibit on the role of the Federal Government in science and technology was used as the subject matter. Two basic groups of viewers were used, casual viewers and paid experimental viewers. Both were tested on knowledge gained…

  3. Memory and Mourning: An Exhibit History

    ERIC Educational Resources Information Center

    Eberle, Scott G.

    2005-01-01

    Mounted by the Strong Museum in Rochester, New York, in 1993, and traveling nationally thereafter, the exhibit Memory and Mourning provided historical and contemporary perspectives to help museum guests explore their own reactions to loss and grief. In the process the exhibit's development team encountered a range of philosophical, historical,…

  4. Science Fiction Exhibits as STEM Gateways

    NASA Astrophysics Data System (ADS)

    Robie, Samantha

    Women continue to hold less than a quarter of all STEM jobs in the United States, prompting many museums to develop programs and exhibits with the express goal of interesting young girls in scientific fields. At the same time, a number of recent museum exhibits have harnessed the popularity of pop culture and science fiction in order to interest general audiences in STEM subject matter, as well as using the exhibits as springboards to expand or shift mission goals and focus. Because science fiction appears to be successful at raising interest in STEM fields, it may be an effective way to garner the interest of young girls in STEM in particular. This research seeks to describe the ways in which museums are currently using science fiction exhibits to interest young girls in STEM fields and careers. Research focused on four institutions across the country hosting three separate exhibits, and included staff interviews and content analysis of exhibit descriptions, promotional materials, a summative evaluation and supplementary exhibit productions. In some ways, science fiction exhibits do serve young girls, primarily through the inclusion of female role models, staff awareness, and prototype testing to ensure interactives are attractive to girls as well as to boys. However, STEM appears to be underutilized, which may be partly due to a concern within the field that the outcome of targeting a specific gender could be construed as "stereotyping".

  5. Learning4Life on the Exhibit Floor

    ERIC Educational Resources Information Center

    Sullivan, Margaret

    2009-01-01

    The exhibit floor is a wealth of knowledge. One can read, view, and listen to information presented in many formats. Somewhere on the exhibit floor there are experts on every topic, ready and waiting for one's questions. But like any research topic, frequently a structured search is required to find the best answers. This article discusses how to…

  6. The novelty-seeking phenotype modulates the long-lasting effects of adolescent MDMA exposure.

    PubMed

    Rodríguez-Arias, Marta; Vaccaro, Sonia; Arenas, M Carmen; Aguilar, María A; Miñarro, José

    2015-03-15

    Exposure to drugs such as ethanol or cocaine during adolescence induces alterations in the central nervous system that are modulated by the novelty-seeking trait. Our aim was to evaluate the influence of this trait on the long-term effects of MDMA administration during adolescence on spontaneous behavior and conditioned rewarding effects in adulthood. Adolescent mice were classified as high or low novelty seekers (HNS or LNS) according to the hole-board test and received either MDMA (0, 10 or 20mg/kg PND 33-42) or saline. Three weeks later, having entered adulthood (PND>68), one set of mice performed the elevated plus maze and social interaction tests, while another set performed the conditioning place preference (CPP) test induced by cocaine-(1mg/kg) or MDMA-(1mg/kg). Only HNS mice treated with MDMA during adolescence acquired CPP in adulthood with a non-effective dose of cocaine or MDMA. Although it did not produce changes in motor activity, exposure to MDMA during adolescence was associated with more aggressive behaviors (threat and attack) and increased social contacts in HNS mice, while an anxiolytic effect was noted in LNS mice pre-treated with the highest dose of MDMA (20mg/kg). Administration of MDMA (10 or 20mg/kg) induced a decrease in DA levels in the striatum in LNS mice only and lower striatal serotonin levels in mice treated with the highest MDMA dose. Our findings show that adolescent MDMA exposure results in higher sensitivity to the conditioned reinforcing properties of MDMA and cocaine in adult HNS mice, which suggests that the relationship between exposure to MDMA in adolescence and a higher probability of substance is a feature of high novelty seekers only.

  7. Children Grow Up: Autism in Adolescents & Adults.

    ERIC Educational Resources Information Center

    Meyers, Kathleen; Griesman, Brenda

    The booklet examines issues associated with autism in adolescents and adults. Teenagers with autism exhibit behaviors not unlike their nondisabled peers, and standard definitions of the syndrome may not be relevant at that age. Brief articles explore the range of emotions families may encounter with a young adult or adult who has autism, typical…

  8. Mice Drawer System

    NASA Technical Reports Server (NTRS)

    Cancedda, Ranieri

    2008-01-01

    The Mice Drawer System (MDS) is an Italian Space Agency (ASI) facility which is able to support mice onboard the International Space Station during long-duration exploration missions (from 100 to 150-days) by living space, food, water, ventilation and lighting. Mice can be accommodated either individually (maximum 6) or in groups (4 pairs). MDS is integrated in the Space Shuttle middeck during transportation (uploading and downloading) to the ISS and in an EXPRESS Rack in Destiny, the US Laboratory during experiment execution. Osteoporosis is a debilitating disease that afflicts millions of people worldwide. One of the physiological changes experienced by astronauts during space flight is the accelerated loss of bone mass due to the lack of gravitational loading on the skeleton. This bone loss experienced by astronauts is similar to osteoporosis in the elderly population. MDS will help investigate the effects of unloading on transgenic (foreign gene that has been inserted into its genome to exhibit a particular trait) mice with the Osteoblast Stimulating Factor-1, OSF-1, a growth and differentiation factor, and to study the genetic mechanisms underlying the bone mass pathophysiology. MDS will test the hypothesis that mice with an increased bone density are likely to be more protected from osteoporosis, when the increased bone mass is a direct effect of a gene involved in skeletogenesis (skeleton formation). Osteoporosis is a debilitating disease that afflicts millions worldwide. One of the physiological changes experienced by astronauts during space flight is the accelerated loss of bone mass due to the lack of gravitational loading on the skeleton, a loss that is similar to osteoporosis in the elderly population on Earth. Osteoblast Stimulating Factor-1 (OSF-1), also known as pleiotrophin (PTN) or Heparin-Binding Growth- Associated Molecule (HB-GAM) belongs to a family of secreted heparin binding proteins..OSF-1 is an extracellular matrix-associated growth and

  9. Astronomy's New Messengers: A traveling exhibit on gravitational-wave physics

    NASA Astrophysics Data System (ADS)

    Cavaglià, Marco; Hendry, Martin; Márka, Szabolcs; Reitze, David H.; Riles, Keith

    2010-01-01

    The Laser Interferometer Gravitational-wave Observatory exhibit Astronomy's New Messengers: Listening to the Universe with Gravitational Waves is traveling to colleges, universities, museums and other public institutions throughout the United States. Astronomy's New Messengers primarily communicates with an adolescent and young adult audience, potentially inspiring them into the field of science. Acknowledging that this audience is traditionally a difficult one to attract, the exhibit publicly announces itself in a charismatic fashion to reach its principal goals of broadening the community of people interested in science and encouraging interest in science among young people.

  10. Activity-dependent neuroprotective protein (ADNP) exhibits striking sexual dichotomy impacting on autistic and Alzheimer's pathologies.

    PubMed

    Malishkevich, A; Amram, N; Hacohen-Kleiman, G; Magen, I; Giladi, E; Gozes, I

    2015-02-03

    Activity-dependent neuroprotective protein (ADNP) is a most frequent autism spectrum disorder (ASD)-associated gene and the only protein significantly decreasing in the serum of Alzheimer's disease (AD) patients. Is ADNP associated with ASD being more prevalent in boys and AD more prevalent in women? Our results revealed sex-related learning/memory differences in mice, reflecting hippocampal expression changes in ADNP and ADNP-controlled AD/ASD risk genes. Hippocampal ADNP transcript content was doubled in male vs female mice, with females showing equal expression to ADNP haploinsufficient (ADNP(+/)(-)) males and no significant genotype-associated reduction. Increased male ADNP expression was replicated in human postmortem hippocampal samples. The hippocampal transcript for apolipoprotein E (the major risk gene for AD) was doubled in female mice compared with males, and further doubled in the ADNP(+/-) females, contrasting a decrease in ADNP(+/-) males. Previously, overexpression of the eukaryotic translation initiation factor 4E (eIF4E) led to ASD-like phenotype in mice. Here, we identified binding sites on ADNP for eIF4E and co-immunoprecipitation. Furthermore, hippocampal eIF4E expression was specifically increased in young ADNP(+/-) male mice. Behaviorally, ADNP(+/-) male mice exhibited deficiencies in object recognition and social memory compared with ADNP(+/+) mice, while ADNP(+/-) females were partially spared. Contrasting males, which preferred novel over familiar mice, ADNP(+/+) females showed no preference to novel mice and ADNP(+/-) females did not prefer mice over object. ADNP expression, positioned as a master regulator of key ASD and AD risk genes, introduces a novel concept of hippocampal gene-regulated sexual dimorphism and an ADNP(+/-) animal model for translational psychiatry.

  11. Activity-dependent neuroprotective protein (ADNP) exhibits striking sexual dichotomy impacting on autistic and Alzheimer's pathologies

    PubMed Central

    Malishkevich, A; Amram, N; Hacohen-Kleiman, G; Magen, I; Giladi, E; Gozes, I

    2015-01-01

    Activity-dependent neuroprotective protein (ADNP) is a most frequent autism spectrum disorder (ASD)-associated gene and the only protein significantly decreasing in the serum of Alzheimer's disease (AD) patients. Is ADNP associated with ASD being more prevalent in boys and AD more prevalent in women? Our results revealed sex-related learning/memory differences in mice, reflecting hippocampal expression changes in ADNP and ADNP-controlled AD/ASD risk genes. Hippocampal ADNP transcript content was doubled in male vs female mice, with females showing equal expression to ADNP haploinsufficient (ADNP+/−) males and no significant genotype-associated reduction. Increased male ADNP expression was replicated in human postmortem hippocampal samples. The hippocampal transcript for apolipoprotein E (the major risk gene for AD) was doubled in female mice compared with males, and further doubled in the ADNP+/− females, contrasting a decrease in ADNP+/− males. Previously, overexpression of the eukaryotic translation initiation factor 4E (eIF4E) led to ASD-like phenotype in mice. Here, we identified binding sites on ADNP for eIF4E and co-immunoprecipitation. Furthermore, hippocampal eIF4E expression was specifically increased in young ADNP+/− male mice. Behaviorally, ADNP+/− male mice exhibited deficiencies in object recognition and social memory compared with ADNP+/+ mice, while ADNP+/− females were partially spared. Contrasting males, which preferred novel over familiar mice, ADNP+/+ females showed no preference to novel mice and ADNP+/− females did not prefer mice over object. ADNP expression, positioned as a master regulator of key ASD and AD risk genes, introduces a novel concept of hippocampal gene-regulated sexual dimorphism and an ADNP+/− animal model for translational psychiatry. PMID:25646590

  12. The Pressured World of Adolescence.

    ERIC Educational Resources Information Center

    Csikszentmihalyi, Mihaly

    1987-01-01

    The author discusses the adolescent experience and why adolescents engage in self-destructive behavior. He suggests some changes in the way that adults treat adolescents that could reduce adolescent behavior problems and self-abuse. (CH)

  13. Marital Conflict and Adolescent Distress: The Role of Adolescent Awareness.

    ERIC Educational Resources Information Center

    Harold, Gordon T.; Conger, Rand D.

    1997-01-01

    Studied role of adolescents' awareness in relationship between marital conflict and adolescent distress. Found marital conflict was related to parental hostility toward adolescents and adolescents' awareness of conflict; parental hostility and adolescents' awareness of marital conflict were related to adolescent-perceived parental hostility. Found…

  14. The MsrA knockout mouse exhibits abnormal behavior and brain dopamine levels

    PubMed Central

    Oien, Derek B.; Osterhaus, Greg L.; Latif, Shaheen A.; Pinkston, Jonathan W.; Fulks, Jenny; Johnson, Michael; Fowler, Stephen C.; Moskovitz, Jackob

    2008-01-01

    Oxidative stress can cause methionine oxidation that has been implicated in various proteins malfunctions, if not adequately reduced by the methionine sulfoxide reductase system. Recent evidence has found oxidized methionine residues in neurodegenerative conditions. Previously, we have described elevated levels of brain pathologies and an abnormal walking pattern in the methionine sulfoxide reductase A knockout (MsrA−/−) mouse. Here we show that MsrA−/− mice have compromised complex task learning capabilities relative to wild-type mice. Likewise, MsrA−/− mice exhibit lower locomotor activity and altered gait that exacerbated with age. Furthermore, MsrA−/− mice were less responsive to amphetamine treatment. Consequently, brain dopamine levels were determined. Surprisingly, relative to wild-type mice, MsrA−/− brains contained significantly higher levels of dopamine up to 12 months of age, while lower level of dopamine was observed at 16 months of age. Moreover, striatal regions of MsrA−/− mice showed an increase of dopamine release parallel to observed dopamine levels. Similarly, the expression pattern of tyrosine hydroxylase activating protein correlated with the age-dependent dopamine levels. Thus, it is suggested that dopamine regulation and signaling pathway are impaired in MsrA−/− mice, which may contribute to their abnormal bio-behavior. These observations may be relevant to age-related neurological diseases associated with oxidative stress. PMID:18466776

  15. MsrA knockout mouse exhibits abnormal behavior and brain dopamine levels.

    PubMed

    Oien, Derek B; Osterhaus, Greg L; Latif, Shaheen A; Pinkston, Jonathan W; Fulks, Jenny; Johnson, Michael; Fowler, Stephen C; Moskovitz, Jackob

    2008-07-15

    Oxidative stress can cause methionine oxidation that has been implicated in various proteins malfunctions, if not adequately reduced by the methionine sulfoxide reductase system. Recent evidence has found oxidized methionine residues in neurodegenerative conditions. Previously, we have described elevated levels of brain pathologies and an abnormal walking pattern in the methionine sulfoxide reductase A knockout (MsrA(-/-)) mouse. Here we show that MsrA(-/-) mice have compromised complex task learning capabilities relative to wild-type mice. Likewise, MsrA(-/-) mice exhibit lower locomotor activity and altered gait that exacerbated with age. Furthermore, MsrA(-/-) mice were less responsive to amphetamine treatment. Consequently, brain dopamine levels were determined. Surprisingly, relative to wild-type mice, MsrA(-/-) brains contained significantly higher levels of dopamine up to 12 months of age, while lower levels of dopamine were observed at 16 months of age. Moreover, striatal regions of MsrA(-/-) mice showed an increase of dopamine release parallel to observed dopamine levels. Similarly, the expression pattern of tyrosine hydroxylase activating protein correlated with the age-dependent dopamine levels. Thus, it is suggested that dopamine regulation and signaling pathways are impaired in MsrA(-/-) mice, which may contribute to their abnormal behavior. These observations may be relevant to age-related neurological diseases associated with oxidative stress.

  16. Enhanced Generalization of Auditory Conditioned Fear in Juvenile Mice

    ERIC Educational Resources Information Center

    Ito, Wataru; Pan, Bing-Xing; Yang, Chao; Thakur, Siddarth; Morozov, Alexei

    2009-01-01

    Increased emotionality is a characteristic of human adolescence, but its animal models are limited. Here we report that generalization of auditory conditioned fear between a conditional stimulus (CS+) and a novel auditory stimulus is stronger in 4-5-wk-old mice (juveniles) than in their 9-10-wk-old counterparts (adults), whereas nonassociative…

  17. Exhibit of School Architecture, 1997. Special Section.

    ERIC Educational Resources Information Center

    Texas Architect, 1998

    1998-01-01

    Presents selected winners of the Texas 1997 Exhibit of School Architecture Design Competition. The Caudill and honor award winning projects are listed along with facility photos, brief descriptions, project credits, and the names of the construction companies used. (GR)

  18. Exhibit of School Architecture, 1996. Special Section.

    ERIC Educational Resources Information Center

    Texas Architect, 1997

    1997-01-01

    Presents selected winners of the Texas 1996 Exhibit of School Architecture Design Competition. The Caudill and honor award-winning projects are listed along with facility photos, brief descriptions, project credits, and the names of the construction companies used. (GR)

  19. The Making of a Museum Exhibition.

    ERIC Educational Resources Information Center

    Bleecker, Samuel E.

    1979-01-01

    Discusses the preparation of the Reptile and Amphibian exhibition at the American Museum of Natural History. Various steps involved in developing the ten showcases in a six-year period are presented. (SA)

  20. 18 CFR 32.2 - Required exhibits.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... of operating such facilities. Exhibit B. A general or key map on a scale not greater than 20 miles to... facilities used for the generation and transmission of electric energy, indicating on said map the...

  1. 18 CFR 32.2 - Required exhibits.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... of operating such facilities. Exhibit B. A general or key map on a scale not greater than 20 miles to... facilities used for the generation and transmission of electric energy, indicating on said map the...

  2. 18 CFR 32.2 - Required exhibits.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... of operating such facilities. Exhibit B. A general or key map on a scale not greater than 20 miles to... facilities used for the generation and transmission of electric energy, indicating on said map the...

  3. 28 CFR 5.201 - Exhibits.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... the existing or proposed activities engaged in or to be engaged in, including political activities, by... be filed as exhibit C: (1) A copy of the registrant's charter, articles of incorporation...

  4. 28 CFR 5.201 - Exhibits.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... the existing or proposed activities engaged in or to be engaged in, including political activities, by... be filed as exhibit C: (1) A copy of the registrant's charter, articles of incorporation...

  5. 32 CFR 705.24 - Exhibits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... public of the Navy's mission and operations. (2) To disseminate technical and scientific information. (3... naval equipment, models, devices and information and orientation material placed on public display for information purposes before audiences at conventions, conferences, seminars, demonstrations, exhibits,...

  6. Communicating Complex Sciences by Means of Exhibitions

    NASA Astrophysics Data System (ADS)

    Schneider, S.

    2011-12-01

    Earth Sciences will have to take over the leading role in global sustainable policy and in discussions about climate change. Efforts to raise attention within the politically responsible communities as well as in the public are getting more and more support by executive and advisory boards all over the world. But how can you successfully communicate complex sciences? For example, to start communication about climate change, the first step is to encourage people to be concerned about climate change. After that, one has to start thinking about how to present data and how to include the presented data into an unprejudiced context. Therefore, the communication toolbox offers various methods to reach diverse audiences. The R&D programme GEOTECHNOLOGIEN conducts roving exhibitions as one of its most successful communication tools. With roving exhibitions GEOTECHNOLOGIEN is able to get in touch with different audiences at once. The main purpose and theme of these exhibitions is to convey the everyday means of climate change to the visitors. It is within the responsibility of science to communicate the effects of a phenomenon like climate change as well as the impact of research results to the everyday life of people. Currently, a GEOTECHNOLOGIEN roving exhibition on remote sensing with satellites deals with various issues of environmental research, including a chapter on climate change. By following the 3M-concept (Meaning - Memorable - Moving), exhibitions allow to connect the visitors daily environment and personal experiences with the presented issues and objects. Therefore, hands-on exhibits, exciting multimedia effects and high-tech artefacts have to be combined with interpretive text elements to highlight the daily significance of the scientific topics and the exhibition theme respectively. To create such an exhibition, strong conceptual planning has to be conducted. This includes the specification of stern financial as well as time wise milestones. In addition

  7. When Do Children Exhibit a "Yes" Bias?

    ERIC Educational Resources Information Center

    Okanda, Mako; Itakura, Shoji

    2010-01-01

    This study investigated whether one hundred and thirty-five 3- to 6-year-old children exhibit a yes bias to various yes-no questions and whether their knowledge status affects the production of a yes bias. Three-year-olds exhibited a yes bias to all yes-no questions such as "preference-object" and "knowledge-object" questions pertaining to…

  8. An Astrobiology Microbes Exhibit and Education Module

    NASA Technical Reports Server (NTRS)

    Lindstrom, Marilyn M.; Allen, Jaclyn S.; Stocco, Karen; Tobola, Kay; Olendzenski, Lorraine

    2001-01-01

    Telling the story of NASA-sponsored scientific research to the public in exhibits is best done by partnerships of scientists and museum professionals. Likewise, preparing classroom activities and training teachers to use them should be done by teams of teachers and scientists. Here we describe how we used such partnerships to develop a new astrobiology augmentation to the Microbes! traveling exhibit and a companion education module. "Additional information is contained in the original extended abstract."

  9. Reaching the Public through Traveling Exhibitions

    NASA Astrophysics Data System (ADS)

    Dusenbery, P. B.; Harold, J. B.; Morrow, C. A.

    2004-11-01

    The Space Science Institute (SSI) of Boulder, Colorado has recently developed two museum exhibits called Alien Earths and MarsQuest. It has just started to develop another exhibit called Giant Planets. These exhibitions provide research scientists the opportunity to engage in a number of activities that are vital to the success of these major outreach programs. Alien Earths was developed in partnership with various research missions. The focus of the presentation will be on MarsQuest and Giant Planets. MarsQuest is a 5000 square-foot, \\$3M, traveling exhibition that is now touring the country. The exhibit's second 3-year tour will enable millions of Americans to share in the excitement of the scientific exploration of Mars and learn more about their own planet in the process. The associated planetarium show and education program will also be described, with particular emphasis on workshops to orient museum staff (e.g. museum educators and docents) and workshops for master educators near host museums and science centers. The workshops make innovative connections between the exhibition's interactive experiences and lesson plans aligned with the National Science Education Standards. These exhibit programs are good models for actively involving scientists and their discoveries to help improve informal science education in the museum community and for forging a stronger connection between formal and informal education. The presentation will also discuss how Giant Planets, a proposed 3500 square-foot traveling exhibition on the mysteries and discoveries of the outer planets, will be able to take advantage of the connections and resources that have been developed by the MarsQuest project.

  10. [All-Russian hygienic exhibitions and museums].

    PubMed

    Kuzybaeva, M P

    2011-01-01

    The material about the popularization of hygiene and health education in Russia in the second half of the 19th century to early 20th century through exhibition and museum activities has been collected for the first time and analyzed in the paper. The role of scientists and scientific medical societies in this process is noted. The significance of museum and exhibition activities in this area for the development of medical science is defined.

  11. Short communication: Flourishing among adolescents with epilepsy: Correlates and comparison to peers.

    PubMed

    Odar Stough, Cathleen; Nabors, Laura; Merianos, Ashley; Zhang, Jiaqi

    2015-11-01

    This study was conducted to examine if adolescents with a seizure disorder/epilepsy display less flourishing (thriving) than peers without seizures using data from the National Survey of Children's Health 2011-2012. Adolescent demographics, symptom severity, and parents' anger toward their child were explored as possible predictors of flourishing. Adolescents with seizures exhibited lower flourishing than peers, and flourishing among adolescents with seizures was predicted by symptom severity, age, race/ethnicity, sex, and parental anger. Study results suggest adolescents with a seizure disorder/epilepsy should be targeted for interventions that promote flourishing. PMID:26313714

  12. Sex differences in science museum exhibit attraction

    NASA Astrophysics Data System (ADS)

    Arámbula Greenfield, Teresa

    This study examines the relative attraction of hands-on, interactive science museum exhibits for females and males. Studies have demonstrated that such exhibits can be effective learning experiences for children, with both academic and affective benefits. Other studies have shown that girls and boys do not always experience the same science-related educational opportunities and that, even when they do, they do not necessarily receive the same benefits from them. These early differences can lead to more serious educational and professional disparities later in life. As interactive museum exhibits represent a science experience that is-readily available to both girls and boys, the question arose as to whether they were being used similarly by the two groups as well as by adult women and men. It was found that both girls and boys used all types of exhibits, but that girls were more likely than boys to use puzzles and exhibits focusing on the human body; boys were more likely than girls to use computers and exhibits illustrating physical science principles. However, this was less true of children accompanied by adults (parents) than it was of unaccompanied children on school field trips who roamed the museum more freely.Received: 16 February 1994; Revised: 3 February 1995;

  13. Mother-adolescent language proficiency and adolescent academic and emotional adjustment among Chinese American families.

    PubMed

    Liu, Lisa L; Benner, Aprile D; Lau, Anna S; Kim, Su Yeong

    2009-04-01

    This study examined the role of adolescents' and mothers' self-reports of English and heritage language proficiency in youth's academic and emotional adjustment among 444 Chinese American families. Adolescents who were proficient in English tended to exhibit higher reading achievement scores, math achievement scores, and overall GPA. Mothers who were English proficient tended to have children with higher academic achievement and fewer depressive symptoms. Results also indicated that adolescents' heritage language maintenance was associated with positive adjustment, particularly amongst foreign-born youth and for youth whose parents were highly proficient in the heritage language. Mother-adolescent match in heritage language proficiency was related to higher math achievement scores and overall GPA. Additionally, higher heritage language proficiency was associated with fewer depressive symptoms for foreign-born but not U.S.-born youth. Overall, the findings suggest that proficiency in both the English and heritage language may confer advantages to Chinese American youth.

  14. Using Comparative Planetology in Exhibit Development

    NASA Astrophysics Data System (ADS)

    Dusenbery, P. B.; Harold, J. B.; Morrow, C. A.

    2004-12-01

    It is critically important for the public to better understand the scientific process. Museum exhibitions are an important part of informal science education that can effectively reach public audiences as well as school groups. They provide an important gateway for the public to learn about compelling scientific endeavors. The Space Science Institute (SSI) is a national leader in producing traveling science exhibitions and their associated educational programming (i.e. interactive websites, educator workshops, public talks, instructional materials). The focus of this presentation will be on three of its exhibit projects: MarsQuest (currently on tour), Alien Earths (in fabrication), and Giant Planets (in development). MarsQuest is enabling millions of Americans to share in the excitement of the scientific exploration of Mars and to learn more about their own planet in the process. Alien Earths will bring origins-related research and discoveries to students and the American public. It has four interrelated exhibit areas: Our Place in Space, Star Birth, PlanetQuest, and Search for Life. Exhibit visitors will explore the awesome events surrounding the birth of stars and planets; they will join scientists in the hunt for planets outside our solar system including those that may be in "habitable zones" around other stars; and finally they will be able to learn about how scientists are looking for signs of life beyond Earth. Giant Planets: Exploring the Outer Solar System will take advantage of the excitement generated by the Cassini mission and bring planetary and origins research and discoveries to students and the public. It will be organized around four thematic areas: Our Solar System; Colossal Worlds; Moons, Rings, and Fields; and Make Space for Kids. Giant Planets will open in 2007. This talk will focus on the importance of making Earth comparisons in the conceptual design of each exhibit and will show several examples of how these comparisons were manifested in

  15. Identity disturbance in adolescence: associations with borderline personality disorder.

    PubMed

    Westen, Drew; Betan, Ephi; Defife, Jared A

    2011-02-01

    Although establishing a coherent identity is often viewed as a normative developmental task of adolescence, an important question is whether forms of identity disturbance seen in adult personality disorders can also be distinguished in adolescents. If so, such disturbances would constitute an essential target for research and clinical interventions. The goal of this study is to investigate the nature of identity disturbance in an adolescent clinical sample and to explore its links with personality pathology, particularly borderline personality disorder. A national random sample of 139 psychiatrists and clinical psychologists completed a battery of instruments on a randomly selected adolescent patient in their care, including measures of Axis II symptoms and the Identity Disturbance Questionnaire-Adolescent Version, an instrument designed for clinically experienced observers that assesses a wide range of manifestations of potential identity disturbance among adolescents. Factor analysis of the Identity Disturbance Questionnaire--Adolescent Version yielded four clinically and conceptually coherent factors that resembled dimensions previously identified in adults: lack of normative commitment, role absorption, painful incoherence, and lack of consistency. As in adults, identity disturbance in adolescents is a clinically meaningful, multidimensional construct exhibiting significant relationships with different forms of severe personality pathology, most notably borderline personality disorder. As such, identity disturbance can be a manifestation of psychopathology above and beyond the typical Sturm und Drang (storm and stress) of adolescence.

  16. A window of vulnerability: impaired fear extinction in adolescence.

    PubMed

    Baker, Kathryn D; Den, Miriam L; Graham, Bronwyn M; Richardson, Rick

    2014-09-01

    There have been significant advances made towards understanding the processes mediating extinction of learned fear. However, despite being of clear theoretical and clinical significance, very few studies have examined fear extinction in adolescence, which is often described as a developmental window of vulnerability to psychological disorders. This paper reviews the relatively small body of research examining fear extinction in adolescence. A prominent finding of this work is that adolescents, both humans and rodents, exhibit a marked impairment in extinction relative to both younger (e.g., juvenile) and older (e.g., adult) groups. We then review some potential mechanisms that could produce the striking extinction deficit observed in adolescence. For example, one neurobiological candidate mechanism for impaired extinction in adolescence involves changes in the functional connectivity within the fear extinction circuit, particularly between prefrontal cortical regions and the amygdala. In addition, we review research on emotion regulation and attention processes that suggests that developmental changes in attention bias to threatening cues may be a cognitive mechanism that mediates age-related differences in extinction learning. We also examine how a differential reaction to chronic stress in adolescence impacts upon extinction retention during adolescence as well as in later life. Finally, we consider the findings of several studies illustrating promising approaches that overcome the typically-observed extinction impairments in adolescent rodents and that could be translated to human adolescents.

  17. Palmoplantar keratoderma in Slurp2-deficient mice

    PubMed Central

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

    2015-01-01

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

  18. [Adaptation and mental-hygienic characteristics of internally displaced adolescents].

    PubMed

    Maksimović, Milos; Kocijancić, Radojka; Backović, Dusan; Ille, Tatjana; Paunović, Katarina

    2005-01-01

    The change in socio-economic status, drastic decrease in living standards, war, and the introduction of sanctions to our country were complicated in addition by a large number of internally displaced people from Kosovo, which culminated with the 1999 NATO bombing. The aim of this investigation was to estimate the influence of internal displacement on the adaptation and mental health of adolescents. The investigation was conducted on 238 adolescents, comprising a control group of 206 adolescents from Belgrade and 32 internally displaced adolescents from Kosovo. A specific questionnaire regarding habits, behaviour, and psychosomatic state was used, as well as the Cornell Medical Index and the Eysenck Personality Questionnaire. Internally displaced adolescents from Kosovo exhibited greater difficulties in adapting and had worse school records than adolescents from Belgrade, one year after the change in their location. Immediately after the NATO bombing, both groups reacted in the same way: they often talked about the events they had survived, they were afraid of the sounds of alarm sirens and of aeroplanes, and in addition had similar dreams (no statistical variation between the groups). Emotional disturbances, one year after the bombing, were not observed in 40.6% of adolescents from Kosovo, compared to the figure of 74.8% for adolescents from Belgrade. Adolescents from Belgrade consumed alcohol significantly more often: 75.7% compared to 56.3% for adolescents from Kosovo. In addition, 20.4% of adolescents from Belgrade consumed psychoactive substances compared to 6.3% of adolescents from Kosovo. There was no significant difference between the examined groups in the total scores on the scale for neuroticism. All in all, the girls from both examined groups displayed neurotic tendencies more frequently than the boys. PMID:16392285

  19. Studying Adolescence

    PubMed Central

    Richter, Linda M.

    2007-01-01

    Young people in their teens constitute the largest age group in the world, in a special stage recognized across the globe as the link in the life cycle between childhood and adulthood. Longitudinal studies in both developed and developing countries and better measurements of adolescent behavior are producing new insights. The physical and psychosocial changes that occur during puberty make manifest generational and early-childhood risks to development, in the form of individual differences in aspects such as growth, educational attainment, self-esteem, peer influences, and closeness to family. They also anticipate threats to adult health and well-being. Multidisciplinary approaches, especially links between the biological and the social sciences, as well as studies of socioeconomic and cultural diversity and determinants of positive outcomes, are needed to advance knowledge about this stage of development. PMID:16809526

  20. Adolescent attraction to cults.

    PubMed

    Hunter, E

    1998-01-01

    This article details the reasons behind adolescents' attraction to cults. It is recommended that parents, teachers, and counselors familiarize themselves with the warning signs. Suggestions are offered on how to make adolescents less vulnerable to cult overtures. PMID:9831888

  1. Adolescent and School Health

    MedlinePlus

    ... Search The CDC Cancel Submit Search The CDC Adolescent and School Health Note: Javascript is disabled or ... behaviors now JAMA Viewpoint: Lesbian, Gay, and Bisexual Adolescents New MMWR Article Learn What State and Local ...

  2. Circulating tumor cells exhibit a biologically aggressive cancer phenotype accompanied by selective resistance to chemotherapy.

    PubMed

    Pavese, Janet M; Bergan, Raymond C

    2014-10-01

    With prostate cancer (PCa), circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) portend a poor clinical prognosis. Their unknown biology precludes rational therapeutic design. We demonstrate that CTC and DTC cell lines, established from mice bearing human PCa orthotopic implants, exhibit increased cellular invasion in vitro, increased metastasis in mice, and express increased epithelial to mesenchymal transition biomarkers. Further, they are selectively resistant to growth inhibition by mitoxantrone-like agents. These findings demonstrate that CTC formation is accompanied by phenotypic progression without obligate reversion. Their increased metastatic potential, selective therapeutic resistance, and differential expression of potential therapeutic targets provide a rational basis to test further interventions.

  3. Nonresident Fathers' Contributions to Adolescent Well-Being

    PubMed Central

    King, Valarie; Sobolewski, Juliana M.

    2007-01-01

    Using data from 453 adolescents in Wave 2 of the National Survey of Families and Households, we examine how multiple dimensions of nonresident father involvement are associated with different dimensions of child well-being. Father-child relationship quality and responsive fathering are modestly associated with fewer externalizing and internalizing problems among adolescents. The quality of the mother-child relationship, however, has stronger effects on child well-being. Nevertheless, even if adolescents have weak ties to mothers, those who have strong ties to nonresident fathers exhibit fewer internalizing problems and less acting out at school than adolescents who have weak ties to both parents. Adolescents are worst off on a range of outcomes when they have weak ties to both their mothers and nonresident fathers. PMID:18270550

  4. After Terror Charges, Artist Exhibits Academic Freedom

    ERIC Educational Resources Information Center

    Wilson, Robin

    2008-01-01

    Steven Kurtz, a professor of visual studies at the State University of New York, has been working with various bacteria as part of his counterculture exhibit artworks for nearly 20 years. Four years ago, federal agents raided his home in a bioterrorism investigation. The federal agents had been called to the house by local police officers…

  5. The medial prefrontal cortex exhibits money illusion

    PubMed Central

    Weber, Bernd; Rangel, Antonio; Wibral, Matthias; Falk, Armin

    2009-01-01

    Behavioral economists have proposed that money illusion, which is a deviation from rationality in which individuals engage in nominal evaluation, can explain a wide range of important economic and social phenomena. This proposition stands in sharp contrast to the standard economic assumption of rationality that requires individuals to judge the value of money only on the basis of the bundle of goods that it can buy—its real value—and not on the basis of the actual amount of currency—its nominal value. We used fMRI to investigate whether the brain's reward circuitry exhibits money illusion. Subjects received prizes in 2 different experimental conditions that were identical in real economic terms, but differed in nominal terms. Thus, in the absence of money illusion there should be no differences in activation in reward-related brain areas. In contrast, we found that areas of the ventromedial prefrontal cortex (vmPFC), which have been previously associated with the processing of anticipatory and experienced rewards, and the valuation of goods, exhibited money illusion. We also found that the amount of money illusion exhibited by the vmPFC was correlated with the amount of money illusion exhibited in the evaluation of economic transactions. PMID:19307555

  6. 18 CFR 153.8 - Required exhibits.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... LNG, evidence that an appropriate and qualified concern will properly and safely receive or deliver such LNG, including a report containing detailed engineering and design information. The Commission... Office of Energy Projects, 888 First Street, NE., Washington, DC 20426; (6) Exhibit E-1. If the...

  7. 28 CFR 68.43 - Exhibits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Exhibits. 68.43 Section 68.43 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) RULES OF PRACTICE AND PROCEDURE FOR ADMINISTRATIVE HEARINGS BEFORE ADMINISTRATIVE LAW JUDGES IN CASES INVOLVING ALLEGATIONS OF UNLAWFUL EMPLOYMENT OF ALIENS,...

  8. Creating Cross-Cultural Exhibits in Schools.

    ERIC Educational Resources Information Center

    Nakamura, Kazuyo; Erickson, Virginia; Ford, Viktoria

    Theory and practice of the Cross-Cultural Arts Exhibit project initiated by the Krannert Art Museum at the University of Illinois at Urbana-Champaign (Illinois) is described in this paper. The project was developed based on the concept of post-museum. Instead of transmitting values and knowledge, communication in the post-museum stresses the…

  9. 18 CFR 50.7 - Applications: exhibits.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... required supporting equipment, such as insulation medium pressurizing or forced cooling; (iii) Cathodic protection scheme; and (iv) Type of dielectric fluid and safeguards used to limit potential spills in...) Exhibit H—System analysis data. An analysis evaluating the impact the proposed facilities will have on...

  10. 17 CFR 232.102 - Exhibits.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... pursuant to the schedule's general instructions. See Rule 311(b) of Regulation S-T (17 CFR 232.311(b)). (b... registered investment company or a business development company). (d) Each electronic filing requiring... AND REGULATIONS FOR ELECTRONIC FILINGS Electronic Filing Requirements § 232.102 Exhibits. (a)...

  11. 18 CFR 50.7 - Applications: exhibits.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Applications: exhibits. 50.7 Section 50.7 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT APPLICATIONS FOR PERMITS TO SITE...

  12. 18 CFR 50.7 - Applications: exhibits.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... relation to the project and other principal interconnected system elements, as well as power flow and loss... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Applications: exhibits. 50.7 Section 50.7 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY...

  13. 18 CFR 50.7 - Applications: exhibits.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Applications: exhibits. 50.7 Section 50.7 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... destination of the project; (ii) Design voltage rating (kV); (iii) Operating voltage rating (kV); (iv)...

  14. The medial prefrontal cortex exhibits money illusion.

    PubMed

    Weber, Bernd; Rangel, Antonio; Wibral, Matthias; Falk, Armin

    2009-03-31

    Behavioral economists have proposed that money illusion, which is a deviation from rationality in which individuals engage in nominal evaluation, can explain a wide range of important economic and social phenomena. This proposition stands in sharp contrast to the standard economic assumption of rationality that requires individuals to judge the value of money only on the basis of the bundle of goods that it can buy-its real value-and not on the basis of the actual amount of currency-its nominal value. We used fMRI to investigate whether the brain's reward circuitry exhibits money illusion. Subjects received prizes in 2 different experimental conditions that were identical in real economic terms, but differed in nominal terms. Thus, in the absence of money illusion there should be no differences in activation in reward-related brain areas. In contrast, we found that areas of the ventromedial prefrontal cortex (vmPFC), which have been previously associated with the processing of anticipatory and experienced rewards, and the valuation of goods, exhibited money illusion. We also found that the amount of money illusion exhibited by the vmPFC was correlated with the amount of money illusion exhibited in the evaluation of economic transactions.

  15. Differential peptidomics assessment of strain and age differences in mice in response to acute cocaine administration.

    PubMed

    Romanova, Elena V; Rubakhin, Stanislav S; Ossyra, John R; Zombeck, Jonathan A; Nosek, Michael R; Sweedler, Jonathan V; Rhodes, Justin S

    2015-12-01

    Neurochemical differences in the hypothalamic-pituitary axis between individuals and between ages may contribute to differential susceptibility to cocaine abuse. This study measured peptide levels in the pituitary gland (Pit) and lateral hypothalamus (LH) in adolescent (age 30 days) and adult (age 65 days) mice from four standard inbred strains, FVB/NJ, DBA/2J, C57BL/6J, and BALB/cByJ, which have previously been characterized for acute locomotor responses to cocaine. Individual peptide profiles were analyzed using mass spectrometric profiling and principal component analysis. Sequences of assigned peptides were verified by tandem mass spectrometry. Principal component analysis classified all strains according to their distinct peptide profiles in Pit samples from adolescent mice, but not adults. Select pro-opiomelanocortin-derived peptides were significantly higher in adolescent BALB/cByJ and DBA/2J mice than in FVB/NJ or C57BL/6J mice. A subset of peptides in the LH, but not in the Pit, was altered by cocaine in adolescents. A 15 mg/kg dose of cocaine induced greater peptide alterations than a 30 mg/kg dose, particularly in FVB/NJ animals, with larger differences in adolescents than adults. Neuropeptides in the LH affected by acute cocaine administration included pro-opiomelanocortin-, myelin basic protein-, and glutamate transporter-derived peptides. The observed peptide differences could contribute to differential behavioral sensitivity to cocaine among strains and ages. Peptides were measured using mass spectrometry (MALDI-TOF) in individual lateral hypothalamus and pituitary samples from four strains and two ages of inbred mice in response to acute cocaine administration. Principal component analyses (PCA) classified the strains according to their peptide profiles from adolescent mice, and a subset of peptides in the lateral hypothalamus was altered by cocaine in adolescents.

  16. Addressing adolescent pregnancy with legislation.

    PubMed

    Montgomery, Tiffany M; Folken, Lori; Seitz, Melody A

    2014-01-01

    Adolescent pregnancy is a concern among many women's health practitioners. While it is practical and appropriate to work to prevent adolescent pregnancy by educating adolescents in health care clinics, schools and adolescent-friendly community-based organizations, suggesting and supporting legislative efforts to reduce adolescent pregnancy can help address the issue on an even larger scale. This article aims to help nurses better understand current legislation that addresses adolescent pregnancy, and to encourage support of future adolescent pregnancy prevention legislation. PMID:25145716

  17. Addressing adolescent pregnancy with legislation.

    PubMed

    Montgomery, Tiffany M; Folken, Lori; Seitz, Melody A

    2014-01-01

    Adolescent pregnancy is a concern among many women's health practitioners. While it is practical and appropriate to work to prevent adolescent pregnancy by educating adolescents in health care clinics, schools and adolescent-friendly community-based organizations, suggesting and supporting legislative efforts to reduce adolescent pregnancy can help address the issue on an even larger scale. This article aims to help nurses better understand current legislation that addresses adolescent pregnancy, and to encourage support of future adolescent pregnancy prevention legislation.

  18. MarsQuest: A National Traveling Exhibition

    NASA Astrophysics Data System (ADS)

    Lee, S. W.; Dusenbery, P. B.

    1998-09-01

    With the successful landing of Mars Pathfinder and the arrival of Mars Global Surveyor, a new decade of Mars exploration has commenced. MarsQuest, a 5000 square foot traveling exhibition, is being developed to further bring the excitement and discoveries of this "Decade of Mars Exploration" to the public. MarsQuest is partially funded by the Informal Science Education Program of the National Science Foundation and NASA's Office of Space Science. The Space Science Institute (SSI) in Boulder, CO, is leading the project. Scientific and educational advisors from many different universities and government laboratories, most of whom are directly involved in the active and planned Mars missions, will ensure the scientific accuracy, timeliness, and relevance of the key concepts presented in the exhibition and accompanying programs. The traveling exhibit is the primary element of the MarsQuest project. The exhibition experience, carefully keyed to current events in Mars exploration, will transport visitors to the surface of the Red Planet via large murals, dioramas, and numerous interactive displays. There they will have the opportunity to share in the spirit and thrill of exploration, and come to appreciate the similarities and differences between Earth and Mars. A planetarium show, geared to the goals of the MarsQuest project, will be an important sensory addition to the traveling exhibit. The planetarium/star-theater venue presents a unique environment where audience members can literally be surrounded by Mars images. Education and outreach programs comprise the remainder of the MarsQuest project. The goal of these is to make scientific concepts and scientific and engineering processes understandable to students via Mars-inspired curricula. MarsQuest will open in late-1999, traveling to about nine sites throughout the United States and reaching an estimated two to three million children and adults during its planned three-year tour. Mars - coming soon to a museum near

  19. Preventing Adolescent Suicide.

    ERIC Educational Resources Information Center

    Capuzzi, David

    The adolescent at risk for suicidal preoccupation and behavior has become an increasing concern for schools and communities. This paper presents some of the causes of teen suicide, things adults should know about adolescent suicide prevention, and what can be done to help such youth. The transition to adolescence is a complex time when many values…

  20. Adolescent Attachment and Psychopathology.

    ERIC Educational Resources Information Center

    Rosenstein, Diana S.; Horowitz, Harvey A.

    1996-01-01

    In relationships among attachment classification, psychopathology, and personality, traits were examined in a group of 60 psychiatrically hospitalized adolescents. Attachment was examined in 27 adolescent-mother pairs. Both adolescent and maternal attachment status were overwhelmingly insecure and were highly concordant. Results support a model of…

  1. Adolescence and Mythology

    ERIC Educational Resources Information Center

    Anastasopoulos, Dimitris; Soumaki, Eugenia; Anagnostopoulos, Dimitris

    2010-01-01

    The article begins with a brief exploration of the various aspects of adolescent's psychic qualities as these are described in Greek mythology. It is argued that myths are an integral part of the way that adolescence is perceived and myths play an important role in adolescents' psychic and external world, as well as in their mythological thinking.…

  2. Life Satisfaction of Adolescents.

    ERIC Educational Resources Information Center

    Torgoff, Irving; And Others

    The feelings and perceptions of adolescents, apart from objective indices, warrent attention from those who are concerned with adolescent development and psychological stress. There is a need for a reliable baseline measure of adolescent subjective well-being, as manifested by self-reports of life satisfaction, to which future measurements can be…

  3. Update on Adolescent Immunizations.

    PubMed

    Schreier, Rebecca; Halady, Tasia; Bishop, Nina; Chatterjee, Archana

    2016-02-01

    Timely and complete adolescent vaccination remains an elusive public health goal. Three infections for which routine adolescent vaccination is recommended in the U.S. are pertussis, meningococcal disease and human papillomavirus (HPV). These infections and the Tdap, meningococcal and HPV vaccines recommended for adolescents are reviewed in this article. PMID:26999915

  4. Demystifying the Adolescent Brain

    ERIC Educational Resources Information Center

    Steinberg, Laurence

    2011-01-01

    Understanding the nature of brain development in adolescence helps explain why adolescents can vacillate so often between mature and immature behavior. Early and middle adolescence, in particular, are times of heightened vulnerability to risky and reckless behavior because the brain's reward center is easily aroused, but the systems that control…

  5. The Adolescent Patient.

    ERIC Educational Resources Information Center

    Daniel, William A., Jr.

    Written to orient the physician and paramedical personnel to the adolescent patient, the book provides information concerning the changes of adolescence, and age-related problems and illnesses. Part 1 discusses the essence of adolescence by describing physical, mental, and emotional growth and development. Part 2, the major section, consists of 21…

  6. Adolescents and the Media.

    ERIC Educational Resources Information Center

    Strasburgber, Victor C., Ed.; Comstock, George A., Ed.

    1993-01-01

    In the 1990s, the media represent the single most easily modifiable influence on children and adolescents. This series of articles offers medically oriented practitioners a review of current research on the influence of the media on children and adolescents. The 13 articles are: (1) "Children, Adolescents, and the Media: Five Crucial Issues"…

  7. 2007 Maryland Adolescent Survey

    ERIC Educational Resources Information Center

    Maryland State Department of Education, 2008

    2008-01-01

    Periodically, Maryland's sixth, eighth, tenth, and twelfth graders are surveyed to determine the nature, extent, and trend of alcohol, tobacco, and other drug (ATOD) use among adolescents. The "2007 Maryland Adolescent Survey (MAS)" presents the latest findings regarding ATOD use by Maryland's adolescents and compares State and local findings with…

  8. Neurobehavioral adaptations to methylphenidate: the issue of early adolescent exposure.

    PubMed

    Marco, Eva M; Adriani, Walter; Ruocco, Lucia A; Canese, Rossella; Sadile, Adolfo G; Laviola, Giovanni

    2011-08-01

    Exposure to psychostimulants, including both abused and therapeutic drugs, can occur first during human adolescence. Animal modeling is useful not only to reproduce adolescent peculiarities but also to study neurobehavioral adaptations to psychostimulant consumption. Human adolescence (generally considered as the period between 9/12 and 18 years old) has been compared with the age window between postnatal days (pnd) 28/35 and 50 in rats and mice. These adolescent rodents display basal hyperlocomotion and higher rates of exploration together with a marked propensity for sensation-seeking and risk-taking behaviors. Moreover, peculiar responses to psychostimulants, including enhanced locomotor sensitization, no drug-induced stereotypy and reduced place conditioning have been described in adolescent rodents. During this age window, forebrain dopamine systems undergo profuse remodeling, thus providing a neuro-biological substrate to explain behavioral peculiarities observed during adolescence, as well as the reported vulnerabilities to several drugs. Further, methylphenidate (MPH, better known as Ritalin®), a psychostimulant extensively prescribed to children and adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD), raises concerns for its long-term safety. Using magnetic resonance techniques, MPH-induced acute effects appear to be different in adolescent rats compared to adult animals. Moreover, adolescent exposure to MPH seems to provoke persistent neurobehavioral consequences: long-term modulation of self-control abilities, decreased sensitivity to natural and drug reward, enhanced stress-induced emotionality, together with an enhanced cortical control over sub-cortical dopamine systems and an enduring up-regulation of Htr7 gene expression within the nucleus accumbens (NAcc). In summary, additional studies in animal models are necessary to better understand the long-term consequences of adolescent MPH, and to further investigate the safety of

  9. Astronomy's New Messengers: A traveling exhibit to reach out to a young adult audience

    NASA Astrophysics Data System (ADS)

    Cavaglià, Marco; Hendry, Martin; Márka, Szabolcs; Reitze, David H.; Riles, Keith

    2010-05-01

    The Laser Interferometer Gravitational-wave Observatory exhibit Astronomy's New Messengers: Listening to the Universe with Gravitational Waves is traveling to colleges, universities, museums and other public institutions throughout the United States. In 2010, an extended version of this exhibit will appear in a New York City venue that is accessible to a large and diverse cross section of the general public. Astronomy's New Messengers primarily communicates with an adolescent and young adult audience, potentially inspiring them into the field of science. Acknowledging that this audience is traditionally a difficult one to attract, the exhibit publicly announces itself in a charismatic fashion to reach its principal goals of broadening the community of people interested in science and encouraging interest in science among young people.

  10. The palaeontological exhibition: a venue for dialogue.

    PubMed

    Murriello, Sandra

    2015-01-01

    Understanding the dialogue between museums and their visitors enables museums to subsist, undergo transformations and become consolidated as socially valued cultural venues. The Museo de La Plata (Argentina) was created in the late nineteenth century as a natural history museum, and this study shows that currently the museum is valued socially as a venue for family leisure and education, at which people make sense to the objects exhibited through characteristics conferred upon them by both the institution and the visitor. Nevertheless, such dialogue is somehow affected by the museographic proposal and the public interpretation of the institutional narrative, which could be analysed within the frame of contextual learning. As a consequence, the evolutionary idea that the museum aims to communicate is distorted by the public. This article highlights the importance of considering the visitors' interpretations when planning museum exhibitions, a perspective that has been rather absent in the Argentinian museums.

  11. Multimodal audio guide for museums and exhibitions

    NASA Astrophysics Data System (ADS)

    Gebbensleben, Sandra; Dittmann, Jana; Vielhauer, Claus

    2006-02-01

    In our paper we introduce a new Audio Guide concept for exploring buildings, realms and exhibitions. Actual proposed solutions work in most cases with pre-defined devices, which users have to buy or borrow. These systems often go along with complex technical installations and require a great degree of user training for device handling. Furthermore, the activation of audio commentary related to the exhibition objects is typically based on additional components like infrared, radio frequency or GPS technology. Beside the necessity of installation of specific devices for user location, these approaches often only support automatic activation with no or limited user interaction. Therefore, elaboration of alternative concepts appears worthwhile. Motivated by these aspects, we introduce a new concept based on usage of the visitor's own mobile smart phone. The advantages in our approach are twofold: firstly the Audio Guide can be used in various places without any purchase and extensive installation of additional components in or around the exhibition object. Secondly, the visitors can experience the exhibition on individual tours only by uploading the Audio Guide at a single point of entry, the Audio Guide Service Counter, and keeping it on her or his personal device. Furthermore, since the user usually is quite familiar with the interface of her or his phone and can thus interact with the application device easily. Our technical concept makes use of two general ideas for location detection and activation. Firstly, we suggest an enhanced interactive number based activation by exploiting the visual capabilities of modern smart phones and secondly we outline an active digital audio watermarking approach, where information about objects are transmitted via an analog audio channel.

  12. Naval Meteorology and Oceanography Command exhibit entrance

    NASA Technical Reports Server (NTRS)

    2000-01-01

    StenniSphere at NASA's John C. Stennis Space Center in Hancock County, Miss., invites visitors to discover why America comes to Stennis Space Center before going into space. Designed to entertain while educating, StenniSphere includes informative displays and exhibits from NASA and other agencies located at Stennis, such as this one from the Naval Meteorology and Oceanography Command. Visitors can 'travel' three-dimensionally under the sea and check on the weather back home in the Weather Center.

  13. Naval Meteorology and Oceanography Command exhibit

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Designed to entertain while educating, StenniSphere at the John C. Stennis Space Center in Hancock County, Miss., includes informative displays and exhibits from NASA and other agencies located at Stennis, such as this one from the Naval Meteorology and Oceanography Command. Visitors can 'travel' three-dimensionally under the sea and check on the weather back home in the Weather Center. StenniSphere is open free of charge from 9 a.m. to 5 p.m. daily.

  14. Art exhibit focuses on African astronomy

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2012-07-01

    Connections between Africans and astronomy are the focus of a new exhibition in the National Museum of African Art in Washington, D. C. "African Cosmos: Stellar Arts," which includes artwork, cultural items, and scientific displays from ancient to contemporary times, is the first major exhibit "that brings together arts and science focused on Africa's contribution to keen observations of the heavens over time," curator Christine Mullen Kreamer said at a 20 June news briefing. Among the exhibit's nearly 100 objects are an ancient Egyptian mummy board that includes a representation of the sky goddess Nut, sculptures by the Dogon people of Mali depicting figures in relation to the cosmos, a video that uses data from two square degrees of the Hubble Space Telescope Cosmic Evolution Survey, and a nearly floor-to-ceiling "Rainbow Serpent" constructed of plastic containers by Benin artist Hazoume. An untitled acrylic painting (Figure 1) by South African Gavin Jantjes evokes a myth of the Khoi San people of southern Africa, as it portrays a girl throwing evening fire embers into the night sky, where they remained as the Milky Way.

  15. Bumblebees exhibit the memory spacing effect

    NASA Astrophysics Data System (ADS)

    Toda, Nicholas R. T.; Song, Jeremy; Nieh, James C.

    2009-10-01

    Associative learning is key to how bees recognize and return to rewarding floral resources. It thus plays a major role in pollinator floral constancy and plant gene flow. Honeybees are the primary model for pollinator associative learning, but bumblebees play an important ecological role in a wider range of habitats, and their associative learning abilities are less well understood. We assayed learning with the proboscis extension reflex (PER), using a novel method for restraining bees (capsules) designed to improve bumblebee learning. We present the first results demonstrating that bumblebees exhibit the memory spacing effect. They improve their associative learning of odor and nectar reward by exhibiting increased memory acquisition, a component of long-term memory formation, when the time interval between rewarding trials is increased. Bombus impatiens forager memory acquisition (average discrimination index values) improved by 129% and 65% at inter-trial intervals (ITI) of 5 and 3 min, respectively, as compared to an ITI of 1 min. Memory acquisition rate also increased with increasing ITI. Encapsulation significantly increases olfactory memory acquisition. Ten times more foragers exhibited at least one PER response during training in capsules as compared to traditional PER harnesses. Thus, a novel conditioning assay, encapsulation, enabled us to improve bumblebee-learning acquisition and demonstrate that spaced learning results in better memory consolidation. Such spaced learning likely plays a role in forming long-term memories of rewarding floral resources.

  16. When do children exhibit a "yes" bias?

    PubMed

    Okanda, Mako; Itakura, Shoji

    2010-01-01

    This study investigated whether one hundred and thirty-five 3- to 6-year-old children exhibit a yes bias to various yes-no questions and whether their knowledge status affects the production of a yes bias. Three-year-olds exhibited a yes bias to all yes-no questions such as preference-object and knowledge-object questions pertaining to objects, and knowledge-face questions pertaining to facial expressions. Four-year-olds tended to say "yes" only to knowledge-object questions. Five-year-olds did not show any strong response tendency. Six-year-olds exhibited a nay-saying bias to knowledge-face questions. Also, 3-year-olds could indicate the correct option when asked questions with 2 response options. It suggested that 3-year-olds tended to inappropriately say "yes" to yes-no questions, although they knew the answers to the questions. The mechanism of a yes bias was discussed.

  17. The E = mc{sup 2} exhibition

    SciTech Connect

    Henderson, D.; Peshkin, M.

    1995-08-01

    The goal of this DOE-supported exhibition is to demystify Einstein`s formula E = mc{sup 2} by illustrating the interchangeability of matter (m) and energy (E), c{sup 2} being the exchange rate. The exhibition has two major parts, {open_quotes}matter into energy{close_quotes} and {open_quotes}energy into matter{close_quotes}, plus a video to connect them. {open_quotes}Matter into energy{close_quotes} has now been completed and has been placed on the museum floor. Positrons from a {sup 22}Na source are annihilated to produce gamma rays that are caught in NaI detectors. The viewer can alter the alignment of the detectors and observe the consequences for the rates of single and coincident counts. The viewer can also observe the effects of placing absorbers in front of the counters. Prototype explanatory graphics were placed around the exhibit and those will probably be changed after we have some experience with their effectiveness. The connecting video is in the process of being produced in collaboration with Fermilab. A cloud chamber for {open_quotes}energy into matter{close_quotes}, where gamma rays from a small Th source will produce observable pairs, was purchased and work to make the pairs visible has commenced.

  18. Health for Adolescents and Youth.

    ERIC Educational Resources Information Center

    Deschamps, Jean-Pierre; And Others

    1989-01-01

    This report discusses the health of adolescents and youth in the tropics. The report is divided into five sections. The first section defines adolescence, youth, the duration of adolescence, the age group and its problems, and societies in adolescence. The second section discusses adolescence in relation to society and culture and focuses on the…

  19. Unsafe abortion in adolescents.

    PubMed

    Olukoya, A A; Kaya, A; Ferguson, B J; AbouZahr, C

    2001-11-01

    Every year, an estimated 2.0-4.4 million adolescents resort to abortion. In comparison with adults, adolescents are more likely to delay the abortion, resort to unskilled persons to perform it, use dangerous methods and present late when complications arise. Adolescents are also more likely to experience complications. Consequently, adolescents seeking abortion or presenting with complications of abortion should be considered as a medical emergency. Issues requiring special attention in the management of abortion complications in adolescents are identified. Approaches to adolescent abortion should involve all levels of the health care system, as well as the community, and should include not only management of the consequences of unsafe abortion, but also post-abortion contraception and counseling. Prevention of unwanted pregnancy by providing information on sexuality, ensuring that reproductive health services are adolescent-friendly, creating a supportive environment, building young people's social and decision-making skills, and offering counseling in times of crisis are highlighted.

  20. Contraception for adolescents.

    PubMed

    Ott, Mary A; Sucato, Gina S

    2014-10-01

    A working knowledge of contraception will assist the pediatrician in both sexual health promotion as well as treatment of common adolescent gynecologic problems. Best practices in adolescent anticipatory guidance and screening include a sexual health history, screening for pregnancy and sexually transmitted infections, counseling, and if indicated, providing access to contraceptives. Pediatricians' long-term relationships with adolescents and families allow them to help promote healthy sexual decision-making, including abstinence and contraceptive use. Additionally, medical indications for contraception, such as acne, dysmenorrhea, and heavy menstrual bleeding, are frequently uncovered during adolescent visits. This technical report provides an evidence base for the accompanying policy statement and addresses key aspects of adolescent contraceptive use, including the following: (1) sexual history taking, confidentiality, and counseling; (2) adolescent data on the use and side effects of newer contraceptive methods; (3) new data on older contraceptive methods; and (4) evidence supporting the use of contraceptives in adolescent patients with complex medical conditions. PMID:25266435

  1. Age associations with neural processing of reward anticipation in adolescents with bipolar disorders.

    PubMed

    Urošević, Snežana; Luciana, Monica; Jensen, Jonathan B; Youngstrom, Eric A; Thomas, Kathleen M

    2016-01-01

    Reward/behavioral approach system hypersensitivity is implicated in bipolar disorders (BD) and in normative development during adolescence. Pediatric onset of BD is associated with a more severe illness course. However, little is known about neural processing of rewards in adolescents with BD or developmental (i.e., age) associations with activation of these neural systems. The present study aims to address this knowledge gap. The present sample included 21 adolescents with BD and 26 healthy adolescents, ages 13 to 19. Participants completed a functional magnetic resonance imaging (fMRI) protocol using the Monetary Incentive Delay (MID) task. Behavioral performance was similar between groups. Group differences in BOLD activation during target anticipation and feedback anticipation periods of the task were examined using whole-brain analyses, as were group differences in age effects. During both target anticipation and feedback anticipation, adolescents with BD, compared to adolescents without psychopathology, exhibited decreased engagement of frontal regions involved in cognitive control (i.e., dorsolateral prefrontal cortex). Healthy adolescents exhibited age-related decreases, while adolescents with BD exhibited age-related increases, in activity of other cognitive control frontal areas (i.e., right inferior frontal gyrus), suggesting altered development in the BD group. Longitudinal research is needed to examine potentially abnormal development of cognitive control during reward pursuit in adolescent BD and whether early therapeutic interventions can prevent these potential deviations from normative development. PMID:27114896

  2. Age associations with neural processing of reward anticipation in adolescents with bipolar disorders

    PubMed Central

    Urošević, Snežana; Luciana, Monica; Jensen, Jonathan B.; Youngstrom, Eric A.; Thomas, Kathleen M.

    2016-01-01

    Reward/behavioral approach system hypersensitivity is implicated in bipolar disorders (BD) and in normative development during adolescence. Pediatric onset of BD is associated with a more severe illness course. However, little is known about neural processing of rewards in adolescents with BD or developmental (i.e., age) associations with activation of these neural systems. The present study aims to address this knowledge gap. The present sample included 21 adolescents with BD and 26 healthy adolescents, ages 13 to 19. Participants completed a functional magnetic resonance imaging (fMRI) protocol using the Monetary Incentive Delay (MID) task. Behavioral performance was similar between groups. Group differences in BOLD activation during target anticipation and feedback anticipation periods of the task were examined using whole-brain analyses, as were group differences in age effects. During both target anticipation and feedback anticipation, adolescents with BD, compared to adolescents without psychopathology, exhibited decreased engagement of frontal regions involved in cognitive control (i.e., dorsolateral prefrontal cortex). Healthy adolescents exhibited age-related decreases, while adolescents with BD exhibited age-related increases, in activity of other cognitive control frontal areas (i.e., right inferior frontal gyrus), suggesting altered development in the BD group. Longitudinal research is needed to examine potentially abnormal development of cognitive control during reward pursuit in adolescent BD and whether early therapeutic interventions can prevent these potential deviations from normative development. PMID:27114896

  3. 7 CFR Exhibit G to Subpart E of... - Exhibit G to Subpart E of Part 1980

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... OF AGRICULTURE (CONTINUED) PROGRAM REGULATIONS (CONTINUED) GENERAL Business and Industrial Loan... 7 Agriculture 14 2014-01-01 2014-01-01 false Exhibit G to Subpart E of Part 1980 G Exhibit G to Subpart E of Part 1980 Agriculture Regulations of the Department of Agriculture (Continued) RURAL...

  4. 7 CFR Exhibit G to Subpart E of... - Exhibit G to Subpart E of Part 1980

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... OF AGRICULTURE (CONTINUED) PROGRAM REGULATIONS (CONTINUED) GENERAL Business and Industrial Loan... 7 Agriculture 14 2011-01-01 2011-01-01 false Exhibit G to Subpart E of Part 1980 G Exhibit G to Subpart E of Part 1980 Agriculture Regulations of the Department of Agriculture (Continued) RURAL...

  5. 7 CFR Exhibit G to Subpart E of... - Exhibit G to Subpart E of Part 1980

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... OF AGRICULTURE (CONTINUED) PROGRAM REGULATIONS (CONTINUED) GENERAL Business and Industrial Loan... 7 Agriculture 14 2012-01-01 2012-01-01 false Exhibit G to Subpart E of Part 1980 G Exhibit G to Subpart E of Part 1980 Agriculture Regulations of the Department of Agriculture (Continued) RURAL...

  6. 7 CFR Exhibit G to Subpart E of... - Exhibit G to Subpart E of Part 1980

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... OF AGRICULTURE (CONTINUED) PROGRAM REGULATIONS (CONTINUED) GENERAL Business and Industrial Loan... 7 Agriculture 14 2010-01-01 2009-01-01 true Exhibit G to Subpart E of Part 1980 G Exhibit G to Subpart E of Part 1980 Agriculture Regulations of the Department of Agriculture (Continued) RURAL...

  7. 7 CFR Exhibit G to Subpart E of... - Exhibit G to Subpart E of Part 1980

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... OF AGRICULTURE (CONTINUED) PROGRAM REGULATIONS (CONTINUED) GENERAL Business and Industrial Loan... 7 Agriculture 14 2013-01-01 2013-01-01 false Exhibit G to Subpart E of Part 1980 G Exhibit G to Subpart E of Part 1980 Agriculture Regulations of the Department of Agriculture (Continued) RURAL...

  8. Health-risk behaviors in early adolescence.

    PubMed

    Rew, Lynn; Horner, Sharon D; Brown, Adama

    2011-01-01

    The major morbidities and mortalities of adolescents are related to preventable risky behaviors, but how, when, and in whom these behaviors develop in early adolescence is unknown. The purpose of this study was to determine which set of risk factors and protective resources of school-age children were best predictors of health-risk behaviors in early adolescence. A longitudinal, cohort sequential design was used with a diverse sample of 1,934 children in grades 4 through 8. Parents provided demographic and neighborhood data for children through a mailed survey. Children completed valid scales annually at schools, using audio-computer-assisted self-interviewing (A-CASI) technology. Significant gender and racial/ethnic differences were found in carrying a weapon and using alcohol. Higher perceived levels of stress increased the risk for alcohol use as did riding in a car with a driver who was drinking. Health behaviors exhibited while in 4th through 6th grades protected early adolescents from alcohol use and riding in a car with a driver who was drinking. A parent's education and perceived safety in neighborhood protected against carrying a weapon and smoking. Many findings are similar to those of national samples, but others show positive differences in this localized sample, over 50% of whom were Latino. Protective resources suggest numerous nursing interventions to promote healthy adolescent development.

  9. Measuring Anhedonia in Adolescents: A Psychometric Analysis.

    PubMed

    Leventhal, Adam M; Unger, Jennifer B; Audrain-McGovern, Janet; Sussman, Steve; Volk, Heather E; Strong, David R

    2015-01-01

    Anhedonia-the reduced capacity to experience pleasure-is a trait implicated in mental and physical health. Yet, psychometric data on anhedonia measures in adolescents are absent. We conducted an in-depth psychometric analysis of the Snaith-Hamilton Pleasure Scale (SHAPS; Snaith et al., 1995 )-a self-report measure of anticipated pleasure response to 14 pleasant experiences-in adolescents. Adolescents (N = 585, M age = 14.5) completed the SHAPS and other paper-and-pencil surveys. Item response theory models were used to evaluate the psychometric performance of each SHAPS item. Correlations of the SHAPS with other personality and psychopathology measures were calculated to evaluate construct validity. Results showed that (a) certain items (e.g., reported pleasure from basic experiences like "seeing smiling faces" or "smelling flowers") provided more information about latent anhedonia than others; and (b) SHAPS scales exhibited construct-consistent convergent and discriminant validity (i.e., stronger correlations with low positive affect constructs, weaker correlations with negative affect). Reporting diminished pleasure from basic pleasant experiences accurately indicates adolescent anhedonia, which is important for future scale development and understanding the phenomenology of anhedonia in teens. These data support using the SHAPS for assessing anhedonia in epidemiological research and school-based universal prevention programming in general adolescent populations.

  10. Measuring Anhedonia in Adolescents: A Psychometric Analysis

    PubMed Central

    Leventhal, Adam M.; Unger, Jennifer B.; Audrain-McGovern, Janet; Sussman, Steve; Volk, Healther E.; Strong, David R.

    2015-01-01

    Anhedonia—the reduced capacity to experience pleasure—is a trait implicated in mental and physical health. Yet, psychometric data on anhedonia measures in adolescents are absent. We conducted an in-depth psychometric analysis of the Snaith-Hamilton Pleasure Scale (SHAPS; Snaith et al., 1995)—a self-report measure of anticipated pleasure response to 14 pleasant experiences—in adolescents. Adolescents (N=585; M age=14.5) completed the SHAPS and other paper-and-pencil surveys. Item response theory models were used to evaluate the psychometric performance of each SHAPS item. Correlations of the SHAPS with other personality and psychopathology measures were calculated to evaluate construct validity. Results showed that: (1) certain items (e.g., reported pleasure from basic experiences like “seeing smiling faces” or “smelling flowers”) provided more information about latent anhedonia than others; and (2) SHAPS scales exhibited construct-consistent convergent and discriminant validity (i.e., stronger correlations with low positive affect constructs; weaker correlations with negative affect). Reporting diminished pleasure from basic pleasant experiences accurately indicates adolescent anhedonia, which is important for future scale development and understanding the phenomenology of anhedonia in teens. These data support using the SHAPS for assessing anhedonia in epidemiological research and school-based universal prevention programming in general adolescent populations. PMID:25893676

  11. Ethnic identity and gender as moderators of the association between discrimination and academic adjustment among Mexican-origin adolescents.

    PubMed

    Umaña-Taylor, Adriana J; Wong, Jessie J; Gonzales, Nancy A; Dumka, Larry E

    2012-08-01

    Existing work has identified perceived discrimination as a risk factor that may contribute to the relatively poorer academic outcomes exhibited by Mexican-origin adolescents in the U.S. The current study examined the longitudinal associations among perceived discrimination and three indices of adolescent adjustment in the school setting (i.e., grade point average, teacher reports of externalizing, adolescents' deviant peer associations) among 178 Mexican-origin adolescents (53% female). Ethnic identity affirmation was examined as a protective factor expected to reduce the negative effects of discrimination on adolescents' adjustment, and gender was examined as a potential moderator of the associations of interest. Findings indicated that the deleterious effects of discrimination on adolescents' adjustment in school were particularly salient for Mexican-origin male adolescents. Importantly, ethnic identity affirmation emerged as a protective factor for Mexican-origin male adolescents by buffering the negative effects of discrimination on their externalizing behaviors in school.

  12. Adolescents with Asperger Syndrome Can Use a Mindfulness-Based Strategy to Control Their Aggressive Behavior

    ERIC Educational Resources Information Center

    Singh, Nirbhay N.; Lancioni, Giulio E.; Singh, Angela D. A.; Winton, Alan S. W.; Singh, Ashvind N. A.; Singh, Judy

    2011-01-01

    Children and adolescents with Asperger syndrome occasionally exhibit aggressive behavior against peers and parents. In a multiple baseline design across subjects, three adolescents with Asperger syndrome were taught to use a mindfulness-based procedure called "Meditation on the Soles of the Feet" to control their physical aggression in the family…

  13. Adolescent Egocentrism, Risk Perceptions, and Sensation Seeking among Smoking and Nonsmoking Youth

    ERIC Educational Resources Information Center

    Frankenberger, Kristina D.

    2004-01-01

    A survey compared adolescents (ages 14 to 18) who have never tried smoking, smoke infrequently, or smoke regularly on three characteristics: adolescent egocentrism, risk perceptions, and sensation seeking. Sensation seeking exhibited the expected result by increasing with smoking experience. Contrary to past research findings, perceptions of…

  14. Progression of Amygdala Volumetric Abnormalities in Adolescents after Their First Manic Episode

    ERIC Educational Resources Information Center

    Bitter, Samantha M.; Mills, Neil P.; Adler, Caleb M.; Strakowski, Stephen M.; DelBello, Melissa P.

    2011-01-01

    Objective: Although previous neuroimaging studies suggest that adolescents with bipolar disorder exhibit smaller amygdala volumes compared with healthy adolescents, whether these abnormalities are present at illness onset or instead develop over time remains unclear. The aim of this study was to conduct a prospective longitudinal investigation…

  15. The Younger Siblings of Childbearing Adolescents: Parenting Influences on Their Academic and Social-Emotional Adjustment

    ERIC Educational Resources Information Center

    Chien, Nina C.; East, Patricia L.

    2012-01-01

    The younger siblings of childbearing adolescents have poorer school outcomes and exhibit more internalizing and externalizing problems compared to their peers without a childbearing sister. We test a model where living with an adolescent childbearing sister constitutes a major family stressor that disrupts mothers' parenting and well-being, and…

  16. Memory Retrieval before or after Extinction Reduces Recovery of Fear in Adolescent Rats

    ERIC Educational Resources Information Center

    Baker, Kathryn D.; McNally, Gavan P.; Richardson, Rick

    2013-01-01

    Adolescent rats exhibit impaired extinction retention compared to pre-adolescent and adult rats. A single nonreinforced exposure to the conditioned stimulus (CS; a retrieval trial) given shortly before extinction has been shown in some circumstances to reduce the recovery of fear after extinction in adult animals. This study investigated whether a…

  17. School Transitions among Military Adolescents: A Qualitative Study of Stress and Coping

    ERIC Educational Resources Information Center

    Bradshaw, Catherine P.; Sudhinaraset, May; Mmari, Kristin; Blum, Robert W.

    2010-01-01

    The research on highly mobile military adolescents has produced mixed findings. Whereas early descriptive studies reported that adolescents experiencing multiple residential moves exhibited symptoms of what was termed "military family syndrome", more recent quantitative studies have found few negative effects after controlling for prior status.…

  18. Adolescent rats are resistant to the development of ethanol-induced chronic tolerance and ethanol-induced conditioned aversion.

    PubMed

    Pautassi, Ricardo Marcos; Godoy, Juan Carlos; Molina, Juan Carlos

    2015-11-01

    The analysis of chronic tolerance to ethanol in adult and adolescent rats has yielded mixed results. Tolerance to some effects of ethanol has been reported in adolescents, yet other studies found adults to exhibit greater tolerance than adolescents or comparable expression of the phenomena at both ages. Another unanswered question is how chronic ethanol exposure affects subsequent ethanol-mediated motivational learning at these ages. The present study examined the development of chronic tolerance to ethanol's hypothermic and motor stimulating effects, and subsequent acquisition of ethanol-mediated odor conditioning, in adolescent and adult male Wistar rats given every-other-day intragastric administrations of ethanol. Adolescent and adult rats exhibited lack of tolerance to the hypothermic effects of ethanol during an induction phase; whereas adults, but not adolescents, exhibited a trend towards a reduction in hypothermia at a challenge phase (Experiment 1). Adolescents, unlike adults, exhibited ethanol-induced motor activation after the first ethanol administration. Adults, but not adolescents, exhibited conditioned odor aversion by ethanol. Subsequent experiments conducted only in adolescents (Experiment 2, Experiment 3 and Experiment 4) manipulated the context, length and predictability of ethanol administration. These manipulations did not promote the expression of ethanol-induced tolerance. This study indicated that, when moderate ethanol doses are given every-other day for a relatively short period, adolescents are less likely than adults to develop chronic tolerance to ethanol-induced hypothermia. This resistance to tolerance development could limit long-term maintenance of ethanol intake. Adolescents, however, exhibited greater sensitivity than adults to the acute motor stimulating effects of ethanol and a blunted response to the aversive effects of ethanol. This pattern of response may put adolescents at risk for early initiation of ethanol intake.

  19. Female adolescent craniofacial growth spurts: real or fiction?

    PubMed

    Buschang, Peter H; Jacob, Helder B; Demirjian, Arto

    2013-12-01

    The purpose of the study is to determine whether the various aspects of the craniofacial complex exhibit female adolescent growth spurts. Multilevel polynomial models were used to estimate the growth curves of a mixed-longitudinal sample of 111 untreated females 10-15 years of age. To evaluate the horizontal and vertical movements of the individual landmarks relative to stable structures, the tracings were superimposed on the natural reference structures in the anterior cranial base. The horizontal and vertical growth changes of four landmarks and the changes of three traditional linear measurements were evaluated. Posterior nasal spine (PNS) moved posteriorly at a constant rate of approximately 0.12mm/year. Five measures showed changes in growth velocity (i.e. quadratic growth curves) but not adolescent growth spurts, including the anterior movements of anterior nasal spine (ANS) and pogonion (Pg), the inferior movements of gonion (Go), and the increases in ANS-PNS and condylion to pogonion (Co-Pg). Five measurements, including the inferior movements of ANS, PNS and Pg, the posterior movements of Go, and the increases of Go-Pg exhibited adolescent growth spurts. Peak growth velocities were attained between 11.4 and 12.8 years of age, approximately 0.7-1.4 years earlier in the maxilla than mandible. While the vertical aspects of craniofacial growth exhibit distinct female adolescent growth spurts, with peak rates occurring earlier in the maxilla than mandible, most horizontal aspects of craniofacial growth do not exhibit an adolescent spurt.

  20. Mars in their eyes - a cartoon exhibition

    NASA Astrophysics Data System (ADS)

    Pillinger, Pi.

    Recently a collection of 120 cartoons which tell the story of Mars exploration and scientific discovery, past, present and future, was held in London. We discuss the aims of the exhibition, to what extent we believe the original aims were met and report on additional outreach opportunities resulting from the project. The overriding aim was to capitalise on the popular appeal of accessible art - most people admit to enjoying cartoons. This was strengthened by hanging the originals of cartoons which had, mostly, been published in newspapers and magazines in a wide selection of countries. The provenances served to indicate the attraction of Mars to a wide public. We were fortunate to work with the Cartoon Art Trust of the UK who was in the process of relocating to new premises and opening as The Cartoon Museum, in the tourist area of Bloomsbury, central London, very close to the British Museum. "Mars in their Eyes" ran for 10 weeks during April to July 2006; immediately following which a selection of the cartoons was displayed at the week-long Royal Society Summer Exhibition. We explore the differences between the two exhibitions and comment on the various audience responses. We use this comparison to discuss whether a project which is primarily art can be extended to explain science. Does the coupling merely result in dumbing-down of both cultures or is there a true synergy? The experience has led us to coin the phrase "extreme outreach". Projects which are as ambitious as "Mars in their Eyes", without the security of a safe, captive audience, for example at a Science Centre, must be judged by different criteria. Indeed if the project does not meet comparable targets like large visitor numbers, then the honest evaluation of such details can only inform future activities and must not be reflected in the future funding of only "safe" outreach activities.

  1. Noisy neural nets exhibiting epileptic features.

    PubMed

    Kokkinidis, M; Anninos, P

    1985-04-01

    On the basis of our previous studies of noisy neural nets we propose a model for the explanation of epileptic phenomena. Our neural net model is capable of exhibiting epileptic features if the number of spontaneously firing neurons is periodically increased beyond a certain threshold. Some alternative epileptogenic mechanisms are also discussed. The epileptic behavior of the neural net is determined by a combination of certain parameters of its phase diagram. The general features of the model are consistent with several experimental observations and explain some poorly understood clinical phenomena. The differences between normal and epileptic neural nets are explained in terms of the structural properties of the model.

  2. Library exhibits and programs boost science education

    NASA Astrophysics Data System (ADS)

    Dusenbery, Paul B.; Curtis, Lisa

    2012-05-01

    Science museums let visitors explore and discover, but for many families there are barriers—such as cost or distance—that prevent them from visiting museums and experiencing hands-on science, technology, engineering, and mathematics (STEM) learning. Now educators are reaching underserved audiences by developing STEM exhibits and programs for public libraries. With more than 16,000 outlets in the United States, public libraries serve almost every community in the country. Nationwide, they receive about 1.5 billion visits per year, and they offer their services for free.

  3. Transgenic Mice Expressing an Inhibitory Truncated Form of p300 Exhibit Long-Term Memory Deficits

    ERIC Educational Resources Information Center

    Oliveira, Ana M. M.; Wood, Marcelo A.; McDonough, Conor B.; Abel, Ted

    2007-01-01

    The formation of many forms of long-term memory requires several molecular mechanisms including regulation of gene expression. The mechanisms directing transcription require not only activation of individual transcription factors but also recruitment of transcriptional coactivators. CBP and p300 are transcriptional coactivators that interact with…

  4. Subregion-Specific p300 Conditional Knock-Out Mice Exhibit Long-Term Memory Impairments

    ERIC Educational Resources Information Center

    Oliveira, Ana M. M.; Estevez, Marcel A.; Hawk, Joshua D.; Grimes, Shannon; Brindle, Paul K.; Abel, Ted

    2011-01-01

    Histone acetylation plays a critical role during long-term memory formation. Several studies have demonstrated that the histone acetyltransferase (HAT) CBP is required during long-term memory formation, but the involvement of other HAT proteins has not been extensively investigated. The HATs CBP and p300 have at least 400 described interacting…

  5. "Gadd45b" Knockout Mice Exhibit Selective Deficits in Hippocampus-Dependent Long-Term Memory

    ERIC Educational Resources Information Center

    Leach, Prescott T.; Poplawski, Shane G.; Kenney, Justin W.; Hoffman, Barbara; Liebermann, Dan A.; Abel, Ted; Gould, Thomas J.

    2012-01-01

    Growth arrest and DNA damage-inducible [beta] ("Gadd45b") has been shown to be involved in DNA demethylation and may be important for cognitive processes. "Gadd45b" is abnormally expressed in subjects with autism and psychosis, two disorders associated with cognitive deficits. Furthermore, several high-throughput screens have identified "Gadd45b"…

  6. Mx1-cre mediated Rgs12 conditional knockout mice exhibit increased bone mass phenotype

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Regulators of G-protein Signaling (Rgs) proteins are the members of a multigene family of GTPase-accelerating proteins (GAP) for the Galpha subunit of heterotrimeric G-proteins. Rgs proteins play critical roles in the regulation of G protein couple receptor (GPCR) signaling in normal physiology and ...

  7. Nematic liquid crystals exhibiting high birefringence

    NASA Astrophysics Data System (ADS)

    Thingujam, Kiranmala; Bhattacharjee, Ayon; Choudhury, Basana; Dabrowski, Roman

    2016-06-01

    Two fluorinated isothiocyanato nematic liquid crystalline compounds, 4'-butylcyclohexyl-3, 5-difluoro-4-isothiocyanatobiphenyl and 4'-pentylcyclohexyl-3, 5-difluoro-4-isothiocynatobiphenyl are studied in detail to obtain their different physical parameters. Optical polarizing microscopy, differential scanning calorimetry, density and dielectric studies have been carried out for the two samples. Both the samples were found to have high clearing temperature (>100 °C) and exhibit small enthalpy of transition. The two samples exhibit high optical birefringence (Δ n > 0.2). The values of order parameters for the two samples were obtained using different approaches, namely, Vuks', Neugebauer's, modified Vuks' and direct extrapolation method from birefringence data. Experimentally obtained values of order parameters have also been compared with theoretical Maier-Saupe values. The parallel and perpendicular components of dielectric permittivity values of the two compounds were also calculated and their anisotropy values were found to be small. The effect of temperature on the molecular dipole moment μ and the angle of inclination β of the dipole axis with the director have also been investigated in this work.

  8. Enhanced brain susceptibility to negative stimuli in adolescents: ERP evidences

    PubMed Central

    Yuan, Jiajin; Ju, Enxia; Meng, Xianxin; Chen, Xuhai; Zhu, Siyu; Yang, Jiemin; Li, Hong

    2015-01-01

    Background: Previous studies investigated neural substrates of emotional face processing in adolescents and its comparison with adults. As emotional faces elicit more of emotional expression recognition rather than direct emotional responding, it remains undetermined how adolescents are different from adults in brain susceptibility to emotionally stressful stimuli. Methods: Event-Related Potentials (ERPs) were recorded for highly negative (HN), moderately negative (MN), and neutral pictures in 20 adolescents and 20 adults while subjects performed a standard/deviant distinction task by pressing different keys, irrespective of the emotionality of deviant stimuli. Results: Adolescents exhibited more negative amplitudes for HN vs. neutral pictures in N1 (100–150 ms), P2 (130–190 ms), N2 (210–290 ms), and P3 (360–440 ms) components. In addition, adolescents showed more negative amplitudes for MN compared to neutral pictures in N1, P2, and N2 components. By contrast, adults exhibited significant emotion effects for HN stimuli in N2 and P3 amplitudes but not in N1 and P2 amplitudes, and they did not exhibit a significant emotion effect for MN stimuli at all these components. In the 210–290 ms time interval, the emotion effect for HN stimuli was significant across frontal and central regions in adolescents, while this emotion effect was noticeable only in the central region for adults. Conclusions: Adolescents are more emotionally sensitive to negative stimuli compared to adults, regardless of the emotional intensity of the stimuli, possibly due to the immature prefrontal control system over the limbic emotional inputs during adolescence. PMID:25972790

  9. Dexrazoxane Diminishes Doxorubicin-Induced Acute Ovarian Damage and Preserves Ovarian Function and Fecundity in Mice

    PubMed Central

    Ringelstetter, Ashley; Khatib, Hasan; Abbott, David H.; Salih, Sana M.

    2015-01-01

    Advances in cancer treatment utilizing multiple chemotherapies have dramatically increased cancer survivorship. Female cancer survivors treated with doxorubicin (DXR) chemotherapy often suffer from an acute impairment of ovarian function, which can persist as long-term, permanent ovarian insufficiency. Dexrazoxane (Dexra) pretreatment reduces DXR-induced insult in the heart, and protects in vitro cultured murine and non-human primate ovaries, demonstrating a drug-based shield to prevent DXR insult. The present study tested the ability of Dexra pretreatment to mitigate acute DXR chemotherapy ovarian toxicity in mice through the first 24 hours post-treatment, and improve subsequent long-term fertility throughout the reproductive lifespan. Adolescent CD-1 mice were treated with Dexra 1 hour prior to DXR treatment in a 1:1 mg or 10:1 mg Dexra:DXR ratio. During the acute injury period (2–24 hours post-injection), Dexra pretreatment at a 1:1 mg ratio decreased the extent of double strand DNA breaks, diminished γH2FAX activation, and reduced subsequent follicular cellular demise caused by DXR. In fertility and fecundity studies, dams pretreated with either Dexra:DXR dose ratio exhibited litter sizes larger than DXR-treated dams, and mice treated with a 1:1 mg Dexra:DXR ratio delivered pups with birth weights greater than DXR-treated females. While DXR significantly increased the “infertility index” (quantifying the percentage of dams failing to achieve pregnancy) through 6 gestations following treatment, Dexra pretreatment significantly reduced the infertility index following DXR treatment, improving fecundity. Low dose Dexra not only protected the ovaries, but also bestowed a considerable survival advantage following exposure to DXR chemotherapy. Mouse survivorship increased from 25% post-DXR treatment to over 80% with Dexra pretreatment. These data demonstrate that Dexra provides acute ovarian protection from DXR toxicity, improving reproductive health in a mouse

  10. Assessment and treatment of multiple behavior problems exhibited by a profoundly retarded adolescent.

    PubMed

    Slifer, K J; Ivancic, M T; Parrish, J M; Page, T J; Burgio, L D

    1986-09-01

    The severe aggression and noncompliance of a profoundly retarded blind male were subjected to extensive behavioral assessment in order to identify controlling variables. The assessment, conducted across settings and therapists, suggested that these inappropriate behaviors functioned to avoid or terminate nonpreferred activities. Intervention consisted of manual guidance when there was noncompliance with instructions and edible reinforcement upon compliance; there were no direct contingencies for the inappropriate behaviors. Treatment procedures were implemented in a multiple baseline design across therapists and settings. Results show that the intervention consistently increased compliance, with concurrent decreases in inappropriate behaviors. Edible reinforcement and neuroleptic medication were withdrawn systematically with no loss of therapeutic gains. Family members and school personnel were trained to use the intervention procedures. Results are discussed in terms of functional assessment, response covariation, compliance training, parent and staff training, and behavioral assessment of the effects of neuroleptic medication. PMID:2876010

  11. Personality and Parenting Processes Associated with Problem Behaviors: A Study of Adolescents in Santiago, Chile

    PubMed Central

    Bares, Cristina B.; Andrade, Fernando; Delva, Jorge; Grogan-Kaylor, Andrew

    2011-01-01

    Considerable research in the U.S. has established that adolescent antisocial, aggressive, and attention problems have a negative influence on adolescents' ability to become productive members of society. However, although these behaviors appear in other cultures, little is known about the development of these problems among adolescents in countries other than the U.S.. This study contributes to our understanding of personality and parenting factors associated with adolescent problem behaviors using an international sample. Data are from a NIDA-funded study of 884 community-dwelling adolescents in Santiago, Chile (Mean age=14, SD=1.4, 48% females) of mid-to-low socioeconomic status. Results revealed that rule-breaking and aggressive behaviors were both associated with greater levels of adolescent drive but lower levels of parental monitoring and positive parenting by both parents. Adolescents who reported more attention problems were more likely to exhibit driven behavior, more behavioral inhibition, to report lower levels of parental monitoring, and positive parenting by mother and father. Results of interactions revealed that the influences of positive parenting and parental monitoring on adolescent aggressive behaviors varied as a function of the gender of the adolescent. Helping parents build on their parenting skills may result in important reductions in adolescent problem behaviors among U.S. and international adolescents. PMID:23100999

  12. Bone Growth and Turnover in Progesterone Receptor Knockout Mice

    PubMed Central

    Rickard, David J.; Iwaniec, Urszula T.; Evans, Glenda; Hefferan, Theresa E.; Hunter, Jamie C.; Waters, Katrina M.; Lydon, John P.; O’Malley, Bert W.; Khosla, Sundeep; Spelsberg, Thomas C.; Turner, Russell T.

    2008-01-01

    The role of progesterone receptor (PR) signaling in skeletal metabolism is controversial. To address whether signaling through the PR is necessary for normal bone growth and turnover, we performed histomorphometric and microcomputed tomography analyses of bone from homozygous female PR knockout (PRKO) mice at 6, 12, and 26 wk of age. These mice possess a null mutation of the PR locus, which blocks the gene expression of A and B isoforms of PR. Body weight gain, uterine weight gain, and tibia longitudinal bone growth were normal in PRKO mice. In contrast, total, cancellous, and cortical bone mass were increased in the humerus of 12-wk-old PRKO mice, whereas cortical and cancellous bone mass in the tibia was normal. At 26 wk of age, cancellous bone area in the proximal tibia metaphysis of PRKO mice was 153% greater than age matched wild-type mice. The improved cancellous bone balance in 6-month-old PRKO mice was associated with elevated bone formation and a tendency toward reduced osteoclast perimeter. Taken together, these findings suggest that PR signaling in mice is not essential for bone growth and turnover. However, at some skeletal sites, PR signaling attenuates the accumulation of cortical and cancellous bone mass during adolescence. PMID:18276762

  13. Bone growth and turnover in progesterone receptor knockout mice.

    SciTech Connect

    Rickard, David J.; Iwaniec, Urszula T.; Evans, Glenda; Hefferan, Theresa E.; Hunter, Jaime C.; Waters, Katrina M.; Lydon, John P.; O'Malley, Bert W.; Khosla, Sundeep; Spelsberg, Thomas C.; Turner, Russell T.

    2008-05-01

    The role of progesterone receptor (PR) signaling in skeletal metabolism is controversial. To address whether signaling through the PR is necessary for normal bone growth and turnover, we performed histomorphometric and mCT analyses of bone from homozygous female PR knockout (PRKO) mice at 6, 12, and 26 weeks of age. These mice possess a null mutation of the PR locus, which blocks the gene expression of A and B isoforms of PR. Body weight gain, uterine weight gain and tibia longitudinal bone growth was normal in PRKO mice. In contrast, total and cortical bone mass were increased in long bones of post-pubertal (12 and 26-week-old) PRKO mice, whereas cancellous bone mass was normal in the tibia but increased in the humerus. The striking 57% decrease in cancellous bone from the proximal tibia metaphysis which occurred between 6 and 26 weeks in WT mice was abolished in PRKO mice. The improved bone balance in aging PRKO mice was associated with elevated bone formation and a tendency toward reduced osteoclast perimeter. Taken together, these findings suggest that PR signaling in mice attenuates the accumulation of cortical bone mass during adolescence and is required for early age-related loss of cancellous bone.

  14. Methylphenidate restores novel object recognition in DARPP-32 knockout mice.

    PubMed

    Heyser, Charles J; McNaughton, Caitlyn H; Vishnevetsky, Donna; Fienberg, Allen A

    2013-09-15

    Previously, we have shown that Dopamine- and cAMP-regulated phosphoprotein of 32kDa (DARPP-32) knockout mice required significantly more trials to reach criterion than wild-type mice in an operant reversal-learning task. The present study was conducted to examine adult male and female DARPP-32 knockout mice and wild-type controls in a novel object recognition test. Wild-type and knockout mice exhibited comparable behavior during the initial exploration trials. As expected, wild-type mice exhibited preferential exploration of the novel object during the substitution test, demonstrating recognition memory. In contrast, knockout mice did not show preferential exploration of the novel object, instead exhibiting an increase in exploration of all objects during the test trial. Given that the removal of DARPP-32 is an intracellular manipulation, it seemed possible to pharmacologically restore some cellular activity and behavior by stimulating dopamine receptors. Therefore, a second experiment was conducted examining the effect of methylphenidate. The results show that methylphenidate increased horizontal activity in both wild-type and knockout mice, though this increase was blunted in knockout mice. Pretreatment with methylphenidate significantly impaired novel object recognition in wild-type mice. In contrast, pretreatment with methylphenidate restored the behavior of DARPP-32 knockout mice to that observed in wild-type mice given saline. These results provide additional evidence for a functional role of DARPP-32 in the mediation of processes underlying learning and memory. These results also indicate that the behavioral deficits in DARPP-32 knockout mice may be restored by the administration of methylphenidate.

  15. Proteolytic regulation of synaptic plasticity in the mouse primary visual cortex: analysis of matrix metalloproteinase 9 deficient mice

    PubMed Central

    Kelly, Emily A.; Russo, Amanda S.; Jackson, Cory D.; Lamantia, Cassandra E.; Majewska, Ania K.

    2015-01-01

    The extracellular matrix (ECM) is known to play important roles in regulating neuronal recovery from injury. The ECM can also impact physiological synaptic plasticity, although this process is less well understood. To understand the impact of the ECM on synaptic function and remodeling in vivo, we examined ECM composition and proteolysis in a well-established model of experience-dependent plasticity in the visual cortex. We describe a rapid change in ECM protein composition during Ocular Dominance Plasticity (ODP) in adolescent mice, and a loss of ECM remodeling in mice that lack the extracellular protease, matrix metalloproteinase-9 (MMP9). Loss of MMP9 also attenuated functional ODP following monocular deprivation (MD) and reduced excitatory synapse density and spine density in sensory cortex. While we observed no change in the morphology of existing dendritic spines, spine dynamics were altered, and MMP9 knock-out (KO) mice showed increased turnover of dendritic spines over a period of 2 days. We also analyzed the effects of MMP9 loss on microglia, as these cells are involved in extracellular remodeling and have been recently shown to be important for synaptic plasticity. MMP9 KO mice exhibited very limited changes in microglial morphology. Ultrastructural analysis, however, showed that the extracellular space surrounding microglia was increased, with concomitant increases in microglial inclusions, suggesting possible changes in microglial function in the absence of MMP9. Taken together, our results show that MMP9 contributes to ECM degradation, synaptic dynamics and sensory-evoked plasticity in the mouse visual cortex. PMID:26441540

  16. Supercomputing meets seismology in earthquake exhibit

    SciTech Connect

    Blackwell, Matt; Rodger, Arthur; Kennedy, Tom

    2013-10-03

    When the California Academy of Sciences created the "Earthquake: Evidence of a Restless Planet" exhibit, they called on Lawrence Livermore to help combine seismic research with the latest data-driven visualization techniques. The outcome is a series of striking visualizations of earthquakes, tsunamis and tectonic plate evolution. Seismic-wave research is a core competency at Livermore. While most often associated with earthquakes, the research has many other applications of national interest, such as nuclear explosion monitoring, explosion forensics, energy exploration, and seismic acoustics. For the Academy effort, Livermore researchers simulated the San Andreas and Hayward fault events at high resolutions. Such calculations require significant computational resources. To simulate the 1906 earthquake, for instance, visualizing 125 seconds of ground motion required over 1 billion grid points, 10,000 time steps, and 7.5 hours of processor time on 2,048 cores of Livermore's Sierra machine.

  17. New Monolayered Materials Exhibiting Unusual Electronic Properties

    NASA Astrophysics Data System (ADS)

    Lopez-Bezanilla, Alejandro; Martin, Ivar; Littlewood, Peter B.

    Computationally based approaches are allowing to progress in the discovery and design of nano-scaled materials. Here we propose a series of new mono-layered compounds with exotic properties. By means of density functional theory calculations we demonstrate that the pentagonal arrangement of SiC2 yields an inverted distribution of the p-bands which leads to an unusual electronic behaviour of the material under strain [J. Phys. Chem. C, 2015, 119 (33), pp 19469]. A different pentagonal arrangement of C atoms enables the formation of Dirac cones which, unlike graphene, exhibit a strain-mediated tunable band gap. This work is supported by DOE-BES under Contract No. DE-AC02-06CH11357.

  18. Supercomputing meets seismology in earthquake exhibit

    ScienceCinema

    Blackwell, Matt; Rodger, Arthur; Kennedy, Tom

    2016-07-12

    When the California Academy of Sciences created the "Earthquake: Evidence of a Restless Planet" exhibit, they called on Lawrence Livermore to help combine seismic research with the latest data-driven visualization techniques. The outcome is a series of striking visualizations of earthquakes, tsunamis and tectonic plate evolution. Seismic-wave research is a core competency at Livermore. While most often associated with earthquakes, the research has many other applications of national interest, such as nuclear explosion monitoring, explosion forensics, energy exploration, and seismic acoustics. For the Academy effort, Livermore researchers simulated the San Andreas and Hayward fault events at high resolutions. Such calculations require significant computational resources. To simulate the 1906 earthquake, for instance, visualizing 125 seconds of ground motion required over 1 billion grid points, 10,000 time steps, and 7.5 hours of processor time on 2,048 cores of Livermore's Sierra machine.

  19. Application of an imaging system to a museum exhibition for developing interactive exhibitions

    NASA Astrophysics Data System (ADS)

    Miyata, Kimiyoshi; Inoue, Yuka; Takiguchi, Takahiro; Tsumura, Norimichi; Nakaguchi, Toshiya; Miyake, Yoichi

    2009-10-01

    In the National Museum of Japanese History, 215,759 artifacts are stored and used for research and exhibitions. In museums, due to the limitation of space in the galleries, a guidance system is required to satisfy visitors' needs and to enhance their understanding of the artifacts. We introduce one exhibition using imaging technology to improve visitors' understanding of a kimono (traditional Japanese clothing) exhibition. In the imaging technology introduced, one data projector, one display with touch panel interface, and magnifiers were used as exhibition tools together with a real kimono. The validity of this exhibition method was confirmed by results from a visitors' interview survey. Second, to further develop the interactive guidance system, an augmented reality system that consisted of cooperation between the projector and a digital video camera was also examined. A white paper board in the observer's hand was used as a projection screen and also as an interface to control the images projected on the board. The basic performance of the proposed system was confirmed; however continuous development was necessary for applying the system to actual exhibitions.

  20. A Traveling Exhibit of Cassini Image Science

    NASA Astrophysics Data System (ADS)

    Burns, Joseph A.; Hedman, M. M.; Tiscareno, M. S.; Ebel, D.; Mac Low, M.; Lovett, L. E.; Burns, J. K.; Schaff, N.; Bilson, E. M.

    2007-10-01

    An exhibit of Cassini's images will open at NYC's American Museum of Natural History in March 2008 and then visit the Johnson Art Museum (Cornell) throughout fall 2008, including during next year's DPS. It is under consideration by several other venues in the States and overseas. The exhibit will feature 40-50 images, ranging from letter size to large posters, taken by remote-sensing instruments aboard Cassini and Huygens. Photos will be organized into a half-dozen thematic clusters (e.g., organized by celestial target or by physical process); a panel will introduce each grouping with individual images identified briefly. The Saturn system is a perfect vehicle to educate citizens about planetary science and origins. The images’ beauty should capture the public's attention, allowing us to then engage their curiosity about the relevant science. Among the Saturn system's broad suite of objects are Enceladus and Titan, two satellites of astrobiological interest; moreover, the rings display many processes active in other astrophysical disks. Several auxiliary ideas will be implemented. In Ithaca, we will project images at night against the museum's sand-colored exterior walls. A 10-12 minute musical composition has been commissioned from Roberto Sierra to open the show. We will encourage school children to participate in a human orrery circling the museum and will seek volunteers to participate in several Saturnalia. At Cornell we will involve the university and local communities, by taping their reactions to the images’ exquisite beauty as well as to their scientific content. Cassini will be the E/PO focus of next year's DPS meeting; those materials will be employed throughout the fall at New York schools and be available to travel with the show. We intend to work with NYC partners to offer teacher credits for associated weekend courses. We will produce classroom materials, including a DVD, for teacher use.

  1. Quiescent Fibroblasts Exhibit High Metabolic Activity

    PubMed Central

    Lemons, Johanna M. S.; Feng, Xiao-Jiang; Bennett, Bryson D.; Legesse-Miller, Aster; Johnson, Elizabeth L.; Raitman, Irene; Pollina, Elizabeth A.; Rabitz, Herschel A.; Rabinowitz, Joshua D.; Coller, Hilary A.

    2010-01-01

    Many cells in mammals exist in the state of quiescence, which is characterized by reversible exit from the cell cycle. Quiescent cells are widely reported to exhibit reduced size, nucleotide synthesis, and metabolic activity. Much lower glycolytic rates have been reported in quiescent compared with proliferating lymphocytes. In contrast, we show here that primary human fibroblasts continue to exhibit high metabolic rates when induced into quiescence via contact inhibition. By monitoring isotope labeling through metabolic pathways and quantitatively identifying fluxes from the data, we show that contact-inhibited fibroblasts utilize glucose in all branches of central carbon metabolism at rates similar to those of proliferating cells, with greater overflow flux from the pentose phosphate pathway back to glycolysis. Inhibition of the pentose phosphate pathway resulted in apoptosis preferentially in quiescent fibroblasts. By feeding the cells labeled glutamine, we also detected a “backwards” flux in the tricarboxylic acid cycle from α-ketoglutarate to citrate that was enhanced in contact-inhibited fibroblasts; this flux likely contributes to shuttling of NADPH from the mitochondrion to cytosol for redox defense or fatty acid synthesis. The high metabolic activity of the fibroblasts was directed in part toward breakdown and resynthesis of protein and lipid, and in part toward excretion of extracellular matrix proteins. Thus, reduced metabolic activity is not a hallmark of the quiescent state. Quiescent fibroblasts, relieved of the biosynthetic requirements associated with generating progeny, direct their metabolic activity to preservation of self integrity and alternative functions beneficial to the organism as a whole. PMID:21049082

  2. An Examination of Psychopathology and Daily Impairment in Adolescents with Social Anxiety Disorder

    PubMed Central

    Mesa, Franklin; Beidel, Deborah C.; Bunnell, Brian E.

    2014-01-01

    Although social anxiety disorder (SAD) is most often diagnosed during adolescence, few investigations have examined the clinical presentation and daily functional impairment of this disorder exclusively in adolescents. Prior studies have demonstrated that some clinical features of SAD in adolescents are unique relative to younger children with the condition. Furthermore, quality of sleep, a robust predictor of anxiety problems and daily stress, has not been examined in socially anxious adolescents. In this investigation, social behavior and sleep were closely examined in adolescents with SAD (n = 16) and normal control adolescents (NC; n = 14). Participants completed a self-report measure and an actigraphy assessment of sleep. Social functioning was assessed via a brief speech and a social interaction task, during which heart rate and skin conductance were measured. Additionally, participants completed a daily social activity journal for 1 week. No differences were observed in objective or subjective quality of sleep. Adolescents with SAD reported greater distress during the analogue social tasks relative to NC adolescents. During the speech task, adolescents with SAD exhibited a trend toward greater speech latency and spoke significantly less than NC adolescents. Additionally, SAD participants manifested greater skin conductance during the speech task. During the social interaction, adolescents with SAD required significantly more confederate prompts to stimulate interaction. Finally, adolescents with SAD reported more frequent anxiety-provoking situations in their daily lives, including answering questions in class, assertive communication, and interacting with a group. The findings suggest that, although adolescents with SAD may not exhibit daily impaired sleep, the group does experience specific behavioral and physiological difficulties in social contexts regularly. Social skills training may be a critical component in therapeutic approaches for this

  3. An examination of psychopathology and daily impairment in adolescents with social anxiety disorder.

    PubMed

    Mesa, Franklin; Beidel, Deborah C; Bunnell, Brian E

    2014-01-01

    Although social anxiety disorder (SAD) is most often diagnosed during adolescence, few investigations have examined the clinical presentation and daily functional impairment of this disorder exclusively in adolescents. Prior studies have demonstrated that some clinical features of SAD in adolescents are unique relative to younger children with the condition. Furthermore, quality of sleep, a robust predictor of anxiety problems and daily stress, has not been examined in socially anxious adolescents. In this investigation, social behavior and sleep were closely examined in adolescents with SAD (n = 16) and normal control adolescents (NC; n = 14). Participants completed a self-report measure and an actigraphy assessment of sleep. Social functioning was assessed via a brief speech and a social interaction task, during which heart rate and skin conductance were measured. Additionally, participants completed a daily social activity journal for 1 week. No differences were observed in objective or subjective quality of sleep. Adolescents with SAD reported greater distress during the analogue social tasks relative to NC adolescents. During the speech task, adolescents with SAD exhibited a trend toward greater speech latency and spoke significantly less than NC adolescents. Additionally, SAD participants manifested greater skin conductance during the speech task. During the social interaction, adolescents with SAD required significantly more confederate prompts to stimulate interaction. Finally, adolescents with SAD reported more frequent anxiety-provoking situations in their daily lives, including answering questions in class, assertive communication, and interacting with a group. The findings suggest that, although adolescents with SAD may not exhibit daily impaired sleep, the group does experience specific behavioral and physiological difficulties in social contexts regularly. Social skills training may be a critical component in therapeutic approaches for this group

  4. Contraception for adolescents.

    PubMed

    2014-10-01

    Contraception is a pillar in reducing adolescent pregnancy rates. The American Academy of Pediatrics recommends that pediatricians develop a working knowledge of contraception to help adolescents reduce risks of and negative health consequences related to unintended pregnancy. Over the past 10 years, a number of new contraceptive methods have become available to adolescents, newer guidance has been issued on existing contraceptive methods, and the evidence base for contraception for special populations (adolescents who have disabilities, are obese, are recipients of solid organ transplants, or are HIV infected) has expanded. The Academy has addressed contraception since 1980, and this policy statement updates the 2007 statement on contraception and adolescents. It provides the pediatrician with a description and rationale for best practices in counseling and prescribing contraception for adolescents. It is supported by an accompanying technical report.

  5. Pregnancy in adolescents.

    PubMed

    Black, Amanda Y; Fleming, Nathalie A; Rome, Ellen S

    2012-04-01

    Adolescent pregnancy remains a public health issue with significant medical, emotional, and societal consequences for the adolescent mother, her child, and her family. Teenage pregnancies are at higher risk of many adverse outcomes, including preterm delivery, low birth weight, and neonatal and infant mortality. Teen pregnancy and motherhood may have detrimental effects on the teen mother and her child; antenatal and postpartum care need to be adapted to meet the special needs of pregnant adolescents because standard obstetrical environments may not do so. This comprehensive review of adolescent pregnancy will highlight global statistics, factors contributing to adolescent pregnancy, social implications of adolescent pregnancy, obstetrical and neonatal outcomes, and the importance of multidisciplinary antenatal and postnatal care.

  6. Exposure of Neonatal Mice to Tobacco Smoke Disturbs Synaptic Proteins and Spatial Learning and Memory from Late Infancy to Early Adulthood.

    PubMed

    Torres, Larissa Helena; Garcia, Raphael C T; Blois, Anne M M; Dati, Lívia M M; Durão, Ana Carolina; Alves, Adilson Silva; Pacheco-Neto, Maurílio; Mauad, Thais; Britto, Luiz R G; Xavier, Gilberto Fernando; Camarini, Rosana; Marcourakis, Tania

    2015-01-01

    Exposure to environmental tobacco smoke (ETS) in the early postnatal period has been associated with several diseases; however, little is known about the brain effects of ETS exposure during this critical developmental period or the long-term consequences of this exposure. This study investigated the effects of the early postnatal ETS exposure on both reference and working memory, synaptic proteins and BDNF from late infancy to early adulthood (P3-P73). BALB/c mice were exposed to ETS generated from 3R4F reference research cigarettes (0.73 mg of nicotine/cigarette) from P3 to P14. Spatial reference and working memory were evaluated in the Morris water maze during infancy (P20-P29), adolescence (P37-P42) and adulthood (P67-P72). Synapsin, synaptophysin, PSD95 and brain-derived neurotrophic factor (BDNF) were assessed at P15, P35 and P65 by immunohistochemistry and immunoblotting. Mice that were exposed to ETS during the early postnatal period showed poorer performance in the spatial reference memory task. Specifically, the ETS-exposed mice exhibited a significantly reduced time and distance traveled in the target quadrant and in the platform location area than the controls at all ages evaluated. In the spatial working memory task, ETS disrupted the maintenance but not the acquisition of the critical spatial information in both infancy and adolescence. ETS also induced changes in synaptic components, including decreases in synapsin, synaptophysin, PSD95 and BDNF levels in the hippocampus. Exposure to ETS in the early postnatal period disrupts both spatial reference and working memory; these results may be related to changes in synaptogenesis in the hippocampus. Importantly, most of these effects were not reversed even after a long exposure-free period.

  7. Exposure of Neonatal Mice to Tobacco Smoke Disturbs Synaptic Proteins and Spatial Learning and Memory from Late Infancy to Early Adulthood

    PubMed Central

    Torres, Larissa Helena; Garcia, Raphael C. T.; Blois, Anne M. M.; Dati, Lívia M. M.; Durão, Ana Carolina; Alves, Adilson Silva; Pacheco-Neto, Maurílio; Mauad, Thais; Britto, Luiz R. G.; Xavier, Gilberto Fernando; Camarini, Rosana; Marcourakis, Tania

    2015-01-01

    Exposure to environmental tobacco smoke (ETS) in the early postnatal period has been associated with several diseases; however, little is known about the brain effects of ETS exposure during this critical developmental period or the long-term consequences of this exposure. This study investigated the effects of the early postnatal ETS exposure on both reference and working memory, synaptic proteins and BDNF from late infancy to early adulthood (P3-P73). BALB/c mice were exposed to ETS generated from 3R4F reference research cigarettes (0.73 mg of nicotine/cigarette) from P3 to P14. Spatial reference and working memory were evaluated in the Morris water maze during infancy (P20-P29), adolescence (P37-P42) and adulthood (P67-P72). Synapsin, synaptophysin, PSD95 and brain-derived neurotrophic factor (BDNF) were assessed at P15, P35 and P65 by immunohistochemistry and immunoblotting. Mice that were exposed to ETS during the early postnatal period showed poorer performance in the spatial reference memory task. Specifically, the ETS-exposed mice exhibited a significantly reduced time and distance traveled in the target quadrant and in the platform location area than the controls at all ages evaluated. In the spatial working memory task, ETS disrupted the maintenance but not the acquisition of the critical spatial information in both infancy and adolescence. ETS also induced changes in synaptic components, including decreases in synapsin, synaptophysin, PSD95 and BDNF levels in the hippocampus. Exposure to ETS in the early postnatal period disrupts both spatial reference and working memory; these results may be related to changes in synaptogenesis in the hippocampus. Importantly, most of these effects were not reversed even after a long exposure-free period. PMID:26305213

  8. Adolescent pregnancy options.

    PubMed

    Resnick, M D

    1992-09-01

    The range of pregnancy options available to adolescents each have significant ramifications for future educational and economic achievement. The changing societal context of adolescent pregnancy decision-making are described, and the characteristics of adolescents who choose to terminate their pregnancy, parent their child, or place for adoption are examined. The role of significant others in decision-making and the implications of mandatory parental involvement in pregnancy decision-making is discussed, as well as the roles of schools in promoting the well-being and potential of adolescents considering pregnancy decisions. PMID:1434557

  9. Providing Contraception to Adolescents.

    PubMed

    Raidoo, Shandhini; Kaneshiro, Bliss

    2015-12-01

    Adolescents have high rates of unintended pregnancy and face unique reproductive health challenges. Providing confidential contraceptive services to adolescents is important in reducing the rate of unintended pregnancy. Long-acting contraception such as the intrauterine device and contraceptive implant are recommended as first-line contraceptives for adolescents because they are highly effective with few side effects. The use of barrier methods to prevent sexually transmitted infections should be encouraged. Adolescents have limited knowledge of reproductive health and contraceptive options, and their sources of information are often unreliable. Access to contraception is available through a variety of resources that continue to expand.

  10. Adolescent pregnancy options.

    PubMed

    Resnick, M D

    1992-09-01

    The range of pregnancy options available to adolescents each have significant ramifications for future educational and economic achievement. The changing societal context of adolescent pregnancy decision-making are described, and the characteristics of adolescents who choose to terminate their pregnancy, parent their child, or place for adoption are examined. The role of significant others in decision-making and the implications of mandatory parental involvement in pregnancy decision-making is discussed, as well as the roles of schools in promoting the well-being and potential of adolescents considering pregnancy decisions.

  11. Hepatic immunophenotyping for streptozotocin-induced hyperglycemia in mice

    PubMed Central

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

    2016-01-01

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

  12. Exhibition of Stochastic Resonance in Vestibular Perception

    NASA Technical Reports Server (NTRS)

    Galvan-Garza, R. C.; Clark, T. K.; Merfeld, D. M.; Bloomberg, J. J.; Oman, C. M.; Mulavara, A. P.

    2016-01-01

    Astronauts experience sensorimotor changes during spaceflight, particularly during G-transitions. Post flight sensorimotor changes include spatial disorientation, along with postural and gait instability that may degrade operational capabilities of the astronauts and endanger the crew. A sensorimotor countermeasure that mitigates these effects would improve crewmember safety and decrease risk. The goal of this research is to investigate the potential use of stochastic vestibular stimulation (SVS) as a technology to improve sensorimotor function. We hypothesize that low levels of SVS will improve sensorimotor perception through the phenomenon of stochastic resonance (SR), when the response of a nonlinear system to a weak input signal is enhanced by the application of a particular nonzero level of noise. This study aims to advance the development of SVS as a potential countermeasure by 1) demonstrating the exhibition of stochastic resonance in vestibular perception, a vital component of sensorimotor function, 2) investigating the repeatability of SR exhibition, and 3) determining the relative contribution of the semicircular canals (SCC) and otolith (OTO) organs to vestibular perceptual SR. A constant current stimulator was used to deliver bilateral bipolar SVS via electrodes placed on each of the mastoid processes, as previously done. Vestibular perceptual motion recognition thresholds were measured using a 6-degree of freedom MOOG platform and a 150 trial 3-down/1-up staircase procedure. In the first test session, we measured vestibular perceptual thresholds in upright roll-tilt at 0.2 Hz (SCC+OTO) with SVS ranging from 0-700 µA. In a second test session a week later, we re-measured roll-tilt thresholds with 0, optimal (from test session 1), and 1500 µA SVS levels. A subset of these subjects, plus naive subjects, participated in two additional test sessions in which we measured thresholds in supine roll-rotation at 0.2 Hz (SCC) and upright y-translation at 1 Hz

  13. Classroom-Based Intervention for Student Exhibiting Depressive Reactions.

    ERIC Educational Resources Information Center

    Schloss, Patrick J.

    1983-01-01

    The article reviews the literature on three major social learning constructs advanced to explain the etiology of reactive depression in children and adolescents: learned helplessness, social skill deficits, and coercive reinforcement patterns. Implications for classroom management are noted. (CL)

  14. Hepatic Src Homology Phosphatase 2 Regulates Energy Balance in Mice

    PubMed Central

    Nagata, Naoto; Matsuo, Kosuke; Bettaieb, Ahmed; Bakke, Jesse; Matsuo, Izumi; Graham, James; Xi, Yannan; Liu, Siming; Tomilov, Alexey; Tomilova, Natalia; Gray, Susan; Jung, Dae Young; Ramsey, Jon J.; Kim, Jason K.; Cortopassi, Gino; Havel, Peter J.

    2012-01-01

    The Src homology 2 domain-containing protein-tyrosine phosphatase Src homology phosphatase 2 (Shp2) is a negative regulator of hepatic insulin action in mice fed regular chow. To investigate the role of hepatic Shp2 in lipid metabolism and energy balance, we determined the metabolic effects of its deletion in mice challenged with a high-fat diet (HFD). We analyzed body mass, lipid metabolism, insulin sensitivity, and glucose tolerance in liver-specific Shp2-deficient mice (referred to herein as LSHKO) and control mice fed HFD. Hepatic Shp2 protein expression is regulated by nutritional status, increasing in mice fed HFD and decreasing during fasting. LSHKO mice gained less weight and exhibited increased energy expenditure compared with control mice. In addition, hepatic Shp2 deficiency led to decreased liver steatosis, enhanced insulin-induced suppression of hepatic glucose production, and impeded the development of insulin resistance after high-fat feeding. At the molecular level, LSHKO exhibited decreased hepatic endoplasmic reticulum stress and inflammation compared with control mice. In addition, tyrosine and serine phosphorylation of total and mitochondrial signal transducer and activator of transcription 3 were enhanced in LSHKO compared with control mice. In line with this observation and the increased energy expenditure of LSHKO, oxygen consumption rate was higher in liver mitochondria of LSHKO compared with controls. Collectively, these studies identify hepatic Shp2 as a novel regulator of systemic energy balance under conditions of high-fat feeding. PMID:22619361

  15. Behavioral and physiologic responses to caloric restriction in mice.

    PubMed

    Overton, J M; Williams, T D

    2004-07-01

    The purpose of the review is to highlight the influences of ambient temperature (T(a)) and caloric restriction (CR) on metabolism, cardiovascular function and behavior in mice. Standard vivarium ambient temperatures (T(a)?23 degrees C) are a mild cold stress for mice requiring elevated metabolic rate and food intake. Increasing T(a) into the zone of thermoneutrality (TMN?29-33 degrees C) markedly reduces food intake, metabolic rate, heart rate (HR) and blood pressure in mice. Mice are members of a diverse, yet unique group of homeothermic animals that respond to thermal and energetic challenges by allowing body temperature (T(b)) to fall to less than 31 degrees C, a condition known as torpor. In mice housed at standard T(a), torpor is induced by a single night of fasting or a few days of CR. The mechanisms responsible for initiating torpor are related to reduced caloric availability, but do not require leptin. Mice housed at TMN and subjected to CR exhibit physiologic reductions in metabolic rate and HR, but do not appear to enter torpor. Finally, mice exhibit differential locomotor activity responses during CR that depends on T(a). At standard T(a), mice display increased light-phase home-cage activity with CR. This response is virtually eliminated when CR is performed at TMN. We suggest that researchers using mice to investigate energy homeostasis and cardiovascular physiology carefully consider the influence of T(a) on physiology and behavior.

  16. Agitated Honeybees Exhibit Pessimistic Cognitive Biases

    PubMed Central

    Bateson, Melissa; Desire, Suzanne; Gartside, Sarah E.; Wright, Geraldine A.

    2011-01-01

    Summary Whether animals experience human-like emotions is controversial and of immense societal concern [1–3]. Because animals cannot provide subjective reports of how they feel, emotional state can only be inferred using physiological, cognitive, and behavioral measures [4–8]. In humans, negative feelings are reliably correlated with pessimistic cognitive biases, defined as the increased expectation of bad outcomes [9–11]. Recently, mammals [12–16] and birds [17–20] with poor welfare have also been found to display pessimistic-like decision making, but cognitive biases have not thus far been explored in invertebrates. Here, we ask whether honeybees display a pessimistic cognitive bias when they are subjected to an anxiety-like state induced by vigorous shaking designed to simulate a predatory attack. We show for the first time that agitated bees are more likely to classify ambiguous stimuli as predicting punishment. Shaken bees also have lower levels of hemolymph dopamine, octopamine, and serotonin. In demonstrating state-dependent modulation of categorization in bees, and thereby a cognitive component of emotion, we show that the bees' response to a negatively valenced event has more in common with that of vertebrates than previously thought. This finding reinforces the use of cognitive bias as a measure of negative emotional states across species and suggests that honeybees could be regarded as exhibiting emotions. Video Abstract PMID:21636277

  17. Ferromagnetism exhibited by nanoparticles of noble metals.

    PubMed

    Maitra, Urmimala; Das, Barun; Kumar, Nitesh; Sundaresan, Athinarayanan; Rao, C N R

    2011-08-22

    Gold nanoparticles with average diameters in the range 2.5-15 nm, prepared at the organic/aqueous interface by using tetrakis(hydroxymethyl)phosphonium chloride (THPC) as reducing agent, exhibit ferromagnetism whereby the saturation magnetization M(S) increases with decreasing diameter and varies linearly with the fraction of surface atoms. The value of M(S) is higher when the particles are present as a film instead of as a sol. Capping with strongly interacting ligands such as alkane thiols results in a higher M(S) value, which varies with the strength of the metal-sulfur bond. Ferromagnetism is also found in Pt and Ag nanoparticles prepared as sols, and the M(S) values vary as Pt>Au>Ag. A careful study of the temperature variation of the magnetization of Au nanoparticles, along with certain other observations, suggests that small bare nanoparticles of noble metals could indeed possess ferromagnetism, albeit weak, which is accentuated in the presence of capping agents, specially alkane thiols which form strong metal-sulfur bonds.

  18. Stress Symptoms Among Adolescent: A Study from Islamic Perspective.

    PubMed

    Sham, Fariza Md

    2015-08-01

    Rapid social changes in current times which can be quite abrupt present a challenge to adolescent life. Adolescents who are unable to adapt themselves experience stress which may affect their health. Psychological issues of adolescents require attention because the long-term consequence is worse than the short-term effects, namely, there will be a group of people within society who live under stress. Stressed people show symptoms such as being aggressive, prone to rebel, uncontrollable anger, depression, mental disorders and health problems. Early recognition of adolescent stress symptoms is vital. Pursuant to this, a study is conducted among adolescents in Kajang, Selangor, Malaysia for the purpose of determining whether they experience stress or otherwise, based on stress symptoms in terms of psychology, physiology and social behaviour. An analysis is conducted on 403 respondents who comprise of male and female adolescents aged 16-17 years. The required data are gathered through questionnaire and structured interview. Analysis is based on descriptive statistical method and is explained in a table in terms of frequency, percentage and mode. Research results show that adolescents do experience stress and that the majority of them exhibit psychological stress symptoms.

  19. Conflict Resolution in Parent-Adolescent Relationships and Adolescent Delinquency

    ERIC Educational Resources Information Center

    Van Doorn, Muriel D.; Branje, Susan J. T.; Meeus, Wim H. J.

    2008-01-01

    This study examines the relation between conflict resolution styles in parent-adolescent relationships and adolescent delinquency. Questionnaires about conflict resolution styles were completed by 284 early adolescents (mean age 13.3) and their parents. Adolescents also completed a questionnaire on delinquency. Hierarchical regression analyses…

  20. Adolescent Literature, Adolescent Reading and the English Class.

    ERIC Educational Resources Information Center

    Donelson, Ken, Ed.

    1972-01-01

    This issue of the Arizona English Bulletin contains articles discussing literature that adolescents read and literature that they might be encouraged to read. Thus there are discussions both of literature specifically written for adolescents and the literature adolescents choose to read. The term adolescent is understood to include young people in…

  1. Osteonecrosis of the Jaw Developed in Mice

    PubMed Central

    Park, Sil; Kanayama, Keiichi; Kaur, Kawaljit; Tseng, Han-Ching Helen; Banankhah, Sina; Quje, Davood Talebi; Sayre, James W.; Jewett, Anahid; Nishimura, Ichiro

    2015-01-01

    Osteonecrosis of the jaw (ONJ), an uncommon co-morbidity in patients treated with bisphosphonates (BP), occurs in the segment of jawbone interfacing oral mucosa. This study aimed to investigate a role of oral mucosal barrier γδ T cells in the pathogenesis of ONJ. Female C57Bl/6J (B6) mice received a bolus zoledronate intravenous injection (ZOL, 540 μg/kg), and their maxillary left first molars were extracted 1 week later. ZOL-treated mice (WT ZOL) delayed oral wound healing with patent open wounds 4 weeks after tooth extraction with characteristic oral epithelial hyperplasia. γδ T cells appeared within the tooth extraction site and hyperplastic epithelium in WT ZOL mice. In ZOL-treated γδ T cell null (Tcrd−/− ZOL) mice, the tooth extraction open wound progressively closed; however, histological ONJ-like lesions were identified in 75 and 60% of WT ZOL and Tcrd−/− ZOL mice, respectively. Although the bone exposure phenotype of ONJ was predominantly observed in WT ZOL mice, Tcrd−/− ZOL mice developed the pustule/fistula disease phenotype. We further addressed the role of γδ T cells from human peripheral blood (h-γδ T cells). When co-cultured with ZOL-pretreated human osteoclasts in vitro, h-γδ T cells exhibited rapid expansion and robust IFN-γ secretion. When h-γδ T cells were injected into ZOL-treated immunodeficient (Rag2−/− ZOL) mice, the oral epithelial hyperplasia developed. However, Rag2−/− ZOL mice did not develop osteonecrosis. The results indicate that γδ T cells are unlikely to influence the core osteonecrosis mechanism; however, they may serve as a critical modifier contributing to the different oral mucosal disease variations of ONJ. PMID:26013832

  2. Understanding overweight adolescents' beliefs using the theory of planned behaviour.

    PubMed

    Rhoades, Debra R; Kridli, Suha Al-Oballi; Penprase, Barbara

    2011-12-01

    This qualitative inquiry examined adolescents' experiences surrounding their beliefs towards being overweight. The purpose of this qualitative study was to understand behavioural, normative and control beliefs of overweight adolescents regarding losing weight, exercising and eating healthy. Purposive sampling was used to obtain 10 overweight adolescents between the ages of 13 and 19. The theory of planned behaviour was used as a theoretical framework for this study. An interview guide based on the Theory of Planned was used to conduct individual semistructured interviews. Content analysis showed that overweight adolescents exhibited positive attitudes in dealing with their weight status and valued their family's support and guidance in helping control their weight. Although friends were important to facilitate regular exercise, families, particularly mothers, were crucial in addressing healthy eating habits. Understanding the subtleties and complexities of living with childhood overweight might assist health professionals in creating more effective and developmentally sensitive interventions.

  3. Death anxiety in adolescents: the contributions of bereavement and religiosity.

    PubMed

    Ens, Carla; Bond, John B

    2007-01-01

    Possible relationships between bereavement and religiosity to death anxiety levels of adolescents were investigated. Scales measuring religiosity, bereavement, and death anxiety were incorporated into one questionnaire. Two hundred and twenty-six adolescents between the ages of 11 and 18 participated in the study based in urban and rural private schools within Manitoba. Females exhibited significantly higher death anxiety levels than did males; differences between the death anxiety levels of adolescents having a no-previous-death-experience death and those who had experienced a familial death were not significant; while religiosity levels were significantly higher for students attending religion-based schools, the relationships between measurements of religiosity and death anxiety were weak. Grief due to bereavement was the major factor in determining death anxiety for the adolescent.

  4. Understanding overweight adolescents' beliefs using the theory of planned behaviour.

    PubMed

    Rhoades, Debra R; Kridli, Suha Al-Oballi; Penprase, Barbara

    2011-12-01

    This qualitative inquiry examined adolescents' experiences surrounding their beliefs towards being overweight. The purpose of this qualitative study was to understand behavioural, normative and control beliefs of overweight adolescents regarding losing weight, exercising and eating healthy. Purposive sampling was used to obtain 10 overweight adolescents between the ages of 13 and 19. The theory of planned behaviour was used as a theoretical framework for this study. An interview guide based on the Theory of Planned was used to conduct individual semistructured interviews. Content analysis showed that overweight adolescents exhibited positive attitudes in dealing with their weight status and valued their family's support and guidance in helping control their weight. Although friends were important to facilitate regular exercise, families, particularly mothers, were crucial in addressing healthy eating habits. Understanding the subtleties and complexities of living with childhood overweight might assist health professionals in creating more effective and developmentally sensitive interventions. PMID:22103822

  5. The MICE luminosity monitor

    NASA Astrophysics Data System (ADS)

    Dobbs, A.; Forrest, D.; Soler, F. J. P.

    2013-02-01

    The MICE experiment will provide the first measurement of ionisation cooling, a technique suitable for reducing the transverse emittance of a tertiary muon beam in a future neutrino factory accelerator facility. MICE is presently in the final stages of commissioning its beam line. The MICE luminosity monitor has proved an invaluable tool throughout this process, providing independent measurements of particle rate from the MICE target, normalisation for beam line detectors and verification of simulation codes.

  6. [Contraception in adolescents].

    PubMed

    1992-12-01

    The proportion of women aged 15-19 in Colombia who are mothers declined from 14% in 1985 to 10% in 1990, but the actual number of cases increased due to population growth. Some 1,780,000 adolescents who have had children or are pregnant require family planning services. An additional, unknown number of adolescent pregnancies are terminated by abortion. It is estimated that 95% of adolescent pregnancies diagnosed or followed by PROFAMILIA's center for young people were unwanted. Reasons for making family planning services available to adolescents include the ever young age at initiation of sexual activity, the very low rates of contraceptive usage among sexually active adolescents, the lack of information of adolescents concerning reproduction and contraception, and their fear and guilt surrounding their sexual activity and contraceptive usage. Obstetrical services appear reluctant to furnish adolescent mothers with information on contraception, and the pharmacists and their employees who provide such information may not be aware of contraindications for this age group or whether adolescents are adequately instructed in use of the method. The rising age at marriage increases the span of time that adolescents are at risk of unwanted pregnancy. Adolescents who are well informed about sexuality and contraception and trained in decision making, self-esteem, and responsible parenthood are likely to postpone sexual activity. Information on contraception and family planning services needs to be made available to adolescents in a way that will actually motivate use. Information on sex and contraception should be made available at puberty and should include the form of use, contraindications, and advantages and disadvantages of all methods appropriate to adolescents. Orientation and assistance in selecting the best method should be individually tailored and should be provided in schools or other places accessible to young people, in a language they can understand. Rhythm and

  7. Identifying Adolescent Sleep Problems

    PubMed Central

    Short, Michelle A.; Gradisar, Michael; Gill, Jason; Camfferman, Danny

    2013-01-01

    Objectives To examine the efficacy of self-report and parental report of adolescent sleep problems and compare these findings to the incidence of adolescents who fulfill clinical criteria for a sleep problem. Sleep and daytime functioning factors that predict adolescents’ self-identification of a sleep problem will also be examined. Method 308 adolescents (aged 13–17 years) from eight socioeconomically diverse South Australian high schools participated in this study. Participants completed a survey battery during class time, followed by a 7-day Sleep Diary and the Flinders Fatigue Scale completed on the final day of the study. Parents completed a Sleep, Medical, Education and Family History Survey. Results The percentage of adolescents fulfilling one or more of the criteria for a sleep problem was inordinately high at 66%. Adolescent self-reporting a sleep problem was significantly lower than the adolescents who had one or more of the clinical criteria for a sleep problem (23.1% vs. 66.6%; χ2 = 17.46, p<.001). Parental report of their adolescent having a sleep problem was significantly lower than adolescent self-report (14.3% vs. 21.1%, p<.001). Adolescents who reported unrefreshing sleep were 4.81 times more likely to report a sleep problem. For every hour that bedtime was delayed, the odds of self-reporting a sleep problem increased by 1.91 times, while each additional 10 minutes taken to fall asleep increased the odds 1.40 times. Conclusion While many adolescents were found to have sleep patterns indicative of a sleep problem, only a third of this number self-identify having a sleep problem, while only a sixth of this number are indicated by parental report. This study highlights important features to target in future sleep education and intervention strategies for both adolescents and parents. PMID:24086501

  8. Marine bacteria exhibit a bipolar distribution.

    PubMed

    Sul, Woo Jun; Oliver, Thomas A; Ducklow, Hugh W; Amaral-Zettler, Linda A; Sogin, Mitchell L

    2013-02-01

    The microbial cosmopolitan dispersion hypothesis often invoked to explain distribution patterns driven by high connectivity of oceanographic water masses and widespread dispersal ability has never been rigorously tested. By using a global marine bacterial dataset and iterative matrix randomization simulation, we show that marine bacteria exhibit a significantly greater dispersal limitation than predicted by our null model using the "everything is everywhere" tenet with no dispersal limitation scenario. Specifically, marine bacteria displayed bipolar distributions (i.e., species occurring exclusively at both poles and nowhere else) significantly less often than in the null model. Furthermore, we observed fewer taxa present in both hemispheres but more taxa present only in a single hemisphere than expected under the null model. Each of these trends diverged further from the null expectation as the compared habitats became more geographically distant but more environmentally similar. Our meta-analysis supported a latitudinal gradient in bacterial diversity with higher richness at lower latitudes, but decreased richness toward the poles. Bacteria in the tropics also demonstrated narrower latitudinal ranges at lower latitudes and relatively larger ranges in higher latitudes, conforming to the controversial macroecological pattern of the "Rapoport rule." Collectively, our findings suggest that bacteria follow biogeographic patterns more typical of macroscopic organisms, and that dispersal limitation, not just environmental selection, likely plays an important role. Distributions of microbes that deliver critical ecosystem services, particularly those in polar regions, may be vulnerable to the same impacts that environmental stressors, climate warming, and degradation in habitat quality are having on biodiversity in animal and plant species.

  9. Waves in geomaterials exhibiting negative stiffness behaviour

    NASA Astrophysics Data System (ADS)

    Esin, Maxim; Dyskin, Arcady; Pasternak, Elena

    2016-04-01

    Negative stiffness denotes the type of material behaviour when the force applied to the body decreases the body's deformation increases. Some geomaterials, for instance, rocks, demonstrate behaviour of this type at certain loads: during the compression tests the loading curves exhibit descending branch (post-peak softening). One of the possible mechanisms of the negative stiffness appearance in geomaterials is rotation of non-spherical grains. It is important to emphasize that in this case the descending branch may be reversible given that the testing machine is stiff enough (in general case it means an importance of boundary conditions). Existence of geomaterials with a negative modulus associated with rotations may have significant importance. In particular, important is understanding of the wave propagation in such materials. We study the stability of geomaterials with negative stiffness inclusions and wave propagation in it using two approaches: Cosserat continuum and discrete mass-spring models. In both cases we consider the rotational degrees of freedom in addition to the conventional translational ones. We show that despite non positiveness of the energy the materials with negative stiffness elements can be stable if certain conditions are met. In the case of Cosserat continuum the Cosserat shear modulus (the modulus relating the non-symmetrical part of shear stress and internal rotations) is allowed to assume negative values as long as its value does not exceed the value of the standard (positive) shear modulus. In the case of discrete mass-spring systems (with translational and rotational springs) the concentration of negative stiffness springs and the absolute values of negative spring stiffness are limited. The critical concentration when the system loses stability and the amplitude of the oscillations tends to infinity is equal to 1/2 and 3/5 for two- and three-dimensional cases respectively.

  10. Rats exhibit reference-dependent choice behavior.

    PubMed

    Bhatti, Mehwish; Jang, Hyeran; Kralik, Jerald D; Jeong, Jaeseung

    2014-07-01

    Human preferences depend on whether a chosen outcome appears to be a loss or a gain compared with what had been expected, i.e., in comparison to a reference point. Because reference dependence has such a strong influence on human decision-making, it is important to uncover its origins, which will in turn help delineate the underlying mechanisms. It remains unknown whether rats use reference points in decision-making, and yet, the study of rats could help address the question of whether reference dependence is evolutionarily conserved among mammals and could provide a nonhuman animal model to investigate the neural mechanisms underlying this important cognitive process. The aim of the current study was to determine whether rats show reference-dependent choice behavior. We developed a novel paradigm by modifying the "T" maze by installing "pockets" to the left and right of the "T" stem that held reward pellets so rats would potentially develop reference values for each option prior to choice. We found that the rats were indeed sensitive to the way alternatives were presented. That is, they exhibited reference-dependent choice behavior by avoiding the choice option framed as a loss (e.g., having four reward pellets in the pocket, but receiving only one), at least under conditions with certain outcomes and clear differences between the reference and outcome quantities. Despite the small number of rats in this study, this species-level capacity suggests that reference dependence in general and loss aversion in particular may be conserved traits that evolved at or before the emergence of mammals.

  11. Chronic Stress During Adolescence Impairs and Improves Learning and Memory in Adulthood.

    PubMed

    Chaby, Lauren E; Cavigelli, Sonia A; Hirrlinger, Amy M; Lim, James; Warg, Kendall M; Braithwaite, Victoria A

    2015-01-01

    HIGHLIGHTS This study tested the effects of adolescent-stress on adult learning and memory.Adolescent-stressed rats had enhanced reversal learning compared to unstressed rats.Adolescent-stress exposure made working memory more vulnerable to disturbance.Adolescent-stress did not affect adult associative learning or reference memory. Exposure to acute stress can cause a myriad of cognitive impairments, but whether negative experiences continue to hinder individual as they age is not as well understood. We determined how chronic unpredictable stress during adolescence affects multiple learning and memory processes in adulthood. Using male Sprague Dawley rats, we measured learning (both associative and reversal) and memory (both reference and working) starting 110 days after completion of an adolescent-stress treatment. We found that adolescent-stress affected adult cognitive abilities in a context-dependent way. Compared to rats reared without stress, adolescent-stressed rats exhibited enhanced reversal learning, an indicator of behavioral flexibility, but showed no change in associative learning and reference memory abilities. Working memory, which in humans is thought to underpin reasoning, mathematical skills, and reading comprehension, may be enhanced by exposure to adolescent-stress. However, when adolescent-stressed animals were tested after a novel disturbance, they exhibited a 5-fold decrease in working memory performance while unstressed rats continued to exhibit a linear learning curve. These results emphasize the capacity for stress during adolescence to transform the cognitive abilities of adult animals, even after stress exposure has ceased and animals have resided in safe environments for the majority of their lifespans.

  12. Chronic Stress During Adolescence Impairs and Improves Learning and Memory in Adulthood

    PubMed Central

    Chaby, Lauren E.; Cavigelli, Sonia A.; Hirrlinger, Amy M.; Lim, James; Warg, Kendall M.; Braithwaite, Victoria A.

    2015-01-01

    HIGHLIGHTS This study tested the effects of adolescent-stress on adult learning and memory.Adolescent-stressed rats had enhanced reversal learning compared to unstressed rats.Adolescent-stress exposure made working memory more vulnerable to disturbance.Adolescent-stress did not affect adult associative learning or reference memory. Exposure to acute stress can cause a myriad of cognitive impairments, but whether negative experiences continue to hinder individual as they age is not as well understood. We determined how chronic unpredictable stress during adolescence affects multiple learning and memory processes in adulthood. Using male Sprague Dawley rats, we measured learning (both associative and reversal) and memory (both reference and working) starting 110 days after completion of an adolescent-stress treatment. We found that adolescent-stress affected adult cognitive abilities in a context-dependent way. Compared to rats reared without stress, adolescent-stressed rats exhibited enhanced reversal learning, an indicator of behavioral flexibility, but showed no change in associative learning and reference memory abilities. Working memory, which in humans is thought to underpin reasoning, mathematical skills, and reading comprehension, may be enhanced by exposure to adolescent-stress. However, when adolescent-stressed animals were tested after a novel disturbance, they exhibited a 5-fold decrease in working memory performance while unstressed rats continued to exhibit a linear learning curve. These results emphasize the capacity for stress during adolescence to transform the cognitive abilities of adult animals, even after stress exposure has ceased and animals have resided in safe environments for the majority of their lifespans. PMID:26696849

  13. Bex1 knock out mice show altered skeletal muscle regeneration

    SciTech Connect

    Koo, Jae Hyung Smiley, Mark A.; Lovering, Richard M.; Margolis, Frank L.

    2007-11-16

    Bex1 and Calmodulin (CaM) are upregulated during skeletal muscle regeneration. We confirm this finding and demonstrate the novel finding that they interact in a calcium-dependent manner. To study the role of Bex1 and its interaction with CaM in skeletal muscle regeneration, we generated Bex1 knock out (Bex1-KO) mice. These mice appeared to develop normally and are fertile, but displayed a functional deficit in exercise performance compared to wild type (WT) mice. After intramuscular injection of cardiotoxin, which causes extensive and reproducible myotrauma followed by recovery, regenerating muscles of Bex1-KO mice exhibited elevated and prolonged cell proliferation, as well as delayed cell differentiation, compared to WT mice. Thus, our results provide the first evidence that Bex1-KO mice show altered muscle regeneration, and allow us to propose that the interaction of Bex1 with Ca{sup 2+}/CaM may be involved in skeletal muscle regeneration.

  14. The Majority of Resorptions in Old Mice Are Euploid

    PubMed Central

    Tao, Yong; Liu, X. Johné

    2015-01-01

    Chromosomal abnormality is a leading cause of aging-related infertility, spontaneous abortion and congenital birth defects in humans. Karyotype analyses of spontaneously aborted human fetuses reveal high proportions (~50%) being chromosomal abnormal with the majority being trisomies of various chromosomes. As a model organism, mice are widely used for studies of reproduction and reproductive aging. Like older women, older mice exhibit high incidences of early embryo death. However, it is not known if aneuploidy is prevalent amongst resorptions in older mice. We have karyotyped 65 retarded/resorbed fetuses in 10-month-old C57BL/6 mice, and found that 55 (84.6%±8.8%, with 95% confidence) were euploid. Similarly, of 40 such fetuses from 17 month-old C57BL/6 mice, we found 38 (95±7%, with 95% confidence 95%) being euploid. Therefore, aneuploidy is not a leading cause of embryo death in older mice. PMID:26636341

  15. Knockout of Foxp2 disrupts vocal development in mice.

    PubMed

    Castellucci, Gregg A; McGinley, Matthew J; McCormick, David A

    2016-03-16

    The FOXP2 gene is important for the development of proper speech motor control in humans. However, the role of the gene in general vocal behavior in other mammals, including mice, is unclear. Here, we track the vocal development of Foxp2 heterozygous knockout (Foxp2+/-) mice and their wildtype (WT) littermates from juvenile to adult ages, and observe severe abnormalities in the courtship song of Foxp2+/- mice. In comparison to their WT littermates, Foxp2+/- mice vocalized less, produced shorter syllable sequences, and possessed an abnormal syllable inventory. In addition, Foxp2+/- song also exhibited irregular rhythmic structure, and its development did not follow the consistent trajectories observed in WT vocalizations. These results demonstrate that the Foxp2 gene is critical for normal vocal behavior in juvenile and adult mice, and that Foxp2 mutant mice may provide a tractable model system for the study of the gene's role in general vocal motor control.

  16. 32 CFR 705.26 - Exhibit availability report.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... of all exhibits is required. (b) A current inventory of exhibits headquartered in Washington, DC, and...: Officer-in-Charge, Navy Recruiting Exhibit Center, Washington Navy Yard, Washington, DC 20374....

  17. 32 CFR 705.26 - Exhibit availability report.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... of all exhibits is required. (b) A current inventory of exhibits headquartered in Washington, DC, and...: Officer-in-Charge, Navy Recruiting Exhibit Center, Washington Navy Yard, Washington, DC 20374....

  18. 32 CFR 705.26 - Exhibit availability report.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... of all exhibits is required. (b) A current inventory of exhibits headquartered in Washington, DC, and...: Officer-in-Charge, Navy Recruiting Exhibit Center, Washington Navy Yard, Washington, DC 20374....

  19. Sexual Health for America's Adolescents.

    ERIC Educational Resources Information Center

    Haffner, Debra W.

    1996-01-01

    The National Commission on Adolescent Sexual Health developed a professional consensus statement about adolescent sexual health. Its report for policymakers recommends that adults face the facts about adolescent sexuality and that public policies on adolescent sexual health be based on appropriate knowledge, accurate data, current theory, ongoing…

  20. Adolescent exposure to cocaine, amphetamine, and methylphenidate cross-sensitizes adults to methamphetamine with drug- and sex-specific effects.

    PubMed

    Shanks, Ryan A; Ross, Jordan M; Doyle, Hillary H; Helton, Amanda K; Picou, Brittany N; Schulz, Jordyn; Tavares, Chris; Bryant, Sarah; Dawson, Bryan L; Lloyd, Steven A

    2015-03-15

    The increasing availability, over-prescription, and misuse and abuse of ADHD psychostimulant medications in adolescent populations necessitates studies investigating the long-term effects of these drugs persisting into adulthood. Male and female C57Bl/6J mice were exposed to amphetamine (AMPH) (1.0 and 10 mg/kg), methylphenidate (MPD) (1.0 and 10 mg/kg), or cocaine (COC) (5.0 mg/kg) from postnatal day 22 to 31, which represents an early adolescent period. After an extended period of drug abstinence, adult mice were challenged with a subacute methamphetamine (METH) dose (0.5 mg/kg), to test the long-term effects of adolescent drug exposures on behavioral cross-sensitization using an open field chamber. There were no sex- or dose-specific effects on motor activity in adolescent, saline-treated controls. However, AMPH, MPD, and COC adolescent exposures induced cross-sensitization to a subacute METH dose in adulthood, which is a hallmark of addiction and a marker of long-lasting plastic changes in the brain. Of additional clinical importance, AMPH-exposed male mice demonstrated increased cross-sensitization to METH in contrast to the female-specific response observed in MPD-treated animals. There were no sex-specific effects after adolescent COC exposures. This study demonstrates differential drug, dose, and sex-specific alterations induced by early adolescent psychostimulant exposure, which leads to behavioral alterations that persist into adulthood.

  1. Cigars, Cigarettes, and Adolescents

    ERIC Educational Resources Information Center

    Brooks, Ashley; Larkin, Elizabeth M. Gaier; Kishore, Sonal; Frank, Scott

    2008-01-01

    Objective: To examine public health implications of adolescent use of cigars only, cigarettes only, and both cigarettes and cigars. Methods: A cross-sectional health risk survey was administered to a random sample of 4486 high school students in a Midwestern county. Results: More adolescents reported using both cigarettes and cigars (10.6%) than…

  2. Adolescent Literacy. Focus On

    ERIC Educational Resources Information Center

    Molineaux, Rebecca

    2009-01-01

    Evidence suggests that there is a crisis in adolescent literacy. Part of the problem is that students often receive little literacy instruction after elementary school. This "Focus On" examines the literacy instruction that adolescents need to be successful as they move on to more challenging texts in middle and high school. In addition, this…

  3. Diagnosing ADHD in Adolescence

    ERIC Educational Resources Information Center

    Sibley, Margaret H.; Pelham, William E., Jr.; Molina, Brooke S. G.; Gnagy, Elizabeth M.; Waschbusch, Daniel A.; Garefino, Allison C.; Kuriyan, Aparajita B.; Babinski, Dara E.; Karch, Kathryn M.

    2012-01-01

    Objective: This study examines adolescent-specific practical problems associated with current practice parameters for diagnosing attention-deficit/hyperactivity disorder (ADHD) to inform recommendations for the diagnosis of ADHD in adolescents. Specifically, issues surrounding the use of self- versus informant ratings, diagnostic threshold, and…

  4. The Adolescent Brain

    ERIC Educational Resources Information Center

    Casey, B. J.; Getz, Sarah; Galvan, Adriana

    2008-01-01

    Adolescence is a developmental period characterized by suboptimal decisions and actions that give rise to an increased incidence of unintentional injuries and violence, alcohol and drug abuse, unintended pregnancy and sexually transmitted diseases. Traditional neurobiological and cognitive explanations for adolescent behavior have failed to…

  5. Adolescence Education Newsletter, 1998.

    ERIC Educational Resources Information Center

    Villanueva, Carmelita L., Ed.; Padilla, Teresita M., Ed.

    1998-01-01

    This document comprises two issues of a new UNESCO newsletter addressing topics related to adolescent well-being in the Asia-Pacific region, particularly reproductive and sexual health. Both issues contain news from the region on various initiatives related to adolescent health and education, as well as Web links and publications on the subject.…

  6. Adolescence Education Newsletter, 2002.

    ERIC Educational Resources Information Center

    Villanueva, Carmelita L., Ed.; Espada-Carlos, Lichelle Dara, Ed.

    2002-01-01

    This document consists of the two 2002 issues of a UNESCO newsletter addressing topics related to adolescent well-being in the Asia-Pacific region, particularly reproductive and sexual health. Each issue includes news from the region on various initiatives related to adolescent health and education, as well as Web links and publications on the…

  7. Classifying Adolescent Perfectionists

    ERIC Educational Resources Information Center

    Rice, Kenneth G.; Ashby, Jeffrey S.; Gilman, Rich

    2011-01-01

    A large school-based sample of 9th-grade adolescents (N = 875) completed the Almost Perfect Scale-Revised (APS-R; Slaney, Mobley, Trippi, Ashby, & Johnson, 1996). Decision rules and cut-scores were developed and replicated that classify adolescents as one of two kinds of perfectionists (adaptive or maladaptive) or as nonperfectionists. A…

  8. Adolescence Education Newsletter, 1999.

    ERIC Educational Resources Information Center

    Villanueva, Carmelita L., Ed.; Padilla, Teresita M., Ed.

    1999-01-01

    This document comprises the two 1999 issues of a UNESCO newsletter addressing topics related to adolescent well-being in the Asia-Pacific region, particularly reproductive and sexual health. Each issue contains news from the region on various initiatives related to adolescent heath and education, as well as Web links and publications on the…

  9. Adolescence Education Newsletter, 2001.

    ERIC Educational Resources Information Center

    Villanueva, Carmelita L., Ed.; Espada-Carlos, Lichelle Dara, Ed.

    2001-01-01

    This document comprises the two 2001 issues of a UNESCO newsletter addressing topics related to adolescent well-being in the Asia-Pacific region, particularly reproductive and sexual health. Each issue contains news from the region on various initiatives related to adolescent health and education, as well as Web links and publications on the…

  10. Adolescence Education Newsletter, 2000.

    ERIC Educational Resources Information Center

    Villanueva, Carmelita L., Ed.; Padilla, Teresita M., Ed.

    2000-01-01

    This document comprises the two 2000 issues of a UNESCO newsletter addressing topics related to adolescent well-being in the Asia-Pacific region, particularly reproductive and sexual health. Each issue contains news from the region on various initiatives related to adolescent health and education, as well as Web links and publications on the…

  11. [Adolescent sexuality in Peru].

    PubMed

    Loli, A; Aramburu, C; Paxman, J M

    1987-01-01

    22% of the population of Peru, or 4.25 million individuals, is between the ages of 11 and 19 years. A survey was performed on a sample of 6,000 adolescents living in Lima, Cajamarca, Huarez, and Supe. Surveys were performed in a variety of locations, including school classrooms, maternity wards, schools, and work places. The questionnaire was constructed based on a format that had been tested in Nigeria; questions dealt with socioeconomic background, sex behavior, contraceptive behavior, pregnancy history, and health practices and knowledge. 60% of the adolescents were women and 40% were men. 41% had had at least 1 sexual experience; among 18-year-olds, this % rose to 55. Only 10% were in stable union. Married adolescents tended to have begun sexual relations sooner in life. Early sexual relations were more common among men than among women, and more common among non-religious adolescents than among Catholics. Fewer than 12% of the adolescents had at 1 time used contraceptives. Contraceptive use was more prevalent among adolescents from wealthier socioeconomic groups, and more prevalent in Lima than in other regions surveyed. Of adolescents using contraceptives, 38% used condoms, 24% used oral contraceptives, and 15% used rhythm methods. Most adolescents who did not use contraceptives failed to do so because of lack of knowledge. Almost 1/4 of the young women had had a pregnancy. 18.5 of these had abortions, usually in a hospital. The importance of supporting educational prevention programs is underlined.

  12. Early Adolescent Ego Development.

    ERIC Educational Resources Information Center

    James, Michael A.

    1980-01-01

    Presented are the theoretical characteristics of social identity in early adolescence (ages 10 to 15). It is suggested that no longer is identity thought to begin with adolescence, but may have its beginnings in the preteen years. The article draws heavily on Eriksonian concepts. (Editor/KC)

  13. Fluency Variation in Adolescents

    ERIC Educational Resources Information Center

    De Andrade, Claudia Regina Furquim; Martins, Vanessa De Oliveira

    2007-01-01

    The Speech Fluency Profile of fluent adolescent speakers of Brazilian Portuguese, were examined with respect to gender and neurolinguistic variations. Speech samples of 130 male and female adolescents, aged between 12;0 and 17;11 years were gathered. They were analysed according to type of speech disruption; speech rate; and frequency of speech…

  14. Inside the Adolescent Brain

    ERIC Educational Resources Information Center

    Drury, Stacy S.

    2009-01-01

    Dr. Jay Giedd says that the main alterations in the adolescent brain are the inverted U-shaped developmental trajectories with late childhood/early teen peaks for gray matter volume among others. Giedd adds that the adolescent brain is vulnerable to substances that artificially modulate dopamine levels since its reward system is in a state of flux.

  15. Defining Early Adolescent Childbearing.

    ERIC Educational Resources Information Center

    Phipps, Maureen G.; Sowers, MaryFran

    2002-01-01

    Determined the age group for defining early adolescent childbearing based on rates of adverse clinical outcomes. Data on infant mortality, very low birth weight, and very pre-term delivery per 1,000 live births for women age 12-23 years in the 1995 U.S. birth cohort indicate that early adolescent childbearing is best defined as giving birth at age…

  16. Adolescence and Body Image.

    ERIC Educational Resources Information Center

    Weinshenker, Naomi

    2002-01-01

    Discusses body image among adolescents, explaining that today's adolescents are more prone to body image distortions and dissatisfaction than ever and examining the historical context; how self-image develops; normative discontent; body image distortions; body dysmorphic disorder (BDD); vulnerability of boys (muscle dysmorphia); who is at risk;…

  17. The Changing Adolescent Brain

    ERIC Educational Resources Information Center

    White, Aaron M.

    2005-01-01

    Adolescence is the transition from childhood to adulthood, a period during which an individual acquires the skills necessary to survive on his or her own, away from parents or other caregivers. Adolescence can be a very confusing time. They experience changes in sleep, diet, mood, weight and attitude and a decreased pleasure from daily activities.…

  18. Adolescence. What is normal?

    PubMed

    Offer, D; Ostrov, E; Howard, K I

    1989-06-01

    We present in some detail what constitutes normal behavior, or mental health, among teenagers. Our data are based on the results of a specially devised psychological questionnaire by one of us (D.O.). This questionnaire has been shown to reliably distinguish mentally healthy from psychiatrically disturbed populations. Results are presented across three decades (1960s, 1970s, and 1980s), across genders, and across the high school years. A conceptual framework is presented to help the clinician working with adolescents to understand the fluctuation in psychopathology among youth. Adolescent density in the total population is shown to be a significant factor in determining the rate of disturbance among teenagers. Our research findings demonstrate that the rate of behavioral disturbance among adolescents is the same as in other parts of the life cycle. The clinician working with adolescents tends to underestimate the severity of adolescent problems because of the near-universal belief that all adolescents undergo "adolescent turmoil." We have found that adolescents who are experiencing turmoil need professional help.

  19. Key Data on Adolescence.

    ERIC Educational Resources Information Center

    Coleman, John

    In order to counteract widespread stereotyping of adolescents and to provide a historical perspective on the lives of youth in Great Britain, this report compiles statistical data in six areas regarding adolescents and youth. Chapter 1, "Population, Families and Households," presents information on the population of the United Kingdom including…

  20. Adolescent Steroid Use.

    ERIC Educational Resources Information Center

    Office of Inspector General (DHHS), Washington, DC.

    The study focused on non-medical steroid use by adolescents according to data obtained from the National Institute on Drug Abuse, professional literature, 30 key informants knowledgeable in steroid issues, and 72 current or former steroid users. The findings indicated: (1) over 250,000 adolescents, primarily males, used or have used steroids, and…