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Sample records for affecting females rett

  1. De novo SHANK3 mutation causes Rett syndrome-like phenotype in a female patient.

    PubMed

    Hara, Munetsugu; Ohba, Chihiro; Yamashita, Yushiro; Saitsu, Hirotomo; Matsumoto, Naomichi; Matsuishi, Toyojiro

    2015-07-01

    Rett syndrome (RTT) is a neurodevelopmental disorder predominantly affecting females. Females with the MECP2 mutations exhibit a broad spectrum of clinical manifestations ranging from classical Rett syndrome to asymptomatic carriers. Mutations of genes encoding cyclin-dependent kinase-like 5 (CDKL5) and forkhead box G1 (FOXG1) are also found in early onset RTT variants. Here, we present the first report of a female patient with RTT-like phenotype caused by SHANK3 (SH3 and multiple ankylin repeat domain 3) mutation, indicating that the clinical spectrum of SHANK3 mutations may extend to RTT-like phenotype in addition to (severe) developmental delay, absence of expressive speech, autistic behaviors and intellectual disability.

  2. Rett Syndrome Symptomatology of Institutionalized Adults with Mental Retardation: Comparison of Males and Females.

    ERIC Educational Resources Information Center

    Burd, Larry; And Others

    1991-01-01

    The study of 297 institutionalized adults with mental retardation found no symptom of Rett syndrome occurred more frequently in males than in females and no single cluster of symptoms appeared to differentiate males from females. Only females were found to meet the necessary criteria for diagnosis of Rett syndrome. (Author/DB)

  3. Breathing abnormalities in a female mouse model of Rett syndrome.

    PubMed

    Johnson, Christopher M; Cui, Ningren; Zhong, Weiwei; Oginsky, Max F; Jiang, Chun

    2015-09-01

    Rett syndrome (RTT) is a female neurodevelopmental disease with breathing abnormalities. To understand whether breathing defects occur in the early lives of a group of female Mecp2(+/-) mice, a mouse model of RTT, and what percentage of mice shows RTT-like breathing abnormality, breathing activity was measured by plethysmography in conscious mice. Breathing frequency variation and central apnea in a group of Mecp2(+/-) females displayed a distribution pattern similar to Mecp2(-/Y) males, while the rest resembled the wild-type mice. Similar results were obtained using the k-mean clustering statistics analysis. With two independent methods, about 20% of female Mecp2(+/-) mice showed RTT-like breathing abnormalities that began as early as 3 weeks of age in the Mecp2(+/-) mice, and were suppressed with 3% CO2. The finding that only a small proportion of Mecp2(+/-) mice develops RTT-like breathing abnormalities suggests incomplete allele inactivation in the RTT-model Mecp2(+/-) mice.

  4. Rett syndrome: a preliminary analysis of stereotypy, stress, and negative affect.

    PubMed

    Quest, Kelsey M; Byiers, Breanne J; Payen, Ameante; Symons, Frank J

    2014-05-01

    Rett syndrome (RTT) is a neurodevelopmental disorder primarily affecting females. It is characterized by apparently normative development of motor and communicative abilities followed by deterioration in these domains. Stereotypic hand movements are one of the core diagnostic criteria for RTT. There is some anecdotal but limited scientific evidence that changes in hand stereotypy may be a sign of increased anxiety or arousal (i.e., a 'stress response') in RTT. Understanding stress responsivity is difficult in RTT because almost all individuals are nonverbal or otherwise severely communicatively impaired. This study used direct behavioral observation to quantify and compare the frequency of hand stereotypy and signs of negative affect during presumed periods of high and low stress associated with functional analysis conditions (negative reinforcement ['escape'] and control ['free play'], respectively) for 5 females with RTT (mean age=17.8; range 4-47). Negative affect was more likely to occur during negative reinforcement ('stress') conditions for each participant whereas hand stereotypies did not differ across conditions for any of the participants. Although preliminary, the results suggest that hand stereotypy may not be a valid behavioral 'stress-response' indicator in females with RTT. Alternatively, the approach we used may have been limited and not sufficient to evoke a stress response. Either way, more work with direct relevance to improving our understanding of hand stereotypy and anxiety in RTT in relation to social context appears warranted.

  5. Homozygous c.1160C>T (P38L) in the MECP2 gene in a female Rett syndrome patient.

    PubMed

    Bhanushali, Aparna A; Mandsaurwala, A; Das, Bibhu R

    2016-03-01

    Rett syndrome is a severe X-linked dominant neurodevelopmental disorder. Mutations in the MECP2 gene on chromosome Xq28 have been shown to be the cause of Rett syndrome. Sequencing of the MECP2 gene in a patient with clinical suspicion of Rett syndrome revealed c.1160C>T (P387L) in exon 4 of the MECP2 gene homozygously. Females with Rett syndrome are usually heterozygous for a mutation in MECP2. Uniparental disomy as a probable cause for the homozygous presence of this mutation was ruled out by quantitative fluorescence-polymerase chain reaction. Moreover to our knowledge this mutation has only been reported in males with X-linked mental retardation (MRX). We hypothesize that the presence of this mutation c.1160C>T (P387L) in the homozygous form is responsible for the Rett syndrome-like phenotype seen in this patient. This novel report reveals for the first time the homozygous presence of a mutation which has hitherto only been reported in males with MRX.

  6. The MECP2 variant c.925C>T (p.Arg309Trp) causes intellectual disability in both males and females without classic features of Rett syndrome.

    PubMed

    Schönewolf-Greulich, B; Tejada, M-I; Stephens, K; Hadzsiev, K; Gauthier, J; Brøndum-Nielsen, K; Pfundt, R; Ravn, K; Maortua, H; Gener, B; Martínez-Bouzas, C; Piton, A; Rouleau, G; Clayton-Smith, J; Kleefstra, T; Bisgaard, A-M; Tümer, Z

    2016-06-01

    Missense MECP2 variants can have various phenotypic effects ranging from a normal phenotype to typical Rett syndrome (RTT). In females, the phenotype can also be influenced by the X-inactivation pattern. In this study, we present detailed clinical descriptions of six patients with a rare base-pair substitution affecting Arg309 at the C-terminal end of the transcriptional repression domain (TRD). All patients have intellectual disability and present with some RTT features, but they do not fulfill the clinical criteria for typical or atypical RTT. Most of the patients also have mild facial dysmorphism. Intriguingly, the mother of an affected male patient is an asymptomatic carrier of this variant. It is therefore likely that the p.(Arg309Trp) variation does not necessarily lead to male lethality, and it results in a wide range of clinical features in females, probably influenced by different X-inactivation patterns in target tissues. PMID:26936630

  7. The MECP2 variant c.925C>T (p.Arg309Trp) causes intellectual disability in both males and females without classic features of Rett syndrome.

    PubMed

    Schönewolf-Greulich, B; Tejada, M-I; Stephens, K; Hadzsiev, K; Gauthier, J; Brøndum-Nielsen, K; Pfundt, R; Ravn, K; Maortua, H; Gener, B; Martínez-Bouzas, C; Piton, A; Rouleau, G; Clayton-Smith, J; Kleefstra, T; Bisgaard, A-M; Tümer, Z

    2016-06-01

    Missense MECP2 variants can have various phenotypic effects ranging from a normal phenotype to typical Rett syndrome (RTT). In females, the phenotype can also be influenced by the X-inactivation pattern. In this study, we present detailed clinical descriptions of six patients with a rare base-pair substitution affecting Arg309 at the C-terminal end of the transcriptional repression domain (TRD). All patients have intellectual disability and present with some RTT features, but they do not fulfill the clinical criteria for typical or atypical RTT. Most of the patients also have mild facial dysmorphism. Intriguingly, the mother of an affected male patient is an asymptomatic carrier of this variant. It is therefore likely that the p.(Arg309Trp) variation does not necessarily lead to male lethality, and it results in a wide range of clinical features in females, probably influenced by different X-inactivation patterns in target tissues.

  8. Affective dysfunction in a mouse model of Rett syndrome: Therapeutic effects of environmental stimulation and physical activity.

    PubMed

    Kondo, Mari A; Gray, Laura J; Pelka, Gregory J; Leang, Sook-Kwan; Christodoulou, John; Tam, Patrick P L; Hannan, Anthony J

    2016-02-01

    Rett syndrome (RTT) is a neurodevelopmental disorder associated with mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2) and consequent dysregulation of brain maturation. Patients suffer from a range of debilitating physical symptoms, however, behavioral and emotional symptoms also severely affect their quality of life. Here, we present previously unreported and clinically relevant affective dysfunction in the female heterozygous Mecp2(tm1Tam) mouse model of RTT (129sv and C57BL6 mixed background). The affective dysfunction and aberrant anxiety-related behavior of the Mecp2(+/-) mice were found to be reversible with environmental enrichment (EE) from 4 weeks of age. The effect of exercise alone (via wheel running) was also explored, providing the first evidence that increased voluntary physical activity in an animal model of RTT is beneficial for some phenotypes. Mecp2(+/-) mutants displayed elevated corticosterone despite decreased Crh expression, demonstrating hypothalamic-pituitary-adrenal axis dysregulation. EE of Mecp2(+/-) mice normalized basal serum corticosterone and hippocampal BDNF protein levels. The enrichment-induced rescue appears independent of the transcriptional regulation of the MeCP2 targets Bdnf exon 4 and Crh. These findings provide new insight into the neurodevelopmental role of MeCP2 and pathogenesis of RTT, in particular the affective dysfunction. The positive outcomes of environmental stimulation and physical exercise have implications for the development of therapies targeting the affective symptoms, as well as behavioral and cognitive dimensions, of this devastating neurodevelopmental disorder.

  9. Learning ability in children with Rett syndrome.

    PubMed

    Elefant, Cochavit; Wigram, Tony

    2005-11-01

    The purpose of this article is to present results of a research study examining learning ability in individuals with Rett syndrome. The material for this article was drawn from a more extensive doctoral study, designed to investigate intentional communication in this population, through the use of songs in music therapy. Rett syndrome is a neurological disorder resulting from an X-linked mutation, affecting mainly females, and found across racial and ethnic groups worldwide. One of the main areas affecting functioning in individuals with Rett syndrome is a severe impairment of receptive and expressive communication. This creates difficulties when attempting to reveal their potential learning abilities. This population has been observed as very responsive to music hence music therapy intervention has been advocated in promoting and motivating them to communicate and to learn. Seven girls with Rett syndrome, between ages 4 and 10 participated in the study. A single subject, multiple probe design was applied during 30-min trials, three times per week and lasted 8 months. During the trials the participants were asked to choose from a selection of 18 familiar and unfamiliar songs, while their ability to learn was observed and measured. Findings revealed that all seven girls demonstrated an ability to learn and to sustain learning over time. This intervention demonstrated that individuals with Rett syndrome could be promoted and motivated to communicate and learn when therapeutically employed by a trained music therapists.

  10. Rett Syndrome

    MedlinePlus

    Rett syndrome is a rare genetic disease that causes developmental and nervous system problems, mostly in girls. It's related to autism spectrum disorder. Babies with Rett syndrome seem to grow and develop normally at first. ...

  11. Autism and Rett Syndrome: Behavioural Investigations and Differential Diagnosis.

    ERIC Educational Resources Information Center

    Olsson, Bo; Rett, Andreas

    1987-01-01

    Differential diagnosis of Rett syndrome and infantile autism among 63 female patients (22 months to 15 years) was investigated. Conclusions concerned: characteristics of some Rett subjects but no autistic subjects, characteristics of all Rett subjects but not all autistic subjects, and characteristics of most Rett subjects and some autistic…

  12. 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.

  13. Trends in the diagnosis of Rett syndrome in Australia

    PubMed Central

    Fehr, Stephanie; Bebbington, Ami; Nassar, Natasha; Downs, Jenny; Ronen, Gabriel M; de Klerk, Nicholas; Leonard, Helen

    2011-01-01

    Modifications to diagnostic criteria and introduction of genetic testing have likely affected the pattern and timing of Rett syndrome diagnosis. The trends in incidence and prevalence of Rett syndrome in Australia were examined; the cumulative risk of a female being diagnosed determined; and the impact of changes to diagnostic criteria and availability of genetic testing on these frequencies investigated. The population-based Australian Rett Syndrome Database was used to identify a total of 349 verified Rett syndrome females born 1976-2006 and diagnosed 1982-2008. The proportion of female cases born and diagnosed per year and the cumulative risk of a diagnosis were determined. The median age of Rett syndrome diagnosis decreased from 4.5 years if diagnosed before 2000 to 3.5 years if diagnosed after 1999. The cumulative risk of diagnosis had almost doubled by 32 y of age [1/8,905 or 11.23 per 100,000 person-years (95% CI, 10.03–12.45)] in comparison with 5 y of age [1/15,361 or 6.51 per 100,000 person-years (95% CI, 5.65–7.39)]. Earlier age of diagnosis may result in families experiencing less stress and emotional strain compared to those with delayed diagnosis. PMID:21587099

  14. Rett Syndrome

    PubMed Central

    Smeets, E.E.J.; Pelc, K.; Dan, B.

    2012-01-01

    Rett syndrome is one of the most common causes of complex disability in girls. It is characterized by early neurological regression that severely affects motor, cognitive and communication skills, by autonomic dysfunction and often a seizure disorder. It is a monogenic X-linked dominant neurodevelopmental disorder related to mutation in MECP2, which encodes the methyl-CpG-binding protein MeCP2. There are several mouse models either based on conditional knocking out of the Mecp2 gene or on a truncating mutation. We discuss the clinical aspects with special emphasis on the behavioral phenotype and we review current perspectives in clinical management alongside with perspectives in altering gene expression. PMID:22670134

  15. Normal Reactions to Orthostatic Stress in Rett Syndrome

    ERIC Educational Resources Information Center

    Larsson, Gunilla; Julu, Peter O. O.; Engerstrom, Ingegerd Witt; Sandlund, Marlene; Lindstrom, Britta

    2013-01-01

    The aim of this study was to investigate orthostatic reactions in females with Rett syndrome (RTT), and also whether the severity of the syndrome had an impact on autonomic reactions. Based on signs of impaired function of the central autonomic system found in RTT, it could be suspected that orthostatic reactions were affected. The orthostatic…

  16. Sensory-Motor Rehabilitation in Rett Syndrome: A Case Report

    ERIC Educational Resources Information Center

    Pizzamiglio, Maria Rosa; Nasti, Marianna; Piccardi, Laura; Zotti, Antonella; Vitturini, Claudio; Spitoni, Grazia; Nanni, Maria Vittoria; Guariglia, Cecilia; Morelli, Daniela

    2008-01-01

    Rett syndrome (RS) is a severe neurodevelopmental disorder that mostly affects females. It is characterized by a regression of motor, cognitive, linguistic, and social abilities and by an inappropriate and stereotypical use of the hands. The purpose of the current study was to explore the possibility of rehabilitating purposeful use of the hands…

  17. Bone Mineral Content and Bone Mineral Density Are Lower in Older than in Younger Females with Rett Syndrome

    PubMed Central

    Motil, Kathleen J.; Ellis, Kenneth J.; Barrish, Judy O.; Caeg, Erwin; Glaze, Daniel G.

    2008-01-01

    Although bone mineral deficits have been identified in Rett syndrome (RTT), the prevalence of low bone mineral density and its association with skeletal fractures and scoliosis has not been characterized fully in girls and women with RTT. Accordingly, we measured total body bone mineral content (BMC) and bone mineral density (BMD) using dual energy x-ray absorptiometry in a cross-sectional group of 50 females, ages 2-38 y, with RTT. Methyl-CpG-binding 2 (MECP2) mutations, skeletal fractures, and scoliosis were documented. The prevalence of BMC and BMD z-scores <-2 SD was 59% and 45%, respectively. Although absolute BMC and BMD increased significantly with increasing age, BMC and BMD z-scores were significantly lower in older than in younger females. The prevalence of fractures and scoliosis was 28% and 64%, respectively. Low BMD z-scores were positively associated with fractures and scoliosis. Deficits in BMD were identified across a broad range of MECP2 mutations. This study identified associations among low bone mineral density, fractures, and scoliosis, and underscored the need for better understanding of the molecular mechanisms of MECP2 in the regulation of bone mineral metabolism. PMID:18535484

  18. Long-lasting beneficial effects of central serotonin receptor 7 stimulation in female mice modeling Rett syndrome.

    PubMed

    De Filippis, Bianca; Chiodi, Valentina; Adriani, Walter; Lacivita, Enza; Mallozzi, Cinzia; Leopoldo, Marcello; Domenici, Maria Rosaria; Fuso, Andrea; Laviola, Giovanni

    2015-01-01

    Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioral and physiological symptoms. Mutations in the methyl CpG binding protein 2 gene (MECP2) cause more than 95% of classic cases, and currently there is no cure for this devastating disorder. Recently we have demonstrated that specific behavioral and brain molecular alterations can be rescued in MeCP2-308 male mice, a RTT mouse model, by pharmacological stimulation of the brain serotonin receptor 7 (5-HT7R). This member of the serotonin receptor family-crucially involved in the regulation of brain structural plasticity and cognitive processes-can be stimulated by systemic repeated treatment with LP-211, a brain-penetrant selective 5-HT7R agonist. The present study extends previous findings by demonstrating that the LP-211 treatment (0.25 mg/kg, once per day for 7 days) rescues RTT-related phenotypic alterations, motor coordination (Dowel test), spatial reference memory (Barnes maze test) and synaptic plasticity (hippocampal long-term-potentiation) in MeCP2-308 heterozygous female mice, the genetic and hormonal milieu that resembles that of RTT patients. LP-211 also restores the activation of the ribosomal protein (rp) S6, the downstream target of mTOR and S6 kinase, in the hippocampus of RTT female mice. Notably, the beneficial effects on neurobehavioral and molecular parameters of a seven-day long treatment with LP-211 were evident up to 2 months after the last injection, thus suggesting long-lasting effects on RTT-related impairments. Taken together with our previous study, these results provide compelling preclinical evidence of the potential therapeutic value for RTT of a pharmacological approach targeting the brain 5-HT7R.

  19. Modulation of Rho GTPases rescues brain mitochondrial dysfunction, cognitive deficits and aberrant synaptic plasticity in female mice modeling Rett syndrome.

    PubMed

    De Filippis, Bianca; Valenti, Daniela; Chiodi, Valentina; Ferrante, Antonella; de Bari, Lidia; Fiorentini, Carla; Domenici, Maria Rosaria; Ricceri, Laura; Vacca, Rosa Anna; Fabbri, Alessia; Laviola, Giovanni

    2015-06-01

    Rho GTPases are molecules critically involved in neuronal plasticity and cognition. We have previously reported that modulation of brain Rho GTPases by the bacterial toxin CNF1 rescues the neurobehavioral phenotype in MeCP2-308 male mice, a model of Rett syndrome (RTT). RTT is a rare X-linked neurodevelopmental disorder and a genetic cause of intellectual disability, for which no effective therapy is available. Mitochondrial dysfunction has been proposed to be involved in the mechanism of the disease pathogenesis. Here we demonstrate that modulation of Rho GTPases by CNF1 rescues the reduced mitochondrial ATP production via oxidative phosphorylation in the brain of MeCP2-308 heterozygous female mice, the condition which more closely recapitulates that of RTT patients. In RTT mouse brain, CNF1 also restores the alterations in the activity of the mitochondrial respiratory chain (MRC) complexes and of ATP synthase, the molecular machinery responsible for the majority of cell energy production. Such effects were achieved through the upregulation of the protein content of those MRC complexes subunits, which were defective in RTT mouse brain. Restored mitochondrial functionality was accompanied by the rescue of deficits in cognitive function (spatial reference memory in the Barnes maze), synaptic plasticity (long-term potentiation) and Tyr1472 phosphorylation of GluN2B, which was abnormally enhanced in the hippocampus of RTT mice. Present findings bring into light previously unknown functional mitochondrial alterations in the brain of female mice modeling RTT and provide the first evidence that RTT brain mitochondrial dysfunction can be rescued by modulation of Rho GTPases.

  20. Long-lasting beneficial effects of central serotonin receptor 7 stimulation in female mice modeling Rett syndrome

    PubMed Central

    De Filippis, Bianca; Chiodi, Valentina; Adriani, Walter; Lacivita, Enza; Mallozzi, Cinzia; Leopoldo, Marcello; Domenici, Maria Rosaria; Fuso, Andrea; Laviola, Giovanni

    2015-01-01

    Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioral and physiological symptoms. Mutations in the methyl CpG binding protein 2 gene (MECP2) cause more than 95% of classic cases, and currently there is no cure for this devastating disorder. Recently we have demonstrated that specific behavioral and brain molecular alterations can be rescued in MeCP2-308 male mice, a RTT mouse model, by pharmacological stimulation of the brain serotonin receptor 7 (5-HT7R). This member of the serotonin receptor family—crucially involved in the regulation of brain structural plasticity and cognitive processes—can be stimulated by systemic repeated treatment with LP-211, a brain-penetrant selective 5-HT7R agonist. The present study extends previous findings by demonstrating that the LP-211 treatment (0.25 mg/kg, once per day for 7 days) rescues RTT-related phenotypic alterations, motor coordination (Dowel test), spatial reference memory (Barnes maze test) and synaptic plasticity (hippocampal long-term-potentiation) in MeCP2-308 heterozygous female mice, the genetic and hormonal milieu that resembles that of RTT patients. LP-211 also restores the activation of the ribosomal protein (rp) S6, the downstream target of mTOR and S6 kinase, in the hippocampus of RTT female mice. Notably, the beneficial effects on neurobehavioral and molecular parameters of a seven-day long treatment with LP-211 were evident up to 2 months after the last injection, thus suggesting long-lasting effects on RTT-related impairments. Taken together with our previous study, these results provide compelling preclinical evidence of the potential therapeutic value for RTT of a pharmacological approach targeting the brain 5-HT7R. PMID:25926782

  1. Italian Rett database and biobank.

    PubMed

    Sampieri, Katia; Meloni, Ilaria; Scala, Elisa; Ariani, Francesca; Caselli, Rossella; Pescucci, Chiara; Longo, Ilaria; Artuso, Rosangela; Bruttini, Mirella; Mencarelli, Maria Antonietta; Speciale, Caterina; Causarano, Vincenza; Hayek, Giuseppe; Zappella, Michele; Renieri, Alessandra; Mari, Francesca

    2007-04-01

    Rett syndrome is the second most common cause of severe mental retardation in females, with an incidence of approximately 1 out of 10,000 live female births. In addition to the classic form, a number of Rett variants have been described. MECP2 gene mutations are responsible for about 90% of classic cases and for a lower percentage of variant cases. Recently, CDKL5 mutations have been identified in the early onset seizures variant and other atypical Rett patients. While the high percentage of MECP2 mutations in classic patients supports the hypothesis of a single disease gene, the low frequency of mutated variant cases suggests genetic heterogeneity. Since 1998, we have performed clinical evaluation and molecular analysis of a large number of Italian Rett patients. The Italian Rett Syndrome (RTT) database has been developed to share data and samples of our RTT collection with the scientific community (http://www.biobank.unisi.it). This is the first RTT database that has been connected with a biobank. It allows the user to immediately visualize the list of available RTT samples and, using the "Search by" tool, to rapidly select those with specific clinical and molecular features. By contacting bank curators, users can request the samples of interest for their studies. This database encourages collaboration projects with clinicians and researchers from around the world and provides important resources that will help to better define the pathogenic mechanisms underlying Rett syndrome.

  2. Respiratory phenotypes are distinctly affected in mice with common Rett syndrome mutations MeCP2 T158A and R168X.

    PubMed

    Bissonnette, J M; Schaevitz, L R; Knopp, S J; Zhou, Z

    2014-05-16

    Respiratory disturbances are a primary phenotype of the neurological disorder, Rett syndrome (RTT), caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2). Mouse models generated with null mutations in Mecp2 mimic respiratory abnormalities in RTT girls. Large deletions, however, are seen in only ∼10% of affected human individuals. Here we characterized respiration in heterozygous females from two mouse models that genetically mimic common RTT point mutations, a missense mutation T158A (Mecp2(T158A/)(+)) or a nonsense mutation R168X (Mecp2(R168X/+)). MeCP2 T158A shows decreased binding to methylated DNA, while MeCP2 R168X retains the capacity to bind methylated DNA but lacks the ability to recruit complexes required for transcriptional repression. We found that both Mecp2(T158A/+) and Mecp2(R168X/+) heterozygotes display augmented hypoxic ventilatory responses and depressed hypercapnic responses, compared to wild-type controls. Interestingly, the incidence of apnea was much greater in Mecp2(R168X/+) heterozygotes, 189 per hour, than Mecp2(T158A/+) heterozygotes, 41 per hour. These results demonstrate that different RTT mutations lead to distinct respiratory phenotypes, suggesting that characterization of the respiratory phenotype may reveal functional differences between MeCP2 mutations and provide insights into the pathophysiology of RTT.

  3. Bone mineral content and bone mineral density are lower in older than in younger females with Rett syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although bone mineral deficits have been identified in Rett syndrome (RTT), the prevalence of low bone mineral density (BMD) and its association with skeletal fractures and scoliosis has not been characterized fully in girls and women with RTT. Accordingly, we measured total body bone mineral conten...

  4. Two Sisters with Rett Syndrome. Brief Report.

    ERIC Educational Resources Information Center

    Haenggeli, Charles A.; And Others

    1990-01-01

    Clinical histories and physical findings are presented for 2 sisters with Rett syndrome. The older sister, age 25, was typically affected, whereas the younger sister, 22 years old, was affected with a seizure disorder showing an unusually early onset. The paper discusses hypotheses in genetic causation of Rett syndrome. (JDD)

  5. Rett Syndrome

    MedlinePlus

    ... binding protein 2 (MeCP2), which is needed for brain development and acts as one of the many biochemical ... the following criteria do not have Rett syndrome: brain injury secondary to ... abnormal psychomotor development in the first 6 months of life. Is ...

  6. Rett Syndrome.

    ERIC Educational Resources Information Center

    Culbert, Linda A.

    This pamphlet reviews the historical process involved in initially recognizing Rett Syndrome as a specific disorder in girls. Its etiology is unknown, but studies have considered factors as hyperammonemia, a two-step mutation, a fragile X chromosome, metabolic disorder, environmental causation, dopamine deficiency, and an inactive X chromosome.…

  7. Conceptualizing a quality of life framework for girls with Rett syndrome using qualitative methods.

    PubMed

    Epstein, Amy; Leonard, Helen; Davis, Elise; Williams, Katrina; Reddihough, Dinah; Murphy, Nada; Whitehouse, Andrew; Downs, Jenny

    2016-03-01

    Rett syndrome is a neurodevelopmental disorder mainly affecting females and associated with a mutation on the MECP2 gene. There has been no systematic evaluation of the domains of quality of life (QOL) in Rett syndrome. The aims of this study were to explore QOL in school-aged children with Rett syndrome and compare domains with those identified in other available QOL scales. The sample comprised 21 families registered with the Australian Rett Syndrome Database whose daughter with Rett syndrome was aged 6-18 years. Semi-structured telephone interviews were conducted with each parent caregiver (19 mothers, 2 fathers) to investigate aspects of their daughter's life that were satisfying or challenging to her. Qualitative thematic analysis using a grounded theory framework was conducted, and emerging domains compared with those in two generic and three disability parent-report child QOL measures. Ten domains were identified: physical health, body pain, and discomfort, behavioral and emotional well-being, communication skills, movement and mobility, social connectedness, variety of activities, provision of targeted services, stability of daily routines, and the natural environment. The two latter domains were newly identified and each domain contained elements not represented in the comparison measures. Our data articulated important aspects of life beyond the genetic diagnosis. Existing QOL scales for children in the general population or with other disabilities did not capture the QOL of children with Rett syndrome. Our findings support the construction of a new parent-report measure to enable measurement of QOL in this group. PMID:26686505

  8. Conceptualizing a quality of life framework for girls with Rett syndrome using qualitative methods.

    PubMed

    Epstein, Amy; Leonard, Helen; Davis, Elise; Williams, Katrina; Reddihough, Dinah; Murphy, Nada; Whitehouse, Andrew; Downs, Jenny

    2016-03-01

    Rett syndrome is a neurodevelopmental disorder mainly affecting females and associated with a mutation on the MECP2 gene. There has been no systematic evaluation of the domains of quality of life (QOL) in Rett syndrome. The aims of this study were to explore QOL in school-aged children with Rett syndrome and compare domains with those identified in other available QOL scales. The sample comprised 21 families registered with the Australian Rett Syndrome Database whose daughter with Rett syndrome was aged 6-18 years. Semi-structured telephone interviews were conducted with each parent caregiver (19 mothers, 2 fathers) to investigate aspects of their daughter's life that were satisfying or challenging to her. Qualitative thematic analysis using a grounded theory framework was conducted, and emerging domains compared with those in two generic and three disability parent-report child QOL measures. Ten domains were identified: physical health, body pain, and discomfort, behavioral and emotional well-being, communication skills, movement and mobility, social connectedness, variety of activities, provision of targeted services, stability of daily routines, and the natural environment. The two latter domains were newly identified and each domain contained elements not represented in the comparison measures. Our data articulated important aspects of life beyond the genetic diagnosis. Existing QOL scales for children in the general population or with other disabilities did not capture the QOL of children with Rett syndrome. Our findings support the construction of a new parent-report measure to enable measurement of QOL in this group.

  9. An Analogue Assessment of Repetitive Hand Behaviours in Girls and Young Women with Rett Syndrome

    ERIC Educational Resources Information Center

    Wales, L.; Charman, T.; Mount, R. H.

    2004-01-01

    Rett syndrome is a neuro-developmental disorder that almost exclusively affects females. In addition to neuro-developmental regression and loss of hand skills, apraxia, deceleration of head growth, and increasing spasticity and scoliosis, a number of behavioural features are also seen, including stereotypic hand movements, hyperventilation and…

  10. Addressing the Needs of Students with Rett Syndrome.

    ERIC Educational Resources Information Center

    Katsiyannis, Antonis; Ellenburg, Jennifer S.; Acton, Olivia M.; Torrey, Gregory

    2001-01-01

    This article discusses symptoms of students with Rett Syndrome, a disability in females characterized by the development of multiple specific deficits following a period of normal functioning after birth. Specific interventions for students with Rett syndrome are provided and address communication, stereotypic movements, self-injurious behaviors,…

  11. Rett Syndrome: Revised Diagnostic Criteria and Nomenclature

    PubMed Central

    Neul, Jeffrey L.; Kaufmann, Walter E.; Glaze, Daniel G.; Christodoulou, John; Clarke, Angus J.; Bahi-Buisson, Nadia; Leonard, Helen; Bailey, Mark E. S.; Schanen, N. Carolyn; Zappella, Michele; Renieri, Alessandra; Huppke, Peter; Percy, Alan K.

    2010-01-01

    Objective Rett syndrome (RTT) is a severe neurodevelopmental disease that affects approximately 1 in 10,000 live female births and is often caused by mutations in Methyl-CpG-binding protein 2 (MECP2). Despite distinct clinical features, the accumulation of clinical and molecular information in recent years has generated considerable confusion regarding the diagnosis of RTT. The purpose of this work was revise and clarify 2002 consensus criteria for the diagnosis of RTT in anticipation of treatment trials. Method RettSearch members, representing the majority of the international clinical RTT specialists, participated in an iterative process to come to a consensus on a revised and simplified clinical diagnostic criteria for RTT. Results The clinical criteria required for the diagnosis of classic and atypical RTT were clarified and simplified. Guidelines for the diagnosis and molecular evaluation of specific variant forms of RTT were developed. Interpretation These revised criteria provide clarity regarding the key features required for the diagnosis of RTT and reinforce the concept that RTT is a clinical diagnosis based on distinct clinical criteria, independent of molecular findings. We recommend that these criteria and guidelines be utilized in any proposed clinical research. PMID:21154482

  12. Rett syndrome and MeCP2.

    PubMed

    Liyanage, Vichithra R B; Rastegar, Mojgan

    2014-06-01

    Rett syndrome (RTT) is a severe and progressive neurological disorder, which mainly affects young females. Mutations of the methyl-CpG binding protein 2 (MECP2) gene are the most prevalent cause of classical RTT cases. MECP2 mutations or altered expression are also associated with a spectrum of neurodevelopmental disorders such as autism spectrum disorders with recent links to fetal alcohol spectrum disorders. Collectively, MeCP2 relation to these neurodevelopmental disorders highlights the importance of understanding the molecular mechanisms by which MeCP2 impacts brain development, mental conditions, and compromised brain function. Since MECP2 mutations were discovered to be the primary cause of RTT, a significant progress has been made in the MeCP2 research, with respect to the expression, function and regulation of MeCP2 in the brain and its contribution in RTT pathogenesis. To date, there have been intensive efforts in designing effective therapeutic strategies for RTT benefiting from mouse models and cells collected from RTT patients. Despite significant progress in MeCP2 research over the last few decades, there is still a knowledge gap between the in vitro and in vivo research findings and translating these findings into effective therapeutic interventions in human RTT patients. In this review, we will provide a synopsis of Rett syndrome as a severe neurological disorder and will discuss the role of MeCP2 in RTT pathophysiology.

  13. Rett Syndrome: A Comprehensive Review of the Literature.

    ERIC Educational Resources Information Center

    Perry, Adrienne

    1991-01-01

    This nontechnical review of the literature on Rett Syndrome, a developmental disability found only in females, examines the syndrome's history, diagnostic criteria, clinical stages, incidence, differential diagnosis, etiology, genetics, treatment approaches, and prognosis. (Author/DB)

  14. Rett Syndrome: A Review of Current Knowledge.

    ERIC Educational Resources Information Center

    Van Acker, Rick

    1991-01-01

    This review describes Rett syndrome as a disorder afflicting females and characterized by a progressive loss of cognitive and motor skills and development of stereotypic hand movements. The paper discusses its clinical manifestations, etiology, diagnostic criteria and differential diagnosis, prevalence, pathogenesis, treatment, and educational…

  15. Communication Skills in Girls with Rett Syndrome

    ERIC Educational Resources Information Center

    Bartolotta, Theresa E.; Zipp, Genevieve P.; Simpkins, Susan D.; Glazewski, Barbara

    2011-01-01

    Rett Syndrome (RS) is an X-linked, neurodevelopmental disorder that occurs primarily in females and causes significant impairment in cognition, motor control, and communication. Teachers and speech-language pathologists (SLPs) encounter girls with RS with increasing frequency as awareness of the disorder increases, yet the literature on clinical…

  16. Epidemiology of Rett syndrome: a population-based registry.

    PubMed

    Kozinetz, C A; Skender, M L; MacNaughton, N; Almes, M J; Schultz, R J; Percy, A K; Glaze, D G

    1993-02-01

    The Texas Rett Syndrome Registry maintains the largest population-based registry of cases and potential cases of Rett syndrome in the world. The most precise estimate of the prevalence of Rett syndrome of 1 per 22800 (0.44/10000) females aged 2 through 18 years of age was generated from this Registry. In addition, the first prevalence figures for black and Hispanic female cases were estimated. Registry cases are actively ascertained from multiple sources. Registry staff identify presumptive cases from review of information provided to the Registry by the parent or guardian. Preliminary diagnostic evaluation includes standardized review of medical records and videotape of key behaviors. Diagnosis is confirmed at clinical evaluation. The active surveillance system is monitored with the two-source capture-recapture methodology and case ascertainment is projected. The 1990 prevalence estimate of Rett syndrome indicates that the syndrome occurs less frequently than previously estimated. Until a biologic marker for Rett syndrome is identified or a standard definition for an incident case of Rett syndrome is designated, the prevalence of Rett syndrome will remain a major investigative issue of its epidemiology, and the Registry will be an important, systematic mean to gather case material for clinical and laboratory studies providing the foundation for the development of preventive interventions.

  17. MECP2e1 isoform mutation affects the form and function of neurons derived from Rett syndrome patient iPS cells.

    PubMed

    Djuric, Ugljesa; Cheung, Aaron Y L; Zhang, Wenbo; Mok, Rebecca S; Lai, Wesley; Piekna, Alina; Hendry, Jason A; Ross, P Joel; Pasceri, Peter; Kim, Dae-Sung; Salter, Michael W; Ellis, James

    2015-04-01

    MECP2 mutations cause the X-linked neurodevelopmental disorder Rett Syndrome (RTT) by consistently altering the protein encoded by the MECP2e1 alternative transcript. While mutations that simultaneously affect both MECP2e1 and MECP2e2 isoforms have been widely studied, the consequence of MECP2e1 deficiency on human neurons remains unknown. Here we report the first isoform-specific patient induced pluripotent stem cell (iPSC) model of RTT. RTTe1 patient iPS cell-derived neurons retain an inactive X-chromosome and express only the mutant allele. Single-cell mRNA analysis demonstrated they have a molecular signature of cortical neurons. Mutant neurons exhibited a decrease in soma size, reduced dendritic complexity and decreased cell capacitance, consistent with impaired neuronal maturation. The soma size phenotype was rescued cell-autonomously by MECP2e1 transduction in a level-dependent manner but not by MECP2e2 gene transfer. Importantly, MECP2e1 mutant neurons showed a dysfunction in action potential generation, voltage-gated Na(+) currents, and miniature excitatory synaptic current frequency and amplitude. We conclude that MECP2e1 mutation affects soma size, information encoding properties and synaptic connectivity in human neurons that are defective in RTT.

  18. Rett syndrome: An autoimmune disease?

    PubMed

    De Felice, Claudio; Leoncini, Silvia; Signorini, Cinzia; Cortelazzo, Alessio; Rovero, Paolo; Durand, Thierry; Ciccoli, Lucia; Papini, Anna Maria; Hayek, Joussef

    2016-04-01

    Rett syndrome (RTT) is a devastating neurodevelopmental disease, previously included into the autistic spectrum disorders, affecting almost exclusively females (frequency 1:10,000). RTT leads to intellective deficit, purposeful hands use loss and late major motor impairment besides featuring breathing disorders, epilepsy and increased risk of sudden death. The condition is caused in up to 95% of the cases by mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene. Our group has shown a number of previously unrecognized features, such as systemic redox imbalance, chronic inflammatory status, respiratory bronchiolitis-associated interstitial lung disease-like lung disease, and erythrocyte morphology changes. While evidence on an intimate involvement of MeCP2 in the immune response is cumulating, we have recently shown a cytokine dysregulation in RTT. Increasing evidence on the relationship between MeCP2 and an immune dysfunction is reported, with, apparently, a link between MECP2 gene polymorphisms and autoimmune diseases, including primary Sjögren's syndrome, systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis. Antineuronal (i.e., brain proteins) antibodies have been shown in RTT. Recently, high levels of anti-N-glucosylation (N-Glc) IgM serum autoantibodies [i.e., anti-CSF114(N-Glc) IgMs] have been detected by our group in a statistically significant number of RTT patients. In the current review, the Authors explore the current evidence, either in favor or against, the presence of an autoimmune component in RTT. PMID:26807990

  19. International Rett Syndrome Foundation

    MedlinePlus

    ... toward treatments for millions of people around the world with Autism, Parkinson's, Alzheimers, Schizophrenia and Traumatic Brain ... your state! State Resources Rettsyndrome.org is the world's leading Rett syndrome research funding organization We have ...

  20. Urinary Peptides in Rett Syndrome.

    ERIC Educational Resources Information Center

    Solaas, K. M.; Skjeldal, O.; Gardner, M. L. G.; Kase, B. F.; Reichelt, K. L.

    2002-01-01

    A study found a significantly higher level of peptides in the urine of 53 girls with Rett syndrome compared with controls. The elevation was similar to that in 35 girls with infantile autism. Levels of peptides were lower in girls with classic Rett syndrome than those with congenital Rett syndrome. (Contains references.) (Author/CR)

  1. Reduced negative affect response in female psychopaths

    PubMed Central

    Eisenbarth, Hedwig; Angrilli, Alessandro; Calogero, Antonio; Harper, Jeremy; Olson, Lacy A.; Bernat, Edward

    2013-01-01

    Studies that investigate the differences between high and low psychopathic persons in brain activity during emotional facial expression processing are rare and commonly focus on males. The current study assessed whether previously reported behavioral differences would be reflected in differential brain activity in a sample of female offenders. The participants included 23 female forensic inpatients with high and low scores on the Psychopathy Checklist Revised (PCL-R). ERPs were recorded during presentation of emotional facial expressions (i.e., fear, angry, and happy). Results revealed no differences in N170, P3 and late positive potential components between groups, but a significant difference in N2 only for angry and fear facial expressions, with high psychopathic participants showing lower reactivity. This N2 effect was found to be related to Factor 2 but not Factor 1 of the PCL-R. In time frequency analysis, theta activity underlying N2 best reflected these differences. Findings in this female sample are consistent with a cortical deficit in processing facial expression of negative emotions in psychopathic men. In addition, differences in processing seem to appear relatively early. PMID:23896396

  2. Female Fertility Affects Men's Linguistic Choices

    PubMed Central

    Coyle, Jacqueline M.; Kaschak, Michael P.

    2012-01-01

    We examined the influence of female fertility on the likelihood of male participants aligning their choice of syntactic construction with those of female confederates. Men interacted with women throughout their menstrual cycle. On critical trials during the interaction, the confederate described a picture to the participant using particular syntactic constructions. Immediately thereafter, the participant described to the confederate a picture that could be described using either the same construction that was used by the confederate or an alternative form of the construction. Our data show that the likelihood of men choosing the same syntactic structure as the women was inversely related to the women's level of fertility: higher levels of fertility were associated with lower levels of linguistic matching. A follow-up study revealed that female participants do not show this same change in linguistic behavior as a function of changes in their conversation partner's fertility. We interpret these findings in the context of recent data suggesting that non-conforming behavior may be a means of men displaying their fitness as a mate to women. PMID:22347361

  3. Odd MECP2-mutated Rett variant-long-term follow-up profile to age 25.

    PubMed

    Hagberg, Bengt; Erlandsson, Anna; Kyllerman, Mårten; Larsson, Gunillla

    2003-01-01

    A 25-year-old MECP2-mutated female with odd developmental and dyspraxic/ataxic features, followed up through two decades, is reported. She does not fit either the classical Rett syndrome or the criteria required for any Rett variant phenotypes so far described. Nevertheless, she belongs clinically to the latter group. This case deserves attention in order, among other things, to provide important clues to better understand the puzzling battery of neuroimpairments and behavioural abnormalities met in classical Rett phenotypes and Rett variants defined thus far. PMID:14623222

  4. Autistic disorder symptoms in Rett syndrome.

    PubMed

    Wulffaert, Josette; Van Berckelaer-Onnes, Ina A; Scholte, Evert M

    2009-11-01

    According to the major classification systems it is not possible to diagnose a comorbid autistic disorder in persons with Rett syndrome. However, this is a controversial issue, and given the level of functioning of persons with Rett syndrome, the autistic disorder is expected to be present in a comparable proportion as in people with the same level of functioning. To investigate, parents of 52 females with classical and atypical Rett syndrome (2.4-49.3 years) completed the Developmental Behavior Checklist (DBC), the Diagnostic Interview for Social and Communication Disorders (DISCO) and the Dutch Vineland Screener 0-6 (VS 0-6). All participants had a severe to profound intellectual disability (ID) according to the VS 0-6. Behavior indicated an autistic disorder in 42 (DBC) to 58 percent (DISCO) of the Rett cases. Autistic behavior had decreased in 19 percent such that they no longer met the criteria for autistic disorder. Some participants were suspected of having a comorbid autistic disorder, though not more often than can be expected at their level of functioning. Clinicians should be aware of the possibility of a comorbid autistic disorder as much as they should be in other people with this level of functioning.

  5. The trajectories of sleep disturbances in Rett syndrome.

    PubMed

    Wong, Kingsley; Leonard, Helen; Jacoby, Peter; Ellaway, Carolyn; Downs, Jenny

    2015-04-01

    Rett syndrome is a rare neurodevelopmental disorder usually affecting females, and is associated with a mutation in the MECP2 gene. Sleep problems occur commonly and we investigated the trajectories and influences of age, mutation and treatments. Data were collected at six time points over 12 years from 320 families registered with the Australian Rett Syndrome Database. Regression analysis was used to investigate relationships between sleep disturbances, age, mutation type and use of treatment, and latent class growth analysis was performed to identify sleep problem phenotypes and model the effect of mutation type. The age range of subjects was 2.0-35.8 years. The study showed that sleep problems occurred in more than 80% of individuals and the prevalence decreased with age. Night laughing and night screaming occurred in 77 and 49%, respectively, when younger. Those with a large deletion had a higher prevalence of night laughing, which often occurred frequently. Treatment was associated with a 1.7% reduction in risk of further sleep problems. High and low baseline prevalence groups were identified. Approximately three-quarters of girls and women with sleep disturbances were in the high baseline group and problems persisted into adulthood. Conversely, 57% with night laughing and 42% with night screaming in the high baseline group exhibited mild improvement over time. Mutation type was not found to be a significant predictor of group membership. In conclusion, the evolution of sleep problems differed between subgroups of girls and women with Rett syndrome, in part explained by age and genotype. Treatment was not associated with improvement in sleep problems.

  6. The Preserved Speech Variant: A Subgroup of the Rett Complex: A Clinical Report of 30 Cases.

    ERIC Educational Resources Information Center

    Zappella, Michele; Gillberg, Christopher; Ehlers, Stephan

    1998-01-01

    Thirty females (ages 5-28) with autism also had many features of classic Rett syndrome (RS). The course of the disorder was more benign that in classic RS. A category of "Rett Complex" is proposed in which individuals have classic RS, but have a preserved speech variant. (Author/CR)

  7. Perceptual adaptation affects attractiveness of female bodies.

    PubMed

    Winkler, Christopher; Rhodes, Gillian

    2005-05-01

    We investigated whether short durations (5 minutes) of exposure to distorted bodies can change subsequent perceptions of attractiveness and normality. Participants rated 110 female bodies, varying in width, on either their attractiveness or normality before and after exposure to either extremely narrow (-50% of original width in Experiments 1 and 2) or extremely wide bodies (+50% of original width in Experiment 1, and +70% of original width in Experiment 2). In both experiments, the most attractive and most normal looking bodies became significantly and substantially narrower after exposure to narrow bodies. The most normal looking body changed significantly after exposure to wide bodies, but the most attractive body did not. These results show that perceptions of body attractiveness can be influenced by experience, but that there is an asymmetry between the effects of exposure to narrow and wide bodies. We consider a possible mechanism for this unexpected asymmetry, as well as possible implications for the effects of media exposure on body-image. The most attractive body shape was consistently narrower than the most normal looking body shape. Substantial changes in what looked normal were accompanied by congruent changes in what looked attractive, suggesting that a normal or average body shape may function as a reference point against which body attractiveness is judged. PMID:15969827

  8. X inactivation in Rett syndrome: A preliminary study showing partial preferential inactivation of paternal X with the M27{beta} probe

    SciTech Connect

    Camus, P.; Abbadi, N.; Gilgenkrantz, S.

    1994-04-15

    Rett syndrome (RS) is a severe progressive neurological disorder occurring exclusively in females. Most cases are sporadic. The few familial cases (less than 1%) cannot be explained by a simple mode of inheritance. Several hypotheses have been proposed: X-linked male lethal mutation, maternal uniparental disomy, fresh mutation on the X chromosome, involvement of mitochondrial DNA and differential inactivation with metabolic interference of X-borne alleles. The authors have examined the pattern of X inactivation in 10 affected girls who were selected according to the clinical criteria previously described and accepted by the French Rett Scientific Committee. The X inactivation pattern was studied by analysis of methylation at the hypervariable locus DXS255 with the M27{beta} probe. The results show a more-or-less skewed inactivation of paternal X in 8 Rett females, and 2 cases of symmetrical inactivation. In control girls, inactivation was symmetrical cases and the maternal X has been preferentially inactivated in the other 2 cases. In no case was a total skewed inactivation observed. Though there was clear evidence for a preferential paternal X inactivation that was statistically significant further studies are necessary to establish a relationship between X inactivation pattern and Rett syndrome.

  9. Rett syndrome: disruption of epigenetic control of postnatal neurological functions.

    PubMed

    Pohodich, Amy E; Zoghbi, Huda Y

    2015-10-15

    Loss-of-function mutations in the X-linked gene Methyl-CpG-binding protein 2 (MECP2) cause a devastating pediatric neurological disorder called Rett syndrome. In males, these mutations typically result in severe neonatal encephalopathy and early lethality. On the other hand, owing to expression of the normal allele in ∼50% of cells, females do not suffer encephalopathy but instead develop Rett syndrome. Typically females with Rett syndrome exhibit a delayed onset of neurologic dysfunction that manifests around the child's first birthday and progresses over the next few years. Features of this disorder include loss of acquired language and motor skills, intellectual impairment and hand stereotypies. The developmental regression observed in patients with Rett syndrome arises from altered neuronal function and is not the result of neurodegeneration. Maintenance of an appropriate level of MeCP2 appears integral to the function of healthy neurons as patients with increased levels of MeCP2, owing to duplication of the Xq28 region encompassing the MECP2 locus, also present with intellectual disability and progressive neurologic symptoms. Despite major efforts over the past two decades to elucidate the molecular functions of MeCP2, the mechanisms underlying the delayed appearance of symptoms remain unclear. In this review, we will highlight recent findings that have expanded our knowledge of MeCP2's functions, and we will discuss how epigenetic regulation, chromatin organization and circuit dynamics may contribute to the postnatal onset of Rett syndrome.

  10. Social isolation during puberty affects female sexual behavior in mice.

    PubMed

    Kercmar, Jasmina; Tobet, Stuart A; Majdic, Gregor

    2014-01-01

    Exposure to stress during puberty can lead to long-term behavioral alterations in adult rodents coincident with sex steroid hormone-dependent brain remodeling and reorganization. Social isolation is a stress for social animals like mice, but little is known about the effects of such stress during adolescence on later reproductive behaviors. The present study examined sexual behavior of ovariectomized, estradiol and progesterone primed female mice that were individually housed from 25 days of age until testing at approximately 95 days, or individually housed from day 25 until day 60 (during puberty), followed by housing in social groups. Mice in these isolated groups were compared to females that were group housed throughout the experiment. Receptive sexual behaviors of females and behaviors of stimulus males were recorded. Females housed in social groups displayed greater levels of receptive behaviors in comparison to both socially isolated groups. Namely, social females had higher lordosis quotients (LQs) and more often displayed stronger lordosis postures in comparison to isolated females. No differences between female groups were observed in stimulus male sexual behavior suggesting that female "attractiveness" was not affected by their social isolation. Females housed in social groups had fewer cells containing immunoreactive estrogen receptor (ER) α in the anteroventral periventricular nucleus (AVPV) and in the ventromedial nucleus of the hypothalamus (VMH) than both isolated groups. These results suggest that isolation during adolescence affects female sexual behavior and re-socialization for 1 month in adulthood is insufficient to rescue lordosis behavior from the effects of social isolation during the pubertal period.

  11. Brief Report: Systematic Review of Rett Syndrome in Males

    ERIC Educational Resources Information Center

    Reichow, Brian; George-Puskar, Annie; Lutz, Tara; Smith, Isaac C.; Volkmar, Fred R.

    2015-01-01

    Rett syndrome (RTT) is a neurogenetic disorder in which a period of typical development is followed by loss of previously acquired skills. Once thought to occur exclusively in females, increasing numbers of male cases of RTT have been reported. This systematic review included 36 articles describing 57 cases of RTT in males. Mutations of the MECP2…

  12. Spectrum of MECP2 gene mutations in a cohort of Indian patients with Rett syndrome: report of two novel mutations.

    PubMed

    Das, Dhanjit Kumar; Raha, Sarbani; Sanghavi, Daksha; Maitra, Anurupa; Udani, Vrajesh

    2013-02-15

    Rett syndrome (RTT) is an X-linked neurodevelopmental disorder, primarily affecting females and characterized by developmental regression, epilepsy, stereotypical hand movements, and motor abnormalities. Its prevalence is about 1 in 10,000 female births. Rett syndrome is caused by mutations within methyl CpG-binding protein 2 (MECP2) gene. Over 270 individual nucleotide changes which cause pathogenic mutations have been reported. However, eight most commonly occurring missense and nonsense mutations account for almost 70% of all patients. We screened 90 individuals with Rett syndrome phenotype. A total of 19 different MECP2 mutations and polymorphisms were identified in 27 patients. Of the 19 mutations, we identified 7 (37%) frameshift, 6 (31%) nonsense, 14 (74%) missense mutations and one duplication (5%). The most frequent pathogenic changes were: missense p.T158M (11%), p.R133C (7.4%), and p.R306C (7.4%) and nonsense p.R168X (11%), p.R255X (7.4%) mutations. We have identified two novel mutations namely p.385-388delPLPP present in atypical patients and p.Glu290AlafsX38 present in a classical patient of Rett syndrome. Sequence homology for p.385-388delPLPP mutation revealed that these 4 amino acids were conserved across mammalian species. This indicated the importance of these 4 amino acids in structure and function of the protein. A novel variant p.T479T has also been identified in a patient with atypical Rett syndrome. A total of 62 (69%) patients remained without molecular genetics diagnosis that necessitates further search for mutations in other genes like CDKL5 and FOXG1 that are known to cause Rett phenotype. The majority of mutations are detected in exon 4 and only one mutation was present in exon 3. Therefore, our study suggests the need for screening exon 4 of MECP2 as first line of diagnosis in these patients.

  13. The Quality of Life in Girls with Rett Syndrome.

    PubMed

    Parisi, Lucia; Di Filippo, Teresa; Roccella, Michele

    2016-05-18

    Nowadays, quality of life is receiving an increasing attention in all scientific areas. Rett syndrome (RTT) is a rare neurological development, affecting mainly females. The congenital disease affects the central nervous system, and is one of the most common causes of severe intellectual disability. The aim of our study is to evaluate the effect of RTT on the quality of life of people who are affected. Both parents of 18 subjects, all female, diagnosed with RTT, took part in the research. Quality of life was assessed using the Italian version of the Impact of Childhood Illness Scale. This scale consists of 30 questions that investigate the effect of illness on children, parents and families. For each question, the parent was asked to rate two variables: frequency and importance. Another questionnaire was administered to obtain medical history, diagnostic and therapeutic data of the persons with RTT. Our data show that RTT has a considerable impact on both the child's development and the entire family. Parents' answers demonstrated that their child's illness had consequences for the child and how the family coped with it. For this reason, attention should be directed at psychological and social aspects, as well as attitudes, manners, reactions and effects such disturbances can have on the entire family. PMID:27403274

  14. The Quality of Life in Girls with Rett Syndrome

    PubMed Central

    Parisi, Lucia; Di Filippo, Teresa; Roccella, Michele

    2016-01-01

    Nowadays, quality of life is receiving an increasing attention in all scientific areas. Rett syndrome (RTT) is a rare neurological development, affecting mainly females. The congenital disease affects the central nervous system, and is one of the most common causes of severe intellectual disability. The aim of our study is to evaluate the effect of RTT on the quality of life of people who are affected. Both parents of 18 subjects, all female, diagnosed with RTT, took part in the research. Quality of life was assessed using the Italian version of the Impact of Childhood Illness Scale. This scale consists of 30 questions that investigate the effect of illness on children, parents and families. For each question, the parent was asked to rate two variables: frequency and importance. Another questionnaire was administered to obtain medical history, diagnostic and therapeutic data of the persons with RTT. Our data show that RTT has a considerable impact on both the child’s development and the entire family. Parents’ answers demonstrated that their child’s illness had consequences for the child and how the family coped with it. For this reason, attention should be directed at psychological and social aspects, as well as attitudes, manners, reactions and effects such disturbances can have on the entire family. PMID:27403274

  15. Examination of X chromosome markers in Rett syndrome: exclusion mapping with a novel variation on multilocus linkage analysis.

    PubMed Central

    Ellison, K A; Fill, C P; Terwilliger, J; DeGennaro, L J; Martin-Gallardo, A; Anvret, M; Percy, A K; Ott, J; Zoghbi, H

    1992-01-01

    Rett syndrome is a neurologic disorder characterized by early normal development followed by regression, acquired deceleration of head growth, autism, ataxia, and stereotypic hand movements. The exclusive occurrence of the syndrome in females and the occurrence of a few familial cases with inheritance through maternal lines suggest that this disorder is most likely secondary to a mutation on the X chromosome. To address this hypothesis and to identify candidate regions for the Rett syndrome gene locus, genotypic analysis was performed in two families with maternally related affected half-sisters by using 63 DNA markers from the X chromosome. Maternal and paternal X chromosomes from the affected sisters were separated in somatic cell hybrids and were examined for concordance/discordance of maternal alleles at the tested loci. Thirty-six markers were informative in at least one of the two families, and 25 markers were informative in both families. Twenty loci were excluded as candidates for the Rett syndrome gene, on the basis of discordance for maternal alleles in the half-sisters. Nineteen of the loci studied were chosen for multipoint linkage analysis because they have been previously genetically mapped using a large number of meioses from reference families. Using the exclusion criterion of a lod score less than -2, we were able to exclude the region between the Duchenne muscular dystrophy locus and the DXS456 locus. This region extends from Xp21.2 to Xq21-q23. The use of the multipoint linkage analysis approach outlined in this study should allow the exclusion of additional regions of the X chromosome as new markers are analyzed. This in turn will result in a defined region of the X chromosome that should be searched for candidate sequences for the Rett syndrome gene in both familial and sporadic cases. Images Figure 2 PMID:1734712

  16. Divorce in families of children with Down Syndrome or Rett Syndrome.

    PubMed

    Lederman, Vivian Renne Gerber; Alves, Bianca dos Santos; Negrão, Juliana; Maria, Juliana Negrão; Schwartzman, José Salomão; D'Antino, Maria Eloisa Famá; Brunoni, Decio

    2015-05-01

    This study evaluates the impact in the stability and management of the marriage of parents of a child with Down or Rett Syndrome. Morbidity of the syndromes and the marital status of the couples before and after the birth of the affected children were considered variables. The divorce rate in families with Down syndrome was 10%, similar to the Brazilian rate population. In Rett Syndrome, the divorce rate was significantly higher, 23.5%. The higher morbidity of Rett Syndrome, and the moment of diagnosis could be relevant factors for the increased divorce rate related to this syndrome.

  17. Divorce in families of children with Down Syndrome or Rett Syndrome.

    PubMed

    Lederman, Vivian Renne Gerber; Alves, Bianca dos Santos; Negrão, Juliana; Maria, Juliana Negrão; Schwartzman, José Salomão; D'Antino, Maria Eloisa Famá; Brunoni, Decio

    2015-05-01

    This study evaluates the impact in the stability and management of the marriage of parents of a child with Down or Rett Syndrome. Morbidity of the syndromes and the marital status of the couples before and after the birth of the affected children were considered variables. The divorce rate in families with Down syndrome was 10%, similar to the Brazilian rate population. In Rett Syndrome, the divorce rate was significantly higher, 23.5%. The higher morbidity of Rett Syndrome, and the moment of diagnosis could be relevant factors for the increased divorce rate related to this syndrome. PMID:26017939

  18. Dysregulated brain immunity and neurotrophin signaling in Rett syndrome and autism spectrum disorders.

    PubMed

    Theoharides, Theoharis C; Athanassiou, Marianna; Panagiotidou, Smaro; Doyle, Robert

    2015-02-15

    Rett syndrome is a neurodevelopmental disorder, which occurs in about 1:15,000 females and presents with neurologic and communication defects. It is transmitted as an X-linked dominant linked to mutations of the methyl-CpG-binding protein (MeCP2), a gene transcription suppressor, but its definitive pathogenesis is unknown thus hindering development of effective treatments. Almost half of children with Rett syndrome also have behavioral symptoms consistent with those of autism spectrum disorders (ASDs). PubMed was searched (2005-2014) using the terms: allergy, atopy, brain, brain-derived neurotrophic factor (BDNF), corticotropin-releasing hormone (CRH), cytokines, gene mutations, inflammation, mast cells (MCs), microglia, mitochondria, neurotensin (NT), neurotrophins, seizures, stress, and treatment. There are a number of intriguing differences and similarities between Rett syndrome and ASDs. Rett syndrome occurs in females, while ASDs more often in males, and the former has neurologic disabilities unlike ASDs. There is evidence of dysregulated immune system early in life in both conditions. Lack of microglial phagocytosis and decreased levels of BDNF appear to distinguish Rett syndrome from ASDs, in which there is instead microglia activation and/or proliferation and possibly defective BDNF signaling. Moreover, brain mast cell (MC) activation and focal inflammation may be more prominent in ASDs than Rett syndrome. The flavonoid luteolin blocks microglia and MC activation, provides BDNF-like activity, reverses Rett phenotype in mouse models, and has a significant benefit in children with ASDs. Appropriate formulations of luteolin or other natural molecules may be useful in the treatment of Rett syndrome.

  19. Does Ramadan Fasting Adversely Affect Cognitive Function in Young Females?

    PubMed Central

    Ghayour Najafabadi, Mahboubeh; Rahbar Nikoukar, Laya; Memari, Amir; Ekhtiari, Hamed; Beygi, Sara

    2015-01-01

    We examined the effects of Ramadan fasting on cognitive function in 17 female athletes. Data were obtained from participants of two fasting (n = 9) and nonfasting (n = 8) groups at three periods of the study (before Ramadan, at the third week in Ramadan, and after Ramadan). Digit span test (DST) and Stroop color test were employed to assess short-term memory and inhibition/cognitive flexibility at each time point. There were no significant changes for DST and Stroop task 1 in both groups, whereas Stroop task 2 and task 3 showed significant improvements in Ramadan condition (p < 0.05). Interference indices did not change significantly across the study except in post-Ramadan period of fasting group (p < 0.05). Group × week interaction was significant only for error numbers (p < 0.05). Athletes in nonfasting showed a significant decrease in number of errors in Ramadan compared to baseline (p < 0.05). The results suggest that Ramadan fasting may not adversely affect cognitive function in female athletes. PMID:26697263

  20. Developmental Dynamics of Rett Syndrome

    PubMed Central

    Feldman, Danielle; Banerjee, Abhishek; Sur, Mriganka

    2016-01-01

    Rett Syndrome was long considered to be simply a disorder of postnatal development, with phenotypes that manifest only late in development and into adulthood. A variety of recent evidence demonstrates that the phenotypes of Rett Syndrome are present at the earliest stages of brain development, including developmental stages that define neurogenesis, migration, and patterning in addition to stages of synaptic and circuit development and plasticity. These phenotypes arise from the pleotropic effects of MeCP2, which is expressed very early in neuronal progenitors and continues to be expressed into adulthood. The effects of MeCP2 are mediated by diverse signaling, transcriptional, and epigenetic mechanisms. Attempts to reverse the effects of Rett Syndrome need to take into account the developmental dynamics and temporal impact of MeCP2 loss. PMID:26942018

  1. Social preferences in Rett syndrome.

    PubMed

    Djukic, Aleksandra; McDermott, Maria Valicenti

    2012-04-01

    Children with Rett syndrome manifest profound impairments in their ability to speak and use their hands, and exhibit a very limited repertoire of abilities to express themselves, to be neuropsychologically tested, and consequently to be understood. This study examined nonverbal cognitive abilities and visual preferences by analyzing the pattern of visual fixation in 49 girls with Rett syndrome, compared with a group of typical control subjects. The girls with Rett syndrome demonstrated a tendency toward socially weighted stimuli/social preferences. They looked at people, and into people's eyes. Eye tracking represents a feasible method to assess cognition, and provide insights into the burden of isolation of these children and the mismatch between their social preferences and incompetence, caused by movement disorder and apraxia. PMID:22490770

  2. How to prevent small stature in Rett syndrome-associated collapsing spine syndrome.

    PubMed

    Thorey, Fritz; Jäger, Marcus; Seller, Konrad; Wild, Alexander; Adam, Rüdiger A; Krauspe, Rüdiger

    2007-04-01

    Severe scoliosis in Rett syndrome is an important orthopedic, neurologic, and pediatric problem. The curve in Rett syndrome is of a neurologic type, has its highest incidence during early childhood, and shows rapid progression. In this study, the authors report the results of a 4-year follow-up of a 10-year-old Rett syndrome female patient with early onset and severe rapid progressive thoracolumbar scoliosis. The first signs of spinal deformity were documented at age 3 years. During adolescence, the patient developed a 115-degree thoracolumbal scoliosis with reduced respiratory volume due to a collapsing spine syndrome. To stop this life-threatening progression of the curve, the patient was treated by a 2-stage surgical procedure. The combination of an anterior release, halo traction, and posterior instrumented fusion from Th3 to L5 using a computer-assisted technique was performed. An excellent reduction of the deformity was achieved (postoperative 24-degree Cobb angle). After 4 years, the authors found a radiologically solid spinal fusion and no progression of the deformity. Operative treatment regimes and etiology of severe spinal deformities in Rett syndrome were discussed. The high perioperative risks in Rett syndrome patients who underwent spinal surgery may be reduced by an early cooperation between orthopedic and pediatric specialists. When considering recent data from literature, it can be concluded that an early correction of spine deformities in Rett syndrome patients may prevent a life-threatening collapsing spine syndrome.

  3. Rett syndrome: clinical review and genetic update

    PubMed Central

    Weaving, L; Ellaway, C; Gecz, J; Christodoulou, J

    2005-01-01

    Rett syndrome (RS) is a severe neurodevelopmental disorder that contributes significantly to severe intellectual disability in females worldwide. It is caused by mutations in MECP2 in the majority of cases, but a proportion of atypical cases may result from mutations in CDKL5, particularly the early onset seizure variant. The relationship between MECP2 and CDKL5, and whether they cause RS through the same or different mechanisms is unknown, but is worthy of investigation. Mutations in MECP2 appear to give a growth disadvantage to both neuronal and lymphoblast cells, often resulting in skewing of X inactivation that may contribute to the large degree of phenotypic variation. MeCP2 was originally thought to be a global transcriptional repressor, but recent evidence suggests that it may have a role in regulating neuronal activity dependent expression of specific genes such as Hairy2a in Xenopus and Bdnf in mouse and rat. PMID:15635068

  4. Communication Abilities and Rett Syndrome.

    ERIC Educational Resources Information Center

    Woodyatt, Gail; Ozanne, Anne

    1992-01-01

    The communicative behaviors of 6 girls with Rett syndrome (ages 2-13) were evaluated. Findings indicated that all subjects were at a preintentional level of communication, which was consistent with their profound intellectual disability and their lack of demonstration of "means-end" behavior beyond Piagetian Sensorimotor Stage III. (Author/DB)

  5. Socio-Economic Affects of Floods on Female Teachers in Jampur (Pakistan)

    ERIC Educational Resources Information Center

    Buzdar, Muhammad Ayub; Ali, Akhtar

    2011-01-01

    Women are major affected segment of society in any disaster in under developed countries. Floods of 2010, in Pakistan, affected more than 17 million people. Ultimately, it created several social, psychological and financial problems for affected females. The current paper aimed to study the socio-economic affects of floods on female teachers of…

  6. Mutational analysis of methyl-CpG binding protein 2 (MECP2) gene in Indian cases of Rett syndrome.

    PubMed

    Das, Dhanjit Kumar; Udani, Vrajesh; Sanghavi, Daksha; Adhia, Rashmi; Maitra, Anurupa

    2013-03-01

    Rett syndrome (RTT) is an X-linked postnatal neurological disorder, primarily affecting females and characterized by regression, epilepsy, stereotypical hand movements, and motor abnormalities. Its prevalence is about 1 in 10,000 female births. RTT is caused by mutations within methyl CpG-binding protein 2 (MECP2) gene. Over 200 individual nucleotide changes in the gene, which cause pathogenic mutations, have been reported; however, eight most commonly occurring missense and nonsense mutations account for almost 70% of all mutations. RTT cases have also been reported from India. The phenotype (classical and atypical inclusive) has many differentials. However, a genetically based confirmed diagnosis would help in management and counseling. In this pilot study we have analyzed MECP2 mutations in ten Indian sporadic patients diagnosed clinically as having RTT. Two mutations and one novel variant in MECP2 have been detected. Missense mutations p.R133C and c.806delG have been detected. The missence mutation p.R133C was the part of eight hotspots reported in Rett patients. This patient met all the essential criteria except delayed onset of regression. The other c.806delG mutation positive patient also fulfilled all the obligatory criteria of classical RTT. Another clinically atypical Rett patient showed a novel mutation p.C339S in MECP2 gene. The preliminary result necessitates a large-scale study of RTT patients to determine more precisely the influence of MECP2 mutations in Indian patients and their correlation with clinical phenotypes.

  7. How multiple mating by females affects sexual selection

    PubMed Central

    Shuster, Stephen M.; Briggs, William R.; Dennis, Patricia A.

    2013-01-01

    Multiple mating by females is widely thought to encourage post-mating sexual selection and enhance female fitness. We show that whether polyandrous mating has these effects depends on two conditions. Condition 1 is the pattern of sperm utilization by females; specifically, whether, among females, male mating number, m (i.e. the number of times a male mates with one or more females) covaries with male offspring number, o. Polyandrous mating enhances sexual selection only when males who are successful at multiple mating also sire most or all of each of their mates' offspring, i.e. only when Cov♂(m,o), is positive. Condition 2 is the pattern of female reproductive life-history; specifically, whether female mating number, m, covaries with female offspring number, o. Only semelparity does not erode sexual selection, whereas iteroparity (i.e. when Cov♀(m,o), is positive) always increases the variance in offspring numbers among females, which always decreases the intensity of sexual selection on males. To document the covariance between mating number and offspring number for each sex, it is necessary to assign progeny to all parents, as well as identify mating and non-mating individuals. To document significant fitness gains by females through iteroparity, it is necessary to determine the relative magnitudes of male as well as female contributions to the total variance in relative fitness. We show how such data can be collected, how often they are collected, and we explain the circumstances in which selection favouring multiple mating by females can be strong or weak. PMID:23339237

  8. How Culture Affects Female Inequality across Countries: An Empirical Study

    ERIC Educational Resources Information Center

    Cheung, Hoi Yan; Chan, Alex W. H.

    2007-01-01

    Many studies have commented that culture has an influence on gender inequality. However, few studies have provided data that could be used to investigate how culture actually influences female inequality. One of the aims of this study is to investigate whether Hofstede's cultural dimensions have an impact on female inequality in education in terms…

  9. Factors Affecting Drug Abuse in Adolescent Females in Rural Communities

    ERIC Educational Resources Information Center

    Renes, Susan L.; Strange, Anthony T.

    2009-01-01

    This article explores factors influencing adolescent female substance use in rural communities. Self-reported data gathered from females 12 to 15 years of age in two northwestern communities in the United States showed an association among gender identity, peer and parental relationships, and substance use. Aggressive masculinity had the strongest…

  10. Aspects of speech-language abilities are influenced by MECP2 mutation type in girls with Rett syndrome.

    PubMed

    Urbanowicz, Anna; Downs, Jenny; Girdler, Sonya; Ciccone, Natalie; Leonard, Helen

    2015-02-01

    This study investigates relationships between methyl-CpG-binding protein 2 gene (MECP2) mutation type and speech-language abilities in girls with Rett syndrome. Cross-sectional data on 766 girls, aged 15 years and under, with genetically confirmed Rett syndrome was obtained from the Australian Rett Syndrome Database (ARSD) (n = 244) and the International Rett Syndrome Phenotype Database (InterRett) (n = 522). Relationships between MECP2 mutation type and age of regression in speech-language abilities, and the level of speech-language abilities before and after this regression were investigated. The females had a median age of 4.95 years in the ARSD and 5.25 years in InterRett. The majority (89%, 685/766) acquired speech-language abilities in the form of babble or words at some point in time. Of those who acquired babble or words, 85% (581/685) experienced a regression in these abilities. Those with a p.Arg133Cys mutation were the most likely to use one or more words, prior to (RRR = 3.45; 95% CI 1.15-10.41) and after (RRR = 5.99; 95% CI 2.00-17.92), speech-language regression. Girls with Rett syndrome vary in their use of speech and language, and in their experience of speech-language regression and these variations are partly explained by genotype.

  11. Binge drinking differentially affects adolescent male and female brain morphometry

    PubMed Central

    Squeglia, Lindsay M.; Sorg, Scott F.; Schweinsburg, Alecia Dager; Wetherill, Reagan R.; Pulido, Carmen; Tapert, Susan F.

    2012-01-01

    Rationale Adolescent binge drinking is concerning, as important neurodevelopments occur during this stage. Previous research suggests that binge drinking may disrupt typical brain development, and females may be particularly vulnerable. Objectives We used magnetic resonance imaging (MRI) to examine cortical thickness in adolescent females and males with and without histories of binge drinking. Methods Participants (N=59) were 16–19-year-old adolescents recruited from local schools. Recent binge drinkers (n=29, 48% female) were matched to non-drinkers (n=30, 50% female) on age, gender, pubertal development, and familial alcoholism. Participants completed a neuropsychological battery and MRI session. Cortical surfaces were reconstructed with FreeSurfer. Results Binge × gender interactions (p<.05) were seen for cortical thickness in four left frontal regions: frontal pole, pars orbitalis, medial orbital frontal, and rostral anterior cingulate. For all interactions, female bingers had thicker cortices than female controls, while male bingers had thinner cortices than male controls. Thicker left frontal cortices corresponded with poorer visuospatial, inhibition, and attention performances for female bingers (r=−0.69 to 0.50, p<0.05) and worse attention for male bingers (r=−0.69, p=0.005). Conclusions Adolescent females with recent binge drinking showed ~8% thicker cortices in left frontal regions than demographically similar female non-drinkers, which was linked to worse visuospatial, inhibition, and attention performances. In contrast, adolescent binge-drinking males showed ~7% thinner cortices in these areas than non-drinking males. These cross-sectional data suggest either different gray matter risk factors for males as for females toward developing heavy drinking, or differential adverse sequelae. PMID:21952669

  12. MECP2 deletions and genotype-phenotype correlation in Rett syndrome.

    PubMed

    Scala, Elisa; Longo, Ilaria; Ottimo, Federica; Speciale, Caterina; Sampieri, Katia; Katzaki, Eleni; Artuso, Rosangela; Mencarelli, Maria Antonietta; D'Ambrogio, Tatiana; Vonella, Giuseppina; Zappella, Michele; Hayek, Giuseppe; Battaglia, Agatino; Mari, Francesca; Renieri, Alessandra; Ariani, Francesca

    2007-12-01

    Rett syndrome is a neurodevelopmental disorder that represents one of the most common genetic causes of mental retardation in girls. MECP2 point mutations in exons 2-4 account for about 80% of classic Rett cases and for a lower percentage of variant patients. We investigated the genetic cause in 77 mutation-negative Rett patients (33 classic, 31 variant, and 13 Rett-like cases) by searching missed MECP2 defects. DHPLC analysis of exon 1 and MLPA analysis allowed us to identify the defect in 17 Rett patients: one exon 1 point mutation (c.47_57del) in a classic case and 16 MECP2 large deletions (15/33 classic and 1/31 variant cases). One identical intragenic MECP2 deletion, probably due to gonadal mosaicism, was found in two sisters with discordant phenotype: one classic and one "highly functioning" preserved speech variant. This result indicates that other epigenetic or genetic factors, beside MECP2, may contribute to phenotype modulation. Three out of 16 MECP2 deletions extend to the adjacent centromeric IRAK1 gene. A putative involvement of the hemizygosity of this gene in the ossification process is discussed. Finally, results reported here clearly indicate that MECP2 large deletions are a common cause of classic Rett, and MLPA analysis is mandatory in MECP2-negative patients, especially in those more severely affected (P = 0.044).

  13. Recent insights into genotype-phenotype relationships in patients with Rett syndrome using a fine grain scale.

    PubMed

    Fabio, Rosa Angela; Colombo, Barbara; Russo, Silvia; Cogliati, Francesca; Masciadri, Maura; Foglia, Silvia; Antonietti, Alessandro; Tavian, Daniela

    2014-11-01

    Mutations in MECP2 gene cause Rett syndrome (RTT), a neurodevelopmental disorder affecting around 1 in 10,000 female births. The clinical picture of RTT appears quite heterogeneous for each single feature. Mutations in MECP2 gene have been associated with the onset of RTT. The most known gene function consists of transcriptional repression of specific target genes, mainly by the binding of its methyl binding domain (MBD) to methylated CpG nucleotides and recruiting co-repressors and histone deacetylase binding to DNA by its transcription repressor domain (TRD). This study aimed at evaluating a cohort of 114 Rett syndrome (RTT) patients with a detailed scale measuring the different kinds of impairments produced by the syndrome. The sample included relatively large subsets of the most frequent mutations, so that genotype-phenotype correlations could be tested. Results revealed that frequent missense mutations showed a specific profile in different areas of impairment. The R306C mutation, considered as producing mild impairment, was associated to a moderate phenotype in which behavioural characteristics were mainly affected. A notable difference emerged by comparing mutations truncating the protein before and after the nuclear localization signal; such a difference concerned prevalently the motor-functional and autonomy skills of the patients, affecting the management of everyday activities.

  14. Along came a spider who sat down beside her: Perceived predation risk, but not female age, affects female mate choosiness.

    PubMed

    Atwell, Ashley; Wagner, William E

    2015-06-01

    Organisms often exhibit behavioral plasticity in response to changes in factors, such as predation risk, mate density, and age. Particularly, female mate choosiness (the strength of female's attraction to male traits as they deviate from preferred trait values) has repeatedly been shown to be plastic. This is due to the costs associated with searching for preferred males fluctuating with changes in such factors. Because these factors can interact naturally, it is important to understand how female mate choosiness responds to these interactions. We studied the interaction between perceived predation risk and female age on the variable field cricket, Gryllus lineaticeps. Females were either exposed or not exposed to predation cues from a sympatric, cursorial, wolf spider predator, Hogna sp. We then tested the females at one of three adult ages and measured their choosiness by recording their responsiveness to a low quality male song. We found female choosiness plasticity was affected by neither age nor the interaction between age and perceived predation risk. Perceived predation risk was the only factor to significantly affect the plasticity of female mate choosiness: females were less choosy when they perceived predation risk and were more choosy when they did not. Predation may be such a strong source of selection that, regardless of differences in other factors, most individuals respond similarly. PMID:25857998

  15. Along came a spider who sat down beside her: Perceived predation risk, but not female age, affects female mate choosiness.

    PubMed

    Atwell, Ashley; Wagner, William E

    2015-06-01

    Organisms often exhibit behavioral plasticity in response to changes in factors, such as predation risk, mate density, and age. Particularly, female mate choosiness (the strength of female's attraction to male traits as they deviate from preferred trait values) has repeatedly been shown to be plastic. This is due to the costs associated with searching for preferred males fluctuating with changes in such factors. Because these factors can interact naturally, it is important to understand how female mate choosiness responds to these interactions. We studied the interaction between perceived predation risk and female age on the variable field cricket, Gryllus lineaticeps. Females were either exposed or not exposed to predation cues from a sympatric, cursorial, wolf spider predator, Hogna sp. We then tested the females at one of three adult ages and measured their choosiness by recording their responsiveness to a low quality male song. We found female choosiness plasticity was affected by neither age nor the interaction between age and perceived predation risk. Perceived predation risk was the only factor to significantly affect the plasticity of female mate choosiness: females were less choosy when they perceived predation risk and were more choosy when they did not. Predation may be such a strong source of selection that, regardless of differences in other factors, most individuals respond similarly.

  16. Progress in Rett Syndrome: from discovery to clinical trials.

    PubMed

    Percy, Alan K

    2016-09-01

    Fifty years ago, Andreas Rett described a disorder in 22 females featuring prominent regression of fine motor and communication skills, cognitive impairment, stereotypic movements, periodic breathing, and gait abnormalities. This disorder became known as Rett syndrome (RTT) following the report of Hagberg et al. in 1983. Although RTT was scarcely recognized at that time in the United States, here the efforts of Rett and Hagberg led to rapid progress in recognition and diagnosis, a clearer understanding of its clinical and pathological underpinnings, and, ultimately, identification of mutations in the methyl-CpG-binding protein 2 (MECP2) gene as the primary cause of this unique and challenging neurodevelopmental disorder. Thereafter, a natural history study and critical translational research in animal models paved the way for potential disease-modifying agents to be assessed in human clinical trials. To be successful, the energies of the international community at all levels, including researchers in clinical and basic science, funding agencies, pharmaceutical companies, patient advocates, and, above all, parents and their children are essential. Otherwise, hopes for effective treatment, if not, a cure, will remain unfulfilled. PMID:27491553

  17. Progress in Rett Syndrome: from discovery to clinical trials.

    PubMed

    Percy, Alan K

    2016-09-01

    Fifty years ago, Andreas Rett described a disorder in 22 females featuring prominent regression of fine motor and communication skills, cognitive impairment, stereotypic movements, periodic breathing, and gait abnormalities. This disorder became known as Rett syndrome (RTT) following the report of Hagberg et al. in 1983. Although RTT was scarcely recognized at that time in the United States, here the efforts of Rett and Hagberg led to rapid progress in recognition and diagnosis, a clearer understanding of its clinical and pathological underpinnings, and, ultimately, identification of mutations in the methyl-CpG-binding protein 2 (MECP2) gene as the primary cause of this unique and challenging neurodevelopmental disorder. Thereafter, a natural history study and critical translational research in animal models paved the way for potential disease-modifying agents to be assessed in human clinical trials. To be successful, the energies of the international community at all levels, including researchers in clinical and basic science, funding agencies, pharmaceutical companies, patient advocates, and, above all, parents and their children are essential. Otherwise, hopes for effective treatment, if not, a cure, will remain unfulfilled.

  18. IgA Antibodies in Rett Syndrome

    ERIC Educational Resources Information Center

    Reichelt, K. L.; Skjeldal, O.

    2006-01-01

    The level of IgA antibodies to gluten and gliadin proteins found in grains and to casein found in milk, as well as the level of IgG to gluten and gliadin, have been examined in 23 girls with Rett syndrome and 53 controls. Highly statistically significant increases were found for the Rett population compared to the controls. The reason for this…

  19. Autistic Disorder Symptoms in Rett Syndrome

    ERIC Educational Resources Information Center

    Wulffaert, Josette; Van Berckelaer-Onnes, Ina A.; Scholte, Evert M.

    2009-01-01

    According to the major classification systems it is not possible to diagnose a comorbid autistic disorder in persons with Rett syndrome. However, this is a controversial issue, and given the level of functioning of persons with Rett syndrome, the autistic disorder is expected to be present in a comparable proportion as in people with the same…

  20. Towards a Behavioral Phenotype for Rett Syndrome.

    ERIC Educational Resources Information Center

    Mount, Rebecca H.; Hastings, Richard P.; Reilly, Sheena; Cass, Hilary; Charman, Tony

    2003-01-01

    A study compared 143 girls (ages 6-14) with Rett syndrome with 85 girls with severe mental retardation on the Developmental Behavior Checklist. Girls with Rett syndrome presented more "autistic relating" and fewer antisocial behaviors. When compared to children with autism, they did not present with classic autistic behavioral features. (Contains…

  1. Rett Syndrome: Of Girls and Mice--Lessons for Regression in Autism

    ERIC Educational Resources Information Center

    Glaze, Daniel G.

    2004-01-01

    Rett syndrome (RTT) is a neurodevelopmental disorder occurring almost exclusively in females. Regression is a defining feature of RTT. During the regression stage, RTT girls display many autistic features, such as loss of communication and social skills, poor eye contact, and lack of interest, and initially may be given the diagnosis of autism.…

  2. Fostering Environmental Control in a Young Child with Rett Syndrome: A Case Study.

    ERIC Educational Resources Information Center

    Sullivan, Margaret Wolan; And Others

    The progress of a 4-year-old child with Rett Syndrome (a developmental disability resulting in severe mental and physical deficits in female children) in learning simple environmental control over an 18-month-period is described. A systematic program providing for contingency control of toys and music via switches was provided in the child's…

  3. Use of Equipment and Respite Services and Caregiver Health among Australian Families Living with Rett Syndrome

    ERIC Educational Resources Information Center

    Urbanowicz, Anna; Downs, Jenny; Bebbington, Ami; Jacoby, Peter; Girdler, Sonya; Leonard, Helen

    2011-01-01

    This study assessed factors that could influence equipment and respite services use among Australian families caring for a girl/woman with Rett syndrome and examined relationships between use of these resources and the health of female caregivers. Data was sourced from questionnaires completed by families (n=170) contributing to the Australian…

  4. The Rett Syndrome Complex: Communicative Functions in Relation to Developmental Level and Autistic Features.

    ERIC Educational Resources Information Center

    Sandberg, Annika Dahlgren; Ehlers, Stephan; Hagberg, Bengt; Gillberg, Christopher

    2000-01-01

    Communicative functions, overall developmental level, and autistic features were studied in eight females (ages 11-36) with Rett Syndrome. Low levels of communicative abilities and overall functioning were demonstrated, and joint attention behaviors and expression of communicative intent were rare. Six subjects, however, showed clear examples of…

  5. Coaching Communication Partners: A Preliminary Investigation of Communication Intervention during Mealtime in Rett Syndrome

    ERIC Educational Resources Information Center

    Bartolotta, Theresa E.; Remshifski, Patricia A.

    2013-01-01

    Rett syndrome (RTT) occurs primarily in females and is characterized by deficits in cognition, communication, hand use and ambulation. This quasi-experimental study explored the use of a coaching program to increase communicative interactions between girls with RTT and their communication partners. Communication coaching strategies were provided…

  6. The Borderland of Autism and Rett Syndrome: Five Case Histories to Highlight Diagnostic Difficulties.

    ERIC Educational Resources Information Center

    Gillberg, Christopher

    1989-01-01

    Case studies of 4 females and 1 male, aged 6-25, with pervasive developmental disorders are described. All met standard diagnostic criteria for autism and showed many Rett syndrome symptoms. It is concluded that there is considerable overlap between the 2 disorders and that symptomatic similarities might mirror common pathopsychological…

  7. Improving Functional Skills and Physical Fitness in Children with Rett Syndrome

    ERIC Educational Resources Information Center

    Lotan, M.; Isakov, E.; Merrick, J.

    2004-01-01

    To investigate the feasibility of a physical exercise programme with treadmill for persons with Rett syndrome (RS) in order to promote fitness and health. A daily training programme on a treadmill was designed for four females with RS over a period of 2 months with tests performed in three intervals, at time 1, 2 and 3, 2 months apart with…

  8. Prenatal stimulation and postnatal testosterone affects infanticide in female rats.

    PubMed

    Miley, W M; Blustein, J; Kennedy, K

    1982-04-01

    Prenatal handling, prenatal stress, and early postnatal exogeneous testosterone were examined in female rats for their effects on rat pup-killing and pup retrieval. During each of the last 5 days of pregnancy. Long-Evans rats received either 3 minutes of handling, 45 minutes of restraint and intense illumination or remained untouched. Half of the offspring of each group received testosterone from Day 1 after birth to Day 30. In adulthood, animals that received handling prenatally and testosterone postnatally killed pups more rapidly than any other group and a larger proportion did so than in the control groups. Animals not manipulated at any time retrieved pups more rapidly and a larger proportion did so than the combined other groups. The study suggests that prenatal handling interacts with testosterone presented immediately postnatally to increase infanticide in female rats. A variety of perinatal manipulations seem to suppress pup retrieval. PMID:7200619

  9. Examination of X chromosome markers in Rett syndrome: Exclusion mapping with a novel variation on multilocus linkage analysis

    SciTech Connect

    Ellison, K.A.; Fill, C.P. ); Terwililger, J.; Percy, A.K.; Zobhbi, H. ); DeGennaro, L.J.; Ott, J. ); Anvret, M.; Martin-Gallardo, A. )

    1992-02-01

    Rett syndrome is a neurologic disorder characterized by early normal development followed by regression, acquired deceleration of head growth, autism, ataxia, and sterotypic hand movements. The exclusive occurrence of the syndrome in females and the occurrence of a few familial cases with inheritance through maternal lines suggest that this disorder is most likely secondary to a mutation on the X chromosome. To address this hypothesis and to identify candidate regions for the Rett syndrome gene locus, genotypic analysis was performed in two families with maternally related affected half-sisters by using 63 DNA markers from the X chromosome. Nineteen of the loci studied were chosen for multipoint linkage analysis because they have been previously genetically mapped using a large number of meioses from reference families. Using the exclusion criterion of a lod score less than [minus]2, the authors were able to exclude the region between the Duchenne muscular dystrophy locus and the DXS456 locus. This region extends from Xp21.2 to Xq21-q23. The use of the multipoint linkage analysis approach outlined in this study should allow the exclusion of additional regions of the X chromosome as new markers are analyzed.

  10. Validating the Rett Syndrome Gross Motor Scale.

    PubMed

    Downs, Jenny; Stahlhut, Michelle; Wong, Kingsley; Syhler, Birgit; Bisgaard, Anne-Marie; Jacoby, Peter; Leonard, Helen

    2016-01-01

    Rett syndrome is a pervasive neurodevelopmental disorder associated with a pathogenic mutation on the MECP2 gene. Impaired movement is a fundamental component and the Rett Syndrome Gross Motor Scale was developed to measure gross motor abilities in this population. The current study investigated the validity and reliability of the Rett Syndrome Gross Motor Scale. Video data showing gross motor abilities supplemented with parent report data was collected for 255 girls and women registered with the Australian Rett Syndrome Database, and the factor structure and relationships between motor scores, age and genotype were investigated. Clinical assessment scores for 38 girls and women with Rett syndrome who attended the Danish Center for Rett Syndrome were used to assess consistency of measurement. Principal components analysis enabled the calculation of three factor scores: Sitting, Standing and Walking, and Challenge. Motor scores were poorer with increasing age and those with the p.Arg133Cys, p.Arg294* or p.Arg306Cys mutation achieved higher scores than those with a large deletion. The repeatability of clinical assessment was excellent (intraclass correlation coefficient for total score 0.99, 95% CI 0.93-0.98). The standard error of measurement for the total score was 2 points and we would be 95% confident that a change 4 points in the 45-point scale would be greater than within-subject measurement error. The Rett Syndrome Gross Motor Scale could be an appropriate measure of gross motor skills in clinical practice and clinical trials.

  11. Florivory affects pollinator visitation and female fitness in Nemophila menziesii.

    PubMed

    McCall, Andrew C

    2008-04-01

    While herbivory has traditionally been studied as damage to leaves, florivory - herbivory to flowers prior to seed set - can also have large effects on plant fitness. Florivory can decrease fitness directly, either through the destruction of gametes or through alterations to plant physiology during fruit set, and can also change the appearance of a flower, deterring pollinators and reducing seed set. In order to distinguish between these hypotheses, it is necessary to both damage flowers and add pollen in excess to study the effects of damage on pollen limitation. Very few studies have used this technique over the lifetime of a plant. Here I describe a series of experiments showing the effects of natural and artificial damage on reproductive success in the annual plant Nemophila menziesii (Hydrophyllaceae, sensu lato). I show that natural and artificial petal damage decreased radial symmetry relative to controls and that both types of damage deterred pollinator activity. Both naturally damaged flowers and artificially damaged flowers in the field set fewer fruit or seed relative to undamaged control flowers. Finally, in an experiment crossing artificial petal damage with pollen addition, petal damage alone over the lifetime of this plant decreased female fitness, but only after a threshold of damage was reached. The fitness effect appeared to be direct because there was no detectable effect of pollen addition on the relationship between florivory and fitness. This result implies that both damaged and undamaged plants show similar amounts of pollen limitation and suggests that pollinator-mediated effects contributed little to the negative effects of florivory on female fitness. Florivores may thus be an under-appreciated agent of selection in certain plants, although more experimental manipulation of florivory is needed to determine if it is important over a range of taxa. PMID:18188605

  12. Brief report: systematic review of Rett syndrome in males.

    PubMed

    Reichow, Brian; George-Puskar, Annie; Lutz, Tara; Smith, Isaac C; Volkmar, Fred R

    2015-10-01

    Rett syndrome (RTT) is a neurogenetic disorder in which a period of typical development is followed by loss of previously acquired skills. Once thought to occur exclusively in females, increasing numbers of male cases of RTT have been reported. This systematic review included 36 articles describing 57 cases of RTT in males. Mutations of the MECP2 gene were present in 56 % of cases, and 68 % of cases reported other genetic abnormalities. This is the first review of published reports of RTT in male patients.

  13. Eye Movements Affect Postural Control in Young and Older Females

    PubMed Central

    Thomas, Neil M.; Bampouras, Theodoros M.; Donovan, Tim; Dewhurst, Susan

    2016-01-01

    Visual information is used for postural stabilization in humans. However, little is known about how eye movements prevalent in everyday life interact with the postural control system in older individuals. Therefore, the present study assessed the effects of stationary gaze fixations, smooth pursuits, and saccadic eye movements, with combinations of absent, fixed and oscillating large-field visual backgrounds to generate different forms of retinal flow, on postural control in healthy young and older females. Participants were presented with computer generated visual stimuli, whilst postural sway and gaze fixations were simultaneously assessed with a force platform and eye tracking equipment, respectively. The results showed that fixed backgrounds and stationary gaze fixations attenuated postural sway. In contrast, oscillating backgrounds and smooth pursuits increased postural sway. There were no differences regarding saccades. There were also no differences in postural sway or gaze errors between age groups in any visual condition. The stabilizing effect of the fixed visual stimuli show how retinal flow and extraocular factors guide postural adjustments. The destabilizing effect of oscillating visual backgrounds and smooth pursuits may be related to more challenging conditions for determining body shifts from retinal flow, and more complex extraocular signals, respectively. Because the older participants matched the young group's performance in all conditions, decreases of posture and gaze control during stance may not be a direct consequence of healthy aging. Further research examining extraocular and retinal mechanisms of balance control and the effects of eye movements, during locomotion, is needed to better inform fall prevention interventions.

  14. Eye Movements Affect Postural Control in Young and Older Females

    PubMed Central

    Thomas, Neil M.; Bampouras, Theodoros M.; Donovan, Tim; Dewhurst, Susan

    2016-01-01

    Visual information is used for postural stabilization in humans. However, little is known about how eye movements prevalent in everyday life interact with the postural control system in older individuals. Therefore, the present study assessed the effects of stationary gaze fixations, smooth pursuits, and saccadic eye movements, with combinations of absent, fixed and oscillating large-field visual backgrounds to generate different forms of retinal flow, on postural control in healthy young and older females. Participants were presented with computer generated visual stimuli, whilst postural sway and gaze fixations were simultaneously assessed with a force platform and eye tracking equipment, respectively. The results showed that fixed backgrounds and stationary gaze fixations attenuated postural sway. In contrast, oscillating backgrounds and smooth pursuits increased postural sway. There were no differences regarding saccades. There were also no differences in postural sway or gaze errors between age groups in any visual condition. The stabilizing effect of the fixed visual stimuli show how retinal flow and extraocular factors guide postural adjustments. The destabilizing effect of oscillating visual backgrounds and smooth pursuits may be related to more challenging conditions for determining body shifts from retinal flow, and more complex extraocular signals, respectively. Because the older participants matched the young group's performance in all conditions, decreases of posture and gaze control during stance may not be a direct consequence of healthy aging. Further research examining extraocular and retinal mechanisms of balance control and the effects of eye movements, during locomotion, is needed to better inform fall prevention interventions. PMID:27695412

  15. How can clinical ethics guide the management of comorbidities in the child with Rett syndrome?

    PubMed

    Downs, Jenny; Forbes, David; Johnson, Michael; Leonard, Helen

    2016-08-01

    Rett syndrome is a rare disorder caused by a mutation in the MECP2 gene. Those affected generally have severe functional impairments, and medical comorbidities such as scoliosis and poor growth are common. There is a paucity of information on the natural history of many rare disorders and an even greater deficit of evidence to guide best practice. The population-based and longitudinal Australian Rett Syndrome Database established in 1993 has supported investigations of the natural history of Rett syndrome and effectiveness of treatments. This paper reviews the disorder Rett syndrome and evidence for the management of scoliosis and poor growth within a clinical ethics framework. Compared with conservative management, we have shown that spinal fusion is associated with reduced mortality and better respiratory health. We have also shown that gastrostomy insertion is associated with subsequent weight gain. Family counselling for both procedures necessarily must include family perspectives and careful clinical attention to their needs and wishes. Vignettes describing family decision-making and experiences are presented to illustrate the principals of beneficence and autonomy in determining the best interests of the child and family. A blend of evidence-based practice with a strong clinical ethics framework has capacity to build existing strengths in families and reduce the negative impacts of disability and in so doing, optimise the health and wellbeing of those with Rett syndrome. PMID:27243819

  16. Quantitative and qualitative insights into the experiences of children with Rett syndrome and their families.

    PubMed

    Downs, Jenny; Leonard, Helen

    2016-09-01

    Rett syndrome is a rare neurodevelopmental disorder caused by a mutation in the MECP2 gene. It is associated with severe functional impairments and medical comorbidities such as scoliosis and poor growth. The population-based and longitudinal Australian Rett Syndrome Database was established in 1993 and has supported investigations of the natural history of Rett syndrome and effectiveness of treatments, as well as a suite of qualitative studies to identify deeper meanings. This paper describes the early presentation of Rett syndrome, including regression and challenges for families seeking a diagnosis. We discuss the importance of implementing strategies to enhance daily communication and movement, describe difficulties interpreting the presence of pain and discomfort, and argue for a stronger evidence base in relation to management. Finally, we outline a framework for understanding quality of life in Rett syndrome and suggest areas of life to which we can direct efforts in order to improve quality of life. Each of these descriptions is illustrated with vignettes of child and family experiences. Clinicians and researchers must continue to build this framework of knowledge and understanding with efforts committed to providing more effective treatments and supporting the best quality of life for those affected. PMID:27491552

  17. Quantitative and qualitative insights into the experiences of children with Rett syndrome and their families.

    PubMed

    Downs, Jenny; Leonard, Helen

    2016-09-01

    Rett syndrome is a rare neurodevelopmental disorder caused by a mutation in the MECP2 gene. It is associated with severe functional impairments and medical comorbidities such as scoliosis and poor growth. The population-based and longitudinal Australian Rett Syndrome Database was established in 1993 and has supported investigations of the natural history of Rett syndrome and effectiveness of treatments, as well as a suite of qualitative studies to identify deeper meanings. This paper describes the early presentation of Rett syndrome, including regression and challenges for families seeking a diagnosis. We discuss the importance of implementing strategies to enhance daily communication and movement, describe difficulties interpreting the presence of pain and discomfort, and argue for a stronger evidence base in relation to management. Finally, we outline a framework for understanding quality of life in Rett syndrome and suggest areas of life to which we can direct efforts in order to improve quality of life. Each of these descriptions is illustrated with vignettes of child and family experiences. Clinicians and researchers must continue to build this framework of knowledge and understanding with efforts committed to providing more effective treatments and supporting the best quality of life for those affected.

  18. How can clinical ethics guide the management of comorbidities in the child with Rett syndrome?

    PubMed

    Downs, Jenny; Forbes, David; Johnson, Michael; Leonard, Helen

    2016-08-01

    Rett syndrome is a rare disorder caused by a mutation in the MECP2 gene. Those affected generally have severe functional impairments, and medical comorbidities such as scoliosis and poor growth are common. There is a paucity of information on the natural history of many rare disorders and an even greater deficit of evidence to guide best practice. The population-based and longitudinal Australian Rett Syndrome Database established in 1993 has supported investigations of the natural history of Rett syndrome and effectiveness of treatments. This paper reviews the disorder Rett syndrome and evidence for the management of scoliosis and poor growth within a clinical ethics framework. Compared with conservative management, we have shown that spinal fusion is associated with reduced mortality and better respiratory health. We have also shown that gastrostomy insertion is associated with subsequent weight gain. Family counselling for both procedures necessarily must include family perspectives and careful clinical attention to their needs and wishes. Vignettes describing family decision-making and experiences are presented to illustrate the principals of beneficence and autonomy in determining the best interests of the child and family. A blend of evidence-based practice with a strong clinical ethics framework has capacity to build existing strengths in families and reduce the negative impacts of disability and in so doing, optimise the health and wellbeing of those with Rett syndrome.

  19. Male irradiation affects female remating behavior in Anastrepha serpentina (Diptera: Tephritidae).

    PubMed

    Landeta-Escamilla, Anais; Hernández, Emilio; Arredondo, José; Díaz-Fleischer, Francisco; Pérez-Staples, Diana

    2016-02-01

    Female remating in target pest species can affect the efficacy of control methods such as the Sterile Insect Technique (SIT) but very little is known about the postcopulatory mating behavior of these pests. In this study, we investigated the remating behavior of female Anastrepha serpentina (Diptera: Tephritidae), an oligophagous pest of Sapotaceae. First, we tested how long the sexual refractory period of females lasted after an initial mating. Second, we tested the effect of male and female sterility, female ovipositing opportunities and male density on female propensity to remate. Lastly, we tested if the amount of sperm stored by females was correlated to the likelihood of females to remate. We found that receptivity of mass-reared A. serpentina females had a bimodal response, with up to 16% of mass-reared A. serpentina females remating five days after the initial copulation, decreasing to 2% at 10 and 15 days and increasing to 13% after 20 days. Compared to fertile males, sterile males were less likely to mate and less likely to inhibit females from remating. Copula duration of sterile males was shorter compared to fertile males. Remating females were less likely to mate with a sterile male as a second mate. Sterile females were less likely to mate or remate compared to fertile females. Opportunity to oviposit and male density had no effect on female remating probability. Sperm numbers were not correlated with female likelihood to remate. Information on the post-copulatory behavior of mass-reared A. serpentina will aid fruit fly managers in improving the quality of sterile males. We discuss our results in terms of the differences this species presents in female remating behavior compared to other tephritids. PMID:26616467

  20. Pathogenesis of Lethal Cardiac Arrhythmias in Mecp2 Mutant Mice: Implication for Therapy in Rett Syndrome

    PubMed Central

    McCauley, Mark D.; Wang, Tiannan; Mike, Elise; Herrera, Jose; Beavers, David L.; Huang, Teng-Wei; Ward, Christopher S.; Skinner, Steven; Percy, Alan K.; Glaze, Daniel G.; Wehrens, Xander H. T.; Neul, Jeffrey L.

    2013-01-01

    Rett Syndrome is a neurodevelopmental disorder typically caused by mutations in Methyl-CpG-Binding Protein 2 (MECP2) in which 26% of deaths are sudden and of unknown cause. To explore the hypothesis that these deaths may be due to cardiac dysfunction, we characterized the electrocardiograms (ECGs) in 379 people with Rett syndrome and found that 18.5% show prolongation of the corrected QT interval (QTc), indicating a repolarization abnormality that can predispose to the development of an unstable fatal cardiac rhythm. Male mice lacking MeCP2 function, Mecp2Null/Y, also have prolonged QTc and show increased susceptibility to induced ventricular tachycardia. Female heterozygous null mice, Mecp2Null/+, show an age-dependent prolongation of QTc associated with ventricular tachycardia and cardiac-related death. Genetic deletion of MeCP2 function in only the nervous system was sufficient to cause long QTc and ventricular tachycardia, implicating neuronally-mediated changes to cardiac electrical conduction as a potential cause of ventricular tachycardia in Rett syndrome. The standard therapy for prolonged QTc in Rett syndrome, β-adrenergic receptor blockers, did not prevent ventricular tachycardia in Mecp2Null/Y mice. To determine whether an alternative therapy would be more appropriate, we characterized cardiomyocytes from Mecp2Null/Y mice and found increased persistent sodium current, which was normalized when cells were treated with the sodium channel-blocking anti-seizure drug phenytoin. Treatment with phenytoin reduced both QTc and sustained ventricular tachycardia in Mecp2Null/Y mice. These results demonstrate that cardiac abnormalities in Rett syndrome are secondary to abnormal nervous system control, which leads to increased persistent sodium current. Our findings suggest that treatment in people with Rett syndrome would be more effective if it targeted the increased persistent sodium current in order to prevent lethal cardiac arrhythmias. PMID:22174313

  1. The Contribution of Qualitative Research Towards the Issues Affecting Female Undergraduate Engineering Students

    ERIC Educational Resources Information Center

    Duggan, Louise Maria

    2015-01-01

    This article explores the use of qualitative research methods towards our understanding of the issues affecting female undergraduate engineers. As outlined in this article female engineering students face many challenges during their undergraduate studies. Qualitative research methods provide an opportunity to gain a deeper understanding of the…

  2. What Are the Symptoms of Rett Syndrome?

    MedlinePlus

    ... Lack of age-related decrease in sleep duration. Brain Development , Dec;23(Suppl 1). [top] Nomura, Y. (2005). ... behavior characteristics and sleep disturbance in Rett syndrome. Brain and Development , Nov;27(Suppl 1). [top] Rare Diseases Clinical ...

  3. Negative Affect, Alcohol Consumption, and Female-to-Male Intimate Partner Violence: A Daily Diary Investigation

    PubMed Central

    Crane, Cory; Eckhardt, Christopher

    2014-01-01

    While research suggests that both negative affect and alcohol use are related to the risk of intimate partner violence (IPV) in male samples, less is known about the status of these risk factors in female samples. Forty-three college-age females who reported a recent history of IPV perpetration submitted six weeks of on-line daily reports pertaining to their levels of negative affect, alcohol consumption habits, and the occurrence of both male-to-female (MFPV) and female-to-male IPV (FMPV). Results indicated that negative affect significantly predicted increases in the daily risk of FMPV. MFPV also significantly predicted FMPV risk. Alcohol consumption failed to predict FMPV perpetration on both levels of analysis. Results are discussed in terms of prevailing models of alcohol use, negative affect, and IPV. PMID:26413212

  4. Female presence affects male behavior and testosterone levels in the European starling (Sturnus vulgaris).

    PubMed

    Pinxten, Rianne; de Ridder, Elke; Eens, Marcel

    2003-08-01

    In this study, we confronted individually housed male European starlings (Sturnus vulgaris) with a female conspecific for 60 min to study the consequences on behavior and plasma testosterone (T) concentrations. Control males experienced a similar procedure, the only difference being that they were tested in the absence of a female. Female presence significantly affected both behavior and plasma T levels of male starlings. Experimental males spent significantly more time singing in the nest box and flew significantly more into the nest box with green nesting material during female presentations than during control periods. Control males never showed these mate attraction behaviors. In total 5 of the 16 experimental males did not respond behaviorally to the female stimulus bird (NR males). In contrast to T levels of control males, plasma T concentrations of both experimental males that did respond to the female (R males) and of NR males (which only perceived the female stimulus) were positively influenced by female presentation. The time spent singing in the nest box by experimental males (R and NR males combined) during female presence tended to be positively correlated with changes in plasma T levels. Finally, before introduction of a female, plasma T levels of R males were significantly higher than those of NR males indicating that individually housed males respond to the presence of a female conspecific by increasing their mate attraction behaviors only when a threshold plasma T concentration has been reached. PMID:13129481

  5. Self-Injurious Behavior in Rett Syndrome: Interactions between Features of Rett Syndrome and Operant Conditioning.

    ERIC Educational Resources Information Center

    Oliver, Chris; And Others

    1993-01-01

    In this case study, interactions were examined between features of Rett syndrome and operant conditioning as determinants of self-injurious behavior (SIB). Analysis suggested different functions for two forms of SIB: automatic reinforcement by sensory stimulation and escape from social interactions. Features of Rett syndrome tended to maximize the…

  6. How Do Health Care Providers Diagnose Rett Syndrome?

    MedlinePlus

    ... Information Clinical Trials Resources and Publications How do health care providers diagnose Rett syndrome? Skip sharing on social ... Rett syndrome may not always be present, so health care providers also need to evaluate the child's symptoms ...

  7. An exploratory study of evoked facial affect in adolescent females with anorexia nervosa.

    PubMed

    Rhind, Charlotte; Mandy, William; Treasure, Janet; Tchanturia, Kate

    2014-12-15

    The aim of this exploratory study was to investigate facial affect in adolescent females with anorexia nervosa (AN). Evoked facial affect was recorded whilst AN and control participants (n=34) viewed emotional films. Significantly less facial affect was found in AN adolescents, despite reporting no differences in subjective emotion experience. These findings correspond with previous studies in adults with AN. Altered facial affect may impair interpersonal functioning and contribute to illness maintenance.

  8. Maternal characteristics and environment affect the costs of reproduction in female mountain goats.

    PubMed

    Hamel, Sandra; Côté, Steeve D; Festa-Bianchet, Marco

    2010-07-01

    Reproduction should reduce resources available for somatic investment and result in fundamental trade-offs among life-history traits. Using 18 years of longitudinal data from marked mountain goats (Oreamnos americanus), we assessed whether reproductive status affected female survival and future reproduction when accounting for parity, age, individual quality, population density, and environmental conditions. Reproduction reduced the probability of parturition and offspring survival in the following year. Female survival, however, was independent of previous reproduction, suggesting that females favored their own survival over that of their offspring. The lower probability of parturition in females that had a kid the previous year was only detected at high population density and among young and prime-aged females, suggesting that fitness costs of reproduction can be masked by variations in resource availability and individual characteristics. Primiparous females were less likely than multiparous females to reproduce in the subsequent year. Offspring survival was reduced at high density and after severe winters. Environmental conditions mainly influenced offspring survival, whereas female survival and fecundity were principally modulated by female characteristics. Our study highlights how different intrinsic and environmental factors can affect the probability of future reproduction and also underlines the value of long-term monitoring of known individuals. PMID:20715626

  9. Maternal characteristics and environment affect the costs of reproduction in female mountain goats.

    PubMed

    Hamel, Sandra; Côté, Steeve D; Festa-Bianchet, Marco

    2010-07-01

    Reproduction should reduce resources available for somatic investment and result in fundamental trade-offs among life-history traits. Using 18 years of longitudinal data from marked mountain goats (Oreamnos americanus), we assessed whether reproductive status affected female survival and future reproduction when accounting for parity, age, individual quality, population density, and environmental conditions. Reproduction reduced the probability of parturition and offspring survival in the following year. Female survival, however, was independent of previous reproduction, suggesting that females favored their own survival over that of their offspring. The lower probability of parturition in females that had a kid the previous year was only detected at high population density and among young and prime-aged females, suggesting that fitness costs of reproduction can be masked by variations in resource availability and individual characteristics. Primiparous females were less likely than multiparous females to reproduce in the subsequent year. Offspring survival was reduced at high density and after severe winters. Environmental conditions mainly influenced offspring survival, whereas female survival and fecundity were principally modulated by female characteristics. Our study highlights how different intrinsic and environmental factors can affect the probability of future reproduction and also underlines the value of long-term monitoring of known individuals.

  10. Modifying Adult Interactional Style as Positive Behavioural Intervention for a Child with Rett Syndrome.

    ERIC Educational Resources Information Center

    Evans, Ian M.; Meyer, Luanna H.

    1999-01-01

    A naturalistic behavioral assessment and intervention program over a 3-year period for a New Zealand girl (age 5) with Rett syndrome is described. The most significant reduction in hand mannerisms and other excess behaviors was related to positive social interactions and play that allowed for communication at the affective level. (Author/CR)

  11. Stress and Family Functioning in Parents of Girls with Rett Syndrome.

    ERIC Educational Resources Information Center

    Perry, Adrienne; And Others

    1992-01-01

    This survey of parents of 29 girls with Rett syndrome found that subjects reported more stress, lower marital satisfaction, and certain adaptations in family functioning compared to norms. However, most parents scored in the normal range. Scores were not related to socioeconomic status or characteristics of the affected child. (DB)

  12. Is Rett Syndrome a Subtype of Pervasive Developmental Disorders?

    ERIC Educational Resources Information Center

    Tsai, Luke Y.

    1992-01-01

    This paper reviews whether Rett syndrome is a subtype of pervasive developmental disorders (PDD). The paper analyzes internal and external diagnostic validity and discusses whether Rett syndrome is a neurological disorder or a mental disorder. The paper concludes that data support the idea of classifying Rett syndrome as a subtype of PDD.…

  13. Determinants of sleep disturbances in Rett syndrome: Novel findings in relation to genotype.

    PubMed

    Boban, Sharolin; Wong, Kingsley; Epstein, Amy; Anderson, Barbara; Murphy, Nada; Downs, Jenny; Leonard, Helen

    2016-09-01

    Rett syndrome is a rare but severe neurological disorder associated with a mutation in the methyl CpG binding protein 2 (MECP2) gene. Sleep problems and epilepsy are two of many comorbidities associated with this disorder. This study investigated the prevalence and determinants of sleep problems in Rett syndrome using an international sample. Families with a child with a confirmed Rett syndrome diagnosis and a MECP2 mutation registered in the International Rett Syndrome Phenotype Database (InterRett) were invited to participate. Questionnaires were returned by 364/461 (78.9%) either in web-based or paper format. Families completed the Sleep Disturbance Scale for Children and provided information on the presence, nature, and frequency of their child's sleep problems. Multivariate multinomial regression was used to investigate the relationships between selected sleep problems, age group, and genotype and linear regression for the relationships between sleep disturbance scales and a range of covariates. Night waking was the most prevalent sleep problem affecting over 80% with nearly half (48.3%) currently waking often at night. Initiating and maintaining sleep was most disturbed for younger children and those with a p.Arg294* mutation. Severe seizure activity was associated with poor sleep after adjusting for age group, mutation type, and mobility. We were surprised to find associations between the p.Arg294* mutation and some sleep disturbances given that other aspects of its phenotype are milder. These findings highlight the complexities of aberrant MECP2 function in Rett syndrome and explain some of the variation in manifestation of sleep disturbances. © 2016 Wiley Periodicals, Inc.

  14. Male seminal fluid substances affect sperm competition success and female reproductive behavior in a seed beetle.

    PubMed

    Yamane, Takashi; Goenaga, Julieta; Rönn, Johanna Liljestrand; Arnqvist, Göran

    2015-01-01

    Male seminal fluid proteins are known to affect female reproductive behavior and physiology by reducing mating receptivity and by increasing egg production rates. Such substances are also though to increase the competitive fertilization success of males, but the empirical foundation for this tenet is restricted. Here, we examined the effects of injections of size-fractioned protein extracts from male reproductive organs on both male competitive fertilization success (i.e., P2 in double mating experiments) and female reproduction in the seed beetle Callosobruchus maculatus. We found that extracts of male seminal vesicles and ejaculatory ducts increased competitive fertilization success when males mated with females 1 day after the females' initial mating, while extracts from accessory glands and testes increased competitive fertilization success when males mated with females 2 days after the females' initial mating. Moreover, different size fractions of seminal fluid proteins had distinct and partly antagonistic effects on male competitive fertilization success. Collectively, our experiments show that several different seminal fluid proteins, deriving from different parts in the male reproductive tract and of different molecular weight, affect male competitive fertilization success in C. maculatus. Our results highlight the diverse effects of seminal fluid proteins and show that the function of such proteins can be contingent upon female mating status. We also document effects of different size fractions on female mating receptivity and egg laying rates, which can serve as a basis for future efforts to identify the molecular identity of seminal fluid proteins and their function in this model species.

  15. Prereproductive stress in adolescent female rats affects behavior and corticosterone levels in second-generation offspring.

    PubMed

    Zaidan, Hiba; Gaisler-Salomon, Inna

    2015-08-01

    Human and animal studies indicate that vulnerability to stress may be heritable. We have previously shown that chronic, mild prereproductive stress (PRS) in adolescent female rats affects behavior and corticotropin releasing factor 1 (CRF1) expression in the brain of first-generation (F1) offspring. Here, we investigated the effects of PRS on anxiogenic behavior and CRF1 expression in male and female second-generation (F2) offspring. Furthermore, we assessed levels of the stress hormone corticosterone (CORT), a direct marker of hypothalamic-pituitary-adrenal (HPA) axis function, in PRS females and their F1 and F2 progeny. F2 offspring demonstrated decreased CRF1 mRNA expression at birth, and alterations in anxiogenic behavior in adulthood. CORT levels were elevated in PRS females and in their F1 female, but not male, offspring. In F2, CORT levels in PRS offspring also varied in a sex-dependent manner. These findings indicate that PRS in adolescent females leads to behavioral alterations that extend to second-generation offspring, and has transgenerational effects on endocrine function. Together with our previous findings, these data indicate that PRS to adolescent females affects behavior and HPA axis function across three generations, and highlight the importance of examining the transgenerational effects of stress in both male and female offspring.

  16. Exposure to PCB 77 affects partner preference but not sexual behavior in the female rat.

    PubMed

    Cummings, J A; Clemens, L G; Nunez, A A

    2008-10-20

    In rats, exposure to the polychlorinated biphenyl congener 3, 4, 3', 4'-tetrachlorobiphenyl (PCB 77) affects the brain and behavior of the offspring as well as the maternal behavior of the dams. In the present study, a cross-fostering design was used to examine the effects of pre- and/or postnatal exposure to PCB 77 on sexual behavior and partner preference in female rats, and to determine the role of altered maternal behavior in the mediation of these effects. Pregnant rats were treated with oil or PCB dissolved in oil (2 mg/kg b.w.) on gestation days 6-18 and then given pups that had been exposed to either the oil vehicle or PCB during gestation. As adults, the female offspring were tested for partner preference (that is, whether they preferred to spend time with a sexually receptive female or a sexually active male) and sexual behavior. None of the treatments affected female sexual behavior. However, both double exposure and postnatal exposure diminished the animals' preference for a male over a female stimulus, but partner preference was not affected by prenatal exposure alone. There were no significant correlations between the changes in partner preferences due to PCB exposure and the amount of maternal grooming and licking received by the treated litters. Thus, female partner preference is affected by early PCB exposure, and the effects depend upon whether the exposure is in utero or via lactation and may be independent of any effects of the PCB on maternal care.

  17. Immune dysfunction in Rett syndrome patients revealed by high levels of serum anti-N(Glc) IgM antibody fraction.

    PubMed

    Papini, Anna Maria; Nuti, Francesca; Real-Fernandez, Feliciana; Rossi, Giada; Tiberi, Caterina; Sabatino, Giuseppina; Pandey, Shashank; Leoncini, Silvia; Signorini, Cinzia; Pecorelli, Alessandra; Guerranti, Roberto; Lavielle, Solange; Ciccoli, Lucia; Rovero, Paolo; De Felice, Claudio; Hayek, Joussef

    2014-01-01

    Rett syndrome (RTT), a neurodevelopmental disorder affecting exclusively (99%) female infants, is associated with loss-of-function mutations in the gene encoding methyl-CpG binding protein 2 (MECP2) and, more rarely, cyclin-dependent kinase-like 5 (CDKL5) and forkhead box protein G1 (FOXG1). In this study, we aimed to evaluate the function of the immune system by measuring serum immunoglobulins (IgG and IgM) in RTT patients (n = 53) and, by comparison, in age-matched children affected by non-RTT pervasive developmental disorders (non-RTT PDD) (n = 82) and healthy age-matched controls (n = 29). To determine immunoglobulins we used both a conventional agglutination assay and a novel ELISA based on antibody recognition by a surrogate antigen probe, CSF114(Glc), a synthetic N-glucosylated peptide. Both assays provided evidence for an increase in IgM titer, but not in IgG, in RTT patients relative to both healthy controls and non-RTT PDD patients. The significant difference in IgM titers between RTT patients and healthy subjects in the CSF114(Glc) assay (P = 0.001) suggests that this procedure specifically detects a fraction of IgM antibodies likely to be relevant for the RTT disease. These findings offer a new insight into the mechanism underlying the Rett disease as they unveil the possible involvement of the immune system in this pathology. PMID:25389532

  18. Immune Dysfunction in Rett Syndrome Patients Revealed by High Levels of Serum Anti-N(Glc) IgM Antibody Fraction

    PubMed Central

    Papini, Anna Maria; Real-Fernandez, Feliciana; Rossi, Giada; Tiberi, Caterina; Sabatino, Giuseppina; Pandey, Shashank; Lavielle, Solange; Ciccoli, Lucia; Hayek, Joussef

    2014-01-01

    Rett syndrome (RTT), a neurodevelopmental disorder affecting exclusively (99%) female infants, is associated with loss-of-function mutations in the gene encoding methyl-CpG binding protein 2 (MECP2) and, more rarely, cyclin-dependent kinase-like 5 (CDKL5) and forkhead box protein G1 (FOXG1). In this study, we aimed to evaluate the function of the immune system by measuring serum immunoglobulins (IgG and IgM) in RTT patients (n = 53) and, by comparison, in age-matched children affected by non-RTT pervasive developmental disorders (non-RTT PDD) (n = 82) and healthy age-matched controls (n = 29). To determine immunoglobulins we used both a conventional agglutination assay and a novel ELISA based on antibody recognition by a surrogate antigen probe, CSF114(Glc), a synthetic N-glucosylated peptide. Both assays provided evidence for an increase in IgM titer, but not in IgG, in RTT patients relative to both healthy controls and non-RTT PDD patients. The significant difference in IgM titers between RTT patients and healthy subjects in the CSF114(Glc) assay (P = 0.001) suggests that this procedure specifically detects a fraction of IgM antibodies likely to be relevant for the RTT disease. These findings offer a new insight into the mechanism underlying the Rett disease as they unveil the possible involvement of the immune system in this pathology. PMID:25389532

  19. Female athletes: a population at risk of vitamin and mineral deficiencies affecting health and performance.

    PubMed

    McClung, James P; Gaffney-Stomberg, Erin; Lee, Jane J

    2014-10-01

    Adequate vitamin and mineral status is essential for optimal human health and performance. Female athletes could be at risk for vitamin and mineral insufficiency due to inadequate dietary intake, menstruation, and inflammatory responses to heavy physical activity. Recent studies have documented poor iron status and associated declines in both cognitive and physical performance in female athletes. Similarly, insufficient vitamin D and calcium status have been observed in female athletes, and may be associated with injuries, such as stress fracture, which may limit a female athlete's ability to participate in regular physical activity. This review will focus on recent studies detailing the prevalence of poor vitamin and mineral status in female athletes, using iron, vitamin D, and calcium as examples. Factors affecting the dietary requirement for these vitamins and minerals during physical training will be reviewed. Lastly, countermeasures for the prevention of inadequate vitamin and mineral status will be described.

  20. A RETT SYNDROME CASE WITH NOVEL NON-IDENTICAL MUTATION IN MECP2 GENE.

    PubMed

    Güngör, O; Kirik, S; Cevizli, D; Karaokur, F; Ozer, L; Uysal, S; Dilber, C

    2015-01-01

    The Rett syndrome (RTT; OMIM #312750) is a rare genetic disease observed predominantly among girls that affects neurological development. The incidence of this disorder is approximately 1 in 10,000 female births. Diagnosis of the RTT is based on specific clinical criteria and the identification of a mutation in the methyl-CpG-binding protein (MECP), which mainly occurs on exons 3 and 4 of the gene. Mutations in the X-linked methyl-CpG binding protein 2 gene (MECP2) are observed in nearly 95% of RTT cases. RTT is associated with considerable genotypic and phenotypic heterogeneity. Recently, it has been observed that mutations in the genes Netrin G1 and cyclin-dependent kinase like 5 (CDKL5) also lead to clinical pictures resembling RTT. In this case report, we describe a 4-years-old female patient who met all the relevant criteria for the diagnosis of RTT. Sequence analyses performed on the patient identified a de novo, heterozygous c.489G>A mutation at exon 4 of the MECP2 gene.

  1. Osteoblast function and bone histomorphometry in a murine model of Rett syndrome.

    PubMed

    Blue, Mary E; Boskey, Adele L; Doty, Stephen B; Fedarko, Neal S; Hossain, Mir Ahamed; Shapiro, Jay R

    2015-07-01

    Rett syndrome (RTT) is an X-linked neurodevelopmental disorder due to mutations affecting the neural transcription factor MeCP2. Approximately 50% of affected females have decreased bone mass. We studied osteoblast function using a murine model of RTT. Female heterozygote (HET) and male Mecp2-null mice were compared to wild type (WT) mice. Micro-CT of tibia from 5 week-old Mecp2-null mice showed significant alterations in trabecular bone including reductions in bone volume fraction (-29%), number (-19%), thickness (-9%) and connectivity density (-32%), and increases in trabecular separation (+28%) compared to WT. We also found significant reductions in cortical bone thickness (-18%) and in polar moment of inertia (-45%). In contrast, cortical and trabecular bone from 8 week-old WT and HET female mice were not significantly different. However, mineral apposition rate, mineralizing surface and bone formation rate/bone surface were each decreased in HET and Mecp2-null mice compared to WT mice. Histomorphometric analysis of femurs showed decreased numbers of osteoblasts but similar numbers of osteoclasts compared to WT, altered osteoblast morphology and decreased tissue synthesis of alkaline phosphatase in Mecp2-null and HET mice. Osteoblasts cultured from Mecp2-null mice, which unlike WT osteoblasts did not express MeCP2, had increased growth rates, but reductions in mRNA expression of type I collagen, Runx2 and Osterix compared to WT osteoblasts. These results indicate that MeCP2 deficiency leads to altered bone growth. Osteoblast dysfunction was more marked in Mecp2-null male than in HET female mice, suggesting that expression of MeCP2 plays a critical role in bone development.

  2. Unexpected cellular players in Rett syndrome pathology.

    PubMed

    Cronk, James C; Derecki, Noel C; Litvak, Vladimir; Kipnis, Jonathan

    2016-08-01

    Rett syndrome is a devastating neurodevelopmental disorder, primarily caused by mutations of methyl CpG-binding protein 2 (MeCP2). Although the genetic cause of disease was identified over a decade ago, a significant gap still remains in both our clinical and scientific understanding of its pathogenesis. Neurons are known to be primary players in pathology, with their dysfunction being the key in Rett syndrome. While studies in mice have demonstrated a clear causative - and potential therapeutic - role for neurons in Rett syndrome, recent work has suggested that other tissues also contribute significantly to progression of the disease. Indeed, Rett syndrome is known to present with several common peripheral pathologies, such as osteopenia, scoliosis, gastrointestinal problems including nutritional defects, and general growth deficit. Mouse models assessing the potential role of non-neuronal cell types have confirmed both roles in disease and potential therapeutic targets. A new picture is emerging in which neurons both initiate and drive pathology, while dysfunction of other cell types and peripheral tissues exacerbate disease, possibly amplifying further neurologic problems, and ultimately result in a positive feedback loop of progressively worsening symptoms. Here, we review what is known about neuronal and non-neuronal cell types, and discuss how this new, integrative understanding of the disease may allow for additional clinical and scientific pathways for treating and understanding Rett syndrome.

  3. Brief Report: Autistic Behaviors among Children with Fragile X or Rett Syndrome: Implications for the Classification of Pervasive Developmental Disorder.

    ERIC Educational Resources Information Center

    Mazzocco, Michele M. M.; Pulsifer, Margaret; Fiumara, Agata; Cocuzza, M.; Nigro, F.; Incorpora, G.; Barone, R.

    1998-01-01

    A study of 14 males with fragile X syndrome, 12 females with Rett Syndrome, and 25 individuals with other developmental disorders found that among those with fragile X syndrome, none of the 11 who did not have a diagnosis of autism met the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for pervasive developmental disorder.…

  4. Male Seminal Fluid Substances Affect Sperm Competition Success and Female Reproductive Behavior in a Seed Beetle

    PubMed Central

    Yamane, Takashi; Goenaga, Julieta; Rönn, Johanna Liljestrand; Arnqvist, Göran

    2015-01-01

    Male seminal fluid proteins are known to affect female reproductive behavior and physiology by reducing mating receptivity and by increasing egg production rates. Such substances are also though to increase the competitive fertilization success of males, but the empirical foundation for this tenet is restricted. Here, we examined the effects of injections of size-fractioned protein extracts from male reproductive organs on both male competitive fertilization success (i.e., P2 in double mating experiments) and female reproduction in the seed beetle Callosobruchus maculatus. We found that extracts of male seminal vesicles and ejaculatory ducts increased competitive fertilization success when males mated with females 1 day after the females’ initial mating, while extracts from accessory glands and testes increased competitive fertilization success when males mated with females 2 days after the females’ initial mating. Moreover, different size fractions of seminal fluid proteins had distinct and partly antagonistic effects on male competitive fertilization success. Collectively, our experiments show that several different seminal fluid proteins, deriving from different parts in the male reproductive tract and of different molecular weight, affect male competitive fertilization success in C. maculatus. Our results highlight the diverse effects of seminal fluid proteins and show that the function of such proteins can be contingent upon female mating status. We also document effects of different size fractions on female mating receptivity and egg laying rates, which can serve as a basis for future efforts to identify the molecular identity of seminal fluid proteins and their function in this model species. PMID:25893888

  5. Chronic mild stressors and diet affect gene expression differently in male and female rats.

    PubMed

    Liang, Shuwen; Byers, Donna M; Irwin, Louis N

    2007-01-01

    While depression is reportedly more prevalent in women than men, a neurobiological basis for this difference has not been documented. Chronic mild stress (CMS) is a widely recognized animal model, which uses mild and unpredictable environmental stressors to induce depression. Studies of chronic stress, mainly in males, have reported an increase in the relative intake of "comfort food" as a means of counteracting the effects of stress. This study was designed to test the hypothesis that genes for certain neurotrophic factors, stress markers, and appetite regulators would be expressed differentially in male and female rats exposed to chronic, mild stressors with access to a preferred diet. Gene expression for neuropeptide Y was upregulated in females purely in response to stressors, whereas that for the epidermal growth factor receptor (EGFR) and arginine vasopressin (AVP) in males and fatty acid synthase (FASN) in females responded primarily to diet. Genes for brain-derived neurotrophic factor (BDNF), AVP, and the cocaine-amphetamine regulator of transcription (CART) in males, and leptin in females, showed a significant response to the interaction between stressors and diet. Every affected gene showed a different pattern of expression in males and females. This study confirms the intimate relationship between dietary intake and response to stress at the molecular level, and emphasizes the sex- and gene-specific nature of those interactions. Therefore, it supports a neurobiological basis for differences in the affective state response to stress in males and females. PMID:17917078

  6. Mixtures of environmentally relevant endocrine disrupting chemicals affect mammary gland development in female and male rats.

    PubMed

    Mandrup, Karen Riiber; Johansson, Hanna Katarina Lilith; Boberg, Julie; Pedersen, Anne Stilling; Mortensen, Mette Sidsel; Jørgensen, Jennifer Solgaard; Vinggaard, Anne Marie; Hass, Ulla

    2015-07-01

    Estrogenic chemicals are able to alter mammary gland development in female rodents, but little is known on the effects of anti-androgens and mixtures of endocrine disrupting chemicals (EDCs) with dissimilar modes of action. Pregnant rat dams were exposed during gestation and lactation to mixtures of environmentally relevant EDCs with estrogenic, anti-androgenic or dissimilar modes of action (TotalMix) of 100-, 200- or 450-fold high end human intake estimates. Mammary glands of prepubertal and adult female and male offspring were examined. Oestrogens increased mammary outgrowth in prepubertal females and the mRNA level of matrix metalloproteinase-3, which may be a potential biomarker for increased outgrowth. Mixtures of EDCs gave rise to ductal hyperplasia in adult males. Adult female mammary glands of the TotalMix group showed morphological changes possibly reflecting increased prolactin levels. In conclusion both estrogenic and anti-androgenic chemicals given during foetal life and lactation affected mammary glands in the offspring.

  7. Host plant affects the sexual attractiveness of the female white-spotted longicorn beetle, Anoplophora malasiaca.

    PubMed

    Yasui, Hiroe; Fujiwara-Tsujii, Nao

    2016-01-01

    Anoplophora malasiaca (Coleoptera: Cerambycidae) is a serious pest that destroys various landscape and crop trees in Japan. We evaluated the precopulatory responses of three different A. malasiaca populations collected from mandarin orange, willow and blueberry trees. Most of the males accepted mates from within the same host plant population as well as females from the willow and blueberry populations. However, significant number of males from the blueberry and willow populations rejected females from the mandarin orange population immediately after touching them with their antennae. Because all three of the female populations produced contact sex pheromones on their elytra, the females of the mandarin orange population were predicted to possess extra chemicals that repelled the males of the other two populations. β-Elemene was identified as a key component that was only found in mandarin orange-fed females and induced a rejection response in willow-fed males. Our results represent the first example of a female-acquired repellent against conspecific males of different host plant populations, indicating that the host plant greatly affects the female's sexual attractiveness. PMID:27412452

  8. Sociocultural and Motivational Factors Affecting Asian American Females Studying Physics and Engineering in High School

    ERIC Educational Resources Information Center

    Sha, Saliha L.

    2012-01-01

    This quantitative study investigated whether and to what extent the motivational and sociocultural factors affect female Asian American high school physics students' achievement, their intended major in college, and their planned career goals at work fields. A survey of 62 questions, extracted from subscales of AAMAS,STPQ and PSE, were…

  9. BDNF deregulation in Rett syndrome

    PubMed Central

    Li, Wei; Pozzo-Miller, Lucas

    2013-01-01

    BDNF is the best-characterized neurotrophin in terms of its gene structure and modulation, secretion processing, and signaling cascades following its release. In addition to diverse features at the genetic and molecular levels, the abundant expression in several regions of the central nervous system has implicated BDNF as a potent modulator in many aspects of neuronal development, as well as synaptic transmission and plasticity. Impairments in any of these critical functions likely contribute to a wide array of neurodevelopmental, neurodegenerative, and neuropsychiatric diseases. In this review, we focus on a prevalent neurodevelopmental disorder, Rett syndrome (RTT), which afflicts 1:15,000 women world-wide. We describe the consequences of loss-of-function mutations in the gene encoding the transcription factor methyl-CpG binding protein 2 (MeCP2) in RTT, and then elaborate on the current understanding of how MeCP2 controls BDNF expression. Finally, we discuss the literature regarding alterations in BDNF levels in RTT individuals and MeCP2-based mouse models, as well as recent progress in searching for rational therapeutic interventions. PMID:23597512

  10. Social and Environmental Factors Affecting Fecal Glucocorticoids in Wild, Female White-Faced Capuchins (Cebus capucinus)

    PubMed Central

    CARNEGIE, SARAH D.; FEDIGAN, LINDA M.; ZIEGLER, TONI E.

    2016-01-01

    Assessing glucocorticoid levels in free-ranging nonhuman primates provides a means to determine the social and environmental stress load for individuals. We investigated the effect of four proximate variables—reproductive state, season, male rank stability, and dominance rank—on the level of fecal glucocorticoids (cortisol metabolites) in eight adult female white-faced capuchin monkeys in Costa Rica. Reproductive state, season, and male rank stability significantly affected fecal glucocorticoids while female dominance rank did not. Cortisol levels were significantly higher in pregnant females as compared with lactating or other reproductive states. Cortisol levels were higher among females during the dry season compared with the wet season, suggesting a metabolic adaptation to maintain homeostasis in drier, hotter conditions. Although unfamiliar males present a greater infanticidal threat than do familiar ones, we found that females experienced higher glucocorticoid levels during male rank instability events, regardless of whether the alpha male role was taken over by a familiar or an unfamiliar male. Our findings provide important benchmark and comparative data for future studies on the variables that affect glucocorticoid levels in this species and other mammals. PMID:21506140

  11. Brain size affects the behavioural response to predators in female guppies (Poecilia reticulata)

    PubMed Central

    van der Bijl, Wouter; Thyselius, Malin; Kotrschal, Alexander; Kolm, Niclas

    2015-01-01

    Large brains are thought to result from selection for cognitive benefits, but how enhanced cognition leads to increased fitness remains poorly understood. One explanation is that increased cognitive ability results in improved monitoring and assessment of predator threats. Here, we use male and female guppies (Poecilia reticulata), artificially selected for large and small brain size, to provide an experimental evaluation of this hypothesis. We examined their behavioural response as singletons, pairs or shoals of four towards a model predator. Large-brained females, but not males, spent less time performing predator inspections, an inherently risky behaviour. Video analysis revealed that large-brained females were further away from the model predator when in pairs but that they habituated quickly towards the model when in shoals of four. Males stayed further away from the predator model than females but again we found no brain size effect in males. We conclude that differences in brain size affect the female predator response. Large-brained females might be able to assess risk better or need less sensory information to reach an accurate conclusion. Our results provide experimental support for the general idea that predation pressure is likely to be important for the evolution of brain size in prey species. PMID:26203003

  12. Brain size affects the behavioural response to predators in female guppies (Poecilia reticulata).

    PubMed

    van der Bijl, Wouter; Thyselius, Malin; Kotrschal, Alexander; Kolm, Niclas

    2015-08-01

    Large brains are thought to result from selection for cognitive benefits, but how enhanced cognition leads to increased fitness remains poorly understood. One explanation is that increased cognitive ability results in improved monitoring and assessment of predator threats. Here, we use male and female guppies (Poecilia reticulata), artificially selected for large and small brain size, to provide an experimental evaluation of this hypothesis. We examined their behavioural response as singletons, pairs or shoals of four towards a model predator. Large-brained females, but not males, spent less time performing predator inspections, an inherently risky behaviour. Video analysis revealed that large-brained females were further away from the model predator when in pairs but that they habituated quickly towards the model when in shoals of four. Males stayed further away from the predator model than females but again we found no brain size effect in males. We conclude that differences in brain size affect the female predator response. Large-brained females might be able to assess risk better or need less sensory information to reach an accurate conclusion. Our results provide experimental support for the general idea that predation pressure is likely to be important for the evolution of brain size in prey species.

  13. Host plant affects the sexual attractiveness of the female white-spotted longicorn beetle, Anoplophora malasiaca

    PubMed Central

    Yasui, Hiroe; Fujiwara-Tsujii, Nao

    2016-01-01

    Anoplophora malasiaca (Coleoptera: Cerambycidae) is a serious pest that destroys various landscape and crop trees in Japan. We evaluated the precopulatory responses of three different A. malasiaca populations collected from mandarin orange, willow and blueberry trees. Most of the males accepted mates from within the same host plant population as well as females from the willow and blueberry populations. However, significant number of males from the blueberry and willow populations rejected females from the mandarin orange population immediately after touching them with their antennae. Because all three of the female populations produced contact sex pheromones on their elytra, the females of the mandarin orange population were predicted to possess extra chemicals that repelled the males of the other two populations. β-Elemene was identified as a key component that was only found in mandarin orange-fed females and induced a rejection response in willow-fed males. Our results represent the first example of a female-acquired repellent against conspecific males of different host plant populations, indicating that the host plant greatly affects the female’s sexual attractiveness. PMID:27412452

  14. Brain size affects the behavioural response to predators in female guppies (Poecilia reticulata).

    PubMed

    van der Bijl, Wouter; Thyselius, Malin; Kotrschal, Alexander; Kolm, Niclas

    2015-08-01

    Large brains are thought to result from selection for cognitive benefits, but how enhanced cognition leads to increased fitness remains poorly understood. One explanation is that increased cognitive ability results in improved monitoring and assessment of predator threats. Here, we use male and female guppies (Poecilia reticulata), artificially selected for large and small brain size, to provide an experimental evaluation of this hypothesis. We examined their behavioural response as singletons, pairs or shoals of four towards a model predator. Large-brained females, but not males, spent less time performing predator inspections, an inherently risky behaviour. Video analysis revealed that large-brained females were further away from the model predator when in pairs but that they habituated quickly towards the model when in shoals of four. Males stayed further away from the predator model than females but again we found no brain size effect in males. We conclude that differences in brain size affect the female predator response. Large-brained females might be able to assess risk better or need less sensory information to reach an accurate conclusion. Our results provide experimental support for the general idea that predation pressure is likely to be important for the evolution of brain size in prey species. PMID:26203003

  15. Rett syndrome - Stimulation of endogenous biogenic amines

    NASA Technical Reports Server (NTRS)

    Pelligra, R.; Norton, R. D.; Wilkinson, R.; Leon, H. A.; Matson, W. R.

    1992-01-01

    Transient hypercapnic hyperoxemia was induced in two Rett syndrome children by the administration of a gaseous mixture of 80 percent O2 and 20 percent CO2. Time course studies of neurotransmitters and their metabolites showed an immediate and marked increase in central biogenic amine turnover following inhalation of the gas mixture. The increased turnover of biogenic amines was associated with improved clinical changes. This suggests a coupled relationship and provides further support for an etiological role of neurotransmitter dysfunction in Rett syndrome. In a complementary study, elevation of pulmonary CO2 by application of a simple rebreathing device resulted in improvement of abnormal blood gases and elimination of the Cheyne-Stokes-like respiratory pattern of the Rett syndrome. Near normalization of the EEG occurred when a normal respiratory pattern was imposed by means of a respirator. Taken together, these results lead to the preliminary conclusion that cerebral hypoxemia secondary to abnormal respiratory function may contribute to diminished production of biogenic amines in Rett syndrome.

  16. Nosology and Diagnosis of Rett Syndrome

    ERIC Educational Resources Information Center

    Matson, Johnny L.; Fodstad, Jill C.; Boisjoli, Jessica A.

    2008-01-01

    Rett Syndrome is one of the least commonly occurring autism spectrum disorders (ASD), but certainly one of the most devastating. A genetic profile has been identified, but checklists still have an important role for prescreening, especially before expensive genetic testing, and to provide precise strengths and weaknesses with respect to the core…

  17. The Invisible Enemy: Fighting Rett Syndrome.

    ERIC Educational Resources Information Center

    Weisz, Chaudia Minden

    1986-01-01

    The mother of a child with Rett Syndrome, a degenerative brain disease, describes difficulties in obtaining a diagnosis and the relief she and her family felt once the diagnosis was made. She emphasizes the need for parents to offer each other support. (CL)

  18. Rett Syndrome: A Longitudinal Developmental Case Report.

    ERIC Educational Resources Information Center

    Garber, Norman; Veydt, Nicole

    1990-01-01

    The clinical course of development of a 14-year-old girl with Rett Syndrome is outlined. Results indicated a general stagnation in gross and fine motor skills, self-help skills, communication, and cognition, beginning at approximately 15 months. No skills progressed beyond the 2-year level despite several years of intensive intervention.…

  19. Attention and Communication in Rett Syndrome

    ERIC Educational Resources Information Center

    Fabio, Rosa Angela; Antonietti, Alessandro; Castelli, Ilaria; Marchetti, Antonella

    2009-01-01

    The study of selective attention and its influence on communication in patients with Rett Syndrome (RS), in which communication abilities are impaired is particularly relevant. The aim of this study was to analyse attention and communication abilities in RS. A sample of 20 children (10 girls with RS and 10 control girls, matched on mental age)…

  20. Recognizing and Treating Rett Syndrome in Schools

    ERIC Educational Resources Information Center

    Wanzek, Megan; Jenson, William R.; Houlihan, Daniel

    2012-01-01

    A review of the literature on Rett syndrome (RS) for school-based professionals is presented from a behavioral perspective. A description of RS is provided, including distinctive physical, behavioral, and emotional features, diagnostic criteria for classic and "formes frustes" forms of RS, and stages of the disorder. The similarities and…

  1. Rett's Syndrome in an Australian Child.

    ERIC Educational Resources Information Center

    Rossiter, E. J. R.; Callaghan, C.

    1987-01-01

    Following a literature review on Rett's Syndrome, a case study is presented of a 15-year-old girl with normal development during the first months of life followed by manifestation of behavior abnormalities and deterioration of intellectual level. The child's medical history and the mother's description of the girl's development are included.…

  2. Sexually transmitted bacteria affect female cloacal assemblages in a wild bird

    PubMed Central

    White, Joël; Mirleau, Pascal; Danchin, Etienne; Mulard, Hervé; Hatch, Scott A.; Heeb, Philipp; Wagner, Richard H.

    2013-01-01

    Sexual transmission is an important mode of disease propagation, yet its mechanisms remain largely unknown in wild populations. Birds comprise an important model for studying sexually transmitted microbes because their cloaca provides a potential for both gastrointestinal pathogens and endosymbionts to become incorporated into ejaculates. We experimentally demonstrate in a wild population of kittiwakes (Rissa tridactyla) that bacteria are transmitted during copulation and affect the composition and diversity of female bacterial communities. We used an anti-insemination device attached to males in combination with a molecular technique (ARISA) that describes bacterial communities. After inseminations were experimentally blocked, the cloacal communities of mates became increasingly dissimilar. Moreover, female cloacal diversity decreased and the extinction of mate-shared bacteria increased, indicating that female cloacal assemblages revert to their pre-copulatory state and that the cloaca comprises a resilient microbial ecosystem. PMID:20961376

  3. Sexually transmitted bacteria affect female cloacal assemblages in a wild bird

    USGS Publications Warehouse

    White, Joël; Mirleau, Pascal; Danchin, Etienne; Mulard, Hervé; Hatch, Scott A.; Heeb, Phillipp; Wagner, Richard H.

    2010-01-01

    Sexual transmission is an important mode of disease propagation, yet its mechanisms remain largely unknown in wild populations. Birds comprise an important model for studying sexually transmitted microbes because their cloaca provides a potential for both gastrointestinal pathogens and endosymbionts to become incorporated into ejaculates. We experimentally demonstrate in a wild population of kittiwakes (Rissa tridactyla) that bacteria are transmitted during copulation and affect the composition and diversity of female bacterial communities. We used an anti-insemination device attached to males in combination with a molecular technique (automated ribosomal intergenic spacer analysis) that describes bacterial communities. After inseminations were experimentally blocked, the cloacal communities of mates became increasingly dissimilar. Moreover, female cloacal diversity decreased and the extinction of mate-shared bacteria increased, indicating that female cloacal assemblages revert to their pre-copulatory state and that the cloaca comprises a resilient microbial ecosystem.

  4. Quantification of functional abilities in Rett syndrome: a comparison between stages III and IV

    PubMed Central

    Monteiro, Carlos BM; Savelsbergh, Geert JP; Smorenburg, Ana RP; Graciani, Zodja; Torriani-Pasin, Camila; de Abreu, Luiz Carlos; Valenti, Vitor E; Kok, Fernando

    2014-01-01

    We aimed to evaluate the functional abilities of persons with Rett syndrome (RTT) in stages III and IV. The group consisted of 60 females who had been diagnosed with RTT: 38 in stage III, mean age (years) of 9.14, with a standard deviation of 5.84 (minimum 2.2/maximum 26.4); and 22 in stage IV, mean age of 12.45, with a standard deviation of 6.17 (minimum 5.3/maximum 26.9). The evaluation was made using the Pediatric Evaluation of Disability Inventory, which has 197 items in the areas of self-care, mobility, and social function. The results showed that in the area of self-care, stage III and stage IV RTT persons had a level of 24.12 and 18.36 (P=0.002), respectively. In the area of mobility, stage III had 37.22 and stage IV had 14.64 (P<0.001), while in the area of social function, stage III had 17.72 and stage IV had 12.14 (P=0.016). In conclusion, although persons with stage III RTT have better functional abilities when compared with stage IV, the areas of mobility, self-care, and social function are quite affected, which shows a great functional dependency and need for help in basic activities of daily life. PMID:25061307

  5. Red blood cells in Rett syndrome: oxidative stress, morphological changes and altered membrane organization.

    PubMed

    Ciccoli, Lucia; De Felice, Claudio; Leoncini, Silvia; Signorini, Cinzia; Cortelazzo, Alessio; Zollo, Gloria; Pecorelli, Alessandra; Rossi, Marcello; Hayek, Joussef

    2015-11-01

    In this review, we summarize the current evidence on the erythrocyte as a previously unrecognized target cell in Rett syndrome, a rare (1:10 000 females) and devastating neurodevelopmental disorder caused by loss-of-function mutations in a single gene (i.e. MeCP2, CDKL5, or rarely FOXG1). In particular, we focus on morphological changes, membrane oxidative damage, altered membrane fatty acid profile, and aberrant skeletal organization in erythrocytes from patients with typical Rett syndrome and MeCP2 gene mutations. The beneficial effects of ω-3 polyunsaturated fatty acids (PUFAs) are also summarized for this condition to be considered as a 'model' condition for autism spectrum disorders.

  6. Day length and estradiol affect same-sex affiliative behavior in the female meadow vole

    PubMed Central

    Beery, Annaliese K.; Loo, Theresa J.; Zucker, Irving

    2008-01-01

    Non-sexual social bonding between adult mammals remains poorly understood, despite its importance in many species. Female meadow voles are territorial and nest alone in long summer day lengths when circulating estradiol concentrations are high, but cohabit in groups in short winter photoperiods when estradiol secretion is low. The influence of day length and estradiol on same-sex huddling behavior was assessed in adult female pairs housed together in long day lengths (LDs) or short day lengths (SDs) from weaning. The behavior of intact, ovariectomized, and estradiol-treated ovariectomized females from each photoperiod was assessed during 3 hour partner preference tests. Intact SD voles, unlike intact LD voles, spent the majority of the test in proximity to their cage mates. Estradiol treatment of SD voles significantly reduced time spent huddling with the partner. Neither ovariectomy nor estradiol treatment significantly affected the amount of time LD females spent in contact with their partners. Low estradiol availability is therefore a necessary but not sufficient condition for maintenance of high levels of huddling. These results establish that ovarian hormones interact with photoperiod to affect same-sex social behavior. PMID:18387611

  7. Day length and estradiol affect same-sex affiliative behavior in the female meadow vole.

    PubMed

    Beery, Annaliese K; Loo, Theresa J; Zucker, Irving

    2008-06-01

    Non-sexual social bonding between adult mammals is poorly understood, despite its importance in many species. Female meadow voles are territorial and nest alone in long summer day lengths when circulating estradiol concentrations are high, but cohabit in groups in short winter photoperiods when estradiol secretion is low. The influence of day length and estradiol on same-sex huddling behavior was assessed in adult female pairs housed together in long day lengths (LDs) or short day lengths (SDs) from weaning. The behavior of intact, ovariectomized, and estradiol-treated ovariectomized females from each photoperiod was assessed during 3 h partner-preference tests. Intact SD voles, unlike intact LD voles, spent the majority of the test in proximity to their cage-mates. Estradiol treatment of SD voles significantly reduced time spent huddling with the partner. Neither ovariectomy nor estradiol treatment significantly affected the amount of time LD females spent in contact with their partners. Low estradiol availability is therefore a necessary but not sufficient condition for maintenance of high levels of huddling. These results establish that ovarian hormones interact with photoperiod to affect same-sex social behavior.

  8. Day length and estradiol affect same-sex affiliative behavior in the female meadow vole.

    PubMed

    Beery, Annaliese K; Loo, Theresa J; Zucker, Irving

    2008-06-01

    Non-sexual social bonding between adult mammals is poorly understood, despite its importance in many species. Female meadow voles are territorial and nest alone in long summer day lengths when circulating estradiol concentrations are high, but cohabit in groups in short winter photoperiods when estradiol secretion is low. The influence of day length and estradiol on same-sex huddling behavior was assessed in adult female pairs housed together in long day lengths (LDs) or short day lengths (SDs) from weaning. The behavior of intact, ovariectomized, and estradiol-treated ovariectomized females from each photoperiod was assessed during 3 h partner-preference tests. Intact SD voles, unlike intact LD voles, spent the majority of the test in proximity to their cage-mates. Estradiol treatment of SD voles significantly reduced time spent huddling with the partner. Neither ovariectomy nor estradiol treatment significantly affected the amount of time LD females spent in contact with their partners. Low estradiol availability is therefore a necessary but not sufficient condition for maintenance of high levels of huddling. These results establish that ovarian hormones interact with photoperiod to affect same-sex social behavior. PMID:18387611

  9. Natural variation in epigenetic pathways affects the specification of female gamete precursors in Arabidopsis.

    PubMed

    Rodríguez-Leal, Daniel; León-Martínez, Gloria; Abad-Vivero, Ursula; Vielle-Calzada, Jean-Philippe

    2015-04-01

    In angiosperms, the transition to the female gametophytic phase relies on the specification of premeiotic gamete precursors from sporophytic cells in the ovule. In Arabidopsis thaliana, a single diploid cell is specified as the premeiotic female gamete precursor. Here, we show that ecotypes of Arabidopsis exhibit differences in megasporogenesis leading to phenotypes reminiscent of defects in dominant mutations that epigenetically affect the specification of female gamete precursors. Intraspecific hybridization and polyploidy exacerbate these defects, which segregate quantitatively in F2 populations derived from ecotypic hybrids, suggesting that multiple loci control cell specification at the onset of female meiosis. This variation in cell differentiation is influenced by the activity of ARGONAUTE9 (AGO9) and RNA-DEPENDENT RNA POLYMERASE6 (RDR6), two genes involved in epigenetic silencing that control the specification of female gamete precursors. The pattern of transcriptional regulation and localization of AGO9 varies among ecotypes, and abnormal gamete precursors in ovules defective for RDR6 share identity with ectopic gamete precursors found in selected ecotypes. Our results indicate that differences in the epigenetic control of cell specification lead to natural phenotypic variation during megasporogenesis. We propose that this mechanism could be implicated in the emergence and evolution of the reproductive alternatives that prevail in flowering plants.

  10. Noise affects the shape of female preference functions for acoustic signals.

    PubMed

    Reichert, Michael S; Ronacher, Bernhard

    2015-02-01

    The shape of female mate preference functions influences the speed and direction of sexual signal evolution. However, the expression of female preferences is modulated by interactions between environmental conditions and the female's sensory processing system. Noise is an especially relevant environmental condition because it interferes directly with the neural processing of signals. Although noise is therefore likely a significant force in the evolution of communication systems, little is known about its effects on preference function shape. In the grasshopper Chorthippus biguttulus, female preferences for male calling song characteristics are likely to be affected by noise because its auditory system is sensitive to fine temporal details of songs. We measured female preference functions for variation in male song characteristics in several levels of masking noise and found strong effects of noise on preference function shape. The overall responsiveness to signals in noise generally decreased. Preference strength increased for some signal characteristics and decreased for others, largely corresponding to expectations based on neurophysiological studies of acoustic signal processing. These results suggest that different signal characteristics will be favored under different noise conditions, and thus that signal evolution may proceed differently depending on the extent and temporal patterning of environmental noise.

  11. Natural Variation in Epigenetic Pathways Affects the Specification of Female Gamete Precursors in Arabidopsis[OPEN

    PubMed Central

    Rodríguez-Leal, Daniel; León-Martínez, Gloria; Abad-Vivero, Ursula; Vielle-Calzada, Jean-Philippe

    2015-01-01

    In angiosperms, the transition to the female gametophytic phase relies on the specification of premeiotic gamete precursors from sporophytic cells in the ovule. In Arabidopsis thaliana, a single diploid cell is specified as the premeiotic female gamete precursor. Here, we show that ecotypes of Arabidopsis exhibit differences in megasporogenesis leading to phenotypes reminiscent of defects in dominant mutations that epigenetically affect the specification of female gamete precursors. Intraspecific hybridization and polyploidy exacerbate these defects, which segregate quantitatively in F2 populations derived from ecotypic hybrids, suggesting that multiple loci control cell specification at the onset of female meiosis. This variation in cell differentiation is influenced by the activity of ARGONAUTE9 (AGO9) and RNA-DEPENDENT RNA POLYMERASE6 (RDR6), two genes involved in epigenetic silencing that control the specification of female gamete precursors. The pattern of transcriptional regulation and localization of AGO9 varies among ecotypes, and abnormal gamete precursors in ovules defective for RDR6 share identity with ectopic gamete precursors found in selected ecotypes. Our results indicate that differences in the epigenetic control of cell specification lead to natural phenotypic variation during megasporogenesis. We propose that this mechanism could be implicated in the emergence and evolution of the reproductive alternatives that prevail in flowering plants. PMID:25829442

  12. Extraneous color affects female macaques’ gaze preference for photographs of male conspecifics

    PubMed Central

    Hughes, Kelly D.; Higham, James P.; Allen, William L.; Elliot, Andrew J.; Hayden, Benjamin Y.

    2014-01-01

    Humans find members of the opposite sex more attractive when their image is spatially associated with the color red. This effect even occurs when the red color is not on the skin or clothing (i.e. is extraneous). We hypothesize that this extraneous color effect could be at least partially explained by a low-level and biologically innate generalization process, and so similar extraneous color effects should be observed in non-humans. To test this possibility, we examined the influence of extraneous color in rhesus macaques (Macaca mulatta). Across two experiments, we determined the influence of extraneous red on viewing preferences (assessed by looking time) in free-ranging rhesus monkeys. We presented male and female monkeys with black and white photographs of the hindquarters of same and opposite sex conspecifics on either a red (experimental condition) or blue (control condition) background. As a secondary control, we also presented neutral stimuli (photographs of seashells) on red and blue backgrounds. We found that female monkeys looked longer at a picture of a male scrotum, but not a seashell, on a red background (Experiment 1), while males showed no bias. Neither male nor female monkeys showed an effect of color on looking time for female hindquarters or seashells (Experiment 2). The finding for females viewing males suggests that extraneous color affects preferences among rhesus macaques. Further, it raises the possibility that evolutionary processes gave rise to extraneous color effects during human evolution. PMID:25530698

  13. Natural variation in epigenetic pathways affects the specification of female gamete precursors in Arabidopsis.

    PubMed

    Rodríguez-Leal, Daniel; León-Martínez, Gloria; Abad-Vivero, Ursula; Vielle-Calzada, Jean-Philippe

    2015-04-01

    In angiosperms, the transition to the female gametophytic phase relies on the specification of premeiotic gamete precursors from sporophytic cells in the ovule. In Arabidopsis thaliana, a single diploid cell is specified as the premeiotic female gamete precursor. Here, we show that ecotypes of Arabidopsis exhibit differences in megasporogenesis leading to phenotypes reminiscent of defects in dominant mutations that epigenetically affect the specification of female gamete precursors. Intraspecific hybridization and polyploidy exacerbate these defects, which segregate quantitatively in F2 populations derived from ecotypic hybrids, suggesting that multiple loci control cell specification at the onset of female meiosis. This variation in cell differentiation is influenced by the activity of ARGONAUTE9 (AGO9) and RNA-DEPENDENT RNA POLYMERASE6 (RDR6), two genes involved in epigenetic silencing that control the specification of female gamete precursors. The pattern of transcriptional regulation and localization of AGO9 varies among ecotypes, and abnormal gamete precursors in ovules defective for RDR6 share identity with ectopic gamete precursors found in selected ecotypes. Our results indicate that differences in the epigenetic control of cell specification lead to natural phenotypic variation during megasporogenesis. We propose that this mechanism could be implicated in the emergence and evolution of the reproductive alternatives that prevail in flowering plants. PMID:25829442

  14. Overexpression of mineralocorticoid receptors does not affect memory and anxiety-like behavior in female mice

    PubMed Central

    Kanatsou, Sofia; Kuil, Laura E.; Arp, Marit; Oitzl, Melly S.; Harris, Anjanette P.; Seckl, Jonathan R.; Krugers, Harm J.; Joels, Marian

    2015-01-01

    Mineralocorticoid receptors (MRs) have been implicated in behavioral adaptation and learning and memory. Since—at least in humans—MR function seems to be sex-dependent, we examined the behavioral relevance of MR in female mice exhibiting transgenic MR overexpression in the forebrain. Transgenic MR overexpression did not affect contextual fear memory or cued fear learning and memory. Moreover, MR overexpressing and control mice discriminated equally well between fear responses in a combined cue and context fear conditioning paradigm. Also context-memory in an object recognition task was unaffected in MR overexpressing mice. We conclude that MR overexpression in female animals does not affect fear conditioned responses and object recognition memory. PMID:26236208

  15. Studies of X inactivation and isodisomy in twins provide further evidence that the X chromosomes is not involved in Rett syndrome

    SciTech Connect

    Migeon, B.R.; Dunn, M.A.; Schmeckpeper, B.J.; Naidu, S.; Thomas, G. |

    1995-03-01

    Rett syndrome (RS), a progressive encephalopathy with onset in infancy, has been attributed to an X-linked mutation, mainly on the basis of its occurrence almost exclusively in females and its concordance in female MZ twins. The underlying mechanisms proposed are an X-linked dominant mutation with male lethality, uniparental disomy of the X chromosome, and/or some disturbance in the process of X inactivation leading to unequal distribution of cells expressing maternal or paternal alleles (referred to as a {open_quotes}nonrandom{close_quotes} or {open_quotes}skewed {close_quotes} inactivation). To determine if the X chromosome is in fact involved in RS, we studied a group of affected females including three pairs of MZ twins, two concordant for RS and one uniquely discordant for RS. Analysis of X-inactivation patterns confirms the frequent nonrandom X inactivation previously observed in MZ twins but indicates that this is independent of RS. Analysis of 29 RS females reveals not one instance of uniparental X disomy, extending the observations previously reported. Therefore, our findings contribute no support for the hypothesis that RS is an X-linked disorder. Furthermore, the concordant phenotype in most MZ females twins with RS, which has not been observed in female twins with known X-linked mutations, argues against an X mutation. 41 refs., 2 figs.

  16. A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett's syndrome: report of 35 cases.

    PubMed

    Hagberg, B; Aicardi, J; Dias, K; Ramos, O

    1983-10-01

    Thirty-five patients, exclusively girls, from three countries had a uniform and striking progressive encephalopathy. After normal general and psychomotor development up to the age of 7 to 18 months, developmental stagnation occurred, followed by rapid deterioration of higher brain functions. Within one-and-a-half years this deterioration led to severe dementia, autism, loss of purposeful use of the hands, jerky truncal ataxia, and acquired microcephaly. The destructive stage was followed by apparent stability lasting through decades. Additional insidious neurological abnormalities supervened, mainly spastic parapareses, vasomotor disturbances of the lower limbs, and epilepsy. Prior extensive laboratory investigations have not revealed the cause. The condition is similar to a virtually overlooked syndrome described by Rett in the German literature. The exclusive involvement of females, correlated with findings in family data analyses, suggests a dominant mutation on one X chromosome that results in affected girls and nonviable male hemizygous conceptuses. PMID:6638958

  17. Profiling Early Socio-Communicative Development in Five Young Girls with the Preserved Speech Variant of Rett Syndrome

    ERIC Educational Resources Information Center

    Marschik, Peter B.; Kaufmann, Walter E.; Einspieler, Christa; Bartl-Pokorny, Katrin D.; Wolin, Thomas; Pini, Giorgio; Budimirovic, Dejan B.; Zappella, Michele; Sigafoos, Jeff

    2012-01-01

    Rett syndrome (RTT) is a developmental disorder characterized by regression of purposeful hand skills and spoken language, although some affected children retain some ability to speech. We assessed the communicative abilities of five young girls, who were later diagnosed with the preserved speech variant of RTT, during the pre-regression period…

  18. Acute stress differentially affects aromatase activity in specific brain nuclei of adult male and female quail.

    PubMed

    Dickens, Molly J; Cornil, Charlotte A; Balthazart, Jacques

    2011-11-01

    The rapid and temporary suppression of reproductive behavior is often assumed to be an important feature of the adaptive acute stress response. However, how this suppression operates at the mechanistic level is poorly understood. The enzyme aromatase converts testosterone to estradiol in the brain to activate reproductive behavior in male Japanese quail (Coturnix japonica). The discovery of rapid and reversible modification of aromatase activity (AA) provides a potential mechanism for fast, stress-induced changes in behavior. We investigated the effects of acute stress on AA in both sexes by measuring enzyme activity in all aromatase-expressing brain nuclei before, during, and after 30 min of acute restraint stress. We show here that acute stress rapidly alters AA in the male and female brain and that these changes are specific to the brain nuclei and sex of the individual. Specifically, acute stress rapidly (5 min) increased AA in the male medial preoptic nucleus, a region controlling male reproductive behavior; in females, a similar increase was also observed, but it appeared delayed (15 min) and had smaller amplitude. In the ventromedial and tuberal hypothalamus, regions associated with female reproductive behavior, stress induced a quick and sustained decrease in AA in females, but in males, only a slight increase (ventromedial) or no change (tuberal) in AA was observed. Effects of acute stress on brain estrogen production, therefore, represent one potential way through which stress affects reproduction.

  19. Brain size affects female but not male survival under predation threat

    PubMed Central

    Kotrschal, Alexander; Buechel, Séverine D; Zala, Sarah M; Corral-Lopez, Alberto; Penn, Dustin J; Kolm, Niclas; Sorci, Gabriele

    2015-01-01

    There is remarkable diversity in brain size among vertebrates, but surprisingly little is known about how ecological species interactions impact the evolution of brain size. Using guppies, artificially selected for large and small brains, we determined how brain size affects survival under predation threat in a naturalistic environment. We cohoused mixed groups of small- and large-brained individuals in six semi-natural streams with their natural predator, the pike cichlid, and monitored survival in weekly censuses over 5 months. We found that large-brained females had 13.5% higher survival compared to small-brained females, whereas the brain size had no discernible effect on male survival. We suggest that large-brained females have a cognitive advantage that allows them to better evade predation, whereas large-brained males are more colourful, which may counteract any potential benefits of brain size. Our study provides the first experimental evidence that trophic interactions can affect the evolution of brain size. PMID:25960088

  20. Brain size affects female but not male survival under predation threat.

    PubMed

    Kotrschal, Alexander; Buechel, Séverine D; Zala, Sarah M; Corral-Lopez, Alberto; Penn, Dustin J; Kolm, Niclas

    2015-07-01

    There is remarkable diversity in brain size among vertebrates, but surprisingly little is known about how ecological species interactions impact the evolution of brain size. Using guppies, artificially selected for large and small brains, we determined how brain size affects survival under predation threat in a naturalistic environment. We cohoused mixed groups of small- and large-brained individuals in six semi-natural streams with their natural predator, the pike cichlid, and monitored survival in weekly censuses over 5 months. We found that large-brained females had 13.5% higher survival compared to small-brained females, whereas the brain size had no discernible effect on male survival. We suggest that large-brained females have a cognitive advantage that allows them to better evade predation, whereas large-brained males are more colourful, which may counteract any potential benefits of brain size. Our study provides the first experimental evidence that trophic interactions can affect the evolution of brain size. PMID:25960088

  1. InterRett, a Model for International Data Collection in a Rare Genetic Disorder

    ERIC Educational Resources Information Center

    Louise, Sandra; Fyfe, Sue; Bebbington, Ami; Bahi-Buisson, Nadia; Anderson, Alison; Pineda, Merce; Percy, Alan; Zeev, Bruria Ben; Wu, Xi Ru; Bao, Xinhua; MacLeod, Patrick; Armstrong, Judith; Leonard, Helen

    2009-01-01

    Rett syndrome (RTT) is a rare genetic disorder within the autistic spectrum. This study compared socio-demographic, clinical and genetic characteristics of the international database, InterRett, and the population-based Australian Rett syndrome database (ARSD). It also explored the strengths and limitations of InterRett in comparison with other…

  2. Perinatal iron deficiency affects locomotor behavior and water maze performance in adult male and female rats.

    PubMed

    Bourque, Stephane L; Iqbal, Umar; Reynolds, James N; Adams, Michael A; Nakatsu, Kanji

    2008-05-01

    Iron deficiency during early growth and development adversely affects multiple facets of cognition and behavior in adult rats. The purpose of this study was to assess the nature of the learning and locomotor behavioral deficits observed in male and female rats in the absence of depressed brain iron levels at the time of testing. Adult female Wistar rats were fed either an iron-enriched diet (>225 mg/kg Fe) or an iron-restricted diet (3 mg/kg Fe) for 2 wk prior to and throughout gestation, and a nonpurified diet (270 mg/kg Fe) thereafter. Open-field (OF) and Morris water maze (MWM) testing began when the offspring reached early adulthood (12 wk). At birth, perinatal iron-deficient (PID) offspring had reduced (P < 0.001) hematocrits (-33%), liver iron stores (-83%), and brain iron concentrations (-38%) compared with controls. Although there were no differences in iron status in adults, the PID males and females exhibited reduced OF exploratory behavior, albeit only PID males had an aversion to the center of the apparatus (2.5 vs. 6.9% in controls, P < 0.001). Additionally, PID males required greater path lengths to reach the hidden platform in the MWM, had reduced spatial bias for the target quadrant, and had a tendency for greater thigmotactic behavior in the probe trials (16.5 vs. 13.0% in controls; P = 0.06). PID females had slower swim speeds in all testing phases (-6.2%; P < 0.001). These results suggest that PID has detrimental programming effects in both male and female rats, although the behaviors suggest different mechanisms may be involved in each sex.

  3. Gait initiation in children with Rett syndrome.

    PubMed

    Isaias, Ioannis Ugo; Dipaola, Mariangela; Michi, Marlies; Marzegan, Alberto; Volkmann, Jens; Rodocanachi Roidi, Marina L; Frigo, Carlo Albino; Cavallari, Paolo

    2014-01-01

    Rett syndrome is an X-linked neurodevelopmental condition mainly characterized by loss of spoken language and a regression of purposeful hand use, with the development of distinctive hand stereotypies, and gait abnormalities. Gait initiation is the transition from quiet stance to steady-state condition of walking. The associated motor program seems to be centrally mediated and includes preparatory adjustments prior to any apparent voluntary movement of the lower limbs. Anticipatory postural adjustments contribute to postural stability and to create the propulsive forces necessary to reach steady-state gait at a predefined velocity and may be indicative of the effectiveness of the feedforward control of gait. In this study, we examined anticipatory postural adjustments associated with gait initiation in eleven girls with Rett syndrome and ten healthy subjects. Muscle activity (tibialis anterior and soleus muscles), ground reaction forces and body kinematic were recorded. Children with Rett syndrome showed a distinctive impairment in temporal organization of all phases of the anticipatory postural adjustments. The lack of appropriate temporal scaling resulted in a diminished impulse to move forward, documented by an impairment in several parameters describing the efficiency of gait start: length and velocity of the first step, magnitude and orientation of centre of pressure-centre of mass vector at the instant of (swing-)toe off. These findings were related to an abnormal muscular activation pattern mainly characterized by a disruption of the synergistic activity of antagonistic pairs of postural muscles. This study showed that girls with Rett syndrome lack accurate tuning of feedforward control of gait.

  4. Music Therapy: A Therapeutic Intervention for Girls with Rett Syndrome.

    ERIC Educational Resources Information Center

    Coleman, Kathleen A.

    The paper reviews music therapy, the educational background of music therapists, music therapy's various settings, and its use as an intervention with girls with Rett Syndrome. Sample music therapy programs for three girls (aged 5, 14, and 20 years) with Rett Syndrome are presented. The sample programs provide: student descriptions; the girls'…

  5. Female Genital Dialogues: Female Genital Self-Image, Sexual Dysfunction, and Quality of Life in Patients With Vitiligo With and Without Genital Affection.

    PubMed

    Sarhan, Deena; Mohammed, Ghada F A; Gomaa, Amal H A; Eyada, Moustafa M K

    2016-01-01

    Vitiligo has a major effect on sexual health because of the disfiguring skin lesions affecting self-image and self-esteem. However, this topic has not explored. This article aimed to assess the effect of vitiligo on genital self-image, sexual function, and quality of life in female patients. This cross-sectional study included 50 sexually active women with vitiligo and 25 women without vitiligo. All participants subjected to full history taking and examination. Extent of vitiligo was assessed with the Vitiligo Area Scoring Index score, sexual function with the Female Sexual Function Index, genital self-image with Female Genital Self-Image Score and quality of life with the Dermatology Life Quality Index questionnaires. The main outcome measures were correlation between Vitiligo Area Scoring Index, Female Genital Self-Image Score, Female Sexual Function Index, and Dermatology Life Quality Index domains was determined using t test and Pearson correlation. This study revealed a negative correlation between the Vitiligo Area Scoring Index score and sexual satisfaction. Vitiligo Area Scoring Index and Dermatology Life Quality Index score was significantly correlated with Arabic Version of the Female Genital Self-Image Score alone and with Arabic Version of the Female Sexual Functioning Index alone and with both the Arabic Version of the Female Genital Self-Image Score and the Arabic Version of the Female Sexual Functioning Index (p <.05). Sexual and psychological assessment of patients with vitiligo is imperative to improve outcomes and increase patients' compliance with treatment.

  6. Oxidative brain damage in Mecp2-mutant murine models of Rett syndrome.

    PubMed

    De Felice, Claudio; Della Ragione, Floriana; Signorini, Cinzia; Leoncini, Silvia; Pecorelli, Alessandra; Ciccoli, Lucia; Scalabrì, Francesco; Marracino, Federico; Madonna, Michele; Belmonte, Giuseppe; Ricceri, Laura; De Filippis, Bianca; Laviola, Giovanni; Valacchi, Giuseppe; Durand, Thierry; Galano, Jean-Marie; Oger, Camille; Guy, Alexandre; Bultel-Poncé, Valérie; Guy, Jacky; Filosa, Stefania; Hayek, Joussef; D'Esposito, Maurizio

    2014-08-01

    Rett syndrome (RTT) is a rare neurodevelopmental disorder affecting almost exclusively females, caused in the overwhelming majority of the cases by loss-of-function mutations in the gene encoding methyl-CpG binding protein 2 (MECP2). High circulating levels of oxidative stress (OS) markers in patients suggest the involvement of OS in the RTT pathogenesis. To investigate the occurrence of oxidative brain damage in Mecp2 mutant mouse models, several OS markers were evaluated in whole brains of Mecp2-null (pre-symptomatic, symptomatic, and rescued) and Mecp2-308 mutated (pre-symptomatic and symptomatic) mice, and compared to those of wild type littermates. Selected OS markers included non-protein-bound iron, isoprostanes (F2-isoprostanes, F4-neuroprostanes, F2-dihomo-isoprostanes) and 4-hydroxy-2-nonenal protein adducts. Our findings indicate that oxidative brain damage 1) occurs in both Mecp2-null (both -/y and stop/y) and Mecp2-308 (both 308/y males and 308/+ females) mouse models of RTT; 2) precedes the onset of symptoms in both Mecp2-null and Mecp2-308 models; and 3) is rescued by Mecp2 brain specific gene reactivation. Our data provide direct evidence of the link between Mecp2 deficiency, oxidative stress and RTT pathology, as demonstrated by the rescue of the brain oxidative homeostasis following brain-specifically Mecp2-reactivated mice. The present study indicates that oxidative brain damage is a previously unrecognized hallmark feature of murine RTT, and suggests that Mecp2 is involved in the protection of the brain from oxidative stress.

  7. Male Age Affects Female Mate Preference, Quantity of Accessory Gland Proteins, and Sperm Traits and Female Fitness in D. melanogaster.

    PubMed

    Rezaei, Abolhasan; Krishna, Mysore Siddaiah; Santhosh, Hassan T

    2015-01-01

    For species in which mating is resource-independent and offspring do not receive parental care, theoretical models of age-based female mate preference predict that females should prefer to mate with older males as they have demonstrated ability to survive. Thus, females should obtain a fitness benefit from mating with older males. However, male aging is often associated with reductions in quantity of sperm. The adaptive significance of age-based mate choice is therefore unclear. Various hypotheses have made conflicting predictions concerning this issue, because published studies have not investigated the effect of age on accessory gland proteins and sperm traits. D. melanogaster exhibits resource-independent mating, and offspring do not receive parental care, making this an appropriate model for studying age-based mate choice. In the present study, we found that D. melanogaster females of all ages preferred to mate with the younger of two competing males. Young males performed significantly greater courtship attempts and females showed least rejection for the same than middle-aged and old males. Young males had small accessory glands that contained very few main cells that were larger than average. Nevertheless, compared with middle-aged or old males, the young males transferred greater quantities of accessory gland proteins and sperm to mated females. As a result, females that mated with young male produced more eggs and progeny than those that mated with older males. Furthermore, mating with young male reduced female's lifespan. These studies indicate that quantity of accessory gland proteins and sperm traits decreased with male age and females obtain direct fitness benefit from mating with preferred young males.

  8. Prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP) affects reproductive outcomes in female mice

    PubMed Central

    Niermann, Sarah; Rattan, Saniya; Brehm, Emily; Flaws, Jodi A.

    2015-01-01

    This study tested the hypothesis that prenatal DEHP exposure affects female reproduction. To test this hypothesis, pregnant female CD-1 mice were orally dosed daily with tocopherol-stripped corn oil (vehicle control) or DEHP (20μg/kg/day-750mg/kg/day) from gestation day 11-birth. Pups were counted, weighed, and sexed at birth, ovaries were subjected to evaluations of follicle numbers on postnatal days (PNDs) 8 and 21, and fertility was evaluated at 3-9 months. The results indicate that prenatal DEHP exposure increased male-to-female ratio compared to controls. Prenatal DEHP exposure also increased preantral follicle numbers at PND 21 compared to controls. Further, 22.2% of the 20 μg/kg/day treated animals took longer than 5 days to get pregnant at 3 months and 28.6% of the 750 mg/kg/day treated animals lost some of their pups at 6 months. Thus, prenatal DEHP exposure alters F1 sex ratio, increases preantral follicle numbers, and causes some breeding abnormalities PMID:25765777

  9. Disruption of insulin signalling affects the neuroendocrine stress reaction in Drosophila females.

    PubMed

    Rauschenbach, Inga Y; Karpova, Evgenia K; Adonyeva, Natalya V; Andreenkova, Olga V; Faddeeva, Natalya V; Burdina, Elena V; Alekseev, Alexander A; Menshanov, Petr N; Gruntenko, Nataly E

    2014-10-15

    Juvenile hormone (JH) and dopamine are involved in the stress response in insects. The insulin/insulin-like growth factor signalling pathway has also recently been found to be involved in the regulation of various processes, including stress tolerance. However, the relationships between the JH, dopamine and insulin signalling pathways remain unclear. Here, we study the role of insulin signalling in the regulation of JH and dopamine metabolism under normal and heat stress conditions in Drosophila melanogaster females. We show that suppression of the insulin-like receptor (InR) in the corpus allatum, a specialised endocrine gland that synthesises JH, causes an increase in dopamine level and JH-hydrolysing activity and alters the activities of enzymes that produce as well as those that degrade dopamine [alkaline phosphatase (ALP), tyrosine hydroxylase (TH) and dopamine-dependent arylalkylamine N-acetyltransferase (DAT)]. We also found that InR suppression in the corpus allatum modulates dopamine, ALP, TH and JH-hydrolysing activity in response to heat stress and that it decreases the fecundity of the flies. JH application restores dopamine metabolism and fecundity in females with decreased InR expression in the corpus allatum. Our data provide evidence that the insulin/insulin-like growth factor signalling pathway regulates dopamine metabolism in females of D. melanogaster via the system of JH metabolism and that it affects the development of the neuroendocrine stress reaction and interacts with JH in the control of reproduction in this species.

  10. Prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP) affects reproductive outcomes in female mice.

    PubMed

    Niermann, Sarah; Rattan, Saniya; Brehm, Emily; Flaws, Jodi A

    2015-06-01

    This study tested the hypothesis that prenatal DEHP exposure affects female reproduction. To test this hypothesis, pregnant female CD-1 mice were orally dosed daily with tocopherol-stripped corn oil (vehicle control) or DEHP (20 μg/kg/day-750 mg/kg/day) from gestation day 11-birth. Pups were counted, weighed, and sexed at birth, ovaries were subjected to evaluations of follicle numbers on postnatal days (PNDs) 8 and 21, and fertility was evaluated at 3-9 months. The results indicate that prenatal DEHP exposure increased male-to-female ratio compared to controls. Prenatal DEHP exposure also increased preantral follicle numbers at PND 21 compared to controls. Further, 22.2% of the 20 μg/kg/day treated animals took longer than 5 days to get pregnant at 3 months and 28.6% of the 750 mg/kg/day treated animals lost some of their pups at 6 months. Thus, prenatal DEHP exposure alters F1 sex ratio, increases preantral follicle numbers, and causes some breeding abnormalities. PMID:25765777

  11. Molecular Screening of "MECP2" Gene in a Cohort of Lebanese Patients Suspected with Rett Syndrome: Report on a Mild Case with a Novel Indel Mutation

    ERIC Educational Resources Information Center

    Corbani, S.; Chouery, E.; Fayyad, J.; Fawaz, A.; El Tourjuman, O.; Badens, C.; Lacoste, C.; Delague, V.; Megarbane, A.

    2012-01-01

    Background: Rett syndrome (RTT), an X-linked, dominant, neurodevelopment disorder represents 10% of female subjects with profound intellectual disability. Mutations in the "MECP2" gene are responsible for up to 95% of the classical RTT cases, and nearly 500 different mutations distributed throughout the gene have been reported. Methods: We report…

  12. Factors affecting interest in orthopedics among female medical students: a prospective analysis.

    PubMed

    Baldwin, Keith; Namdari, Surena; Bowers, Andrea; Keenan, Mary Ann; Levin, L Scott; Ahn, Jaimo

    2011-12-01

    The field of orthopedics has a limited ability to recruit high-quality female applicants. The purpose of this study was to determine whether early exposure to the field affects a woman's decision to pursue orthopedics. We performed a prospective, nonrandomized cohort study between academic years 2005 and 2009 and compared interest in orthopedic surgery among female (n=271) and male (n=71) medical students at 2 urban teaching institutions. Elective lectures and orthopedic literature were distributed via e-mail to the study participants. These materials included articles published in the medical literature, materials produced and distributed by the American Academy of Orthopaedic Surgeons, and Web sites providing educational materials. The primary outcome was the likelihood of application for orthopedic residency. We studied the influence of demographics, exposure, and attitudes on interest in pursuing an orthopedic career. Men had a significantly higher baseline level of interest in orthopedic surgery than women (P=.005). Younger age (P<.001) and personal (P<.001), independent (P<.001), and school (P=.023) exposures to orthopedics were significantly related to interest among women. At final follow-up, total personal exposures (P=.003) and total independent exposures (P<.001) in the form of our literature and lectures were correlated with final interest in women. Female interest was decreased by the long hours, physical demands, and predominantly male nature of the field. Early exposure to orthopedic educational resources may be useful in generating female interest. Perceptions and attitudes regarding orthopedic surgery must to be changed to attract the best and brightest minds, regardless of sex. PMID:22146211

  13. Factors affecting interest in orthopedics among female medical students: a prospective analysis.

    PubMed

    Baldwin, Keith; Namdari, Surena; Bowers, Andrea; Keenan, Mary Ann; Levin, L Scott; Ahn, Jaimo

    2011-12-01

    The field of orthopedics has a limited ability to recruit high-quality female applicants. The purpose of this study was to determine whether early exposure to the field affects a woman's decision to pursue orthopedics. We performed a prospective, nonrandomized cohort study between academic years 2005 and 2009 and compared interest in orthopedic surgery among female (n=271) and male (n=71) medical students at 2 urban teaching institutions. Elective lectures and orthopedic literature were distributed via e-mail to the study participants. These materials included articles published in the medical literature, materials produced and distributed by the American Academy of Orthopaedic Surgeons, and Web sites providing educational materials. The primary outcome was the likelihood of application for orthopedic residency. We studied the influence of demographics, exposure, and attitudes on interest in pursuing an orthopedic career. Men had a significantly higher baseline level of interest in orthopedic surgery than women (P=.005). Younger age (P<.001) and personal (P<.001), independent (P<.001), and school (P=.023) exposures to orthopedics were significantly related to interest among women. At final follow-up, total personal exposures (P=.003) and total independent exposures (P<.001) in the form of our literature and lectures were correlated with final interest in women. Female interest was decreased by the long hours, physical demands, and predominantly male nature of the field. Early exposure to orthopedic educational resources may be useful in generating female interest. Perceptions and attitudes regarding orthopedic surgery must to be changed to attract the best and brightest minds, regardless of sex.

  14. Delayed breeding affects lifetime reproductive success differently in male and female green woodhoopoes.

    PubMed

    Hawn, Amanda T; Radford, Andrew N; du Plessis, Morné A

    2007-05-15

    In cooperatively breeding species, many individuals only start breeding long after reaching physiological maturity [1], and this delay is expected to reduce lifetime reproductive success (LRS) [1-3]. Although many studies have investigated how nonbreeding helpers might mitigate the assumed cost of delayed breeding (reviewed in [3]), few have directly quantified the cost itself [4, 5] (but see [6, 7]). Moreover, although life-history tradeoffs frequently influence the sexes in profoundly different ways [8, 9], it has been generally assumed that males and females are similarly affected by a delayed start to breeding [7]. Here, we use 24 years of data to investigate the sex-specific cost of delayed breeding in the cooperatively breeding green woodhoopoe (Phoeniculus purpureus) and show that age at first breeding is related to LRS differently in males and females. As is traditionally expected, males that started to breed earlier in life had greater LRS than those that started later. However, females showed the opposite pattern: Those individuals that started to breed later in life actually had greater LRS than those that started earlier. In both sexes, the association between age at first breeding and LRS was driven by differences in breeding-career length, rather than per-season productivity. We hypothesize that the high mortality rate of young female breeders, and thus their short breeding careers, is related to a reduced ability to deal with the high physiological costs of reproduction in this species. These results demonstrate the importance of considering sex-specific reproductive costs when estimating the payoffs of life-history decisions and bring into question the long-held assumption that delayed breeding is necessarily costly. PMID:17412589

  15. Forniceal deep brain stimulation rescues hippocampal memory in Rett syndrome mice

    PubMed Central

    Hao, Shuang; Tang, Bin; Wu, Zhenyu; Ure, Kerstin; Sun, Yaling; Tao, Huifang; Gao, Yan; Patel, Akash J.; Curry, Daniel J.; Samaco, Rodney C.; Zoghbi, Huda Y.; Tang, Jianrong

    2016-01-01

    Deep brain stimulation (DBS) has improved the prospects for many individuals with diseases affecting motor control, and recently it has shown promise for improving cognitive function as well. Several studies in individuals with Alzheimer disease and in amnestic rats have demonstrated that DBS targeted to the fimbria-fornix1-3, the region that appears to regulate hippocampal activity, can mitigate defects in hippocampus-dependent memory3-5. Despite these promising results, DBS has not been tested for its ability to improve cognition in any childhood intellectual disability disorder (IDD). IDDs are a pressing concern: they affect as much as 3% of the population and involve hundreds of different genes. We hypothesized that stimulating the neural circuits that underlie learning and memory might provide a more promising route to treating these otherwise intractable disorders than seeking to adjust levels of one molecule at a time. We therefore studied the effects of forniceal DBS in a well-characterized mouse model of Rett Syndrome (RTT), which is a leading cause of intellectual disability in females. Caused by mutations that impair the function of MeCP26, RTT appears by the second year of life, causing profound impairment in cognitive, motor, and social skills along with an array of neurological features7; RTT mice, which reproduce the broad phenotype of this disorder, also show clear deficits in hippocampus-dependent learning and memory and hippocampal synaptic plasticity8-11. Here we show that forniceal DBS in RTT mice rescued contextual fear memory as well as spatial learning and memory. In parallel, forniceal DBS restored in vivo hippocampal long-term potentiation (LTP) and hippocampal neurogenesis. These results indicate that forniceal DBS might mitigate cognitive dysfunction in RTT. PMID:26469053

  16. Forniceal deep brain stimulation rescues hippocampal memory in Rett syndrome mice.

    PubMed

    Hao, Shuang; Tang, Bin; Wu, Zhenyu; Ure, Kerstin; Sun, Yaling; Tao, Huifang; Gao, Yan; Patel, Akash J; Curry, Daniel J; Samaco, Rodney C; Zoghbi, Huda Y; Tang, Jianrong

    2015-10-15

    Deep brain stimulation (DBS) has improved the prospects for many individuals with diseases affecting motor control, and recently it has shown promise for improving cognitive function as well. Several studies in individuals with Alzheimer disease and in amnesic rats have demonstrated that DBS targeted to the fimbria-fornix, the region that appears to regulate hippocampal activity, can mitigate defects in hippocampus-dependent memory. Despite these promising results, DBS has not been tested for its ability to improve cognition in any childhood intellectual disability disorder. Such disorders are a pressing concern: they affect as much as 3% of the population and involve hundreds of different genes. We proposed that stimulating the neural circuits that underlie learning and memory might provide a more promising route to treating these otherwise intractable disorders than seeking to adjust levels of one molecule at a time. We therefore studied the effects of forniceal DBS in a well-characterized mouse model of Rett syndrome (RTT), which is a leading cause of intellectual disability in females. Caused by mutations that impair the function of MeCP2 (ref. 6), RTT appears by the second year of life in humans, causing profound impairment in cognitive, motor and social skills, along with an array of neurological features. RTT mice, which reproduce the broad phenotype of this disorder, also show clear deficits in hippocampus-dependent learning and memory and hippocampal synaptic plasticity. Here we show that forniceal DBS in RTT mice rescues contextual fear memory as well as spatial learning and memory. In parallel, forniceal DBS restores in vivo hippocampal long-term potentiation and hippocampal neurogenesis. These results indicate that forniceal DBS might mitigate cognitive dysfunction in RTT.

  17. Rett syndrome: basic features of visual processing-a pilot study of eye-tracking.

    PubMed

    Djukic, Aleksandra; Valicenti McDermott, Maria; Mavrommatis, Kathleen; Martins, Cristina L

    2012-07-01

    Consistently observed "strong eye gaze" has not been validated as a means of communication in girls with Rett syndrome, ubiquitously affected by apraxia, unable to reply either verbally or manually to questions during formal psychologic assessment. We examined nonverbal cognitive abilities and basic features of visual processing (visual discrimination attention/memory) by analyzing patterns of visual fixation in 44 girls with Rett syndrome, compared with typical control subjects. To determine features of visual fixation patterns, multiple pictures (with the location of the salient and presence/absence of novel stimuli as variables) were presented on the screen of a TS120 eye-tracker. Of the 44, 35 (80%) calibrated and exhibited meaningful patterns of visual fixation. They looked longer at salient stimuli (cartoon, 2.8 ± 2 seconds S.D., vs shape, 0.9 ± 1.2 seconds S.D.; P = 0.02), regardless of their position on the screen. They recognized novel stimuli, decreasing the fixation time on the central image when another image appeared on the periphery of the slide (2.7 ± 1 seconds S.D. vs 1.8 ± 1 seconds S.D., P = 0.002). Eye-tracking provides a feasible method for cognitive assessment and new insights into the "hidden" abilities of individuals with Rett syndrome. PMID:22704012

  18. Rett syndrome: basic features of visual processing-a pilot study of eye-tracking.

    PubMed

    Djukic, Aleksandra; Valicenti McDermott, Maria; Mavrommatis, Kathleen; Martins, Cristina L

    2012-07-01

    Consistently observed "strong eye gaze" has not been validated as a means of communication in girls with Rett syndrome, ubiquitously affected by apraxia, unable to reply either verbally or manually to questions during formal psychologic assessment. We examined nonverbal cognitive abilities and basic features of visual processing (visual discrimination attention/memory) by analyzing patterns of visual fixation in 44 girls with Rett syndrome, compared with typical control subjects. To determine features of visual fixation patterns, multiple pictures (with the location of the salient and presence/absence of novel stimuli as variables) were presented on the screen of a TS120 eye-tracker. Of the 44, 35 (80%) calibrated and exhibited meaningful patterns of visual fixation. They looked longer at salient stimuli (cartoon, 2.8 ± 2 seconds S.D., vs shape, 0.9 ± 1.2 seconds S.D.; P = 0.02), regardless of their position on the screen. They recognized novel stimuli, decreasing the fixation time on the central image when another image appeared on the periphery of the slide (2.7 ± 1 seconds S.D. vs 1.8 ± 1 seconds S.D., P = 0.002). Eye-tracking provides a feasible method for cognitive assessment and new insights into the "hidden" abilities of individuals with Rett syndrome.

  19. A de-novo STXBP1 gene mutation in a patient showing the Rett syndrome phenotype.

    PubMed

    Romaniello, Romina; Saettini, Francesco; Panzeri, Elena; Arrigoni, Filippo; Bassi, Maria T; Borgatti, Renato

    2015-03-25

    This study reports on a 9-year-old girl who developed West syndrome and showed clinical features fulfilling the main revised diagnostic criteria for typical Rett syndrome (hand washing, severe cognitive impairment with absence of language, ataxic gait, progressive scoliosis and autistic features). Mutation analyses for methyl-CpG-binding protein 2 (MECP2), cyclin-dependent kinase-like 5 (CDKL5/STK9), ARX and Forkhead box G1 (FOXG1) genes were carried out, with negative results. A known de-novo c.1217G>A missense mutation in exon 14 leading to the substitution of a conserved residue, p.R406H in domain3b of the syntaxin-binding protein 1 (STXBP1) gene, was detected. The STXBP1 gene encodes the syntaxin-binding protein 1, a neuron-specific protein involved in synaptic vesicle release at both glutaminergic and GABAergic synapses. This function is also affected by MECP2 gene mutations, which are known to lead to a decrease in glutamate and GABA receptors' density. It is possible to speculate that the impairment in synaptic plasticity represents the pathogenic link between MECP2 and STXBP1 gene mutations. On reviewing the clinical features of the reported patients with the same mutation in the STXBP1 gene, it has been observed that poor eye contact, tremour, dyskinesia, head/hand stereotypies and both cognitive and motor progressive deterioration are common symptoms, although never considered as indicative of a Rett syndrome phenotype. In conclusion, the case described here suggests a relationship between the Rett syndrome and the STXBP1 gene not described so far, making the search for STXBP1 gene mutations advisable in patients with Rett syndrome and early onset of epilepsy.

  20. Neonatal adrenoleukodystrophy: clinical, pathologic, and biochemical delineation of a syndrome affecting both males and females.

    PubMed

    Jaffe, R; Crumrine, P; Hashida, Y; Moser, H W

    1982-07-01

    We describe the detailed clinical, pathologic, and biochemical features of brother and sister with the neonatal onset form of adrenoleukodystrophy, together with evidence of the biochemical defect. When compared with reports of previous cases, it becomes clear that this is a newly described clinical entity with remarkable uniformity of signs and very different from the usual childhood form. Some pathologic features are shared, including the morphologic abnormality of the adrenal in both neonatal and childhood forms, but deposition of abnormally metabolized lipids is more systemic and widespread in the neonatal form. The biochemistry of the disease is presented in both children and parents. Plasma values of long-chain fatty acid C26:0 are 0.328 +/- 0.18 micrograms/ml in a control population and 0.381 +/- 0.312 micrograms/ml in the father and mother. Values for C26:0 in the plasma of childhood adrenoleukodystrophy are 1.62 +/- 0.87 micrograms/ml and in our two cases, 2.79 micrograms/ml in the male, 1.83 micrograms/ml in the female. The basic biochemical defect appears to be a diminished capacity to oxidize these fatty acids leading to accumulation in cholesterol esters. Fatty acid oxidation to CO2 by cultured skin fibroblasts was 51% of control value for stearic acid, 5% for lignoceric acid in the male, and 39% of control value for stearic acid, 5% for lignoceric acid in the female. The genetics of this disease is different; whereas childhood adrenoleukodystrophy is X-linked, the neonatal onset form affects males and females equally and is most probably autosomally recessive in inheritance.

  1. Neonatal adrenoleukodystrophy: clinical, pathologic, and biochemical delineation of a syndrome affecting both males and females.

    PubMed Central

    Jaffe, R.; Crumrine, P.; Hashida, Y.; Moser, H. W.

    1982-01-01

    We describe the detailed clinical, pathologic, and biochemical features of brother and sister with the neonatal onset form of adrenoleukodystrophy, together with evidence of the biochemical defect. When compared with reports of previous cases, it becomes clear that this is a newly described clinical entity with remarkable uniformity of signs and very different from the usual childhood form. Some pathologic features are shared, including the morphologic abnormality of the adrenal in both neonatal and childhood forms, but deposition of abnormally metabolized lipids is more systemic and widespread in the neonatal form. The biochemistry of the disease is presented in both children and parents. Plasma values of long-chain fatty acid C26:0 are 0.328 +/- 0.18 micrograms/ml in a control population and 0.381 +/- 0.312 micrograms/ml in the father and mother. Values for C26:0 in the plasma of childhood adrenoleukodystrophy are 1.62 +/- 0.87 micrograms/ml and in our two cases, 2.79 micrograms/ml in the male, 1.83 micrograms/ml in the female. The basic biochemical defect appears to be a diminished capacity to oxidize these fatty acids leading to accumulation in cholesterol esters. Fatty acid oxidation to CO2 by cultured skin fibroblasts was 51% of control value for stearic acid, 5% for lignoceric acid in the male, and 39% of control value for stearic acid, 5% for lignoceric acid in the female. The genetics of this disease is different; whereas childhood adrenoleukodystrophy is X-linked, the neonatal onset form affects males and females equally and is most probably autosomally recessive in inheritance. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:7091298

  2. Neurophysiology versus clinical genetics in Rett syndrome: A multicenter study.

    PubMed

    Halbach, Nicky; Smeets, Eric E; Julu, Peter; Witt-Engerström, Ingegerd; Pini, Giorgio; Bigoni, Stefania; Hansen, Stig; Apartopoulos, Flora; Delamont, Robert; van Roozendaal, Kees; Scusa, Maria F; Borelli, Paolo; Candel, Math; Curfs, Leopold

    2016-09-01

    Many studies have attempted to establish the genotype-phenotype correlation in Rett syndrome (RTT). Cardiorespiratory measurements provide robust objective data, to correlate with each of the different clinical phenotypes. It has important implications for the management and treatment of this syndrome. The aim of this study was to correlate the genotype with the quantitative cardiorespiratory data obtained by neurophysiological measurement combined with a clinical severity score. This international multicenter study was conducted in four European countries from 1999 to 2012. The study cohort consisted of a group of 132 well-defined RTT females aged between 2 and 43 years with extended clinical, molecular, and neurophysiological assessments. Diagnosis of RTT was based on the consensus criteria for RTT and molecular confirmation. Genotype-phenotype analyses of clinical features and cardiorespiratory data were performed after grouping mutations by the same type and localization or having the same putative biological effect on the MeCP2 protein, and subsequently on eight single recurrent mutations. A less severe phenotype was seen in females with CTS, p.R133C, and p.R294X mutations. Autonomic disturbances were present in all females, and not restricted to nor influenced by one specific group or any single recurrent mutation. The objective information from non-invasive neurophysiological evaluation of the disturbed central autonomic control is of great importance in helping to organize the lifelong care for females with RTT. Further research is needed to provide insights into the pathogenesis of autonomic dysfunction, and to develop evidence-based management in RTT. © 2016 Wiley Periodicals, Inc.

  3. Spermatophore affects the egg-spawning and egg-carrying behavior in the female giant freshwater prawn, Macrobrachium rosenbergii.

    PubMed

    Kruangkum, Thanapong; Vanichviriyakit, Rapeepun; Chotwiwatthanakun, Charoonroj; Saetan, Jirawat; Tinikul, Yotsawan; Wanichanon, Chaitip; Cummins, Scott F; Hanna, Peter J; Sobhon, Prasert

    2015-10-01

    In crustaceans, mating occurs during the ecdysis after female molting. During this period, a male transfers its spermatophore into a female which, in some species, stores the spermatophore for a long period prior to spawning and fertilization. However, in some species including the giant freshwater prawn, Macrobrachium rosenbergii, the male deposits its spermataphore onto the external surface of the thoracic segment of the female which affects the spawning time and maternal behavior. This study investigated the spawning behavior of the M. rosenbergii females, which was divided into pre-spawning, spawning, and post-spawning phases. It was revealed that mated female prawns with attached spermatophore exhibited an earlier spawning than unmated individuals, leading to assessment of the factors that may elicit this phenomenon. Four groups of female prawns were allocated to groups including mating females with spermatophore still attached, mating females with the spermatophore removed, artificially inseminated females with spermatophores, and an unmated control. There was a significant reduction in the time of egg-spawning in the presence of spermatophores, and the mating activity was also a contributing factor. Furthermore, over 90% of the mated and artificially inseminated females in which spermatophores were deposited carried the eggs in the abdominal brood chamber until completion of embryonic development while others discarded the eggs within 2 days post-spawning. This study implies that the spermatophore may contain ovulation-inducing factors which stimulate an earlier spawning and fostering of brooding behavior.

  4. Factors Affecting Female Attitude Formation toward Science. Specific Reference to 12-14 Year Old Female Adolescents and Their Affective Orientation toward Middle School Science.

    ERIC Educational Resources Information Center

    Schreiber, Deborah A.

    This paper: (1) briefly reviews the existing literature which supports that female adolescents possess significantly more negative attitudes toward middle school science than do males; (2) examines the process of gender socialization in the United States to establish the socio-cultural and social psychological framework within which an attitudinal…

  5. Social Brains in Context: Lesions Targeted to the Song Control System in Female Cowbirds Affect Their Social Network

    PubMed Central

    Maguire, Sarah E.; Schmidt, Marc F.; White, David J.

    2013-01-01

    Social experiences can organize physiological, neural, and reproductive function, but there are few experimental preparations that allow one to study the effect individuals have in structuring their social environment. We examined the connections between mechanisms underlying individual behavior and social dynamics in flocks of brown-headed cowbirds (Molothrus ater). We conducted targeted inactivations of the neural song control system in female subjects. Playback tests revealed that the lesions affected females' song preferences: lesioned females were no longer selective for high quality conspecific song. Instead, they reacted to all cowbird songs vigorously. When lesioned females were introduced into mixed-sex captive flocks, they were less likely to form strong pair-bonds, and they no longer showed preferences for dominant males. This in turn created a cascade of effects through the groups. Social network analyses showed that the introduction of the lesioned females created instabilities in the social structure: males in the groups changed their dominance status and their courtship patterns, and even the competitive behavior of other female group-mates was affected. These results reveal that inactivation of the song control system in female cowbirds not only affects individual behavior, but also exerts widespread effects on the stability of the entire social system. PMID:23650558

  6. A contribution regarding the Rett syndrome.

    PubMed

    Külz, J; Pohl, H; Schober, S

    1985-01-01

    Andreas Rett described a "cerebral atrophic syndrome accompanying hyperammonemia" for the first time in 1966, and by 1983 over 80 such cases had been identified and described not only in Austria but also in other countries. If the information at our disposal is correct, we have reported on what we believe is the first case of a patient with a definite Rett syndrome in the German Democratic Republic. We are, regrettably, still unable to contribute decisively to the clarification of the etiology and pathogenesis of the disease, but will, through further publications and papers at pediatric and child-neuropsychiatric meetings, continue to spread the knowledge of the symptomatology. It is remarkable that in the present case neither computer tomography nor electroencephalography showed definite abnormalities despite much effort. Definite proof of cerebral atrophy cannot, therefore, yet be furnished. But we still have no doubt that our diagnosis is correct. We intend, within the framework of a joint study being conducted by the University Pediatric Hospital Rostock and the Ludwig Boltzmann Institute, Vienna, as part of the scientific and technical cooperation between the Republic of Austria and the German Democratic Republic, to investigate further the epidemiology and etiology of this disease in cooperation with our Departments of Metabolic Disturbances and Genetics.

  7. Structural, Dynamical, and Energetical Consequences of Rett Syndrome Mutation R133C in MeCP2.

    PubMed

    Kucukkal, Tugba G; Alexov, Emil

    2015-01-01

    Rett Syndrome (RTT) is a progressive neurodevelopmental disease affecting females. RTT is caused by mutations in the MECP2 gene and various amino acid substitutions have been identified clinically in different domains of the multifunctional MeCP2 protein encoded by this gene. The R133C variant in the methylated-CpG-binding domain (MBD) of MeCP2 is the second most common disease-causing mutation in the MBD. Comparative molecular dynamics simulations of R133C mutant and wild-type MBD have been performed to understand the impact of the mutation on structure, dynamics, and interactions of the protein and subsequently understand the disease mechanism. Two salt bridges within the protein and two critical hydrogen bonds between the protein and DNA are lost upon the R133C mutation. The mutation was found to weaken the interaction with DNA and also cause loss of helicity within the 141-144 region. The structural, dynamical, and energetical consequences of R133C mutation were investigated in detail at the atomic resolution. Several important implications of this have been shown regarding protein stability and hydration dynamics as well as its interaction with DNA. The results are in agreement with previous experimental studies and further provide atomic level understanding of the molecular origin of RTT associated with R133C variant.

  8. Identification of MeCP2 mutations in a series of females with autistic disorder.

    PubMed

    Carney, Regina M; Wolpert, Chantelle M; Ravan, Sarah A; Shahbazian, Mona; Ashley-Koch, Allison; Cuccaro, Michael L; Vance, Jeffery M; Pericak-Vance, Margaret A

    2003-03-01

    Rett disorder and autistic disorder are both pervasive developmental disorders. Recent studies indicate that at least 80% of Rett Disorder cases are caused by mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. Since there is some phenotypic overlap between autistic disorder and Rett disorder, we analyzed 69 females clinically diagnosed with autistic disorder for the presence of mutations in the MeCP2 gene. Two autistic disorder females were found to have de novo mutations in the MeCP2 gene. These data provide additional evidence of variable expression in the Rett disorder phenotype and suggest MeCP2 testing may be warranted for females presenting with autistic disorder.

  9. First case report of Rett syndrome in the Azeri Turkish population and brief review of the literature

    PubMed Central

    Gharesouran, Jalal; Khalili, Azizeh Farshbaf; Azari, Noushin Sorkhkoh; Vahedi, Leila

    2015-01-01

    Rett syndrome is a dominant X-linked male-lethal disorder largely caused by mutations in the gene encoding methyl-CpG binding protein 2 (MECP2). Clinical manifestations include neurodevelopmental disorder characterized by early-onset intractable seizures, severe developmental delay, intellectual disability, and abnormal electroencephalograms. Afflicted females show normal development until the age of 6 to 18 months, followed by gradual loss of speech abilities, microcephaly, social impairment, ataxia, and stereotypic hand movements. We report a 7-year-old girl who was born of a nonconsanguineous marriage presenting with mental retardation and delayed development. Physical examination revealed loss of speech, repetitive hand-wringing movement, short stature (120 cm), strabismus, microcephaly, and autistic behavior. The diagnosis was confirmed by sequencing MECP2 gene with heterozygous mutation C385A in exon 2. The current study aimed to report the first case of Rett syndrome in the Azeri Turkish population. PMID:25737965

  10. Investigation of Rett syndrome using pluripotent stem cells.

    PubMed

    Dajani, Rana; Koo, Sung-Eun; Sullivan, Gareth J; Park, In-Hyun

    2013-11-01

    Rett syndrome (RTT) is one of most prevalent female neurodevelopmental disorders. De novo mutations in X-linked MECP2 are mostly responsible for RTT. Since the identification of MeCP2 as the underlying cause of RTT, murine models have contributed to understanding the pathophysiology of RTT and function of MeCP2. Reprogramming is a procedure to produce induced pluripotent stem cells (iPSCs) by overexpression of four transcription factors. iPSCs obtain similar features as embryonic stem cells and are capable of self-renewing and differentiating into cells of all three layers. iPSCs have been utilized in modeling human diseases in vitro. Neurons differentiated from RTT-iPSCs showed the recapitulation of RTT phenotypes. Despite the early success, genetic and epigenetic instability upon reprogramming and ensuing maintenance of iPSCs raise concerns in using RTT-iPSCs as an accurate in vitro model. Here, we update the current iPSC-based RTT modeling, and its concerns and challenges. PMID:23744605

  11. Reproductive state affects hiding behaviour under risk of predation but not exploratory activity of female Spanish terrapins.

    PubMed

    Ibáñez, Alejandro; Marzal, Alfonso; López, Pilar; Martín, José

    2015-02-01

    Female investment during reproduction may reduce survivorship due to increased predation risk. During pregnancy, the locomotor performance of gravid females might be diminished due to the additional weight acquired. In addition, egg production may also increase thermoregulatory, metabolic and physiological costs. Also, pregnant females have greater potential fitness and should take fewer risks. Thus, females should ponder their reproductive state when considering their behavioural responses under risky situations. Here, we examine how reproductive state influence risk-taking behaviour in different contexts in female Spanish terrapins (Mauremys leprosa). We simulated predator attacks of different risk levels and measured the time that the turtles spent hiding entirely inside their own shells (i.e. appearance times). We also assessed the subsequent time after emergence from the shell that the turtles spent immobile monitoring for predators before starting to escape actively (i.e. waiting times). Likewise, we performed a novel-environment test and measured the exploratory activity of turtles. We found no correlations between appearance time, waiting time or exploratory activity, but appearance times were correlated across different risk levels. Only appearance time was affected by the reproductive state, where gravid females reappeared relatively later from their shells after a predator attack than non-gravid ones. Moreover, among gravid females, those carrying greater clutches tended to have longer appearance times. This suggests that only larger clutches could affect hiding behaviour in risky contexts. In contrast, waiting time spent scanning for predators and exploratory activity were not affected by the reproductive state. These differences between gravid and non-gravid females might be explained by the metabolic-physiological costs associated with egg production and embryo maintenance, as well as by the relatively higher potential fitness of gravid females.

  12. A new Rett syndrome family consistent with X-linked inheritance expands the X chromosome exclusion map.

    PubMed Central

    Schanen, N C; Dahle, E J; Capozzoli, F; Holm, V A; Zoghbi, H Y; Francke, U

    1997-01-01

    Although familial recurrences of Rett syndrome (RTT) comprise only approximately 1% of the reported cases, it is these cases that hold the key for the understanding of the genetic basis of the disorder. Families in which RTT occurs in mother and daughter, aunt and niece, and half sisters are consistent with dominant inheritance and variable expressivity of the phenotype. Recurrence of RTT in sisters is likely due to germ-line mosaicism in one of the parents, rather than to recessive inheritance. The exclusive occurrence of classic RTT in females led to the hypothesis that it is X-linked and may be lethal in males. In an X-linked dominant disorder, unaffected obligate-carrier females would be expected to show nonrandom or skewed inactivation of the X chromosome bearing the mutant allele. We investigated the X chromosome inactivation (XCI) patterns in the female members of a newly identified family with recurrence of RTT in a maternal aunt and a niece. Skewing of XCI is present in the obligate carrier in this family, supporting the hypothesis that RTT is an X-linked disorder. However, evaluation of the XCI pattern in the mother of affected half sisters shows random XCI, suggesting germ-line mosaicism as the cause of repeated transmission in this family. To determine which regions of the X chromosome were inherited concordantly/discordantly by the probands, we genotyped the individuals in the aunt-niece family and two previously reported pairs of half sisters. These combined exclusion-mapping data allow us to exclude the RTT locus from the interval between DXS1053 in Xp22.2 and DXS1222 in Xq22.3. This represents an extension of the previous exclusion map. Images Figure 1 Figure 2 PMID:9326329

  13. Improving Treatment Trial Outcomes for Rett Syndrome: the development of Rett-specific anchors for the Clinical Global Impression Scale

    PubMed Central

    Neul, Jeff; Glaze, Daniel; Percy, Alan; Feyma, Tim; Beisang, Arthur; Dinh, Thuy; Suter, Bernhard; Anagnostou, Evdokia; Snape, Mike; Horrigan, Joseph; Jones, Nancy E.

    2015-01-01

    Rett syndrome is a genetically based neurodevelopmental disorder. While the clinical consequences of Rett syndrome are profound and life-long, currently no approved drug treatments are available specifically targeted to Rett symptoms. High quality outcome measures, specific to the core symptoms of a disorder are a critical component to well-designed clinical trials for individuals with neurodevelopmental disorders. The Clinical Global Impression Scale is a measure of global clinical change with strong face validity that has been widely used as an outcome measure in clinical trials of central nervous system disorders. Despite its favorable assay sensitivity in clinical trials, as a global measure, the Clinical Global Impression Scale is not specific to the signs and symptoms of the disorder under study. Development of key anchors for the scale, specific to the disorder being assessed, holds promise for enhancing the validity and reliability of the measure for disorders such as Rett syndrome. PMID:25895911

  14. Improving Treatment Trial Outcomes for Rett Syndrome: The Development of Rett-specific Anchors for the Clinical Global Impression Scale.

    PubMed

    Neul, Jeffrey L; Glaze, Daniel G; Percy, Alan K; Feyma, Tim; Beisang, Arthur; Dinh, Thuy; Suter, Bernhard; Anagnostou, Evdokia; Snape, Mike; Horrigan, Joseph; Jones, Nancy E

    2015-11-01

    Rett syndrome is a genetically based neurodevelopmental disorder. Although the clinical consequences of Rett syndrome are profound and lifelong, currently no approved drug treatments are available specifically targeted to Rett symptoms. High quality outcome measures, specific to the core symptoms of a disorder are a critical component of well-designed clinical trials for individuals with neurodevelopmental disorders. The Clinical Global Impression Scale is a measure of global clinical change with strong face validity that has been widely used as an outcome measure in clinical trials of central nervous system disorders. Despite its favorable assay sensitivity in clinical trials, as a global measure, the Clinical Global Impression Scale is not specific to the signs and symptoms of the disorder under study. Development of key anchors for the scale, specific to the disorder being assessed, holds promise for enhancing the validity and reliability of the measure for disorders such as Rett syndrome.

  15. Paliperidone and aripiprazole differentially affect the strength of calcium-secretion coupling in female pituitary lactotrophs.

    PubMed

    Kucka, Marek; Tomić, Melanija; Bjelobaba, Ivana; Stojilkovic, Stanko S; Budimirovic, Dejan B

    2015-03-10

    Hyperprolactinemia is a common adverse in vivo effect of antipsychotic medications that are used in the treatment of patients with schizophrenia. Here, we compared the effects of two atypical antipsychotics, paliperidone and aripiprazole, on cAMP/calcium signaling and prolactin release in female rat pituitary lactotrophs in vitro. Dopamine inhibited spontaneous cAMP/calcium signaling and prolactin release. In the presence of dopamine, paliperidone rescued cAMP/calcium signaling and prolactin release in a concentration-dependent manner, whereas aripiprazole was only partially effective. In the absence of dopamine, paliperidone stimulated cAMP/calcium signaling and prolactin release, whereas aripiprazole inhibited signaling and secretion more potently but less effectively than dopamine. Forskolin-stimulated cAMP production was facilitated by paliperidone and inhibited by aripiprazole, although the latter was not as effective as dopamine. None of the compounds affected prolactin transcript activity, intracellular prolactin accumulation, or growth hormone secretion. These data indicate that paliperidone has dual hyperprolactinemic actions in lactotrophs i) by preserving the coupling of spontaneous electrical activity and prolactin secretion in the presence of dopamine and ii) by inhibiting intrinsic dopamine receptor activity in the absence of dopamine, leading to enhanced calcium signaling and secretion. In contrast, aripiprazole acts on prolactin secretion by attenuating, but not abolishing, calcium-secretion coupling.

  16. HIV-related stigma in a sample of HIV-affected older female African American caregivers

    PubMed

    Poindexter; Linsk

    1999-01-01

    Older women of color increasingly act as informal caregivers for adults and children with HIV disease. Nineteen older female (mostly African American) informal caregivers of HIV-infected individuals participated in qualitative interviews to explore their experiences with HIV-related stigma. Perceived and directly experienced stigma were examined in the context of disclosure of the presence of HIV disease. Overt HIV-related stigma was rarely experienced by these respondents, primarily because they had not widely disclosed the presence of HIV in the family and therefore had not given anyone the opportunity to ostracize or judge them. HIV-related stigma was internalized, so that disclosure decisions were based on their anticipation of censure. There also was evidence of associative stigma and of stigma management. The findings suggest the need for social work practitioners to increase awareness of the needs of stigmatized, isolated HIV-affected caregivers. Practitioners should conduct aggressive outreach and strive to provide more support to this often invisible population of caregivers to HIV-infected people. PMID:9922729

  17. Hypothyroidism Affects Vascularization and Promotes Immune Cells Infiltration into Pancreatic Islets of Female Rabbits

    PubMed Central

    Rodríguez-Castelán, Julia; Martínez-Gómez, Margarita; Castelán, Francisco; Cuevas, Estela

    2015-01-01

    Thyroidectomy induces pancreatic edema and immune cells infiltration similarly to that observed in pancreatitis. In spite of the controverted effects of hypothyroidism on serum glucose and insulin concentrations, the number and proliferation of Langerhans islet cells as well as the presence of extracellular matrix are affected depending on the islet size. In this study, we evaluated the effect of methimazole-induced hypothyroidism on the vascularization and immune cells infiltration into islets. A general observation of pancreas was also done. Twelve Chinchilla-breed female adult rabbits were divided into control (n = 6) and hypothyroid groups (n = 6, methimazole, 0.02% in drinking water for 30 days). After the treatment, rabbits were sacrificed and their pancreas was excised, histologically processed, and stained with Periodic Acid-Schiff (PAS) or Masson's Trichrome techniques. Islets were arbitrarily classified into large, medium, and small ones. The external and internal portions of each islet were also identified. Student-t-test and Mann-Whitney-U test or two-way ANOVAs were used to compare variables between groups. In comparison with control rabbits, hypothyroidism induced a strong infiltration of immune cells and a major presence of collagen and proteoglycans in the interlobular septa. Large islets showed a high vascularization and immune cells infiltration. The present results show that hypothyroidism induces pancreatitis and insulitis. PMID:26175757

  18. Hypothyroidism Affects Vascularization and Promotes Immune Cells Infiltration into Pancreatic Islets of Female Rabbits.

    PubMed

    Rodríguez-Castelán, Julia; Martínez-Gómez, Margarita; Castelán, Francisco; Cuevas, Estela

    2015-01-01

    Thyroidectomy induces pancreatic edema and immune cells infiltration similarly to that observed in pancreatitis. In spite of the controverted effects of hypothyroidism on serum glucose and insulin concentrations, the number and proliferation of Langerhans islet cells as well as the presence of extracellular matrix are affected depending on the islet size. In this study, we evaluated the effect of methimazole-induced hypothyroidism on the vascularization and immune cells infiltration into islets. A general observation of pancreas was also done. Twelve Chinchilla-breed female adult rabbits were divided into control (n = 6) and hypothyroid groups (n = 6, methimazole, 0.02% in drinking water for 30 days). After the treatment, rabbits were sacrificed and their pancreas was excised, histologically processed, and stained with Periodic Acid-Schiff (PAS) or Masson's Trichrome techniques. Islets were arbitrarily classified into large, medium, and small ones. The external and internal portions of each islet were also identified. Student-t-test and Mann-Whitney-U test or two-way ANOVAs were used to compare variables between groups. In comparison with control rabbits, hypothyroidism induced a strong infiltration of immune cells and a major presence of collagen and proteoglycans in the interlobular septa. Large islets showed a high vascularization and immune cells infiltration. The present results show that hypothyroidism induces pancreatitis and insulitis. PMID:26175757

  19. Competition affects gene flow from oilseed rape (female symbol) to Brassica rapa (male symbol).

    PubMed

    Johannessen, M M; Andersen, B A; Jørgensen, R B

    2006-05-01

    Unlike most studies on hybridisation between oilseed rape and Brassica rapa, this study focused on hybridisation with oilseed rape as the maternal parent. This is a key cross because, assuming that plastids are inherited maternally, F(1)-hybrid production with maternal oilseed rape (B. napus) is the only transgene escape route from transplastomic oilseed rape. We investigated such F(1)-hybrid production in winter oilseed rape co-cultivated with weedy B. rapa at three plant densities each with two proportions of the different species. The paternity of the progeny produced on oilseed rape was assessed, and several fitness parameters were determined in oilseed rape mother plants in order to correlate hybridisation and plant competition. At higher density, the vegetative fitness per mother plant decreased significantly, but the density only affected the frequency of F(1)-hybrids significantly (a decrease) in the treatment with equal proportions of each species. As to the proportions, at higher B. napus frequencies, there were fewer F(1)-hybrids per mother plant and a significant increase in most biomass components. Thus, B. rapa was the stronger competitor in its effect on both the vegetative and reproductive fitness in B. napus, and the hybridisation frequency. In conclusion, the relative frequency of the two species was a more influential parameter than the density. Hybridisation with B. napus as the female will be most likely at current field densities of B. napus and when B. rapa is an abundant weed.

  20. Competition affects gene flow from oilseed rape (female symbol) to Brassica rapa (male symbol).

    PubMed

    Johannessen, M M; Andersen, B A; Jørgensen, R B

    2006-05-01

    Unlike most studies on hybridisation between oilseed rape and Brassica rapa, this study focused on hybridisation with oilseed rape as the maternal parent. This is a key cross because, assuming that plastids are inherited maternally, F(1)-hybrid production with maternal oilseed rape (B. napus) is the only transgene escape route from transplastomic oilseed rape. We investigated such F(1)-hybrid production in winter oilseed rape co-cultivated with weedy B. rapa at three plant densities each with two proportions of the different species. The paternity of the progeny produced on oilseed rape was assessed, and several fitness parameters were determined in oilseed rape mother plants in order to correlate hybridisation and plant competition. At higher density, the vegetative fitness per mother plant decreased significantly, but the density only affected the frequency of F(1)-hybrids significantly (a decrease) in the treatment with equal proportions of each species. As to the proportions, at higher B. napus frequencies, there were fewer F(1)-hybrids per mother plant and a significant increase in most biomass components. Thus, B. rapa was the stronger competitor in its effect on both the vegetative and reproductive fitness in B. napus, and the hybridisation frequency. In conclusion, the relative frequency of the two species was a more influential parameter than the density. Hybridisation with B. napus as the female will be most likely at current field densities of B. napus and when B. rapa is an abundant weed. PMID:16508664

  1. Pair housing differentially affects motivation to self-administer cocaine in male and female rats

    PubMed Central

    Westenbroek, Christel; Perry, Adam N.; Becker, Jill B.

    2013-01-01

    Female rats exhibit greater intake and motivation to self-administer cocaine. In females but not males, isolation by itself is a stressor, which could lead to increased drug intake. Therefore, we hypothesized that social housing would buffer against stress and reduce the motivation to self-administer cocaine primarily in females. Male and female Sprague-Dawley rats were housed individually or in same-sex pairs. The individually housed rats and one of each pair were allowed to self-administer (SA) a low dose of cocaine (0.2 mg/kg/inf) on a fixed ratio (FR1) schedule for one week. Motivation for cocaine SA was measured for an additional 2 weeks on a progressive ratio schedule. Isolated females had greater cocaine-intake on the FR1 schedule and greater motivation to take cocaine than males. Pair-housing in females, but not males, attenuated the motivation to take cocaine. Isolated females, but not males, showed escalation of their motivation to take cocaine, which was attenuated by pair housing of females. Concluding, the motivation to take cocaine escalates in females but not males, and pair-housing of females attenuates this escalation. PMID:23727175

  2. Bone microarchitecture in Rett syndrome and treatment with teriparatide: a case report.

    PubMed

    Zanchetta, M B; Scioscia, M F; Zanchetta, J R

    2016-09-01

    We present the case of a 28-year-old female Rett syndrome patient with low bone mass and a recent fracture who was successfully treated with teriparatide. Bone mineral density and microarchitecture substantially improved after treatment. Rett syndrome (RTT), an X-linked progressive neuro-developmental disorder caused by mutations in the methyl-CpG-binding 2 (MECP2) gene, has been consistently associated with low bone mass. Consequently, patients with RTT are at increased risk of skeletal fractures. Teriparatide is a bone-forming agent for the treatment of osteoporosis that has demonstrated its effectiveness in increasing bone strength and reducing the risk of fractures in postmenopausal women, but, recently, its positive action has also been reported in premenopausal women. We present the case of a 28-year-old female RTT patient with low bone mass and a recent fracture who was successfully treated with teriparatide. Both bone mass measured by DXA and microarchitecture assessed by high resolution peripheral computed tomography (HR pQCT) were substantially improved after treatment.

  3. International Conference on Rett Syndrome (4th, Vienna, Austria, October 2-5, 1986). Synopsis.

    ERIC Educational Resources Information Center

    Percy, Alan

    Presentations from speakers at a conference on Rett Syndrome are summarized. The presentations focused on Rett Syndrome's genetic basis and identification as a clinical syndrome, involving, among other things, mental subnormality, epilepsy, infantile spasms, hand stereotypes, and poor hand use. Also discussed were: Rett Syndrome's predictive…

  4. A case of the Rett syndrome.

    PubMed

    Brunel, R; Gilly, R

    1985-01-01

    This is a case report of the Rett syndrome in a girl with normal general and psychomotor development during the first 12 mos. Afterwards developmental stagnation and retrogression appeared which led within one yr to dementia, autism, loss of purposeful hand use, truncal ataxia and apraxia of gait. Characteristic stereotypic movements of the hands occurred, and, furthermore, rhythmic truncal balancing and episodic hyperpnea. At 2 yrs, neurological examination showed slight hypertonia and hyperreflexia of the legs without extensor plantar signs, there was relative microcephaly, and visceral examination was normal. The diagnosis was made on the basis of clinical signs: all laboratory investigations were negative except EEG which showed unspecific modifications. We didn't find hyperammonemia. No progression of the symptoms appeared in the 15 mos following the diagnosis. PMID:4061764

  5. Dendritic spine dysgenesis in Rett syndrome

    PubMed Central

    Xu, Xin; Miller, Eric C.; Pozzo-Miller, Lucas

    2014-01-01

    Spines are small cytoplasmic extensions of dendrites that form the postsynaptic compartment of the majority of excitatory synapses in the mammalian brain. Alterations in the numerical density, size, and shape of dendritic spines have been correlated with neuronal dysfunction in several neurological and neurodevelopmental disorders associated with intellectual disability, including Rett syndrome (RTT). RTT is a progressive neurodevelopmental disorder associated with intellectual disability that is caused by loss of function mutations in the transcriptional regulator methyl CpG-binding protein 2 (MECP2). Here, we review the evidence demonstrating that principal neurons in RTT individuals and Mecp2-based experimental models exhibit alterations in the number and morphology of dendritic spines. We also discuss the exciting possibility that signaling pathways downstream of brain-derived neurotrophic factor (BDNF), which is transcriptionally regulated by MeCP2, offer promising therapeutic options for modulating dendritic spine development and plasticity in RTT and other MECP2-associated neurodevelopmental disorders. PMID:25309341

  6. Rett's syndrome in the west of Scotland.

    PubMed Central

    Kerr, A M; Stephenson, J B

    1985-01-01

    Nineteen girls with characteristic features of Rett's syndrome, including normal initial development, regression at about 12 months of age, repetitive hand movements, and severe mental handicap were studied. This represents an estimated incidence of one in 30 000 live births (one in 15 000 girls) in the west of Scotland. Although the children were often initially considered to be autistic, they did not conform to this diagnosis as they made good personal contact within the limits of their mental development. The developmental regression was sometimes falsely attributed to vaccination. Each child showed striking involuntary movements and abnormality of tone, varying from hypotonia, which was found only in the youngest, to rigidity, which was common in older girls; this permitted classification into three clinical subtypes. The abnormalities were highly suggestive of an extrapyramidal disorder, and this has implications for further research and possible treatment. Images FIG 3 PMID:2412628

  7. Factors Affecting the Unemployment (Rate) of Female Art Graduates in Iran

    ERIC Educational Resources Information Center

    Hedayat, Mina; Kahn, Sabzali Musa; Hanafi, Jaffri

    2013-01-01

    The aim of this study is to explore the relationship between the opportunities of female artist graduates in Tehran Province and the current employment market. Mixed method was employed in this study. The population of the current study consisted of 240 female artist graduates selected using a systematic random sampling method from both public and…

  8. Factors that affect the physical science career interest of female students: Testing five common hypotheses

    NASA Astrophysics Data System (ADS)

    Hazari, Zahra; Potvin, Geoff; Lock, Robynne M.; Lung, Florin; Sonnert, Gerhard; Sadler, Philip M.

    2013-12-01

    There are many hypotheses regarding factors that may encourage female students to pursue careers in the physical sciences. Using multivariate matching methods on national data drawn from the Persistence Research in Science and Engineering (PRiSE) project (n=7505), we test the following five commonly held beliefs regarding what factors might impact females’ physical science career interest: (i) having a single-sex physics class, (ii) having a female physics teacher, (iii) having female scientist guest speakers in physics class, (iv) discussing the work of female scientists in physics class, and (v) discussing the underrepresentation of women in physics class. The effect of these experiences on physical science career interest is compared for female students who are matched on several factors, including prior science interests, prior mathematics interests, grades in science, grades in mathematics, and years of enrollment in high school physics. No significant effects are found for single-sex classes, female teachers, female scientist guest speakers, and discussing the work of female scientists. However, discussions about women’s underrepresentation have a significant positive effect.

  9. Factors that affect self-care behaviour of female high school students with dysmenorrhoea: a cluster sampling study.

    PubMed

    Chang, Shu-Fang; Chuang, Mei-hua

    2012-04-01

    The purpose of this study was to identify factors that affect the self-care behaviour of female high school students with dysmenorrhoea. This cross-sectional study utilized a questionnaire-based survey to understand the self-care behaviour of female high school students dysmenorrhoeal, along with the factors that affect this behaviour. A cluster random sampling method was adopted and questionnaires were used for data collection. Study participants experienced a moderate level of discomfort from dysmenorrhoea, and perceived dysmenorrhoea as serious. This investigation finds that cues to action raised perceived susceptibility to dysmenorrhoea and the perceived effectiveness of self-care behaviour and, therefore, increased the adoption of self-care behaviour. Hence, school nurses should offer female high school students numerous resources to apply correct self-care behaviour.

  10. Undergraduate African American females in the sciences: A qualitative study of student experiences affecting academic success and persistence

    NASA Astrophysics Data System (ADS)

    Essien-Wood, Idara R.

    Given the lack of literature on Undergraduate African American females in the sciences (UAAFS), this study sought to explicate their experiences at one large, predominantly White, Research I institution in the southwestern United States. In particular, the purpose of this study was to identify factors that affect the academic success and persistence of Black females in the natural and physical sciences. Data was collected via in-depth, semi-structured interviews with 15 Black female science majors. Findings from this study identified several supportive mechanisms for academic success: family, religion, teaching assistants and friends. Also identified were seven barriers to academic success: employment, lack of diversity, cultural dissonance, unwelcoming Research I environment, faculty, advisors, classmates, and lab groups. Further, an analysis of students' responses revealed numerous instances of racial and gender micro-aggressions. Recommendations are provided to address factors identified as affecting student academic success and persistence as well as a culture of micro-aggressive behavior.

  11. Female Clerical Workers' Occupational Stress: The Role of Person and Social Resources, Negative Affectivity, and Stress Appraisals.

    ERIC Educational Resources Information Center

    Morris, Jodi E.; Long, Bonita C.

    2002-01-01

    Relations among person and social resources, work-stress appraisals, and depression were examined with data from 2 longitudinal studies of female clerical workers. Results were consistent with predictions that primary appraisals contribute to change in depression beyond the effects of person and social resources and negative affectivity. There was…

  12. Male and female mate choice affects offspring quality in a sex-role-reversed pipefish.

    PubMed

    Sandvik, M; Rosenqvist, G; Berglund, A

    2000-11-01

    Where both sexes invest substantially in offspring, both females and males should discriminate between potential partners when choosing mates. The degree of choosiness should relate to the costs of choice and to the potential benefits to be gained. We measured offspring quality from experimentally staged matings with preferred and non-preferred partners in a sex-role-reversed pipefish, Syngnathus typhle L. Here, a substantial male investment in offspring results in a lower potential reproductive rate in males than in females, and access to males limits female reproductive success rather than vice versa. Thus, males are choosier than females and females compete more intensely over mates than do males. Broods from preferred matings were superior at escaping predation, when either males or females were allowed to choose a partner. However, only 'choosing' females benefited in terms of faster-growing offspring. Our results have important implications for mate-choice research: here we show that even the more competitive and less choosy sex may contribute significantly to sexual selection through mate choice. PMID:11413626

  13. Deliberate self-harm in female patients with affective disorders: investigation of personality structure and affect regulation by means of operationalized psychodynamic diagnostics.

    PubMed

    Boeker, Heinz; Himmighoffen, Holger; Straub, Miriam; Schopper, Christian; Endrass, Jerome; Kuechenhoff, Bernhard; Weber, Silvan; Hell, Daniel

    2008-10-01

    This study investigated psychodynamically relevant dimensions in female depressive patients with and without deliberate self-harm (DSH). DSH is often observed in depressive patients and frequently shows a correlation with personality disorders. Forty female depressive patients with and without DSH were investigated after recovery from acute depressive pathology by means of "operationalized psychodynamic diagnostics" (OPD). Patients with DSH had a significantly lower level of integration in the OPD dimension "structure," and their "interpersonal relationships" showed dysfunctional interaction patterns. They also had a significantly higher rate of personality disorders. These results underline the significance of aspects of personality structure in female depressive patients with DSH, and enable a deeper understanding of their dysfunctional defense strategies, the connections with underlying disturbed affect regulation, and vicious circles in the therapeutic transference-countertransference relationship. OPD has been shown to be a useful tool for empirical research into therapeutically relevant dimensions of personality.

  14. Reproductive rate, not dominance status, affects fecal glucocorticoid levels in breeding female meerkats.

    PubMed

    Barrette, Marie-France; Monfort, Steven L; Festa-Bianchet, Marco; Clutton-Brock, Tim H; Russell, Andrew F

    2012-04-01

    Glucocorticoid hormones (GCs) have been studied intensively to understand the associations between physiological stress and reproductive skew in animal societies. However, we have little appreciation of the range of either natural levels within and among individuals, or the associations among dominance status, reproductive rate and GCs levels during breeding. To address these shortcomings, we examined variation in fecal glucocorticoid metabolites (fGC) during breeding periods in free-ranging female meerkats (Suricata suricatta) over 11 years. The vast majority of variation in fGC levels was found within breeding events by the same female (~87%), with the remaining variation arising among breeding events and among females. Concentrations of fGC generally tripled as pregnancy progressed. However, females with a high reproductive rate, defined as those conceiving within a month following parturition (mean = 9 days postpartum), showed significant reductions in fGC in the final 2 weeks before parturition. Despite these reductions, females with a high reproductive rate had higher fGC levels at conception of the following litter than those breeding at a low rate. After controlling for the higher reproductive rate of dominants, we found no association between levels of fGC and either age or dominance status. Our results suggest that one should be cautious about interpreting associations between dominance status, reproductive skew and GCs levels, without knowledge of the natural variation in GCs levels within and among females.

  15. Reproductive rate, not dominance status, affects fecal glucocorticoid levels in breeding female meerkats.

    PubMed

    Barrette, Marie-France; Monfort, Steven L; Festa-Bianchet, Marco; Clutton-Brock, Tim H; Russell, Andrew F

    2012-04-01

    Glucocorticoid hormones (GCs) have been studied intensively to understand the associations between physiological stress and reproductive skew in animal societies. However, we have little appreciation of the range of either natural levels within and among individuals, or the associations among dominance status, reproductive rate and GCs levels during breeding. To address these shortcomings, we examined variation in fecal glucocorticoid metabolites (fGC) during breeding periods in free-ranging female meerkats (Suricata suricatta) over 11 years. The vast majority of variation in fGC levels was found within breeding events by the same female (~87%), with the remaining variation arising among breeding events and among females. Concentrations of fGC generally tripled as pregnancy progressed. However, females with a high reproductive rate, defined as those conceiving within a month following parturition (mean = 9 days postpartum), showed significant reductions in fGC in the final 2 weeks before parturition. Despite these reductions, females with a high reproductive rate had higher fGC levels at conception of the following litter than those breeding at a low rate. After controlling for the higher reproductive rate of dominants, we found no association between levels of fGC and either age or dominance status. Our results suggest that one should be cautious about interpreting associations between dominance status, reproductive skew and GCs levels, without knowledge of the natural variation in GCs levels within and among females. PMID:22210199

  16. Exposure to Palladium Nanoparticles Affects Serum Levels of Cytokines in Female Wistar Rats

    PubMed Central

    Iavicoli, Ivo; Fontana, Luca; Corbi, Maddalena; Leso, Veruscka; Marinaccio, Alessandro; Leopold, Kerstin; Schindl, Roland; Sgambato, Alessandro

    2015-01-01

    Background Information currently available on the impact of palladium on the immune system mainly derives from studies assessing the biological effects of palladium salts. However, in the last years, there has been a notable increase in occupational and environmental levels of fine and ultrafine palladium particles released from automobile catalytic converters, which may play a role in palladium sensitization. In this context, the evaluation of the possible effects exerted by palladium nanoparticles (Pd-NPs) on the immune system is essential to comprehensively assess palladium immunotoxic potential. Aim Therefore, the aim of this study was to investigate the effects of Pd-NPs on the immune system of female Wistar rats exposed to this xenobiotic for 14 days, by assessing possible quantitative changes in a number of cytokines: IL-1α, IL-2, IL-4, IL-6, IL-10, IL-12, GM-CSF, INF-γ and TNF-α. Methods Twenty rats were randomly divided into four exposure groups and one of control. Animals were given a single tail vein injection of vehicle (control group) and different concentrations of Pd-NPs (0.012, 0.12, 1.2 and 12 μg/kg). A multiplex biometric enzyme linked immunosorbent assay was used to evaluate cytokine serum levels. Results The mean serum concentrations of all cytokines decreased after the administration of 0.012 μg/kg of Pd-NPs, whereas exceeded the control levels at higher exposure doses. The highest concentration of Pd-NPs (12 μg/kg) induced a significant increase of IL-1α, IL-4, IL-6, IL-10, IL-12, GM-CSF and INF-γ compared to controls. Discussion and Conclusions These results demonstrated that Pd-NP exposure can affect the immune response of rats inducing a stimulatory action that becomes significant at the highest administered dose. Our findings did not show an imbalance between cytokines produced by CD4+ T helper (Th) cells 1 and 2, thus suggesting a generalized stimulation of the immune system with a simultaneous activation and polarization of the

  17. Factors affecting utilization of dental health services and satisfaction among adolescent females in Riyadh City

    PubMed Central

    Al-Hussyeen, Al Johara A.

    2009-01-01

    Objectives This study was conducted to determine factors affecting utilization of dental health services among intermediate female school students in Riyadh. In addition to assessing their satisfaction with the dental care received during the last dental visit. Subjects and methods Self-administered questionnaires were distributed among students attending eight public and four private schools. These schools were selected randomly to represent the four different administrative zones in Riyadh. Results Of 600 questionnaires distributed, 531 were complete and suitable for analysis. Nearly three quarters of the students visited the dentist more than once during the last 2 years. A bout 75% had their treatment in private dental clinics and 63% made their visits for routine treatment. The quality of dental care was found to be the most encouraging factor for utilization of dental services, whereas, far geographic location of the dental clinics was the most discouraging factor. For those who received treatment in the government clinics, the most discouraging factor was post operative complications (P < 0.0001), while the most encouraging factor was the availability of friendly staff (P < 0.0001). The high cost of dental care was the most discouraging factor for utilizing the dental services for those who visited private clinics (P < 0.0001), while the high quality of dental care was the most encouraging factor (P < 0.009). Students who made their visits because of pain highly considered modern clinics and those recommended by friends as highly encouraging factors (P < 0.002), while they considered the high cost of dental care as discouraging factor for using dental services (P < 0.038). Students who visited the dentist for routine treatment gave the quality of dental care as encouraging for the use of dental clinics (P < 0.0001). Satisfaction with dental care was found to be significantly associated with high quality of dental care, convenient appointment

  18. A case of a Tunisian Rett patient with a novel double-mutation of the MECP2 gene

    SciTech Connect

    Fendri-Kriaa, Nourhene; Hsairi, Ines; Kifagi, Chamseddine; Ellouze, Emna; Mkaouar-Rebai, Emna; Triki, Chahnez; Fakhfakh, Faiza

    2011-06-03

    Highlights: {yields} Sequencing of the MECP2 gene, modeling and comparison of the two variants were performed in a Tunisian classical Rett patient. {yields} A double-mutation: a new and de novo mutation c.535C > T and the common one c.763C > T of the MECP2 gene was identified. {yields} The P179S transition may change local electrostatic properties which may affect the function and stability of the protein MeCP2. -- Abstract: Rett syndrome is an X-linked dominant disorder caused frequently by mutations in the methyl-CpG-binding protein 2 gene (MECP2). Rett patients present an apparently normal psychomotor development during the first 6-18 months of life. Thereafter, they show a short period of developmental stagnation followed by a rapid regression in language and motor development. The aim of this study was to perform a mutational analysis of the MECP2 gene in a classical Rett patient by sequencing the corresponding gene and modeling the found variants. The results showed the presence of a double-mutation: a new and de novo mutation c.535C > T (p.P179S) and the common c.763C > T (p.R255X) transition of the MECP2 gene. The p.P179S mutation was located in a conserved amino acid in CRIR domain (corepressor interacting region). Modeling results showed that the P179S transition could change local electrostatic properties by adding a negative charge due to serine hydroxyl group of this region of MeCP2 which may affect the function and stability of the protein. The p.R255X mutation is located in TRD-NLS domain (transcription repression domain-nuclear localization signal) of MeCP2 protein.

  19. Repeated ethanol exposure affects the acquisition of spatial memory in adolescent female rats.

    PubMed

    Sircar, Ratna; Basak, Ashim K; Sircar, Debashish

    2009-09-14

    Ethanol has been reported to disrupt spatial learning and memory in adolescent male rats. The present study was undertaken to determine the effects of ethanol on the acquisition of spatial memory in adolescent female rats. Adolescent female rats were subjected to repeated ethanol or saline treatments, and spatial learning was tested in the Morris water maze. For comparison, adult female rats were subjected to similar ethanol treatment and behavioral assessments as for adolescent rats. Ethanol-treated adolescent rats took longer and swam greater distances to find the hidden platform than saline controls. In the probe trial, ethanol-treated adolescent rats showed a trend towards reduced time spent in the target quadrant, and made significantly fewer target location crossings than saline-treated controls. Adult saline-treated control rats did not learn the spatial memory task as well as the adolescent saline-treated rats. Although ethanol in adult rats increased both latency and swim distance to find the platform, in the probe trial there was no difference between ethanol-treated adult rats and age-matched saline controls. Ethanol did not alter swim speed or performance in the cued visual task at either age. Together, these data suggest that ethanol specifically impairs the acquisition of spatial memory in adolescent female rats. Since adult females did not learn the task, ethanol-induced alterations in water maze performance may not reflect true learning and memory dysfunction. PMID:19463705

  20. Factors affecting winter survival of female mallards in the lower Mississippi alluvial valley

    USGS Publications Warehouse

    Davis, B.E.; Afton, A.D.; Cox, R.R.

    2011-01-01

    The lower Mississippi Alluvial Valley (hereafter LMAV) provides winter habitat for approximately 40% of the Mississippi Flyway's Mallard (Anas platyrhynhcos) population; information on winter survival rates of female Mallards in the LMAV is restricted to data collected prior to implementation of the North American Waterfowl Management Plan. To estimate recent survival and cause-specific mortality rates in the LMAV, 174 radio-marked female Mallards were tracked for a total of 11,912 exposure days. Survival varied by time periods defined by hunting seasons, and females with lower body condition (size adjusted body mass) at time of capture had reduced probability of survival. Female survival was less and the duration of our tracking period was greater than those in previous studies of similarly marked females in the LMAV; the product-limit survival estimate (??????SE) through the entire tracking period (136 days) was 0.54 ??0.10. Cause-specific mortality rates were 0.18 ??0.04 and 0.34 ??0.12 for hunting and other sources of mortality, respectively; the estimated mortality rate from other sources (including those from avian, mammalian, or unknown sources) was higher than mortality from non-hunting sources reported in previous studies of Mallards in the LMAV. Models that incorporate winter survival estimates as a factor in Mallard population growth rates should be adjusted for these reduced winter survival estimates.

  1. Leaf damage and gender but not flower damage affect female fitness in Nemophila menziesii (Hydrophyllaceae).

    PubMed

    McCall, Andrew C

    2007-03-01

    Researchers can answer questions about the evolution or maintenance of separate sexes using dioecious plant systems. Because females in these species typically put more resources into reproductive effort than male plants, researchers have hypothesized that females may be less tolerant of the stresses found in marginal habitats. Herbivory can act as a biotic stressor that reduces resources in plants much like a marginal habitat can. Females may be limited by resources, and may thus be less tolerant to herbivory than males. Here, I explore the relationships between florivory, leaf herbivory, and gender in a gynodioecious, annual plant, Nemophila menziesii (Hydrophyllaceae, senso lato). I performed a crossed design experiment examining the main effects and interactions of plant gender, artificial leaf damage, and artificial flower damage on components of female plant fitness. Leaf damage decreased fruit set and females made significantly more fruit than hermaphrodites. However, contrary to theory, I found little evidence for a gender by damage interaction for either type of artificial herbivory. Based on these results, I propose more work exploring the effects of both source and sink damage in dioecious species to help elucidate where and when different sexual morphs are favored by natural selection. PMID:21636414

  2. Populus cathayana males are less affected than females by excess manganese: comparative proteomic and physiological analyses.

    PubMed

    Chen, Fugui; Zhang, Sheng; Zhu, Guoping; Korpelainen, Helena; Li, Chunyang

    2013-08-01

    The comprehension of sexually different responses in dioecious plants to excess manganese (Mn) stress requires molecular explanation. Physiological and proteomic changes in leaves of Populus cathayana males and females were analyzed after 4 wk of exposure to Mn stress. Under excess Mn conditions, shoot height and photosynthesis decreased more in females than in males. Females also showed severe browning and subcellular damage, higher Mn2+ absorption, and different antioxidant enzyme activities compared with males. There were ten differently regulated protein spots induced by excess Mn stress. They were mainly related to photosynthesis, ROS cleaning, and cell signaling associated to ROS, plant cell death, heat shock, cell defense and rescue, and gene expression and regulation. Variation in protein expression between the sexes clearly showed that males have evolved more efficient photosynthesis capacity, more stable gene expression and regulation, and better cell defense and rescue to prevent further injury under excess Mn stress. PMID:23868850

  3. A study of the factors affecting the attitudes of young female students toward chemistry at the high school level

    NASA Astrophysics Data System (ADS)

    Banya, Santonino K.

    Chemistry is a human endeavor that relies on basic human qualities like creativity, insights, reasoning, and skills. It depends on habits of the mind: skepticism, tolerance of ambiguity, openness to new ideas, intellectual honesty, curiosity, and communication. Young female students begin studying chemistry curiosity; however, when unconvinced, they become skeptical. Researches focused on gender studies have indicated that attitudes toward science education differ between males and females. A declining interest in chemistry and the under representation of females in the chemical science was found (Jacobs, 2000). This study investigated whether self-confidence toward chemistry, the influence of role models, and knowledge about the usefulness of chemistry were affecting the attitudes toward chemistry, of 183 high school young females across the United States. The young female students surveyed, had studied chemistry for at least one year prior to participating in the study during the fall semester of 2003. The schools were randomly selected represented diverse economic backgrounds and geographical locations. Data were obtained using Chemistry Attitude Influencing Factors (CAIF) instrument and from interviews with a focus group of three young female students about the effect of self-confidence toward chemistry, the influence of role models, and knowledge about the usefulness of chemistry on their decision to study chemistry. The CAIF instrument consisted of a 12-items self-confidence questionnaire (ConfiS), 12-items each of the influence of role models (RoMoS) and knowledge about usefulness of chemistry (US) questionnaire. ConfiS was adopted (with permission) from CAEQ (Coll & Dalgety, 2001), and both RoMoS and US were modified from TOSRA (Fraser, 1978), public domain document. The three young female students interviewed, gave detailed responses about their opinions regarding self-confidence toward chemistry, the influence of role models, and knowledge about the

  4. Vitellogenin knockdown strongly affects cotton boll weevil egg viability but not the number of eggs laid by females.

    PubMed

    Coelho, Roberta R; de Souza Júnior, José Dijair Antonino; Firmino, Alexandre A P; de Macedo, Leonardo L P; Fonseca, Fernando C A; Terra, Walter R; Engler, Gilbert; de Almeida Engler, Janice; da Silva, Maria Cristina M; Grossi-de-Sa, Maria Fatima

    2016-09-01

    Vitellogenin (Vg), a yolk protein precursor, is the primary egg nutrient source involved in insect reproduction and embryo development. The Cotton Boll weevil (CBW) Anthonomus grandis Boheman, the most important cotton pest in Americas, accumulates large amounts of Vg during reproduction. However, the precise role of this protein during embryo development in this insect remains unknown. Herein, we investigated the effects of vitellogenin (AgraVg) knockdown on the egg-laying and egg viability in A. grandis females, and also characterized morphologically the unviable eggs. AgraVg transcripts were found during all developmental stages of A. grandis, with highest abundance in females. Silencing of AgraVg culminated in a significant reduction in transcript amount, around 90%. Despite this transcriptional reduction, egg-laying was not affected in dsRNA-treated females but almost 100% of the eggs lost their viability. Eggs from dsRNA-treated females showed aberrant embryos phenotype suggesting interference at different stages of embryonic development. Unlike for other insects, the AgraVg knockdown did not affect the egg-laying ability of A. grandis, but hampered A. grandis reproduction by perturbing embryo development. We concluded that the Vg protein is essential for A. grandis reproduction and a good candidate to bio-engineer the resistance against this devastating cotton pest. PMID:27419079

  5. An Investigation of Factors Affecting Elementary Female Student Teachers' Choice of Science as a Major at College Level in Zimbabwe

    NASA Astrophysics Data System (ADS)

    Mlenga, Francis

    This article focuses on factors affecting elementary female student teachers' choice of science as a major at college level in Zimbabwe. In Sub-Saharan Africa, there has been an unprecedented expansion in education in the last 2 decades. This reflects the broad recognition that education contributes to national development. This expansion has not been matched with equal access and opportunity to education. The education of females still lags behind that of males in most developing countries, and in Sub-Saharan Africa in particular (Hyde, 1989). Fewer girls than boys study science at both secondary and college levels. The study took place in Zimbabwe at Mkoba Teachers' College. Two groups of elementary female student teachers participated in the study, namely science majors and nonscience majors. Ten science majors and nine nonscience majors took part in individual interviews. For focus group interviews, there were three groups of six each from science and nonscience majors. The study was conducted between May 2004 and July 2004. Out-of-school experiences, culture, and attitudes toward science emerged as factors affecting female student teachers' choice of science as a major. A number of implications have been discussed as well as suggestions for further research. Limitations of the study have been analyzed as well.

  6. Vitellogenin knockdown strongly affects cotton boll weevil egg viability but not the number of eggs laid by females.

    PubMed

    Coelho, Roberta R; de Souza Júnior, José Dijair Antonino; Firmino, Alexandre A P; de Macedo, Leonardo L P; Fonseca, Fernando C A; Terra, Walter R; Engler, Gilbert; de Almeida Engler, Janice; da Silva, Maria Cristina M; Grossi-de-Sa, Maria Fatima

    2016-09-01

    Vitellogenin (Vg), a yolk protein precursor, is the primary egg nutrient source involved in insect reproduction and embryo development. The Cotton Boll weevil (CBW) Anthonomus grandis Boheman, the most important cotton pest in Americas, accumulates large amounts of Vg during reproduction. However, the precise role of this protein during embryo development in this insect remains unknown. Herein, we investigated the effects of vitellogenin (AgraVg) knockdown on the egg-laying and egg viability in A. grandis females, and also characterized morphologically the unviable eggs. AgraVg transcripts were found during all developmental stages of A. grandis, with highest abundance in females. Silencing of AgraVg culminated in a significant reduction in transcript amount, around 90%. Despite this transcriptional reduction, egg-laying was not affected in dsRNA-treated females but almost 100% of the eggs lost their viability. Eggs from dsRNA-treated females showed aberrant embryos phenotype suggesting interference at different stages of embryonic development. Unlike for other insects, the AgraVg knockdown did not affect the egg-laying ability of A. grandis, but hampered A. grandis reproduction by perturbing embryo development. We concluded that the Vg protein is essential for A. grandis reproduction and a good candidate to bio-engineer the resistance against this devastating cotton pest.

  7. Rett networked database: an integrated clinical and genetic network of Rett syndrome databases.

    PubMed

    Grillo, Elisa; Villard, Laurent; Clarke, Angus; Ben Zeev, Bruria; Pineda, Mercedes; Bahi-Buisson, Nadia; Hryniewiecka-Jaworska, Anna; Bienvenu, Thierry; Armstrong, Judith; Roche-Martinez, Ana; Mari, Francesca; Veneselli, Edvige; Russo, Silvia; Vignoli, Aglaia; Pini, Giorgio; Djuric, Milena; Bisgaard, Anne-Marie; Mejaški Bošnjak, Vlatka; Polgár, Noémi; Cogliati, Francesca; Ravn, Kirstine; Pintaudi, Maria; Melegh, Béla; Craiu, Dana; Djukic, Aleksandra; Renieri, Alessandra

    2012-07-01

    Rett syndrome (RTT) is a neurodevelopmental disorder with one principal phenotype and several distinct, atypical variants (Zappella, early seizure onset and congenital variants). Mutations in MECP2 are found in most cases of classic RTT but at least two additional genes, CDKL5 and FOXG1, can underlie some (usually variant) cases. There is only limited correlation between genotype and phenotype. The Rett Networked Database (http://www.rettdatabasenetwork.org/) has been established to share clinical and genetic information. Through an "adaptor" process of data harmonization, a set of 293 clinical items and 16 genetic items was generated; 62 clinical and 7 genetic items constitute the core dataset; 23 clinical items contain longitudinal information. The database contains information on 1838 patients from 11 countries (December 2011), with or without mutations in known genes. These numbers can expand indefinitely. Data are entered by a clinician in each center who supervises accuracy. This network was constructed to make available pooled international data for the study of RTT natural history and genotype-phenotype correlation and to indicate the proportion of patients with specific clinical features and mutations. We expect that the network will serve for the recruitment of patients into clinical trials and for developing quality measures to drive up standards of medical management. PMID:22415763

  8. An unexpected affected female patient in a classical Lesch-Nyhan family.

    PubMed

    De Gregorio, L; Nyhan, W L; Serafin, E; Chamoles, N A

    2000-03-01

    Lesch-Nyhan disease is a genetic disorder of purine metabolism caused by defective activity of the enzyme hypoxanthine-guanine phosphoribosyl transferase (HPRT), resulting from mutation in the corresponding gene on the long arm of the X chromosome (Xq26). The classical phenotype, which includes spasticity, involuntary movements, developmental disability, and self-injurious behavior, occurs exclusively in males, while heterozygous, carrier females are clinically normal. We analyzed an Argentine family in which there were male and female siblings with clinically identical classic features of Lesch-Nyhan disease. The mother and an older daughter were carriers and had normal phenotypes. We identified the HPRT mutation in the family. It is a C --> T transition at position 508 of the cDNA (c.508 C --> T) that changes the CGA codon for Arg(169) to the TGA stop codon (R169X). The female patient was karyotypically normal and heterozygous for the mutation. She inherited the HPRT mutation from her mother, but she also had unexpected nonrandom inactivation of the paternal X chromosome carrying the normal HPRT gene. This additional genetic alteration is the cause of the clinical expression of disease in this female patient.

  9. Female prairie vole mate-choice is affected by the males' birth litter composition.

    PubMed

    Curtis, J Thomas

    2010-08-01

    Experimental testing and retrospective examination of breeding records were used to examine the influence of sex composition and/or size of males' birth litters on female mate-choice. Sexually naïve female prairie voles (Microtus ochrogaster) avoided males derived from all-male litters, but showed no preference for, or aversion to, males from single-male litters or from more typical mixed-sex litters. Examination of the pregnancy status of females after two weeks of pairing with a male allowed us to estimate the probabilites of a pups' intrauterine position relative to siblings for various litter sizes. The typical prairie vole pup derived from a mixed-sex litter comprised of 4.4 pups, and had a 13% chance of being isolated from siblings in utero and a 22% chance of being between siblings in utero. Pups from single-sex litters tended to be larger at weaning than did pups from mixed-sex litters; however, male size did not influence female choice behavior. These results suggest that some aspect of the perinatal experience of prairie vole pups from single sex litters can influence social interactions later in life.

  10. Females' Evaluations of Males as a Function of Affect Arousing Musical Stimuli.

    ERIC Educational Resources Information Center

    May, James L.; Hamilton, Phyllis Ann

    Female subjects were asked to evaluate either an attractive or unattractive male stimulus person under one of the three experimental conditions; while listening to avant-garde, rock music, or no music at all. Responding on the Interpersonal Judgement Scale (IJS: Byrne, 1971) and a seven-point physical attractiveness scale, subjects indicated more…

  11. Inbreeding affects sexual signalling in males but not females of Tenebrio molitor.

    PubMed

    Pölkki, Mari; Krams, Indrikis; Kangassalo, Katariina; Rantala, Markus J

    2012-06-23

    In many species of animals, individuals advertise their quality with sexual signals to obtain mates. Chemical signals such as volatile pheromones are species specific, and their primary purpose is to influence mate choice by carrying information about the phenotypic and genetic quality of the sender. The deleterious effects of consanguineous mating on individual quality are generally known, whereas the effect of inbreeding on sexual signalling is poorly understood. Here, we tested whether inbreeding reduces the attractiveness of sexual signalling in the mealworm beetle, Tenebrio molitor, by testing the preferences for odours of inbred and outbred (control) individuals of the opposite sex. Females were more attracted to the odours produced by outbred males than the odours produced by inbred males, suggesting that inbreeding reduces the attractiveness of male sexual signalling. However, we did not find any difference between the attractiveness of inbred and outbred female odours, which may indicate that the quality of females is either irrelevant for T. molitor males or quality is not revealed through female odours. PMID:22237501

  12. Factors that Affect the Physical Science Career Interest of Female Students: Testing Five Common Hypotheses

    ERIC Educational Resources Information Center

    Hazari, Zahra; Potvin, Geoff; Lock, Robynne M.; Lung, Florin; Sonnert, Gerhard; Sadler, Philip M.

    2013-01-01

    There are many hypotheses regarding factors that may encourage female students to pursue careers in the physical sciences. Using multivariate matching methods on national data drawn from the Persistence Research in Science and Engineering (PRiSE) project ("n" = 7505), we test the following five commonly held beliefs regarding what…

  13. Latent Inhibition Is Affected by Phase of Estrous Cycle in Female Rats

    ERIC Educational Resources Information Center

    Quinlan, Matthew G.; Duncan, Andrew; Loiselle, Catherine; Graffe, Nicole; Brake, Wayne G.

    2010-01-01

    Estrogen has been shown to have a strong modulatory influence on several types of cognition in both women and female rodents. Latent inhibition is a task in which pre-exposure to a neutral stimulus, such as a tone, later impedes the association of that stimulus with a particular consequence, such as a shock. Previous work from our lab demonstrates…

  14. Test Administrator's Gender Affects Female and Male Students' Self-Estimated Verbal General Knowledge

    ERIC Educational Resources Information Center

    Ortner, Tuulia M.; Vormittag, Isabella

    2011-01-01

    Effects of test administrator's gender on test takers' self-estimated verbal general knowledge and de facto verbal general knowledge were investigated. Based on three theories previously applied in research dealing with the effects of test administrator's ethnicity, it was expected male and female test takers to show higher scores under female…

  15. Radio-transmitters do not affect seasonal productivity of female Golden-winged Warblers

    USGS Publications Warehouse

    Streby, Henry M.; Peterson, Sean M.; Gesmundo, Callie; Johnson, Michael K.; Fish, Alexander C.; Lehman, Justin A.; Andersen, David E.

    2013-01-01

    Investigating the potential effects of handling and marking techniques on study animals is important for correct interpretation of research results and to effect progress in data-collection methods. Few investigators have compared the reproductive output of radio-tagged and non-radio-tagged songbirds, and no one to date has examined the possible effect of radio-tagging adult songbirds on the survival of their fledglings. In 2011 and 2012, we compared several parameters of reproductive output of two groups of female Golden-winged Warblers (Vermivora chrysoptera) breeding in Minnesota, including 45 females with radio-transmitters and 73 females we did not capture, handle, or mark. We found no difference between groups in clutch sizes, hatching success, brood sizes, length of incubation and nestling stages, fledging success, number of fledglings, or survival of fledglings to independence. Thus, radio-tags had no measurable impact on the productivity of female Golden-winged Warblers. Our results build upon previous studies where investigators have reported no effects of radio-tagging on the breeding parameters of songbirds by also demonstrating no effect of radio-tagging through the post-fledging period and, therefore, the entire breeding season.

  16. Developmental Exposure to Ethinylestradiol Affects Reproductive Physiology, the GnRH Neuroendocrine Network and Behaviors in Female Mouse

    PubMed Central

    Derouiche, Lyes; Keller, Matthieu; Martini, Mariangela; Duittoz, Anne H.; Pillon, Delphine

    2015-01-01

    During development, environmental estrogens are able to induce an estrogen mimetic action that may interfere with endocrine and neuroendocrine systems. The present study investigated the effects on the reproductive function in female mice following developmental exposure to pharmaceutical ethinylestradiol (EE2), the most widespread and potent synthetic steroid present in aquatic environments. EE2 was administrated in drinking water at environmentally relevant (ENVIR) or pharmacological (PHARMACO) doses [0.1 and 1 μg/kg (body weight)/day respectively], from embryonic day 10 until postnatal day 40. Our results show that both groups of EE2-exposed females had advanced vaginal opening and shorter estrus cycles, but a normal fertility rate compared to CONTROL females. The hypothalamic population of GnRH neurons was affected by EE2 exposure with a significant increase in the number of perikarya in the preoptic area of the PHARMACO group and a modification in their distribution in the ENVIR group, both associated with a marked decrease in GnRH fibers immunoreactivity in the median eminence. In EE2-exposed females, behavioral tests highlighted a disturbed maternal behavior, a higher lordosis response, a lack of discrimination between gonad-intact and castrated males in sexually experienced females, and an increased anxiety-related behavior. Altogether, these results put emphasis on the high sensitivity of sexually dimorphic behaviors and neuroendocrine circuits to disruptive effects of EDCs. PMID:26696819

  17. Exposure to methylphenidate during peri-adolescence affects endocrine functioning and sexual behavior in female Long-Evans rats.

    PubMed

    Guarraci, Fay A; Holifield, Caroline; Morales-Valenzuela, Jessica; Greene, Kasera; Brown, Jeanette; Lopez, Rebecca; Crandall, Christina; Gibbs, Nicole; Vela, Rebekah; Delgado, Melissa Y; Frohardt, Russell J

    2016-03-01

    The present study was designed to test the effects of methylphenidate (MPH) exposure on the maturation of endocrine functioning and sexual behavior. Female rat pups received either MPH (2.0mg/kg, i.p.) or saline twice daily between postnatal days 20-35. This period of exposure represents the time just prior to puberty as well as puberty onset. Approximately five weeks after the last injection of MPH or saline, female subjects were hormone-primed and tested during their first sexual experience. Subjects were given the choice to interact with a sexually active male or a sexually receptive female rat (i.e., the partner-preference test). The partner-preference paradigm allows us to assess multiple aspects of female sexual behavior. MPH exposure during peri-adolescence delayed puberty and, when mated for the first time, affected sexual behavior (e.g., increased time spent with the male stimulus and decreased the likelihood of leaving after mounts) during the test of partner preference. When monitoring estrous cyclicity, female subjects treated with MPH during peri-adolescence frequently experienced irregular estrous cycles. The results of the present study suggest that chronic exposure to a therapeutic dose of MPH around the onset of puberty alters long-term endocrine functioning, but with hormone priming, increases sensitivity to sexual stimuli.

  18. A case of a Tunisian Rett patient with a novel double-mutation of the MECP2 gene.

    PubMed

    Fendri-Kriaa, Nourhene; Hsairi, Ines; Kifagi, Chamseddine; Ellouze, Emna; Mkaouar-Rebai, Emna; Triki, Chahnez; Fakhfakh, Faiza

    2011-06-01

    Rett syndrome is an X-linked dominant disorder caused frequently by mutations in the methyl-CpG-binding protein 2 gene (MECP2). Rett patients present an apparently normal psychomotor development during the first 6-18 months of life. Thereafter, they show a short period of developmental stagnation followed by a rapid regression in language and motor development. The aim of this study was to perform a mutational analysis of the MECP2 gene in a classical Rett patient by sequencing the corresponding gene and modeling the found variants. The results showed the presence of a double-mutation: a new and de novo mutation c.535C>T (p.P179S) and the common c.763C>T (p.R255X) transition of the MECP2 gene. The p.P179S mutation was located in a conserved amino acid in CRIR domain (corepressor interacting region). Modeling results showed that the P179S transition could change local electrostatic properties by adding a negative charge due to serine hydroxyl group of this region of MeCP2 which may affect the function and stability of the protein. The p.R255X mutation is located in TRD-NLS domain (transcription repression domain-nuclear localization signal) of MeCP2 protein. PMID:21575601

  19. Environmental-like exposure to low levels of estrogen affects sexual behavior and physiology of female rats.

    PubMed

    Della Seta, Daniele; Farabollini, Francesca; Dessì-Fulgheri, Francesco; Fusani, Leonida

    2008-11-01

    Xenoestrogens are endocrine-disrupting chemicals that mimic the action of endogenous estrogen hormones. Effects of xenoestrogen on aquatic wildlife are well documented, whereas the experimental evidence for impairment of reproductive behavior and physiology in mammals after exposure to xenoestrogens has been debated. The strongest arguments against such studies have been that the route, time course, and intensity of exposure did not simulate environmental exposure and that the chemicals tested have additional nonestrogenic toxic effects, hindering generalization of actual xenoestrogenic effects. Here we show that environmental-like exposure to the pure estrogen 17alpha-ethinylestradiol during development alters reproductive behavior and physiology in adult female Sprague-Dawley rats. We simulated environmental exposure by giving low doses (0.4 and 0.004 microg/kg.d) of 17alpha-ethinylestradiol orally to pregnant females from conception to weaning of the pups, which continued to receive the treatment until puberty. We studied the sexual behavior, estrous cycle, and estradiol plasma levels of intact female rats when they reached 3 months of age. Exposure to the higher dose strongly affected female sexual behavior and physiology, with suppression of lordosis and the estrous cycle and enhanced aggression toward males. The lower dose disrupted appetitive components of sexual behavior that influence the rate of copulation. Estradiol plasma levels were not affected by the treatment. Our study revealed that exposure to low oral doses of a pure estrogen during development alters female sexual behavior and physiology. These results suggest potential risks of reproductive failure from xenoestrogen exposure in realistic ecological conditions.

  20. Activity and social factors affect cohesion among individuals in female Japanese macaques: A simultaneous focal-follow study.

    PubMed

    Nishikawa, Mari; Suzuki, Mariko; Sprague, David S

    2014-07-01

    Understanding cohesion among individuals within a group is necessary to reveal the social system of group-living primates. Japanese macaques (Macaca fuscata) are female-philopatric primates that reside in social groups. We investigated whether individual activity and social factors can affect spatio-temporal cohesion in wild female Japanese macaques. We conducted behavioral observation on a group, which contained 38 individuals and ranged over ca. 60 ha during the study period. Two observers carried out simultaneous focal-animal sampling of adult female pairs during full-day follows using global positioning system which enabled us to quantify interindividual distances (IIDs), group members within visual range (i.e., visual unit), and separation duration beyond visual range as indicators of cohesion among individuals. We found considerable variation in spatio-temporal group cohesion. The overall mean IID was 99.9 m (range = 0-618.2 m). The percentage of IIDs within visual range was 23.1%, within auditory range was 59.8%, and beyond auditory range was 17.1%. IIDs varied with activity; they were shorter during grooming and resting, and longer during foraging and traveling. Low-ranking females showed less cohesion than high-ranking ones. Kin females stayed nearly always within audible range. The macaques were weakly cohesive with small mean visual unit size (3.15 counting only adults, 5.99 counting all individuals). Both-sex units were the most frequently observed visual unit type when they were grooming/resting. Conversely, female units were the most frequently observed visual unit type when they were foraging. The overall mean visual separation duration was 25.7 min (range = 3-513 min). Separation duration was associated with dominance rank. These results suggest that Japanese macaques regulate cohesion among individuals depending on their activity and on social relationships; they were separated to adapt food distribution and aggregated to maintain social

  1. Estrous cycle affects the neurochemical and neurobehavioral profile of carvacrol-treated female rats

    SciTech Connect

    Trabace, L.; Zotti, M.; Morgese, M.G.; Tucci, P.; Colaianna, M.; Schiavone, S.; Avato, P.; Cuomo, V.

    2011-09-01

    Carvacrol is the major constituent of essential oils from aromatic plants. It showed antimicrobial, anticancer and antioxidant properties. Although it was approved for food use and included in the chemical flavorings list, no indication on its safety has been estimated. Since the use of plant extracts is relatively high among women, aim of this study was to evaluate carvacrol effects on female physiology and endocrine profiles by using female rats in proestrus and diestrus phases. Serotonin and metabolite tissue content in prefrontal cortex and nucleus accumbens, after carvacrol administration (0.15 and 0.45 g/kg p.o.), was measured. Drug effects in behavioral tests for alterations in motor activity, depression, anxiety-related behaviors and endocrine alterations were also investigated. While in proestrus carvacrol reduced serotonin and metabolite levels in both brain areas, no effects were observed in diestrus phase. Only in proestrus phase, carvacrol induced a depressive-like behavior in forced swimming test, without accompanying changes in ambulation. The improvement of performance in FST after subchronic treatment with fluoxetine (20 mg/kg) suggested a specific involvement of serotonergic system. No differences were found across the groups with regard to self-grooming behavior. Moreover, in proestrus phase, carvacrol reduced only estradiol levels without binding hypothalamic estradiol receptors. Our study showed an estrous-stage specific effect of carvacrol on depressive behaviors and endocrine parameters, involving serotonergic system. Given the wide carvacrol use not only as feed additive, but also as cosmetic essence and herbal remedy, our results suggest that an accurate investigation on the effects of its chronic exposure is warranted. - Highlights: > Carvacrol induced a depressive-like phenotype in rats, depending on ovarian cyclicity. > Carvacrol selectively reduced serotonin content in female rats in proestrus phase. > Carvacrol reduced serotonin levels

  2. Sex and Gender: How Being Male or Female Can Affect Your Health

    MedlinePlus

    ... smoking to create “movies” of how smoking affects dopamine, the chemical messenger that triggers feelings of pleasure ... brain. These brain movies showed that smoking alters dopamine in the brain at different rates and in ...

  3. Longitudinal bone mineral content and density in Rett syndrome and their contributing factors.

    PubMed

    Jefferson, Amanda; Fyfe, Sue; Downs, Jenny; Woodhead, Helen; Jacoby, Peter; Leonard, Helen

    2015-05-01

    Bone mass and density are low in females with Rett syndrome. This study used Dual energy x-ray absorptiometry to measure annual changes in z-scores for areal bone mineral density (aBMD) and bone mineral content (BMC) in the lumbar spine and total body in an Australian Rett syndrome cohort at baseline and then after three to four years. Bone mineral apparent density (BMAD) was calculated in the lumbar spine. Annual changes in lean tissue mass (LTM) and bone area (BA) were also assessed. The effects of age, genotype, mobility, menstrual status and epilepsy diagnosis on these parameters were also investigated. The baseline sample included 97 individuals who were representative of the total live Australian Rett syndrome population under 30years in 2005 (n=274). Of these 74 had a follow-up scan. Less than a quarter of females were able to walk on their own at follow-up. Bone area and LTM z-scores declined over the time between the baseline and follow-up scans. Mean height-standardised z-scores for the bone outcomes were obtained from multiple regression models. The lumbar spine showed a positive mean annual BMAD z-score change (0.08) and a marginal decrease in aBMD (-0.04). The mean z-score change per annum for those 'who could walk unaided' was more positive for LS BMAD (p=0.040). Total body BMD mean annual z-score change from baseline to follow-up was negative (-0.03). However this change was positive in those who had achieved menses prior to the study (0.03, p=0,040). Total body BMC showed the most negative change (-0.60), representing a decrease in bone mineral content over time. This normalised to a z-score change of 0.21 once adjusted for the reduced lean tissue mass mean z-score change (-0.21) and bone area mean z-score change (-0.14). Overall, the bone mineral content, bone mineral density, bone area and lean tissue mass z-scores for all outcome measures declined, with the TB BMC showing significant decreases. Weight, height and muscle mass appear to have

  4. Exposure of Female Rats to an Environmentally Relevant Mixture of Brominated Flame Retardants Targets the Ovary, Affecting Folliculogenesis and Steroidogenesis.

    PubMed

    Lefèvre, Pavine L C; Berger, Robert G; Ernest, Sheila R; Gaertner, Dean W; Rawn, Dorothea F K; Wade, Michael G; Robaire, Bernard; Hales, Barbara F

    2016-01-01

    Brominated flame retardants (BFRs) are incorporated into various consumer products to prevent flame propagation. These compounds leach into the domestic environment, resulting in chronic exposure and contamination. Pregnancy failure is associated with high levels of BFRs in human follicular fluid, raising serious questions regarding their impact on female reproductive health. The goal of this study is to elucidate the effects of an environmentally relevant BFR mixture on female rat ovarian functions (i.e., folliculogenesis and steroidogenesis). A BFR dietary mixture formulated to mimic the relative BFR congener levels in North American house dust was administered to adult female Sprague-Dawley rats from 2 to 3 wk before mating until Gestational Day 20; these diets were designed to deliver nominal doses of 0, 0.06, 20, or 60 mg/kg/day of the BFR mixture. Exposure to BFRs triggered an approximately 50% increase in the numbers of preantral and antral follicles and an enlargement of the antral follicles in the ovaries of the dams. A significant reduction in the expression of catalase, an antioxidant enzyme, and downregulation of the expression of insulin-like factor 3 (Insl3) and 17alpha-hydroxylase (Cyp17a1) were observed in the ovary. In addition, BFR exposure affected steroidogenesis; we observed a significant decrease in circulating 17-hydroxypregnenolone and an increase in testosterone concentrations in BFR-exposed dams. Thus, BFRs target ovarian function in the rat, adversely affecting both folliculogenesis and steroidogenesis.

  5. Cytochrome P450 differences in normal and imposex-affected female whelk Buccinum undatum from the open North Sea.

    PubMed

    Santos, M M; ten Hallers-Tjabbes, C C; Vieira, N; Boon, J P; Porte, C

    2002-01-01

    Normal and imposex-affected female Buccinum undatum were sampled from the open North Sea at three locations, one with low, and two with high shipping densities. Cytochrome P450 components and P450 aromatase activity were determined in the microsomal fractions isolated from pooled digestive gland/gonads. Cytochrome P450 aromatase activity was significantly higher (P < 0.05) in normal females collected in the low shipping density area (1,325 +/- 295 fmol/h/mg protein) than levels from imposex animals from a high shipping density area (620 +/- 287 fmol/h/mg protein). A negative correlation was found between aromatase activity and organotin body burden (r = -0.99). Levels of CYP450, cytochrome b5 and NADPH cytochrome c reductase activity did not show differences among groups. This is the first field evidence of depressed aromatase activity in imposex affected females, although additional research under laboratory controlled conditions is required to fully understand the mechanisms underlying the development of imposex in this species.

  6. Retracing Atypical Development: A Preserved Speech Variant of Rett Syndrome

    ERIC Educational Resources Information Center

    Marschik, Peter B.; Einspieler, Christa; Oberle, Andreas; Laccone, Franco; Prechtl, Heinz F. R.

    2009-01-01

    The subject of the present study is the development of a girl with the preserved speech variant of Rett disorder. Our data are based on detailed retrospective and prospective video analyses. Despite achieving developmental milestones, movement quality was already abnormal during the girl's first half year of life. In addition, early hand…

  7. Communication Intervention in Rett Syndrome: A Systematic Review

    ERIC Educational Resources Information Center

    Sigafoos, Jeff; Green, Vanessa A.; Schlosser, Ralf; O'eilly, Mark F.; Lancioni, Giulio E.; Rispoli, Mandy; Lang, Russell

    2009-01-01

    We reviewed communication intervention studies involving people with Rett syndrome. Systematic searches of five electronic databases, selected journals, and reference lists identified nine studies meeting the inclusion criteria. These studies were evaluated in terms of: (a) participant characteristics, (b) target skills, (c) procedures, (d) main…

  8. Functional Communication Training in Rett Syndrome: A Preliminary Study

    ERIC Educational Resources Information Center

    Byiers, Breanne J.; Dimian, Adele; Symons, Frank J.

    2014-01-01

    Rett syndrome (RTT) is associated with a range of serious neurodevelopmental consequences including severe communicative impairments. Currently, no evidence-based communication interventions exist for the population (Sigafoos et al., 2009). The purpose of the current study was to examine the effectiveness of functional assessment (FA) and…

  9. Intentionality and Communication in Four Children with Rett Syndrome.

    ERIC Educational Resources Information Center

    Woodyatt, Gail; Ozanne, Anne

    1994-01-01

    A multiple case study design was used to describe the cognitive and communicative behaviors of four girls with Rett syndrome (RS). Three subjects were at a preintentional level of communication. Communication levels for all subjects was consistent with cognitive status. Dyspraxia appeared to interfere with communicative attempts of the one subject…

  10. Changing the Perspective on Early Development of Rett Syndrome

    ERIC Educational Resources Information Center

    Marschik, Peter B.; Kaufmann, Walter E.; Sigafoos, Jeff; Wolin, Thomas; Zhang, Dajie; Bartl-Pokorny, Katrin D.; Pini, Giorgio; Zappella, Michele; Tager-Flusberg, Helen; Einspieler, Christa; Johnston, Michael V.

    2013-01-01

    We delineated the achievement of early speech-language milestones in 15 young children with Rett syndrome ("MECP2" positive) in the first two years of life using retrospective video analysis. By contrast to the commonly accepted concept that these children are normal in the pre-regression period, we found markedly atypical development of…

  11. The Role of Stereotypies in Overselectivity Process in Rett Syndrome

    ERIC Educational Resources Information Center

    Fabio, Rosa Angela; Giannatiempo, Samantha; Antonietti, Alessandro; Budden, Sarojini

    2009-01-01

    Ten Rett syndrome (RS) girls and 10 control girls executed an attentional task in which a complex stimulus was shown followed by individual stimuli presented with distractors. Participants had to discriminate previously presented stimuli from distractors. RS girls carried out the task both in a condition with the containment of stereotypies and in…

  12. Preliminary Assessment of Choice Making among Children with Rett Syndrome.

    ERIC Educational Resources Information Center

    Sigafoos, Jeff; And Others

    1995-01-01

    Choice making was studied among 7 students (ages 7-17) with Rett syndrome. Half the opportunities to choose food, beverage, and leisure items elapsed without a choice being made. Results suggest that the relationship between selecting and accepting items vary as a function of task configuration, and lack of choice may not necessarily indicate lack…

  13. Features of Autism in Rett Syndrome and Severe Mental Retardation.

    ERIC Educational Resources Information Center

    Mount, Rebecca H.; Charman, Tony; Hastings, Richard P.; Reilly, Sheena; Cass, Hilary

    2003-01-01

    The Autism Behavior Checklist measured autistic symptoms in 15 girls (ages 11-16) with Rett Syndrome (RS) and 14 with severe mental retardation. Girls with RS scored higher on the Sensory and Relating subscales. There were no differences on the Body and Object Use, Language, and Social and Self-Help subscales. (Contains references.) (Author/CR)

  14. SATB2-associated syndrome presenting with Rett-like phenotypes.

    PubMed

    Lee, J S; Yoo, Y; Lim, B C; Kim, K J; Choi, M; Chae, J-H

    2016-06-01

    The SATB2-associated syndrome (SAS) was proposed recently, after the SATB2 gene was initially discovered to be associated with isolated cleft palate. This syndrome is characterized by intellectual disability with delayed speech development, facial dysmorphism, cleft or high-arched palate, and dentition problems. Here, we describe two novel SATB2 sequence variants in two unrelated patients presenting with Rett-like phenotypes. We performed trio-based whole-exome sequencing in a 17-month-old girl presenting with severe retardation and Rett-like phenotypes, which revealed a de novo missense variant in SATB2 (p.Glu396Gln). Moreover, targeted sequencing of the SATB2 gene was performed in a 2-year-old girl with severe psychomotor retardation, facial hypotonia, and cleft palate who also exhibited some features of Rett syndrome. A nonsense variant in SATB2 was identified in this patient (p.Arg459*). This study expanded the clinical and genetic spectrum of SAS. SATB2 variants should be considered in cases with psychomotor retardation alone or in any cases with Rett-like phenotypes, regardless of the typical features of SAS such as cleft palate.

  15. Communication Assessment for Individuals with Rett Syndrome: A Systematic Review

    ERIC Educational Resources Information Center

    Sigafoos, Jeff; Kagohara, Debora; van der Meer, Larah; Green, Vanessa A.; O'Reilly, Mark F.; Lancioni, Giulio E.; Lang, Russell; Rispoli, Mandy; Zisimopoulos, Dimitrios

    2011-01-01

    We reviewed studies that aimed to determine whether behaviors, such as body movements, vocalizations, eye gaze, and facial expressions, served a communicative function for individuals with Rett syndrome. A systematic search identified eight studies, which were summarized in terms of (a) participants, (b) assessment targets, (c) assessment…

  16. Isolation of MECP2-null Rett Syndrome patient hiPS cells and isogenic controls through X-chromosome inactivation

    PubMed Central

    Cheung, Aaron Y.L.; Horvath, Lindsay M.; Grafodatskaya, Daria; Pasceri, Peter; Weksberg, Rosanna; Hotta, Akitsu; Carrel, Laura; Ellis, James

    2011-01-01

    Rett syndrome (RTT) is a neurodevelopmental autism spectrum disorder that affects girls due primarily to mutations in the gene encoding methyl-CpG binding protein 2 (MECP2). The majority of RTT patients carry missense and nonsense mutations leading to a hypomorphic MECP2, while null mutations leading to the complete absence of a functional protein are rare. MECP2 is an X-linked gene subject to random X-chromosome inactivation resulting in mosaic expression of mutant MECP2. The lack of human brain tissue motivates the need for alternative human cellular models to study RTT. Here we report the characterization of a MECP2 mutation in a classic female RTT patient involving rearrangements that remove exons 3 and 4 creating a functionally null mutation. To generate human neuron models of RTT, we isolated human induced pluripotent stem (hiPS) cells from RTT patient fibroblasts. RTT-hiPS cells retained the MECP2 mutation, are pluripotent and fully reprogrammed, and retained an inactive X-chromosome in a nonrandom pattern. Taking advantage of the latter characteristic, we obtained a pair of isogenic wild-type and mutant MECP2 expressing RTT-hiPS cell lines that retained this MECP2 expression pattern upon differentiation into neurons. Phenotypic analysis of mutant RTT-hiPS cell-derived neurons demonstrated a reduction in soma size compared with the isogenic control RTT-hiPS cell-derived neurons from the same RTT patient. Analysis of isogenic control and mutant hiPS cell-derived neurons represents a promising source for understanding the pathogenesis of RTT and the role of MECP2 in human neurons. PMID:21372149

  17. Estradiol affects liver mitochondrial function in ovariectomized and tamoxifen-treated ovariectomized female rats

    SciTech Connect

    Moreira, Paula I.; Custodio, Jose B.A.; Nunes, Elsa; Moreno, Antonio; Seica, Raquel; Oliveira, Catarina R.; Santos, Maria S. . E-mail: mssantos@ci.uc.pt

    2007-05-15

    Given the tremendous importance of mitochondria to basic cellular functions as well as the critical role of mitochondrial impairment in a vast number of disorders, a compelling question is whether 17{beta}-estradiol (E2) modulates mitochondrial function. To answer this question we exposed isolated liver mitochondria to E2. Three groups of rat females were used: control, ovariectomized and ovariectomized treated with tamoxifen. Tamoxifen has antiestrogenic effects in the breast tissue and is the standard endocrine treatment for women with breast cancer. However, under certain circumstances and in certain tissues, tamoxifen can also exert estrogenic agonist properties. We observed that at basal conditions, ovariectomy and tamoxifen treatment do not induce any statistical alteration in oxidative phosphorylation system and respiratory chain parameters. Furthermore, tamoxifen treatment increases the capacity of mitochondria to accumulate Ca{sup 2+} delaying the opening of the permeability transition pore. The presence of 25 {mu}M E2 impairs respiration and oxidative phosphorylation system these effects being similar in all groups of animals studied. Curiously, E2 protects against lipid peroxidation and increases the production of H{sub 2}O{sub 2} in energized mitochondria of control females. Our results indicate that E2 has in general deleterious effects that lead to mitochondrial impairment. Since mitochondrial dysfunction is a triggering event of cell degeneration and death, the use of exogenous E2 must be carefully considered.

  18. Sialylation Facilitates the Maturation of Mammalian Sperm and Affects Its Survival in Female Uterus.

    PubMed

    Ma, Xue; Pan, Qian; Feng, Ying; Choudhury, Biswa P; Ma, Qianhong; Gagneux, Pascal; Ma, Fang

    2016-06-01

    Establishment of adequate levels of sialylation is crucial for sperm survival and function after insemination; however, the mechanism for the addition of the sperm sialome has not been identified. Here, we report evidence for several different mechanisms that contribute to the establishment of the mature sperm sialome. Directly quantifying the source of the nucleotide sugar CMP-beta-N-acetylneuraminic acid in epididymal fluid indicates that transsialylation occurs in the upper epididymis. Western blots for the low-molecular-mass sialoglycoprotein (around 20-50 kDa) in C57BL/6 mice epididymal fluid reflect that additional sialome could be obtained by glycosylphosphatidylinositol-anchored sialoglycopeptide incorporation during epididymal transit in the caput of the epididymis. Additionally, we found that in Cmah (CMP-N-acetylneuraminic acid hydroxylase)-/- transgenic mice, epididymal sperm obtained sialylated-CD52 from seminal vesicle fluid (SVF). Finally, we used Gfp (green fluorescent protein)+/+ mouse sperm to test the role of sialylation on sperm for protection from female leukocyte attack. There is very low phagocytosis of the epididymal sperm when compared to that of sperm coincubated with SVF. Treating sperm with Arthrobacter ureafaciens sialidase (AUS) increased phagocytosis even further. Our results highlight the different mechanisms of increasing sialylation, which lead to the formation of the mature sperm sialome, as well as reveal the sialome's function in sperm survival within the female genital tract.

  19. Upper body heavy strength training does not affect performance in junior female cross-country skiers.

    PubMed

    Skattebo, Ø; Hallén, J; Rønnestad, B R; Losnegard, T

    2016-09-01

    We investigated the effects of adding heavy strength training to a high volume of endurance training on performance and related physiological determinants in junior female cross-country skiers. Sixteen well-trained athletes (17 ± 1 years, 60 ± 6 kg, 169 ± 6 cm, VO2max running: 60 ± 5 mL/kg/min) were assigned either to an intervention group (INT; n = 9) or a control group (CON; n = 7). INT completed two weekly sessions of upper body heavy strength training in a linear periodized fashion for 10 weeks. Both groups continued their normal aerobic endurance and muscular endurance training. One repetition maximum in seated pull-down increased significantly more in INT than in CON, with a group difference of 15 ± 8% (P < 0.01). Performance, expressed as average power output on a double poling ergometer over 20 s and as 3 min with maximal effort in both rested (sprint-test) and fatigued states (finishing-test), showed similar changes in both groups. Submaximal O2 -cost and VO2peak in double poling showed similar changes or were unchanged in both groups. In conclusion, 10 weeks of heavy strength training increased upper body strength but had trivial effects on performance in a double poling ergometer in junior female cross-country skiers.

  20. Gender separation increases somatic growth in females but does not affect lifespan in Nothobranchius furzeri.

    PubMed

    Graf, Michael; Cellerino, Alessandro; Englert, Christoph

    2010-08-03

    According to life history theory, physiological and ecological traits and parameters influence an individual's life history and thus, ultimately, its lifespan. Mating and reproduction are costly activities, and in a variety of model organisms, a negative correlation of longevity and reproductive effort has been demonstrated. We are employing the annual killifish Nothobranchius furzeri as a vertebrate model for ageing. N. furzeri is the vertebrate displaying the shortest known lifespan in captivity with particular strains living only three to four months under optimal laboratory conditions. The animals show explosive growth, early sexual maturation and age-dependent physiological and behavioural decline. Here, we have used N. furzeri to investigate a potential reproduction-longevity trade-off in both sexes by means of gender separation. Though female reproductive effort and offspring investment were significantly reduced after separation, as investigated by analysis of clutch size, eggs in the ovaries and ovary mass, the energetic surplus was not reallocated towards somatic maintenance. In fact, a significant extension of lifespan could not be observed in either sex. This is despite the fact that separated females, but not males, grew significantly larger and heavier than the respective controls. Therefore, it remains elusive whether lifespan of an annual species evolved in periodically vanishing habitats can be prolonged on the cost of reproduction at all.

  1. Deletion of protein tyrosine phosphatase, non-receptor type 4 (PTPN4) in twins with a Rett syndrome-like phenotype.

    PubMed

    Williamson, Sarah L; Ellaway, Carolyn J; Peters, Greg B; Pelka, Gregory J; Tam, Patrick P L; Christodoulou, John

    2015-09-01

    Rett syndrome (RTT), a neurodevelopmental disorder that predominantly affects females, is primarily caused by variants in MECP2. Variants in other genes such as CDKL5 and FOXG1 are usually associated with individuals who manifest distinct phenotypes that may overlap with RTT. Individuals with phenotypes suggestive of RTT are typically screened for variants in MECP2 and then subsequently the other genes dependent on the specific phenotype. Even with this screening strategy, there are individuals in whom no causative variant can be identified, suggesting that there are other novel genes that contribute to the RTT phenotype. Here we report a de novo deletion of protein tyrosine phosphatase, non-receptor type 4 (PTPN4) in identical twins with a RTT-like phenotype. We also demonstrate the reduced expression of Ptpn4 in a Mecp2 null mouse model of RTT, as well as the activation of the PTPN4 promoter by MeCP2. Our findings suggest that PTPN4 should be considered for addition to the growing list of genes that warrant screening in individuals with a RTT-like phenotype.

  2. Deletion of protein tyrosine phosphatase, non-receptor type 4 (PTPN4) in twins with a Rett syndrome-like phenotype

    PubMed Central

    Williamson, Sarah L; Ellaway, Carolyn J; Peters, Greg B; Pelka, Gregory J; Tam, Patrick PL; Christodoulou, John

    2015-01-01

    Rett syndrome (RTT), a neurodevelopmental disorder that predominantly affects females, is primarily caused by variants in MECP2. Variants in other genes such as CDKL5 and FOXG1 are usually associated with individuals who manifest distinct phenotypes that may overlap with RTT. Individuals with phenotypes suggestive of RTT are typically screened for variants in MECP2 and then subsequently the other genes dependent on the specific phenotype. Even with this screening strategy, there are individuals in whom no causative variant can be identified, suggesting that there are other novel genes that contribute to the RTT phenotype. Here we report a de novo deletion of protein tyrosine phosphatase, non-receptor type 4 (PTPN4) in identical twins with a RTT-like phenotype. We also demonstrate the reduced expression of Ptpn4 in a Mecp2 null mouse model of RTT, as well as the activation of the PTPN4 promoter by MeCP2. Our findings suggest that PTPN4 should be considered for addition to the growing list of genes that warrant screening in individuals with a RTT-like phenotype. PMID:25424712

  3. Phenotypic plasticity in growth and fecundity induced by strong population fluctuations affects reproductive traits of female fish.

    PubMed

    Karjalainen, Juha; Urpanen, Olli; Keskinen, Tapio; Huuskonen, Hannu; Sarvala, Jouko; Valkeajärvi, Pentti; Marjomäki, Timo J

    2016-02-01

    Fish are known for their high phenotypic plasticity in life-history traits in relation to environmental variability, and this is particularly pronounced among salmonids in the Northern Hemisphere. Resource limitation leads to trade-offs in phenotypic plasticity between life-history traits related to the reproduction, growth, and survival of individual fish, which have consequences for the age and size distributions of populations, as well as their dynamics and productivity. We studied the effect of plasticity in growth and fecundity of vendace females on their reproductive traits using a series of long-term incubation experiments. The wild parental fish originated from four separate populations with markedly different densities, and hence naturally induced differences in their growth and fecundity. The energy allocation to somatic tissues and eggs prior to spawning served as a proxy for total resource availability to individual females, and its effects on offspring survival and growth were analyzed. Vendace females allocated a rather constant proportion of available energy to eggs (per body mass) despite different growth patterns depending on the total resources in the different lakes; investment into eggs thus dictated the share remaining for growth. The energy allocation to eggs per mass was higher in young than in old spawners and the egg size and the relative fecundity differed between them: Young females produced more and smaller eggs and larvae than old spawners. In contrast to earlier observations of salmonids, a shortage of maternal food resources did not increase offspring size and survival. Vendace females in sparse populations with ample resources and high growth produced larger eggs and larvae. Vendace accommodate strong population fluctuations by their high plasticity in growth and fecundity, which affect their offspring size and consequently their recruitment and productivity, and account for their persistence and resilience in the face of high

  4. How various drugs affect anxiety-related behavior in male and female rats prenatally exposed to methamphetamine.

    PubMed

    Macúchová, E; Ševčíková, M; Hrebíčková, I; Nohejlová, K; Šlamberová, R

    2016-06-01

    Different forms of anxiety-related behavior have been reported after a single drug use of many abused substances, however, less is known about how males and females are affected differently from exposure to various drugs. Furthermore, chronic prenatal methamphetamine (MA) exposure was shown to predispose the animal to an increased sensitivity to drugs administrated in adulthood. Using the Elevated plus-maze test (EPM), the first aim of the present study was to examine how male and female rats are affected by acute drug treatment with subcutaneously (s.c.) administrated (a) MA (1mg/kg); (b) drugs with a similar mechanism of action to MA: amphetamine (AMP, 1mg/kg), cocaine (COC, 5mg/kg), 3,4-methylenedioxymethamphetamine (MDMA, 5mg/kg); and (c) drugs with different mechanisms of action: morphine (MOR, 5mg/kg), and Δ 9-tetrahydrocannabinol (THC, 2mg/kg). The second aim was to determine if prenatally MA-exposed (5mg/kg) animals show an increased sensitivity to adult drug treatment. The parameters analyzed were divided into two categories: anxiety-related behavior and anxiety-unrelated/exploratory behavior. Our results showed in female rats a decreased percentage of the time spent in the closed arms (CA) after MA, and an increased percentage of the time spent in the open arms (OA) after MA, AMP, and COC treatment, indicating an anxiolytic-like effect. In females, MDMA and THC treatment increased the percentage of the time spent in the CA. An increased percentage of the time spent in the CA was also seen after MOR treatment in females as well as in males, indicating an anxiogenic-like effect. As far as the interaction between prenatal MA exposure and adult drug treatment is concerned, there was no effect found. In conclusion, it seems that: (a) in some cases female rats are more vulnerable to acute drug treatment, in terms of either anxiogenic- or anxiolytic-like effects; (b) prenatal MA exposure does not sensitize animals to the anxiety-related effects of any of the

  5. Does self-esteem affect body dissatisfaction levels in female adolescents?☆

    PubMed Central

    Fortes, Leonardo de Sousa; Cipriani, Flávia Marcele; Coelho, Fernanda Dias; Paes, Santiago Tavares; Ferreira, Maria Elisa Caputo

    2014-01-01

    Objective: To evaluate the influence of self-esteem on levels of body dissatisfaction among adolescent females. Methods: A group of 397 adolescents aged 12 to 17 years were enrolled in the study. The Body Shape Questionnaire (BSQ) was applied to assess body dissatisfaction. The Rosenberg Self-Esteem Scale was used to assess self-esteem. Weight, height, and skinfold thickness were also measured. These anthropometric data were controlled in the statistical analyses. Results: The multiple regression model indicated influence of "positive self-esteem" (R2=0.16; p=0.001) and "negative self-esteem" (R2=0.23; p=0.001) subscales on the BSQ scores. Univariate analysis of covariance demonstrated differences in BSQ scores (p=0.001) according to groups of self-esteem. Conclusion: It was concluded that self-esteem influenced body dissatisfaction in adolescent girls from Juiz de Fora, MG. PMID:25479855

  6. Rehabilitation Counselor Narratives on Factors Affecting Vocational Goal Acquisition of Female Immigrant Clients: Incorporating Policy

    ERIC Educational Resources Information Center

    Akande, Abigail O.

    2014-01-01

    This dissertation examines factors affecting the service outcomes of immigrant women with disabilities who received vocational rehabilitation services, from the perspectives of their rehabilitation counselors. The participants were eight rehabilitation counselors who had received their Master's degrees from programs accredited by the Council on…

  7. Restoration of Mecp2 expression in GABAergic neurons is sufficient to rescue multiple disease features in a mouse model of Rett syndrome.

    PubMed

    Ure, Kerstin; Lu, Hui; Wang, Wei; Ito-Ishida, Aya; Wu, Zhenyu; He, Ling-Jie; Sztainberg, Yehezkel; Chen, Wu; Tang, Jianrong; Zoghbi, Huda Y

    2016-01-01

    The postnatal neurodevelopmental disorder Rett syndrome, caused by mutations in MECP2, produces a diverse array of symptoms, including loss of language, motor, and social skills and the development of hand stereotypies, anxiety, tremor, ataxia, respiratory dysrhythmias, and seizures. Surprisingly, despite the diversity of these features, we have found that deleting Mecp2 only from GABAergic inhibitory neurons in mice replicates most of this phenotype. Here we show that genetically restoring Mecp2 expression only in GABAergic neurons of male Mecp2 null mice enhanced inhibitory signaling, extended lifespan, and rescued ataxia, apraxia, and social abnormalities but did not rescue tremor or anxiety. Female Mecp2(+/-) mice showed a less dramatic but still substantial rescue. These findings highlight the critical regulatory role of GABAergic neurons in certain behaviors and suggest that modulating the excitatory/inhibitory balance through GABAergic neurons could prove a viable therapeutic option in Rett syndrome. PMID:27328321

  8. Restoration of Mecp2 expression in GABAergic neurons is sufficient to rescue multiple disease features in a mouse model of Rett syndrome.

    PubMed

    Ure, Kerstin; Lu, Hui; Wang, Wei; Ito-Ishida, Aya; Wu, Zhenyu; He, Ling-Jie; Sztainberg, Yehezkel; Chen, Wu; Tang, Jianrong; Zoghbi, Huda Y

    2016-06-21

    The postnatal neurodevelopmental disorder Rett syndrome, caused by mutations in MECP2, produces a diverse array of symptoms, including loss of language, motor, and social skills and the development of hand stereotypies, anxiety, tremor, ataxia, respiratory dysrhythmias, and seizures. Surprisingly, despite the diversity of these features, we have found that deleting Mecp2 only from GABAergic inhibitory neurons in mice replicates most of this phenotype. Here we show that genetically restoring Mecp2 expression only in GABAergic neurons of male Mecp2 null mice enhanced inhibitory signaling, extended lifespan, and rescued ataxia, apraxia, and social abnormalities but did not rescue tremor or anxiety. Female Mecp2(+/-) mice showed a less dramatic but still substantial rescue. These findings highlight the critical regulatory role of GABAergic neurons in certain behaviors and suggest that modulating the excitatory/inhibitory balance through GABAergic neurons could prove a viable therapeutic option in Rett syndrome.

  9. Stressors affect the response of male and female rats to clomipramine in a model of behavioral despair (forced swim test).

    PubMed

    Consoli, Daniele; Fedotova, Julia; Micale, Vincenzo; Sapronov, Nikolay S; Drago, Filippo

    2005-09-27

    blunted the hormonal response. However, severe shocks were followed by a surge of plasma corticosterone levels in both male and female clomipramine-treated rats. These results demonstrate that duration and intensity of stressful stimuli may deeply affect the behavioral response of rats in forced swim test and influence clomipramine effect in this behavioral model depending on gender-based variables, probably of the hormonal type. Plasma corticosterone levels correlate with the behavioral response to clomipramine treatment suggesting that reactivity of hypothalamus-pituitary-adrenal axis to stress may be involved in the antidepressant effect of this drug.

  10. An investigation of factors affecting elementary female student teachers' choice of science as a major at college level in Zimbabwe

    NASA Astrophysics Data System (ADS)

    Mlenga, Francis Howard

    The purpose of the study was to determine factors affecting elementary female student teachers' choice of science as a major at college level in Zimbabwe. The study was conducted at one of the Primary School Teachers' Colleges in Zimbabwe. A sample of two hundred and thirty-eight female student teachers was used in the study. Of these one hundred and forty-two were non-science majors who had been randomly selected, forty-one were science majors and forty-five were math majors. Both science and math majors were a convenient sample because the total enrollment of the two groups was small. All the subjects completed a survey questionnaire that had sixty-eight items. Ten students from the non-science majors were selected for individual interviews and the same was done for the science majors. A further eighteen were selected from the non-science majors and divided into three groups of six each for focus group interviews. The same was done for the science majors. The interviews were audio taped and transcribed. Data from the survey questionnaires were analyzed using Binary Logistic Regression which predicted factors that affected students' choice of science as a major. The transcribed interview data were analyzed used using domain, taxonomic and componential analyses. Results of the study indicated that elementary female students' choice of science as a major at college level is affected by students' attitudes toward science, teacher behavior, out-of-school experiences, role models, gender stereotyping, parental influence, peer influence, in-school experiences, and societal expectations, namely cultural and social expectations.

  11. Does Severe Maternal Morbidity Affect Female Sexual Activity and Function? Evidence from a Brazilian Cohort Study

    PubMed Central

    Andreucci, Carla B.; Cecatti, José G.; Pacagnella, Rodolfo C.; Silveira, Carla; Parpinelli, Mary A.; Ferreira, Elton C.; Angelini, Carina R.; Santos, Juliana P.; Zanardi, Dulce M.; Bussadori, Jamile C.; Cecchino, Gustavo N.; Souza, Renato T.; Sousa, Maria H.; Costa, Maria L.

    2015-01-01

    Objective to assess Female Sexual Function Index (FSFI) scores and delay to resume sexual activity associated with a previous severe maternal morbidity. Method This was a multidimensional retrospective cohort study. Women who gave birth at a Brazilian tertiary maternity between 2008 and 2012 were included, with data extraction from the hospital information system. Those with potentially life-threatening conditions and maternal near miss episodes (severe maternal morbidity) were considered the exposed group. The control group was a random sample of women who had had uncomplicated pregnancy. Female sexual function was evaluated through FSFI questionnaire, and general and reproductive aspects were addressed through specific questions. Statistical analyses were performed using Mann-Whitney and Pearson´s Chi-square for bivariate analyses. Logistic regression was used to identify variables independently associated with lower FSFI scores. Results 638 women were included (315 at exposed and 323 at not exposed groups). The majority of women were under 30 years-old in the control group and between 30 and 46 years-old in the exposed group (p = 0.003). Women who experienced severe maternal morbidity (SMM) had statistically significant differences regarding cesarean section (82.4% versus 47.1% among deliveries without complications, p<0.001), and some previous pathological conditions. FSFI mean scores were similar among groups ranging from 24.39 to 24.42. It took longer for exposed women to resume sexual activity after index pregnancy (mean 84 days after SMM and 65 days for control group, p = 0.01). Multiple analyses showed no significant association of FSFI below cut-off value with any predictor. Conclusion FSFI scores were not different in both groups. However, they were lower than expected. SMM delayed resumption of sexual activity after delivery, beyond postpartum period. However, the proportion of women in both groups having sex at 3 months after delivery was similar

  12. [A sociological study of factors affecting reproductive health of female teenagers and young women].

    PubMed

    Nizamov, I G; Chechulina, O V

    2003-01-01

    The reproductive health of teenagers deserves a special attention and must be regarded from the viewpoint of their future prospects as well as their social and cultural media. The mentioned social-and-cultural factors affecting the teenagers' attitude towards sexuality and preconditioning their access to information and services of healthcare have an impact on the status of their reproductive health and on their general well-being, including the ability of teenagers to avoid an undesired pregnancy or sexually transmitted diseases.

  13. ERα Variants Affect Age at Onset of Alzheimer's Disease in a Multiethnic Female Cohort

    PubMed Central

    Janicki, S.C.; Park, N.; Cheng, R.; Clark, L.N.; Lee, J. H.; Schupf, N.

    2014-01-01

    Background/Aims Few studies of gene variants that affect estrogen activity investigate their association with age at onset of Alzheimer's disease (AD) in women of different ethnicities. We investigated the influence of ESR1 polymorphisms on age at onset of AD in a multiethnic cohort of women. Methods Among 1,436 women participating in the Washington Heights Inwood Columbia Aging Project (WHICAP), association with age at AD onset was assessed for 41 single-nucleotide polymorphisms (SNPs) on the ESR1 gene using Cox proportional hazard models, adjusting for presence of an APOE ε4 allele, years of education, and body mass index (BMI). Results Six SNPs in self-identified White women were protectively associated with delayed age of AD onset in this self-identified group, including the two restriction fragment length polymorphisms (RFLPs) PvuII (rs2234693) and XbaI (rs9340799) (HR range 0.420 – 0.483). Two separate SNPs were found to affect age of AD onset in self-identified Black women. Conclusions ESR1 polymorphisms affect age of onset for AD in women, and risk alleles vary by ethnicity. These effects are possibly due to different linkage disequilibrium patterns or differences in comorbid environmental or cultural risk factors mediating SNP effect on risk for AD. PMID:24732579

  14. Mutations in epilepsy and intellectual disability genes in patients with features of Rett syndrome.

    PubMed

    Olson, Heather E; Tambunan, Dimira; LaCoursiere, Christopher; Goldenberg, Marti; Pinsky, Rebecca; Martin, Emilie; Ho, Eugenia; Khwaja, Omar; Kaufmann, Walter E; Poduri, Annapurna

    2015-09-01

    Rett syndrome and neurodevelopmental disorders with features overlapping this syndrome frequently remain unexplained in patients without clinically identified MECP2 mutations. We recruited a cohort of 11 patients with features of Rett syndrome and negative initial clinical testing for mutations in MECP2. We analyzed their phenotypes to determine whether patients met formal criteria for Rett syndrome, reviewed repeat clinical genetic testing, and performed exome sequencing of the probands. Using 2010 diagnostic criteria, three patients had classical Rett syndrome, including two for whom repeat MECP2 gene testing had identified mutations. In a patient with neonatal onset epilepsy with atypical Rett syndrome, we identified a frameshift deletion in STXBP1. Among seven patients with features of Rett syndrome not fulfilling formal diagnostic criteria, four had suspected pathogenic mutations, one each in MECP2, FOXG1, SCN8A, and IQSEC2. MECP2 mutations are highly correlated with classical Rett syndrome. Genes associated with atypical Rett syndrome, epilepsy, or intellectual disability should be considered in patients with features overlapping with Rett syndrome and negative MECP2 testing. While most of the identified mutations were apparently de novo, the SCN8A variant was inherited from an unaffected parent mosaic for the mutation, which is important to note for counseling regarding recurrence risks.

  15. Oral contraceptives did not affect biochemical folate indexes and homocysteine concentrations in adolescent females.

    PubMed

    Green, T J; Houghton, L A; Donovan, U; Gibson, R S; O'Connor, D L

    1998-01-01

    The impact of oral contraceptive (OC) use, smoking, and alcohol drinking on biochemical indexes of folate and vitamin B-12 was investigated in 229 adolescents 14-20 years old recruited from advertisements in Ontario, Canada. Subjects completed a life-style questionnaire and a 3-day, weighed food record, followed by overnight fasting and the collection of blood samples. Of the 48 participants (21%) who were OC users, 30 had used the pill for more than 12 months. Only 37 adolescents (16%) smoked, but 94 (60%) had consumed alcohol in the month preceding the study. Median daily intake of folate and vitamin B-12 (including intake from supplements) was 215 mcg and 1.9 mcg, respectively. OC use, smoking, and alcohol consumption were not significantly associated with lower serum or red blood cell folate levels, after controlling for folate intake. Serum homocysteine levels were not correlated with smoking or OC use, but were 13% higher among alcohol drinkers than nondrinkers. Finally, although smoking and alcohol use were not associated with serum B-12 levels, OC use was linked with an estimated 33% lower serum B-12 level than was nonuse. These findings fail to validate concerns that OC use has a negative impact on the folate status of adolescent females, but suggest a need to improve the dietary folate intake of young women who smoke.

  16. Transgenerational interactions involving parental age and immune status affect female reproductive success in Drosophila melanogaster.

    PubMed

    Nystrand, M; Dowling, D K

    2014-11-01

    It is well established that the parental phenotype can influence offspring phenotypic expression, independent of the effects of the offspring's own genotype. Nonetheless, the evolutionary implications of such parental effects remain unclear, partly because previous studies have generally overlooked the potential for interactions between parental sources of non-genetic variance to influence patterns of offspring phenotypic expression. We tested for such interactions, subjecting male and female Drosophila melanogaster of two different age classes to an immune activation challenge or a control treatment. Flies were then crossed in all age and immune status combinations, and the reproductive success of their immune- and control-treated daughters measured. We found that daughters produced by two younger parents exhibited reduced reproductive success relative to those of other parental age combinations. Furthermore, immune-challenged daughters exhibited higher reproductive success when produced by immune-challenged relative to control-treated mothers, a pattern consistent with transgenerational immune priming. Finally, a complex interplay between paternal age and parental immune statuses influenced daughter's reproductive success. These findings demonstrate the dynamic nature of age- and immune-mediated parental effects, traceable to both parents, and regulated by interactions between parents and between parents and offspring.

  17. A cognitive-perceptual model of symptom perception in males and females: the roles of negative affect, selective attention, health anxiety and psychological job demands.

    PubMed

    Goodwin, Laura; Fairclough, Stephen H; Poole, Helen M

    2013-06-01

    Kolk et al.'s model of symptom perception underlines the effects of trait negative affect, selective attention and external stressors. The current study tested this model in 263 males and 498 females from an occupational sample. Trait negative affect was associated with symptom reporting in females only, and selective attention and psychological job demands were associated with symptom reporting in both genders. Health anxiety was associated with symptom reporting in males only. Future studies might consider the inclusion of selective attention, which was more strongly associated with symptom reporting than negative affect. Psychological job demands appear to influence symptom reporting in both males and females.

  18. [A sociological study of factors affecting reproductive health of female teenagers and young women].

    PubMed

    Nizamov, I G; Chechulina, O V

    2003-01-01

    The reproductive health of teenagers deserves a special attention and must be regarded from the viewpoint of their future prospects as well as their social and cultural media. The mentioned social-and-cultural factors affecting the teenagers' attitude towards sexuality and preconditioning their access to information and services of healthcare have an impact on the status of their reproductive health and on their general well-being, including the ability of teenagers to avoid an undesired pregnancy or sexually transmitted diseases. PMID:12882120

  19. Environmental manipulation affects depressive-like behaviours in female Wistar-Kyoto rats.

    PubMed

    Mileva, Guergana R; Bielajew, Catherine

    2015-10-15

    While the efficacy of pharmacological interventions to treat depression has been well-studied in animal models, much less work has been done to shed light on how changes in the immediate environment can impact behaviour. Furthermore, most studies have focused on male rodents despite the prevalence of mood disorders in women. In this study, 36 Wistar Kyoto (validated animal model of depression) and 36 Wistar (control) female rats were used to examine the effects of environmental manipulation on depressive- and anxiety-like behaviours. Animals were assigned to one of three groups: standard (3 rats/cage), enriched (6 rats/cage plus physical enrichment), and isolation (1 rat/cage) housing. The elevated plus maze (EPM) and forced swim test (FST) were conducted prior to, and four weeks after environmental assignment to measure anxiety-like and depressive-like behaviours, respectively. Sucrose preference assessed anhedonia both before and after environmental assignment. Weight was measured every week to monitor weight-gain over time. Post-environment sucrose preference was significantly increased in animals in enriched housing as compared to those in isolated housing in both strains. While there were significant differences between strains in measures of open arm duration in the EPM and immobility in the FST, there appeared to be no differences between environmental groups. The results of this study highlight the importance of environmental factors in the expression of anhedonia. Enrichment appears to reduce anhedonia while isolation increases anhedonia. These effects should be studied further to assess whether longer periods of social and physical enrichment alleviate other symptoms of depression.

  20. Acute exposure to gas-supersaturated water does not affect reproductive success of female adult chinook salmon late in maturation

    USGS Publications Warehouse

    Gale, William L.; Maule, A.G.; Postera, A.; Peters, M.H.

    2004-01-01

    At times, total dissolved gas concentrations in the Columbia and Snake rivers have been elevated due to involuntary spill from high spring runoff and voluntary spill used as a method to pass juvenile salmonids over dams. The goal of this project was to determine if acute exposure to total dissolved gas supersaturation (TDGS) affects the reproductive performance of female chinook salmon late in their maturation. During this study, adult female spring chinook salmon were exposed to mean TDGS levels of 114.1 % to 125.5%. We ended exposures at first mortality, or at the appearance of impending death. Based on this criterion, exposures lasted from 10 to 68 h and were inversely related to TDGS. There was no effect of TDGS on pre-spawning mortality or fecundity when comparing treatment fish to experimental controls or the general hatchery population four to six weeks after exposures. Egg quality, based on egg weight and egg diameter, did not differ between treatment and control fish. Fertilization rate and survival to eyed-stage was high (>94%) for all groups. With the exception of Renibacterium salmoninarum (the causative agent of bacterial kidney disease; BKD), no viral or bacterial fish pathogens were isolated from experimental fish. The prevalence (about 45%) and severity of R. salmoninarum did not differ among the groups or the general hatchery population. We conclude that these acute exposures to moderate levels of gas-supersaturated water-perhaps similar to that experienced by immigrating adult salmon as they approach and pass a hydropower dam on the Columbia River-did not affect reproductive success of female chinook salmon late in their maturation. These results are most applicable to summer and fall chinook salmon, which migrate in the summer/fall and spawn shortly after reaching their natal streams. Published in 2004 by John Wiley and Sons, Ltd.

  1. WDR45 mutations in Rett (-like) syndrome and developmental delay: Case report and an appraisal of the literature.

    PubMed

    Hoffjan, Sabine; Ibisler, Aysegül; Tschentscher, Anne; Dekomien, Gabriele; Bidinost, Carla; Rosa, Alberto L

    2016-02-01

    Mutations in the WDR45 gene have been identified as causative for the only X-linked type of neurodegeneration with brain iron accumulation (NBIA), clinically characterized by global developmental delay in childhood, followed by a secondary neurological decline with parkinsonism and/or dementia in adolescence or early adulthood. Recent reports suggest that WDR45 mutations are associated with a broader phenotypic spectrum. We identified a novel splice site mutation (c.440-2 A > G) in a 5-year-old Argentinian patient with Rett-like syndrome, exhibiting developmental delay, microcephaly, seizures and stereotypic hand movements, and discuss this finding, together with a review of the literature. Additional patients with a clinical diagnosis of Rett (-like) syndrome were also found to carry WDR45 mutations before (or without) clinical decline or signs of iron accumulation by magnetic resonance imaging (MRI). This information indicates that WDR45 mutations should be added to the growing list of genetic alterations linked to Rett-like syndrome. Further, clinical symptoms associated with WDR45 mutations ranged from early-onset epileptic encephalopathy in a male patient with a deletion of WDR45 to only mild cognitive delay in a female patient, suggesting that analysis of this gene should be considered more often in patients with developmental delay, regardless of severity. The increasing use of next generation sequencing technologies as well as longitudinal follow-up of patients with an early diagnosis will help to gain additional insight into the phenotypic spectrum associated with WDR45 mutations.

  2. Acute stress eliminates female advantage in detection of ambiguous negative affect.

    PubMed

    DeDora, Daniel J; Carlson, Joshua M; Mujica-Parodi, Lilianne R

    2011-11-15

    The human stress response evolved to maximize an individual's probability of survival when threatened. The present study addressed whether physical danger modulates perception of an unrelated ambiguous threat and, if so, to what extent this response is sex- specific. The authors utilized a first-time tandem skydive as a stressor, which had been previously validated as producing a highly-controlled, genuinely stressful environment. In a counter-balanced within-subjects design, participants wore a virtual reality helmet to complete an emotion-identification task during the plane's ascent (stress condition) and in the laboratory (control condition). Participants were presented static male faces morphed between 20-80% aggression, which gradually emerged from degraded images. Using a binary forced-choice design, participants identified each ambiguous face as aggressive or neutral. Results showed that participants characterized emotion more rapidly under stress versus control conditions. Unexpectedly, the results also show that while women were more sensitive to affect ambiguity than men under control conditions, they exhibited a marked decrease in sensitivity equivalent to men while under stress.

  3. Female reproductive function in areas affected by radiation after the Chernobyl power station accident

    SciTech Connect

    Kulakov, V.I.; Sokur, T.N.; Volobuev, A.I.

    1993-07-01

    This paper reports the results of a comprehensive survey of the effects of the accidental release of radiation caused by the accident at the Chernobyl nuclear power station in April 1986. The accident and the resulting release of radiation and radioactive products into the atmosphere produced the most serious environmental contamination so far recorded. We have concentrated on evaluating the outcomes and health risks to women, their reproductive situation, and consequences for their progeny. We have concentrated on two well-defined areas: the Chechersky district of the Gomel region in Belorussia and the Polessky district of the Kiev region in the Ukraine. A number of investigations were carried out on 688 pregnant women and their babies, and data were obtained from 7000 labor histories of the development of newborns for a period of 8 years (3 years before the accident and 5 years after it). Parameters examined included birth rate, thyroid pathology, extragenital pathology such as anemias, renal disorders, hypertension, and abnormalities in the metabolism of fats, complications of gestation, spontaneous abortions, premature deliveries, perinatal morbidity and mortality, stillbirths and early neonatal mortality, infections and inflammatory diseases, neurological symptoms and hemic disturbances in both mothers and infants, trophic anomalies, and biochemical and structural changes in the placenta. Several exogenous, complicating influences were also considered such as psycho-emotional factors, stress, lifestyle changes, and others caused directly by the hazardous situation and by its consequences such as treatment, removal from affected areas, etc. 9 figs.

  4. Tributyltin affects shoaling and anxiety behavior in female rare minnow (Gobiocypris rarus).

    PubMed

    Zhang, Jiliang; Zhang, Chunnuan; Sun, Ping; Shao, Xian

    2016-09-01

    Effects of tributyltin (TBT) on reproduction are well established in many fish species. However, few studies report the effects of TBT on non-reproductive behaviors, which is a novel aspect of endocrine disruption in fish. Thus, the present study used rare minnow (Gobiocypris rarus) to investigate the effects of TBT, at environmental concentrations of 1, 10 and 100ng/L, on shoaling and anxiety behaviors. The results showed that fish exposed to TBT had less group cohesion during the course of the 10-min observation period as compared with the control fish. Further, TBT altered the shoaling in the Novel tank test, where shoaling is determined as the tendency to leave a shoal of littermates trapped behind a Plexiglas barrier at one end of the test tank. Fish exposed to TBT had shorter latency before leaving shoal mates and spent more time away from shoal than control fish. In addition, we also used Novel tanks to study the anxiety behavior as the tendency to stay at the bottom when introduced into an unfamiliar environment. The fish exposed to TBT showed increased anxiety, manifested as increased latency to enter the upper half and decreased time in upper half when compared with the control fish. TBT exposure increased the levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid, and decreased the levels of 5-hydroxytryptamine and its metabolite 5-hydroxy indole acetic acid in the brain. Thus, the hypofunction of the dopaminergic system or of the serotoninergic system or the combination of the two may underlie the observed behavioral change, which might affect the fitness of fish in their natural environment. PMID:27472783

  5. Bone resorption is affected by follicular phase length in female rotating shift workers.

    PubMed Central

    Lohstroh, Pete N; Chen, Jiangang; Ba, Jianming; Ryan, Louise M; Xu, Xiping; Overstreet, James W; Lasley, Bill L

    2003-01-01

    Stressors as subtle as night work or shift work can lead to irregular menstrual cycles, and changes in reproductive hormone profiles can adversely affect bone health. This study was conducted to determine if stresses associated with the disruption of regular work schedule can induce alterations in ovarian function which, in turn, are associated with transient bone resorption. Urine samples from 12 rotating shift workers from a textile mill in Anqing, China, were collected in 1996-1998 during pairs of sequential menstrual cycles, of which one was longer than the other (28.4 vs. 37.4 days). Longer cycles were characterized by a prolonged follicular phase. Work schedules during the luteal-follicular phase transition (LFPT) preceding each of the two cycles were evaluated. All but one of the shorter cycles were associated with regular, forward phase work shift progression during the preceding LFPT. In contrast, five longer cycles were preceded by a work shift interrupted either by an irregular shift or a number of "off days." Urinary follicle-stimulating hormone levels were reduced in the LFPT preceding longer cycles compared with those in the LFPT preceding shorter cycles. There was greater bone resorption in the follicular phase of longer cycles than in that of shorter cycles, as measured by urinary deoxypyridinoline. These data confirm reports that changes in work shift can lead to irregularity in menstrual cycle length. In addition, these data indicate that there may be an association between accelerated bone resorption in menstrual cycles and changes of regularity in work schedule during the preceding LFPT. PMID:12676625

  6. Aging Negatively Affects Estrogens-Mediated Effects on Nitric Oxide Bioavailability by Shifting ERα/ERβ Balance in Female Mice

    PubMed Central

    Novensà, Laura; Novella, Susana; Medina, Pascual; Segarra, Gloria; Castillo, Nadia; Heras, Magda; Hermenegildo, Carlos; Dantas, Ana Paula

    2011-01-01

    Aims Aging is among the major causes for the lack of cardiovascular protection by estrogen (E2) during postmenopause. Our study aims to determine the mechanisms whereby aging changes E2 effects on nitric oxide (NO) production in a mouse model of accelerated senescence (SAM). Methods and Results Although we found no differences on NO production in females SAM prone (SAMP, aged) compared to SAM resistant (SAMR, young), by either DAF-2 fluorescence or plasmatic nitrite/nitrate (NO2/NO3), in both cases, E2 treatment increased NO production in SAMR but had no effect in SAMP. Those results are in agreement with changes of eNOS protein and gene expression. E2 up-regulated eNOS expression in SAMR but not in SAMP. E2 is also known to increase NO by decreasing its catabolism by superoxide anion (O2-). Interestingly, E2 treatment decreased O2− production in young females, while increased O2− in aged ones. Furthermore, we observed that aging changed expression ratio of estrogen receptors (ERβ/ERα) and levels of DNA methylation. Increased ratio ERβ/ERα in aged females is associated to a lack of estrogen modulation of NO production and with a reversal in its antioxidant effect to a pro-oxidant profile. Conclusions Together, our data suggest that aging has detrimental effects on E2-mediated benefits on NO bioavailability, partially by affecting the ability of E2 to induce up regulation of eNOS and decrease of O2−. These modifications may be associated to aging-mediated modifications on global DNA methylation status, but not to a specific methylation at 5′flanking region of ERα gene. PMID:21966501

  7. Remating behavior in Anastrepha fraterculus (Diptera: Tephritidae) females is affected by male juvenile hormone analog treatment but not by male sterilization.

    PubMed

    Abraham, S; Liendo, M C; Devescovi, F; Peralta, P A; Yusef, V; Ruiz, J; Cladera, J L; Vera, M T; Segura, D F

    2013-06-01

    The sterile insect technique (SIT) has been proposed as an area-wide method to control the South American fruit fly, Anastrepha fraterculus (Wiedemann). This technique requires sterilization, a procedure that affects, along with other factors, the ability of males to modulate female sexual receptivity after copulation. Numerous pre-release treatments have been proposed to counteract the detrimental effects of irradiation, rearing and handling and increase SIT effectiveness. These include treating newly emerged males with a juvenile hormone mimic (methoprene) or supplying protein to the male's diet to accelerate sexual maturation prior to release. Here, we examine how male irradiation, methoprene treatment and protein intake affect remating behavior and the amount of sperm stored in inseminated females. In field cage experiments, we found that irradiated laboratory males were equally able to modulate female remating behavior as fertile wild males. However, females mated with 6-day-old, methoprene-treated males remated more and sooner than females mated with naturally matured males, either sterile or wild. Protein intake by males was not sufficient to overcome reduced ability of methoprene-treated males to induce refractory periods in females as lengthy as those induced by wild and naturally matured males. The amount of sperm stored by females was not affected by male irradiation, methoprene treatment or protein intake. This finding revealed that factors in addition to sperm volume intervene in regulating female receptivity after copulation. Implications for SIT are discussed.

  8. Adult Phenotypes in Angelman- and Rett-Like Syndromes

    PubMed Central

    Willemsen, M.H.; Rensen, J.H.M.; van Schrojenstein-Lantman de Valk, H.M.J.; Hamel, B.C.J.; Kleefstra, T.

    2012-01-01

    Background Angelman- and Rett-like syndromes share a range of clinical characteristics, including intellectual disability (ID) with or without regression, epilepsy, infantile encephalopathy, postnatal microcephaly, features of autism spectrum disorder, and variable other neurological symptoms. The phenotypic spectrum generally has been well studied in children; however, evolution of the phenotypic spectrum into adulthood has been documented less extensively. To obtain more insight into natural course and prognosis of these syndromes with respect to developmental, medical, and socio-behavioral outcomes, we studied the phenotypes of 9 adult patients who were recently diagnosed with 6 different Angelman- and Rett-like syndromes. Methods All these patients were ascertained during an ongoing cohort study involving a systematic clinical genetic diagnostic evaluation of over 250, mainly adult patients with ID of unknown etiology. Results We describe the evolution of the phenotype in adults with EHMT1, TCF4, MECP2, CDKL5, and SCN1A mutations and 22qter deletions and also provide an overview of previously published adult cases with similar diagnoses. Conclusion These data are highly valuable in adequate management and follow-up of patients with Angelman- and Rett-like syndromes and accurate counseling of their family members. Furthermore, they will contribute to recognition of these syndromes in previously undiagnosed adult patients. PMID:22670143

  9. The clinical recognition and differential diagnosis of Rett syndrome.

    PubMed

    Trevathan, E; Naidu, S

    1988-01-01

    Rett syndrome (RS) is characterized by progressive loss of intellectual functioning and fine and gross motor skills as well as development of stereotypic hand movement abnormalities, occurring after 6 to 18 months of normal development. Rett syndrome has been previously reported only in girls, but the possibility of the syndrome existing in male children cannot be currently excluded. Although the syndrome is thought to be relatively common, it was only described in the English literature 5 years ago. There is currently no marker for the syndrome; diagnosis is based on clinical criteria. The newly developed diagnostic criteria for RS are reviewed, with special attention given to the historical aspects of the diagnosis in the prenatal, perinatal, neonatal, and early childhood periods. Rett syndrome is characterized by a predictable, orderly progression of signs and symptoms. Four stages of RS have been described; each stage has special characteristics and offers different diagnostic challenges for the neurologist. Infantile autism is the most common incorrect diagnosis made for children with RS. The simultaneous regression of both motor and language skills, as well as the stereotypic hand movements, hyperventilation, bruxism, and seizures in early childhood are all typical in RS and help distinguish RS from infantile autism.

  10. Perioperative management of a patient with Rett syndrome

    PubMed Central

    Kako, Hiromi; Martin, David P; Cartabuke, Richard; Beebe, Allan; Klamar, Jan; Tobias, Joseph D

    2013-01-01

    Rett syndrome is a neurodevelopmental disorder that results from mutations in the genes encoding methyl-cytosine-guanosine binding protein 2 located on the X chromosome. Clinical features of central nervous system involvement include regression of developmental milestones in the late infant and early toddler stages, mental retardation, seizures and other electroencephalographic abnormalities. Given the invariable association of this degenerative disorder with orthopedic deformities including scoliosis, patients with Rett syndrome may present for anesthetic care during various surgical procedures. The complexity of the end-organ involvement, specifically the progressive nature of respiratory and cardiac involvement, makes the anesthetic care of such patients challenging. Specific perioperative concerns include potential difficulties with airway management, an underlying seizure disorder, an increased sensitivity to anesthetic agents, prolonged QT syndrome, and diabetes mellitus. We present an 11-year-old girl with Rett syndrome who required anesthetic care for posterior spinal fusion. Previous reports of anesthetic care for these patients are reviewed, the end-organ involvement discussed, and options for anesthetic care presented. PMID:23724160

  11. People with "MECP2" Mutation-Positive Rett Disorder Who Converse

    ERIC Educational Resources Information Center

    Kerr, A. M.; Archer, H. L.; Evans, J. C.; Prescott, R. J.; Gibbon, F.

    2006-01-01

    Background: People with useful speech after regression constitute a distinct group of those with mutation-positive Rett disorder, 6% (20/331) reported among mutation-positive people in the British Survey. We aimed to determine the physical, mental and genetic characteristics of this group and to gain insight into their experience of Rett syndrome.…

  12. Contributing to the Early Detection of Rett Syndrome: The Potential Role of Auditory Gestalt Perception

    ERIC Educational Resources Information Center

    Marschik, Peter B.; Einspieler, Christa; Sigafoos, Jeff

    2012-01-01

    To assess whether there are qualitatively deviant characteristics in the early vocalizations of children with Rett syndrome, we had 400 native Austrian-German speakers listen to audio recordings of vocalizations from typically developing girls and girls with Rett syndrome. The audio recordings were rated as (a) inconspicuous, (b) conspicuous or…

  13. Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females.

    PubMed

    Depienne, Christel; Bouteiller, Delphine; Keren, Boris; Cheuret, Emmanuel; Poirier, Karine; Trouillard, Oriane; Benyahia, Baya; Quelin, Chloé; Carpentier, Wassila; Julia, Sophie; Afenjar, Alexandra; Gautier, Agnès; Rivier, François; Meyer, Sophie; Berquin, Patrick; Hélias, Marie; Py, Isabelle; Rivera, Serge; Bahi-Buisson, Nadia; Gourfinkel-An, Isabelle; Cazeneuve, Cécile; Ruberg, Merle; Brice, Alexis; Nabbout, Rima; Leguern, Eric

    2009-02-01

    Dravet syndrome (DS) is a genetically determined epileptic encephalopathy mainly caused by de novo mutations in the SCN1A gene. Since 2003, we have performed molecular analyses in a large series of patients with DS, 27% of whom were negative for mutations or rearrangements in SCN1A. In order to identify new genes responsible for the disorder in the SCN1A-negative patients, 41 probands were screened for micro-rearrangements with Illumina high-density SNP microarrays. A hemizygous deletion on chromosome Xq22.1, encompassing the PCDH19 gene, was found in one male patient. To confirm that PCDH19 is responsible for a Dravet-like syndrome, we sequenced its coding region in 73 additional SCN1A-negative patients. Nine different point mutations (four missense and five truncating mutations) were identified in 11 unrelated female patients. In addition, we demonstrated that the fibroblasts of our male patient were mosaic for the PCDH19 deletion. Patients with PCDH19 and SCN1A mutations had very similar clinical features including the association of early febrile and afebrile seizures, seizures occurring in clusters, developmental and language delays, behavioural disturbances, and cognitive regression. There were, however, slight but constant differences in the evolution of the patients, including fewer polymorphic seizures (in particular rare myoclonic jerks and atypical absences) in those with PCDH19 mutations. These results suggest that PCDH19 plays a major role in epileptic encephalopathies, with a clinical spectrum overlapping that of DS. This disorder mainly affects females. The identification of an affected mosaic male strongly supports the hypothesis that cellular interference is the pathogenic mechanism.

  14. The Langerhans islet cells of female rabbits are differentially affected by hypothyroidism depending on the islet size.

    PubMed

    Rodríguez-Castelán, J; Nicolás, L; Morimoto, S; Cuevas, E

    2015-04-01

    Effects of hypothyroidism on the glucose and insulin levels are controversial, and its impact on the Langerhans islet morphology of adult subjects has been poorly addressed. In spite of hypothyroidism and diabetes mellitus are more frequent in females than in males, most studies using animal models have been done in males. The effect of hypothyroidism on the immunolabeling of thyroid hormone receptors (TRs) and thyrotropin receptor (TSHR) of islet cells is unknown. The aim of this study was to determine the effect of hypothyroidism on the glucose and insulin concentrations, morphometry of islets, and immunostaining of TRs α1-2 and β1 and TSHR of islet cells in female rabbits. Control and hypothyroid (0.02% of methimazole for 30 days) animals were used to quantify blood levels of glucose and insulin, density of islets, cross-sectional area (CSA) of islets, number of cells per islet, cell proliferation, and the immunolabeling of TRs α1-2, TRβ1, and TSHR. Student's t or Mann-Whitney-U tests, two-way ANOVAs, and Fischer's tests were applied. Concentrations of glucose and insulin, as well as the insulin resistance were similar between groups. Hypothyroidism did not affect the density or the CSA of islets. The analysis of islets by size showed that hypothyroidism reduced the cell number in large and medium islets, but not in small ones. In small islets, cell proliferation was increased. The immunoreactivity of TRα1-2, TRβ1, and TSHR was increased by hypothyroidism in all islet sizes. Our results show that hypothyroidism affects differentially the islet cells depending on the size of islets.

  15. Contributing to the early detection of Rett syndrome: the potential role of auditory Gestalt perception.

    PubMed

    Marschik, Peter B; Einspieler, Christa; Sigafoos, Jeff

    2012-01-01

    To assess whether there are qualitatively deviant characteristics in the early vocalizations of children with Rett syndrome, we had 400 native Austrian-German speakers listen to audio recordings of vocalizations from typically developing girls and girls with Rett syndrome. The audio recordings were rated as (a) inconspicuous, (b) conspicuous or (c) not able to decide between (a) and (b). The results showed that participants were accurate in differentiating the vocalizations of typically developing children compared to children with Rett syndrome. However, the accuracy for rating verbal behaviors was dependent on the type of vocalization with greater accuracy for canonical babbling compared to cooing vocalizations. The results suggest a potential role for the use of rating child vocalizations for early detection of Rett syndrome. This is important because clinical criteria related to speech and language development remain important for early identification of Rett syndrome.

  16. Abnormal general movements in girls with Rett disorder: the first four months of life.

    PubMed

    Einspieler, Christa; Kerr, Alison M; Prechtl, Heinz F R

    2005-11-01

    An apparently normal early development was one of the initial criteria for classical Rett syndrome. However, several investigators considered Rett syndrome to be a developmental disorder manifesting very soon after birth. Videos of 14 infants with Rett disorder were carefully assessed for their spontaneous movements, in particular general movements (GMs), during the first 4 months of life. A detailed analysis clearly demonstrated that none of the infants had normal GMs. However, a specific abnormal GM pattern could not be detected for Rett disorder. The abnormal GMs described here, and their individual developmental trajectories are different from the abnormal GMs described in infants with acquired brain lesion. Our study is the first to apply specific standardised measures of early spontaneous movements to infants with Rett syndrome, proving conclusively that the disorder is manifest within the first weeks of life.

  17. A qualitative motion analysis study of voluntary hand movement induced by music in patients with Rett syndrome

    PubMed Central

    Go, Tohshin; Mitani, Asako

    2009-01-01

    Patients with Rett syndrome are known to respond well to music irrespective of their physical and verbal disabilities. Therefore, the relationship between auditory rhythm and their behavior was investigated employing a two-dimensional motion analysis system. Ten female patients aged from three to 17 years were included. When music with a simple regular rhythm started, body rocking appeared automatically in a back and forth direction in all four patients who showed the same rocking motion as their stereotyped movement. Through this body rocking, voluntary movement of the hand increased gradually, and finally became sufficient to beat a tambourine. However, the induction of body rocking by music was not observed in the other six patients who did not show stereotyped body rocking in a back and forth direction. When the music stopped suddenly, voluntary movement of the hand disappeared. When the music changed from a simple regular rhythm to a continuous tone without an auditory rhythm, the periodic movement of both the hand and body prolonged. Auditory rhythm shows a close relationship with body movement and facilitates synchronized body movement. This mechanism was demonstrated to be preserved in some patients with Rett syndrome, and stimulation with music could be utilized for their rehabilitation. PMID:19851517

  18. Female major histocompatibility complex type affects male testosterone levels and sperm number in the horse (Equus caballus)

    PubMed Central

    Burger, D.; Dolivo, G.; Marti, E.; Sieme, H.; Wedekind, C.

    2015-01-01

    Odours of vertebrates often contain information about the major histocompatibility complex (MHC), and are used in kin recognition, mate choice or female investment in pregnancy. It is, however, still unclear whether MHC-linked signals can also affect male reproductive strategies. We used horses (Equus caballus) to study this question under experimental conditions. Twelve stallions were individually exposed either to an unfamiliar MHC-similar mare and then to an unfamiliar MHC-dissimilar mare, or vice versa. Each exposure lasted over a period of four weeks. Peripheral blood testosterone levels were determined weekly. Three ejaculates each were collected in the week after exposure to both mares (i.e. in the ninth week) to determine mean sperm number and sperm velocity. We found high testosterone levels when stallions were kept close to MHC-dissimilar mares and significantly lower ones when kept close to MHC-similar mares. Mean sperm number per ejaculate (but not sperm velocity) was positively correlated to mean testosterone levels and also affected by the order of presentation of mares: sperm numbers were higher if MHC-dissimilar mares were presented last than if MHC-similar mares were presented last. We conclude that MHC-linked signals influence testosterone secretion and semen characteristics, two indicators of male reproductive strategies. PMID:25904670

  19. Comparison of Genomic and Epigenomic Expression in Monozygotic Twins Discordant for Rett Syndrome.

    PubMed

    Miyake, Kunio; Yang, Chunshu; Minakuchi, Yohei; Ohori, Kenta; Soutome, Masaki; Hirasawa, Takae; Kazuki, Yasuhiro; Adachi, Noboru; Suzuki, Seiko; Itoh, Masayuki; Goto, Yu-Ichi; Andoh, Tomoko; Kurosawa, Hiroshi; Oshimura, Mitsuo; Sasaki, Masayuki; Toyoda, Atsushi; Kubota, Takeo

    2013-01-01

    Monozygotic (identical) twins have been widely used in genetic studies to determine the relative contributions of heredity and the environment in human diseases. Discordance in disease manifestation between affected monozygotic twins has been attributed to either environmental factors or different patterns of X chromosome inactivation (XCI). However, recent studies have identified genetic and epigenetic differences between monozygotic twins, thereby challenging the accepted experimental model for distinguishing the effects of nature and nurture. Here, we report the genomic and epigenomic sequences in skin fibroblasts of a discordant monozygotic twin pair with Rett syndrome, an X-linked neurodevelopmental disorder characterized by autistic features, epileptic seizures, gait ataxia and stereotypical hand movements. The twins shared the same de novo mutation in exon 4 of the MECP2 gene (G269AfsX288), which was paternal in origin and occurred during spermatogenesis. The XCI patterns in the twins did not differ in lymphocytes, skin fibroblasts, and hair cells (which originate from ectoderm as does neuronal tissue). No reproducible differences were detected between the twins in single nucleotide polymorphisms (SNPs), insertion-deletion polymorphisms (indels), or copy number variations. Differences in DNA methylation between the twins were detected in fibroblasts in the upstream regions of genes involved in brain function and skeletal tissues such as Mohawk Homeobox (MKX), Brain-type Creatine Kinase (CKB), and FYN Tyrosine Kinase Protooncogene (FYN). The level of methylation in these upstream regions was inversely correlated with the level of gene expression. Thus, differences in DNA methylation patterns likely underlie the discordance in Rett phenotypes between the twins. PMID:23805272

  20. Factors affecting mammary tumor incidence in chlorotriazine-treated female rats: hormonal properties, dosage, and animal strain.

    PubMed Central

    Eldridge, J C; Tennant, M K; Wetzel, L T; Breckenridge, C B; Stevens, J T

    1994-01-01

    Chlorotriazines are widely used in agriculture as broadleaf herbicides. The compounds specifically inhibit photosynthesis, and, as such, display little interaction with animal systems. However, a 24-month feeding study with atrazine (ATR) revealed a significant dose-related increase of mammary tumors in female Sprague-Dawley (SD) rats. Because numerous studies indicated that ATR had a low mutagenic and oncogenic potential, it was decided to test a hypothesis that the herbicide possessed endocrine activity. Among tests for estrogenic action, oral dosing of ATR up to 300 mg/kg did not stimulate uterine weight of ovariectomized rats. However, ATR administration did reduce estrogen-stimulated uterine weight gain. Further evidence of inhibition came from measures of [3H]-thymidine incorporation into uterine DNA of ATR-treated immature rats. Again, no intrinsic estrogenic activity was observed up to a 300-mg/kg dose. In vitro, ATR competed poorly against estradiol binding to cytosolic receptors, with an approximate IC50 of 10(-5) M. Atrazine administration to SD and Fischer-344 (F-344) rats for 12 months, up to 400 ppm in food, was correlated with significant alterations of estrous cycling activity; but there was a divergent strain response. SD rats showed an increased number of days in vaginal estrus, increased plasma estradiol, and decreased plasma progesterone by 9 to 12 months of treatment. F-344 rats did not demonstrate treatment-related affects. A study of ultrastructure in the hypothalamic arcuate nucleus of female SD rats that were fed diaminochlorotriazine (DACT), an ATR metabolite, suggested that age-associated glial pathology was enhanced by treatment.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 8. PMID:7737039

  1. Feeding frequency, but not dietary water content, affects voluntary physical activity in young lean adult female cats.

    PubMed

    de Godoy, M R C; Ochi, K; de Oliveira Mateus, L F; de Justino, A C C; Swanson, K S

    2015-05-01

    The objective of this study was to investigate whether increased dietary water content and feeding frequency increased voluntary physical activity of young, lean adult female cats. A replicated 4 × 4 Latin square design with a 2 × 2 factorial treatment arrangement (feeding frequency and water content) was used. The 4 treatments consisted of 1 meal daily dry pet food without added water (1D; 12% moisture as is), 1 meal daily dry pet food with added water (1W; 70% total water content), 4 meals daily dry pet food without added water (4D; 12% moisture as is), and 4 meals daily dry pet food with added water (4W; 70% total water content). Eight healthy adult, lean, intact, young, female domestic shorthair cats were used in this experiment. Voluntary physical activity was evaluated using Actical activity monitors placed on collars and worn around the cats' necks for the last 7 d of each experimental period of 14 d. Food anticipatory activity (FAA) was calculated based on 2 h prior to feeding periods and expressed as a percentage of total daily voluntary physical activity. Increased feeding frequency (4 vs. 1 meal daily) resulted in greater average daily activity (P = 0.0147), activity during the light period (P = 0.0023), and light:dark activity ratio (P = 0.0002). In contrast, physical activity during the dark period was not altered by feeding frequency (P > 0.05). Cats fed 4 meals daily had increased afternoon FAA (P= 0.0029) compared with cats fed once daily. Dietary water content did not affect any measure of voluntary physical activity. Increased feeding frequency is an effective strategy to increase the voluntary physical activity of cats. Thus, it may assist in the prevention and management of obesity.

  2. Vascular Dysfunction in a Mouse Model of Rett Syndrome and Effects of Curcumin Treatment

    PubMed Central

    Panighini, Anna; Duranti, Emiliano; Santini, Ferruccio; Maffei, Margherita; Pizzorusso, Tommaso; Funel, Niccola; Taddei, Stefano; Bernardini, Nunzia; Ippolito, Chiara; Virdis, Agostino; Costa, Mario

    2013-01-01

    Mutations in the coding sequence of the X-linked gene MeCP2 (Methyl CpG–binding protein) are present in around 80% of patients with Rett Syndrome, a common cause of intellectual disability in female and to date without any effective pharmacological treatment. A relevant, and so far unexplored feature of RTT patients, is a marked reduction in peripheral circulation. To investigate the relationship between loss of MeCP2 and this clinical aspect, we used the MeCP2 null mouse model B6.129SF1-MeCP2tm1Jae for functional and pharmacological studies. Functional experiments were performed on isolated resistance mesenteric vessels, mounted on a pressurized myograph. Vessels from female MeCP2+/− mice show a reduced endothelium-dependent relaxation, due to a reduced Nitric Oxide (NO) availability secondary to an increased Reactive Oxygen Species (ROS) generation. Such functional aspects are associated with an intravascular increase in superoxide anion production, and a decreased vascular eNOS expression. These alterations are reversed by curcumin administration (5% (w/w) dietary curcumin for 21 days), which restores endothelial NO availability, decreases intravascular ROS production and normalizes vascular eNOS gene expression. In conclusion our findings highlight alterations in the vascular/endothelial system in the absence of a correct function of MeCP2, and uncover related cellular/molecular mechanisms that are rescued by an anti-oxidant treatment. PMID:23705018

  3. Loss of MeCP2 in Parvalbumin-and Somatostatin-Expressing Neurons in Mice Leads to Distinct Rett Syndrome-like Phenotypes.

    PubMed

    Ito-Ishida, Aya; Ure, Kerstin; Chen, Hongmei; Swann, John W; Zoghbi, Huda Y

    2015-11-18

    Inhibitory neurons are critical for proper brain function, and their dysfunction is implicated in several disorders, including autism, schizophrenia, and Rett syndrome. These neurons are heterogeneous, and it is unclear which subtypes contribute to specific neurological phenotypes. We deleted Mecp2, the mouse homolog of the gene that causes Rett syndrome, from the two most populous subtypes, parvalbumin-positive (PV+) and somatostatin-positive (SOM+) neurons. Loss of MeCP2 partially impairs the affected neuron, allowing us to assess the function of each subtype without profound disruption of neuronal circuitry. We found that mice lacking MeCP2 in either PV+ or SOM+ neurons have distinct, non-overlapping neurological features: mice lacking MeCP2 in PV+ neurons developed motor, sensory, memory, and social deficits, whereas those lacking MeCP2 in SOM+ neurons exhibited seizures and stereotypies. Our findings indicate that PV+ and SOM+ neurons contribute complementary aspects of the Rett phenotype and may have modular roles in regulating specific behaviors.

  4. Loss of MeCP2 in Parvalbumin-and Somatostatin-Expressing Neurons in Mice Leads to Distinct Rett Syndrome-like Phenotypes.

    PubMed

    Ito-Ishida, Aya; Ure, Kerstin; Chen, Hongmei; Swann, John W; Zoghbi, Huda Y

    2015-11-18

    Inhibitory neurons are critical for proper brain function, and their dysfunction is implicated in several disorders, including autism, schizophrenia, and Rett syndrome. These neurons are heterogeneous, and it is unclear which subtypes contribute to specific neurological phenotypes. We deleted Mecp2, the mouse homolog of the gene that causes Rett syndrome, from the two most populous subtypes, parvalbumin-positive (PV+) and somatostatin-positive (SOM+) neurons. Loss of MeCP2 partially impairs the affected neuron, allowing us to assess the function of each subtype without profound disruption of neuronal circuitry. We found that mice lacking MeCP2 in either PV+ or SOM+ neurons have distinct, non-overlapping neurological features: mice lacking MeCP2 in PV+ neurons developed motor, sensory, memory, and social deficits, whereas those lacking MeCP2 in SOM+ neurons exhibited seizures and stereotypies. Our findings indicate that PV+ and SOM+ neurons contribute complementary aspects of the Rett phenotype and may have modular roles in regulating specific behaviors. PMID:26590342

  5. KCC2 rescues functional deficits in human neurons derived from patients with Rett syndrome

    PubMed Central

    Tang, Xin; Kim, Julie; Zhou, Li; Wengert, Eric; Zhang, Lei; Wu, Zheng; Carromeu, Cassiano; Muotri, Alysson R.; Marchetto, Maria C. N.; Gage, Fred H.; Chen, Gong

    2016-01-01

    Rett syndrome is a severe form of autism spectrum disorder, mainly caused by mutations of a single gene methyl CpG binding protein 2 (MeCP2) on the X chromosome. Patients with Rett syndrome exhibit a period of normal development followed by regression of brain function and the emergence of autistic behaviors. However, the mechanism behind the delayed onset of symptoms is largely unknown. Here we demonstrate that neuron-specific K+-Cl− cotransporter2 (KCC2) is a critical downstream gene target of MeCP2. We found that human neurons differentiated from induced pluripotent stem cells from patients with Rett syndrome showed a significant deficit in KCC2 expression and consequently a delayed GABA functional switch from excitation to inhibition. Interestingly, overexpression of KCC2 in MeCP2-deficient neurons rescued GABA functional deficits, suggesting an important role of KCC2 in Rett syndrome. We further identified that RE1-silencing transcriptional factor, REST, a neuronal gene repressor, mediates the MeCP2 regulation of KCC2. Because KCC2 is a slow onset molecule with expression level reaching maximum later in development, the functional deficit of KCC2 may offer an explanation for the delayed onset of Rett symptoms. Our studies suggest that restoring KCC2 function in Rett neurons may lead to a potential treatment for Rett syndrome. PMID:26733678

  6. KCC2 rescues functional deficits in human neurons derived from patients with Rett syndrome.

    PubMed

    Tang, Xin; Kim, Julie; Zhou, Li; Wengert, Eric; Zhang, Lei; Wu, Zheng; Carromeu, Cassiano; Muotri, Alysson R; Marchetto, Maria C N; Gage, Fred H; Chen, Gong

    2016-01-19

    Rett syndrome is a severe form of autism spectrum disorder, mainly caused by mutations of a single gene methyl CpG binding protein 2 (MeCP2) on the X chromosome. Patients with Rett syndrome exhibit a period of normal development followed by regression of brain function and the emergence of autistic behaviors. However, the mechanism behind the delayed onset of symptoms is largely unknown. Here we demonstrate that neuron-specific K(+)-Cl(-) cotransporter2 (KCC2) is a critical downstream gene target of MeCP2. We found that human neurons differentiated from induced pluripotent stem cells from patients with Rett syndrome showed a significant deficit in KCC2 expression and consequently a delayed GABA functional switch from excitation to inhibition. Interestingly, overexpression of KCC2 in MeCP2-deficient neurons rescued GABA functional deficits, suggesting an important role of KCC2 in Rett syndrome. We further identified that RE1-silencing transcriptional factor, REST, a neuronal gene repressor, mediates the MeCP2 regulation of KCC2. Because KCC2 is a slow onset molecule with expression level reaching maximum later in development, the functional deficit of KCC2 may offer an explanation for the delayed onset of Rett symptoms. Our studies suggest that restoring KCC2 function in Rett neurons may lead to a potential treatment for Rett syndrome. PMID:26733678

  7. KCC2 rescues functional deficits in human neurons derived from patients with Rett syndrome.

    PubMed

    Tang, Xin; Kim, Julie; Zhou, Li; Wengert, Eric; Zhang, Lei; Wu, Zheng; Carromeu, Cassiano; Muotri, Alysson R; Marchetto, Maria C N; Gage, Fred H; Chen, Gong

    2016-01-19

    Rett syndrome is a severe form of autism spectrum disorder, mainly caused by mutations of a single gene methyl CpG binding protein 2 (MeCP2) on the X chromosome. Patients with Rett syndrome exhibit a period of normal development followed by regression of brain function and the emergence of autistic behaviors. However, the mechanism behind the delayed onset of symptoms is largely unknown. Here we demonstrate that neuron-specific K(+)-Cl(-) cotransporter2 (KCC2) is a critical downstream gene target of MeCP2. We found that human neurons differentiated from induced pluripotent stem cells from patients with Rett syndrome showed a significant deficit in KCC2 expression and consequently a delayed GABA functional switch from excitation to inhibition. Interestingly, overexpression of KCC2 in MeCP2-deficient neurons rescued GABA functional deficits, suggesting an important role of KCC2 in Rett syndrome. We further identified that RE1-silencing transcriptional factor, REST, a neuronal gene repressor, mediates the MeCP2 regulation of KCC2. Because KCC2 is a slow onset molecule with expression level reaching maximum later in development, the functional deficit of KCC2 may offer an explanation for the delayed onset of Rett symptoms. Our studies suggest that restoring KCC2 function in Rett neurons may lead to a potential treatment for Rett syndrome.

  8. Supplementary Low-Intensity Aerobic Training Improves Aerobic Capacity and Does Not Affect Psychomotor Performance in Professional Female Ballet Dancers

    PubMed Central

    Smol, Ewelina; Fredyk, Artur

    2012-01-01

    We investigated whether 6-week low-intensity aerobic training program used as a supplement to regular dance practice might improve both the aerobic capacity and psychomotor performance in female ballet dancers. To assess their maximal oxygen uptake (VO2max) and anaerobic threshold (AT), the dancers performed a standard graded bicycle ergometer exercise test until volitional exhaustion prior to and after the supplementary training. At both these occasions, the psychomotor performance (assessed as multiple choice reaction time) and number of correct responses to audio-visual stimuli was assessed at rest and immediately after cessation of maximal intensity exercise. The supplementary low-intensity exercise training increased VO2max and markedly shifted AT toward higher absolute workload. Immediately after completion of the graded exercise to volitional exhaustion, the ballerinas’ psychomotor performance remained at the pre-exercise (resting) level. Neither the resting nor the maximal multiple choice reaction time and accuracy of responses were affected by the supplementary aerobic training. The results of this study indicate that addition of low-intensity aerobic training to regular dance practice increases aerobic capacity of ballerinas with no loss of speed and accuracy of their psychomotor reaction. PMID:23485962

  9. Selective behavioral responses to male song are affected by the dopamine agonist GBR-12909 in female European starlings (Sturnus vulgaris).

    PubMed

    Pawlisch, Benjamin A; Riters, Lauren V

    2010-09-24

    Female songbirds use attributes of male song to select mates. Different types of male song differ in incentive value (or the ability to attract females). Dopamine plays a role in incentive value and reward; however, little is known about its role in selective female behavioral responses to male courtship signals. We examined the effects of the indirect dopamine agonist (dopamine reuptake inhibitor) GBR-12909 on female songbird responses to male song stimuli. Female European starlings were played recordings of long starling song (presumed high incentive value), short starling song (presumed lower incentive value), or purple martin song (lowest incentive value). Vehicle-treated females investigated nest boxes playing starling song more than purple martin song. However, GBR-12909 disrupted preferential responses to the starling song stimuli. GBR-12909 also increased cFOS immunolabeling in the ventromedial nucleus of the hypothalamus (VMH) at the same dose that disrupted female selective responses to male starling song. The results suggest that dopamine receptors play an important role in female selective responses to biologically meaningful stimuli and that the VMH may be influenced by dopamine to alter female responses to male song. PMID:20633541

  10. What Affects Reintegration of Female Drug Users after Prison Release? Results of a European Follow-Up Study

    ERIC Educational Resources Information Center

    Zurhold, Heike; Moskalewicz, Jacek; Sanclemente, Cristina; Schmied, Gabriele; Shewan, David; Verthein, Uwe

    2011-01-01

    The main objective of this follow-up study is to explore factors influencing the success or failure of women in reintegrating after their release from prison. Female drug users in five European cities were tracked after being released from prison. Out of 234 female prisoners contacted in prisons, 59 were included in the follow-up study. Structured…

  11. Lack of Evidence for Increased Genetic Loading for Autism among Families of Affected Females: A Replication from Family History Data in Two Large Samples

    ERIC Educational Resources Information Center

    Goin-Kochel, Robin P.; Abbacchi, Anna; Constantino, John N.

    2007-01-01

    Both the broad and narrow phenotypes of autism have been consistently observed in family members of affected individuals. Additionally, autism spectrum disorders (ASDs) present four times more often in males than in females, for reasons that are currently unknown. In this study, we examined whether there were differences in familial loading of ASD…

  12. Evaluation of the Relationship between Critical Thinking Skills and Affective Control in Child Training Students of the Female Technical and Vocational College in the City of Broujerd

    ERIC Educational Resources Information Center

    Esmaeili, Zohreh; Bagheri, Mahdi

    2015-01-01

    This study is a descriptive-correlational study with the purpose of evaluating the relationship between critical thinking skills and affective control in child training students of the female technical and Vocational College in the city of Broujerd. Statistical population of this study consisted of all students in the field of child training of…

  13. PTP1B inhibition suggests a therapeutic strategy for Rett syndrome

    PubMed Central

    Krishnan, Navasona; Krishnan, Keerthi; Connors, Christopher R.; Choy, Meng S.; Page, Rebecca; Peti, Wolfgang; Van Aelst, Linda; Shea, Stephen D.; Tonks, Nicholas K.

    2015-01-01

    The X-linked neurological disorder Rett syndrome (RTT) presents with autistic features and is caused primarily by mutations in a transcriptional regulator, methyl CpG–binding protein 2 (MECP2). Current treatment options for RTT are limited to alleviating some neurological symptoms; hence, more effective therapeutic strategies are needed. We identified the protein tyrosine phosphatase PTP1B as a therapeutic candidate for treatment of RTT. We demonstrated that the PTPN1 gene, which encodes PTP1B, was a target of MECP2 and that disruption of MECP2 function was associated with increased levels of PTP1B in RTT models. Pharmacological inhibition of PTP1B ameliorated the effects of MECP2 disruption in mouse models of RTT, including improved survival in young male (Mecp2–/y) mice and improved behavior in female heterozygous (Mecp2–/+) mice. We demonstrated that PTP1B was a negative regulator of tyrosine phosphorylation of the tyrosine kinase TRKB, the receptor for brain-derived neurotrophic factor (BDNF). Therefore, the elevated PTP1B that accompanies disruption of MECP2 function in RTT represents a barrier to BDNF signaling. Inhibition of PTP1B led to increased tyrosine phosphorylation of TRKB in the brain, which would augment BDNF signaling. This study presents PTP1B as a mechanism-based therapeutic target for RTT, validating a unique strategy for treating the disease by modifying signal transduction pathways with small-molecule drugs. PMID:26214522

  14. New insights in Rett syndrome using pathway analysis for transcriptomics data.

    PubMed

    Ehrhart, Friederike; Coort, Susan L M; Cirillo, Elisa; Smeets, Eric; Evelo, Chris T; Curfs, Leopold

    2016-09-01

    The analysis of transcriptomics data is able to give an overview of cellular processes, but requires sophisticated bioinformatics tools and methods to identify the changes. Pathway analysis software, like PathVisio, captures the information about biological pathways from databases and brings this together with the experimental data to enable visualization and understanding of the underlying processes. Rett syndrome is a rare disease, but still one of the most abundant causes of intellectual disability in females. Cause of this neurological disorder is mutation of one single gene, the methyl-CpG-binding protein 2 (MECP2) gene. This gene is responsible for many steps in neuronal development and function. Although the genetic mutation and the clinical phenotype are well described, the molecular pathways linking them are not yet fully elucidated. In this study we demonstrate a workflow for the analysis of transcriptomics data to identify biological pathways and processes which are changed in a Mecp2 (-/y) mouse model. PMID:27517371

  15. Altered cholinergic function in the basal forebrain of girls with Rett syndrome.

    PubMed

    Wenk, G L; Hauss-Wegrzyniak, B

    1999-06-01

    Rett syndrome (RS) is a neurodevelopmental disorder that is predominant in females and is associated with cortical atrophy, stereotyped hand movements and severe mental deficiency. Previous studies have demonstrated a significant decline in number of choline acetyltransferase (ChAT)-containing neurons throughout the forebrain of RS girls. The loss of these ChAT-positive cells may be caused by a lack of nerve growth factor (NGF). In the current study, cortical levels of NGF were normal in RS girls as compared to age-and sex-matched controls. The number of neurons within the basal forebrain that express the 75 kDa (p75) low-affinity receptor for NGF was unchanged. In contrast, the number of ChAT-positive neurons was significantly decreased. The results suggest that normal amounts of NGF are available for binding to the p75 receptor and for retrograde transport to forebrain cholinergic cells, however, these neurons do not respond by producing the ChAT protein that is necessary for the production of the neurotransmitter acetylcholine.

  16. PTP1B inhibition suggests a therapeutic strategy for Rett syndrome.

    PubMed

    Krishnan, Navasona; Krishnan, Keerthi; Connors, Christopher R; Choy, Meng S; Page, Rebecca; Peti, Wolfgang; Van Aelst, Linda; Shea, Stephen D; Tonks, Nicholas K

    2015-08-01

    The X-linked neurological disorder Rett syndrome (RTT) presents with autistic features and is caused primarily by mutations in a transcriptional regulator, methyl CpG-binding protein 2 (MECP2). Current treatment options for RTT are limited to alleviating some neurological symptoms; hence, more effective therapeutic strategies are needed. We identified the protein tyrosine phosphatase PTP1B as a therapeutic candidate for treatment of RTT. We demonstrated that the PTPN1 gene, which encodes PTP1B, was a target of MECP2 and that disruption of MECP2 function was associated with increased levels of PTP1B in RTT models. Pharmacological inhibition of PTP1B ameliorated the effects of MECP2 disruption in mouse models of RTT, including improved survival in young male (Mecp2-/y) mice and improved behavior in female heterozygous (Mecp2-/+) mice. We demonstrated that PTP1B was a negative regulator of tyrosine phosphorylation of the tyrosine kinase TRKB, the receptor for brain-derived neurotrophic factor (BDNF). Therefore, the elevated PTP1B that accompanies disruption of MECP2 function in RTT represents a barrier to BDNF signaling. Inhibition of PTP1B led to increased tyrosine phosphorylation of TRKB in the brain, which would augment BDNF signaling. This study presents PTP1B as a mechanism-based therapeutic target for RTT, validating a unique strategy for treating the disease by modifying signal transduction pathways with small-molecule drugs.

  17. New insights in Rett syndrome using pathway analysis for transcriptomics data.

    PubMed

    Ehrhart, Friederike; Coort, Susan L M; Cirillo, Elisa; Smeets, Eric; Evelo, Chris T; Curfs, Leopold

    2016-09-01

    The analysis of transcriptomics data is able to give an overview of cellular processes, but requires sophisticated bioinformatics tools and methods to identify the changes. Pathway analysis software, like PathVisio, captures the information about biological pathways from databases and brings this together with the experimental data to enable visualization and understanding of the underlying processes. Rett syndrome is a rare disease, but still one of the most abundant causes of intellectual disability in females. Cause of this neurological disorder is mutation of one single gene, the methyl-CpG-binding protein 2 (MECP2) gene. This gene is responsible for many steps in neuronal development and function. Although the genetic mutation and the clinical phenotype are well described, the molecular pathways linking them are not yet fully elucidated. In this study we demonstrate a workflow for the analysis of transcriptomics data to identify biological pathways and processes which are changed in a Mecp2 (-/y) mouse model.

  18. Case report: Retracing atypical development: a preserved speech variant of Rett syndrome.

    PubMed

    Marschik, Peter B; Einspieler, Christa; Oberle, Andreas; Laccone, Franco; Prechtl, Heinz F R

    2009-06-01

    The subject of the present study is the development of a girl with the preserved speech variant of Rett disorder. Our data are based on detailed retrospective and prospective video analyses. Despite achieving developmental milestones, movement quality was already abnormal during the girl's first half year of life. In addition, early hand stereotypies, idiosyncratic vocalizations, asymmetric eye opening, and abnormal facial expressions are early signs proving that this variant of the Rett complex, too, manifests itself within the first months of life.

  19. Neurodevelopmental and neurobehavioral characteristics in males and females with CDKL5 duplications.

    PubMed

    Szafranski, Przemyslaw; Golla, Sailaja; Jin, Weihong; Fang, Ping; Hixson, Patricia; Matalon, Reuben; Kinney, Daniel; Bock, Hans-Georg; Craigen, William; Smith, Janice L; Bi, Weimin; Patel, Ankita; Wai Cheung, Sau; Bacino, Carlos A; Stankiewicz, Paweł

    2015-07-01

    Point mutations and genomic deletions of the CDKL5 (STK9) gene on chromosome Xp22 have been reported in patients with severe neurodevelopmental abnormalities, including Rett-like disorders. To date, only larger-sized (8-21 Mb) duplications harboring CDKL5 have been described. We report seven females and four males from seven unrelated families with CDKL5 duplications 540-935 kb in size. Three families of different ethnicities had identical 667kb duplications containing only the shorter CDKL5 isoform. Four affected boys, 8-14 years of age, and three affected girls, 6-8 years of age, manifested autistic behavior, developmental delay, language impairment, and hyperactivity. Of note, two boys and one girl had macrocephaly. Two carrier mothers of the affected boys reported a history of problems with learning and mathematics while at school. None of the patients had epilepsy. Similarly to CDKL5 mutations and deletions, the X-inactivation pattern in all six studied females was random. We hypothesize that the increased dosage of CDKL5 might have affected interactions of this kinase with its substrates, leading to perturbation of synaptic plasticity and learning, and resulting in autistic behavior, developmental and speech delay, hyperactivity, and macrocephaly. PMID:25315662

  20. Neurodevelopmental and neurobehavioral characteristics in males and females with CDKL5 duplications.

    PubMed

    Szafranski, Przemyslaw; Golla, Sailaja; Jin, Weihong; Fang, Ping; Hixson, Patricia; Matalon, Reuben; Kinney, Daniel; Bock, Hans-Georg; Craigen, William; Smith, Janice L; Bi, Weimin; Patel, Ankita; Wai Cheung, Sau; Bacino, Carlos A; Stankiewicz, Paweł

    2015-07-01

    Point mutations and genomic deletions of the CDKL5 (STK9) gene on chromosome Xp22 have been reported in patients with severe neurodevelopmental abnormalities, including Rett-like disorders. To date, only larger-sized (8-21 Mb) duplications harboring CDKL5 have been described. We report seven females and four males from seven unrelated families with CDKL5 duplications 540-935 kb in size. Three families of different ethnicities had identical 667kb duplications containing only the shorter CDKL5 isoform. Four affected boys, 8-14 years of age, and three affected girls, 6-8 years of age, manifested autistic behavior, developmental delay, language impairment, and hyperactivity. Of note, two boys and one girl had macrocephaly. Two carrier mothers of the affected boys reported a history of problems with learning and mathematics while at school. None of the patients had epilepsy. Similarly to CDKL5 mutations and deletions, the X-inactivation pattern in all six studied females was random. We hypothesize that the increased dosage of CDKL5 might have affected interactions of this kinase with its substrates, leading to perturbation of synaptic plasticity and learning, and resulting in autistic behavior, developmental and speech delay, hyperactivity, and macrocephaly.

  1. Neurodevelopmental and neurobehavioral characteristics in males and females with CDKL5 duplications

    PubMed Central

    Szafranski, Przemyslaw; Golla, Sailaja; Jin, Weihong; Fang, Ping; Hixson, Patricia; Matalon, Reuben; Kinney, Daniel; Bock, Hans-georg; Craigen, William; Smith, Janice L; Bi, Weimin; Patel, Ankita; Wai Cheung, Sau; Bacino, Carlos A; Stankiewicz, Paweł

    2015-01-01

    Point mutations and genomic deletions of the CDKL5 (STK9) gene on chromosome Xp22 have been reported in patients with severe neurodevelopmental abnormalities, including Rett-like disorders. To date, only larger-sized (8–21 Mb) duplications harboring CDKL5 have been described. We report seven females and four males from seven unrelated families with CDKL5 duplications 540–935 kb in size. Three families of different ethnicities had identical 667kb duplications containing only the shorter CDKL5 isoform. Four affected boys, 8–14 years of age, and three affected girls, 6–8 years of age, manifested autistic behavior, developmental delay, language impairment, and hyperactivity. Of note, two boys and one girl had macrocephaly. Two carrier mothers of the affected boys reported a history of problems with learning and mathematics while at school. None of the patients had epilepsy. Similarly to CDKL5 mutations and deletions, the X-inactivation pattern in all six studied females was random. We hypothesize that the increased dosage of CDKL5 might have affected interactions of this kinase with its substrates, leading to perturbation of synaptic plasticity and learning, and resulting in autistic behavior, developmental and speech delay, hyperactivity, and macrocephaly. PMID:25315662

  2. Teriparatide in the treatment of recurrent fractures in a Rett patient

    PubMed Central

    Caffarelli, Carla; Hayek, Jussef; Nuti, Ranuccio; Gonnelli, Stefano

    2015-01-01

    Summary Rett syndrome is a common X-linked neurodevelopmental disorder caused by mutations in the MECP2 gene. Patients with Rett syndrome have a low bone mineral density and increased risk of fracture. The present case report describes a successful novel therapeutic intervention with teriparatide with one patient with Rett syndrome, after suffering from recurrent low-trauma fractures at intervals of several years. Because of the severity of bone involvement, the decision was made to treat with teriparatide and subsequently with intravenous bisphosphonate. Since the initiation of the treatment, there was an evident improvement at densitometric and QUS parameters. Furthermore, until the present, no new fractures have appeared. This is the first report in which teriparatide was administered to a subjects with Rett syndrome. In conclusion, this report has shown the effectiveness of teriparatide in the management of osteoporotic fractures in one subjects with Rett syndrome. This report provides evidence that increased knowledge of bone pathology and fracture prevention in Rett subjects is important and should be addressed in future studies. PMID:26811706

  3. Links between breeding readiness, opioid immunolabeling, and the affective state induced by hearing male courtship song in female European starlings (Sturnus vulgaris)

    PubMed Central

    Riters, Lauren V.; Ellis, Jesse M. S.; Angyal, Caroline S.; Borkowski, Vincent; Cordes, Melissa A.; Stevenson, Sharon A.

    2013-01-01

    Male courtship vocalizations represent a potent signal designed to attract females; however, not all females find male signals equally attractive. We explored the possibility that the affective state induced by hearing courtship vocalizations depends on the motivational state of a receiver. We used a conditioned place preference test of reward to determine the extent to which the rewarding properties of hearing male courtship song differed in female European starlings categorized as nest box owners (a sign of breeding readiness) or non-owners. Nest box owners developed a preference for a chamber in which they previously heard male courtship song. Non-owners displayed no preference for a chamber in which they previously heard song. Positive correlations were identified between the preference a female developed for the song-paired chamber and female nesting and dominance behaviors observed prior to conditioning (indices of the motivation to breed). Immunolabeling for met-enkephalin (an opioid neuropeptide involved in reward) in the medial preoptic nucleus, ventromedial nucleus of the hypothalamus, nucleus accumbens, and periaqueductal gray was higher in females with compared to those without nest boxes. Both nest box entries and song-induced place preference also correlated positively with met-enkephalin labeling in the ventromedial nucleus of the hypothalamus. These findings indicate that the reward value of vocal signals is linked to individual differences in motivational state; and that differences in enkephalin activity may play a role in modifying an individual’s motivational state and/or the reward value of song. PMID:23473880

  4. Links between breeding readiness, opioid immunolabeling, and the affective state induced by hearing male courtship song in female European starlings (Sturnus vulgaris).

    PubMed

    Riters, Lauren V; Ellis, Jesse M S; Angyal, Caroline S; Borkowski, Vincent J; Cordes, Melissa A; Stevenson, Sharon A

    2013-06-15

    Male courtship vocalizations represent a potent signal designed to attract females; however, not all females find male signals equally attractive. We explored the possibility that the affective state induced by hearing courtship vocalizations depends on the motivational state of a receiver. We used a conditioned place preference test of reward to determine the extent to which the rewarding properties of hearing male courtship song differed in female European starlings categorized as nest box owners (a sign of breeding readiness) or non-owners. Nest box owners developed a preference for a chamber in which they previously heard male courtship song. Non-owners displayed no preference for a chamber in which they previously heard song. Positive correlations were identified between the preference a female developed for the song-paired chamber and female nesting and dominance behaviors observed prior to conditioning (indices of the motivation to breed). Immunolabeling for met-enkephalin (an opioid neuropeptide involved in reward) in the medial preoptic nucleus, ventromedial nucleus of the hypothalamus, nucleus accumbens, and periaqueductal gray was higher in females with compared to those without nest boxes. Both nest box entries and song-induced place preference also correlated positively with met-enkephalin labeling in the ventromedial nucleus of the hypothalamus. These findings indicate that the reward value of vocal signals is linked to individual differences in motivational state; and that differences in enkephalin activity may play a role in modifying an individual's motivational state and/or the reward value of song. PMID:23473880

  5. Neighbours' Breeding Success and the Sex Ratio of Their Offspring Affect the Mate Preferences of Female Zebra Finches

    PubMed Central

    Drullion, Dominique; Dubois, Frédérique

    2011-01-01

    Several hypotheses on divorce predict that monogamous pairs should split up more frequently after a breeding failure. Yet, deviations from the expected pattern “success-stay, failure-leave” have been reported in several species. One possible explanation for these deviations would be that individuals do not use only their own breeding performance (i.e., private information) but also that of others (i.e., public information) to decide whether or not to divorce. To test this hypothesis, we investigated the relative importance of private and public information for mate choice decisions in female zebra finches (Taeniopygia guttata).We manipulated the reproductive performance of breeding pairs and measured females' preferences for their mate and the neighbouring male first following pair formation and then seven weeks later when all females had laid eggs and the young were independent. Although all females reduced their preference for their mate after a breeding failure, the decrease was significant only when the neighbouring pair had reproduced successfully. Furthermore, there was no evidence that females biased the sex ratio of their offspring according to their mate's attractiveness. On the other hand, after reproduction, both successful and unsuccessful females increased their preferences for males who had produced a larger proportion of sons. Despite the fact that other mechanisms may have also contributed to our findings, we suggest that females changed their mate preferences based on the proportion of sons produced by successful males, because offspring sex ratio reflects the male's testosterone level at the moment of fertilization and hence is an indicator of his immune condition. PMID:22216351

  6. Neighbours' breeding success and the sex ratio of their offspring affect the mate preferences of female zebra finches.

    PubMed

    Drullion, Dominique; Dubois, Frédérique

    2011-01-01

    Several hypotheses on divorce predict that monogamous pairs should split up more frequently after a breeding failure. Yet, deviations from the expected pattern "success-stay, failure-leave" have been reported in several species. One possible explanation for these deviations would be that individuals do not use only their own breeding performance (i.e., private information) but also that of others (i.e., public information) to decide whether or not to divorce. To test this hypothesis, we investigated the relative importance of private and public information for mate choice decisions in female zebra finches (Taeniopygia guttata).We manipulated the reproductive performance of breeding pairs and measured females' preferences for their mate and the neighbouring male first following pair formation and then seven weeks later when all females had laid eggs and the young were independent. Although all females reduced their preference for their mate after a breeding failure, the decrease was significant only when the neighbouring pair had reproduced successfully. Furthermore, there was no evidence that females biased the sex ratio of their offspring according to their mate's attractiveness. On the other hand, after reproduction, both successful and unsuccessful females increased their preferences for males who had produced a larger proportion of sons. Despite the fact that other mechanisms may have also contributed to our findings, we suggest that females changed their mate preferences based on the proportion of sons produced by successful males, because offspring sex ratio reflects the male's testosterone level at the moment of fertilization and hence is an indicator of his immune condition. PMID:22216351

  7. Factors affecting the retention of first-year female science and engineering students at the University of Michigan

    NASA Astrophysics Data System (ADS)

    Ballard, Juliet Webb

    Alarming to many academics is that while the numbers of female students (at the University of Michigan in particular) in SEM (Science, Engineering, and Mathematics) departments have shown increases in enrollment over the past decades, the number of female professionals in the field has decreased. The purpose of the study was to determine the environmental perceptions of female SEM students in the Women in Science and Engineering (WISE) Program at the University of Michigan. The WISE-RP (Residence Program) is an existing living and learning education program at the university that was designed to facilitate the successful retention and graduation of undergraduate female SEM students in the capacity that the admissions statistics should logically imply. The objectives of the study included identification of the perceptions of female students that contribute to, and foster retention of students participating in the WISE-RP program. The knowledge obtained from this evaluation will guide the University of Michigan in formulating specific interventions and retention approaches, both in and out of the classroom. This was achieved by identifying (among other things) commonality of experiences, and female student's perceptions of acceptance, integration and interactivity. The data used in this secondary analysis was collected over a 2 year period (1999--2001). The primary instrument used for data collection was a structured interview protocol utilizing focus groups. The population and samples studied were comprised of: a research project consisting of 36 focus groups from WISE-RP, University Research Opportunity Program, and the University Research Opportunity in Residence Programs; the sample size of the initial project was 180 first year SEM male and female students. The research project consisted of working with a senior research team at the University of Michigan to develop a structured interview instrument, pilot the instrument, and select focus groups. Content

  8. Female access and diet affect insemination success, senescence, and the cost of reproduction in male Mexican fruit flies Anastrepha ludens

    PubMed Central

    HARWOOD, JAMES F.; CHEN, KEHUI; LIEDO, PABLO; MÜLLER, HANS-GEORG; WANG, JANE-LING; MORICE, AMY E.; CAREY, JAMES R.

    2014-01-01

    Hypotheses exploring the influence of dietary conditions on the life history trade-off between survival and reproductive success are extensively tested in female insects, but are rarely explored in males. Here, the impact of dietary quality and female access on age-specific reproduction and survival of male Mexican fruit flies, Anastrepha ludens Loew (Diptera: Tephritidae), are examined. There is a clear cost of female access for males with access to dietary protein, measurable as a decrease in life expectancy, which is further influenced by the age when females are introduced. A protein deficient diet reduces the lifespan benefit of virginity and masks the detrimental effect of female access on male life expectancy. Dietary protein is not necessary for reproductive success, but access to protein at eclosion improves the lifetime reproductive success of males compared to when it is delayed. Overall, reproductive success diminishes as the male flies age, regardless of the dietary conditions, providing evidence for reproductive senescence in males. Delaying the males’ access to a protein source fails to influence the negative effect of age on reproductive ability. Because age specific reproductive rates decline with age, regardless of diet, male fitness does not benefit from lifespan extension. Therefore, males can be expected to allocate available resources towards reproductive effort in favour of extended lifespan, regardless of mate and protein availability. PMID:25709143

  9. Measuring Use and Cost of Health Sector and Related Care in a Population of Girls and Young Women with Rett Syndrome

    ERIC Educational Resources Information Center

    Hendrie, Delia; Bebbington, Ami; Bower, Carol; Leonard, Helen

    2011-01-01

    This study measured use and cost of health sector and related services in Rett syndrome and effects of socio-demographic, clinical severity and genetic factors on costs. The study population consisted of individuals with Rett syndrome registered with the Australian Rett Syndrome Database in 2004. Descriptive analysis was used to examine patterns…

  10. Reversibility of functional deficits in experimental models of Rett syndrome.

    PubMed

    Cobb, Stuart; Guy, Jacky; Bird, Adrian

    2010-04-01

    Mutations in the X-linked MECP2 gene are the primary cause of the severe autism spectrum disorder RTT (Rett syndrome). Deletion of Mecp2 in mice recapitulates many of the overt neurological features seen in humans, and the delayed onset of symptoms is accompanied by deficits in neuronal morphology and synaptic physiology. Recent evidence suggests that reactivation of endogenous Mecp2 in young and adult mice can reverse aspects of RTT-like pathology. In the current perspective, we discuss these findings as well as other genetic, pharmacological and environmental interventions that attempt phenotypic rescue in RTT. We believe these studies provide valuable insights into the tractability of RTT and related conditions and are useful pointers for the development of future therapeutic strategies.

  11. Rett Syndrome: Crossing the Threshold to Clinical Translation

    PubMed Central

    Katz, David M.; Bird, Adrian; Coenraads, Monica; Gray, Steven J.; Menon, Debashish U.; Philpot, Benjamin D.; Tarquinio, Daniel C.

    2016-01-01

    Lying at the intersection between neurobiology and epigenetics, Rett syndrome (RTT) has garnered intense interest in recent years, not only from a broad range of academic scientists, but also from the pharmaceutical and biotechnology industries. In addition to the critical need for treatments for this devastating disorder, optimism for developing RTT treatments derives from a unique convergence of factors, including a known monogenic cause, reversibility of symptoms in preclinical models, a strong clinical research infrastructure highlighted by an NIH-funded natural history study and well-established clinics with significant patient populations. Here, we review recent advances in understanding the biology of RTT, particularly promising preclinical findings, lessons from past clinical trials, and critical elements of trial design for rare disorders. PMID:26830113

  12. Rett Syndrome: Crossing the Threshold to Clinical Translation.

    PubMed

    Katz, David M; Bird, Adrian; Coenraads, Monica; Gray, Steven J; Menon, Debashish U; Philpot, Benjamin D; Tarquinio, Daniel C

    2016-02-01

    Lying at the intersection between neurobiology and epigenetics, Rett syndrome (RTT) has garnered intense interest in recent years, not only from a broad range of academic scientists, but also from the pharmaceutical and biotechnology industries. In addition to the critical need for treatments for this devastating disorder, optimism for developing RTT treatments derives from a unique convergence of factors, including a known monogenic cause, reversibility of symptoms in preclinical models, a strong clinical research infrastructure highlighted by an NIH-funded natural history study and well-established clinics with significant patient populations. Here, we review recent advances in understanding the biology of RTT, particularly promising preclinical findings, lessons from past clinical trials, and critical elements of trial design for rare disorders.

  13. Brief report: MECP2 mutations in people without Rett syndrome.

    PubMed

    Suter, Bernhard; Treadwell-Deering, Diane; Zoghbi, Huda Y; Glaze, Daniel G; Neul, Jeffrey L

    2014-03-01

    Mutations in Methyl-CpG-Binding protein 2 (MECP2) are commonly associated with the neurodevelopmental disorder Rett syndrome (RTT). However, some people with RTT do not have mutations in MECP2, and interestingly there have been people identified with MECP2 mutations that do not have the clinical features of RTT. In this report we present four people with neurodevelopmental abnormalities and clear RTT-disease causing MECP2 mutation but lacking the characteristic clinical features of RTT. One patient's symptoms suggest an extension of the known spectrum of MECP2 associated phenotypes to include global developmental delay with obsessive compulsive disorder and attention deficit hyperactivity disorder. These results reemphasize that RTT should remain a clinical diagnosis, based on the recent consensus criteria.

  14. A role for metabolism in Rett syndrome pathogenesis

    PubMed Central

    Justice, Monica J; Buchovecky, Christie M; Kyle, Stephanie M; Djukic, Aleksandra

    2013-01-01

    Rett syndrome (RTT), an X-linked neurological disorder caused by mutations in MECP2, may have a metabolic component. We reported a genetic suppressor screen in a Mecp2-null mouse model to identify pathways for therapeutic improvement of RTT symptoms. Of note, one suppressor mutation implied that cholesterol homeostasis was perturbed in Mecp2 null mice; indeed, cholesterol synthesis was elevated in the brain and body system. Remarkably, the genetic effect of downregulating the cholesterol pathway could be mimicked chemically by statin drugs, improving motor symptoms, and increasing longevity in the mouse. Our work linked cholesterol metabolism to RTT pathology for the first time. Both neurological and systemic effects of perturbed cholesterol homeostasis overlap with many RTT symptoms. Here we show in patients that peripheral cholesterol, triglycerides, and/or LDLs may be elevated early in RTT disease onset, providing a biomarker for patients that could be aided by therapeutic interventions that modulate lipid metabolism. PMID:25003017

  15. MECP2 Mutations in People without Rett Syndrome

    PubMed Central

    Suter, Bernhard; Treadwell-Deering, Diane; Zoghbi, Huda Y.; Glaze, Daniel G.; Neul, Jeffrey L.

    2013-01-01

    Mutations in Methyl-CpG-Binding protein 2 (MECP2) are commonly associated with and the neurodevelopmental disorder Rett syndrome (RTT). However, some people with RTT do not have mutations in MECP2, and interestingly there have been people identified with MECP2 mutations that do not have the clinical features of RTT. In this report we present four people with neurodevelopmental abnormalities and clear RTT-disease causing MECP2 mutation but lacking the characteristic clinical features of RTT. One patient's symptoms suggest an extension of the known spectrum of MECP2 associated phenotypes to include Global Developmental Delay (GDD) with Obsessive Compulsive Disorder (OCD) and Attention Deficit Hyperactivity Disorder (ADHD). These results furthermore reemphasize that RTT should remain a clinical diagnosis, based on the recent refurbished consensus criteria. PMID:23921973

  16. [Rett syndrome: the state of research, and future perspectives].

    PubMed

    Matsuishi, Toyojiro

    2013-11-01

    Rett syndrome (RTT) is a neurodevelopmental disorder characterized by normal early psychomotor development followed by the loss of psychomotor and acquired purposeful hand skills and the onset of stereotyped movement of the hands and gait disturbance. The causative gene was discovered, and the disease was found to be caused by a mutation of methyl-CpG-binding protein 2. However, in many ways this clinically peculiar condition remains a mystery. I review the current status of clinical and basic research on RTT including data on the neurophysiology of the disease, neurotransmitter involvement, neuroimaging and neuropathology findings, molecular biology, animal models, regenerative medicine including ES cells and iPS cells, and other interventions and therapeutic trials.

  17. Functional communication training in rett syndrome: a preliminary study.

    PubMed

    Byiers, Breanne J; Dimian, Adele; Symons, Frank J

    2014-07-01

    Rett syndrome (RTT) is associated with a range of serious neurodevelopmental consequences including severe communicative impairments. Currently, no evidence-based communication interventions exist for the population ( Sigafoos et al., 2009 ). The purpose of the current study was to examine the effectiveness of functional assessment (FA) and functional communication training (FCT) methods for teaching 3 individuals (ages 15-47 years) with classic RTT novel communicative behaviors. Using single-case experimental designs, functional reinforcers were identified (FA) and each participant quickly learned to activate a voice-output switch to obtain a reinforcer (FCT). These results suggest that individuals with classic RTT can learn novel communicative responses, which has important implications for future intervention research.

  18. Life-long environmental enrichment differentially affects the mnemonic response to estrogen in young, middle-aged, and aged female mice.

    PubMed

    Gresack, Jodi E; Kerr, Kristin M; Frick, Karyn M

    2007-11-01

    The present study was designed to examine whether life-long exposure to standard or enriched housing affects the ability of estrogen to improve spatial and object memory throughout the lifespan. Three-week-old female mice were maintained in standard or enriched housing up to and through ovariectomy and behavioral testing at 5, 17, or 22 months of age. Spatial memory was tested in the Morris water maze and object memory was tested using an object recognition task. Immediately after training each day, mice were injected intraperitoneally with vehicle or 0.2 mg/kg 17beta-estradiol. Among young females, object recognition was enhanced by estradiol alone, an effect that was reduced by enrichment. In contrast, spatial water maze performance was impaired by estradiol alone, but improved by the combination of both estradiol and enrichment. At middle-age, object recognition was enhanced by estradiol or enrichment alone, and the combination of both treatments. Spatial memory in the water maze was also improved by both treatments at middle-age, but the beneficial effects of estradiol were limited to standard-housed females. Finally, whereas enrichment in aged females significantly enhanced performance in both tasks, estradiol had no effect at this age in either task. In total, the data indicate that life-long enrichment can significantly alter the extent to which estradiol affects memory in mice throughout the lifespan. Importantly, the interaction between these treatments is highly dependent on age and type of memory tested.

  19. Experimental defoliation affects male but not female reproductive performance of the tropical monoecious plant Croton suberosus (Euphorbiaceae)

    PubMed Central

    Narbona, Eduardo; Dirzo, Rodolfo

    2010-01-01

    Background and Aims Monoecious plants have the capacity to allocate resources separately to male and female functions more easily than hermaphrodites. This can be advantageous against environmental stresses such as leaf herbivory. However, studies showing effects of herbivory on male and female functions and on the interaction with the plant's pollinators are limited, particularly in tropical plants. Here, the effects of experimental defoliation were examined in the monoecious shrub Croton suberosus (Euphorbiaceae), a wasp-pollinated species from a Mexican tropical dry forest. Methods Three defoliation treatments were applied: 0 % (control), 25 % (low) or 75 % (high) of plant leaf area removed. Vegetative (production of new leaves) and reproductive (pistillate and staminate flower production, pollen viability, nectar production, fruit set, and seed set) performance variables, and the abundance and activity of floral visitors were examined. Key Results Defoliated plants overcompensated for tissue loss by producing more new leaves than control plants. Production of staminate flowers gradually decreased with increasing defoliation and the floral sex ratio (staminate : pistillate flowers) was drastically reduced in high-defoliation plants. In contrast, female reproductive performance (pistillate flower production, fruit set and seed set) and pollinator visitation and abundance were not impacted by defoliation. Conclusions The asymmetrical effects of defoliation on male and female traits of C. suberosus may be due to the temporal and spatial flexibility in the allocation of resources deployed by monoecious plants. We posit that this helps to maintain the plant's pollination success in the face of leaf herbivory stress. PMID:20519239

  20. Ovarian development in a primitively eusocial wasp: social interactions affect behaviorally dominant and subordinate wasps in opposite directions relative to solitary females.

    PubMed

    Shukla, Shantanu; Pareek, Vidhi; Gadagkar, Raghavendra

    2014-07-01

    In many primitively eusocial wasp species new nests are founded either by a single female or by a small group of females. In the single foundress nests, the lone female develops her ovaries, lays eggs as well as tends her brood. In multiple foundress nests social interactions, especially dominance-subordinate interactions, result in only one 'dominant' female developing her ovaries and laying eggs. Ovaries of the remaining 'subordinate' cofoundresses remain suppressed and these individuals function as workers and tend the dominant's brood. Using the tropical, primitively eusocial polistine wasp Ropalidia marginata and by comparing wasps held in isolation and those kept as pairs in the laboratory, we demonstrate that social interactions affect ovarian development of dominant and subordinate wasps among the pairs in opposite directions, suppressing the ovaries of the subordinate member of the pair below that of solitary wasps and boosting the ovaries of dominant member of the pair above that of solitary females. In addition to being of physiological interest, such mirror image effects of aggression on the ovaries of the aggressors and their victims, suggest yet another mechanism by which subordinates can enhance their indirect fitness and facilitate the evolution of worker behavior by kin selection.

  1. Neurophysiological responses to music and vibroacoustic stimuli in Rett syndrome.

    PubMed

    Bergström-Isacsson, Märith; Lagerkvist, Bengt; Holck, Ulla; Gold, Christian

    2014-06-01

    People with Rett syndrome (RTT) have severe communicative difficulties. They have as well an immature brainstem that implies dysfunction of the autonomic nervous system. Music plays an important role in their life, is often used as a motivating tool in a variety of situations and activities, and caregivers are often clear about people with RTTs favourites. The aim of this study was to investigate physiological and emotional responses related to six different musical stimuli in people with RTT. The study included 29 participants with RTT who were referred to the Swedish Rett Center for medical brainstem assessment during the period 2006-2007. 11 children with a typical developmental pattern were used as comparison. A repeated measures design was used, and physiological data were collected from a neurophysiological brainstem assessment. The continuous dependent variables measured were Cardiac Vagal Tone (CVT), Cardiac Sensitivity to Baroreflex (CSB), Mean Arterial Blood Pressure (MAP) and the Coefficient of Variation of Mean Arterial Blood Pressure (MAP-CV). These parameters were used to categorise brainstem responses as parasympathetic (calming) response, sympathetic (activating) response, arousal (alerting) response and unclear response. The results showed that all participants responded to the musical stimuli, but not always in the expected way. It was noticeable that both people with and without RTT responded with an arousal to all musical stimuli to begin with. Even though the initial expressions sometimes changed after some time due to poor control functions of their brainstem, the present results are consistent with the possibility that the RTT participants' normal responses to music are intact. These findings may explain why music is so important for individuals with RTT throughout life.

  2. Risk factors for deliberate self-harm among female college students: the role and interaction of childhood maltreatment, emotional inexpressivity, and affect intensity/reactivity.

    PubMed

    Gratz, Kim L

    2006-04-01

    Despite the clinical importance of deliberate self-harm, research on the risk factors for self-harm among nonclinical populations has been limited. This study examined the role of childhood maltreatment, emotional inexpressivity, and affect intensity/reactivity in the self-harm behavior of 249 female college students. Childhood maltreatment and low positive affect intensity/reactivity reliably distinguished women with frequent self-harm from women with no history of self-harm, as did the combination of greater maltreatment, greater inexpressivity, and higher levels of affect intensity/reactivity (global and negative). Among women with a history of self-harm, emotional inexpressivity was associated with more frequent self-harm, as was the combination of greater maltreatment, greater inexpressivity, and lower levels of positive affect intensity/reactivity.

  3. The Temporal Relationship Between Alcohol, Marijuana, Angry Affect, and Dating Violence Perpetration: A Daily Diary Study With Female College Students

    PubMed Central

    Shorey, Ryan C.; Stuart, Gregory L.; Moore, Todd M.; McNulty, James K.

    2014-01-01

    Although a robust literature documents a positive association between alcohol and intimate partner violence (IPV), there is limited temporal research on this relation. Moreover, the role of marijuana in influencing IPV has been mixed. Thus, the primary aim of the current study was to examine the temporal relationship between alcohol and marijuana use and dating violence perpetration. A secondary aim was to examine whether angry affect moderated the temporal relation between alcohol and marijuana use and IPV perpetration. Participants were college women who had consumed alcohol in the previous month and were in a dating relationship (N = 173). For up to 90 consecutive days, women completed daily surveys that assessed their alcohol use, marijuana use, angry affect (anger, hostility, and irritation), and violence perpetration (psychological and physical). On alcohol use days, marijuana use days, and with increases in angry affect, the odds of psychological aggression increased. Only alcohol use days and increases in angry affect increased the odds of physical aggression. Moreover, the main effects of alcohol and marijuana use on aggression were moderated by angry affect. Alcohol was positively associated with psychological and physical aggression when angry affect was high, but was unrelated to aggression when angry affect was low. Marijuana use was associated with psychological aggression when angry affect was high. Findings advance our understanding of the proximal effect of alcohol and marijuana use on dating violence, including the potential moderating effect of angry affect on this relation. PMID:24274434

  4. Misregulation of Alternative Splicing in a Mouse Model of Rett Syndrome.

    PubMed

    Li, Ronghui; Dong, Qiping; Yuan, Xinni; Zeng, Xin; Gao, Yu; Chiao, Cassandra; Li, Hongda; Zhao, Xinyu; Keles, Sunduz; Wang, Zefeng; Chang, Qiang

    2016-06-01

    Mutations in the human MECP2 gene cause Rett syndrome (RTT), a severe neurodevelopmental disorder that predominantly affects girls. Despite decades of work, the molecular function of MeCP2 is not fully understood. Here we report a systematic identification of MeCP2-interacting proteins in the mouse brain. In addition to transcription regulators, we found that MeCP2 physically interacts with several modulators of RNA splicing, including LEDGF and DHX9. These interactions are disrupted by RTT causing mutations, suggesting that they may play a role in RTT pathogenesis. Consistent with the idea, deep RNA sequencing revealed misregulation of hundreds of splicing events in the cortex of Mecp2 knockout mice. To reveal the functional consequence of altered RNA splicing due to the loss of MeCP2, we focused on the regulation of the splicing of the flip/flop exon of Gria2 and other AMPAR genes. We found a significant splicing shift in the flip/flop exon toward the flop inclusion, leading to a faster decay in the AMPAR gated current and altered synaptic transmission. In summary, our study identified direct physical interaction between MeCP2 and splicing factors, a novel MeCP2 target gene, and established functional connection between a specific RNA splicing change and synaptic phenotypes in RTT mice. These results not only help our understanding of the molecular function of MeCP2, but also reveal potential drug targets for future therapies. PMID:27352031

  5. Does microglial dysfunction play a role in autism and Rett syndrome?

    PubMed Central

    MAEZAWA, IZUMI; CALAFIORE, MARCO; WULFF, HEIKE; JIN, LEE-WAY

    2016-01-01

    Autism spectrum disorders (ASDs) including classic autism is a group of complex developmental disabilities with core deficits of impaired social interactions, communication difficulties and repetitive behaviors. Although the neurobiology of ASDs has attracted much attention in the last two decades, the role of microglia has been ignored. Existing data are focused on their recognized role in neuroinflammation, which only covers a small part of the pathological repertoire of microglia. This review highlights recent findings on the broader roles of microglia, including their active surveillance of brain microenvironments and regulation of synaptic connectivity, maturation of brain circuitry and neurogenesis. Emerging evidence suggests that microglia respond to pre- and postnatal environmental stimuli through epigenetic interface to change gene expression, thus acting as effectors of experience-dependent synaptic plasticity. Impairments of these microglial functions could substantially contribute to several major etiological factors of autism, such as environmental toxins and cortical underconnectivity. Our recent study on Rett syndrome, a syndromic autistic disorder, provides an example that intrinsic microglial dysfunction due to genetic and epigenetic aberrations could detrimentally affect the developmental trajectory without evoking neuroinflammation. We propose that ASDs provide excellent opportunities to study the influence of microglia on neurodevelopment, and this knowledge could lead to novel therapies. PMID:22717189

  6. Early socio-communicative forms and functions in typical Rett syndrome.

    PubMed

    Bartl-Pokorny, Katrin D; Marschik, Peter B; Sigafoos, Jeff; Tager-Flusberg, Helen; Kaufmann, Walter E; Grossmann, Tobias; Einspieler, Christa

    2013-10-01

    Rett syndrome (RTT) is a severe neurological disorder characterized by a developmental regression in motor and speech-language domains. There is, however, limited research on socio-communicative development of affected children before the onset of regression. We analyzed audio-video recordings made by parents of six 9- to 12-month old girls later diagnosed with typical RTT, applying the Inventory of Potential Communicative Acts (IPCA) to identify early communicative forms and functions. Each girl used at least one communicative form (e.g., body movement, eye gaze, or vocalizations) to gain attention and answer, but none were observed to make choices or request information. Varying numbers of children were observed to perform other communicative functions according to the IPCA including social convention, rejecting or requesting an object. Non-verbal forms (e.g., reaching, moving closer, eye contact, smiling) were more common than non-linguistic verbal forms (e.g., unspecified vocalizations, pleasure vocalizations, crying). (Pre-)linguistic verbal forms (e.g., canonical or variegated babbling, proto-words) were not used for communicative purposes. These data suggest that atypical developmental patterns in the socio-communicative domain are evident prior to regression in young individuals later diagnosed with RTT. PMID:23891731

  7. Early socio-communicative forms and functions in typical Rett syndrome.

    PubMed

    Bartl-Pokorny, Katrin D; Marschik, Peter B; Sigafoos, Jeff; Tager-Flusberg, Helen; Kaufmann, Walter E; Grossmann, Tobias; Einspieler, Christa

    2013-10-01

    Rett syndrome (RTT) is a severe neurological disorder characterized by a developmental regression in motor and speech-language domains. There is, however, limited research on socio-communicative development of affected children before the onset of regression. We analyzed audio-video recordings made by parents of six 9- to 12-month old girls later diagnosed with typical RTT, applying the Inventory of Potential Communicative Acts (IPCA) to identify early communicative forms and functions. Each girl used at least one communicative form (e.g., body movement, eye gaze, or vocalizations) to gain attention and answer, but none were observed to make choices or request information. Varying numbers of children were observed to perform other communicative functions according to the IPCA including social convention, rejecting or requesting an object. Non-verbal forms (e.g., reaching, moving closer, eye contact, smiling) were more common than non-linguistic verbal forms (e.g., unspecified vocalizations, pleasure vocalizations, crying). (Pre-)linguistic verbal forms (e.g., canonical or variegated babbling, proto-words) were not used for communicative purposes. These data suggest that atypical developmental patterns in the socio-communicative domain are evident prior to regression in young individuals later diagnosed with RTT.

  8. Misregulation of Alternative Splicing in a Mouse Model of Rett Syndrome

    PubMed Central

    Li, Ronghui; Dong, Qiping; Yuan, Xinni; Zeng, Xin; Gao, Yu; Li, Hongda; Keles, Sunduz; Wang, Zefeng; Chang, Qiang

    2016-01-01

    Mutations in the human MECP2 gene cause Rett syndrome (RTT), a severe neurodevelopmental disorder that predominantly affects girls. Despite decades of work, the molecular function of MeCP2 is not fully understood. Here we report a systematic identification of MeCP2-interacting proteins in the mouse brain. In addition to transcription regulators, we found that MeCP2 physically interacts with several modulators of RNA splicing, including LEDGF and DHX9. These interactions are disrupted by RTT causing mutations, suggesting that they may play a role in RTT pathogenesis. Consistent with the idea, deep RNA sequencing revealed misregulation of hundreds of splicing events in the cortex of Mecp2 knockout mice. To reveal the functional consequence of altered RNA splicing due to the loss of MeCP2, we focused on the regulation of the splicing of the flip/flop exon of Gria2 and other AMPAR genes. We found a significant splicing shift in the flip/flop exon toward the flop inclusion, leading to a faster decay in the AMPAR gated current and altered synaptic transmission. In summary, our study identified direct physical interaction between MeCP2 and splicing factors, a novel MeCP2 target gene, and established functional connection between a specific RNA splicing change and synaptic phenotypes in RTT mice. These results not only help our understanding of the molecular function of MeCP2, but also reveal potential drug targets for future therapies. PMID:27352031

  9. Choline Ameliorates Disease Phenotypes in Human iPSC Models of Rett Syndrome.

    PubMed

    Chin, Eunice W M; Marcy, Guillaume; Yoon, Su-In; Ma, Dongliang; Rosales, Francisco J; Augustine, George J; Goh, Eyleen L K

    2016-09-01

    Rett syndrome (RTT) is a postnatal neurodevelopmental disorder that primarily affects girls. Mutations in the methyl-CpG-binding protein 2 (MECP2) gene account for approximately 95 % of all RTT cases. To model RTT in vitro, we generated induced pluripotent stem cells (iPSCs) from fibroblasts of two RTT patients with different mutations (MECP2 (R306C) and MECP2 (1155Δ32)) in their MECP2 gene. We found that these iPSCs were capable of differentiating into functional neurons. Compared to control neurons, the RTT iPSC-derived cells had reduced soma size and a decreased amount of synaptic input, evident both as fewer Synapsin 1-positive puncta and a lower frequency of spontaneous excitatory postsynaptic currents. Supplementation of the culture media with choline rescued all of these defects. Choline supplementation may act through changes in the expression of choline acetyltransferase, an important enzyme in cholinergic signaling, and also through alterations in the lipid metabolite profiles of the RTT neurons. Our study elucidates the possible mechanistic pathways for the effect of choline on human RTT cell models, thereby illustrating the potential for using choline as a nutraceutical to treat RTT.

  10. Prenatal and neonatal testosterone exposure interact to affect differentiation of sexual behavior and partner preference in female ferrets.

    PubMed

    Baum, M J; Erskine, M S; Kornberg, E; Weaver, C E

    1990-02-01

    Implanting testosterone (T) subcutaneously over Postnatal Days 5-20 masculinized sexual behavior, reduced proceptive responsiveness, and shifted sexual preference more readily in male than in female ferrets gonadectomized on Day 5. This enhanced sensitivity of males to neonatal T was best duplicated in females exposed transplacentally to T over Embryonic Days (E) 27-39 (41-day gestation) and injected at birth with T (2.5 micrograms sc in oil: 10% ethanol). Extended exposure of male ferrets to high levels of T, beginning shortly after the onset of testicular steroidogenesis (E25) and continuing for several hours after birth (E41) normally sensitizes their brains to the subsequent organizational effects on coital performance and sexual motivation of the relatively low levels of T that circulate in male ferrets during the first 3 postnatal weeks.

  11. Is the Performance of a Specialist Herbivore Affected by Female Choices and the Adaptability of the Offspring?

    PubMed Central

    Galdino, Tarcísio Visintin da Silva; Picanço, Marcelo Coutinho; Ferreira, Dalton Oliveira; Silva, Geverson Aelton Resende; de Souza, Thadeu Carlos; Silva, Gerson Adriano

    2015-01-01

    The performance of herbivorous insects is related to the locations of defenses and nutrients found in the different plant organs on which they feed. In this context, the females of herbivorous insect species select certain parts of the plant where their offspring can develop well. In addition, their offspring can adapt to plant defenses. A system where these ecological relationships can be studied occurs in the specialist herbivore, Tuta absoluta, on tomato plants. In our experiments we evaluated: (i) the performance of the herbivore T. absoluta in relation to the tomato plant parts on which their offspring had fed, (ii) the spatial distribution of the insect stages on the plant canopy and (iii) the larval resistance to starvation and their walking speed at different instar stages. We found that the T. absoluta females preferred to lay their eggs in the tomato plant parts where their offspring had greater chances of success. We verified that the T. absoluta females laid their eggs on both sides of the leaves to better exploit resources. We also observed that the older larvae (3rd and 4th instars) moved to the most nutritious parts of the plant, thus increasing their performance. The T. absoluta females and offspring (larvae) were capable of identifying plant sites where their chances of better performance were higher. Additionally, their offspring (larvae) spread across the plant to better exploit the available plant nutrients. These behavioral strategies of T. absoluta facilitate improvement in their performance after acquiring better resources, which help reduce their mortality by preventing the stimulation of plant defense compounds and the action of natural enemies. PMID:26600074

  12. Long-term pyrene exposure of grass shrimp, Palaemonetes pugio, affects molting and reproduction of exposed males and offspring of exposed females.

    PubMed Central

    Oberdörster, E; Brouwer, M; Hoexum-Brouwer, T; Manning, S; McLachlan, J A

    2000-01-01

    The objective of this study was to investigate the impact of long-term pyrene exposure on molting and reproduction in the model estuarine invertebrate, the grass shrimp (Palaemonetes pugio). Grass shrimp were exposed to measured concentrations of 5.1, 15.0, and 63. 4 ppb (microg/L) pyrene for 6 weeks, during which time we determined molting and survivorship. At the end of the exposure, we immediately sacrificed some of the shrimp for biomarker (CYP1A and vitellin) analyses. The remaining shrimp were used to analyze fecundity and embryo survivorship during an additional 6 weeks after termination of pyrene exposure. Male shrimp at the highest pyrene dose (63 ppb) experienced a significant delay in molting and in time until reproduction, and showed elevated ethoxycoumarin o-deethylase (ECOD) activity immediately after the 6-week exposure period. In contrast, 63 ppb pyrene did not affect these parameters in female shrimp. Females produced the same number of eggs per body weight, with high egg viability (98-100%) at all exposure levels, but with decreased survival for the offspring of the 63-ppb pyrene-exposed females. In addition, vitellin levels were elevated only in females at 63 ppb pyrene after the 6-week exposure. We hypothesize that the elevated vitellin binds pyrene and keeps it biologically unavailable to adult females, resulting in maternal transfer of pyrene to the embryos. This would account for the lack of effect of pyrene exposure on ECOD activity, molting, and reproduction in the adult females, and for reduced survival of their offspring. Images Figure 1 Figure 2 Figure 3 PMID:10903618

  13. Spinal Fusion for Scoliosis in Rett Syndrome With an Emphasis on Respiratory Failure and Opioid Usage.

    PubMed

    Rumbak, Dania M; Mowrey, Wenzhu; W Schwartz, Skai; Sarwahi, Vishal; Djukic, Aleksandra; Killinger, James S; Katyal, Chhavi

    2016-02-01

    Our objective was to characterize our experience with 8 patients with Rett syndrome undergoing scoliosis surgery in regard to rates of respiratory failure and rates of ventilator-acquired pneumonia in comparison to patients with neurologic scoliosis and adolescent idiopathic scoliosis. This study was a retrospective chart review of patients undergoing scoliosis surgery at a tertiary children's hospital. Patients were divided into 3 groups: (1) adolescent idiopathic scoliosis, (2) neurologic scoliosis, and (3) Rett syndrome. There were 133 patients with adolescent idiopathic scoliosis, 48 patients with neurologic scoliosis, and 8 patients with Rett syndrome. We found that patients with Rett syndrome undergoing scoliosis surgery have higher rates of respiratory failure and longer ventilation times in the postoperative period when compared with both adolescent idiopathic scoliosis and neurologic scoliosis patients. There is insufficient evidence to suggest a difference in the incidence of ventilator-acquired pneumonia between the Rett syndrome and the neurologic scoliosis group. We believe our findings are the first in the literature to show a statistically significant difference between these 3 groups in regard to incidence of respiratory failure. PMID:25991642

  14. Spinal Fusion for Scoliosis in Rett Syndrome With an Emphasis on Respiratory Failure and Opioid Usage.

    PubMed

    Rumbak, Dania M; Mowrey, Wenzhu; W Schwartz, Skai; Sarwahi, Vishal; Djukic, Aleksandra; Killinger, James S; Katyal, Chhavi

    2016-02-01

    Our objective was to characterize our experience with 8 patients with Rett syndrome undergoing scoliosis surgery in regard to rates of respiratory failure and rates of ventilator-acquired pneumonia in comparison to patients with neurologic scoliosis and adolescent idiopathic scoliosis. This study was a retrospective chart review of patients undergoing scoliosis surgery at a tertiary children's hospital. Patients were divided into 3 groups: (1) adolescent idiopathic scoliosis, (2) neurologic scoliosis, and (3) Rett syndrome. There were 133 patients with adolescent idiopathic scoliosis, 48 patients with neurologic scoliosis, and 8 patients with Rett syndrome. We found that patients with Rett syndrome undergoing scoliosis surgery have higher rates of respiratory failure and longer ventilation times in the postoperative period when compared with both adolescent idiopathic scoliosis and neurologic scoliosis patients. There is insufficient evidence to suggest a difference in the incidence of ventilator-acquired pneumonia between the Rett syndrome and the neurologic scoliosis group. We believe our findings are the first in the literature to show a statistically significant difference between these 3 groups in regard to incidence of respiratory failure.

  15. A single long day triggers follicle growth in captive female great tits (Parus major) in winter but does not affect laying dates in the wild in spring.

    PubMed

    te Marvelde, Luc; Schaper, Sonja V; Visser, Marcel E

    2012-01-01

    In many forest passerine bird species, rapid climate warming has led to a phenological mismatch between the period of maximum nestlings' food requirements and the period of maximum food availability (seasonal caterpillar biomass peak) due to an insufficient advancement of the birds' laying dates. The initiation of laying is preceded by the development of the gonads, which in birds are regressed outside the breeding season. Increasing day length in late winter and early spring triggers a cascade of hormones which induces gonadal development. Since day length is not altered by climate change, one potential restriction to advancing laying date is the seasonal timing of gonadal development. To assess the importance of gonadal growth for timing of reproduction we experimentally manipulated the timing of gonadal development. We show that the growth of the largest follicle of captive female great tits (Parus major) increased after being exposed to just a single long day in winter (20 hours of light followed by 4 hours darkness). We then photostimulated wild female great tits from two study areas in a field experiment in spring for a single day and determined their laying date. These populations differed in the availability of food allowing us to test if food availability in combination with photostimulation affected egg laying dates. Despite an expected difference in the onset of gonadal growth, laying dates of photostimulated females did not differ from control females in both populations. These results suggest that wild great tits are not restricted in the advancement of their laying date by limited gonadal development.

  16. Restoration of Mecp2 expression in GABAergic neurons is sufficient to rescue multiple disease features in a mouse model of Rett syndrome

    PubMed Central

    Ure, Kerstin; Lu, Hui; Wang, Wei; Ito-Ishida, Aya; Wu, Zhenyu; He, Ling-jie; Sztainberg, Yehezkel; Chen, Wu; Tang, Jianrong; Zoghbi, Huda Y

    2016-01-01

    The postnatal neurodevelopmental disorder Rett syndrome, caused by mutations in MECP2, produces a diverse array of symptoms, including loss of language, motor, and social skills and the development of hand stereotypies, anxiety, tremor, ataxia, respiratory dysrhythmias, and seizures. Surprisingly, despite the diversity of these features, we have found that deleting Mecp2 only from GABAergic inhibitory neurons in mice replicates most of this phenotype. Here we show that genetically restoring Mecp2 expression only in GABAergic neurons of male Mecp2 null mice enhanced inhibitory signaling, extended lifespan, and rescued ataxia, apraxia, and social abnormalities but did not rescue tremor or anxiety. Female Mecp2+/- mice showed a less dramatic but still substantial rescue. These findings highlight the critical regulatory role of GABAergic neurons in certain behaviors and suggest that modulating the excitatory/inhibitory balance through GABAergic neurons could prove a viable therapeutic option in Rett syndrome. DOI: http://dx.doi.org/10.7554/eLife.14198.001 PMID:27328321

  17. Variant Rett syndrome in a girl with a pericentric X-chromosome inversion leading to epigenetic changes and overexpression of the MECP2 gene.

    PubMed

    Vieira, José Pedro; Lopes, Fátima; Silva-Fernandes, Anabela; Sousa, Maria Vânia; Moura, Sofia; Sousa, Susana; Costa, Bruno M; Barbosa, Mafalda; Ylstra, Bauke; Temudo, Teresa; Lourenço, Teresa; Maciel, Patrícia

    2015-11-01

    Rett syndrome is a neurodevelopmental disorder caused by mutations in the MECP2 gene. We investigated the genetic basis of disease in a female patient with a Rett-like clinical. Karyotype analysis revealed a pericentric inversion in the X chromosome -46,X,inv(X)(p22.1q28), with breakpoints in the cytobands where the MECP2 and CDKL5 genes are located. FISH analysis revealed that the MECP2 gene is not dislocated by the inversion. However, and in spite of a balanced pattern of X inactivation, this patient displayed hypomethylation and an overexpression of the MECP2 gene at the mRNA level in the lymphocytes (mean fold change: 2.55±0.38) in comparison to a group of control individuals; the expression of the CDKL5 gene was similar to that of controls (mean fold change: 0.98±0.10). No gains or losses were detected in the breakpoint regions encompassing known or suspected transcription regulatory elements. We propose that the de-regulation of MECP2 expression in this patient may be due to alterations in long-range genomic interactions caused by the inversion and hypothesize that this type of epigenetic de-regulation of the MECP2 may be present in other RTT-like patients.

  18. Hormonal status and age differentially affect tolerance to the disruptive effects of delta-9-tetrahydrocannabinol (Δ9-THC) on learning in female rats

    PubMed Central

    Winsauer, Peter J.; Filipeanu, Catalin M.; Weed, Peter F.; Sutton, Jessie L.

    2015-01-01

    The effects of hormone status and age on the development of tolerance to Δ9-THC were assessed in sham-operated (intact) or ovariectomized (OVX) female rats that received either intraperitoneal saline or 5.6 mg/kg of Δ9-THC daily from postnatal day (PD) 75–180 (early adulthood onward) or PD 35–140 (adolescence onward). During this time, the four groups for each age (i.e., intact/saline, intact/THC, OVX/saline, and OVX/THC) were trained in a learning and performance procedure and dose-effect curves were established for Δ9-THC (0.56–56 mg/kg) and the cannabinoid type-1 receptor (CB1R) antagonist rimonabant (0.32–10 mg/kg). Despite the persistence of small rate-decreasing and error-increasing effects in intact and OVX females from both ages during chronic Δ9-THC, all of the Δ9-THC groups developed tolerance. However, the magnitude of tolerance, as well as the effect of hormone status, varied with the age at which chronic Δ9-THC was initiated. There was no evidence of dependence in any of the groups. Hippocampal protein expression of CB1R, AHA1 (a co-chaperone of CB1R) and HSP90β (a molecular chaperone modulated by AHA-1) was affected more by OVX than chronic Δ9-THC; striatal protein expression was not consistently affected by either manipulation. Hippocampal brain-derived neurotrophic factor expression varied with age, hormone status, and chronic treatment. Thus, hormonal status differentially affects the development of tolerance to the disruptive effects of delta-9-tetrahydrocannabinol (Δ9-THC) on learning and performance behavior in adolescent, but not adult, female rats. These factors and their interactions also differentially affect cannabinoid signaling proteins in the hippocampus and striatum, and ultimately, neural plasticity. PMID:26191005

  19. Rett syndrome induced pluripotent stem cell-derived neurons reveal novel neurophysiological alterations.

    PubMed

    Farra, N; Zhang, W-B; Pasceri, P; Eubanks, J H; Salter, M W; Ellis, J

    2012-12-01

    Rett syndrome (RTT) is a neurodevelopmental autism spectrum disorder caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Here, we describe the first characterization and neuronal differentiation of induced pluripotent stem (iPS) cells derived from Mecp2-deficient mice. Fully reprogrammed wild-type (WT) and heterozygous female iPS cells express endogenous pluripotency markers, reactivate the X-chromosome and differentiate into the three germ layers. We directed iPS cells to produce glutamatergic neurons, which generated action potentials and formed functional excitatory synapses. iPS cell-derived neurons from heterozygous Mecp2(308) mice showed defects in the generation of evoked action potentials and glutamatergic synaptic transmission, as previously reported in brain slices. Further, we examined electrophysiology features not yet studied with the RTT iPS cell system and discovered that MeCP2-deficient neurons fired fewer action potentials, and displayed decreased action potential amplitude, diminished peak inward currents and higher input resistance relative to WT iPS-derived neurons. Deficiencies in action potential firing and inward currents suggest that disturbed Na(+) channel function may contribute to the dysfunctional RTT neuronal network. These phenotypes were additionally confirmed in neurons derived from independent WT and hemizygous mutant iPS cell lines, indicating that these reproducible deficits are attributable to MeCP2 deficiency. Taken together, these results demonstrate that neuronally differentiated MeCP2-deficient iPS cells recapitulate deficits observed previously in primary neurons, and these identified phenotypes further illustrate the requirement of MeCP2 in neuronal development and/or in the maintenance of normal function. By validating the use of iPS cells to delineate mechanisms underlying RTT pathogenesis, we identify deficiencies that can be targeted for in vitro translational screens.

  20. Pain experience and expression in Rett syndrome: Subjective and objective measurement approaches

    PubMed Central

    Barney, Chantel C.; Feyma, Timothy; Beisang, Arthur; Symons, Frank J.

    2015-01-01

    Rett syndrome (RTT) is associated with myriad debilitating health issues and significant motor and communicative impairments. Because of the former there is concern about the possibility of recurrent and chronic pain but because of the latter it remains difficult to determine what pain ‘looks like’ in RTT. This study investigated pain experience and expression using multiple complementary subjective and objective approaches among a clinical RTT sample. Following informed consent, 18 participants (all female) with RTT (mean age= 12.8 years, SD= 6.32) were characterized in terms of pain experience and interference, typical pain expression, and elicited pain behavior during a passive range of motion-like examination procedure. Parents completed the Dalhousie Pain Interview (DPI; pain type, frequency, duration, intensity), the Brief Pain Inventory (BPI; pain interference), and the Non-Communicating Children’s Pain Checklist – Revised (NCCPC-R; typical pain expression). A Pain Examination Procedure (PEP) was conducted and scored using the Pain and Discomfort Scale (PADS). The majority of the sample (89%) were reported to experience pain in the previous week which presented as gastrointestinal (n=8), musculoskeletal (n=5), and seizure related pain (n=5) that was intense (scored 0–10; M= 5.67, SD= 3.09) and long in duration (M= 25.22 hours, SD= 53.52). Numerous pain-expressive behaviors were inventoried (e.g., vocal, facial, mood/interaction changes) when parents reported their child’s typical pain behaviors and based on independent direct observation during a reliably coded pain exam. This study provides subjective and objective evidence that individuals with RTT experience recurring and chronic pain for which pain expression appears intact. PMID:26425056

  1. Biomechanical properties of bone in a mouse model of Rett syndrome

    PubMed Central

    Kamal, Bushra; Russell, David; Payne, Anthony; Constante, Diogo; Tanner, K. Elizabeth; Isaksson, Hanna; Mathavan, Neashan; Cobb, Stuart R.

    2015-01-01

    Rett syndrome (RTT) is an X-linked genetic disorder and a major cause of intellectual disability in girls. Mutations in the methyl-CpG binding protein 2 (MECP2) gene are the primary cause of the disorder. Despite the dominant neurological phenotypes, MECP2 is expressed ubiquitously throughout the body and a number of peripheral phenotypes such as scoliosis, reduced bone mineral density and skeletal fractures are also common and important clinical features of the disorder. In order to explore whether MeCP2 protein deficiency results in altered structural and functional properties of bone and to test the potential reversibility of any defects, we have conducted a series of histological, imaging and biomechanical tests of bone in a functional knockout mouse model of RTT. Both hemizygous Mecp2stop/y male mice in which Mecp2 is silenced in all cells and female Mecp2stop/+ mice in which Mecp2 is silenced in ~ 50% of cells as a consequence of random X-chromosome inactivation, revealed significant reductions in cortical bone stiffness, microhardness and tensile modulus. Microstructural analysis also revealed alterations in both cortical and cancellous femoral bone between wild-type and MeCP2-deficient mice. Furthermore, unsilencing of Mecp2 in adult mice cre-mediated stop cassette deletion resulted in a restoration of biomechanical properties (stiffness, microhardness) towards wild-type levels. These results show that MeCP2-deficiency results in overt, but potentially reversible, alterations in the biomechanical integrity of bone and highlights the importance of targeting skeletal phenotypes in considering the development of pharmacological and gene-based therapies. PMID:25445449

  2. Biomechanical properties of bone in a mouse model of Rett syndrome.

    PubMed

    Kamal, Bushra; Russell, David; Payne, Anthony; Constante, Diogo; Tanner, K Elizabeth; Isaksson, Hanna; Mathavan, Neashan; Cobb, Stuart R

    2015-02-01

    Rett syndrome (RTT) is an X-linked genetic disorder and a major cause of intellectual disability in girls. Mutations in the methyl-CpG binding protein 2 (MECP2) gene are the primary cause of the disorder. Despite the dominant neurological phenotypes, MECP2 is expressed ubiquitously throughout the body and a number of peripheral phenotypes such as scoliosis, reduced bone mineral density and skeletal fractures are also common and important clinical features of the disorder. In order to explore whether MeCP2 protein deficiency results in altered structural and functional properties of bone and to test the potential reversibility of any defects, we have conducted a series of histological, imaging and biomechanical tests of bone in a functional knockout mouse model of RTT. Both hemizygous Mecp2(stop/y) male mice in which Mecp2 is silenced in all cells and female Mecp2(stop/+) mice in which Mecp2 is silenced in ~50% of cells as a consequence of random X-chromosome inactivation, revealed significant reductions in cortical bone stiffness, microhardness and tensile modulus. Microstructural analysis also revealed alterations in both cortical and cancellous femoral bone between wild-type and MeCP2-deficient mice. Furthermore, unsilencing of Mecp2 in adult mice cre-mediated stop cassette deletion resulted in a restoration of biomechanical properties (stiffness, microhardness) towards wild-type levels. These results show that MeCP2-deficiency results in overt, but potentially reversible, alterations in the biomechanical integrity of bone and highlights the importance of targeting skeletal phenotypes in considering the development of pharmacological and gene-based therapies.

  3. Targeted pharmacological treatment of autism spectrum disorders: fragile X and Rett syndromes

    PubMed Central

    Wang, Hansen; Pati, Sandipan; Pozzo-Miller, Lucas; Doering, Laurie C.

    2015-01-01

    Autism spectrum disorders (ASDs) are genetically and clinically heterogeneous and lack effective medications to treat their core symptoms. Studies of syndromic ASDs caused by single gene mutations have provided insights into the pathophysiology of autism. Fragile X and Rett syndromes belong to the syndromic ASDs in which preclinical studies have identified rational targets for drug therapies focused on correcting underlying neural dysfunction. These preclinical discoveries are increasingly translating into exciting human clinical trials. Since there are significant molecular and neurobiological overlaps among ASDs, targeted treatments developed for fragile X and Rett syndromes may be helpful for autism of different etiologies. Here, we review the targeted pharmacological treatment of fragile X and Rett syndromes and discuss related issues in both preclinical studies and clinical trials of potential therapies for the diseases. PMID:25767435

  4. Solitary Encapsulated Neurofibroma Not Associated with Neurofibromatosis-1 Affecting Tongue in a 73-Year-Old Female

    PubMed Central

    Mahmud, Sk. Abdul; Chattaraj, Moumita; Gayen, Swagata

    2016-01-01

    Neurofibromas are benign tumors of nerve cell origin arising due to proliferation of Schwann cells and fibroblasts. They are usually asymptomatic and hence remain undiagnosed. They are commonly found on the skin and intraorally tongue is the most common site for their occurrence. Here, we present a unique case of solitary encapsulated neurofibroma in the oral cavity without any clinical manifestations or family history of Neurofibromatosis type 1 in a 73-year-old female patient who presented with a painless swelling on the tongue. The histopathologic findings closely mimicked benign fibrous histiocytoma. In our case, definitive diagnosis of neurofibroma was made based on clinical findings, family history, and histopathological and immunohistochemical evaluation. Through this case report we want to emphasize the role of biopsy and immunohistochemistry in arriving at a confirmatory diagnosis. The patient was treated by surgical excision and showed no signs of recurrence over a follow-up period of 12 months. PMID:27525129

  5. Solitary Encapsulated Neurofibroma Not Associated with Neurofibromatosis-1 Affecting Tongue in a 73-Year-Old Female.

    PubMed

    Mahmud, Sk Abdul; Shah, Neha; Chattaraj, Moumita; Gayen, Swagata

    2016-01-01

    Neurofibromas are benign tumors of nerve cell origin arising due to proliferation of Schwann cells and fibroblasts. They are usually asymptomatic and hence remain undiagnosed. They are commonly found on the skin and intraorally tongue is the most common site for their occurrence. Here, we present a unique case of solitary encapsulated neurofibroma in the oral cavity without any clinical manifestations or family history of Neurofibromatosis type 1 in a 73-year-old female patient who presented with a painless swelling on the tongue. The histopathologic findings closely mimicked benign fibrous histiocytoma. In our case, definitive diagnosis of neurofibroma was made based on clinical findings, family history, and histopathological and immunohistochemical evaluation. Through this case report we want to emphasize the role of biopsy and immunohistochemistry in arriving at a confirmatory diagnosis. The patient was treated by surgical excision and showed no signs of recurrence over a follow-up period of 12 months. PMID:27525129

  6. Fetal programming: prenatal androgen disrupts positive feedback actions of estradiol but does not affect timing of puberty in female sheep.

    PubMed

    Sharma, Tejinder Pal; Herkimer, Carol; West, Christine; Ye, Wen; Birch, Rachel; Robinson, Jane E; Foster, Douglas L; Padmanabhan, Vasantha

    2002-04-01

    We studied the impact of prenatal androgen exposure on the timing of onset of puberty, maintenance of cyclicity in the first breeding season, and the LH surge mechanism in female sheep. Pregnant sheep were injected with testosterone propionate (100 mg i.m.) twice each week from Day 30 to Day 90 (D30-90) or from Day 60 to Day 90 (D60-90) of gestation (term = 147 days). Concentrations of plasma progesterone and gonadotropins were measured in blood samples collected twice each week from control (n = 10), D60-90 (n = 13), and D30-90 (n = 3) animals. Rate of weight gain and initiation of estrous behavior were also monitored. After the first breeding season, when the animals entered anestrus, competency of the gonadotropin surge system to respond to estradiol positive feedback was tested in the absence or presence of progesterone priming for 12 days. Prenatally androgenized females had similar body weight gain and achieved puberty (start of first progestogenic cycle) at the same time as controls. Duration of the breeding season and the number of cycles that occurred during the first breeding season were similar between control and prenatally androgenized sheep. In contrast, prenatal exposure to androgens compromised the positive feedback effects of estradiol. Onset of LH/FSH surges following the estradiol stimulus was delayed in both groups of androgenized ewes compared with the controls in both the absence and presence of progesterone priming. In addition, the magnitude of LH and FSH surges in the two animals that surged in the D30-90 group were only one third and one half, respectively, of the magnitudes observed in the control and D60-90 groups. The present findings indicate that disruption of the surge system can account for the fertility problems that occur during adulthood in prenatally androgenized sheep.

  7. Acute estradiol treatment affects the expression of cocaine-induced conditioned place preference in ovariectomized female rats.

    PubMed

    Bobzean, Samara A M; Dennis, Torry S; Perrotti, Linda I

    2014-04-01

    Women and female rodents are more responsive to the subjective effects of psychostimulant drugs of abuse compared to males. A growing body of literature supports a role for estradiol as a mechanism underlying these sex differences. However, little is known about the influence of acute elevations in levels of estradiol on drug conditioned behaviors. The aim of the present study was to evaluate the influence of an acute increase in systemic estradiol levels on the expression of cocaine conditioned place preference (CPP). Using a six day conditioning procedure, ovariectomized (OVX) female rats were conditioned with one of four doses of cocaine (2.5, 5, 10, or 15mg/kg) to associate one of two large chambers of a CPP apparatus with cocaine or saline. Thirty minutes prior to the start of the CPP preference test, rats were pretreated with either 5μg estradiol benzoate (EB) or peanut oil (PO). PO-treated rats expressed a significant preference for only the mid-range conditioning doses of cocaine (5 and 10mg/kg). However, acute EB treatment resulted in a rightward shift in the cocaine dose-response curve; rats demonstrated a significant preference at only the moderate and high conditioning doses of cocaine (10 and 15mg/kg). These findings demonstrate that acute elevations in estradiol may dampen the expression of conditioned responses to cocaine's secondary rewards at lower conditioning doses of the drug and facilitate CPP at higher doses while estradiol deficiency decreases the threshold dose of cocaine necessary to induce CPP.

  8. A Novel Mutation p.A59P in N-Terminal Domain of Methyl-CpG-Binding Protein 2 Confers Phenotypic Variability in 3 Cases of Tunisian Rett Patients: Clinical Evaluations and In Silico Investigations.

    PubMed

    Kharrat, Marwa; Hsairi, Ines; Fendri-Kriaa, Nourhene; Kenoun, Houda; Othmen, Houda Ben; Ben Mahmoud, Afif; Ghorbel, Rania; Abid, Imen; Triki, Chahnez; Fakhfakh, Faiza

    2015-11-01

    Rett syndrome is a monogenic X-linked dominant neurodevelopmental disorder related to mutation in MECP2, which encodes the methyl-CpG-binding protein MeCP2. The aim of this study was to search for mutations of MECP2 gene in Tunisian Rett patients and to evaluate the impact of the found variants on structural and functional features of MeCP2. The result of mutation analysis revealed that 3 Rett patients shared the same novel heterozygous point mutation c.175G>C (p.A59P). The p.A59P mutation was located in a conserved amino acid in the N-terminal segment of MeCP2. This novel mutation confers a phenotypic variability with different clinical severity scores (3, 8, and 9) and predicted by Sift and PolyPhen to be damaging. Modeling results showed that p.A59P adds 2 hydrogen bonds and changes the structural conformation of MeCP2 with a significant root mean square deviation value (9.66 Å), suggesting that this mutation could probably affect the conformation, function and stability of MeCP2.

  9. Training communication abilities in Rett Syndrome through reading and writing

    PubMed Central

    Fabio, Rosa Angela; Castelli, Ilaria; Marchetti, Antonella; Antonietti, Alessandro

    2013-01-01

    The goal of this clinical case study is to investigate the possibility of training communication abilities in people with Rett Syndrome (RS). Usually, girls with RS never exceed the sensorimotor stage of development, but the inter-individual variability typical of RS may lead us to doubt the irrevocability of that developmental limit, especially for those girls who are engaged in cognitive rehabilitation. The case study reported here concerns a 21-year-old girl with RS who was engaged in cognitive rehabilitation training based upon the principles of Feuerstein's modificability and mediated learning theory. The training aimed to teach her basic concepts and enhance reading-writing abilities. Statistical analyses showed that the girl reached adequate reading-writing abilities, proving the validity of the cognitive intervention which allowed her to communicate by composing words with her forefinger on an alphabetic table. Although these results need to be cautiously considered as they derive from a single case study, they have implications for future cognitive rehabilitation for deeply impaired clinical conditions as in the case of RS. PMID:24367345

  10. Behavioural biomarkers of typical Rett syndrome: moving towards early identification.

    PubMed

    Einspieler, Christa; Freilinger, Michael; Marschik, Peter B

    2016-09-01

    The dynamic course of Rett syndrome (RTT) is still said to begin with a period of apparently normal development although there is mounting evidence that individuals with RTT show behavioural peculiarities and abnormalities during their infancy. Their spontaneous general movements are abnormal from birth onwards. Normal cooing vocalisation and canonical babbling (if at all required) are interspersed with abnormalities such as proto-vowel and proto-consonant alternations produced on ingressive airstream, breathy voice characteristics, and pressed or high-pitched vocalisations. The gestural repertoire is limited. Certain developmental motor and speech-language milestones are not at all acquired or show a significant delay. Besides abnormal blinking, repetitive and/or long lasting tongue protrusion, and bizarre smiling, there are already the first body and/or hand stereotypies during the first year of life. We are currently on a promising way to define a specific set of behavioural biomarkers pinpointing RTT. PMID:27514944

  11. Does negative affect mediate the relationship between daily PTSD symptoms and daily alcohol involvement in female rape victims? Evidence from 14 days of interactive voice response assessment

    PubMed Central

    Cohn, Amy; Hagman, Brett T.; Moore, Kathleen; Mitchell, Jessica; Ehlke, Sarah

    2014-01-01

    The negative reinforcement model of addiction posits that individuals may use alcohol to reduce with negative affective (NA) distress. The current study investigated the mediating effect of daily NA on the relationship between daily PTSD symptoms and same-day and next-day alcohol involvement (consumption and desire to drink) in a sample of 54 non-treatment-seeking female rape victims who completed 14 days of interactive voice response assessment. The moderating effect of lifetime alcohol use disorder diagnosis (AUD) on daily relationships was also examined. Multilevel models suggested that NA mediated the relationship between PTSD and same-day, but not next-day alcohol involvement. NA was greater on days characterized by more severe PTSD symptoms, and alcohol consumption and desire to drink were greater on days characterized by higher NA. Further, daily PTSD symptoms and NA were more strongly associated with same-day (but not next-day) alcohol consumption and desire to drink for women with an AUD than without. Results suggest that NA plays an important role in female rape victims’ daily alcohol use. Differences between women with and without an AUD indicate the need for treatment matching to sub-types of female rape victims. PMID:24731112

  12. Reduced neuronal size and mTOR pathway activity in the Mecp2 A140V Rett syndrome mouse model

    PubMed Central

    Rangasamy, Sampathkumar; Olfers, Shannon; Gerald, Brittany; Hilbert, Alex; Svejda, Sean; Narayanan, Vinodh

    2016-01-01

    Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutation in the X-linked MECP2 gene, encoding methyl-CpG-binding protein 2. We have created a mouse model ( Mecp2 A140V “knock-in” mutant) expressing the recurrent human MECP2 A140V mutation linked to an X-linked mental retardation/Rett syndrome phenotype. Morphological analyses focused on quantifying soma and nucleus size were performed on primary hippocampus and cerebellum granule neuron (CGN) cultures from mutant ( Mecp2 A140V/y) and wild type ( Mecp2 +/y) male mice. Cultured hippocampus and cerebellar granule neurons from mutant animals were significantly smaller than neurons from wild type animals. We also examined soma size in hippocampus neurons from individual female transgenic mice that express both a mutant  (maternal allele) and a wild type Mecp2 gene linked to an eGFP transgene (paternal allele). In cultures from such doubly heterozygous female mice, the size of neurons expressing the mutant (A140V) allele also showed a significant reduction compared to neurons expressing wild type MeCP2, supporting a cell-autonomous role for MeCP2 in neuronal development. IGF-1 (insulin growth factor-1) treatment of neuronal cells from Mecp2 mutant mice rescued the soma size phenotype. We also found that Mecp2   mutation leads to down-regulation of the mTOR signaling pathway, known to be involved in neuronal size regulation. Our results suggest that i) reduced neuronal size is an important in vitro cellular phenotype of Mecp2 mutation in mice, and ii) MeCP2 might play a critical role in the maintenance of neuronal structure by modulation of the mTOR pathway. The definition of a quantifiable cellular phenotype supports using neuronal size as a biomarker in the development of a high-throughput, in vitro assay to screen for compounds that rescue small neuronal phenotype (“phenotypic assay”). PMID:27781091

  13. Physical Activity Differentially Affects the Cecal Microbiota of Ovariectomized Female Rats Selectively Bred for High and Low Aerobic Capacity

    PubMed Central

    Liu, Tzu-Wen; Park, Young-Min; Holscher, Hannah D.; Padilla, Jaume; Scroggins, Rebecca J.; Welly, Rebecca; Britton, Steven L.; Koch, Lauren G.; Vieira-Potter, Victoria J.; Swanson, Kelly S.

    2015-01-01

    host metabolism and gut microbial communities of female HCR and LCR rats without ovarian function. PMID:26301712

  14. Consumption of different sources of omega-3 polyunsaturated fatty acids by growing female rats affects long bone mass and microarchitecture.

    PubMed

    Lukas, Robin; Gigliotti, Joseph C; Smith, Brenda J; Altman, Stephanie; Tou, Janet C

    2011-09-01

    Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) consumption has been reported to improve bone health. However, sources of ω-3 PUFAs differ in the type of fatty acids and structural form. The study objective was to determine the effect of various ω-3 PUFAs sources on bone during growth. Young (age 28d) female Sprague-Dawley rats were randomly assigned (n=10/group) to a high fat 12% (wt) diet consisting of either corn oil (CO) or ω-3 PUFA rich, flaxseed (FO), krill (KO), menhaden (MO), salmon (SO) or tuna (TO) for 8 weeks. Bone mass was assessed by dual-energy X-ray absorptiometry (DXA) and bone microarchitecture by micro-computed tomography (μCT). Bone turnover markers were measured by enzyme immunoassay. Lipid peroxidation was measured by calorimetric assays. Results showed that rats fed TO, rich in docosahexaenoic acid (DHA, 22:6ω-3) had higher (P<0.009) tibial bone mineral density (BMD) and bone mineral content (BMC) and lower (P=0.05) lipid peroxidation compared to the CO-fed rats. Reduced lipid peroxidation was associated with increased tibial BMD (r2=0.08, P=0.02) and BMC (r2=0.71, P=0.01). On the other hand, rats fed FO or MO, rich in alpha-linolenic acid (ALA, 18:3ω-3), improved bone microarchitecture compared to rats fed CO or SO. Serum osteocalcin was higher (P=0.03) in rats fed FO compared to rats fed SO. Serum osteocalcin was associated with improved trabecular bone microarchitecture. The animal study results suggest consuming a variety of ω-3 PUFA sources to promote bone health during the growth stage.

  15. Estrogen deprivation does not affect vascular heat shock response in female rats: a comparison with oxidative stress markers.

    PubMed

    Miragem, Antônio Azambuja; Ludwig, Mirna Stela; Heck, Thiago Gomes; Baldissera, Fernanda Giesel; dos Santos, Analu Bender; Frizzo, Matias Nunes; Homem de Bittencourt, Paulo Ivo

    2015-09-01

    Hot flashes, which involve a tiny rise in core temperature, are the most common complaint of peri- and post-menopausal women, being tightly related to decrease in estrogen levels. On the other hand, estradiol (E2) induces the expression of HSP72, a member of the 70 kDa family of heat shock proteins (HSP70), which are cytoprotective, cardioprotective, and heat inducible. Since HSP70 expression is compromised in age-related inflammatory diseases, we argued whether the capacity of triggering a robust heat shock (HS) response would be still present after E2 withdrawal. Hence, we studied the effects of HS treatment (hot tub) in female Wistar rats subjected to bilateral ovariectomy (OVX) after a 7-day washout period. Twelve h after HS, the animals were killed and aortic arches were surgically excised for molecular analyses. The results were compared with oxidative stress markers in the plasma (superoxide dismutase, catalase, and lipoperoxidation) because HSP70 expression is also sensitive to redox regulation. Extracellular (plasma) to intracellular HSP70 ratio, an index of systemic inflammatory status, was also investigated. The results showed that HS response was preserved in OVX animals, as inferred from HSP70 expression (up to 40% rise, p < 0.01) in the aortas, which was accompanied by no further alterations in oxidative stress, hematological parameters, and glycemic control either. This suggests that the lack of estrogen per se could not be solely ascribed as the unique source of low HSP70 expression as observed in long-term post-menopausal individuals. As a consequence, periodic evaluation of HSP70 status (iHSP70 vs. eHSP70) may be of clinical relevance because decreased HS response capacity is at the center of the onset of menopause-related dysfunctions.

  16. Physical Activity Differentially Affects the Cecal Microbiota of Ovariectomized Female Rats Selectively Bred for High and Low Aerobic Capacity.

    PubMed

    Liu, Tzu-Wen; Park, Young-Min; Holscher, Hannah D; Padilla, Jaume; Scroggins, Rebecca J; Welly, Rebecca; Britton, Steven L; Koch, Lauren G; Vieira-Potter, Victoria J; Swanson, Kelly S

    2015-01-01

    host metabolism and gut microbial communities of female HCR and LCR rats without ovarian function.

  17. Dairy-based preexercise meal does not affect gut comfort or time-trial performance in female cyclists.

    PubMed

    Haakonssen, Eric C; Ross, Megan L; Cato, Louise E; Nana, Alisa; Knight, Emma J; Jenkins, David G; Martin, David T; Burke, Louise M

    2014-10-01

    Some athletes avoid dairy in the meal consumed before exercise due to fears about gastrointestinal discomfort. Regular exclusion of dairy foods may unnecessarily reduce intake of high quality proteins and calcium with possible implications for body composition and bone health. This study compared the effects of meals that included (Dairy) or excluded (Control) dairy foods on gastric comfort and subsequent cycling performance. Well-trained female cyclists (n = 32; mean ± SD; 24.3 ± 4.1 y; VO(2peak) 57.1 ± 4.9 ml/kg/min) completed two trials (randomized cross-over design) in which they consumed a meal (2 g/kg carbohydrate and 54 kJ/kg) 2 hr before a 90-min cycle session (80 min at 60% maximal aerobic power followed by a 10-min time trial; TT). The dairy meal contained 3 servings of dairy foods providing ~1350 mg calcium. Gut comfort and palatability were measured using questionnaires. Performance was measured as maximum mean power during the TT (MMP10(min)). There was no statistical or clinical evidence of an effect of meal type on MMP10(min) with a mean difference (Dairy - Control) of 4 W (95% CI [-2, 9]). There was no evidence of an association between pretrial gut comfort and meal type (p = .15) or between gut comfort delta scores and meal type postmeal (p = .31), preexercise (p = .17) or postexercise (p = .80). There was no statistical or clinical evidence of a difference in palatability between meal types. In summary, substantial amounts of dairy foods can be included in meals consumed before strenuous cycling without impairing either gut comfort or performance.

  18. ESTROGEN AND AGING AFFECT THE SYNAPTIC DISTRIBUTION OF ESTROGEN RECEPTOR BETA-IMMUNOREACTIVITY IN THE CA1 REGION OF FEMALE RAT HIPPOCAMPUS

    PubMed Central

    Waters, Elizabeth M.; Yildirim, Murat; Janssen, William G.M.; Lou, W.Y. Wendy; McEwen, Bruce S.; Morrison, John H.; Milner, Teresa A.

    2010-01-01

    Estradiol (E) mediates increased synaptogenesis in the hippocampal CA1 stratum radiatum (sr) and enhances memory in young and some aged female rats, depending on dose and age. Young females rats express more estrogen receptor α (ERα) immunolabeling in CA1sr spine synapse complexes than aged rats and ERα regulation is E sensitive in young but not aged rats. The current study examined whether estrogen receptor β (ERβ) expression in spine synapse complexes may be altered by age or E treatment. Young (3–4 months) and aged (22–23 months) female rats were ovariectomized 7 days prior to implantation of silastic capsules containing either vehicle (cholesterol) or E (10% in cholesterol) for 2 days. ERβ immunoreactivity (ir) in CA1sr was quantitatively analyzed using post-embedding electron microscopy. ERβ-ir was more prominent postsynaptically than presynaptically and both age and E treatment affected its synaptic distribution. While age decreased the spine synaptic complex localization of ERβ-ir (i.e., within 60 nm of the pre- and post-synaptic membranes), E treatment increased synaptic ERβ in both young and aged rats. In addition, the E treatment, but not age, increased dendritic shaft labeling. This data demonstrates that like ERα the levels of ERβ-ir decrease in CA1 axospinous synapses with age, however, unlike ERα the levels of ERβ-ir increase in these synapses in both young and aged rats in response to E. This suggests that synaptic ERβ may be a more responsive target to E, particularly in aged females. PMID:20875808

  19. Growth performance and reproductive traits at first parity of New Zealand white female rabbits as affected by heat stress and its alleviation under Egyptian conditions.

    PubMed

    Marai, I F; Ayyat, M S; Abd el-Monem, U M

    2001-12-01

    Exposing growing and adult New Zealand White (NZW) female rabbits to severe heat stress (temperature-humidity index = 28.9) during summer adversely affected their growth and reproductive traits. The traits that declined significantly (p < 0.01) were the live body weight, daily weight gain and feed intake of growing rabbits, and the litter size and litter weight at weaning (p < 0.05) and the pre-weaning weight gain of pups (p < 0.01) for adult females. The conception rate declined considerably with heat stress. The declines in the values of the digestibility coefficients due to heat stress were 7.9% (p < 0.05) for dry matter (DM), 8.1% (p < 0.05) for crude protein (CP) and 1.0% for crude fibre (CF). The traits that increased significantly (p < 0.01) due to heat stress were water intake, water/feed ratio and rectal temperature in growing rabbits and pre-weaning mortality for adult females. Alleviation of heat stress in the growing and adult female NZW rabbits was more efficient with drinking cool water (10-15 degrees C; between 10:00 and 17:00) than with supplementation with palm oil (as a source of energy) or natural clay (as a natural enhancer to growth and milk production). Supplying the animals with cool drinking water gave the highest body weight and weight gain, conception rate, litter size and weight and digestibility coefficients for DM and CP and the lowest rectal temperature, respiration rate and pre-weaning mortality. The loss in rabbit production pertaining to heat stress estimated from the percentages of decline in conception rate x pre-weaning mortality x litter weight at weaning was 73.0%. The provision of cool water restored 11/12 of heat loss. PMID:11770200

  20. Excitatory synapses are stronger in the hippocampus of Rett syndrome mice due to altered synaptic trafficking of AMPA-type glutamate receptors

    PubMed Central

    Li, Wei; Xu, Xin

    2016-01-01

    Deficits in long-term potentiation (LTP) at central excitatory synapses are thought to contribute to cognitive impairments in neurodevelopmental disorders associated with intellectual disability and autism. Using the methyl-CpG-binding protein 2 (Mecp2) knockout (KO) mouse model of Rett syndrome, we show that naïve excitatory synapses onto hippocampal pyramidal neurons of symptomatic mice have all of the hallmarks of potentiated synapses. Stronger Mecp2 KO synapses failed to undergo LTP after either theta-burst afferent stimulation or pairing afferent stimulation with postsynaptic depolarization. On the other hand, basal synaptic strength and LTP were not affected in slices from younger presymptomatic Mecp2 KO mice. Furthermore, spine synapses in pyramidal neurons from symptomatic Mecp2 KO are larger and do not grow in size or incorporate GluA1 subunits after electrical or chemical LTP. Our data suggest that LTP is occluded in Mecp2 KO mice by already potentiated synapses. The higher surface levels of GluA1-containing receptors are consistent with altered expression levels of proteins involved in AMPA receptor trafficking, suggesting previously unidentified targets for therapeutic intervention for Rett syndrome and other MECP2-related disorders. PMID:26929363

  1. Excitatory synapses are stronger in the hippocampus of Rett syndrome mice due to altered synaptic trafficking of AMPA-type glutamate receptors.

    PubMed

    Li, Wei; Xu, Xin; Pozzo-Miller, Lucas

    2016-03-15

    Deficits in long-term potentiation (LTP) at central excitatory synapses are thought to contribute to cognitive impairments in neurodevelopmental disorders associated with intellectual disability and autism. Using the methyl-CpG-binding protein 2 (Mecp2) knockout (KO) mouse model of Rett syndrome, we show that naïve excitatory synapses onto hippocampal pyramidal neurons of symptomatic mice have all of the hallmarks of potentiated synapses. Stronger Mecp2 KO synapses failed to undergo LTP after either theta-burst afferent stimulation or pairing afferent stimulation with postsynaptic depolarization. On the other hand, basal synaptic strength and LTP were not affected in slices from younger presymptomatic Mecp2 KO mice. Furthermore, spine synapses in pyramidal neurons from symptomatic Mecp2 KO are larger and do not grow in size or incorporate GluA1 subunits after electrical or chemical LTP. Our data suggest that LTP is occluded in Mecp2 KO mice by already potentiated synapses. The higher surface levels of GluA1-containing receptors are consistent with altered expression levels of proteins involved in AMPA receptor trafficking, suggesting previously unidentified targets for therapeutic intervention for Rett syndrome and other MECP2-related disorders.

  2. Cytokines profile and peripheral blood mononuclear cells morphology in Rett and autistic patients.

    PubMed

    Pecorelli, Alessandra; Cervellati, Franco; Belmonte, Giuseppe; Montagner, Giulia; Waldon, PhiAnh; Hayek, Joussef; Gambari, Roberto; Valacchi, Giuseppe

    2016-01-01

    A potential role for immune dysfunction in autism spectrum disorders (ASD) has been well established. However, immunological features of Rett syndrome (RTT), a genetic neurodevelopmental disorder closely related to autism, have not been well addressed yet. By using multiplex Luminex technology, a panel of 27 cytokines and chemokines was evaluated in serum from 10 RTT patients with confirmed diagnosis of MECP2 mutation (typical RTT), 12 children affected by classic autistic disorder and 8 control subjects. The cytokine/chemokine gene expression was assessed by real time PCR on mRNA of isolated peripheral blood mononuclear cells (PBMCs). Moreover, ultrastructural analysis of PBMCs was performed using transmission electron microscopy (TEM). Significantly higher serum levels of interleukin-8 (IL-8), IL-9, IL-13 were detected in RTT compared to control subjects, and IL-15 shows a trend toward the upregulation in RTT. In addition, IL-1β and VEGF were the only down-regulated cytokines in autistic patients with respect to RTT. No difference in cytokine/chemokine profile between autistic and control groups was detected. These data were also confirmed by ELISA real time PCR. At the ultrastructural level, the most severe morphological abnormalities were observed in mitochondria of both RTT and autistic PBMCs. In conclusion, our study shows a deregulated cytokine/chemokine profile together with morphologically altered immune cells in RTT. Such abnormalities were not quite as evident in autistic subjects. These findings indicate a possible role of immune dysfunction in RTT making the clinical features of this pathology related also to the immunology aspects, suggesting, therefore, novel possible therapeutic interventions for this disorder.

  3. An optogenetic mouse model of rett syndrome targeting on catecholaminergic neurons.

    PubMed

    Zhang, Shuang; Johnson, Christopher M; Cui, Ningren; Xing, Hao; Zhong, Weiwei; Wu, Yang; Jiang, Chun

    2016-10-01

    Rett syndrome (RTT) is a neurodevelopmental disorder affecting multiple functions, including the norepinephrine (NE) system. In the CNS, NE is produced mostly by neurons in the locus coeruleus (LC), where defects in intrinsic neuronal properties, NE biosynthetic enzymes, neuronal CO2 sensitivity, and synaptic currents have been reported in mouse models of RTT. LC neurons in methyl-CpG-binding protein 2 gene (Mecp2) null mice show a high rate of spontaneous firing, although whether such hyperexcitability might increase or decrease the NE release from synapses is unknown. To activate the NEergic axonal terminals selectively, we generated an optogenetic mouse model of RTT in which NEergic neuronal excitability can be manipulated with light. Using commercially available mouse breeders, we produced a new strain of double-transgenic mice with Mecp2 knockout and channelrhodopsin (ChR) knockin in catecholaminergic neurons. Several RTT-like phenotypes were found in the tyrosine hydroxylase (TH)-ChR-Mecp2(-/Y) mice, including hypoactivity, low body weight, hindlimb clasping, and breathing disorders. In brain slices, optostimulation produced depolarization and an increase in the firing rate of LC neurons from TH-ChR control mice. In TH-ChR control mice, optostimulation of presynaptic NEergic neurons augmented the firing rate of hypoglossal neurons (HNs), which was blocked by the α-adrenoceptor antagonist phentolamine. Such optostimulation of NEergic terminals had almost no effect on HNs from two or three TH-ChR-Mecp2(-/Y) mice, indicating that excessive excitation of presynaptic neurons does not benefit NEergic modulation in mice with Mecp2 disruption. These results also demonstrate the feasibility of generating double-transgenic mice for studies of RTT with commercially available mice, which are inexpensive, labor/time efficient, and promising for cell-specific stimulation. © 2016 Wiley Periodicals, Inc. PMID:27317352

  4. X-Chromosome Inactivation in Rett Syndrome Human Induced Pluripotent Stem Cells

    PubMed Central

    Cheung, Aaron Y. L.; Horvath, Lindsay M.; Carrel, Laura; Ellis, James

    2012-01-01

    Rett syndrome (RTT) is a neurodevelopmental disorder that affects girls due primarily to heterozygous mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MECP2). Random X-chromosome inactivation (XCI) results in cellular mosaicism in which some cells express wild-type (WT) MECP2 while other cells express mutant MECP2. The generation of patient-specific human induced pluripotent stem cells (hiPSCs) facilitates the production of RTT-hiPSC-derived neurons in vitro to investigate disease mechanisms and identify novel drug treatments. The generation of RTT-hiPSCs has been reported by many laboratories, however, the XCI status of RTT-hiPSCs has been inconsistent. Some report RTT-hiPSCs retain the inactive X-chromosome (post-XCI) of the founder somatic cell allowing isogenic RTT-hiPSCs that express only the WT or mutant MECP2 allele to be isolated from the same patient. Post-XCI RTT-hiPSCs-derived neurons retain this allele-specific expression pattern of WT or mutant MECP2. Conversely, others report RTT-hiPSCs in which the inactive X-chromosome of the founder somatic cell reactivates (pre-XCI) upon reprogramming into RTT-hiPSCs. Pre-XCI RTT-hiPSC-derived neurons exhibit random XCI resulting in cellular mosaicism with respect to WT and mutant MECP2 expression. Here we review and attempt to interpret the inconsistencies in XCI status of RTT-hiPSCs generated to date by comparison to other pluripotent systems in vitro and in vivo and the methods used to analyze XCI. Finally, we discuss the relative strengths and weaknesses of post- and pre-XCI hiPSCs in the context of RTT, and other X-linked and autosomal disorders for translational medicine. PMID:22470355

  5. MECP2 Duplication Syndrome: Evidence of Enhanced Oxidative Stress. A Comparison with Rett Syndrome

    PubMed Central

    Leoncini, Silvia; Møller, Rikke S.; Zollo, Gloria; Buoni, Sabrina; Cortelazzo, Alessio; Guerranti, Roberto; Durand, Thierry; Ciccoli, Lucia; D’Esposito, Maurizio; Ravn, Kirstine; Hayek, Joussef

    2016-01-01

    Rett syndrome (RTT) and MECP2 duplication syndrome (MDS) are neurodevelopmental disorders caused by alterations in the methyl-CpG binding protein 2 (MECP2) gene expression. A relationship between MECP2 loss-of-function mutations and oxidative stress has been previously documented in RTT patients and murine models. To date, no data on oxidative stress have been reported for the MECP2 gain-of-function mutations in patients with MDS. In the present work, the pro-oxidant status and oxidative fatty acid damage in MDS was investigated (subjects n = 6) and compared to RTT (subjects n = 24) and healthy condition (subjects n = 12). Patients with MECP2 gain-of-function mutations showed increased oxidative stress marker levels (plasma non-protein bound iron, intraerythrocyte non-protein bound iron, F2-isoprostanes, and F4-neuroprostanes), as compared to healthy controls (P ≤ 0.05). Such increases were similar to those observed in RTT patients except for higher plasma F2-isoprostanes levels (P < 0.0196). Moreover, plasma levels of F2-isoprostanes were significantly correlated (P = 0.0098) with the size of the amplified region. The present work shows unique data in patients affected by MDS. For the first time MECP2 gain-of-function mutations are indicated to be linked to an oxidative damage and related clinical symptoms overlapping with those of MECP2 loss-of-function mutations. A finely tuned balance of MECP2 expression appears to be critical to oxidative stress homeostasis, thus shedding light on the relevance of the redox balance in the central nervous system integrity. PMID:26930212

  6. An optogenetic mouse model of rett syndrome targeting on catecholaminergic neurons.

    PubMed

    Zhang, Shuang; Johnson, Christopher M; Cui, Ningren; Xing, Hao; Zhong, Weiwei; Wu, Yang; Jiang, Chun

    2016-10-01

    Rett syndrome (RTT) is a neurodevelopmental disorder affecting multiple functions, including the norepinephrine (NE) system. In the CNS, NE is produced mostly by neurons in the locus coeruleus (LC), where defects in intrinsic neuronal properties, NE biosynthetic enzymes, neuronal CO2 sensitivity, and synaptic currents have been reported in mouse models of RTT. LC neurons in methyl-CpG-binding protein 2 gene (Mecp2) null mice show a high rate of spontaneous firing, although whether such hyperexcitability might increase or decrease the NE release from synapses is unknown. To activate the NEergic axonal terminals selectively, we generated an optogenetic mouse model of RTT in which NEergic neuronal excitability can be manipulated with light. Using commercially available mouse breeders, we produced a new strain of double-transgenic mice with Mecp2 knockout and channelrhodopsin (ChR) knockin in catecholaminergic neurons. Several RTT-like phenotypes were found in the tyrosine hydroxylase (TH)-ChR-Mecp2(-/Y) mice, including hypoactivity, low body weight, hindlimb clasping, and breathing disorders. In brain slices, optostimulation produced depolarization and an increase in the firing rate of LC neurons from TH-ChR control mice. In TH-ChR control mice, optostimulation of presynaptic NEergic neurons augmented the firing rate of hypoglossal neurons (HNs), which was blocked by the α-adrenoceptor antagonist phentolamine. Such optostimulation of NEergic terminals had almost no effect on HNs from two or three TH-ChR-Mecp2(-/Y) mice, indicating that excessive excitation of presynaptic neurons does not benefit NEergic modulation in mice with Mecp2 disruption. These results also demonstrate the feasibility of generating double-transgenic mice for studies of RTT with commercially available mice, which are inexpensive, labor/time efficient, and promising for cell-specific stimulation. © 2016 Wiley Periodicals, Inc.

  7. MECP2 Duplication Syndrome: Evidence of Enhanced Oxidative Stress. A Comparison with Rett Syndrome.

    PubMed

    Signorini, Cinzia; De Felice, Claudio; Leoncini, Silvia; Møller, Rikke S; Zollo, Gloria; Buoni, Sabrina; Cortelazzo, Alessio; Guerranti, Roberto; Durand, Thierry; Ciccoli, Lucia; D'Esposito, Maurizio; Ravn, Kirstine; Hayek, Joussef

    2016-01-01

    Rett syndrome (RTT) and MECP2 duplication syndrome (MDS) are neurodevelopmental disorders caused by alterations in the methyl-CpG binding protein 2 (MECP2) gene expression. A relationship between MECP2 loss-of-function mutations and oxidative stress has been previously documented in RTT patients and murine models. To date, no data on oxidative stress have been reported for the MECP2 gain-of-function mutations in patients with MDS. In the present work, the pro-oxidant status and oxidative fatty acid damage in MDS was investigated (subjects n = 6) and compared to RTT (subjects n = 24) and healthy condition (subjects n = 12). Patients with MECP2 gain-of-function mutations showed increased oxidative stress marker levels (plasma non-protein bound iron, intraerythrocyte non-protein bound iron, F2-isoprostanes, and F4-neuroprostanes), as compared to healthy controls (P ≤ 0.05). Such increases were similar to those observed in RTT patients except for higher plasma F2-isoprostanes levels (P < 0.0196). Moreover, plasma levels of F2-isoprostanes were significantly correlated (P = 0.0098) with the size of the amplified region. The present work shows unique data in patients affected by MDS. For the first time MECP2 gain-of-function mutations are indicated to be linked to an oxidative damage and related clinical symptoms overlapping with those of MECP2 loss-of-function mutations. A finely tuned balance of MECP2 expression appears to be critical to oxidative stress homeostasis, thus shedding light on the relevance of the redox balance in the central nervous system integrity.

  8. Suggestions for Educational and Therapeutic Interventions with the Rett Syndrome Child.

    ERIC Educational Resources Information Center

    International Rett Syndrome Association, Inc., Fort Washington, MD.

    This paper comprises a compilation of nine case studies of girls (aged 4-16 years) with Rett Syndrome. The educational settings involved are various and include private day school, public elementary school in both integrated and special needs classrooms, and a county-operated preschool program for handicapped children. Each case study outlines the…

  9. Expression profiling of clonal lymphocyte cell cultures from Rett syndrome patients

    Technology Transfer Automated Retrieval System (TEKTRAN)

    More than 85% of Rett syndrome (RTT) patients have heterozygous mutations in the X-linked MECP2 gene which encodes methyl-CpG-binding protein 2, a transcriptional repressor that binds methylated CpG sites. Because MECP2 is subject to X chromosome inactivation (XCI), girls with RTT express either the...

  10. Vitamin D deficiency is prevalent in girls and women with rett syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The aim of the study was to determine the prevalence of vitamin D deficiency and identify the relation between 25-hydroxyvitamin D (25-(OH)D) levels and the consumption of dietary sources of vitamin D or exposure to anticonvulsants in girls and women with Rett syndrome (RTT). Retrospective review of...

  11. Is the early development of girls with Rett disorder really normal?

    PubMed

    Einspieler, Christa; Kerr, Alison M; Prechtl, Heinz F R

    2005-05-01

    An apparently normal early development was one of the initial criteria for classical Rett syndrome. However, several investigators considered Rett syndrome to be a developmental disorder manifesting very soon after birth. Videos of 22 Rett cases were assessed carefully for movements, posture, and behavior during the first 6 mo of life. All signs that deviated from the normal standard were recorded meticulously. Special attention was paid to the face, the hands, and body movements. A detailed analysis clearly demonstrated an abnormal quality of general movements (100%), tongue protrusion (62%), postural stiffness (58%), asymmetric eye opening and closing (56%), abnormal finger movements (52%), hand stereotypies (42%), bursts of abnormal facial expressions (42%), bizarre smile (32%), tremor (28%), and stereotyped body movements (15%). Our study is the first to apply specific standardized measures of early spontaneous movements to Rett infants, proving conclusively that the disorder is manifested within the first months of life. Although not necessarily specific, the signs that we have observed will be of value in alerting clinicians to the possibility of the diagnosis at an early stage, when intervention is likely to be most effective.

  12. Brief Report:MECP2 Mutations in People without Rett Syndrome

    ERIC Educational Resources Information Center

    Suter, Bernhard; Treadwell-Deering, Diane; Zoghbi, Huda Y.; Glaze, Daniel G.; Neul, Jeffrey L.

    2014-01-01

    Mutations in "Methyl-CpG-Binding protein 2" ("MECP2") are commonly associated with the neurodevelopmental disorder Rett syndrome (RTT). However, some people with RTT do not have mutations in "MECP2," and interestingly there have been people identified with "MECP2" mutations that do not have the clinical…

  13. Social Impairments in Rett Syndrome: Characteristics and Relationship with Clinical Severity

    ERIC Educational Resources Information Center

    Kaufmann, W. E.; Tierney, E.; Rohde, C. A.; Suarez-Pedraza, M. C.; Clarke, M. A.; Salorio, C. F.; Bibat, G.; Bukelis, I.; Naram, D.; Lanham, D. C.; Naidu, S.

    2012-01-01

    Background: While behavioural abnormalities are fundamental features of Rett syndrome (RTT), few studies have examined the RTT behavioural phenotype. Most of these reports have focused on autistic features, linked to the early regressive phase of the disorder, and few studies have applied standardised behavioural measures. We used a battery of…

  14. Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes.

    PubMed

    Chao, Hsiao-Tuan; Chen, Hongmei; Samaco, Rodney C; Xue, Mingshan; Chahrour, Maria; Yoo, Jong; Neul, Jeffrey L; Gong, Shiaoching; Lu, Hui-Chen; Heintz, Nathaniel; Ekker, Marc; Rubenstein, John L R; Noebels, Jeffrey L; Rosenmund, Christian; Zoghbi, Huda Y

    2010-11-11

    Mutations in the X-linked MECP2 gene, which encodes the transcriptional regulator methyl-CpG-binding protein 2 (MeCP2), cause Rett syndrome and several neurodevelopmental disorders including cognitive disorders, autism, juvenile-onset schizophrenia and encephalopathy with early lethality. Rett syndrome is characterized by apparently normal early development followed by regression, motor abnormalities, seizures and features of autism, especially stereotyped behaviours. The mechanisms mediating these features are poorly understood. Here we show that mice lacking Mecp2 from GABA (γ-aminobutyric acid)-releasing neurons recapitulate numerous Rett syndrome and autistic features, including repetitive behaviours. Loss of MeCP2 from a subset of forebrain GABAergic neurons also recapitulates many features of Rett syndrome. MeCP2-deficient GABAergic neurons show reduced inhibitory quantal size, consistent with a presynaptic reduction in glutamic acid decarboxylase 1 (Gad1) and glutamic acid decarboxylase 2 (Gad2) levels, and GABA immunoreactivity. These data demonstrate that MeCP2 is critical for normal function of GABA-releasing neurons and that subtle dysfunction of GABAergic neurons contributes to numerous neuropsychiatric phenotypes. PMID:21068835

  15. Physical and Mental Health of Mothers Caring for a Child with Rett Syndrome

    ERIC Educational Resources Information Center

    Laurvick, Crystal L.; Msall, Michael E.; Silburn, Sven; Bower, Carol; de Klerk, Nicholas; Leonard, Helen

    2007-01-01

    Objectives: Our goal was to investigate the physical and mental health of mothers who care for a child with Rett syndrome. Methods: We assessed maternal physical and mental health by using the SF-12 version 1 physical component summary and mental component summary scores as the outcome measures of interest. Mothers (n = 135) of children with Rett…

  16. Cognitive Performance in Rett Syndrome Girls: A Pilot Study Using Eyetracking Technology

    ERIC Educational Resources Information Center

    Baptista, P. M.; Mercadante, M. T.; Macedo, E. C.; Schwartzman, J. S.

    2006-01-01

    Background: Rett syndrome (RS) is a pervasive developmental disorder with cognitive and neuromotor impairments (including loss of handiness and loss of communicative skills). Objective: To verify whether girls with RS use their gaze intentionally, by observing their performance in three cognitive tasks: (1) verbal instruction condition (look at…

  17. Fostering Environmental Control in a Young Child with Rett Syndrome: A Case Study.

    ERIC Educational Resources Information Center

    Sullivan, Margaret Wolan; And Others

    1995-01-01

    The performance of a 3-year-old with Rett Syndrome in a Contingency Intervention Program using head and hand switches and adapted toys was assessed over 18 months. Learning contingent control of the stimuli positively motivated the child, promoted attention to toys and objects, and generalized to the classroom. (SW)

  18. Development of a Video-Based Evaluation Tool in Rett Syndrome

    ERIC Educational Resources Information Center

    Fyfe, S.; Downs, J.; McIlroy, O.; Burford, B.; Lister, J.; Reilly, S.; Laurvick, C. L.; Philippe, C.; Msall, M.; Kaufmann, W. E.; Ellaway, C.; Leonard, H.

    2007-01-01

    This paper describes the development of a video-based evaluation tool for use in Rett syndrome (RTT). Components include a parent-report checklist, and video filming and coding protocols that contain items on eating, drinking, communication, hand function and movements, personal care and mobility. Ninety-seven of the 169 families who initially…

  19. Sleep Disturbance in Children with Rett Syndrome: A Qualitative Investigation of the Parental Experience

    ERIC Educational Resources Information Center

    McDougall, Allyson; Kerr, Alison M.; Espie, Colin A.

    2005-01-01

    Background: Sleep problems in children with intellectual disability can be precipitated and maintained by intrinsic and external factors. The present study comprised a qualitative investigation of the experiences of parents of children with Rett syndrome, a neurodevelopmental disorder where sleep disturbance is common. Method: Audio-taped…

  20. Peculiarities in the Gestural Repertoire: An Early Marker for Rett Syndrome?

    ERIC Educational Resources Information Center

    Marschik, Peter B.; Sigafoos, Jeff; Kaufmann, Walter E.; Wolin, Thomas; Talisa, Victor B.; Bartl-Pokorny, Katrin D.; Budimirovic, Dejan B.; Vollmann, Ralf; Einspieler, Christa

    2012-01-01

    We studied the gestures used by children with classic Rett syndrome (RTT) to provide evidence as to how this essential aspect of communicative functions develops. Seven participants with RTT were longitudinally observed between 9 and 18 months of life. The gestures used by these participants were transcribed and coded from a retrospective analysis…

  1. Degraded neural and behavioral processing of speech sounds in a rat model of Rett syndrome.

    PubMed

    Engineer, Crystal T; Rahebi, Kimiya C; Borland, Michael S; Buell, Elizabeth P; Centanni, Tracy M; Fink, Melyssa K; Im, Kwok W; Wilson, Linda G; Kilgard, Michael P

    2015-11-01

    Individuals with Rett syndrome have greatly impaired speech and language abilities. Auditory brainstem responses to sounds are normal, but cortical responses are highly abnormal. In this study, we used the novel rat Mecp2 knockout model of Rett syndrome to document the neural and behavioral processing of speech sounds. We hypothesized that both speech discrimination ability and the neural response to speech sounds would be impaired in Mecp2 rats. We expected that extensive speech training would improve speech discrimination ability and the cortical response to speech sounds. Our results reveal that speech responses across all four auditory cortex fields of Mecp2 rats were hyperexcitable, responded slower, and were less able to follow rapidly presented sounds. While Mecp2 rats could accurately perform consonant and vowel discrimination tasks in quiet, they were significantly impaired at speech sound discrimination in background noise. Extensive speech training improved discrimination ability. Training shifted cortical responses in both Mecp2 and control rats to favor the onset of speech sounds. While training increased the response to low frequency sounds in control rats, the opposite occurred in Mecp2 rats. Although neural coding and plasticity are abnormal in the rat model of Rett syndrome, extensive therapy appears to be effective. These findings may help to explain some aspects of communication deficits in Rett syndrome and suggest that extensive rehabilitation therapy might prove beneficial.

  2. An Effective Computer-Based Requesting System for Persons with Rett Syndrome.

    ERIC Educational Resources Information Center

    Van Acker, Richard; Grant, Sharon H.

    1995-01-01

    This study explored the use of a computer-based requesting system, employing animated graphics and touch-sensitive screen input, with three girls with Rett syndrome (characterized by severe motor disorder, impaired cognitive function, and language disorder). All three girls displayed increased item requesting when provided computer-based…

  3. Supporting Communication of Girls with Rett Syndrome and Their Mothers in Storybook Reading.

    ERIC Educational Resources Information Center

    Koppenhaver, David A.; Erickson, Karen A.; Skotko, Brian G.

    2001-01-01

    In this study, mother-child storybook reading was explored as a context within which to support early symbolic communication of four girls (ages 3-7) with Rett syndrome. Access to communication symbols, assistive technologies, and parent training consistently enhanced children's frequency of labeling/commenting and appropriate symbolic…

  4. Parent Reading Behaviors and Communication Outcomes in Girls with Rett Syndrome

    ERIC Educational Resources Information Center

    Skotko, Brian G.; Koppenhaver, Dave A.; Erickson, Karen A.

    2004-01-01

    We describe evidence and intervention strategies for parents, educators, and researchers who seek to enhance communication and literacy in children with Rett syndrome (RS). Four girls with RS and their mothers videotaped their storybook interactions at home for 4 months. Parent-child storybook interactions were coded for child behaviors (e.g., use…

  5. Cognitive and Adaptive Functioning in 28 Girls with Rett Syndrome. Brief Report.

    ERIC Educational Resources Information Center

    Perry, Adrienne; And Others

    1991-01-01

    This study of 28 girls (ages 2-19) with Rett Syndrome found profound handicaps in the intellectual and adaptive areas, according to standardized tests. Subjects seemed capable of learning some self-help skills at a basic level. The Cattell Mental Age was significantly negatively correlated with chronological age. (JDD)

  6. The Use of Assistive Technology for Symbol Identification by Children with Rett Syndrome.

    ERIC Educational Resources Information Center

    Hetzroni, Orit; Rubin, Corinne; Konkol, Orna

    2002-01-01

    A study investigated whether the use of assistive technology would assist in the ability to identify symbols by three girls (ages 8-10) with Rett syndrome. Individualized multimedia programs resulted in a steady learning curve across symbol sets and a partial retention of knowledge throughout maintenance probes. (Contains references.) (CR)

  7. Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes.

    PubMed

    Chao, Hsiao-Tuan; Chen, Hongmei; Samaco, Rodney C; Xue, Mingshan; Chahrour, Maria; Yoo, Jong; Neul, Jeffrey L; Gong, Shiaoching; Lu, Hui-Chen; Heintz, Nathaniel; Ekker, Marc; Rubenstein, John L R; Noebels, Jeffrey L; Rosenmund, Christian; Zoghbi, Huda Y

    2010-11-11

    Mutations in the X-linked MECP2 gene, which encodes the transcriptional regulator methyl-CpG-binding protein 2 (MeCP2), cause Rett syndrome and several neurodevelopmental disorders including cognitive disorders, autism, juvenile-onset schizophrenia and encephalopathy with early lethality. Rett syndrome is characterized by apparently normal early development followed by regression, motor abnormalities, seizures and features of autism, especially stereotyped behaviours. The mechanisms mediating these features are poorly understood. Here we show that mice lacking Mecp2 from GABA (γ-aminobutyric acid)-releasing neurons recapitulate numerous Rett syndrome and autistic features, including repetitive behaviours. Loss of MeCP2 from a subset of forebrain GABAergic neurons also recapitulates many features of Rett syndrome. MeCP2-deficient GABAergic neurons show reduced inhibitory quantal size, consistent with a presynaptic reduction in glutamic acid decarboxylase 1 (Gad1) and glutamic acid decarboxylase 2 (Gad2) levels, and GABA immunoreactivity. These data demonstrate that MeCP2 is critical for normal function of GABA-releasing neurons and that subtle dysfunction of GABAergic neurons contributes to numerous neuropsychiatric phenotypes.

  8. Report of the first case of precocious puberty in Rett syndrome.

    PubMed

    Baş, Veysel Nijat; Çetinkaya, Semra; Ağladıoğlu, Sebahat Yılmaz; Aksoy, Ayşe; Gülpınar, Başak; Aycan, Zehra

    2013-01-01

    Rett syndrome is an X-linked dominant disorder frequently caused by the mutations in the methyl-CpG-binding protein 2 gene (MECP2). Its prevalence in the population is 1/15,000-20,000. Patients with Rett syndrome present apparently normal psychomotor developments during the first 6-18 months of life. Subsequently, they show a short period of developmental stagnation followed by a rapid regression in language and motor development. Precocious puberty is characterized by premature breast and pubic hair development, and advanced bone age development at 8 years of age. We present a case of Rett syndrome and precocious puberty in a 6-year-old girl. At the age of 6, the first signs of precocious puberty appeared (Tanner stage 3). Laboratory measurements were detected as follows: luteinizing hormone (LH), 0.2 mIU/mL; follicle-stimulating hormone (FSH), 1.1 mIU/mL; estradiol, 36 pg/mL; bone age, 9 years. The response to luteinizing hormone releasing hormone (gonadotropin-releasing hormone stimulation test) was characteristic for true precocious puberty (LH, 32 mIU/mL; FSH, 26 mIU/mL). This is the first reported case of precocious puberty related to Rett syndrome.

  9. Dietary antioxidants and flight exercise in female birds affect allocation of nutrients to eggs: how carry-over effects work.

    PubMed

    Skrip, Megan M; Seeram, Navindra P; Yuan, Tao; Ma, Hang; McWilliams, Scott R

    2016-09-01

    Physiological challenges during one part of the annual cycle can carry over and affect performance at a subsequent phase, and antioxidants could be one mediator of trade-offs between phases. We performed a controlled experiment with zebra finches to examine how songbirds use nutrition to manage trade-offs in antioxidant allocation between endurance flight and subsequent reproduction. Our treatment groups included (1) a non-supplemented, non-exercised group (control group) fed a standard diet with no exercise beyond that experienced during normal activity in an aviary; (2) a supplemented non-exercised group fed a water- and lipid-soluble antioxidant-supplemented diet with no exercise; (3) a non-supplemented exercised group fed a standard diet and trained to perform daily endurance flight for 6 weeks; and (4) a supplemented exercised group fed an antioxidant-supplemented diet and trained to perform daily flight for 6 weeks. After flight training, birds were paired within treatment groups for breeding. We analyzed eggs for lutein and vitamin E concentrations and the plasma of parents throughout the experiment for non-enzymatic antioxidant capacity and oxidative damage. Exercised birds had higher oxidative damage levels than non-exercised birds after flight training, despite supplementation with dietary antioxidants. Supplementation with water-soluble antioxidants decreased the deposition of lipid-soluble antioxidants into eggs and decreased yolk size. Flight exercise also lowered deposition of lutein, but not vitamin E, to eggs. These findings have important implications for future studies of wild birds during migration and other oxidative challenges.

  10. Dietary antioxidants and flight exercise in female birds affect allocation of nutrients to eggs: how carry-over effects work.

    PubMed

    Skrip, Megan M; Seeram, Navindra P; Yuan, Tao; Ma, Hang; McWilliams, Scott R

    2016-09-01

    Physiological challenges during one part of the annual cycle can carry over and affect performance at a subsequent phase, and antioxidants could be one mediator of trade-offs between phases. We performed a controlled experiment with zebra finches to examine how songbirds use nutrition to manage trade-offs in antioxidant allocation between endurance flight and subsequent reproduction. Our treatment groups included (1) a non-supplemented, non-exercised group (control group) fed a standard diet with no exercise beyond that experienced during normal activity in an aviary; (2) a supplemented non-exercised group fed a water- and lipid-soluble antioxidant-supplemented diet with no exercise; (3) a non-supplemented exercised group fed a standard diet and trained to perform daily endurance flight for 6 weeks; and (4) a supplemented exercised group fed an antioxidant-supplemented diet and trained to perform daily flight for 6 weeks. After flight training, birds were paired within treatment groups for breeding. We analyzed eggs for lutein and vitamin E concentrations and the plasma of parents throughout the experiment for non-enzymatic antioxidant capacity and oxidative damage. Exercised birds had higher oxidative damage levels than non-exercised birds after flight training, despite supplementation with dietary antioxidants. Supplementation with water-soluble antioxidants decreased the deposition of lipid-soluble antioxidants into eggs and decreased yolk size. Flight exercise also lowered deposition of lutein, but not vitamin E, to eggs. These findings have important implications for future studies of wild birds during migration and other oxidative challenges. PMID:27582563

  11. Mutations in JMJD1C are involved in Rett syndrome and intellectual disability

    PubMed Central

    Sáez, Mauricio A.; Fernández-Rodríguez, Juana; Moutinho, Catia; Sanchez-Mut, Jose V.; Gomez, Antonio; Vidal, Enrique; Petazzi, Paolo; Szczesna, Karolina; Lopez-Serra, Paula; Lucariello, Mario; Lorden, Patricia; Delgado-Morales, Raul; de la Caridad, Olga J.; Huertas, Dori; Gelpí, Josep L.; Orozco, Modesto; López-Doriga, Adriana; Milà, Montserrat; Perez-Jurado, Luís A.; Pineda, Mercedes; Armstrong, Judith; Lázaro, Conxi; Esteller, Manel

    2016-01-01

    Purpose: Autism spectrum disorders are associated with defects in social response and communication that often occur in the context of intellectual disability. Rett syndrome is one example in which epilepsy, motor impairment, and motor disturbance may co-occur. Mutations in histone demethylases are known to occur in several of these syndromes. Herein, we aimed to identify whether mutations in the candidate histone demethylase JMJD1C (jumonji domain containing 1C) are implicated in these disorders. Genet Med 18 1, 378–385. Methods: We performed the mutational and functional analysis of JMJD1C in 215 cases of autism spectrum disorders, intellectual disability, and Rett syndrome without a known genetic defect. Genet Med 18 1, 378–385. Results: We found seven JMJD1C variants that were not present in any control sample (~ 6,000) and caused an amino acid change involving a different functional group. From these, two de novo JMJD1C germline mutations were identified in a case of Rett syndrome and in a patient with intellectual disability. The functional study of the JMJD1C mutant Rett syndrome patient demonstrated that the altered protein had abnormal subcellular localization, diminished activity to demethylate the DNA damage-response protein MDC1, and reduced binding to MECP2. We confirmed that JMJD1C protein is widely expressed in brain regions and that its depletion compromises dendritic activity. Genet Med 18 1, 378–385. Conclusions: Our findings indicate that mutations in JMJD1C contribute to the development of Rett syndrome and intellectual disability. Genet Med 18 1, 378–385. PMID:26181491

  12. Prenatal LPS-exposure--a neurodevelopmental rat model of schizophrenia--differentially affects cognitive functions, myelination and parvalbumin expression in male and female offspring.

    PubMed

    Wischhof, Lena; Irrsack, Ellen; Osorio, Carmen; Koch, Michael

    2015-03-01

    Maternal infection during pregnancy increases the risk for the offspring to develop schizophrenia. Gender differences can be seen in various features of the illness and sex steroid hormones (e.g. estrogen) have strongly been implicated in the disease pathology. In the present study, we evaluated sex differences in the effects of prenatal exposure to a bacterial endotoxin (lipopolysaccharide, LPS) in rats. Pregnant dams received LPS-injections (100 μg/kg) at gestational day 15 and 16. The offspring was then tested for prepulse inhibition (PPI), locomotor activity, anxiety-like behavior and object recognition memory at various developmental time points. At postnatal day (PD) 33 and 60, prenatally LPS-exposed rats showed locomotor hyperactivity which was similar in male and female offspring. Moreover, prenatal LPS-treatment caused PPI deficits in pubertal (PD45) and adult (PD90) males while PPI impairments were found only at PD45 in prenatally LPS-treated females. Following prenatal LPS-administration, recognition memory for objects was impaired in both sexes with males being more severely affected. Additionally, we assessed prenatal infection-induced alterations of parvalbumin (Parv) expression and myelin fiber density. Male offspring born to LPS-challenged mothers showed decreased myelination in cortical and limbic brain regions as well as reduced numbers of Parv-expressing cells in the medial prefrontal cortex (mPFC), hippocampus and entorhinal cortex. In contrast, LPS-exposed female rats showed only a modest decrease in myelination and Parv immunoreactivity. Collectively, our data indicate that some of the prenatal immune activation effects are sex dependent and further strengthen the importance of taking into account gender differences in animal models of schizophrenia. PMID:25455585

  13. Chronic unpredictable stress and long-term ovariectomy affect arginine-vasopressin expression in the paraventricular nucleus of adult female mice.

    PubMed

    Grassi, D; Lagunas, N; Calmarza-Font, I; Diz-Chaves, Y; Garcia-Segura, L M; Panzica, G C

    2014-11-01

    Arginine-Vasopressin (AVP) may regulate the hypothalamic-pituitary-adrenal axis (HPA) and its effects on depressive responses. In a recent study, we demonstrated that Chronic Unpredictable Stress (CUS) depressive effects are enhanced by long-term ovariectomy (a model of post-menopause). In the present study, we investigated the effects of long-term ovariectomy and CUS on AVP expression in different subdivision of the paraventricular nucleus (PVN) of female mice. Both long-term ovariectomy and CUS affect AVP immunoreactivity in some of the PVN subnuclei of adult female mice. In particular, significant changes on AVP immunoreactivity were observed in magnocellular subdivisions, the paraventricular lateral magnocellular (PaLM) and the paraventricular medial magnocellular (PaMM), the 2 subnuclei projecting to the neurohypophysis for the hormonal regulation of body homeostasis. AVP immunoreactivity was decreased in the PaLM by both the long-term deprivation of ovarian hormones and the CUS. In contrast, AVP immunoreactivity was increased in the PaMM by CUS, whereas it was decreased by ovariectomy. Therefore, present results suggest morphological and functional differences among the PVN's subnuclei and complex interactions among CUS, gonadal hormones and AVP immunoreactivity.

  14. Singing on the wings! Male wing fanning performances affect female willingness to copulate in the aphid parasitoid Lysiphlebus testaceipes (Hymenoptera: Braconidae: Aphidiinae).

    PubMed

    Benelli, Giovanni; Kavallieratos, Nickolas G; Donati, Elisa; Giunti, Giulia; Stefanini, Cesare; Canale, Angelo

    2016-08-01

    Lysiphlebus testaceipes (Hymenoptera: Braconidae: Aphidiinae) is a generalist endoparasitoid attacking more than 100 aphid species. In L. testaceipes, wing fanning is a main male courtship display evoked by a female-borne sex pheromone. However, no information is available on the characteristics and behavioral role of male fanning during courtship in this parasitoid. Here, the courtship behavior of a wild strain of L. testaceipes was quantified and the male wing fanning performances were analyzed through high-speed video recordings and examined in relation to mating success. Courtship sequence of wild L. testaceipes did not substantially differ from that previously reported for other populations mass reared on aphids. We observed that the male courtship duration did not affect mating success. However, video analysis revealed that the males producing high-frequency fanning signals achieved higher mating success over those that display low-frequency fanning. Wing fanning before successful and unsuccessful courtship differed in amplitude of wing movements and alignment toward the mate, highlighting that frontal courtship positively influence the female mating decisions. This study increases knowledge on sexual behavior in a key parasitoid of aphids, highlighting the importance of wing fanning among the range of sensory modalities used in the sexual communication of L. testaceipes. From a practical point of view, this information is useful in L. testaceipes-based biocontrol strategies, since it can help to establish parameters for quality checking of mass-reared wasps over time.

  15. Rett syndrome and the urge of novel approaches to study MeCP2 functions and mechanisms of action.

    PubMed

    Bedogni, Francesco; Rossi, Riccardo L; Galli, Francesco; Cobolli Gigli, Clementina; Gandaglia, Anna; Kilstrup-Nielsen, Charlotte; Landsberger, Nicoletta

    2014-10-01

    Rett syndrome (RTT) is a devastating genetic disorder that worldwide represents the most common genetic cause of severe intellectual disability in females. Most cases are caused by mutations in the X-linked MECP2 gene. Several recent studies have demonstrated that RTT mimicking animal models do not develop an irreversible condition and phenotypic rescue is possible. However, no cure for RTT has been identified so far, and patients are only given symptomatic and supportive treatments. The development of clinical applications imposes a more comprehensive knowledge of MeCP2 functional role(s) and their relevance for RTT pathobiology. Herein, we thoroughly survey the knowledge about MeCP2 structure and functions, highlighting the necessity of identifying more functional domains and the value of molecular genetics. Given that, in our opinion, RTT ultimately is generated by perturbations in gene transcription and so far no genes/pathways have been consistently linked to a dysfunctional MeCP2, we have used higher-level bioinformatic analyses to identify commonly deregulated mechanisms in MeCP2-defective samples. In this review we present our results and discuss the possible value of the utilized approach.

  16. Disruption of MeCP2 attenuates circadian rhythm in CRISPR/Cas9-based Rett syndrome model mouse.

    PubMed

    Tsuchiya, Yoshiki; Minami, Yoichi; Umemura, Yasuhiro; Watanabe, Hitomi; Ono, Daisuke; Nakamura, Wataru; Takahashi, Tomoyuki; Honma, Sato; Kondoh, Gen; Matsuishi, Toyojiro; Yagita, Kazuhiro

    2015-12-01

    Methyl-CpG-binding protein 2 (Mecp2) is an X-linked gene encoding a methylated DNA-binding nuclear protein which regulates transcriptional activity. The mutation of MECP2 in humans is associated with Rett syndrome (RTT), a neurodevelopmental disorder. Patients with RTT frequently show abnormal sleep patterns and sleep-associated problems, in addition to autistic symptoms, raising the possibility of circadian clock dysfunction in RTT. In this study, we investigated circadian clock function in Mecp2-deficient mice. We successfully generated both male and female Mecp2-deficient mice on the wild-type C57BL/6 background and PER2(Luciferase) (PER2(Luc)) knock-in background using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system. Generated Mecp2-deficient mice recapitulated reduced activity in mouse models of RTT, and their activity rhythms were diminished in constant dark conditions. Furthermore, real-time bioluminescence imaging showed that the amplitude of PER2(Luc)-driven circadian oscillation was significantly attenuated in Mecp2-deficient SCN neurons. On the other hand, in vitro circadian rhythm development assay using Mecp2-deficient mouse embryonic stem cells (ESCs) did not show amplitude changes of PER2(Luc) bioluminescence rhythms. Together, these results show that Mecp2 deficiency abrogates the circadian pacemaking ability of the SCN, which may be a therapeutic target to treat the sleep problems of patients with RTT.

  17. Considering an affect regulation framework for examining the association between body dissatisfaction and positive body image in Black older adolescent females: does body mass index matter?

    PubMed

    Webb, Jennifer B; Butler-Ajibade, Phoebe; Robinson, Seronda A

    2014-09-01

    The present study provided an initial evaluation of an affect regulation model describing the association between body dissatisfaction and two contemporary measures of positive body image among 247 Black college-bound older adolescent females. We further tested whether possessing a higher body mass index (BMI) would strengthen these associations. Self-reported height and weight were used to calculate BMI. Respondents also completed a culturally-sensitive figure rating scale along with assessments of body appreciation and body image flexibility. Results indicated a robust positive association between the two measures of positive body image; BMI was the strongest predictor of both body appreciation and body image flexibility with body size discrepancy (current minus ideal) contributing incremental variance to both models tested. Implications for improving our understanding of the association between positive and negative body image and bolstering positive body image to promote health-protective behaviors among Black young women at this developmental juncture are discussed. PMID:25079011

  18. Considering an affect regulation framework for examining the association between body dissatisfaction and positive body image in Black older adolescent females: does body mass index matter?

    PubMed

    Webb, Jennifer B; Butler-Ajibade, Phoebe; Robinson, Seronda A

    2014-09-01

    The present study provided an initial evaluation of an affect regulation model describing the association between body dissatisfaction and two contemporary measures of positive body image among 247 Black college-bound older adolescent females. We further tested whether possessing a higher body mass index (BMI) would strengthen these associations. Self-reported height and weight were used to calculate BMI. Respondents also completed a culturally-sensitive figure rating scale along with assessments of body appreciation and body image flexibility. Results indicated a robust positive association between the two measures of positive body image; BMI was the strongest predictor of both body appreciation and body image flexibility with body size discrepancy (current minus ideal) contributing incremental variance to both models tested. Implications for improving our understanding of the association between positive and negative body image and bolstering positive body image to promote health-protective behaviors among Black young women at this developmental juncture are discussed.

  19. Considering an Affect Regulation Framework for Examining the Association Between Body Dissatisfaction and Positive Body Image in Black Older Adolescent Females: Does Body Mass Index Matter?

    PubMed Central

    Butler-Ajibade, Phoebe; Robinson, Seronda A.

    2014-01-01

    The present study provided an initial evaluation of an affect regulation model describing the association between body dissatisfaction and two contemporary measures of positive body image among 247 Black college-bound older adolescent females. We further tested whether possessing a higher body mass index (BMI) would strengthen these associations. Self-reported height and weight were used to calculate BMI. Respondents also completed a culturally-sensitive figure rating scale along with assessments of body appreciation and body image flexibility. Results indicated a robust positive association between the two measures of positive body image; BMI was the strongest predictor of both body appreciation and body image flexibility with body size discrepancy (current minus ideal) contributing incremental variance to both models tested. Implications for improving our understanding of the association between positive and negative body image and bolstering positive body image to promote health-protective behaviors among Black young women at this developmental juncture are discussed. PMID:25079011

  20. Tumor necrosis factor-alpha during neonatal brain development affects anxiety- and depression-related behaviors in adult male and female mice.

    PubMed

    Babri, Shirin; Doosti, Mohammad-Hossein; Salari, Ali-Akbar

    2014-03-15

    A nascent literature suggests that neonatal infection is a risk factor for the development of brain, behavior and hypothalamic-pituitary-adrenal axis which can affect anxiety- and depression-related behaviors in later life. It has been documented that neonatal infection raises the concentrations of tumor necrosis factor-alpha (TNF-α) in neonate rodents and such infections may result in neonatal brain injury, at least in part, through pro-inflammatory cytokines. In addition, previous studies have shown that TNF-α is involved in cellular differentiation, neurogenesis and programmed cell death during the development of the central nervous system. We investigated for the first time whether neonatal exposure to TNF-α can affect body weight, stress-induced corticosterone (COR), anxiety- and depression-related behaviors in adult mice. In the present study, neonatal mice were treated to recombinant mouse TNF-α (0.2, 0.4, 0.7 and 1 μg/kg) or saline on postnatal days 3 and 5, then adult male and female mice were exposed to different behavioral tests. The results indicated that neonatal TNF-α treatment reduced body weight in neonatal period in both sexes. In addition, this study presents findings indicating that high doses of TNF- increase stress-induced COR levels, anxiety- and depression-related behaviors in adult males, but increase levels of anxiety without significantly influencing depression in adult female mice [corrected]. Our findings suggest that TNF-α exposure during neonatal period can alter brain and behavior development in a dose and sex-dependent manner in mice.

  1. Tumor necrosis factor-alpha during neonatal brain development affects anxiety- and depression-related behaviors in adult male and female mice.

    PubMed

    Babri, Shirin; Doosti, Mohammad-Hossein; Salari, Ali-Akbar

    2014-03-15

    A nascent literature suggests that neonatal infection is a risk factor for the development of brain, behavior and hypothalamic-pituitary-adrenal axis which can affect anxiety- and depression-related behaviors in later life. It has been documented that neonatal infection raises the concentrations of tumor necrosis factor-alpha (TNF-α) in neonate rodents and such infections may result in neonatal brain injury, at least in part, through pro-inflammatory cytokines. In addition, previous studies have shown that TNF-α is involved in cellular differentiation, neurogenesis and programmed cell death during the development of the central nervous system. We investigated for the first time whether neonatal exposure to TNF-α can affect body weight, stress-induced corticosterone (COR), anxiety- and depression-related behaviors in adult mice. In the present study, neonatal mice were treated to recombinant mouse TNF-α (0.2, 0.4, 0.7 and 1 μg/kg) or saline on postnatal days 3 and 5, then adult male and female mice were exposed to different behavioral tests. The results indicated that neonatal TNF-α treatment reduced body weight in neonatal period in both sexes. In addition, this study presents findings indicating that high doses of TNF- increase stress-induced COR levels, anxiety- and depression-related behaviors in adult males, but increase levels of anxiety without significantly influencing depression in adult female mice [corrected]. Our findings suggest that TNF-α exposure during neonatal period can alter brain and behavior development in a dose and sex-dependent manner in mice. PMID:24398264

  2. Exposure to altered gravity during specific developmental periods differentially affects growth, development, the cerebellum and motor functions in male and female rats

    NASA Astrophysics Data System (ADS)

    Nguon, K.; Ladd, B.; Sajdel-Sulkowska, E. M.

    2006-01-01

    We previously reported that perinatal exposure to hypergravity affects cerebellar structure and motor coordination in rat neonates. In the present study, we explored the hypothesis that neonatal cerebellar structure and motor coordination may be particularly vulnerable to the effects of hypergravity during specific developmental stages. To test this hypothesis, we compared neurodevelopment, motor behavior and cerebellar structure in rat neonates exposed to 1.65 G on a 24-ft centrifuge during discrete periods of time: the 2nd week of pregnancy [gestational day (G) 8 through G15; group A], the 3rd week of pregnancy (G15 through birth on G22/G23; group B), the 1st week of nursing [birth through postnatal day (P) 6; group C], the 2nd and 3rd weeks of nursing (P6 through P21; group D), the combined 2nd and 3rd weeks of pregnancy and nursing (G8 through P21; group E) and stationary control (SC) neonates (group F). Prenatal exposure to hypergravity resulted in intrauterine growth retardation as reflected by a decrease in the number of pups in a litter and lower average mass at birth. Exposure to hypergravity immediately after birth impaired the righting response on P3, while the startle response in both males and females was most affected by exposure during the 2nd and 3rd weeks after birth. Hypergravity exposure also impaired motor functions, as evidenced by poorer performance on a rotarod; while both males and females exposed to hypergravity during the 2nd and 3rd weeks after birth performed poorly on P21, male neonates were most dramatically affected by exposure to hypergravity during the second week of gestation, when the duration of their recorded stay on the rotarod was one half that of SC males. Cerebellar mass was most reduced by later postnatal exposure. Thus, for the developing rat cerebellum, the postnatal period that overlaps the brain growth spurt is the most vulnerable to hypergravity. However, male motor behavior is also affected by midpregnancy exposure to

  3. Genes Related to Mitochondrial Functions, Protein Degradation, and Chromatin Folding Are Differentially Expressed in Lymphomonocytes of Rett Syndrome Patients

    PubMed Central

    Leoni, Guido; Cervellati, Franco; Canali, Raffaella; Cortelazzo, Alessio; De Felice, Claudio; Ciccoli, Lucia; Hayek, Joussef

    2013-01-01

    Rett syndrome (RTT) is mainly caused by mutations in the X-linked methyl-CpG binding protein (MeCP2) gene. By binding to methylated promoters on CpG islands, MeCP2 protein is able to modulate several genes and important cellular pathways. Therefore, mutations in MeCP2 can seriously affect the cellular phenotype. Today, the pathways that MeCP2 mutations are able to affect in RTT are not clear yet. The aim of our study was to investigate the gene expression profiles in peripheral blood lymphomonocytes (PBMC) isolated from RTT patients to try to evidence new genes and new pathways that are involved in RTT pathophysiology. LIMMA (Linear Models for MicroArray) and SAM (Significance Analysis of Microarrays) analyses on microarray data from 12 RTT patients and 7 control subjects identified 482 genes modulated in RTT, of which 430 were upregulated and 52 were downregulated. Functional clustering of a total of 146 genes in RTT identified key biological pathways related to mitochondrial function and organization, cellular ubiquitination and proteosome degradation, RNA processing, and chromatin folding. Our microarray data reveal an overexpression of genes involved in ATP synthesis suggesting altered energy requirement that parallels with increased activities of protein degradation. In conclusion, these findings suggest that mitochondrial-ATP-proteasome functions are likely to be involved in RTT clinical features. PMID:24453408

  4. Prenatal dietary load of Maillard reaction products combined with postnatal Coca-Cola drinking affects metabolic status of female Wistar rats

    PubMed Central

    Gurecká, Radana; Koborová, Ivana; Janšáková, Katarína; Tábi, Tamás; Szökő, Éva; Somoza, Veronika; Šebeková, Katarína; Celec, Peter

    2015-01-01

    Aim To assess the impact of prenatal exposure to Maillard reaction products (MRPs) -rich diet and postnatal Coca-Cola consumption on metabolic status of female rats. Diet rich in MRPs and consumption of saccharose/fructose sweetened soft drinks is presumed to impose increased risk of development of cardiometabolic afflictions, such as obesity or insulin resistance. Methods At the first day of pregnancy, 9 female Wistar rats were randomized into two groups, pair-fed either with standard rat chow (MRP-) or MRPs-rich diet (MRP+). Offspring from each group of mothers was divided into two groups and given either water (Cola-) or Coca-Cola (Cola+) for drinking ad libitum for 18 days. Oral glucose tolerance test was performed, and circulating markers of inflammation, oxidative stress, glucose and lipid metabolism were assessed. Results MRP+ groups had higher weight gain, significantly so in the MRP+/Cola- vs MRP-/Cola-. Both prenatal and postnatal intervention increased carboxymethyllysine levels and semicarbazide-sensitive amine oxidase activity, both significantly higher in MRP+/Cola + than in MRP-/Cola-. Total antioxidant capacity was lower in MRP+ groups, with significant decrease in MRP+/Cola + vs MRP-/Cola+. Rats drinking Coca-Cola had higher insulin, homeostatic model assessment of insulin resistance, heart rate, advanced oxidation of protein products, triacylglycerols, and oxidative stress markers measured as thiobarbituric acid reactive substances compared to rats drinking water, with no visible effect of MRPs-rich diet. Conclusion Metabolic status of rats was affected both by prenatal and postnatal dietary intervention. Our results suggest that combined effect of prenatal MRPs load and postnatal Coca-Cola drinking may play a role in development of metabolic disorders in later life. PMID:25891868

  5. A Mixture Reflecting Polybrominated Diphenyl Ether (PBDE) Profiles Detected in Human Follicular Fluid Significantly Affects Steroidogenesis and Induces Oxidative Stress in a Female Human Granulosa Cell Line.

    PubMed

    Lefevre, Pavine L C; Wade, Mike; Goodyer, Cindy; Hales, Barbara F; Robaire, Bernard

    2016-07-01

    Brominated flame retardants are incorporated into consumer products to prevent flame propagation. These compounds leach into the domestic environment, resulting in chronic exposure. Pregnancy failure is associated with high levels of polybrominated diphenyl ethers (PBDEs), a major class of brominated flame retardants, in human follicular fluid, raising serious questions regarding their impact on female fertility. Our goal was to elucidate the effects of a mixture of PBDEs, similar to the profile found in human follicular fluid, on an immortalized human granulosa cell line, the KGN cell line. We showed that cell viability was altered and oxidative stress was induced as reflected by increased reactive oxygen species formation at 100 μM of the PBDE mixture. Transcriptomic analysis revealed that PBDE treatments of 1, 5, and 20 μM altered the expression of several genes involved in the reactive oxygen species signaling pathway. Significant dose-dependent reductions in progesterone and estradiol levels in the culture medium were measured after PBDE treatment; in parallel, the expression of genes involved in estradiol metabolism, namely CYP1A1, was up-regulated by 5 and 20 μM of the PBDE mixture. Treatment with 20 μM PBDE also increased the expression and secretion of the proinflammatory factor, IL-6, into the KGN cell culture medium. Our results demonstrate that PBDEs can alter human granulosa cell functions by inducing oxidative stress and disrupting steroidogenesis. These results indicate that PBDEs may be detrimental to ovarian functions and thus may adversely affect female reproductive health after chronic exposure. PMID:27219277

  6. Co-occurrence of Dystonic and Dyskinetic Tongue Movements with Oral Apraxia in Post-regression Dysphagia in Classical Rett Syndrome Years of Life 1 Through 5.

    PubMed

    Abraham, Suzanne S; Taragin, Ben; Djukic, Alesandra

    2015-04-01

    We do not know the natural history of dysphagia in classical Rett syndrome (RTT) by stage or age. This study investigated swallowing physiology in 23 females ages 1:7 to 5:8 (years, months) with classical Rett syndrome to determine common and distinguishing features of dysphagia in post-regression early Pseudostationary Stage III. In-depth analysis of videofluoroscopic swallowing studies (VFSS) found dysmotility of oral stage events across subjects implicating oral apraxia. Impaired motility was further compromised by recurrent dystonic and dyskinetic movements that co-occurred with oral apraxia during oral ingestion in 78 % (n = 18) of the subjects with RTT. Of this group, 44 % displayed rocking and/or rolling lingual pattern, 56 % had recurrent oral tongue retroflexions, and/or elevated posturing of the tongue tip, and, 72 % displayed multi-wave oropharyngeal transfer pattern. The proportion of subjects whose swallowing motility was disrupted by aberrant involuntary tongue movements did not differ significantly between bolus types (liquid, puree, and solid) trialed. Liquid ingestion was significantly more efficient in subjects using bottles with nipples than their counterparts who used spouted or straw cups. Dystonic and dyskinetic tongue movements disrupted liquid ingestion in subjects using cups with spouts or straws significantly more than those using bottles. Analysis of food ingestion revealed that significantly more subjects were able to orally form, transport, and transfer a puree bolus into the pharynx than they were a solid bolus. A significantly larger number of subjects aspirated and penetrated liquid than they did puree or solid. No significant relationship was found between subjects with airway contamination and those with dystonic and dyskinetic tongue movements. Subjects' rocking and rolling lingual patterns were consistent with those evidenced in adults with Parkinson's disease. Subjects' tongue retroflexions were classified as provisionally

  7. Co-occurrence of Dystonic and Dyskinetic Tongue Movements with Oral Apraxia in Post-regression Dysphagia in Classical Rett Syndrome Years of Life 1 Through 5.

    PubMed

    Abraham, Suzanne S; Taragin, Ben; Djukic, Alesandra

    2015-04-01

    We do not know the natural history of dysphagia in classical Rett syndrome (RTT) by stage or age. This study investigated swallowing physiology in 23 females ages 1:7 to 5:8 (years, months) with classical Rett syndrome to determine common and distinguishing features of dysphagia in post-regression early Pseudostationary Stage III. In-depth analysis of videofluoroscopic swallowing studies (VFSS) found dysmotility of oral stage events across subjects implicating oral apraxia. Impaired motility was further compromised by recurrent dystonic and dyskinetic movements that co-occurred with oral apraxia during oral ingestion in 78 % (n = 18) of the subjects with RTT. Of this group, 44 % displayed rocking and/or rolling lingual pattern, 56 % had recurrent oral tongue retroflexions, and/or elevated posturing of the tongue tip, and, 72 % displayed multi-wave oropharyngeal transfer pattern. The proportion of subjects whose swallowing motility was disrupted by aberrant involuntary tongue movements did not differ significantly between bolus types (liquid, puree, and solid) trialed. Liquid ingestion was significantly more efficient in subjects using bottles with nipples than their counterparts who used spouted or straw cups. Dystonic and dyskinetic tongue movements disrupted liquid ingestion in subjects using cups with spouts or straws significantly more than those using bottles. Analysis of food ingestion revealed that significantly more subjects were able to orally form, transport, and transfer a puree bolus into the pharynx than they were a solid bolus. A significantly larger number of subjects aspirated and penetrated liquid than they did puree or solid. No significant relationship was found between subjects with airway contamination and those with dystonic and dyskinetic tongue movements. Subjects' rocking and rolling lingual patterns were consistent with those evidenced in adults with Parkinson's disease. Subjects' tongue retroflexions were classified as provisionally

  8. Seizures and pain uncertainty associated with parenting stress and Rett syndrome.

    PubMed

    Byiers, Breanne J; Tervo, Raymond C; Feyma, Timothy J; Symons, Frank J

    2014-04-01

    Data were collected parenting stress, adaptive behavior, pain, and health issues from the caregivers of 35 girls and women with Rett syndrome (mean age = 20.3). A majority (60%) of parents reported stress in the clinical range on at least 1 subscale of the Parenting Stress Index-Short Form. Seizures and uncertainty about their daughter's gastrointestinal pain experience were significantly associated with higher levels of parenting stress. No other child factors (adaptive behavior, age, residential status) were significantly related to parenting stress. Factors related to chronic health concerns (seizures, ambiguous pain presentation) may be important when considering family stress issues in relation to general outcomes for girls with Rett syndrome and related developmental disorders.

  9. Mitochondrial dysfunction as a central actor in intellectual disability-related diseases: an overview of Down syndrome, autism, Fragile X and Rett syndrome.

    PubMed

    Valenti, Daniela; de Bari, Lidia; De Filippis, Bianca; Henrion-Caude, Alexandra; Vacca, Rosa Anna

    2014-10-01

    Clinical manifestations typical of mitochondrial diseases are often present in various genetic syndromes associated with intellectual disability, a condition leading to deficit in cognitive functions and adaptive behaviors. Until now, the causative mechanism leading to intellectual disability is unknown and the progression of the condition is poorly understood. We first report latest advances on genetic and environmental regulation of mitochondrial function and its role in brain development. Starting from the structure, function and regulation of the oxidative phosphorylation apparatus, we review how mitochondrial biogenesis and dynamics play a central role in neurogenesis and neuroplasticity. We then discuss how dysfunctional mitochondria and alterations in reactive oxygen species homeostasis are potentially involved in the pathogenesis of various neurodevelopmental syndromes with a special focus on Down, Rett, Fragile X syndromes and autism spectrum disorders. Finally, we review and suggest novel therapeutic approaches aimed at improving intellectual disability by activating mitochondrial function and reducing oxidative stress to amiliorate the quality of life in the subjects affected.

  10. MeCP2-mediated alterations of striatal features accompany psychomotor deficits in a mouse model of Rett syndrome.

    PubMed

    Kao, Fang-Chi; Su, San-Hua; Carlson, Gregory C; Liao, Wenlin

    2015-01-01

    Rett Syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Affected individuals develop motor deficits including stereotypic hand movements, impaired motor learning and difficulties with movement. To understand the neural mechanisms of motor deficits in RTT, we characterized the molecular and cellular phenotypes in the striatum, the major input nucleus of the basal ganglia that controls psychomotor function, in mice carrying a null allele of Mecp2. These mice showed significant hypoactivity associated with impaired motor coordination and motor skill learning. We found that dopamine content was significantly reduced in the striatum of Mecp2 null mice. Reduced dopamine was accompanied by down-regulation of tyrosine hydroxylase and up-regulation of dopamine D2 receptors, particularly in the rostral striatum. We also observed that loss of MeCP2 induced compartment-specific alterations in the striatum, including reduced expression of μ-opioid receptors in the striosomes and increased number of calbindin-positive neurons in the striatal matrix. The total number of parvalbumin-positive interneurons and their dendritic arborization were also significantly increased in the striatum of Mecp2 null mice. Together, our findings support that MeCP2 regulates a unique set of genes critical for modulating motor output of the striatum, and that aberrant structure and function of the striatum due to MeCP2 deficiency may underlie the motor deficits in RTT.

  11. Profiling early socio-communicative development in five young girls with the preserved speech variant of Rett syndrome.

    PubMed

    Marschik, Peter B; Kaufmann, Walter E; Einspieler, Christa; Bartl-Pokorny, Katrin D; Wolin, Thomas; Pini, Giorgio; Budimirovic, Dejan B; Zappella, Michele; Sigafoos, Jeff

    2012-01-01

    Rett syndrome (RTT) is a developmental disorder characterized by regression of purposeful hand skills and spoken language, although some affected children retain some ability to speech. We assessed the communicative abilities of five young girls, who were later diagnosed with the preserved speech variant of RTT, during the pre-regression period (aged 12-24 months). Videotapes, obtained by parents during routine family situations and celebrations, were analyzed to identify communicative forms and functions used by these toddlers. Non-verbal communicative forms dominated over verbal-communicative forms for six of the eight identified communication functions. Although the girls used various non-verbal forms to make requests, for example, none of the individuals were observed to make choices or request information. Early peculiarities in the speech-language domain during the first year of life became more prominent and evident during the second year of life as general differences between typical development and atypical development become more obvious in RTT. These findings highlight the importance of assessing socio-communicative forms and functions at early age in children with RTT. The results suggest that speech-language functions did not appear to play a major role in the children's communicative attempts. We conclude that, even among children with the preserved speech variant, socio-communicative deficits are present before regression and persist after this period.

  12. Single nucleotide polymorphisms linked to mitochondrial uncoupling protein genes UCP2 and UCP3 affect mitochondrial metabolism and healthy aging in female nonagenarians.

    PubMed

    Kim, Sangkyu; Myers, Leann; Ravussin, Eric; Cherry, Katie E; Jazwinski, S Michal

    2016-08-01

    Energy expenditure decreases with age, but in the oldest-old, energy demand for maintenance of body functions increases with declining health. Uncoupling proteins have profound impact on mitochondrial metabolic processes; therefore, we focused attention on mitochondrial uncoupling protein genes. Alongside resting metabolic rate (RMR), two SNPs in the promoter region of UCP2 were associated with healthy aging. These SNPs mark potential binding sites for several transcription factors; thus, they may affect expression of the gene. A third SNP in the 3'-UTR of UCP3 interacted with RMR. This UCP3 SNP is known to impact UCP3 expression in tissue culture cells, and it has been associated with body weight and mitochondrial energy metabolism. The significant main effects of the UCP2 SNPs and the interaction effect of the UCP3 SNP were also observed after controlling for fat-free mass (FFM) and physical-activity related energy consumption. The association of UCP2/3 with healthy aging was not found in males. Thus, our study provides evidence that the genetic risk factors for healthy aging differ in males and females, as expected from the differences in the phenotypes associated with healthy aging between the two sexes. It also has implications for how mitochondrial function changes during aging. PMID:26965008

  13. Beta-carotene affects gene expression in lungs of male and female Bcmo1−/− mice in opposite directions

    PubMed Central

    van Helden, Yvonne G. J.; Godschalk, Roger W. L.; Swarts, Hans J. M.; Hollman, Peter C. H.; van Schooten, Frederik J.

    2010-01-01

    Molecular mechanisms triggered by high dietary beta-carotene (BC) intake in lung are largely unknown. We performed microarray gene expression analysis on lung tissue of BC supplemented beta-carotene 15,15′-monooxygenase 1 knockout (Bcmo1−/−) mice, which are—like humans—able to accumulate BC. Our main observation was that the genes were regulated in an opposite direction in male and female Bcmo1−/− mice by BC. The steroid biosynthetic pathway was overrepresented in BC-supplemented male Bcmo1−/− mice. Testosterone levels were higher after BC supplementation only in Bcmo1−/− mice, which had, unlike wild-type (Bcmo1+/+) mice, large variations. We hypothesize that BC possibly affects hormone synthesis or metabolism. Since sex hormones influence lung cancer risk, these data might contribute to an explanation for the previously found increased lung cancer risk after BC supplementation (ATBC and CARET studies). Moreover, effects of BC may depend on the presence of frequent human BCMO1 polymorphisms, since these effects were not found in wild-type mice. PMID:20820853

  14. Evoking communication in Rett syndrome: comparisons with conversations and games in mother-infant interaction.

    PubMed

    Burford, B; Trevarthen, C

    1997-01-01

    Girls with Rett syndrome retain a responsiveness with care-givers that corresponds in many respects with the preverbal communication observed with normal infants. This has characteristic rhythmic patterns and phrases, mutual imitation, reciprocal emotional phases and rudimentary oral, vocal and gestural expressions. After individuals with Rett syndrome have passed the critical stage in dissolution of their attention, co-ordination and voluntary control, they retain positive orientation to human faces and eyes with smiling. Video analyses show that they can engage with rhythms and phrases of conversation, sometimes showing a sense of humour and sensitivity to playful teasing. They respond to repeated patterns of expression in rhythmic/prosodic play and to certain forms in music. It is suggested that sensitive and appropriately attuned support for the rudimentary motives for human contact that survive in Rett syndrome can help stabilisation of self-regulatory states, alleviate panic and confusion and facilitate learning. The effects of the disorder may be a consequence of a genetic fault in the elaboration of an Intrinsic Motive Formation in the reticular core of the embryo brain, leading to dysregulation of differentiation in higher cognitive systems and learning, but leaving partially intact motive principles for human intersubjective response.

  15. Evoking communication in Rett syndrome: comparisons with conversations and games in mother-infant interaction.

    PubMed

    Burford, B; Trevarthen, C

    1997-01-01

    Girls with Rett syndrome retain a responsiveness with care-givers that corresponds in many respects with the preverbal communication observed with normal infants. This has characteristic rhythmic patterns and phrases, mutual imitation, reciprocal emotional phases and rudimentary oral, vocal and gestural expressions. After individuals with Rett syndrome have passed the critical stage in dissolution of their attention, co-ordination and voluntary control, they retain positive orientation to human faces and eyes with smiling. Video analyses show that they can engage with rhythms and phrases of conversation, sometimes showing a sense of humour and sensitivity to playful teasing. They respond to repeated patterns of expression in rhythmic/prosodic play and to certain forms in music. It is suggested that sensitive and appropriately attuned support for the rudimentary motives for human contact that survive in Rett syndrome can help stabilisation of self-regulatory states, alleviate panic and confusion and facilitate learning. The effects of the disorder may be a consequence of a genetic fault in the elaboration of an Intrinsic Motive Formation in the reticular core of the embryo brain, leading to dysregulation of differentiation in higher cognitive systems and learning, but leaving partially intact motive principles for human intersubjective response. PMID:9452916

  16. Neurotrophic effects of Cerebrolysin in the Mecp2308/Y transgenic model of Rett Syndrome

    PubMed Central

    Doppler, Edith; Rockenstein, Edward; Ubhi, Kiren; Inglis, Chandra; Mante, Michael; Adame, Anthony; Crews, Leslie; Hitzl, Monika; Moessler, Herbert; Masliah, Eliezer

    2009-01-01

    Rett syndrome is a childhood neurodevelopmental disorder caused by mutations in the gene encoding for methyl CpG binding protein (MeCP2). Neuropathological studies in patients with Rett syndrome and in MeCP2 mutant models have shown reduced dendritic arborization and abnormal neuronal packing. We have previously shown that Cerebrolysin (CBL), a neurotrophic peptide mixture, ameliorates the synaptic and dendritic pathology in models of aging and neurodegeneration. This study aimed to determine whether CBL was capable of reducing behavioral and neuronal alterations in Mecp2308/Y mutant mice. Two sets of experiments were performed, the first with 4 month old male Mecp2308/Y mutant mice treated with CBL or vehicle for 3 months (Group A) and the second with 1 month old mice treated for 6 months (Group B). Behavioral analysis showed improved motor performance with CBL in Group A and a trend toward improvement in Group B. Consistent with behavioral findings, neuropathological analysis of the basal ganglia showed amelioration of dendritic simplification in CBL-treated Mecp2308/Y mutant mice. CBL treatment also ameliorated dendritic pathology and neuronal loss in the hippocampus and neocortex in Mecp2308/Y mutant mice. In conclusion, this study demonstrates that CBL promotes recovery of dendritic and neuronal damage and behavioral improvements in young adult Mecp2308/Y mutant mice and suggests that CBL may have neurotrophic effects in this model. These findings support the possibility that CBL may have beneficial effects in the management of Rett syndrome. PMID:18600331

  17. The Relationship between "MECP2" Mutation Type and Health Status and Service Use Trajectories over Time in a Rett Syndrome Population

    ERIC Educational Resources Information Center

    Young, Deidra; Bebbington, Ami; de Klerk, Nick; Bower, Carol; Nagarajan, Lakshmi; Leonard, Helen

    2011-01-01

    This study aimed to investigate the trajectories over time of health status and health service use in Rett syndrome by mutation type. Data were obtained from questionnaires administered over 6 years to 256 participants from the Australian Rett Syndrome Database. Health status (episodes of illness and medication load) and health service use…

  18. Female sexuality.

    PubMed

    Rao, T S Sathyanarana; Nagaraj, Anil Kumar M

    2015-07-01

    Sex is a motive force bringing a man and a woman into intimate contact. Sexuality is a central aspect of being human throughout life and encompasses sex, gender identities and roles, sexual orientation, eroticism, pleasure, intimacy, and reproduction. Sexuality is experienced and expressed in thoughts, fantasies, desires, beliefs, attitudes, values, behaviors, practices, roles and relationships. Though generally, women are sexually active during adolescence, they reach their peak orgasmic frequency in their 30 s, and have a constant level of sexual capacity up to the age of 55 with little evidence that aging affects it in later life. Desire, arousal, and orgasm are the three principle stages of the sexual response cycle. Each stage is associated with unique physiological changes. Females are commonly affected by various disorders in relation to this sexual response cycle. The prevalence is generally as high as 35-40%. There are a wide range of etiological factors like age, relationship with a partner, psychiatric and medical disorders, psychotropic and other medication. Counseling to overcome stigma and enhance awareness on sexuality is an essential step in management. There are several effective psychological and pharmacological therapeutic approaches to treat female sexual disorders. This article is a review of female sexuality. PMID:26330647

  19. Female sexuality

    PubMed Central

    Rao, T.S. Sathyanarana; Nagaraj, Anil Kumar M.

    2015-01-01

    Sex is a motive force bringing a man and a woman into intimate contact. Sexuality is a central aspect of being human throughout life and encompasses sex, gender identities and roles, sexual orientation, eroticism, pleasure, intimacy, and reproduction. Sexuality is experienced and expressed in thoughts, fantasies, desires, beliefs, attitudes, values, behaviors, practices, roles and relationships. Though generally, women are sexually active during adolescence, they reach their peak orgasmic frequency in their 30 s, and have a constant level of sexual capacity up to the age of 55 with little evidence that aging affects it in later life. Desire, arousal, and orgasm are the three principle stages of the sexual response cycle. Each stage is associated with unique physiological changes. Females are commonly affected by various disorders in relation to this sexual response cycle. The prevalence is generally as high as 35–40%. There are a wide range of etiological factors like age, relationship with a partner, psychiatric and medical disorders, psychotropic and other medication. Counseling to overcome stigma and enhance awareness on sexuality is an essential step in management. There are several effective psychological and pharmacological therapeutic approaches to treat female sexual disorders. This article is a review of female sexuality. PMID:26330647

  20. Exploring the possible link between MeCP2 and oxidative stress in Rett syndrome.

    PubMed

    Filosa, Stefania; Pecorelli, Alessandra; D'Esposito, Maurizio; Valacchi, Giuseppe; Hajek, Joussef

    2015-11-01

    Rett syndrome (RTT, MIM 312750) is a rare and orphan progressive neurodevelopmental disorder affecting girls almost exclusively, with a frequency of 1/15,000 live births of girls. The disease is characterized by a period of 6 to 18 months of apparently normal neurodevelopment, followed by early neurological regression, with a progressive loss of acquired cognitive, social, and motor skills. RTT is known to be caused in 95% of the cases by sporadic de novo loss-of-function mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene encoding methyl-CpG binding protein 2 (MeCP2), a nuclear protein able to regulate gene expression. Despite almost two decades of research into the functions and role of MeCP2, little is known about the mechanisms leading from MECP2 mutation to the disease. Oxidative stress (OS) is involved in the pathogenic mechanisms of several neurodevelopmental and neurodegenerative disorders, although in many cases it is not clear whether OS is a cause or a consequence of the pathology. Fairly recently, the presence of a systemic OS has been demonstrated in RTT patients with a strong correlation with the patients' clinical status. The link between MECP2 mutation and the redox imbalance found in RTT is not clear. Animal studies have suggested a possible direct correlation between Mecp2 mutation and increased OS levels. In addition, the restoration of Mecp2 function in astrocytes significantly improves the developmental outcome of Mecp2-null mice and reexpression of Mecp2 gene in the brain of null mice restored oxidative damage, suggesting that Mecp2 loss of function can be involved in oxidative brain damage. Starting from the evidence that oxidative damage in the brain of Mecp2-null mice precedes the onset of symptoms, we evaluated whether, based on the current literature, the dysfunctions described in RTT could be a consequence or, in contrast, could be caused by OS. We also analyzed whether therapies that at least partially treated some RTT

  1. Family affection as a protective factor against the negative effects of perceived Asian values gap on the parent-child relationship for Asian American male and female college students.

    PubMed

    Park, Yong S; Vo, Leyna P; Tsong, Yuying

    2009-01-01

    The study examined whether family affection (i.e., affective responsiveness, affectionate communication, and affective orientation) protected against the negative effects of perceived parent-child Asian values gap on the quality of their parent relationships for 259 female and 77 male Asian American college students. Asian values gap was higher for women than men, and inversely related to a perceived healthy parent-child relationship for both genders. Participants rated the relationship with their mothers as more positive and affectionate than with their fathers. Both parents were reported to communicate more supportive affection than verbal and nonverbal affection. Affective responsiveness was identified as a protective factor in the father-son relationship whereas verbal affection protected the mother-daughter relationship. The study also revealed that daughters' affective orientation had beneficial effects on the father-daughter relationship at lower levels of Asian values gap. Clinical implications and directions for future research are discussed. PMID:19209977

  2. Magnetic field exposure increases cell proliferation but does not affect melatonin levels in the mammary gland of female Sprague Dawley rats.

    PubMed

    Fedrowitz, Maren; Westermann, Jürgen; Löscher, Wolfgang

    2002-03-01

    In line with the possible relationship between electric power and breast cancer risk as well as the underlying "melatonin hypothesis," we have shown previously (Thun-Battersby et al., Cancer Res., 59: 3627-3633, 1999) that 50-Hz magnetic fields (MFs) of low (100 microTesla) flux density enhance mammary gland tumor development and growth in the 7,12-dimethylbenz(a)anthracene model of breast cancer in female Sprague Dawley rats. On the basis of the melatonin hypothesis and previous observations of induction of ornithine decarboxylase in response to MF, we proposed that the effect of MF exposure on mammary carcinogenesis is related to enhanced proliferation of the mammary epithelium. The objective of the present study was to directly assess this proposal by the use of proliferation markers. Female Sprague Dawley rats were MF or sham exposed for 2 weeks at a flux density of 100 microTesla. Proliferation of epithelial cells in the mammary tissue and adjacent skin was examined by in vivo labeling of proliferating cells with bromodeoxyuridine (BrdUrd) and in situ labeling of the nuclear proliferation-associated Ki-67 protein by the antibody MIB-5. Furthermore, melatonin levels were determined after MF or sham exposure in the pineal gland and directly in the mammary tissue. In additional experiments, the tumor promoter 12-O-tetradecanoylphorbol-13-acetate was used for comparison with the effects of MF exposure. MF exposure significantly enhanced BrdUrd and Ki-67 labeling in the mammary epithelium, indicating a marked increase in cell proliferation. The most pronounced effect on proliferation was seen in the cranial thoracic (or cervical) mammary complexes, in which we previously had seen the most marked effects of MF exposure on mammary carcinogenesis. In contrast to the melatonin hypothesis, melatonin levels in pineal or mammary glands were not affected by MF exposure. Topical application of 12-O-tetradecanoylphorbol-13-acetate increased BrdUrd and Ki-67 labeling in

  3. Contributing Factors That Affect the Achievement of African-American Females Taught by Caucasian Teachers on the Arkansas Literacy Exam: A Case Study

    ERIC Educational Resources Information Center

    Smith, Felicia R.

    2013-01-01

    This qualitative intrinsic case study was designed to assist Caucasian educators with the researched academic skills and behaviors to engage African-American females in the learning environment. The study provided strategies and recommendations to promote self-worth, self-motivation, self-efficacy, and morale in African-American females when they…

  4. Insulin-like peptides (AmILP1 and AmILP2) differentially affect female caste development in the honey bee (Apis mellifera L.)

    PubMed Central

    Wang, Ying; Azevedo, Sergio V.; Hartfelder, Klaus; Amdam, Gro V.

    2013-01-01

    SUMMARY The food a honey bee female larva receives determines whether she develops into a large long-lived fertile queen or a short-lived sterile worker. Through well-established nutrient-sensing and growth-promoting functions in metazoans, the insulin/insulin-like growth factor 1 signaling (IIS) pathway has become a focal topic in investigations on how differences in food environment can be translated into internal signals responsible for queen–worker determination. However, low expression levels of two insulin receptors (AmInRs) in honey bee larvae and the failure of one AmInR to influence caste differentiation are in potential conflict with such a classical growth-promoting role of IIS in queen–worker development. In view of such an apparent contradiction, and the fact that binding partners and affinities of these two AmInRs have not been worked out, we performed a functional study on insulin-like peptide genes (AmILP1 and AmILP2) in honey bee larvae by using a double-stranded RNA (dsRNA)-mediated gene knockdown approach. We found that juvenile hormone (JH) levels were diminished by AmILP1 dsRNA treatment, while the AmILP2 knockdown caused a reduction in ovary size. Blood sugar titers were not significantly affected by the treatments. From these results we conclude that AmILP2 transcript levels may influence specific organ development, such as the ovary and body mass, while more general traits of caste differentiation, such as mandibles, may require additional regulators. In addition, JH production may be regulated by AmILP1 expressed locally in the brain, similar to the function of certain ILPs in Drosophila. PMID:23997199

  5. Does violence affect one gender more than the other? The mental health impact of violence among male and female university students.

    PubMed

    Romito, Patrizia; Grassi, Michele

    2007-09-01

    The impact of violence on health has been studied mostly among women. While the studies including men show that violence is detrimental for them also, knowledge concerning gender differences is scarce. This study explores whether violence has a different impact on males and females in a sample of 502 Italian university students, responding to a self-administered questionnaire. We considered violence by family members, witnessed family violence, peers/school violence, intimate partner violence, and sexual violence. Mental health outcomes included: depression, panic attacks, heavy alcohol use, eating problems, suicidal ideation and attempts, and self-evaluation of health. Both males and females reported similar rates of experienced and witnessed family violence as well as of intimate partner violence, to which women reacted more negatively than men. Peers/school violence was more common among men. Sexual violence was more common and more severe among females. Among mental health effects, panic attacks were more common among females, and alcohol problems among males. We considered the cumulative impact of violence, calculating the odds ratios (ORs) for reporting each health outcome after having experienced zero, one, two, three or four/five types of violence. For both men and women, the more violence, the higher the risk of health problems; however, the real jump in the risk of mental suffering occurred between three and four /five types of violence, the latter category more often female. Moreover, we obtained ORs for the relationships between health outcome and each type of violence, after adjustment for the other types of violence. For experienced and witnessed family violence, the health impact was similar for males and females; for intimate partner violence, sexual violence, and peer/school violence it was larger for females. In the literature, women report more violence-related health problems than men. Results of the present study imply that the excess health

  6. Astrocyte Transcriptome from the Mecp2(308)-Truncated Mouse Model of Rett Syndrome.

    PubMed

    Delépine, Chloé; Nectoux, Juliette; Letourneur, Franck; Baud, Véronique; Chelly, Jamel; Billuart, Pierre; Bienvenu, Thierry

    2015-12-01

    Mutations in the gene encoding the transcriptional modulator methyl-CpG binding protein 2 (MeCP2) are responsible for the neurodevelopmental disorder Rett syndrome which is one of the most frequent sources of intellectual disability in women. Recent studies showed that loss of Mecp2 in astrocytes contributes to Rett-like symptoms and restoration of Mecp2 can rescue some of these defects. The goal of this work is to compare gene expression profiles of wild-type and mutant astrocytes from Mecp2(308/y) mice (B6.129S-MeCP2/J) by using Affymetrix mouse 2.0 microarrays. Results were confirmed by quantitative real-time RT-PCR and by Western blot analysis. Gene set enrichment analysis utilizing Ingenuity Pathways was employed to identify pathways disrupted by Mecp2 deficiency. A total of 2152 genes were statistically differentially expressed between wild-type and mutated samples, including 1784 coding transcripts. However, only 257 showed fold changes >1.2. We confirmed our data by replicative studies in independent primary cultures of cortical astrocytes from Mecp2-deficient mice. Interestingly, two genes known to encode secreted proteins, chromogranin B and lipocalin-2, showed significant dysregulation. These proteins secreted from Mecp2-deficient glia may exert negative non-cell autonomous effects on neuronal properties, including dendritic morphology. Moreover, transcriptional profiling revealed altered Nr2f2 expression which may explain down- and upregulation of several target genes in astrocytes such as Ccl2, Lcn2 and Chgb. Unraveling Nr2f2 involvement in Mecp2-deficient astrocytes could pave the way for a better understanding of Rett syndrome pathophysiology and offers new therapeutic perspectives.

  7. Scavenger receptor B1 post-translational modifications in Rett syndrome.

    PubMed

    Sticozzi, Claudia; Belmonte, Giuseppe; Pecorelli, Alessandra; Cervellati, Franco; Leoncini, Silvia; Signorini, Cinzia; Ciccoli, Lucia; De Felice, Claudio; Hayek, Joussef; Valacchi, Giuseppe

    2013-07-11

    The modulation of the HDL receptor scavenger receptor B1 (SRB1) was evaluated in skin fibroblasts isolated from patients with Rett syndrome (RTT), a genetic form of infantile autism. Patients showed an altered plasma lipid profile, while their skin fibroblasts showed a dramatic reduction in SRB1 (immunogold, Western blot and immunohistochemistry). The decreased SRB1 levels were demonstrated to be the consequence of its binding with 4-hydroxy-2-nonenal (4HNE), a product of lipid peroxidation, and its increased ubiquitination. Our findings show for the first time a loss of SRB1 in RTT cells and its relationship with a chronic oxidative stress status.

  8. Cellular Origins of Auditory Event-Related Potential Deficits in Rett Syndrome

    PubMed Central

    Goffin, Darren; Brodkin, Edward S.; Blendy, Julie A.; Siegel, Steve J.; Zhou, Zhaolan

    2014-01-01

    Dysfunction in sensory information processing is a hallmark of many neurological disorders including autism spectrum disorders (ASDs), schizophrenia and Rett syndrome (RTT)1. Using mouse models of RTT, a monogenic disorder caused by mutations in MECP22, we demonstrate that the large scale loss of MeCP2 from forebrain GABAergic interneurons leads to deficits in auditory event-related potentials (ERPs) and seizure manifestation; but the restoration of MeCP2 in specific classes of interneurons ameliorates these deficits. PMID:24777420

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

    PubMed

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

    2015-08-01

    Tyrosine kinase inhibitor sunitinib (used in GIST, advanced RCC, and pancreatic neuroendocrine tumors) undergoes CYP3A4 metabolism and is an ABCB1B and ABCG2 efflux transporters substrate. We assessed the pharmacokinetic interaction with ibuprofen (an NSAID used by patients with cancer) in Balb/c male and female mice. Mice (study group) were coadministered (30 min apart) 30 mg/kg of ibuprofen and 60 mg/kg of sunitinib PO and compared with the control groups, which received sunitinib alone (60 mg/kg, PO). Sunitinib concentration in plasma, brain, kidney, and liver was measured by HPLC as scheduled and noncompartmental pharmacokinetic parameters estimated. In female control mice, sunitinib AUC0→∞ decreased in plasma (P < 0.05), was higher in liver and brain (P < 0.001), and lower in kidney (P < 0.001) vs. male control mice. After ibuprofen coadministration, female mice showed lower AUC0→∞ in plasma (P < 0.01), brain, liver, and kidney (all P < 0.001). However, in male mice, AUC0→∞ remained unchanged in plasma, increased in liver and kidney, and decreased in brain (all P < 0.001). The tissue-to-plasma AUC0→∞ ratio was similar between male and female control mice, but changed after ibuprofen coadministration: Male mice showed 1.6-fold higher liver-to-plasma ratio (P < 0.001) while remained unchanged in female mice and in kidney (male and female mice) but decreased 55% in brain (P < 0.05). The tissue-to-plasma partial AUC ratio, the drug tissue targeting index, and the tissue-plasma hysteresis-like plots also showed sex-based ibuprofen-sunitinib drug interaction differences. The results illustrate the relevance of this DDI on sunitinib pharmacokinetics and tissue uptake. These may be due to gender-based P450 and efflux/transporters differences.

  10. Male sexual harassment alters female social behaviour towards other females.

    PubMed

    Darden, Safi K; Watts, Lauren

    2012-04-23

    Male harassment of females to gain mating opportunities is a consequence of an evolutionary conflict of interest between the sexes over reproduction and is common among sexually reproducing species. Male Trinidadian guppies Poecilia reticulata spend a large proportion of their time harassing females for copulations and their presence in female social groups has been shown to disrupt female-female social networks and the propensity for females to develop social recognition based on familiarity. In this study, we investigate the behavioural mechanisms that may lead to this disruption of female sociality. Using two experiments, we test the hypothesis that male presence will directly affect social behaviours expressed by females towards other females in the population. In experiment one, we tested for an effect of male presence on female shoaling behaviour and found that, in the presence of a free-swimming male guppy, females spent shorter amounts of time with other females than when in the presence of a free-swimming female guppy. In experiment two, we tested for an effect of male presence on the incidence of aggressive behaviour among female guppies. When males were present in a shoal, females exhibited increased levels of overall aggression towards other females compared with female only shoals. Our work provides direct evidence that the presence of sexually harassing males alters female-female social behaviour, an effect that we expect will be recurrent across taxonomic groups.

  11. Male sexual harassment alters female social behaviour towards other females.

    PubMed

    Darden, Safi K; Watts, Lauren

    2012-04-23

    Male harassment of females to gain mating opportunities is a consequence of an evolutionary conflict of interest between the sexes over reproduction and is common among sexually reproducing species. Male Trinidadian guppies Poecilia reticulata spend a large proportion of their time harassing females for copulations and their presence in female social groups has been shown to disrupt female-female social networks and the propensity for females to develop social recognition based on familiarity. In this study, we investigate the behavioural mechanisms that may lead to this disruption of female sociality. Using two experiments, we test the hypothesis that male presence will directly affect social behaviours expressed by females towards other females in the population. In experiment one, we tested for an effect of male presence on female shoaling behaviour and found that, in the presence of a free-swimming male guppy, females spent shorter amounts of time with other females than when in the presence of a free-swimming female guppy. In experiment two, we tested for an effect of male presence on the incidence of aggressive behaviour among female guppies. When males were present in a shoal, females exhibited increased levels of overall aggression towards other females compared with female only shoals. Our work provides direct evidence that the presence of sexually harassing males alters female-female social behaviour, an effect that we expect will be recurrent across taxonomic groups. PMID:21976624

  12. Mice with an isoform-ablating Mecp2 exon 1 mutation recapitulate the neurologic deficits of Rett syndrome.

    PubMed

    Yasui, Dag H; Gonzales, Michael L; Aflatooni, Justin O; Crary, Florence K; Hu, Daniel J; Gavino, Bryant J; Golub, Mari S; Vincent, John B; Carolyn Schanen, N; Olson, Carl O; Rastegar, Mojgan; Lasalle, Janine M

    2014-05-01

    Mutations in MECP2 cause the neurodevelopmental disorder Rett syndrome (RTT OMIM 312750). Alternative inclusion of MECP2/Mecp2 exon 1 with exons 3 and 4 encodes MeCP2-e1 or MeCP2-e2 protein isoforms with unique amino termini. While most MECP2 mutations are located in exons 3 and 4 thus affecting both isoforms, MECP2 exon 1 mutations but not exon 2 mutations have been identified in RTT patients, suggesting that MeCP2-e1 deficiency is sufficient to cause RTT. As expected, genetic deletion of Mecp2 exons 3 and/or 4 recapitulates RTT-like neurologic defects in mice. However, Mecp2 exon 2 knockout mice have normal neurologic function. Here, a naturally occurring MECP2 exon 1 mutation is recapitulated in a mouse model by genetic engineering. A point mutation in the translational start codon of Mecp2 exon 1, transmitted through the germline, ablates MeCP2-e1 translation while preserving MeCP2-e2 production in mouse brain. The resulting MeCP2-e1 deficient mice developed forelimb stereotypy, hindlimb clasping, excessive grooming and hypo-activity prior to death between 7 and 31 weeks. MeCP2-e1 deficient mice also exhibited abnormal anxiety, sociability and ambulation. Despite MeCP2-e1 and MeCP2-e2 sharing, 96% amino acid identity, differences were identified. A fraction of phosphorylated MeCP2-e1 differed from the bulk of MeCP2 in subnuclear localization and co-factor interaction. Furthermore, MeCP2-e1 exhibited enhanced stability compared with MeCP2-e2 in neurons. Therefore, MeCP2-e1 deficient mice implicate MeCP2-e1 as the sole contributor to RTT with non-redundant functions.

  13. How Facial Expressions in a Rett Syndrome Population Are Recognised and Interpreted by Those around Them as Conveying Emotions

    ERIC Educational Resources Information Center

    Bergstrom-Isacsson, Marith; Lagerkvist, Bengt; Holck, Ulla; Gold, Christian

    2013-01-01

    Rett syndrome (RTT) is a neurodevelopmental disorder, including autonomic nervous system dysfunctions and severe communication impairment with an extremely limited ability to use verbal language. These individuals are therefore dependent on the capacity of caregivers to observe and interpret communicative signals, including emotional expressions.…

  14. Psychological Well-Being of Mothers and Siblings in Families of Girls and Women with Rett Syndrome

    ERIC Educational Resources Information Center

    Cianfaglione, Rina; Hastings, Richard P.; Felce, David; Clarke, Angus; Kerr, Michael P.

    2015-01-01

    Few published studies have reported on the psychological well-being of family members of individuals with Rett syndrome (RTT). Eighty-seven mothers of girls and women with RTT completed a questionnaire survey about their daughters' behavioral phenotype, current health, and behavior problems, and their own and a sibling's well-being. Mothers…

  15. A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome.

    PubMed

    Buchovecky, Christie M; Turley, Stephen D; Brown, Hannah M; Kyle, Stephanie M; McDonald, Jeffrey G; Liu, Benny; Pieper, Andrew A; Huang, Wenhui; Katz, David M; Russell, David W; Shendure, Jay; Justice, Monica J

    2013-09-01

    Mutations in MECP2, encoding methyl CpG-binding protein 2, cause Rett syndrome, the most severe autism spectrum disorder. Re-expressing Mecp2 in symptomatic Mecp2-null mice markedly improves function and longevity, providing hope that therapeutic intervention is possible in humans. To identify pathways in disease pathology for therapeutic intervention, we carried out a dominant N-ethyl-N-nitrosourea (ENU) mutagenesis suppressor screen in Mecp2-null mice and isolated five suppressors that ameliorate the symptoms of Mecp2 loss. We show that a stop codon mutation in Sqle, encoding squalene epoxidase, a rate-limiting enzyme in cholesterol biosynthesis, underlies suppression in one line. Subsequently, we also show that lipid metabolism is perturbed in the brains and livers of Mecp2-null male mice. Consistently, statin drugs improve systemic perturbations of lipid metabolism, alleviate motor symptoms and confer increased longevity in Mecp2 mutant mice. Our genetic screen therefore points to cholesterol homeostasis as a potential target for the treatment of patients with Rett syndrome.

  16. The role of microglia in brain maintenance: implications for Rett syndrome.

    PubMed

    Derecki, Noël C; Cronk, James C; Kipnis, Jonathan

    2013-03-01

    The role of microglia in central nervous system (CNS) pathology has been studied extensively, and more recently, examination of microglia in the healthy brain has yielded important insights into their many functions. It was long assumed that microglia were essentially quiescent cells, unless provoked into activation, which was considered a hallmark of disease. More recently, however, it has become increasingly clear that they are extraordinarily dynamic cells, constantly sampling their environment and adjusting to exquisitely delicate stimuli. Along these lines, our laboratory has identified a new and unexpected role for microglial phagocytosis - or lack thereof - in the pathophysiology of Rett syndrome, a neurodevelopmental disease caused by mutation of the gene encoding methyl-CpG binding protein (MECP)2. We have shown that specific expression of wild type Mecp2 in myeloid cells of Mecp2-null mice is sufficient to arrest major symptoms associated with this devastating disease. This beneficial effect, however, is abolished if phagocytic activity of microglia is inhibited. Here, we discuss microglial origins, the role of microglia in brain development and maintenance, and the phenomenon of microglial augmentation by myeloid progenitor cells in the adult brain. Finally, we address in some detail the beneficial roles of microglia as clinical targets in Rett syndrome and other neurological disorders.

  17. Clinical Guidelines for Management of Bone Health in Rett Syndrome Based on Expert Consensus and Available Evidence

    PubMed Central

    Jefferson, Amanda; Leonard, Helen; Siafarikas, Aris; Woodhead, Helen; Fyfe, Sue; Ward, Leanne M.; Munns, Craig; Motil, Kathleen; Tarquinio, Daniel; Shapiro, Jay R.; Brismar, Torkel; Ben-Zeev, Bruria; Bisgaard, Anne-Marie; Coppola, Giangennaro; Ellaway, Carolyn; Freilinger, Michael; Geerts, Suzanne; Humphreys, Peter; Jones, Mary; Lane, Jane; Larsson, Gunilla; Lotan, Meir; Percy, Alan; Pineda, Mercedes; Skinner, Steven; Syhler, Birgit; Thompson, Sue; Weiss, Batia; Witt Engerström, Ingegerd; Downs, Jenny

    2016-01-01

    Objectives We developed clinical guidelines for the management of bone health in Rett syndrome through evidence review and the consensus of an expert panel of clinicians. Methods An initial guidelines draft was created which included statements based upon literature review and 11 open-ended questions where literature was lacking. The international expert panel reviewed the draft online using a 2-stage Delphi process to reach consensus agreement. Items describe the clinical assessment of bone health, bone mineral density assessment and technique, and pharmacological and non-pharmacological interventions. Results Agreement was reached on 39 statements which were formulated from 41 statements and 11 questions. When assessing bone health in Rett syndrome a comprehensive assessment of fracture history, mutation type, prescribed medication, pubertal development, mobility level, dietary intake and biochemical bone markers is recommended. A baseline densitometry assessment should be performed with accommodations made for size, with the frequency of surveillance determined according to individual risk. Lateral spine x-rays are also suggested. Increasing physical activity and initiating calcium and vitamin D supplementation when low are the first approaches to optimizing bone health in Rett syndrome. If individuals with Rett syndrome meet the ISCD criterion for osteoporosis in children, the use of bisphosphonates is recommended. Conclusion A clinically significant history of fracture in combination with low bone densitometry findings is necessary for a diagnosis of osteoporosis. These evidence and consensus-based guidelines have the potential to improve bone health in those with Rett syndrome, reduce the frequency of fractures, and stimulate further research that aims to ameliorate the impacts of this serious comorbidity. PMID:26849438

  18. Transcriptional regulation of the MET receptor tyrosine kinase gene by MeCP2 and sex-specific expression in autism and Rett syndrome.

    PubMed

    Plummer, J T; Evgrafov, O V; Bergman, M Y; Friez, M; Haiman, C A; Levitt, P; Aldinger, K A

    2013-10-22

    Single nucleotide variants (SNV) in the gene encoding the MET receptor tyrosine kinase have been associated with an increased risk for autism spectrum disorders (ASD). The MET promoter SNV rs1858830 C 'low activity' allele is enriched in ASD, associated with reduced protein expression, and impacts functional and structural circuit connectivity in humans. To gain insight into the transcriptional regulation of MET on ASD-risk etiology, we examined an interaction between the methyl CpG-binding protein 2 (MeCP2) and the MET 5' promoter region. Mutations in MeCP2 cause Rett syndrome (RTT), a predominantly female neurodevelopmental disorder sharing some ASD clinical symptoms. MeCP2 binds to a region of the MET promoter containing the ASD-risk SNV, and displays rs1858830 genotype-specific binding in human neural progenitor cells derived from the olfactory neuroepithelium. MeCP2 binding enhances MET expression in the presence of the rs1858830 C allele, but MET transcription is attenuated by RTT-specific mutations in MeCP2. In the postmortem temporal cortex, a region normally enriched in MET, gene expression is reduced dramatically in females with RTT, although not due to enrichment of the rs1858830 C 'low activity' allele. We newly identified a sex-based reduction in MET expression, with male ASD cases, but not female ASD cases compared with sex-matched controls. The experimental data reveal a prominent allele-specific regulation of MET transcription by MeCP2. The mechanisms underlying the pronounced reduction of MET in ASD and RTT temporal cortex are distinct and likely related to factors unique to each disorder, including a noted sex bias.

  19. Neonatal treatment with lipopolysaccharide differentially affects adult anxiety responses in the light-dark test and taste neophobia test in male and female rats.

    PubMed

    Tenk, Christine M; Kavaliers, Martin; Ossenkopp, Klaus-Peter

    2013-05-01

    Neonatal administration of the bacterial cell wall component, lipopolysaccharide (LPS) has been shown to alter a variety of behavioural and physiological processes in the adult rat, including altering adult anxiety-like behaviour. Research conducted to date, however, has produced conflicting findings with some results demonstrating increases in adult anxiety-like behaviour while others report decreases or no changes in anxiety-like behaviour. Thus, the current study conducted additional evaluation of the effects of neonatal LPS exposure on adult anxiety-like behaviours by comparing the behavioural outcomes in the more traditional light-dark test, together with the less common hyponeophagia to sucrose solution paradigm. Male and female Long-Evans rats were treated systemically with either LPS (50μg/kg) or saline (0.9%) on postnatal days 3 and 5. Animals were then tested in the light-dark apparatus on postnatal day 90 for 30min. Next, following 5 days of habituation to distilled water delivery in Lickometer drinking boxes, animal were tested for neophagia to a 10% sucrose solution (0.3M) for 30min daily on postnatal days 96 and 97. In the light-dark test, neonatal LPS treatment decreased adult anxiety-like behaviour in females, but not males. In contrast, neonatal exposure to LPS did not influence adult anxiety-like behaviour as measured by hyponeophagia, but altered the licking patterns of drinking displayed towards a novel, palatable sucrose solution in adult males and females, in a manner that may reflect a decrease in situational anxiety. The current study supports the idea that neonatal LPS treatment results in highly specific alterations of adult anxiety-like behaviour, the nature of which seems to depend not only on the measure of anxiety behaviour used, but also possibly, on the degree of anxiety experienced during the behavioural test.

  20. AVR/NAVR deficiency lowers blood pressure and differentially affects urinary concentrating ability, cognition, and anxiety-like behavior in male and female mice

    PubMed Central

    Herrera, Victoria L. M.; Bagamasbad, Pia; Decano, Julius L.

    2011-01-01

    Arginine vasopressin (AVP) and angiotensin II (ANG II) are distinct peptide hormones involved in multiple organs modulating renal, cardiovascular, and brain functions. They achieve these functions via specific G protein-coupled receptors, respectively. The AVR/NAVR locus encodes two overlapping V2-type vasopressin isoreceptors: angiotensin-vasopressin receptor (AVR) responding to ANG II and AVP equivalently, and nonangiotensin vasopressin receptor (NAVR), which binds vasopressin exclusively. AVR and NAVR are expressed from a single gene by alternative promoter usage that is synergistically upregulated by testosterone and estrogen. This study tested the hypothesis that AVR/NAVR modulates urinary concentrating ability, blood pressure, and cognitive performance in vivo in a sex-specific manner. We developed a C57BL/6 inbred AVR/NAVR−/− knockout mouse that showed lower blood pressure in both male and female subjects and a urinary-concentrating defect restricted to male mice. We also detected sex-specific effects on cognitive and anxiety-like behaviors. AVR/NAVR−/− male mice exhibited impaired visuospatial and associative learning, while female mice showed improved performance in both type of cognition. AVR/NAVR deficiency produced an anxiolytic-like effect in female mice, while males were unaffected. Analysis of AVR- and NAVR-mediated phosphorylation/dephosphorylation of signaling proteins revealed activation/deactivation of known modulators of cognitive function. Our studies identify AVR/NAVR as key receptors involved in blood pressure regulation and sex-specific modulation of renal water homeostasis, cognitive function, and anxiety-like behavior. As such, the AVR/NAVR receptor system provides a molecular mechanism for sexually diergic traits and a putative common pathway for the emerging association of hypertension and cognitive decline and dementia. PMID:20923861

  1. Maternal lipopolysaccharide treatment differentially affects 5-HT(2A) and mGlu2/3 receptor function in the adult male and female rat offspring.

    PubMed

    Wischhof, Lena; Irrsack, Ellen; Dietz, Frank; Koch, Michael

    2015-10-01

    Maternal infection during pregnancy increases the risk for the offspring to develop schizophrenia. However, it is still not fully understood which biochemical mechanisms are responsible for the emergence of neuropsychiatric symptoms following prenatal immune activation. The serotonin (5-hydroxytryptamine, 5-HT) and glutamate system have prominently been associated with the schizophrenia pathophysiology but also with the mechanism of antipsychotic drug actions. Here, we investigated the behavioral and cellular response to 5-HT2A and metabotropic glutamate (mGlu)2/3 receptor stimulation in male and female offspring born to lipopolysaccharide (LPS)-treated mothers. Additionally, we assessed protein expression levels of prefrontal 5-HT2A and mGlu2 receptors. Prenatally LPS-exposed male and female offspring showed locomotor hyperactivity and increased head-twitch behavior in response to the 5-HT2A receptor agonist DOI. In LPS-exposed male offspring, the mGlu2/3 receptor agonist LY379268 failed to reduce DOI-induced prepulse inhibition deficits. In LPS-males, the behavioral changes were further accompanied by enhanced DOI-induced c-Fos protein expression and an up-regulation of prefrontal 5-HT2A receptors. No changes in either 5-HT2A or mGlu2 receptor protein levels were found in female offspring. Our data support the hypothesis of an involvement of maternal infection during pregnancy contributing, at least partially, to the pathology of schizophrenia. Identifying biochemical alterations that parallel the behavioral deficits may help to improve therapeutic strategies in the treatment of this mental illness. Since most studies in rodents almost exclusively include male subjects, our data further contribute to elucidating possible gender differences in the effects of prenatal infection on 5-HT2A and mGlu2/3 receptor function. PMID:26051401

  2. The Independent Contributions of Emotion Dysregulation and Hypermentalization to the "Double Dissociation" of Affective and Cognitive Empathy in Female Adolescent Inpatients With BPD.

    PubMed

    Kalpakci, Allison; Vanwoerden, Salome; Elhai, Jon D; Sharp, Carla

    2016-04-01

    Harari, Shamay-Tsoory, Ravid, and Levkovitz (2010) demonstrated a "double dissociation" in empathy in borderline personality disorder (BPD), such that BPD patients had higher affective than cognitive empathy, whereas controls exhibited the opposite pattern. Two processes that may relate to this dissociation are emotion dysregulation (ER) and hypermentalization. However, these interrelated processes have not been studied concomitantly, and the dissociation of empathy types has not been examined in adolescents with BPD. This study examined the relations between ER, hypermentalization, and cognitive and affective empathy in 252 adolescent inpatients with and without BPD. Participants completed a computerized task of hypermentalization and measures of ER and empathy. Findings only partially replicated Harari et al.'s findings, with differential performance in cognitive and affective empathy demonstrated across groups. Multivariate analyses revealed that in both groups, ER related to increased affective empathy. Hypermentalizing related to decreased cognitive empathy in BPD patients, whereas hypermentalizing did not relate to either empathy type in non-BPD patients.

  3. Lack of sensorial innervation in the newborn female rats affects the activity of hypothalamic monoaminergic system and steroid hormone secretion during puberty.

    PubMed

    Quiróz, Ubaldo; Morales-Ledesma, Leticia; Morán, Carolina; Trujillo, Angélica; Domínguez, Roberto

    2014-06-01

    There is evidence that sensory innervation plays a role regulating ovarian functions, including fertility.Since sensory denervation by means of capsaicin in newborn female rats results in a lower response togonadotropins, the present study analyzed the effects that sensory denervation by means of capsaicin in neonatal rats has on the concentration of monoamines in the anterior(AH) and medium (MH) hypothalamus, and on steroid hormone levels in serum. Groups of newborn female rats were injected subcutaneously with capsaicin and killed at 10, 20, and 30 days of age and on the first vaginal estrous.The concentrations of noradrenaline, dopamine, serotonin(5-HT), and their metabolites in the AH and MH were measured using HPLC, and the levels of estradiol (E),progesterone (P), testosterone (T), FSH, and luteinizing hormone using radioimmunoanalysis. The results show thatat 20 days of age, capsaicin-treated rats have lowernoradrenergic and serotonergic activities in the AH, and that the dopaminergic activity was lower in the MH. These results suggest that the sensorial system connections within the monoaminergic systems of the AH and MH are different.Capsaicin-treated animals had lower T, E, and P levels than in the control group, suggesting that the lower activity in the AH monoaminergic system and lower hormonesecretion could be explained by the blockade of information mediated by the sensory innervation (probably substance P), mainly between the ovary and the AH.

  4. Effectiveness of different corticosterone administration methods to elevate corticosterone serum levels, induce depressive-like behavior, and affect neurogenesis levels in female rats.

    PubMed

    Kott, J M; Mooney-Leber, S M; Shoubah, F A; Brummelte, S

    2016-01-15

    High levels of chronic stress or stress hormones are associated with depressive-like behavior in animal models. However, slight elevations in corticosterone (CORT) - the major stress hormone in rodents - have also been associated with improved performances, albeit in a sex-dependent manner. Some of the discrepancies in the literature regarding the effects of high CORT levels may be due to different administrations methods. The current study aims to compare the effects of ∼40mg/kg given either via subcutaneous injection, through an implanted pellet, or in the drinking water, for ∼21days on CORT serum levels, depressive-like behavior in the forced swim test (FST), and neurogenesis levels in the dentate gyrus (DG) in adult female rats. We found that animals exposed to the daily injections showed elevated CORT levels throughout the administration period, while the pellet animals showed only a transient increase, and drinking water animals revealed no elevation in CORT in serum. In addition, only the injection group exhibited higher levels of immobility in the FST. Interestingly, animals receiving CORT via injection or drinking water had lower numbers of doublecortin-positive cells in the ventral DG one week after the last CORT administration compared to animals implanted with a CORT pellet. These results will contribute to the growing literature on the effects of chronic CORT exposure and may help to clarify some of the discrepancies among previous studies, particularly in females.

  5. Rett Syndrome Mutant Neural Cells Lacks MeCP2 Immunoreactive Bands

    PubMed Central

    Bueno, Carlos; Tabares-Seisdedos, Rafael; Moraleda, Jose M.; Martinez, Salvador

    2016-01-01

    Dysfunctions of MeCP2 protein lead to various neurological disorders such as Rett syndrome and Autism. The exact functions of MeCP2 protein is still far from clear. At a molecular level, there exist contradictory data. MeCP2 protein is considered a single immunoreactive band around 75 kDa by western-blot analysis but several reports have revealed the existence of multiple MeCP2 immunoreactive bands above and below the level where MeCP2 is expected. MeCP2 immunoreactive bands have been interpreted in different ways. Some researchers suggest that multiple MeCP2 immunoreactive bands are unidentified proteins that cross-react with the MeCP2 antibody or degradation product of MeCP2, while others suggest that MeCP2 post-transcriptional processing generates multiple molecular forms linked to cell signaling, but so far they have not been properly analyzed in relation to Rett syndrome experimental models. The purpose of this study is to advance understanding of multiple MeCP2 immunoreactive bands in control neural cells and p.T158M MeCP2e1 mutant cells. We have generated stable wild-type and p.T158M MeCP2e1-RFP mutant expressing cells. Application of N- and C- terminal MeCP2 antibodies, and also, RFP antibody minimized concerns about nonspecific cross-reactivity, since they react with the same antigen at different epitopes. We report the existence of multiple MeCP2 immunoreactive bands in control cells, stable wild-type and p.T158M MeCP2e1-RFP mutant expressing cells. Also, MeCP2 immunoreactive bands differences were found between wild-type and p.T158M MeCP2e1-RFP mutant expressing cells. Slower migration phosphorylated band around 70kDa disappeared in p.T158M MeCP2e1-RFP mutant expressing cells. These data suggest that threonine 158 could represent an important phosphorylation site potentially involved in protein function. Our results clearly indicate that MeCP2 antibodies have no cross-reactivity with similar epitopes on others proteins, supporting the idea that MeCP2 may

  6. Rett Syndrome Mutant Neural Cells Lacks MeCP2 Immunoreactive Bands.

    PubMed

    Bueno, Carlos; Tabares-Seisdedos, Rafael; Moraleda, Jose M; Martinez, Salvador

    2016-01-01

    Dysfunctions of MeCP2 protein lead to various neurological disorders such as Rett syndrome and Autism. The exact functions of MeCP2 protein is still far from clear. At a molecular level, there exist contradictory data. MeCP2 protein is considered a single immunoreactive band around 75 kDa by western-blot analysis but several reports have revealed the existence of multiple MeCP2 immunoreactive bands above and below the level where MeCP2 is expected. MeCP2 immunoreactive bands have been interpreted in different ways. Some researchers suggest that multiple MeCP2 immunoreactive bands are unidentified proteins that cross-react with the MeCP2 antibody or degradation product of MeCP2, while others suggest that MeCP2 post-transcriptional processing generates multiple molecular forms linked to cell signaling, but so far they have not been properly analyzed in relation to Rett syndrome experimental models. The purpose of this study is to advance understanding of multiple MeCP2 immunoreactive bands in control neural cells and p.T158M MeCP2e1 mutant cells. We have generated stable wild-type and p.T158M MeCP2e1-RFP mutant expressing cells. Application of N- and C- terminal MeCP2 antibodies, and also, RFP antibody minimized concerns about nonspecific cross-reactivity, since they react with the same antigen at different epitopes. We report the existence of multiple MeCP2 immunoreactive bands in control cells, stable wild-type and p.T158M MeCP2e1-RFP mutant expressing cells. Also, MeCP2 immunoreactive bands differences were found between wild-type and p.T158M MeCP2e1-RFP mutant expressing cells. Slower migration phosphorylated band around 70kDa disappeared in p.T158M MeCP2e1-RFP mutant expressing cells. These data suggest that threonine 158 could represent an important phosphorylation site potentially involved in protein function. Our results clearly indicate that MeCP2 antibodies have no cross-reactivity with similar epitopes on others proteins, supporting the idea that MeCP2 may

  7. Blockage of the Neonatal Leptin Surge Affects the Gene Expression of Growth Factors, Glial Proteins, and Neuropeptides Involved in the Control of Metabolism and Reproduction in Peripubertal Male and Female Rats.

    PubMed

    Mela, Virginia; Díaz, Francisca; Lopez-Rodriguez, Ana Belen; Vázquez, María Jesús; Gertler, Arieh; Argente, Jesús; Tena-Sempere, Manuel; Viveros, María-Paz; Chowen, Julie A

    2015-07-01

    Leptin (Lep) is important in the development of neuroendocrine circuits involved in metabolic control. Because both Lep and metabolism influence pubertal development, we hypothesized that early changes in Lep signaling could also modulate hypothalamic (HT) systems involved in reproduction. We previously demonstrated that a single injection of a Lep antagonist (Antag) on postnatal day (PND)9, coincident with the neonatal Lep peak, induced sexually dimorphic modifications in trophic factors and markers of cell turnover and neuronal maturation in the HT on PND13. Here, our aim was to investigate whether the alterations induced by Lep antagonism persist into puberty. Accordingly, male and female rats were treated with a pegylated super Lep Antag from PND5 to PND9 and killed just before the normal appearance of external signs of puberty (PND33 in females and PND43 in males). There was no effect on body weight, but in males food intake increased, subcutaneous adipose tissue decreased and HT neuropeptide Y and Agouti-related peptide mRNA levels were reduced, with no effect in females. In both sexes, the Antag increased HT mRNA levels of the kisspeptin receptor, G protein-coupled recepter 54 (Gpr54). Expression of the Lep receptor, trophic factors, and glial markers were differently affected in the HT of peripubertal males and females. Lep production in adipose tissue was decreased in Antag-treated rats of both sexes, with production of other cytokines being differentially regulated between sexes. In conclusion, in addition to the long-term effects on metabolism, changes in neonatal Lep levels modifies factors involved in reproduction that could possibly affect sexual maturation.

  8. After BRCA1 and BRCA2-what next? Multifactorial segregation analyses of three-generation, population-based Australian families affected by female breast cancer.

    PubMed

    Cui, J; Antoniou, A C; Dite, G S; Southey, M C; Venter, D J; Easton, D F; Giles, G G; McCredie, M R; Hopper, J L

    2001-02-01

    Mutations in BRCA1 and BRCA2 that cause a dominantly inherited high risk of female breast cancer seem to explain only a small proportion of the aggregation of the disease. To study the possible additional genetic components, we conducted single-locus and two-locus segregation analyses, with and without a polygenic background, using three-generation families ascertained through 858 women with breast cancer diagnosed at age <40 years, ascertained through population cancer registries in Melbourne and Sydney, Australia. Extensive testing for deleterious mutations in BRCA1 and BRCA2, to date, has identified 34 carriers. Our analysis suggested that, after other possible unmeasured familial factors are adjusted for and the known BRCA1 and BRCA2 mutation carriers are excluded, there appears to be a residual dominantly inherited risk of female breast cancer in addition to that derived from mutations in BRCA1 and BRCA2. This study also suggests that there is a substantial recessively inherited risk of early-onset breast cancer. According to the best-fitting model, after excluding known carriers of mutations in BRCA1 and BRCA2, about 1/250 (95% confidence interval [CI] 1/500 to 1/125) women have a recessive risk of 86% (95% CI 69%-100%) by age 50 years and of almost 100% by age 60 years. Possible reasons that our study has implicated a novel strong recessive effect include our inclusion of data on lineal aunts and grandmothers, study of families ascertained through women with early-onset breast cancer, allowance for multiple familial factors in the analysis, and removal of families for whom the cause (i.e., BRCA1 or BRCA2) is known. Our findings may have implications for attempts to identify new breast cancer-susceptibility genes. PMID:11133358

  9. The Independent Contributions of Emotion Dysregulation and Hypermentalization to the "Double Dissociation" of Affective and Cognitive Empathy in Female Adolescent Inpatients With BPD.

    PubMed

    Kalpakci, Allison; Vanwoerden, Salome; Elhai, Jon D; Sharp, Carla

    2016-04-01

    Harari, Shamay-Tsoory, Ravid, and Levkovitz (2010) demonstrated a "double dissociation" in empathy in borderline personality disorder (BPD), such that BPD patients had higher affective than cognitive empathy, whereas controls exhibited the opposite pattern. Two processes that may relate to this dissociation are emotion dysregulation (ER) and hypermentalization. However, these interrelated processes have not been studied concomitantly, and the dissociation of empathy types has not been examined in adolescents with BPD. This study examined the relations between ER, hypermentalization, and cognitive and affective empathy in 252 adolescent inpatients with and without BPD. Participants completed a computerized task of hypermentalization and measures of ER and empathy. Findings only partially replicated Harari et al.'s findings, with differential performance in cognitive and affective empathy demonstrated across groups. Multivariate analyses revealed that in both groups, ER related to increased affective empathy. Hypermentalizing related to decreased cognitive empathy in BPD patients, whereas hypermentalizing did not relate to either empathy type in non-BPD patients. PMID:25905730

  10. Isogenic pairs of wild type and mutant induced pluripotent stem cell (iPSC) lines from Rett syndrome patients as in vitro disease model.

    PubMed

    Ananiev, Gene; Williams, Emily Cunningham; Li, Hongda; Chang, Qiang

    2011-01-01

    Rett syndrome (RTT) is an autism spectrum developmental disorder caused by mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene. Excellent RTT mouse models have been created to study the disease mechanisms, leading to many important findings with potential therapeutic implications. These include the identification of many MeCP2 target genes, better understanding of the neurobiological consequences of the loss- or mis-function of MeCP2, and drug testing in RTT mice and clinical trials in human RTT patients. However, because of potential differences in the underlying biology between humans and common research animals, there is a need to establish cell culture-based human models for studying disease mechanisms to validate and expand the knowledge acquired in animal models. Taking advantage of the nonrandom pattern of X chromosome inactivation in female induced pluripotent stem cells (iPSC), we have generated isogenic pairs of wild type and mutant iPSC lines from several female RTT patients with common and rare RTT mutations. R294X (arginine 294 to stop codon) is a common mutation carried by 5-6% of RTT patients. iPSCs carrying the R294X mutation has not been studied. We differentiated three R294X iPSC lines and their isogenic wild type control iPSC into neurons with high efficiency and consistency, and observed characteristic RTT pathology in R294X neurons. These isogenic iPSC lines provide unique resources to the RTT research community for studying disease pathology, screening for novel drugs, and testing toxicology. PMID:21966470

  11. Breathing challenges in Rett Syndrome: Lessons learned from humans and animal models✩,✩✩

    PubMed Central

    Ramirez, Jan-Marino; Ward, Christopher Scott; Neul, Jeffrey Lorenz

    2013-01-01

    Breathing disturbances are a major challenge in Rett Syndrome (RTT). These disturbances are more pronounced during wakefulness; but irregular breathing occurs also during sleep. During the day patients can exhibit alternating bouts of hypoventilation and irregular hyperventilation. But there is significant individual variability in severity, onset, duration and type of breathing disturbances. Research in mouse models of RTT suggests that different areas in the ventrolateral medulla and pons give rise to different aspects of this breathing disorder. Pre-clinical experiments in mouse models that target different neuromodulatory and neurotransmitter receptors and MeCP2 function within glia cells can partly reverse breathing abnormalities. The success in animal models raises optimism that one day it will be possible to control or potentially cure the devastating symptoms also in human patients with RTT. PMID:23816600

  12. Technological aids to support choice strategies by three girls with Rett syndrome.

    PubMed

    Stasolla, Fabrizio; Perilli, Viviana; Di Leone, Antonia; Damiani, Rita; Albano, Vincenza; Stella, Anna; Damato, Concetta

    2015-01-01

    This study was aimed at extending the use of assistive technology (i.e., photocells, interface and personal computer) to support choice strategies by three girls with Rett syndrome and severe to profound developmental disabilities. A second purpose of the study was to reduce stereotypic behaviors exhibited by the participants involved (i.e., body rocking, hand washing and hand mouthing). Finally, a third goal of the study was to monitor the effects of such program on the participants' indices of happiness. The study was carried out according to a multiple probe design across responses for each participant. Results showed that the three girls increased the adaptive responses and decreased the stereotyped behaviors during intervention phases compared to baseline. Moreover, during intervention phases, the indices of happiness augmented for each girl as well. Clinical, psychological and rehabilitative implications of the findings are discussed.

  13. A role for metabolism in Rett syndrome pathogenesis: New clinical findings and potential treatment targets.

    PubMed

    Justice, Monica J; Buchovecky, Christie M; Kyle, Stephanie M; Djukic, Aleksandra

    2013-01-01

    Rett syndrome (RTT), an X-linked neurological disorder caused by mutations in MECP2, may have a metabolic component. We reported a genetic suppressor screen in a Mecp2-null mouse model to identify pathways for therapeutic improvement of RTT symptoms. Of note, one suppressor mutation implied that cholesterol homeostasis was perturbed in Mecp2 null mice; indeed, cholesterol synthesis was elevated in the brain and body system. Remarkably, the genetic effect of downregulating the cholesterol pathway could be mimicked chemically by statin drugs, improving motor symptoms, and increasing longevity in the mouse. Our work linked cholesterol metabolism to RTT pathology for the first time. Both neurological and systemic effects of perturbed cholesterol homeostasis overlap with many RTT symptoms. Here we show in patients that peripheral cholesterol, triglycerides, and/or LDLs may be elevated early in RTT disease onset, providing a biomarker for patients that could be aided by therapeutic interventions that modulate lipid metabolism. PMID:25003017

  14. The pathophysiology of the Rett syndrome from the standpoint of polysomnography.

    PubMed

    Segawa, M; Nomura, Y

    1990-01-01

    Twelve polysomnographies were performed on eight cases of the Rett syndrome and the results were compared between cases under and over 5 years of age. There observed an increase in the ratio of stage REM (sREM) against slow wave sleep (SWS) with age. The ratio of the number of mentalis twitch movement (ment TM) during sREM against the number of rapid eye movements (REMs) (reflecting dopaminergic activities) was below normal in the younger cases but increased markedly. The ratio of ment TM in the period of REMs burst against the total ment TM during sREM (reflecting the noradrenergic hypofunction) was high in the younger group, while it decreased later. The nocturnal variation became inapparent with age in % SWS and the phasic components of sREM, while that of % sREM exaggerated at later ages. The early hypofunctions of the noradrenergic and dopaminergic neurons later modified by the serotonergic dysfunction and dopaminergic postsynaptic supersensitivity are suggested.

  15. Development of a video-based evaluation tool in Rett syndrome.

    PubMed

    Fyfe, S; Downs, J; McIlroy, O; Burford, B; Lister, J; Reilly, S; Laurvick, C L; Philippe, C; Msall, M; Kaufmann, W E; Ellaway, C; Leonard, H

    2007-10-01

    This paper describes the development of a video-based evaluation tool for use in Rett syndrome (RTT). Components include a parent-report checklist, and video filming and coding protocols that contain items on eating, drinking, communication, hand function and movements, personal care and mobility. Ninety-seven of the 169 families who initially agreed to participate returned a videotape within 8 months of the first request. Subjects whose videos were returned had a similar age profile to those who did not provide a video but were more likely to have classical than atypical RTT. Evidence of the content and social validity and inter-rater reliability on 11 videos is provided. Video may provide detailed, objective assessment of function and behaviour in RTT.

  16. Alterations in the cholinergic system of brain stem neurons in a mouse model of Rett syndrome.

    PubMed

    Oginsky, Max F; Cui, Ningren; Zhong, Weiwei; Johnson, Christopher M; Jiang, Chun

    2014-09-15

    Rett syndrome is an autism-spectrum disorder resulting from mutations to the X-linked gene, methyl-CpG binding protein 2 (MeCP2), which causes abnormalities in many systems. It is possible that the body may develop certain compensatory mechanisms to alleviate the abnormalities. The norepinephrine system originating mainly in the locus coeruleus (LC) is defective in Rett syndrome and Mecp2-null mice. LC neurons are subject to modulation by GABA, glutamate, and acetylcholine (ACh), providing an ideal system to test the compensatory hypothesis. Here we show evidence for potential compensatory modulation of LC neurons by post- and presynaptic ACh inputs. We found that the postsynaptic currents of nicotinic ACh receptors (nAChR) were smaller in amplitude and longer in decay time in the Mecp2-null mice than in the wild type. Single-cell PCR analysis showed a decrease in the expression of α3-, α4-, α7-, and β3-subunits and an increase in the α5- and α6-subunits in the mutant mice. The α5-subunit was present in many of the LC neurons with slow-decay nAChR currents. The nicotinic modulation of spontaneous GABAA-ergic inhibitory postsynaptic currents in LC neurons was enhanced in Mecp2-null mice. In contrast, the nAChR manipulation of glutamatergic input to LC neurons was unaffected in both groups of mice. Our current-clamp studies showed that the modulation of LC neurons by ACh input was reduced moderately in Mecp2-null mice, despite the major decrease in nAChR currents, suggesting possible compensatory processes may take place, thus reducing the defects to a lesser extent in LC neurons.

  17. Spectrum and distribution of MECP2 mutations in 64 Italian Rett syndrome girls: tentative genotype/phenotype correlation.

    PubMed

    Giunti, L; Pelagatti, S; Lazzerini, V; Guarducci, S; Lapi, E; Coviello, S; Cecconi, A; Ombroni, L; Andreucci, E; Sani, I; Brusaferri, A; Lasagni, A; Ricotti, G; Giometto, B; Nicolao, P; Gasparini, P; Granatiero, M; Uzielli, M L

    2001-12-01

    We report a direct DNA sequencing analysis of the MECP2 gene undertaken on a further 64 Italian patients with Rett syndrome by using a LICOR 4200 Automated Sequencer. All of the girls entering the study had a consistent clinical diagnosis for this disorder. All coding regions and the flanking intronic splice site sequences were amplified as three non-overlapping fragments by using both forward and reverse primers. The results were then compared to the MECP2 reference sequences published in GenBank. Mutations of the MECP2 gene were identified in 64 of 75 (85.33%) unrelated sporadic Rett syndrome girls. Genotype/phenotype correlation studies, in particular in groups of patients with the same mutation, did not offer definitive and interesting data. PMID:11738883

  18. Downstream targets of methyl CpG binding protein 2 and their abnormal expression in the frontal cortex of the human Rett syndrome brain

    PubMed Central

    2010-01-01

    Background The Rett Syndrome (RTT) brain displays regional histopathology and volumetric reduction, with frontal cortex showing such abnormalities, whereas the occipital cortex is relatively less affected. Results Using microarrays and quantitative PCR, the mRNA expression profiles of these two neuroanatomical regions were compared in postmortem brain tissue from RTT patients and normal controls. A subset of genes was differentially expressed in the frontal cortex of RTT brains, some of which are known to be associated with neurological disorders (clusterin and cytochrome c oxidase subunit 1) or are involved in synaptic vesicle cycling (dynamin 1). RNAi-mediated knockdown of MeCP2 in vitro, followed by further expression analysis demonstrated that the same direction of abnormal expression was recapitulated with MeCP2 knockdown, which for cytochrome c oxidase subunit 1 was associated with a functional respiratory chain defect. Chromatin immunoprecipitation (ChIP) analysis showed that MeCP2 associated with the promoter regions of some of these genes suggesting that loss of MeCP2 function may be responsible for their overexpression. Conclusions This study has shed more light on the subset of aberrantly expressed genes that result from MECP2 mutations. The mitochondrion has long been implicated in the pathogenesis of RTT, however it has not been at the forefront of RTT research interest since the discovery of MECP2 mutations. The functional consequence of the underexpression of cytochrome c oxidase subunit 1 indicates that this is an area that should be revisited. PMID:20420693

  19. [Subchromosomal microdeletion identified by molecular karyotyping using DNA microarrays (array CGH) in Rett syndrome girls negative for MECP2 gene mutations].

    PubMed

    Vorsanova, S G; Iurov, I Iu; Voinova, V Iu; Kurinnaia, O S; Zelenova, M A; Demidova, I A; Ulas, E V; Iurov, Iu B

    2013-01-01

    Molecular karyotyping using DNA microarrays (array CGH) was applied for identification of subchromosomal microdeletions in a cohort of 12 girls with clinical features of RETT syndrome, but negative for MECP2 gene mutations. Recurrent microdeletions of MECP2 gene in chromosome X (locus Xq28) were identified in 5 girls of 12 studied. Probably RTT girls with subchromosomic microdeletions in Xq28 could represent a special subtype of the disease, which appears as clinically milder than the classic form of disease. In one case, an atypical form of RTT was associated with genomic abnormalities affecting CDKL5 gene and region critical for microdeletion Prader-Willi and Angelman syndromes (15q11.2). In addition, data are presented for the first time that genetic variation in regions 3p13, 3q27.1, and 1q21.1-1q21.2 could associate with RTT-like clinical manifestations. Without application of molecular karyotyping technology and bioinformatic method of assessing the pathogenic significance of genomic rearrangements these RTT-like girls negative for MECP2 gene mutations were considered as cases of idiopathic mental retardation associated with autism. It should be noted that absence of intragenic mutations in MECP2 gene is not sufficient criteria to reject the clinical diagnosis of RTT. To avoid errors in the genetic diagnosis of this genetically heterogeneous brain disease molecular cytogenetic studies using high resolution oligonucleotide array CGH (molecular karyotyping) are needed.

  20. Intrauterine growth restriction increases the preference for palatable foods and affects sensitivity to food rewards in male and female adult rats.

    PubMed

    Dalle Molle, Roberta; Laureano, Daniela Pereira; Alves, Márcio Bonesso; Reis, Tatiane Madeira; Desai, Mina; Ross, Michael G; Silveira, Patrícia Pelufo

    2015-08-27

    Clinical evidence suggests that intrauterine growth restriction (IUGR) can cause persistent changes in the preference for palatable foods. In this study, we compared food preferences, the response to food rewards, and the role of the mesolimbic dopaminergic system in feeding behavior, between IUGR and control rats. Time-mated pregnant Sprague-Dawley rats were randomly allocated to a control group (standard chow ad libitum) or a 50% food restriction (FR) group, which received 50% of the control dams׳ habitual intake. These diets were provided from gestation day 10 to the 21st day of lactation. Within 24h of birth, pups were cross-fostered and divided into four groups: Adlib/Adlib, FR/Adlib, FR/FR, Adlib/FR. Standard chow consumption was compared between all groups. Food preferences, conditioned place preference to a palatable diet, and the levels of tyrosine hydroxylase (TH) phosphorylation and D2 receptors in the nucleus accumbens were analyzed and compared between the two groups of interest: Adlib/Adlib (control) and FR/Adlib (exposed to growth restriction during the fetal period only). IUGR adult rats had a stronger preference for palatable foods, but showed less conditioned place preference to a palatable diet than controls. D2 receptors levels were lower in IUGR rats. At baseline, TH and pTH levels were higher in FR/Adlib than control males. Measurements taken after exposure to sweet foods revealed higher levels of TH and pTH in FR/Adlib than control females. These data showed that IUGR rats exhibited a preference for palatable foods, potentially due to alterations in their mesolimbic reward pathway. Additionally, the changes observed in the mesolimbic dopaminergic system of IUGR rats proved to be sex-specific. This article is part of a Special Issue entitled 1618.

  1. Flibanserin, a drug intended for treatment of hypoactive sexual desire disorder in pre-menopausal women, affects spontaneous motor activity and brain neurochemistry in female rats.

    PubMed

    Ferger, Boris; Shimasaki, Makoto; Ceci, Angelo; Ittrich, Carina; Allers, Kelly A; Sommer, Bernd

    2010-06-01

    Flibanserin, a 5-HT(1A) receptor agonist and 5-HT(2A) receptor antagonist, is being developed for the treatment of hypoactive sexual desire disorder (HSDD) in pre-menopausal women. Here, we investigated the effects of acute administration of flibanserin (15 and 45 mg/kg, p.o.) and the selective 5-HT(1A) receptor agonist (+)-8-OH-DPAT (1 mg/kg, i.p.) on neurotransmitter levels in brain areas of female rats. Specifically, levels of dopamine (DA) and serotonin (5-HT) and neurotransmitter metabolites were examined in prefrontal cortex (PFC), nucleus accumbens, hypothalamus and brain stem using high performance liquid chromatography coupled to electrochemical detection. In addition, spontaneous motor activity was determined in an automated motor activity system. Flibanserin (45 mg/kg) but not (+)-8-OH-DPAT significantly reduced motor activity, when compared to vehicle controls. Specifically, the DA turnover was significantly increased (279%) in the PFC after flibanserin treatment but less pronounced (159%) after 8-OH-DPAT administration. Serotonin tissue levels were not altered in any of the investigated brain regions upon flibanserin treatment. However, flibanserin produced a significant decrease of the major serotonin metabolite 5-hydroxyindoleacetic acid and 5-HT turnover in the PFC, nucleus accumbens, hypothalamus and brain stem similar to (+)-8-OH-DPAT. In conclusion, the present study indicates that flibanserin is able to modulate dopaminergic and serotonergic activity in distinct brain areas. The observed effects in the PFC on dopaminergic markers are different from those induced by (+)-8-OH-DPAT and may contribute to its therapeutic efficacy in HSDD. The effects of flibanserin on spontaneous motor behaviour are in agreement with its receptor profile and underscore that flibanserin is devoid of any locomotor hyperactivity inducing properties.

  2. Rett Syndrome

    MedlinePlus

    ... may be used to control seizures. Occupational therapy, physiotherapy, and hydrotherapy may prolong mobility. Some children may require special equipment and aids such as braces to arrest scoliosis, splints to modify hand movements, and nutritional programs ...

  3. Rett syndrome

    MedlinePlus

    ... the first sign Intellectual disabilities and learning difficulties Scoliosis Shaky, unsteady, stiff gait or toe walking Seizures ... help prevent hand problems Weight bearing exercises with scoliosis Supplemental feedings can help with slowed growth. A ...

  4. Female Infertility

    MedlinePlus

    Infertility means not being able to get pregnant after at least one year of trying (or 6 ... woman keeps having miscarriages, it is also called infertility. Female infertility can result from age, physical problems, ...

  5. Mitochondrial free radical overproduction due to respiratory chain impairment in the brain of a mouse model of Rett syndrome: protective effect of CNF1.

    PubMed

    De Filippis, Bianca; Valenti, Daniela; de Bari, Lidia; De Rasmo, Domenico; Musto, Mattia; Fabbri, Alessia; Ricceri, Laura; Fiorentini, Carla; Laviola, Giovanni; Vacca, Rosa Anna

    2015-06-01

    Rett syndrome (RTT) is a pervasive neurodevelopmental disorder mainly caused by mutations in the X-linked MECP2 gene associated with severe intellectual disability, movement disorders, and autistic-like behaviors. Its pathogenesis remains mostly not understood and no effective therapy is available. High circulating levels of oxidative stress markers in patients and the occurrence of oxidative brain damage in MeCP2-deficient mouse models suggest the involvement of oxidative stress in RTT pathogenesis. However, the molecular mechanism and the origin of the oxidative stress have not been elucidated. Here we demonstrate that a redox imbalance arises from aberrant mitochondrial functionality in the brain of MeCP2-308 heterozygous female mice, a condition that more closely recapitulates that of RTT patients. The marked increase in the rate of hydrogen peroxide generation in the brain of RTT mice seems mainly produced by the dysfunctional complex II of the mitochondrial respiratory chain. In addition, both membrane potential generation and mitochondrial ATP synthesis are decreased in RTT mouse brains when succinate, the complex II respiratory substrate, is used as an energy source. Respiratory chain impairment is brain area specific, owing to a decrease in either cAMP-dependent phosphorylation or protein levels of specific complex subunits. Further, we investigated whether the treatment of RTT mice with the bacterial protein CNF1, previously reported to ameliorate the neurobehavioral phenotype and brain bioenergetic markers in an RTT mouse model, exerts specific effects on brain mitochondrial function and consequently on hydrogen peroxide production. In RTT brains treated with CNF1, we observed the reactivation of respiratory chain complexes, the rescue of mitochondrial functionality, and the prevention of brain hydrogen peroxide overproduction. These results provide definitive evidence of mitochondrial reactive oxygen species overproduction in RTT mouse brain and

  6. Female pattern hair loss.

    PubMed

    Ioannides, Dimitrios; Lazaridou, Elizabeth

    2015-01-01

    Female pattern hair loss, or female pattern androgenetic alopecia, is a nonscarring alopecia with a multi-factorial etiology that mostly affects postmenopausal women and is characterized by a reduction in hair density over the crown and frontal scalp. The clinical picture is characterized by a diffuse rarefaction of scalp hair over the mid-frontal scalp and a more-or-less intact frontal hairline without any signs of inflammation or scarring. Although the disease poses only a cosmetic concern, it is chronic and may have a significant negative psychological impact on the affected person. The aim of treating female pattern hair loss is to reduce hair loss and, to a certain extent, succeed in promoting hair regrowth. Various treatment methods are available, but it remains unclear which are the most effective. Early initiation of treatment and the combination of various modalities seem to be more efficacious than monotherapy. PMID:26370643

  7. Vaccination with a genetically modified Brugia malayi cysteine protease inhibitor-2 reduces adult parasite numbers and affects the fertility of female worms following a subcutaneous challenge of Mongolian gerbils (Meriones unguiculatus) with B. malayi infective larvae.

    PubMed

    Arumugam, Sridhar; Wei, Junfei; Ward, Danielle; Abraham, David; Lustigman, Sara; Zhan, Bin; Klei, Thomas R

    2014-09-01

    Vaccination of Mongolian gerbils with Brugia malayi cysteine protease inhibitor-2 in which the amino acid Asn66 was mutated to Lys66 (Bm-CPI-2M) resulted in reduced parasite numbers of 48.6% and 48.0% at 42 and 90 days p.i. with B. malayi L3s. Fertility of female worms was also affected at 90 days p.i. In vitro killing of L3s observed in the presence of gerbil peritoneal exudate cells and anti-Bm-CPI-2M sera suggests antibody-dependent cell-mediated cytotoxicity as a putative protective mechanism. These observations suggest that Bm-CPI-2M is a promising prophylactic and anti-fecundity vaccine candidate.

  8. The expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats

    SciTech Connect

    Katayama, Seiichi . E-mail: katayama@ankaken.co.jp; Ashizawa, Koji; Gohma, Hiroshi; Fukuhara, Tadahiro; Narumi, Kazunori; Tsuzuki, Yasuhiro; Tatemoto, Hideki; Nakada, Tadashi; Nagai, Kenji

    2006-12-15

    The objective of this study was to investigate the effects of estrogen receptor (ER) agonists and an ER antagonist on the expression of Hedgehog genes (Indian hedgehog: Ihh; Desert hedgehog: Dhh) and Hedgehog target genes (Patched 1: Ptc1; glioma-associated oncogene homolog 1: Gli1; chicken ovalbumin upstream promoter transcription factor II: Coup-TfII) in the rat uterus. Immature female rats were administered once with 17{alpha}-ethynyl estradiol (EE, an ER agonist), propyl pyrazole triole (PPT, an ER{alpha}-selective agonist), diarylpropionitrile (DPN, an ER{beta}-selective agonist), or ICI 182,780 (an ER antagonist). Expression of mRNA for Ihh, Dhh, and Ptc1 was dose-dependently downregulated by EE in the uterus of immature rats, mediated by ER as confirmed by coadministration of ICI 182,780. The mRNA expression levels of Ptc1, Gli1, and Coup-TfII were simultaneously downregulated during the period in which the mRNA expression levels of Ihh and Dhh were downregulated in the uterus after administration of EE. PPT downregulated the transcription of Ihh, Dhh, Ptc1, Gli1, and Coup-TfII, indicating that expression of these genes was regulated by the ER{alpha}-dependent pathway. DPN also downregulated the transcription of Ihh and Dhh, although the effect was weaker than that of PPT, indicating that the regulation of uterine Ihh and Dhh transcription was also affected by the ER{beta}-dependent pathway. These results suggest that the expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats.

  9. The free radical scavenger Trolox dampens neuronal hyperexcitability, reinstates synaptic plasticity, and improves hypoxia tolerance in a mouse model of Rett syndrome

    PubMed Central

    Janc, Oliwia A.; Müller, Michael

    2014-01-01

    Rett syndrome (RS) causes severe cognitive impairment, loss of speech, epilepsy, and breathing disturbances with intermittent hypoxia. Also mitochondria are affected; a subunit of respiratory complex III is dysregulated, the inner mitochondrial membrane is leaking protons, and brain ATP levels seem reduced. Our recent assessment of mitochondrial function in MeCP2 (methyl-CpG-binding protein 2)-deficient mouse (Mecp2-/y) hippocampus confirmed early metabolic alterations, an increased oxidative burden, and a more vulnerable cellular redox balance. As these changes may contribute to the manifestation of symptoms and disease progression, we now evaluated whether free radical scavengers are capable of improving neuronal and mitochondrial function in RS. Acute hippocampal slices of adult mice were incubated with the vitamin E derivative Trolox for 3–5 h. In Mecp2-/y slices this treatment dampened neuronal hyperexcitability, improved synaptic short-term plasticity, and fully restored synaptic long-term potentiation (LTP). Furthermore, Trolox specifically attenuated the increased hypoxia susceptibility of Mecp2-/y slices. Also, the anticonvulsive effects of Trolox were assessed, but the severity of 4-aminopyridine provoked seizure-like discharges was not significantly affected. Adverse side effects of Trolox on mitochondria can be excluded, but clear indications for an improvement of mitochondrial function were not found. Since several ion-channels and neurotransmitter receptors are redox modulated, the mitochondrial alterations and the associated oxidative burden may contribute to the neuronal dysfunction in RS. We confirmed in Mecp2-/y hippocampus that Trolox dampens neuronal hyperexcitability, reinstates synaptic plasticity, and improves the hypoxia tolerance. Therefore, radical scavengers are promising compounds for the treatment of neuronal dysfunction in RS and deserve further detailed evaluation. PMID:24605086

  10. Global transcriptional and translational repression in human embryonic stem cells-derived Rett Syndrome neurons

    PubMed Central

    Li, Yun; Wang, Haoyi; Muffat, Julien; Cheng, Albert W.; Orlando, David A.; Lovén, Jakob; Kwok, Show-ming; Feldman, Danielle A.; Bateup, Helen S.; Gao, Qing; Hockemeyer, Dirk; Mitalipova, Maisam; Lewis, Caroline A.; Vander Heiden, Matthew G.; Sur, Mriganka; Young, Richard A.; Jaenisch, Rudolf

    2014-01-01

    Summary Rett Syndrome (RTT) is caused by mutations of MECP2, a methyl CpG binding protein thought to act as a global transcriptional repressor. Here we show, using an isogenic human embryonic stem cell model of RTT, that MECP2 mutant neurons display key molecular and cellular features of this disorder. Unbiased global gene expression analyses demonstrate that MECP2 functions as global gene activator in neurons but not in neural precursors. Decreased transcription in neurons was coupled with a significant reduction in nascent protein synthesis and lack of MECP2 was manifested as a severe defect in the activity of the AKT/mTOR pathway. Lack of MECP2 also leads to impaired mitochondrial function in mutant neurons. Activation of AKT/mTOR signaling by exogenous growth factors or by depleting PTEN boosted protein synthesis and ameliorated disease phenotypes in mutant neurons. Our findings indicate a vital function for MECP2 in maintaining active gene transcription in human neuronal cells. PMID:24094325

  11. GABAergic dysfunction mediates autism-like stereotypies and Rett syndrome phenotypes

    PubMed Central

    Chao, Hsiao-Tuan; Chen, Hongmei; Samaco, Rodney C.; Xue, Mingshan; Chahrour, Maria; Yoo, Jong; Neul, Jeffrey L.; Gong, Shiaoching; Lu, Hui-Chen; Heintz, Nathaniel; Ekker, Marc; Rubenstein, John L.R.; Noebels, Jeffrey L.; Rosenmund, Christian; Zoghbi, Huda Y.

    2010-01-01

    Summary Mutations in the X-linked MECP2, which encodes the transcriptional regulator methyl-CpG-binding protein 2 (MeCP2) cause Rett syndrome (RTT) and several neurodevelopmental disorders including cognitive disorders, autism, juvenile-onset schizophrenia, and encephalopathy with early lethality. RTT is characterized by apparently normal early development followed by regression, motor abnormalities, seizures, and features of autism, especially stereotyped behaviors. The mechanisms mediating these striking features are poorly understood. Here we show that mice lacking Mecp2 from γ-amino-butyric-acid-(GABA)-ergic neurons recapitulate numerous RTT and autistic features, including repetitive behaviors. Loss of MeCP2 from a subset of forebrain GABAergic neurons also recapitulates many features of RTT. MeCP2-deficient GABAergic neurons show reduced inhibitory quantal size consistent with presynaptic reduction in glutamic acid decarboxylase-1 and -2 levels and GABA immunoreactivity. These data demonstrate that MeCP2 is critical for normal GABAergic neuronal function and that subtle dysfunction of GABAergic neurons contributes to numerous neuropsychiatric phenotypes. PMID:21068835

  12. Disruption of DNA-methylation-dependent long gene repression in Rett syndrome.

    PubMed

    Gabel, Harrison W; Kinde, Benyam; Stroud, Hume; Gilbert, Caitlin S; Harmin, David A; Kastan, Nathaniel R; Hemberg, Martin; Ebert, Daniel H; Greenberg, Michael E

    2015-06-01

    Disruption of the MECP2 gene leads to Rett syndrome (RTT), a severe neurological disorder with features of autism. MECP2 encodes a methyl-DNA-binding protein that has been proposed to function as a transcriptional repressor, but despite numerous mouse studies examining neuronal gene expression in Mecp2 mutants, no clear model has emerged for how MeCP2 protein regulates transcription. Here we identify a genome-wide length-dependent increase in gene expression in MeCP2 mutant mouse models and human RTT brains. We present evidence that MeCP2 represses gene expression by binding to methylated CA sites within long genes, and that in neurons lacking MeCP2, decreasing the expression of long genes attenuates RTT-associated cellular deficits. In addition, we find that long genes as a population are enriched for neuronal functions and selectively expressed in the brain. These findings suggest that mutations in MeCP2 may cause neurological dysfunction by specifically disrupting long gene expression in the brain.

  13. Stereotypical hand movements in 144 subjects with Rett syndrome from the population-based Australian database.

    PubMed

    Carter, Philippa; Downs, Jenny; Bebbington, Ami; Williams, Simon; Jacoby, Peter; Kaufmann, Walter E; Leonard, Helen

    2010-02-15

    Stereotypic hand movements are a feature of Rett Syndrome but few studies have observed their nature systematically. Video data in familiar settings were obtained on subjects (n = 144) identified from an Australian population-based database. Hand stereotypies were demonstrated by most subjects (94.4%), 15 categories were observed and midline wringing was seen in approximately 60% of subjects. There was a median of two stereotypies per subject but this number decreased with age. Clapping and mouthing of hands were more prevalent in girls younger than 8 years and wringing was more prevalent in women 19 years or older. Clapping was commoner in those with p.R306C and early truncating mutations, and much rarer in those with p.R106W, p.R270X, p.R168X, and p.R255X. Stereotypies tended to be less frequent in those with more severe mutations. Otherwise, there were no clear relationships between our categories of stereotypies and mutation. Approximately a quarter each had predominantly right and left handed stereotypies and for the remaining half, no clear laterality was seen. Results were similar for all cases and when restricted to those with a pathogenic mutation. Hand stereotypies changed with increasing age but limited relationships with MECP2 mutations were identified.

  14. Disruption of DNA-methylation-dependent long gene repression in Rett syndrome.

    PubMed

    Gabel, Harrison W; Kinde, Benyam; Stroud, Hume; Gilbert, Caitlin S; Harmin, David A; Kastan, Nathaniel R; Hemberg, Martin; Ebert, Daniel H; Greenberg, Michael E

    2015-06-01

    Disruption of the MECP2 gene leads to Rett syndrome (RTT), a severe neurological disorder with features of autism. MECP2 encodes a methyl-DNA-binding protein that has been proposed to function as a transcriptional repressor, but despite numerous mouse studies examining neuronal gene expression in Mecp2 mutants, no clear model has emerged for how MeCP2 protein regulates transcription. Here we identify a genome-wide length-dependent increase in gene expression in MeCP2 mutant mouse models and human RTT brains. We present evidence that MeCP2 represses gene expression by binding to methylated CA sites within long genes, and that in neurons lacking MeCP2, decreasing the expression of long genes attenuates RTT-associated cellular deficits. In addition, we find that long genes as a population are enriched for neuronal functions and selectively expressed in the brain. These findings suggest that mutations in MeCP2 may cause neurological dysfunction by specifically disrupting long gene expression in the brain. PMID:25762136

  15. A national survey of Rett syndrome: age, clinical characteristics, current abilities, and health.

    PubMed

    Cianfaglione, Rina; Clarke, Angus; Kerr, Mike; Hastings, Richard P; Oliver, Chris; Felce, David

    2015-07-01

    As part of a wider study to investigate the behavioral phenotype of a national sample of girls and women with Rett syndrome (RTT) in comparison to a well-chosen contrast group and its relationship to parental well-being, the development, clinical severity, current abilities and health of 91 participants were analyzed in relation to diagnostic, clinical and genetic mutation categories. Early truncating mutations or large deletions were associated with greater severity. Early regression was also associated with greater severity. All three were associated with lower current abilities. Epilepsy and weight, gastrointestinal and bowel problems were common co-morbidities. Participants with classic RTT had greater health problems than those with atypical RTT. A substantial minority of respondents reported fairly frequent signs of possible pain experienced by their relative with RTT. Overall, the study provides new data on the current abilities and general health of people with RTT and adds to the evidence that the severity of the condition and variation of subsequent disability, albeit generally within the profound range, may be related to gene mutation. The presence of certain co-morbidities represents a substantial ongoing need for better health. The experience of pain requires further investigation. PMID:25820775

  16. Cognitive training modifies frequency EEG bands and neuropsychological measures in Rett syndrome.

    PubMed

    Fabio, Rosa Angela; Billeci, Lucia; Crifaci, Giulia; Troise, Emilia; Tortorella, Gaetano; Pioggia, Giovanni

    2016-01-01

    Rett syndrome (RS) is a childhood neurodevelopmental disorder characterized by a primary disturbance in neuronal development. Neurological abnormalities in RS are reflected in several behavioral and cognitive impairments such as stereotypies, loss of speech and hand skills, gait apraxia, irregular breathing with hyperventilation while awake, and frequent seizures. Cognitive training can enhance both neuropsychological and neurophysiological parameters. The aim of this study was to investigate whether behaviors and brain activity were modified by training in RS. The modifications were assessed in two phases: (a) after a short-term training (STT) session, i.e., after 30 min of training and (b) after long-term training (LTT), i.e., after 5 days of training. Thirty-four girls with RS were divided into two groups: a training group (21 girls) who underwent the LTT and a control group (13 girls) that did not undergo LTT. The gaze and quantitative EEG (QEEG) data were recorded during the administration of the tasks. A gold-standard eye-tracker and a wearable EEG equipment were used. Results suggest that the participants in the STT task showed a habituation effect, decreased beta activity and increased right asymmetry. The participants in the LTT task looked faster and longer at the target, and show increased beta activity and decreased theta activity, while a leftward asymmetry was re-established. The overall result of this study indicates a positive effect of long-term cognitive training on brain and behavioral parameters in subject with RS. PMID:26859707

  17. Disruption of DNA methylation-dependent long gene repression in Rett syndrome

    PubMed Central

    Gabel, Harrison W.; Kinde, Benyam Z.; Stroud, Hume; Gilbert, Caitlin S.; Harmin, David A.; Kastan, Nathaniel R.; Hemberg, Martin; Ebert, Daniel H.; Greenberg, Michael E.

    2015-01-01

    Disruption of the MECP2 gene leads to Rett syndrome (RTT), a severe neurological disorder with features of autism1. MECP2 encodes a methyl-DNA-binding protein2 that has been proposed to function as a transcriptional repressor, but despite numerous studies examining neuronal gene expression in Mecp2 mutants, no clear model has emerged for how MeCP2 regulates transcription3–9. Here we identify a genome-wide length-dependent increase in gene expression in MeCP2 mutant mouse models and human RTT brains. We present evidence that MeCP2 represses gene expression by binding to methylated CA sites within long genes, and that in neurons lacking MeCP2, decreasing the expression of long genes attenuates RTT-associated cellular deficits. In addition, we find that long genes as a population are enriched for neuronal functions and selectively expressed in the brain. These findings suggest that mutations in MeCP2 may cause neurological dysfunction by specifically disrupting long gene expression in the brain. PMID:25762136

  18. A national survey of Rett syndrome: age, clinical characteristics, current abilities, and health.

    PubMed

    Cianfaglione, Rina; Clarke, Angus; Kerr, Mike; Hastings, Richard P; Oliver, Chris; Felce, David

    2015-07-01

    As part of a wider study to investigate the behavioral phenotype of a national sample of girls and women with Rett syndrome (RTT) in comparison to a well-chosen contrast group and its relationship to parental well-being, the development, clinical severity, current abilities and health of 91 participants were analyzed in relation to diagnostic, clinical and genetic mutation categories. Early truncating mutations or large deletions were associated with greater severity. Early regression was also associated with greater severity. All three were associated with lower current abilities. Epilepsy and weight, gastrointestinal and bowel problems were common co-morbidities. Participants with classic RTT had greater health problems than those with atypical RTT. A substantial minority of respondents reported fairly frequent signs of possible pain experienced by their relative with RTT. Overall, the study provides new data on the current abilities and general health of people with RTT and adds to the evidence that the severity of the condition and variation of subsequent disability, albeit generally within the profound range, may be related to gene mutation. The presence of certain co-morbidities represents a substantial ongoing need for better health. The experience of pain requires further investigation.

  19. Reduced synaptic activity in neuronal networks derived from embryonic stem cells of murine Rett syndrome model.

    PubMed

    Barth, Lydia; Sütterlin, Rosmarie; Nenniger, Markus; Vogt, Kaspar E

    2014-01-01

    Neurodevelopmental diseases such as the Rett syndrome (RTT) have received renewed attention, since the mechanisms involved may underlie a broad range of neuropsychiatric disorders such as schizophrenia and autism. In vertebrates early stages in the functional development of neurons and neuronal networks are difficult to study. Embryonic stem cell-derived neurons provide an easily accessible tool to investigate neuronal differentiation and early network formation. We used in vitro cultures of neurons derived from murine embryonic stem cells missing the methyl-CpG-binding protein 2 (MECP2) gene (MeCP2-/y) and from wild type cells of the corresponding background. Cultures were assessed using whole-cell patch-clamp electrophysiology and immunofluorescence. We studied the functional maturation of developing neurons and the activity of the synaptic connections they formed. Neurons exhibited minor differences in the developmental patterns for their intrinsic parameters, such as resting membrane potential and excitability; with the MeCP2-/y cells showing a slightly accelerated development, with shorter action potential half-widths at early stages. There was no difference in the early phase of synapse development, but as the cultures matured, significant deficits became apparent, particularly for inhibitory synaptic activity. MeCP2-/y embryonic stem cell-derived neuronal cultures show clear developmental deficits that match phenotypes observed in slice preparations and thus provide a compelling tool to further investigate the mechanisms behind RTT pathophysiology.

  20. Repeated Insulin-Like Growth Factor 1 Treatment in a Patient with Rett Syndrome: A Single Case Study

    PubMed Central

    Pini, Giorgio; Scusa, M. Flora; Benincasa, Alberto; Bottiglioni, Ilaria; Congiu, Laura; Vadhatpour, Cyrus; Romanelli, Anna Maria; Gemo, Ilaria; Puccetti, Chetti; McNamara, Rachel; O’Leary, Seán; Corvin, Aiden; Gill, Michael; Tropea, Daniela

    2014-01-01

    Rett syndrome (RTT) is a devastating neurodevelopmental disorder that has no cure. Patients show regression of acquired skills, motor, and speech impairment, cardio-respiratory distress, microcephaly, and stereotyped hand movements. The majority of RTT patients display mutations in the gene that codes for the Methyl-CpG binding protein 2 (MeCP2), which is involved in the development of the central nervous system, especially synaptic and circuit maturation. Thus, agents that promote brain development and synaptic function are good candidates for ameliorating the symptoms of RTT. In particular, insulin-like growth factor 1 (IGF1) and its active peptide (1–3) IGF1 cross the Blood Brain Barrier, and therefore are ideal treatments for RTT Indeed, both (1–3) IGF1 and IGF1 treatment significantly ameliorates RTT symptoms in a mouse model of the disease In a previous study, we established that IGF1 is safe and well tolerated on Rett patients. In this open label clinical case study, we assess the safety and tolerability of IGF1 administration in two cycles of the treatment. Before and after each cycle, we monitored the clinical and blood parameters, autonomic function, and social and cognitive abilities, and we found that IGF1 was well tolerated each time and did not induce any side effect, nor it interfered with the other treatments that the patient was undergoing. We noticed a moderate improvement in the cognitive, social, and autonomic abilities of the patient after each cycle but the benefits were not retained between the two cycles, consistent with the pre-clinical observation that treatments for RTT should be administered through life. We find that repeated IGF1 treatment is safe and well tolerated in Rett patients but observed effects are not retained between cycles. These results have applications to other pathologies considering that IGF1 has been shown to be effective in other disorders of the autism spectrum. PMID:24918098