Characterization of Rett Syndrome-like phenotypes in Mecp2-knockout rats / Y. WU in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.23 Titre : Characterization of Rett Syndrome-like phenotypes in Mecp2-knockout rats Type de document : Texte imprimé et/ou numérique Auteurs : Y. WU, Auteur ; W. ZHONG, Auteur ; N. CUI, Auteur ; C. M. JOHNSON, Auteur ; H. XING, Auteur ; S. ZHANG, Auteur ; C. JIANG, Auteur Article en page(s) : p.23 Langues : Anglais (eng) Mots-clés : Behaviors  Breathing  Locus coeruleus  Mecp2-null rat  Rett syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett Syndrome (RTT) is a neurodevelopmental disease caused by the disruption of the MECP2 gene. Several mouse models of RTT have been developed with Mecp2 disruptions. Although the mouse models are widely used in RTT research, results obtained need to be validated in other species. Therefore, we performed these studies to characterize phenotypes of a novel Mecp2 (-/Y) rat model and compared them with the Mecp2 (tm1.1Bird) mouse model of RTT. METHODS: RTT-like phenotypes were systematically studied and compared between Mecp2 (-/Y) rats and Mecp2 (-/Y) mice. In-cage conditions of the rats were monitored. Grip strength and spontaneous locomotion were used to evaluate the motor function. Three-chamber test was performed to show autism-type behaviors. Breathing activity was recorded with the plethysmograph. Individual neurons in the locus coeruleus (LC) were studied in the whole-cell current clamp. The lifespan of the rats was determined with their survival time. RESULTS: Mecp2 (-/Y) rats displayed growth retardation, malocclusion, and lack of movements, while hindlimb clasping was not seen. They had weaker forelimb grip strength and a lower rate of locomotion than the WT littermates. Defects in social interaction with other rats were obvious. Breathing frequency variation and apnea in the null rats were significantly higher than in the WT. LC neurons in the null rats showed excessive firing activity. A half of the null rats died in 2 months. Most of the RTT-like symptoms were comparable to those seen in Mecp2 (-/Y) mice, while some appeared more or less severe. The findings that most RTT-like symptoms exist in the rat model with moderate variations and differences from the mouse models support the usefulness of both Mecp2 (-/Y) rodent models. CONCLUSIONS: The novel Mecp2 (-/Y) rat model recapitulated numerous RTT-like symptoms as Mecp2 (-/Y) mouse models did, which makes it a valuable alternative model in the RTT studies when the body size matters. En ligne : http://dx.doi.org/10.1186/s11689-016-9156-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Characterization of Rett Syndrome-like phenotypes in Mecp2-knockout rats [Texte imprimé et/ou numérique] / Y. WU, Auteur ; W. ZHONG, Auteur ; N. CUI, Auteur ; C. M. JOHNSON, Auteur ; H. XING, Auteur ; S. ZHANG, Auteur ; C. JIANG, Auteur . - p.23. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.23 Mots-clés : Behaviors  Breathing  Locus coeruleus  Mecp2-null rat  Rett syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett Syndrome (RTT) is a neurodevelopmental disease caused by the disruption of the MECP2 gene. Several mouse models of RTT have been developed with Mecp2 disruptions. Although the mouse models are widely used in RTT research, results obtained need to be validated in other species. Therefore, we performed these studies to characterize phenotypes of a novel Mecp2 (-/Y) rat model and compared them with the Mecp2 (tm1.1Bird) mouse model of RTT. METHODS: RTT-like phenotypes were systematically studied and compared between Mecp2 (-/Y) rats and Mecp2 (-/Y) mice. In-cage conditions of the rats were monitored. Grip strength and spontaneous locomotion were used to evaluate the motor function. Three-chamber test was performed to show autism-type behaviors. Breathing activity was recorded with the plethysmograph. Individual neurons in the locus coeruleus (LC) were studied in the whole-cell current clamp. The lifespan of the rats was determined with their survival time. RESULTS: Mecp2 (-/Y) rats displayed growth retardation, malocclusion, and lack of movements, while hindlimb clasping was not seen. They had weaker forelimb grip strength and a lower rate of locomotion than the WT littermates. Defects in social interaction with other rats were obvious. Breathing frequency variation and apnea in the null rats were significantly higher than in the WT. LC neurons in the null rats showed excessive firing activity. A half of the null rats died in 2 months. Most of the RTT-like symptoms were comparable to those seen in Mecp2 (-/Y) mice, while some appeared more or less severe. The findings that most RTT-like symptoms exist in the rat model with moderate variations and differences from the mouse models support the usefulness of both Mecp2 (-/Y) rodent models. CONCLUSIONS: The novel Mecp2 (-/Y) rat model recapitulated numerous RTT-like symptoms as Mecp2 (-/Y) mouse models did, which makes it a valuable alternative model in the RTT studies when the body size matters. En ligne : http://dx.doi.org/10.1186/s11689-016-9156-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Effects of early-life exposure to THIP on phenotype development in a mouse model of Rett syndrome / W. ZHONG in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.37 Titre : Effects of early-life exposure to THIP on phenotype development in a mouse model of Rett syndrome Type de document : Texte imprimé et/ou numérique Auteurs : W. ZHONG, Auteur ; C. M. JOHNSON, Auteur ; Y. WU, Auteur ; N. CUI, Auteur ; H. XING, Auteur ; S. ZHANG, Auteur ; C. JIANG, Auteur Article en page(s) : p.37 Langues : Anglais (eng) Mots-clés : Behavior  Gaboxadol  Locus coeruleus  Mecp2  Rett syndrome  Thip Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett syndrome (RTT) is a neurodevelopmental disorder caused mostly by disruptions in the MECP2 gene. MECP2-null mice show imbalances in neuronal excitability and synaptic communications. Several previous studies indicate that augmenting synaptic GABA receptors (GABAARs) can alleviate RTT-like symptoms in mice. In addition to the synaptic GABAARs, there is a group of GABAARs found outside the synaptic cleft with the capability to produce sustained inhibition, which may be potential therapeutic targets for the control of neuronal excitability in RTT. METHODS: Wild-type and MECP2-null mice were randomly divided into four groups, receiving the extrasynaptic GABAAR agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol hydrochloride (THIP) and vehicle control, respectively. Low-dose THIP was administered to neonatal mice through lactation. RTT-like symptoms including lifespan, breathing, motor function, and social behaviors were studied when mice became mature. Changes in neuronal excitability and norepinephrine biosynthesis enzyme expression were studied in electrophysiology and molecular biology. RESULTS: With no evident sedation and other adverse side effects, early-life exposure to THIP extended the lifespan, alleviated breathing abnormalities, enhanced motor function, and improved social behaviors of MECP2-null mice. Such beneficial effects were associated with stabilization of locus coeruleus neuronal excitability and improvement of norepinephrine biosynthesis enzyme expression. CONCLUSIONS: THIP treatment in early lives might be a therapeutic approach to RTT-like symptoms in MECP2-null mice and perhaps in people with RTT as well. En ligne : http://dx.doi.org/10.1186/s11689-016-9169-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Effects of early-life exposure to THIP on phenotype development in a mouse model of Rett syndrome [Texte imprimé et/ou numérique] / W. ZHONG, Auteur ; C. M. JOHNSON, Auteur ; Y. WU, Auteur ; N. CUI, Auteur ; H. XING, Auteur ; S. ZHANG, Auteur ; C. JIANG, Auteur . - p.37. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.37 Mots-clés : Behavior  Gaboxadol  Locus coeruleus  Mecp2  Rett syndrome  Thip Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett syndrome (RTT) is a neurodevelopmental disorder caused mostly by disruptions in the MECP2 gene. MECP2-null mice show imbalances in neuronal excitability and synaptic communications. Several previous studies indicate that augmenting synaptic GABA receptors (GABAARs) can alleviate RTT-like symptoms in mice. In addition to the synaptic GABAARs, there is a group of GABAARs found outside the synaptic cleft with the capability to produce sustained inhibition, which may be potential therapeutic targets for the control of neuronal excitability in RTT. METHODS: Wild-type and MECP2-null mice were randomly divided into four groups, receiving the extrasynaptic GABAAR agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol hydrochloride (THIP) and vehicle control, respectively. Low-dose THIP was administered to neonatal mice through lactation. RTT-like symptoms including lifespan, breathing, motor function, and social behaviors were studied when mice became mature. Changes in neuronal excitability and norepinephrine biosynthesis enzyme expression were studied in electrophysiology and molecular biology. RESULTS: With no evident sedation and other adverse side effects, early-life exposure to THIP extended the lifespan, alleviated breathing abnormalities, enhanced motor function, and improved social behaviors of MECP2-null mice. Such beneficial effects were associated with stabilization of locus coeruleus neuronal excitability and improvement of norepinephrine biosynthesis enzyme expression. CONCLUSIONS: THIP treatment in early lives might be a therapeutic approach to RTT-like symptoms in MECP2-null mice and perhaps in people with RTT as well. En ligne : http://dx.doi.org/10.1186/s11689-016-9169-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

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