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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)
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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
in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.37[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