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Auteur Xian ZHANG |
Documents disponibles écrits par cet auteur (2)
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Tau reduction attenuates autism-like features in Fmr1 knockout mice / Xiangyu JIANG ; Linkun HAN ; Yiru JIANG ; Yong WANG ; Jian MENG ; Xiang ZHU ; Xian ZHANG ; Hong LUO ; Yun-Wu ZHANG in Molecular Autism, 14 (2023)
[article]
Titre : Tau reduction attenuates autism-like features in Fmr1 knockout mice Type de document : Texte imprimé et/ou numérique Auteurs : Xiangyu JIANG, Auteur ; Linkun HAN, Auteur ; Yiru JIANG, Auteur ; Yong WANG, Auteur ; Jian MENG, Auteur ; Xiang ZHU, Auteur ; Xian ZHANG, Auteur ; Hong LUO, Auteur ; Yun-Wu ZHANG, Auteur Article en page(s) : 42 p. Langues : Anglais (eng) Mots-clés : Animals Mice Male Female Mice, Knockout *Autism Spectrum Disorder *Autistic Disorder/genetics tau Proteins/genetics/metabolism Fragile X Mental Retardation Protein/genetics/metabolism *Fragile X Syndrome/genetics/metabolism Disease Models, Animal Antisense oligonucleotide Autism spectrum disorder Fmr1 Fragile X syndrome P38/MAPK signaling Tau Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is a leading cause of autism spectrum disorder (ASD) and resulted from a loss of the FMR1-encoded fragile X messenger ribonucleoprotein 1 (FMRP) protein due to large CGG repeat expansions in the promoter region of the FMR1 gene. The microtubule-associated protein Tau is a promising target for Tauopathic diseases and our preliminary study found that Tau protein levels were increased in the brain of Fmr1 knockout (KO) mice, a model of FXS. However, whether Tau reduction can prevent autism-like features in Fmr1 KO mice and become a novel strategy for FXS treatment remain unknown. METHODS: Tau was genetically reduced in Fmr1 KO mice through crossing Fmr1(+) female mice with Mapt(+) male mice. The male offspring with different genotypes were subjected to various autism-related behavioral tests, RNA sequencing, and biochemical analysis. Fmr1 KO male mice were treated with Tau-targeting antisense oligonucleotide (ASO) and then subjected to behavioral tests and biochemical analysis. RESULTS: Tau expression was increased in the cortex of Fmr1 KO mice. Genetically reducing Tau prevented social defects, stereotyped and repetitive behavior, and spine abnormality in Fmr1 KO mice. Tau reduction also reversed increased periodic activity and partially rescued Per1 expression reduction in Fmr1 KO mice. Moreover, Tau reduction reversed compromised P38/MAPK signaling in Fmr1 KO mice. Finally, Tau-targeting ASO also effectively alleviated autism-like phenotypes and promoted P38/MAPK signaling in Fmr1 KO mice. LIMITATIONS: Our study is limited to male mice, in agreement with the higher incidence of FXS in males than females. Whether Tau reduction also exerts protection in females deserves further scrutiny. Moreover, although Tau reduction rescues impaired P38/MAPK signaling in Fmr1 KO mice, whether this is the responsible molecular mechanism requires further determination. CONCLUSION: Our data indicate that Tau reduction prevents autism-like phenotypes in Fmr1 KO mice. Tau may become a new target for FXS treatment. En ligne : https://dx.doi.org/10.1186/s13229-023-00574-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518
in Molecular Autism > 14 (2023) . - 42 p.[article] Tau reduction attenuates autism-like features in Fmr1 knockout mice [Texte imprimé et/ou numérique] / Xiangyu JIANG, Auteur ; Linkun HAN, Auteur ; Yiru JIANG, Auteur ; Yong WANG, Auteur ; Jian MENG, Auteur ; Xiang ZHU, Auteur ; Xian ZHANG, Auteur ; Hong LUO, Auteur ; Yun-Wu ZHANG, Auteur . - 42 p.
Langues : Anglais (eng)
in Molecular Autism > 14 (2023) . - 42 p.
Mots-clés : Animals Mice Male Female Mice, Knockout *Autism Spectrum Disorder *Autistic Disorder/genetics tau Proteins/genetics/metabolism Fragile X Mental Retardation Protein/genetics/metabolism *Fragile X Syndrome/genetics/metabolism Disease Models, Animal Antisense oligonucleotide Autism spectrum disorder Fmr1 Fragile X syndrome P38/MAPK signaling Tau Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is a leading cause of autism spectrum disorder (ASD) and resulted from a loss of the FMR1-encoded fragile X messenger ribonucleoprotein 1 (FMRP) protein due to large CGG repeat expansions in the promoter region of the FMR1 gene. The microtubule-associated protein Tau is a promising target for Tauopathic diseases and our preliminary study found that Tau protein levels were increased in the brain of Fmr1 knockout (KO) mice, a model of FXS. However, whether Tau reduction can prevent autism-like features in Fmr1 KO mice and become a novel strategy for FXS treatment remain unknown. METHODS: Tau was genetically reduced in Fmr1 KO mice through crossing Fmr1(+) female mice with Mapt(+) male mice. The male offspring with different genotypes were subjected to various autism-related behavioral tests, RNA sequencing, and biochemical analysis. Fmr1 KO male mice were treated with Tau-targeting antisense oligonucleotide (ASO) and then subjected to behavioral tests and biochemical analysis. RESULTS: Tau expression was increased in the cortex of Fmr1 KO mice. Genetically reducing Tau prevented social defects, stereotyped and repetitive behavior, and spine abnormality in Fmr1 KO mice. Tau reduction also reversed increased periodic activity and partially rescued Per1 expression reduction in Fmr1 KO mice. Moreover, Tau reduction reversed compromised P38/MAPK signaling in Fmr1 KO mice. Finally, Tau-targeting ASO also effectively alleviated autism-like phenotypes and promoted P38/MAPK signaling in Fmr1 KO mice. LIMITATIONS: Our study is limited to male mice, in agreement with the higher incidence of FXS in males than females. Whether Tau reduction also exerts protection in females deserves further scrutiny. Moreover, although Tau reduction rescues impaired P38/MAPK signaling in Fmr1 KO mice, whether this is the responsible molecular mechanism requires further determination. CONCLUSION: Our data indicate that Tau reduction prevents autism-like phenotypes in Fmr1 KO mice. Tau may become a new target for FXS treatment. En ligne : https://dx.doi.org/10.1186/s13229-023-00574-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518 Unpacking complexities in ethnic-racial socialization in transracial adoptive families: A process-oriented transactional system / Ellen E. PINDERHUGHES in Development and Psychopathology, 33-2 (May 2021)
[article]
Titre : Unpacking complexities in ethnic-racial socialization in transracial adoptive families: A process-oriented transactional system Type de document : Texte imprimé et/ou numérique Auteurs : Ellen E. PINDERHUGHES, Auteur ; Jessica A. K. MATTHEWS, Auteur ; Xian ZHANG, Auteur ; Judith C. SCOTT, Auteur Année de publication : 2021 Article en page(s) : p.493-505 Langues : Anglais (eng) Mots-clés : adoptees adoption ethnic–racial socialization parenting transracial adoption Index. décimale : PER Périodiques Résumé : Over 50% of adoptions are transracial, involving primarily White parents and children of color from different ethnic or racial backgrounds. Transracial adoptive (TRA) parents are tasked with providing ethnic-racial socialization processes (ERS) to support TRA adoptees' ethnic-racial identity development and prepare them to cope with ethnic-racial discrimination. However, unlike nonadoptive families of color, TRA parents lack shared cultural history with adoptees and have limited experience navigating racial discrimination. Knowledge of ERS among TRA families has centered on unidirectional processes between parenting constructs, ERS processes, and children's functioning. However, ERS processes in this population have complexities and nuances that warrant more sensitive and robust conceptualization. This paper proposes a process-oriented dynamic ecological model of the system of ERS, situating transacting processes in and across multiple family levels (parent, adoptee, family) and incorporating developmental and contextual considerations. With its framing of the complexities in ERS among TRA families, the model offers three contributions: a conceptual organization of parenting constructs related to ERS, a more robust understanding of ERS processes that inform how parents provide ERS, and framing of transacting processes within and between parenting constructs, ERS processes, and children's functioning. Implications for research, policy, and practice are discussed. En ligne : http://dx.doi.org/10.1017/s0954579420001741 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=444
in Development and Psychopathology > 33-2 (May 2021) . - p.493-505[article] Unpacking complexities in ethnic-racial socialization in transracial adoptive families: A process-oriented transactional system [Texte imprimé et/ou numérique] / Ellen E. PINDERHUGHES, Auteur ; Jessica A. K. MATTHEWS, Auteur ; Xian ZHANG, Auteur ; Judith C. SCOTT, Auteur . - 2021 . - p.493-505.
Langues : Anglais (eng)
in Development and Psychopathology > 33-2 (May 2021) . - p.493-505
Mots-clés : adoptees adoption ethnic–racial socialization parenting transracial adoption Index. décimale : PER Périodiques Résumé : Over 50% of adoptions are transracial, involving primarily White parents and children of color from different ethnic or racial backgrounds. Transracial adoptive (TRA) parents are tasked with providing ethnic-racial socialization processes (ERS) to support TRA adoptees' ethnic-racial identity development and prepare them to cope with ethnic-racial discrimination. However, unlike nonadoptive families of color, TRA parents lack shared cultural history with adoptees and have limited experience navigating racial discrimination. Knowledge of ERS among TRA families has centered on unidirectional processes between parenting constructs, ERS processes, and children's functioning. However, ERS processes in this population have complexities and nuances that warrant more sensitive and robust conceptualization. This paper proposes a process-oriented dynamic ecological model of the system of ERS, situating transacting processes in and across multiple family levels (parent, adoptee, family) and incorporating developmental and contextual considerations. With its framing of the complexities in ERS among TRA families, the model offers three contributions: a conceptual organization of parenting constructs related to ERS, a more robust understanding of ERS processes that inform how parents provide ERS, and framing of transacting processes within and between parenting constructs, ERS processes, and children's functioning. Implications for research, policy, and practice are discussed. En ligne : http://dx.doi.org/10.1017/s0954579420001741 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=444