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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 Cost-effectiveness of cognitive-behavioral therapy versus treatment as usual for anxiety disorders in children with autism spectrum disorder / Francisca J. A. VAN STEENSEL in Research in Autism Spectrum Disorders, 8-2 (February 2014)
[article]
Titre : Cost-effectiveness of cognitive-behavioral therapy versus treatment as usual for anxiety disorders in children with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Francisca J. A. VAN STEENSEL, Auteur ; Carmen D. DIRKSEN, Auteur ; Susan M. BOGELS, Auteur Article en page(s) : p.127-137 Langues : Anglais (eng) Mots-clés : Anxiety CBT TAU Cost-effectiveness Index. décimale : PER Périodiques Résumé : Abstract The study's aim was to evaluate the cost-effectiveness of CBT compared to treatment as usual (TAU). In total, 49 children aged 8–18 years with ASD and comorbid anxiety disorders, and their parents, participated; 24 were assigned to CBT and 25 were assigned to TAU. Outcome measures were the percentage of children free from their primary anxiety disorder and quality adjusted life years (QALYs). Costs were measured using a retrospective cost-questionnaire. Effects and costs were assessed at pre-, post-, and three months after treatment. Effects and costs were not statistically different between CBT and TAU, however the incremental cost-effectiveness ratio (ICER) demonstrated that CBT dominates TAU. Bootstrapped ICERs demonstrated that CBT has a high probability to be more effective than TAU, however, the probability that either CBT or TAU is more costly did not differ much. Secondary analyses demonstrated fairly robust results. CBT seems a cost-effective intervention compared to TAU, however, long-term follow-ups and comparisons between CBT and specific TAUs are necessary. Cost-effectiveness analyses may help inform policy makers to decide how to treat anxiety disorders in children with ASD. En ligne : http://dx.doi.org/10.1016/j.rasd.2013.11.001 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=221
in Research in Autism Spectrum Disorders > 8-2 (February 2014) . - p.127-137[article] Cost-effectiveness of cognitive-behavioral therapy versus treatment as usual for anxiety disorders in children with autism spectrum disorder [Texte imprimé et/ou numérique] / Francisca J. A. VAN STEENSEL, Auteur ; Carmen D. DIRKSEN, Auteur ; Susan M. BOGELS, Auteur . - p.127-137.
Langues : Anglais (eng)
in Research in Autism Spectrum Disorders > 8-2 (February 2014) . - p.127-137
Mots-clés : Anxiety CBT TAU Cost-effectiveness Index. décimale : PER Périodiques Résumé : Abstract The study's aim was to evaluate the cost-effectiveness of CBT compared to treatment as usual (TAU). In total, 49 children aged 8–18 years with ASD and comorbid anxiety disorders, and their parents, participated; 24 were assigned to CBT and 25 were assigned to TAU. Outcome measures were the percentage of children free from their primary anxiety disorder and quality adjusted life years (QALYs). Costs were measured using a retrospective cost-questionnaire. Effects and costs were assessed at pre-, post-, and three months after treatment. Effects and costs were not statistically different between CBT and TAU, however the incremental cost-effectiveness ratio (ICER) demonstrated that CBT dominates TAU. Bootstrapped ICERs demonstrated that CBT has a high probability to be more effective than TAU, however, the probability that either CBT or TAU is more costly did not differ much. Secondary analyses demonstrated fairly robust results. CBT seems a cost-effective intervention compared to TAU, however, long-term follow-ups and comparisons between CBT and specific TAUs are necessary. Cost-effectiveness analyses may help inform policy makers to decide how to treat anxiety disorders in children with ASD. En ligne : http://dx.doi.org/10.1016/j.rasd.2013.11.001 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=221