LiCl treatment leads to long-term restoration of spine maturation and synaptogenesis in adult Tbr1 mutants / Siavash FAZEL DARBANDI in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : LiCl treatment leads to long-term restoration of spine maturation and synaptogenesis in adult Tbr1 mutants Type de document : texte imprimé Auteurs : Siavash FAZEL DARBANDI, Auteur ; Andrew D. NELSON, Auteur ; Emily Ling-Lin PAI, Auteur ; Kevin J. BENDER, Auteur ; John L.R. RUBENSTEIN, Auteur Langues : Anglais (eng) Mots-clés : Animals  Autism Spectrum Disorder/genetics  Humans  Mice  Neurogenesis/physiology  Neurons  Synaptic Transmission  T-Box Domain Proteins/genetics  Transcription Factors  Autism spectrum disorder  Cortex  Dendritic spine  Excitatory neuron  Synaptic rescue  Synaptogenesis  Tbr1  mPFCx  Neurona, a company studying the potential therapeutic use of interneuron  transplantation. The other authors declare that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Tbr1 encodes a T-box transcription factor and is considered a high confidence autism spectrum disorder (ASD) gene. Tbr1 is expressed in the postmitotic excitatory neurons of the deep neocortical layers 5 and 6. Postnatally and neonatally, Tbr1 conditional mutants (CKOs) have immature dendritic spines and reduced synaptic density. However, an understanding of Tbr1's function in the adult mouse brain remains elusive. METHODS: We used conditional mutagenesis to interrogate Tbr1's function in cortical layers 5 and 6 of the adult mouse cortex. RESULTS: Adult Tbr1 CKO mutants have dendritic spine and synaptic deficits as well as reduced frequency of mEPSCs and mIPSCs. LiCl, a WNT signaling agonist, robustly rescues the dendritic spine maturation, synaptic defects, and excitatory and inhibitory synaptic transmission deficits. CONCLUSIONS: LiCl treatment could be used as a therapeutic approach for some cases of ASD with deficits in synaptic transmission. En ligne : https://dx.doi.org/10.1186/s11689-022-09421-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] LiCl treatment leads to long-term restoration of spine maturation and synaptogenesis in adult Tbr1 mutants [texte imprimé] / Siavash FAZEL DARBANDI, Auteur ; Andrew D. NELSON, Auteur ; Emily Ling-Lin PAI, Auteur ; Kevin J. BENDER, Auteur ; John L.R. RUBENSTEIN, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Animals  Autism Spectrum Disorder/genetics  Humans  Mice  Neurogenesis/physiology  Neurons  Synaptic Transmission  T-Box Domain Proteins/genetics  Transcription Factors  Autism spectrum disorder  Cortex  Dendritic spine  Excitatory neuron  Synaptic rescue  Synaptogenesis  Tbr1  mPFCx  Neurona, a company studying the potential therapeutic use of interneuron  transplantation. The other authors declare that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Tbr1 encodes a T-box transcription factor and is considered a high confidence autism spectrum disorder (ASD) gene. Tbr1 is expressed in the postmitotic excitatory neurons of the deep neocortical layers 5 and 6. Postnatally and neonatally, Tbr1 conditional mutants (CKOs) have immature dendritic spines and reduced synaptic density. However, an understanding of Tbr1's function in the adult mouse brain remains elusive. METHODS: We used conditional mutagenesis to interrogate Tbr1's function in cortical layers 5 and 6 of the adult mouse cortex. RESULTS: Adult Tbr1 CKO mutants have dendritic spine and synaptic deficits as well as reduced frequency of mEPSCs and mIPSCs. LiCl, a WNT signaling agonist, robustly rescues the dendritic spine maturation, synaptic defects, and excitatory and inhibitory synaptic transmission deficits. CONCLUSIONS: LiCl treatment could be used as a therapeutic approach for some cases of ASD with deficits in synaptic transmission. En ligne : https://dx.doi.org/10.1186/s11689-022-09421-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

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