Disruption of visual circuit formation and refinement in a mouse model of autism / Ning CHENG in Autism Research, 10-2 (February 2017)  

Public ISBD [article]  inAutism Research > 10-2 (February 2017) . - p.212-223 Titre : Disruption of visual circuit formation and refinement in a mouse model of autism Type de document : Texte imprimé et/ou numérique Auteurs : Ning CHENG, Auteur ; Maryam KHANBABAEI, Auteur ; Kartikeya MURARI, Auteur ; Jong M. RHO, Auteur Article en page(s) : p.212-223 Langues : Anglais (eng) Mots-clés : autism spectrum disorder  brain circuit  synaptic patterning  visual system  lateral geniculate nucleus  eye-specific segregation  BTBR mouse Index. décimale : PER Périodiques Résumé : Aberrant connectivity is believed to contribute to the pathophysiology of autism spectrum disorder (ASD). Recent neuroimaging studies have increasingly identified such impairments in patients with ASD, including alterations in sensory systems. However, the cellular substrates and molecular underpinnings of disrupted connectivity remain poorly understood. Utilizing eye-specific segregation in the dorsal lateral geniculate nucleus (dLGN) as a model system, we investigated the formation and refinement of precise patterning of synaptic connections in the BTBR T?+?tf/J (BTBR) mouse model of ASD. We found that at the neonatal stage, the shape of the dLGN occupied by retinal afferents was altered in the BTBR group compared to C57BL/6J (B6) animals. Notably, the degree of overlap between the ipsi- and contralateral afferents was significantly greater in the BTBR mice. Moreover, these abnormalities continued into mature stage in the BTBR animals, suggesting persistent deficits rather than delayed maturation of axonal refinement. Together, these results indicate disrupted connectivity at the synaptic patterning level in the BTBR mice, suggesting that in general, altered neural circuitry may contribute to autistic behaviours seen in this animal model. In addition, these data are consistent with the notion that lower-level, primary processing mechanisms contribute to altered visual perception in ASD. En ligne : http://dx.doi.org/10.1002/aur.1687 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=303 [article] Disruption of visual circuit formation and refinement in a mouse model of autism [Texte imprimé et/ou numérique] / Ning CHENG, Auteur ; Maryam KHANBABAEI, Auteur ; Kartikeya MURARI, Auteur ; Jong M. RHO, Auteur . - p.212-223. Langues : Anglais (eng) in Autism Research > 10-2 (February 2017) . - p.212-223 Mots-clés : autism spectrum disorder  brain circuit  synaptic patterning  visual system  lateral geniculate nucleus  eye-specific segregation  BTBR mouse Index. décimale : PER Périodiques Résumé : Aberrant connectivity is believed to contribute to the pathophysiology of autism spectrum disorder (ASD). Recent neuroimaging studies have increasingly identified such impairments in patients with ASD, including alterations in sensory systems. However, the cellular substrates and molecular underpinnings of disrupted connectivity remain poorly understood. Utilizing eye-specific segregation in the dorsal lateral geniculate nucleus (dLGN) as a model system, we investigated the formation and refinement of precise patterning of synaptic connections in the BTBR T?+?tf/J (BTBR) mouse model of ASD. We found that at the neonatal stage, the shape of the dLGN occupied by retinal afferents was altered in the BTBR group compared to C57BL/6J (B6) animals. Notably, the degree of overlap between the ipsi- and contralateral afferents was significantly greater in the BTBR mice. Moreover, these abnormalities continued into mature stage in the BTBR animals, suggesting persistent deficits rather than delayed maturation of axonal refinement. Together, these results indicate disrupted connectivity at the synaptic patterning level in the BTBR mice, suggesting that in general, altered neural circuitry may contribute to autistic behaviours seen in this animal model. In addition, these data are consistent with the notion that lower-level, primary processing mechanisms contribute to altered visual perception in ASD. En ligne : http://dx.doi.org/10.1002/aur.1687 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=303

Genetic modifications associated with ketogenic diet treatment in the BTBRT+Tf/J mouse model of autism spectrum disorder / Richelle MYCHASIUK in Autism Research, 10-3 (March 2017)  

Public ISBD [article]  inAutism Research > 10-3 (March 2017) . - p.456-471 Titre : Genetic modifications associated with ketogenic diet treatment in the BTBRT+Tf/J mouse model of autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Richelle MYCHASIUK, Auteur ; Jong M. RHO, Auteur Article en page(s) : p.456-471 Langues : Anglais (eng) Mots-clés : autism spectrum disorder  ketogenic diet  RNAseq  temporal cortex  hippocampus  mitochondria  development Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is a prevalent and heterogeneous neurodevelopmental disorder characterized by hallmark behavioral features. The spectrum of disorders that fall within the ASD umbrella encompass a distinct but overlapping symptom complex that likely results from an array of molecular and genetic aberrations rather than a single genetic mutation. The ketogenic diet (KD) is a high-fat low-carbohydrate anti-seizure and neuroprotective diet that has demonstrated efficacy in the treatment of ASD-like behaviors in animal and human studies. Methods: We investigated changes in mRNA and gene expression in the BTBR mouse model of ASD that may contribute to the behavioral phenotype. In addition, we sought to examine changes in gene expression following KD treatment in BTBR mice. Results: Despite significant behavioral abnormalities, expression changes in BTBR mice did not differ substantially from controls; only 33 genes were differentially expressed in the temporal cortex, and 48 in the hippocampus. Examination of these differentially expressed genes suggested deficits in the stress response and in neuronal signaling/communication. After treatment with the KD, both brain regions demonstrated improvements in ASD deficits associated with myelin formation and white matter development. Conclusions: Although our study supports many of the previously known impairments associated with ASD, such as excessive myelin formation and impaired GABAergic transmission, the RNAseq data and pathway analysis utilized here identified new therapeutic targets for analysis, such as Vitamin D pathways and cAMP signaling. En ligne : http://dx.doi.org/10.1002/aur.1682 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=304 [article] Genetic modifications associated with ketogenic diet treatment in the BTBRT+Tf/J mouse model of autism spectrum disorder [Texte imprimé et/ou numérique] / Richelle MYCHASIUK, Auteur ; Jong M. RHO, Auteur . - p.456-471. Langues : Anglais (eng) in Autism Research > 10-3 (March 2017) . - p.456-471 Mots-clés : autism spectrum disorder  ketogenic diet  RNAseq  temporal cortex  hippocampus  mitochondria  development Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is a prevalent and heterogeneous neurodevelopmental disorder characterized by hallmark behavioral features. The spectrum of disorders that fall within the ASD umbrella encompass a distinct but overlapping symptom complex that likely results from an array of molecular and genetic aberrations rather than a single genetic mutation. The ketogenic diet (KD) is a high-fat low-carbohydrate anti-seizure and neuroprotective diet that has demonstrated efficacy in the treatment of ASD-like behaviors in animal and human studies. Methods: We investigated changes in mRNA and gene expression in the BTBR mouse model of ASD that may contribute to the behavioral phenotype. In addition, we sought to examine changes in gene expression following KD treatment in BTBR mice. Results: Despite significant behavioral abnormalities, expression changes in BTBR mice did not differ substantially from controls; only 33 genes were differentially expressed in the temporal cortex, and 48 in the hippocampus. Examination of these differentially expressed genes suggested deficits in the stress response and in neuronal signaling/communication. After treatment with the KD, both brain regions demonstrated improvements in ASD deficits associated with myelin formation and white matter development. Conclusions: Although our study supports many of the previously known impairments associated with ASD, such as excessive myelin formation and impaired GABAergic transmission, the RNAseq data and pathway analysis utilized here identified new therapeutic targets for analysis, such as Vitamin D pathways and cAMP signaling. En ligne : http://dx.doi.org/10.1002/aur.1682 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=304

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