Progress toward treatments for synaptic defects in autism

Delorme, Richard; Ey, Elodie; Toro, Roberto; Leboyer, Marion; Gillberg, Christopher; Bourgeron, Thomas

doi:10.1038/nm.3193

Cited by 178 publications

(131 citation statements)

References 118 publications

(132 reference statements)

Supporting

Mentioning

128

Contrasting

Order By: Relevance

“…Heterogeneity in ASDs points toward multiple primary causes, with genetic factors playing a critical role. Largescale genetic studies in patients and preclinical work using animal models have identified over 280 candidate vulnerability genes for ASD (SFARIgene 2.0 database, https:// gene.sfari.org/autdb/Welcome.do) (Buxbaum et al, 2012;Delorme et al, 2013;Ecker et al, 2012a;State and Levitt, 2011) and suggest that altered synaptic function and disrupted excitation-inhibition balance contribute to the pathology. Neuroimaging studies have confirmed atypical brain connectivity in ASD patients (Ecker et al, 2012b;Just et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Autistic-Like Syndrome in Mu Opioid Receptor Null Mice is Relieved by Facilitated mGluR4 Activity

Becker

Clesse

Spiegelhalter

et al. 2014

Neuropsychopharmacol

107

161

View full text Add to dashboard Cite

The etiology of Autism Spectrum Disorders (ASDs) remains largely unknown. Identifying vulnerability genes for autism represents a major challenge in the field and allows the development of animal models for translational research. Mice lacking the mu opioid receptor gene (Oprm1 À / À ) were recently proposed as a monogenic mouse model of autism, based on severe deficits in social behavior and communication skills. We confirm this hypothesis by showing that adult Oprm1 À / À animals recapitulate core and multiple comorbid behavioral symptoms of autism and also display anatomical, neurochemical, and genetic landmarks of the disease. Chronic facilitation of mGluR4 signaling, which we identified as a novel pharmacological target in ASDs in these mice, was more efficient in alleviating behavioral deficits than the reference molecule risperidone. Altogether, our data provide first evidence that disrupted mu opioid receptor signaling is sufficient to trigger a comprehensive autistic syndrome, maybe through blunted social reward processes, and this mouse model opens promising avenues for therapeutic innovation.

show abstract

Section: Introductionmentioning

confidence: 99%

Autistic-Like Syndrome in Mu Opioid Receptor Null Mice is Relieved by Facilitated mGluR4 Activity

Becker

Clesse

Spiegelhalter

et al. 2014

Neuropsychopharmacol

107

161

View full text Add to dashboard Cite

show abstract

“…As a result, between 400 and 700 genes have been associated with these conditions, many of which converge on pathways involved in regulation of neuronal function. 29,30,[34][35][36] Particularly, it has been shown that most of the genes associated to ID and autism have a role in the control of formation and function of synapses. 37,38 Interestingly, a biological systems study indicates that there are up to 4 000 genes that may contribute to neurodevelopmental and neuropsychiatric disorders 39 suggesting that a large number of genes associated with disorders as ID and autism have not been identified yet.…”

Section: Artículo Originalmentioning

confidence: 99%

The intellectual developmental disorders Mexico study: situational diagnosis, burden, genomics and intervention proposal

et al. 2016

View full text Add to dashboard Cite

Objective. This study aims to generate evidence on intellectual development disorders (IDD) in Mexico. Materials and methods. IDD disease burden will be estimated with a probabilistic model, using population-based surveys. Direct and indirect costs of catastrophic expenses of families with a member with an IDD will be evaluated. Genomic characterization of IDD will include: sequencing participant exomes and performing bioinformatics analyses to identify de novo or inherited variants through trio analysis; identifying genetic variants associated with IDD, and validating randomly selected variants by polymerase chain reaction (PCR) and sequencing or real-time quantitative PCR (qPCR). Delphi surveys will be done on best practices for IDD diagnosis and management. An external evaluation will employ qualitative case studies of two social and labor inclusion programs for people with IDD. Conclusions. The results will constitute scientific evidence for the design, promotion and evaluation of public policies, which are currently absent on IDD. ResumenObjetivo. Esta investigación busca generar evidencia sobre trastornos del desarrollo intelectual (TDI) en México. Material y métodos. La carga de la enfermedad por TDI se estimará con un modelo probabilístico usando encuestas poblacionales. Se estimarán costos directos e indirectos de gastos catastróficos de familias con un integrante con TDI. La caracterización genómica de TDI incluirá secuenciar exomas, realizar análisis bioinformático para identificar variantes de novo o heredadas a través de análisis de tríos, identificar variantes genéticas asociadas con TDI, y validar variantes aleatoriamente seleccionadas con reacción en cadena de polimerasa y secuenciación o qPCR. Se harán encuestas Delphi sobre mejores prácticas de diagnóstico y manejo de TDI. Una evaluación externa empleará estudios cualitativos de caso de dos programas de inclusión social y laboral para personas con TDI. Conclusiones. Los resultados serán evidencia científica que podrá ser la base para el diseño, promoción y evaluación de políticas públicas, actualmente ausentes para TDI.Palabras clave: trastornos del desarrollo intelectual; TDAH; trastorno autista; gasto; México

show abstract

“…Several genetic studies have identified a large number of genes which are related to ASD [4]. Many of the genes implicated in ASD encode synaptic proteins [5]. However, most of those gene mutations are rare and may only account for a small part of the cases of ASD.…”

Section: Introductionmentioning

confidence: 99%

Roles of PTEN/PI3K/AKT/GSK3? Pathway in Neuron Signaling Involved in Autism

Murai¹

2015

Brain Disord Ther

View full text Add to dashboard Cite

Autism spectrum disorder is a set of neurodevelopmental disorders in terms of prevalence, morbidity and impact to the society, which is characterized by intricate behavioral phenotype and deficits in both social and cognitive functions. The molecular pathogenesis of autism spectrum disorder has not been well understood, however, it seems that PI3K, AKT, and its downstream molecules have crucial roles in the molecular pathogenesis of autism spectrum disorder. The PI3K/AKT signaling pathway plays an important role in the regulation of cell proliferation, differentiation, motility, and protein synthesis. Deregulated PI3K/AKT signaling has also been shown to be associated with the autism spectrum disorder. Discovery of molecular biochemical phenotypes would represent a breakthrough in autism research. This study has provided new insight on the mechanism of the disorder and would open up future opportunity for contributions to understand the pathophysiology.

show abstract

Progress toward treatments for synaptic defects in autism

Cited by 178 publications

References 118 publications

Autistic-Like Syndrome in Mu Opioid Receptor Null Mice is Relieved by Facilitated mGluR4 Activity

Autistic-Like Syndrome in Mu Opioid Receptor Null Mice is Relieved by Facilitated mGluR4 Activity

The intellectual developmental disorders Mexico study: situational diagnosis, burden, genomics and intervention proposal

Roles of PTEN/PI3K/AKT/GSK3? Pathway in Neuron Signaling Involved in Autism

Contact Info

Product

Resources

About