Evidence against the “normalization” prediction of the early brain overgrowth hypothesis of autism
ConclusionsThese findings challenge the “normalization” prediction of the brain overgrowth hypothesis by demonstrating that brain enlargement persists across childhood into early adulthood. The findings raise questions about the clinical implications of brain enlargement, since we find that it neither confers cognitive benefits nor pr edicts increased symptom severity in ASD. (Source: Molecular Autism)
Source: Molecular Autism - June 17, 2020 Category: Molecular Biology Source Type: research
The sociability spectrum: evidence from reciprocal genetic copy number variations
AbstractSociability entails some of the most complex behaviors processed by the central nervous system. It includes the detection, integration, and interpretation of social cues and elaboration of context-specific responses that are quintessentially species-specific. There is an ever-growing accumulation of molecular associations to autism spectrum disorders (ASD), from causative genes to endophenotypes across multiple functional layers; these however, have rarely been put in context with the opposite manifestation featured in hypersociability syndromes. Genetic copy number variations (CNVs) allow to investigate the rela...
Source: Molecular Autism - June 15, 2020 Category: Molecular Biology Source Type: research
Sex differences in the first impressions made by girls and boys with autism
ConclusionsFirst impressions made during naturalistic conversations with non-expert conversation partners could —in combination with clinical ratings and parent report—shed light on the nature and effects of behavioral differences between girls and boys on the autism spectrum. (Source: Molecular Autism)
Source: Molecular Autism - June 15, 2020 Category: Molecular Biology Source Type: research
Defining clusters of young autistic and typically developing children based on loudness-dependent auditory electrophysiological responses
ConclusionsTaken together, these data demonstrate the broader benefits of using electrophysiology to explore individual differences. They illuminate different neural response patterns and suggest relationships between sensory neural responses and sensory behaviors, cognitive abilities, and autism diagnostic status. (Source: Molecular Autism)
Source: Molecular Autism - June 14, 2020 Category: Molecular Biology Source Type: research
Absence of parvalbumin increases mitochondria volume and branching of dendrites in inhibitory Pvalb neurons in vivo: a point of convergence of autism spectrum disorder (ASD) risk gene phenotypes
ConclusionPV is involved in most proposed mechanisms implicated in ASD etiology: alterations in Ca2+ signaling affecting E/I balance, changes in mitochondria structure/function, and increased dendritic length and branching, possibly resulting in local hyperconnectivity, all in a likely cell autonomous way. (Source: Molecular Autism)
Source: Molecular Autism - June 8, 2020 Category: Molecular Biology Source Type: research
Neuroanatomical underpinnings of autism symptomatology in carriers and non-carriers of the 22q11.2 microdeletion
ConclusionsOur findings indicate that neuroanatomical correlates of ASD symptomatology in carriers of the 22q11.2 microdeletion diverge from those in idiopathic ASD. (Source: Molecular Autism)
Source: Molecular Autism - June 7, 2020 Category: Molecular Biology Source Type: research
Transcriptional consequences of MBD5 disruption in mouse brain and CRISPR-derived neurons
ConclusionsOur study points to modest and context-dependent transcriptional consequences ofMbd5 disruption in the brain. It also suggests a possible link betweenMBD5 and perturbations in ciliary function, which is an established pathogenic mechanism in developmental disorders and syndromes. (Source: Molecular Autism)
Source: Molecular Autism - June 4, 2020 Category: Molecular Biology Source Type: research
Electronic communication in autism spectrum conditions
(Source: Molecular Autism)
Source: Molecular Autism - June 4, 2020 Category: Molecular Biology Source Type: research
Decreased nuclear Pten in neural stem cells contributes to deficits in neuronal maturation
ConclusionsConstitutional disruption of Pten nuclear localization with subsequent global decrease in Pten expression generates abnormal patterns of differentiation, a stunting of neuronal maturation. The propensity of Pten disruption to restrain neurons to a more progenitor-like state may be an important feature contributing to PTEN-ASD pathogenesis.Graphical abstract (Source: Molecular Autism)
Source: Molecular Autism - May 31, 2020 Category: Molecular Biology Source Type: research
Copy number variants (CNVs): a powerful tool for iPSC-based modelling of ASD
AbstractPatients diagnosed with chromosome microdeletions or duplications, known as copy number variants (CNVs), present a unique opportunity to investigate the relationship between patient genotype and cell phenotype. CNVs have high genetic penetrance and give a good correlation between gene locus and patient clinical phenotype. This is especially effective for the study of patients with neurodevelopmental disorders (NDD), including those falling within the autism spectrum disorders (ASD). A key question is whether this correlation between genetics and clinical presentation at the level of the patient can be translated to...
Source: Molecular Autism - May 31, 2020 Category: Molecular Biology Source Type: research
Dysregulation of protein synthesis and dendritic spine morphogenesis in ASD: studies in human pluripotent stem cells
AbstractAutism spectrum disorder (ASD) is a brain disorder that involves changes in neuronal connections. Abnormal morphology of dendritic spines on postsynaptic neurons has been observed in ASD patients and transgenic mice that model different monogenetic causes of ASD. A number of ASD-associated genetic variants are known to disrupt dendritic local protein synthesis, which is essential for spine morphogenesis, synaptic transmission, and plasticity. Most of our understanding on the molecular mechanism underlying ASD depends on studies using rodents. However, recent advance in human pluripotent stem cells and their neural ...
Source: Molecular Autism - May 26, 2020 Category: Molecular Biology Source Type: research
Quantitative proteomic analysis of Rett iPSC-derived neuronal progenitors
ConclusionsDuring early neuronal differentiation, there are consistent and time-point specific proteomic alterations in RTT patient cells carrying exons 3 –4 deletion inMECP2. We found changes in proteins involved in pathway associated with RTT phenotypes, including dendrite morphology and synaptogenesis. Our results provide a valuable resource of proteins and pathways for follow-up studies, investigating common mechanisms involved during early disease stages of RTT syndrome. (Source: Molecular Autism)
Source: Molecular Autism - May 26, 2020 Category: Molecular Biology Source Type: research
Identification of amygdala-expressed genes associated with autism spectrum disorder
ConclusionsOur pipeline narrows down the number of amygdala-expressed genes possibly involved in the social pathophysiology of ASD. Our human single-nucleus gene expression analyses revealed that ASD is characterized by changes in gene expression in specific cell types in the early postnatal amygdala. (Source: Molecular Autism)
Source: Molecular Autism - May 26, 2020 Category: Molecular Biology Source Type: research
Elevated de novo protein synthesis in FMRP-deficient human neurons and its correction by metformin treatment
AbstractFXS is the most common genetic cause of intellectual (ID) and autism spectrum disorders (ASD). FXS is caused by loss of FMRP, an RNA-binding protein involved in the translational regulation of a large number of neuronal mRNAs. Absence of FMRP has been shown to lead to elevated protein synthesis and is thought to be a major cause of the synaptic plasticity and behavioural deficits in FXS. The increase in protein synthesis results in part from abnormal activation of key protein translation pathways downstream of ERK1/2 and mTOR signalling. Pharmacological and genetic interventions that attenuate hyperactivation of th...
Source: Molecular Autism - May 26, 2020 Category: Molecular Biology Source Type: research
Cell therapy approaches to autism: a review of clinical trial data
AbstractA number of clinical trials of cell therapies for autism spectrum disorder have been conducted, and some have published their outcomes. This review considers the data that have emerged from this small set of published trials, evaluates their success, and proposes further steps that could be taken if this field of endeavour is to be pursued further. A number of reservations arise from this tranche of studies, specifically the absence of identified therapeutic targets, and deficiencies in the therapeutic approach that is being employed. If this therapeutic direction is to be pursued further, then additional pre-clini...
Source: Molecular Autism - May 23, 2020 Category: Molecular Biology Source Type: research
