Topic: shank3

Autism spectrum disorders (ASDs) are a range of neurodevelopmental disorders affecting social communication and behavior. Brain network dysfunctions are supported as a neurobiological basis for ASDs. Thus, functional connectivity (FC) studies are pivotal for unraveling autism-related large-scale network dynamics. Although functional imaging studies during development can be instrumental for autism diagnosis, longitudinal studies of FC consolidation over development to adulthood are missing in mice. SHANK3 is a postsynaptic scaffolding protein of excitatory synapses. Its deletion or mutation is

Autism Spectrum Disorder (ASD) is characterized mainly by social and sensory-motor abnormal and repetitive behavior patterns. Over hundreds of genes and thousands of genetic variants were reported to be highly penetrant and causative of ASD. Many of these mutations cause comorbidities such as epilepsy and intellectual disabilities (ID). In this study, we measured cortical neurons derived from induced pluripotent stem cells (iPSCs) of patients with four mutations in the genes GRIN2B, SHANK3, UBTF, as well as chromosomal duplication in the 7q11.23 region and compared them to neurons derived from

A strong link between the SHANK3 gene mutations and autism spectrum disorder (ASD) has been established but its molecular mechanisms remain unknown. Here we hypothesize that a mutation in the Shank3 gene leads to alterations in the global proteome, and consequently, these alterations converge into cellular and behavioral deficits of ASD. To test this hypothesis, we comprehensively mapped the global proteome within the cortex of the Shank3Δ4-22 mice. Our preliminary results revealed a significant increase in one of the ATP synthase subunits (ATP-S) expression levels in the cortex of Shank3Δ4-22

Shank3 is a postsynaptic cytoskeletal protein that acts as an intracellular scaffold supporting various subsequent synaptic components. Its deficiency is associated with significant changes in the morphology and electrophysiological properties of dopaminergic neurons and the expression of various synaptic proteins affecting normal brain development primarily during the early stages. These disruptions in neuronal circuits lead to changes in social interactions, communication skills, and behavioral patterns, commonly observed in neurodevelopmental disorders like autism. To better understand thes

Many studies have demonstrated a role for alternative polyadenylation (APA) of the 3'UTR region in the subcellular localization of mRNA in neurons, but to date, there has been little evidence of a link to psychiatric disorders, particularly schizophrenia.However, our group has recently demonstrated an alteration of polyadenylation in a large cohort of iPSC-derived cortical glutamatergic neurons from healthy controls and schizophrenic (SCZ) patients as well as from post-mortem brains.104 iPSCs-derived cortical glutamatergic neurons were characterized by RNA-Seq, revealing that the use of the ca

Autism Spectrum Disorders (ASD) are a range of neurodevelopmental disorders, characterized by behavioral and neuronal anomalies. Phelan-McDermid Syndrome (PMS) constitutes a specific neurodevelopmental disorder exhibiting ASD-like behaviors, caused by mutations or deletions of SHANK3 gene. Mice lacking the SHANK3 gene are widely considered a reliable model to study PMS, since they show autism-like behaviors and sensory deficits, such as aberrant whisker-dependent texture discrimination and local hyperactivation of the barrel-field cortex. These local alterations mirror dysfunctions of the enti

Social interaction is a core aspect of mammalian behavior, and alterations in social behaviors are found across many neurodevelopmental and psychiatric conditions. Mice display a range of socioemotional behaviors and are commonly used as models to investigate the neuronal circuits and molecular mechanisms underlying differences in social behaviors. Analyzing social interactions in mice is often done by manual quantification of videos. Although multiple methods for automated tracking have been developed, reliable tracking and automated behavioral classification of multiple freely-moving unmarke