Genetics of structural and functional brain changes in autism spectrum disorder

Translational Psychiatry, Journal Year: 2020, Volume and Issue: 10(1)

Published: July 13, 2020

Abstract Autism spectrum disorder (ASD) is a neurological and developmental characterized by social impairment restricted interactive communicative behaviors. It may occur as an isolated or in the context of other neurological, psychiatric, developmental, genetic disorders. Due to rapid developments genomics imaging technologies, genetics studies ASD have evolved last few years. Increased risk for diagnosis found be related many specific single-nucleotide polymorphisms, study mechanisms noninvasive has opened various approaches that can help diagnose at nascent level. Identifying genes structural functional changes brain patients provide better understanding disease’s neuropsychiatry identify targets therapeutic intervention could useful clinical management patients.

Language: Английский

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Aralar Sequesters GABA into Hyperactive Mitochondria, Causing Social Behavior Deficits

Cell, Journal Year: 2020, Volume and Issue: 180(6), P. 1178 - 1197.e20

Published: March 1, 2020

Language: Английский

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Role of Oligodendrocytes and Myelin in the Pathophysiology of Autism Spectrum Disorder

Brain Sciences, Journal Year: 2020, Volume and Issue: 10(12), P. 951 - 951

Published: Dec. 8, 2020

Autism Spectrum Disorder (ASD) is an early neurodevelopmental disorder that involves deficits in interpersonal communication, social interaction, and repetitive behaviors. Although ASD pathophysiology still uncertain, alterations the abnormal development of frontal lobe, limbic areas, putamen generate imbalance between inhibition excitation neuronal activity. Interestingly, recent findings suggest a disruption connectivity associated with neural white matter production myelination diverse brain regions patients ASD. This review aimed to summarize most evidence supports notion abnormalities oligodendrocyte generation axonal specific are involved Fundamental molecular mediators these pathological processes also examined. Determining role oligodendrogenesis fundamental step understand identify possible therapeutic targets.

Language: Английский

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The autism- and schizophrenia-associated protein CYFIP1 regulates bilateral brain connectivity and behaviour

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Aug. 1, 2019

Copy-number variants of the CYFIP1 gene in humans have been linked to autism spectrum disorders (ASD) and schizophrenia (SCZ), two neuropsychiatric characterized by defects brain connectivity. Here, we show that plays an important role functional connectivity callosal functions. We find Cyfip1-heterozygous mice reduced white matter architecture, similar phenotypes found patients with ASD, SCZ other disorders. Cyfip1-deficient also present decreased myelination axons, altered presynaptic function, impaired bilateral Finally, Cyfip1 deficiency leads abnormalities motor coordination, sensorimotor gating sensory perception, which are known disorder-related symptoms. These results haploinsufficiency compromises might explain its genetic association

Language: Английский

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Altered motor learning and coordination in mouse models of autism spectrum disorder

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Nov. 8, 2023

Autism spectrum disorder (ASD) is a complex neurodevelopmental with increasing prevalence. Over 1,000 risk genes have now been implicated in ASD, suggesting diverse etiology. However, the diagnostic criteria for still comprise two major behavioral domains - deficits social communication and interaction, presence of restricted repetitive patterns behavior (RRBs). The RRBs associated ASD include both stereotyped movements other motor manifestations including changes gait, balance, coordination, skill learning. In recent years, striatum, primary input center basal ganglia, has these ASD-associated behaviors, due to striatum’s role action selection, learning, habit formation. Numerous mouse models mutations developed shown alterations ASD-relevant behaviors. One commonly used assay, accelerating rotarod, allows assessment basic coordination this corticostriatal-dependent task, mice walk on rotating rod that gradually increases speed. extended version engage striatal-dependent learning mechanisms optimize their routine stay longer periods. This review summarizes findings studies examining rotarod performance across range models, resulting implications involvement striatal circuits ASD-related While task not uniform there cohort show increased performance. A growing number suggest propensity learn fixed may reflect common enhancement corticostriatal drive subset ASD-risk genes.

Language: Английский

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Mapping and comparing fMRI connectivity networks across species

Communications Biology, Journal Year: 2023, Volume and Issue: 6(1)

Published: Dec. 7, 2023

Abstract Technical advances in neuroimaging, notably fMRI, have allowed distributed patterns of functional connectivity to be mapped the human brain with increasing spatiotemporal resolution. Recent years seen a growing interest extending this approach rodents and non-human primates understand mechanism fMRI complement investigations connectome. Here, we discuss current challenges opportunities mapping across species. We underscore critical importance physiologically decoding neuroimaging measures (dys)connectivity via multiscale mechanistic animals. next highlight set general principles governing organization mammalian networks These include presence evolutionarily conserved network systems, dominant cortical axis connectivity, common repertoire topographically modes. finally describe emerging approaches allowing comparisons extrapolations findings As neuroscientists gain access increasingly sophisticated perturbational, computational recording tools, cross-species offers novel investigate large-scale health disease.

Language: Английский

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Presynaptic dysfunction in neurodevelopmental disorders: Insights from the synaptic vesicle life cycle

Journal of Neurochemistry, Journal Year: 2020, Volume and Issue: 157(2), P. 179 - 207

Published: May 7, 2020

Abstract The activity‐dependent fusion, retrieval and recycling of synaptic vesicles is essential for the maintenance neurotransmission. Until relatively recently it was believed that most mutations in genes were this process would be incompatible with life, because fundamental role. However, an ever‐expanding number very cohort are being identified individuals neurodevelopmental disorders, including autism, intellectual disability epilepsy. This article will summarize current state knowledge linking presynaptic to disorders by sequentially covering various stages vesicle life cycle. It also discuss how perturbations specific within could translate into human disease. Finally, provide perspectives on potential future therapy targeted function. image

Language: Английский

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Rho GTPase Regulators and Effectors in Autism Spectrum Disorders: Animal Models and Insights for Therapeutics

Cells, Journal Year: 2020, Volume and Issue: 9(4), P. 835 - 835

Published: March 31, 2020

The Rho family GTPases are small G proteins that act as molecular switches shuttling between active and inactive forms. regulated by two classes of regulatory proteins, guanine nucleotide exchange factors (GEFs) GTPase-activating (GAPs). transduce the upstream signals to downstream effectors, thus regulating diverse cellular processes, such growth, migration, adhesion, differentiation. In particular, play essential roles in neuronal morphology function. Recent evidence suggests dysfunction GTPase signaling contributes substantially pathogenesis autism spectrum disorder (ASD). It has been found 20 genes encoding regulators effectors listed ASD risk Simons foundation research initiative (SFARI). This review summarizes clinical evidence, protein structure, expression pattern these genes. Moreover, ASD-related behavioral phenotypes animal models reviewed, therapeutic approaches show successful treatment effects discussed.

Language: Английский

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The neurodevelopmental role of dopaminergic signaling in neurological disorders

Neuroscience Letters, Journal Year: 2020, Volume and Issue: 741, P. 135540 - 135540

Published: Dec. 2, 2020

Language: Английский

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Effects of copy number variations on brain structure and risk for psychiatric illness: Large‐scale studies from theENIGMAworking groups onCNVs

Human Brain Mapping, Journal Year: 2021, Volume and Issue: 43(1), P. 300 - 328

Published: Feb. 21, 2021

The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development related cognitive, psychiatric behavioral manifestations. To that end, ENIGMA-CNV WG has collated CNV magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one largest studies date on effects CNVs structures general population. 22q-ENIGMA includes 12 international centers assessed over 533 with a confirmed deletion syndrome, 40 duplications, 333 typically developing controls, creating largest-ever neuroimaging set. In this review, we outline ENIGMA infrastructure procedures for multi-site analysis MRI data. So far, identified 22q11.2, 16p11.2 distal, 15q11.2, 1q21.1 distal subcortical cortical structures. Each is associated differences neurodevelopmental neuropsychiatric traits, characteristic patterns structural abnormalities. Evidence gene-dosage distinct regions also emerged, providing further genotype-phenotype relationships. Taken together, these results offer more comprehensive picture molecular mechanisms involved typical atypical development. This "genotype-first" approach contributes our understanding etiopathogenesis disorders. Finally, future directions better understand structure behavior.

Language: Английский

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