Delving into the Complexity of Valproate-Induced Autism Spectrum Disorder: The Use of Zebrafish Models DOI Creative Commons

Diletta Camussi,

Valentina Naef, Letizia Brogi

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(16), P. 1349 - 1349

Published: Aug. 14, 2024

Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental condition with several identified risk factors, both genetic and non-genetic. Among these, prenatal exposure to valproic acid (VPA) has been extensively associated the development of disorder. The zebrafish, cost- time-effective model, useful for studying ASD features. Using validated VPA-induced zebrafish models, we aimed provide new insights into VPA effects during embryonic identify potential biomarkers ASD-like Dose-response analyses were performed in vivo study larval phenotypes mechanisms underlying neuroinflammation, mitochondrial dysfunction, oxidative stress, microglial cell status, motor behaviour. Wild-type transgenic

Language: Английский

Autism Spectrum Disorder DOI
Tomoya Hirota, Bryan H. King

JAMA, Journal Year: 2023, Volume and Issue: 329(2), P. 157 - 157

Published: Jan. 10, 2023

Autism spectrum disorder (ASD), characterized by deficits in social communication and the presence of restricted, repetitive behaviors or interests, is a neurodevelopmental affecting approximately 2.3% children aged 8 years US 2.2% adults. This review summarizes evidence on diagnosis treatment ASD.The estimated prevalence ASD has been increasing US, from 1.1% 2008 to 2018, which likely associated with changes diagnostic criteria, improved performance screening tools, increased public awareness. No biomarkers specific have identified. Common early signs symptoms child's first 2 life include no response name when called, limited use gestures communication, lack imaginative play. The criterion standard for comprehensive evaluation multidisciplinary team clinicians based semistructured direct observation behavior caregiver interview focused individual's development using standardized measures, such as Diagnostic Observation Schedule-Second Edition Interview. These measures sensitivity 91% 80% specificity 76% 72%, respectively. Compared people without ASD, individuals higher rates depression (20% vs 7%), anxiety (11% 5%), sleep difficulties (13% epilepsy (21% co-occurring intellectual disability 0.8%). Intensive behavioral interventions, Early Start Denver Model, are beneficial 5 younger improvement language, play, (small medium effect size mean difference). Pharmacotherapy indicated psychiatric conditions, emotion dysregulation attention-deficit/hyperactivity disorder. Risperidone aripiprazole can improve irritability aggression (standardized difference 1.1, consistent large size) compared placebo. Psychostimulants effective 0.6, moderate medications adverse effects including, most commonly, appetite, weight, sleep.ASD affects adults US. First-line therapy consists while aggression, may be treated medication.

Language: Английский

Citations

358
Genomics, convergent neuroscience and progress in understanding autism spectrum disorder DOI
Helen Rankin Willsey, A. Jeremy Willsey, Belinda Wang

et al.

Nature reviews. Neuroscience, Journal Year: 2022, Volume and Issue: 23(6), P. 323 - 341

Published: April 19, 2022

Language: Английский

Citations

140
A functional cellular framework for sex and estrous cycle-dependent gene expression and behavior DOI Creative Commons
Joseph R. Knoedler,

Sayaka Inoue,

Daniel W. Bayless

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(4), P. 654 - 671.e22

Published: Jan. 21, 2022

Language: Английский

Citations

110
Impaired neurogenesis alters brain biomechanics in a neuroprogenitor-based genetic subtype of congenital hydrocephalus DOI
Phan Q. Duy,

Stefan Weise,

Claudia Marini

et al.

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 25(4), P. 458 - 473

Published: April 1, 2022

Language: Английский

Citations

79
High-throughput functional analysis of autism genes in zebrafish identifies convergence in dopaminergic and neuroimmune pathways DOI Creative Commons
Hellen Weinschutz Mendes,

Uma Neelakantan,

Yunqing Liu

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(3), P. 112243 - 112243

Published: March 1, 2023

Advancing from gene discovery in autism spectrum disorders (ASDs) to the identification of biologically relevant mechanisms remains a central challenge. Here, we perform parallel vivo functional analysis 10 ASD genes at behavioral, structural, and circuit levels zebrafish mutants, revealing both unique overlapping effects loss function. Whole-brain mapping identifies forebrain cerebellum as most significant contributors brain size differences, while regions involved sensory-motor control, particularly dopaminergic regions, are associated with altered baseline activity. Finally, show global increase microglia resulting function select implicating neuroimmune dysfunction key pathway biology.

Language: Английский

Citations

44
Role of estrogen in sex differences in memory, emotion and neuropsychiatric disorders DOI
Javed Iqbal,

Geng-Di Huang,

Yanxue Xue

et al.

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 51(1)

Published: March 12, 2024

Language: Английский

Citations

17
Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy DOI Creative Commons
Hongbin Zhuang, Zhiyuan Liang,

Guanwei Ma

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(3)

Published: March 1, 2024

Abstract Autism spectrum disorder (ASD) has become a common neurodevelopmental disorder. The heterogeneity of ASD poses great challenges for its research and clinical translation. On the basis reviewing ASD, this review systematically summarized current status progress pathogenesis, diagnostic markers, interventions ASD. We provided an overview molecular mechanisms identified by multi‐omics studies convergent mechanism in different genetic backgrounds. comorbidities, associated with important physiological metabolic abnormalities (i.e., inflammation, immunity, oxidative stress, mitochondrial dysfunction), gut microbial were reviewed. non‐targeted omics targeting markers also Moreover, we methods behavioral educational interventions, intervention related to technological devices, on medical potential drug targets. This highlighted application high‐throughput emphasized importance seeking homogeneity from exploring convergence disease mechanisms, biomarkers, approaches, proposes that taking into account individuality commonality may be key achieve accurate diagnosis treatment

Language: Английский

Citations

16
From Cohorts to Molecules: Adverse Impacts of Endocrine Disrupting Mixtures DOI Creative Commons
Nicolò Caporale, Michelle Leemans, Lina Birgersson

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2017, Volume and Issue: unknown

Published: Oct. 23, 2017

ABSTRACT Convergent evidence associates endocrine disrupting chemicals (EDCs) with major, increasingly-prevalent human disorders. Regulation requires elucidation of EDC-triggered molecular events causally linked to adverse health outcomes, but two factors limit their identification. First, experiments frequently use individual chemicals, whereas real life entails simultaneous exposure multiple EDCs. Second, population-based and experimental studies are seldom integrated. This drawback was exacerbated until recently by lack physiopathologically meaningful systems that link epidemiological data results from model organisms. We developed a novel approach, integrating evidence. Starting 1,874 mother-child pairs we identified mixtures measured during early pregnancy, associated language delay or low-birth weight in offspring. These were then tested on complementary vitro vivo models. demonstrate each EDC mixture, at levels found pregnant women, disrupts hormone-regulated disease-relevant gene regulatory networks both the cellular organismal scale.

Language: Английский

Citations

139
Brain ventricles as windows into brain development and disease DOI Creative Commons
Phan Q. Duy, Pasko Rakić, Seth L. Alper

et al.

Neuron, Journal Year: 2022, Volume and Issue: 110(1), P. 12 - 15

Published: Jan. 1, 2022

Language: Английский

Citations

44
Aberrant cortical development is driven by impaired cell cycle and translational control in a DDX3X syndrome model DOI Creative Commons
Mariah L. Hoye, Lorenzo Calviello, Abigail Poff

et al.

eLife, Journal Year: 2022, Volume and Issue: 11

Published: June 28, 2022

Mutations in the RNA helicase, DDX3X , are a leading cause of Intellectual Disability and present as syndrome, neurodevelopmental disorder associated with cortical malformations autism. Yet, cellular molecular mechanisms by which controls development largely unknown. Here, using mouse model Ddx3x loss-of-function we demonstrate that directs translational cell cycle control neural progenitors, underlies precise corticogenesis. First, show brain is sensitive to dosage; complete loss from progenitors causes microcephaly females, whereas hemizygous males heterozygous females reduced neurogenesis without marked microcephaly. In addition, sexually dimorphic, its paralog, Ddx3y compensates for developing male neocortex. Using live imaging promotes neuronal generation regulating both duration neurogenic divisions. Finally, use ribosome profiling vivo discover repertoire translated transcripts including those DDX3X-dependent essential neurogenesis. Our study reveals invaluable new insights into etiology implicating dysregulated progenitor dynamics translation pathogenic mechanisms.

Language: Английский

Citations

44