A Mechanical Biosensor Based on Magnetic-Mediated Sensitization for 5-Ht Detection DOI
Dong Zhao,

Penglong Yao,

Zhaosheng Yan

et al.

Published: Jan. 1, 2024

The real-time detection of neurotransmitters had attracted more attention due to the potential provide vital information for pathology research, disease diagnosis, and clinical efficacy evaluation. Here, a magnetic-mediated biosensor was developed improve sensitivity serotonin (5-HT). PDMS membrane doped with magnetic particles serves as conversion element, enhancing deformation thin film caused by surface stress under action field amplifying resistance response signal biosensor. 5-HT associated neurotransmitter diseases serve proof concept revealing sensitization. limit decreased 3.21 nM in linear range 5-500 nM, which lower than that without field. samples were also been accurately detected, indicating positive application as-prepared All these results reveal high practicality new method diagnosis.

Language: Английский

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
Molecular profiling of the hippocampus of children with autism spectrum disorder DOI Creative Commons
Lindsay Rexrode,

Joshua Hartley,

Kurt C. Showmaker

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(7), P. 1968 - 1979

Published: Feb. 14, 2024

Abstract Several lines of evidence point to a key role the hippocampus in Autism Spectrum Disorders (ASD). Altered hippocampal volume and deficits memory for person emotion related stimuli have been reported, along with enhanced ability declarative memories. Mouse models demonstrated critical social dysfunction, associated ASD, together decreased synaptic plasticity. Chondroitin sulfate proteoglycans (CSPGs), family extracellular matrix molecules, represent potential link between neurodevelopment, plasticity, immune system signaling. There is lack information regarding molecular pathology ASD. We conducted RNAseq profiling on postmortem human brain samples containing from male children ASD ( n = 7) normal (3–14 yrs old), 6) NIH NeuroBioBank. Gene expression analysis implicated pathways involved organization, regulation, qRT-PCR Western blotting were used confirm several top markers identified. The CSPG protein BCAN was examined multiplex immunofluorescence analyze cell-type specific astrocyte morphology. observed proteins PSD95 p < 0.02) SYN1 0.02), increased (ECM) protease MMP9 0.03), MEF2C 0.03). also astrocytes altered Our results alterations signaling, glia cell differentiation, signaling molecules. Furthermore, our demonstrate genes genetic studies including MEF2C.

Language: Английский

Citations

12
The Mechanisms of CHD8 in Neurodevelopment and Autism Spectrum Disorders DOI Open Access
Orly Weissberg, Evan Elliott

Genes, Journal Year: 2021, Volume and Issue: 12(8), P. 1133 - 1133

Published: July 26, 2021

Chromodomain-helicase-DNA-binding protein 8 (CHD8) has been identified as one of the genes with strongest association autism. The CHD8 is a transcriptional regulator that expressed in nearly all cell types and implicated multiple cellular processes, including cycle, adhesion, neuronal development, myelination, synaptogenesis. Considering central role genetics autism, deeper understanding physiological functions important to understand development autism phenotype potential therapeutic targets. Different mutant mouse models were developed determine autism-like phenotypes fully their mechanisms. Here, we review current knowledge on CHD8, an emphasis mechanistic lessons gained from animal have studied.

Language: Английский

Citations

45
Autism spectrum disorders and the gastrointestinal tract: insights into mechanisms and clinical relevance DOI
Lin Y. Hung, Kara Gross Margolis

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2023, Volume and Issue: 21(3), P. 142 - 163

Published: Dec. 19, 2023

Language: Английский

Citations

22
Synaptic dysfunction connects autism spectrum disorder and sleep disturbances: A perspective from studies in model organisms DOI Creative Commons
Fusun Doldur-Balli,

Toshihiro Imamura,

Olivia J. Veatch

et al.

Sleep Medicine Reviews, Journal Year: 2022, Volume and Issue: 62, P. 101595 - 101595

Published: Jan. 25, 2022

Language: Английский

Citations

25
Autism-associated CHD8 controls reactive gliosis and neuroinflammation via remodeling chromatin in astrocytes DOI Creative Commons
Platon Megagiannis, Mei Yuan, Rachel Yan

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(8), P. 114637 - 114637

Published: Aug. 1, 2024

Reactive changes of glial cells during neuroinflammation impact brain disorders and disease progression. Elucidating the mechanisms that control reactive gliosis may help us to understand pathophysiology improve outcomes. Here, we report adult ablation autism spectrum disorder (ASD)-associated CHD8 in astrocytes attenuates via remodeling chromatin accessibility, changing gene expression. Conditional Chd8 deletion astrocytes, but not microglia, suppresses by impeding astrocyte proliferation morphological elaboration. Astrocyte alleviates lipopolysaccharide-induced septic-associated hypothermia mice. Astrocytic plays an important role altering landscape, regulating metabolic lipid-associated pathways, astrocyte-microglia crosstalk. Moreover, show can be directly mitigated vivo using adeno-associated virus (AAV)-mediated editing strategy. These findings uncover a ASD-associated brain, which warrant future exploration targeting remodelers injury neurological diseases.

Language: Английский

Citations

5
Decoding microRNAs in autism spectrum disorder DOI Creative Commons
Jinyu Li, Xiaohui Xu,

Jiane Liu

et al.

Molecular Therapy — Nucleic Acids, Journal Year: 2022, Volume and Issue: 30, P. 535 - 546

Published: Nov. 7, 2022

Autism spectrum disorder (ASD)-a congenital mental accompanied by social dysfunction and stereotyped behaviors-has attracted a great deal of attention worldwide. A combination genetic environmental factors may determine the pathogenesis ASD. Recent research multiple ASD models indicates that microRNAs (miRNAs) play central role at onset progression repressing translation key mRNAs in neural development functions. As such, miRNAs show potential to serve as biomarkers for diagnosis or prognosis therapeutic targets treatment In this review, we discuss regulatory mechanisms which influence phenotypes through various vivo vitro models, including necropsy specimens, animal cellular and, particular, induced pluripotent stem cells derived from patients with We then miRNA-based strategies currently being evaluated preclinical studies.

Language: Английский

Citations

20
Mutation of the Drosophila melanogaster serotonin transporter dSERT impacts sleep, courtship, and feeding behaviors DOI Creative Commons

Elizabeth M. Knapp,

Andrea Kaiser,

Rebecca C. Arnold

et al.

PLoS Genetics, Journal Year: 2022, Volume and Issue: 18(11), P. e1010289 - e1010289

Published: Nov. 21, 2022

The Serotonin Transporter (SERT) regulates extracellular serotonin levels and is the target of most current drugs used to treat depression. mechanisms by which inhibition SERT activity influences behavior are poorly understood. To address this question in model organism Drosophila melanogaster , we developed new loss function mutations ( dSERT) . Previous studies both flies mammals have implicated as an important neuromodulator sleep, our newly generated dSERT mutants show increase total sleep altered architecture that mimicked feeding SSRI citalopram. Differences daytime versus nighttime well genetic rescue experiments unexpectedly suggest distinct serotonergic circuits may modulate sleep. also defects copulation food intake, akin clinical side effects SSRIs consistent with pleomorphic influence on D Starvation did not overcome drive male mutants, mate failed drive. be further explore its interplay other complex behaviors.

Language: Английский

Citations

20
The Drosophila blood–brain barrier regulates sleep via Moody G protein-coupled receptor signaling DOI Creative Commons
Sofia Axelrod, Xiaoling Li,

Yingwo Sun

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(42)

Published: Oct. 13, 2023

Sleep is vital for most animals, yet its mechanism and function remain unclear. We found that permeability of the BBB (blood–brain barrier)—the organ required maintenance homeostatic levels nutrients, ions, other molecules in brain—is modulated by sleep deprivation (SD) can cell-autonomously effect changes. observed increased known mutants as well acutely sleep-deprived animals. In addition to molecular tracers, SD–induced changes also penetration drugs used treatment brain pathologies. After chronic/genetic or acute SD, rebound administration sleeping aid gaboxadol normalized permeability, showing SD effects on are reversible. Along with RNA master regulator moody sleep. Conversely, altering alone through glia-specific modulation moody, gαo, loco, lachesin , neuroglian —each a well-studied function—was sufficient induce robust phenotypes. These studies demonstrate tight link between indicate unique role regulation

Language: Английский

Citations

12
Serum claudin-5, claudin-11, occludin, vinculin, paxillin, and beta-catenin levels in preschool children with autism spectrum disorder DOI
Ayhan Bi̇lgi̇ç, Hurşit Ferahkaya, Hülya Karagöz

et al.

Nordic Journal of Psychiatry, Journal Year: 2023, Volume and Issue: 77(5), P. 506 - 511

Published: Jan. 20, 2023

Increased intestinal and blood-brain barriers (BBB) permeability has been suggested to have a role in autism spectrum disorder (ASD). Claudin-5, claudin-11, occludin, β-catenin, vinculin, paxillin are crucial components of these barriers. This study assessed concentrations molecules preschool children with ASD.A total 80 ASD 40 controls aged 18-60 months were enrolled this study. Serum levels biochemical variables determined using commercial enzyme-linked immunosorbent assay kits.Serum β-catenin significantly higher the group than control group. However, no significant difference for serum claudin-5, was detected between groups.These findings suggest that may be involved pathogenesis ASD. These proteins affect brain by causing dysregulation or barrier other unknown mechanisms.

Language: Английский

Citations

10