Advances in Zebrafish as a Comprehensive Model of Mental Disorders

Depression and Anxiety, Journal Year: 2023, Volume and Issue: 2023, P. 1 - 48

Published: June 20, 2023

As an important part in international disease, mental disorders seriously damage human health and social stability, which show the complex pathogenesis increasing incidence year by year. In order to analyze of as soon possible look for targeted drug treatment psychiatric diseases, a more reasonable animal model is imperious demands. Benefiting from its high homology with genome, brain tissue highly similar that humans, it easy realize whole-body optical visualization high-throughput screening; zebrafish stands out among many models disorders. Here, valuable qualified could be established through behavioral test sociological analysis, are simulated combined molecular analyses other detection methods. This review focuses on advances simulate disorders; summarizes various characterization means, use equipment, operation principle; sums up disorder modeling methods; puts forward current challenges future development trend, contribute theoretical supports exploration mechanisms strategies

Language: Английский

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Allelic contribution of Nrxn1α to autism-relevant behavioral phenotypes in mice

PLoS Genetics, Journal Year: 2023, Volume and Issue: 19(2), P. e1010659 - e1010659

Published: Feb. 27, 2023

Copy number variations (CNVs) in the Neurexin 1 ( NRXN1 ) gene, which encodes a presynaptic protein involved neurotransmitter release, are some of most frequently observed single-gene variants associated with autism spectrum disorder (ASD). To address functional contribution CNVs to behavioral phenotypes relevant ASD, we carried out systematic phenotyping an allelic series Nrxn1 mouse models: one carrying promoter and exon deletion abolishing α transcription, 9 disrupting translation, intronic no observable effect on expression. We found that homozygous loss resulted enhanced aggression males, reduced affiliative social behaviors females, significantly altered circadian activities both sexes. Heterozygous or affected preference for novelty male mice, notably, repetitive motor skills coordination In contrast, mice bearing did not display alterations any assessed. These findings demonstrate importance gene dosage regulating social, circadian, functions, variables sex genomic positioning expression autism-related phenotypes. Importantly, heterozygous , as numerous autistic individuals, show elevated propensity manifest phenotypes, supporting use models this architecture study ASD etiology assess additional genetic autism.

Language: Английский

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Effect of Surface-engineered AuNPs on gene expression, bacterial interaction, protein denaturation, and toxicology assay: An in vitro and in vivo model

Journal of Materials Chemistry B, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

We investigated the in vitro and vivo uses of pamoic acid functionalized gold nanoparticles (PA@AuNPs), with a focus on determining their safety potential toxicity living beings. To test this theory, bacterial interaction PA@AuNPs was studied using Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa cultures, as well inhibition bovine serum albumin (BSA) protein. The real-time polymerase chain reaction (RT-PCR) is used to measure expression target genes. caused dose-dependent cell death MDA-MB-231, triple-negative breast cancer (BC) line, an LC50 -42.23 μL mL-1. It also apoptosis BC cells. results indicated that early weeks, inflammatory cells (mostly neutrophils macrophages) penetrated connective tissue, but latter substantial number fibroblasts fibrocytes were identified. Changes vascular channels, extravasated red blood (RBCs), necrosis are all indicators growing tissue pathology. These data could point dynamic process including anti-inflammatory response followed by remodeling or repair. findings show not hazardous tested Sprague Dawley rats, highly biocompatible, can be variety biological applications.

Language: Английский

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Gangliosides and Cholesterol: Dual Regulators of Neuronal Membrane Framework in Autism Spectrum Disorder

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1322 - 1322

Published: Feb. 4, 2025

Autism spectrum disorder (ASD) is a neurodevelopmental with heterogeneous clinical presentation. Diagnosing ASD complex, and the criteria for diagnosis, as well term ASD, have changed during last decades. Diagnosis made based on observation accomplishment of specific diagnostic criteria, while particular biomarker does not yet exist. However, studies universally report disequilibrium in membrane lipid content, pointing to unique neurolipid signature ASD. This review sheds light possible role cholesterol gangliosides, complex glycosphingolipids, development In addition maintaining integrity, neuronal signaling, synaptic plasticity, these lipids play neurotransmitter release calcium signaling. Evidence linking lipidome changes includes low levels, unusual ganglioside metabolic profiles. symptoms may be mitigated therapeutic interventions targeting composition membranes. restoring equilibrium central nervous system remains challenge. underscores need comprehensive research into metabolism uncover practical insights etiology treatment lipidomics emerges major area research.

Language: Английский

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Sleep disturbances in autism spectrum disorder: Animal models, neural mechanisms, and therapeutics

Neurobiology of Sleep and Circadian Rhythms, Journal Year: 2023, Volume and Issue: 14, P. 100095 - 100095

Published: April 27, 2023

Sleep is crucial for brain development. disturbances are prevalent in children with autism spectrum disorder (ASD). Strikingly, these sleep problems positively correlated the severity of ASD core symptoms such as deficits social skills and stereotypic behavior, indicating that behavioral characteristics may be related. In this review, we will discuss highlight mouse models to study phenotypes ASD. addition, review neuromodulators controlling wakefulness how neuromodulatory systems disrupted animal patients Lastly, address therapeutic interventions improve various aspects sleep. Together, gaining mechanistic insights into neural mechanisms underlying help us develop better interventions.

Language: Английский

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Enhanced memory despite severe sleep loss in Drosophila insomniac mutants

PLoS Biology, Journal Year: 2025, Volume and Issue: 23(3), P. e3003076 - e3003076

Published: March 20, 2025

Sleep is crucial for cognitive functions and life span across species. While sleep homeostasis processes are linked through cellular synaptic plasticity, the signaling pathways connecting them remain unclear. Here, we show that Drosophila insomniac ( inc ) short mutants, which lack an adaptor protein autism-associated Cullin-3 ubiquitin ligase, exhibited enhanced Pavlovian aversive olfactory learning memory, unlike other mutants with normal or reduced memory. Through a genetic modifier screen, found mild reduction of Protein Kinase A (PKA) specifically rescued longevity phenotypes mutants. However, this further increased their excessive memory mushroom body overgrowth. Since displayed higher PKA signaling, propose loss-of-function suppresses via activity, also constrains Our data identify cascade balancing functions, provide plausible explanation suggesting hyperfunction can provoke deficits.

Language: Английский

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Shank3 influences mammalian sleep development

Journal of Neuroscience Research, Journal Year: 2022, Volume and Issue: 100(12), P. 2174 - 2186

Published: Sept. 2, 2022

Abstract Sleep problems are prevalent in autism spectrum disorder (ASD), can be observed before diagnosis, and associated with increased restricted repetitive behaviors. Therefore, sleep abnormalities may a core feature of the disorder, but developmental trajectory remains unknown. Animal models provide unique opportunity to understand ontogenesis ASD. Previously we showed that adult mice truncation high‐confidence ASD gene Shank3 (Shank3 ∆C ) recapitulate clinical phenotype. In this study used longitudinal electro‐encephalographic (EEG) recordings define, for first time, changes from weaning young adulthood an mouse model. We show male less overall throughout their lifespan, have rapid eye movement (REM) early life despite significantly reduced non‐rapid (NREM) sleep, abnormal responses pressure emerge during specific period. demonstrate ability fall asleep quickly response loss develops normally between 24 30 days mice. However, mutants unable reduce latency after periods prolonged waking maintain same regardless age. This phenomenon seems independent homeostatic NREM slow‐wave dynamics. Overall, our recapitulates both preclinical studies showing is consistently suggests falling reflect development arousal mechanisms.

Language: Английский

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Remembering and forgetting in sleep: Selective synaptic plasticity during sleep driven by scaling factors Homer1a and Arc

Neurobiology of Stress, Journal Year: 2022, Volume and Issue: 22, P. 100512 - 100512

Published: Dec. 31, 2022

Sleep is a conserved and essential process that supports learning memory. Synapses are major target of sleep function locus need. Evidence in the literature suggests need for has cellular or microcircuit level basis, can accumulate within localized brain regions as waking activity. Activation promoting kinases accumulation synaptic phosphorylation was recently shown to be part molecular basis A prominent hypothesis field some benefits mediated by broad but selective weakening, scaling-down, strength during order offset increased excitability from potentiation wake. The also shows synapses strengthened sleep, raising question what mechanisms may allow selection plasticity types sleep. Here I describe action scaling factors Arc Homer1a links with induced neurons response neuronal activity time spent awake. suggest drive weakening through homeostatic manner sensitive history individual synapses, based on patterned proteins. Therefore, offer insights into intricate between memory consolidation

Language: Английский

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Structural neuroplasticity after sleep loss modifies behavior and requires neurexin and neuroligin

iScience, Journal Year: 2024, Volume and Issue: 27(4), P. 109477 - 109477

Published: March 11, 2024

Structural neuroplasticity (changes in the size, strength, number, and targets of synaptic connections) can be modified by sleep disruption. However, causal relationships between genetic perturbations, loss, neuroplasticity, behavior remain unclear. The

Language: Английский

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Stem cell-specific ecdysone signaling regulates the development of dorsal fan-shaped body neurons and sleep homeostasis

Current Biology, Journal Year: 2024, Volume and Issue: 34(21), P. 4951 - 4967.e5

Published: Oct. 8, 2024

Highlights•Sleep-regulating 23E10 dFB neurons originate from late larval type II NSCs•DL1 and DM1 NSCs specifically produce neurons•Ecdysone signaling in is essential for neuronal fate•E93 regulates fate sleep homeostasisSummaryComplex behaviors arise neural circuits that assemble diverse cell types. Sleep a conserved behavior survival, yet little known about how the nervous system generates neuron types of sleep-wake circuit. Here, we focus on specification Drosophila 23E10-labeled dorsal fan-shaped body (dFB) long-field tangential input project to layers neuropil central complex. We use lineage analysis genetic birth dating identify two bilateral stem cells (NSCs) generate neurons. show adult express ecdysone-induced protein 93 (E93) loss ecdysone or E93 results their misspecification. Finally, knockdown impairs behavior. Our provide insight into extrinsic hormonal acts diversity required These findings suggest some disorders might derive defects cell-specific temporal neurodevelopmental programs.Graphical abstract

Language: Английский

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