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https://www.readbyqxmd.com/read/29021890/zebrafish-knockout-of-down-syndrome-gene-dyrk1a-shows-social-impairments-relevant-to-autism
#1
Oc-Hee Kim, Hyun-Ju Cho, Enna Han, Ted Inpyo Hong, Krishan Ariyasiri, Jung-Hwa Choi, Kyu-Seok Hwang, Yun-Mi Jeong, Se-Yeol Yang, Kweon Yu, Doo-Sang Park, Hyun-Woo Oh, Erica E Davis, Charles E Schwartz, Jeong-Soo Lee, Hyung-Goo Kim, Cheol-Hee Kim
BACKGROUND: DYRK1A maps to the Down syndrome critical region at 21q22. Mutations in this kinase-encoding gene have been reported to cause microcephaly associated with either intellectual disability or autism in humans. Intellectual disability accompanied by microcephaly was recapitulated in a murine model by overexpressing Dyrk1a which mimicked Down syndrome phenotypes. However, given embryonic lethality in homozygous knockout (KO) mice, no murine model studies could present sufficient evidence to link Dyrk1a dysfunction with autism...
2017: Molecular Autism
https://www.readbyqxmd.com/read/28993314/mecp2-regulates-tnfa-during-zebrafish-embryonic-development-and-acute-inflammation
#2
M van der Vaart, O Svoboda, B G Weijts, R Espín-Palazón, V Sapp, T Pietri, M Bagnat, A R Muotri, D Traver
Mutations in MECP2 cause Rett syndrome, a severe neurological disorder with autism-like features. Duplication of MECP2 also causes severe neuropathology. Both diseases display immunological abnormalities that suggest a role for MeCP2 in controlling immune and inflammatory responses. Here, we used mecp2-null zebrafish to study the potential function of Mecp2 as an immunological regulator. Mecp2-deficiency resulted in an increase in neutrophil infiltration and upregulated expression of the pro- and anti-inflammatory cytokines Il1b and Il10 as a secondary response to disturbances in tissue homeostasis...
October 9, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28984854/adult-zebrafish-in-cns-disease-modeling-a-tank-that-s-half-full-not-half-empty-and-still-filling
#3
Darya A Meshalkina, Elana V Kysil, Jason E Warnick, Konstantin A Demin, Allan V Kalueff
The zebrafish (Danio rerio) is increasingly used in a broad array of biomedical studies, from cancer research to drug screening. Zebrafish also represent an emerging model organism for studying complex brain diseases. The number of zebrafish neuroscience studies is exponentially growing, significantly outpacing those conducted with rodents or other model organisms. Yet, there is still a substantial amount of resistance in adopting zebrafish as a first-choice model system. Studies of the repertoire of zebrafish neural and behavioral functions continue to reveal new opportunities for understanding the pathobiology of various CNS deficits...
October 6, 2017: Lab Animal
https://www.readbyqxmd.com/read/28965845/the-immune-signaling-adaptor-lat-contributes-to-the-neuroanatomical-phenotype-of-16p11-2-bp2-bp3-cnvs
#4
Maria Nicla Loviglio, Thomas Arbogast, Aia Elise Jønch, Stephan C Collins, Konstantin Popadin, Camille S Bonnet, Giuliana Giannuzzi, Anne M Maillard, Sébastien Jacquemont, Binnaz Yalcin, Nicholas Katsanis, Christelle Golzio, Alexandre Reymond
Copy-number changes in 16p11.2 contribute significantly to neuropsychiatric traits. Besides the 600 kb BP4-BP5 CNV found in 0.5%-1% of individuals with autism spectrum disorders and schizophrenia and whose rearrangement causes reciprocal defects in head size and body weight, a second distal 220 kb BP2-BP3 CNV is likewise a potent driver of neuropsychiatric, anatomical, and metabolic pathologies. These two CNVs are engaged in complex reciprocal chromatin looping, intimating a functional relationship between genes in these regions that might be relevant to pathomechanism...
October 5, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28887224/the-zebrafish-as-a-promising-tool-for-modeling-human-brain-disorders-a-review-based-upon-an-ibns-symposium
#5
REVIEW
Soaleha Shams, Jason Rihel, Jose G Ortiz, Robert Gerlai
The zebrafish represents an excellent compromise between system complexity and practical simplicity, features that make it useful for modeling and mechanistic analysis of complex brain disorders. Also promising are screens for psychoactive drugs with effects on larval and adult zebrafish behavior. This review, based upon a recent symposium held at the 2016 IBNS Congress, provides different perspectives on how the zebrafish may be utilized to advance research into human central nervous system disorders. It starts with a discussion on an important bottleneck in zebrafish research, measuring the behavior of this species (specifically shoaling), and continues with examples on research on autism spectrum disorder in larval zebrafish, on screening natural products for compounds with psychoactive properties in adult zebrafish, and on the development of a zebrafish model of fetal alcohol spectrum disorders...
September 5, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28829283/fragile-x-mental-retardation-1-knockout-zebrafish-shows-precocious-development-in-social-behavior
#6
Yao-Ju Wu, Mao-Ting Hsu, Ming-Chong Ng, Tamara G Amstislavskaya, Maria A Tikhonova, Yi-Ling Yang, Kwok-Tung Lu
Fragile X syndrome (FXS) is a generally hereditary form of human mental retardation that is caused by triplet repeat expansion (CGG) mutation in fragile X mental retardation 1 (fmr1) gene promoter and that results in the absence of the fragile X mental retardation protein (FMRP) expression. The common symptoms of FXS patients include learning disabilities, anxiety, autistic behaviors, as well as other behavioral abnormalities. Our previous results demonstrated the behavioral abnormalities in fmr1 knockout (KO) zebrafish such as fear memory impairment and autism-like behavior...
October 2017: Zebrafish
https://www.readbyqxmd.com/read/28626003/transcriptional-complexity-and-distinct-expression-patterns-of-auts2-paralogs-in-danio-rerio
#7
Igor Kondrychyn, Lena Robra, Vatsala Thirumalai
Several genes that have been implicated in autism spectrum disorders (ASDs) have multiple transcripts. Therefore, comprehensive transcript annotation is critical for determining the respective gene function. The autism susceptibility candidate 2 (AUTS2) gene is associated with various neurological disorders, including autism and brain malformation. AUTS2 is important for activation of transcription of neural specific genes, neuronal migration, and neurite outgrowth. Here, we present evidence for significant transcriptional complexity in the auts2 gene locus in the zebrafish genome, as well as in genomic loci of auts2 paralogous genes fbrsl1 and fbrs Several genes that have been implicated in ASDs are large and have multiple transcripts...
August 7, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28442991/a-novel-long-non-coding-rna-durga-modulates-dendrite-density-and-expression-of-kalirin-in-zebrafish
#8
Mayuresh A Sarangdhar, Divya Chaubey, Abhishek Bhatt, Monisha Km, Manish Kumar, Shashi Ranjan, Beena Pillai
Kalirin, a key player in axonal development, nerve growth and synaptic re-modeling, is implicated in many pathological conditions like schizophrenia and autism-spectrum disorders. Alternative promoters and splicing lead to functionally distinct isoforms, but the post-transcriptional regulation of Kalirin has not been studied. Here, we report a novel non-coding RNA, which we name durga, arising from the first exon of kalirin a (kalrna) in the antisense orientation in zebrafish. The kalrna and durga transcripts are barely detectable during early development, but steadily increase by 24 hours post-fertilization (hpf) as the brain develops...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28414966/modeling-sleep-and-neuropsychiatric-disorders-in-zebrafish
#9
REVIEW
Talia Levitas-Djerbi, Lior Appelbaum
What are the molecular and cellular mechanisms that link neurological disorders and sleep disturbances? The transparent zebrafish model could bridge this gap in knowledge due to its unique genetic and imaging toolbox, and amenability to high-throughput screening. Sleep is well-characterized in zebrafish and key regulators of the sleep/wake cycle are conserved, including melatonin and hypocretin/orexin (Hcrt), whereas novel sleep regulating proteins are continually being identified, such as Kcnh4a, Neuromedin U, and QRFP...
June 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28365779/personalized-genome-sequencing-coupled-with-ipsc-technology-identifies-gtdc1-as-a-gene-involved-in-neurodevelopmental-disorders
#10
Irene Aksoy, Kagistia H Utami, Cecilia L Winata, Axel M Hillmer, Sigrid L Rouam, Sylvain Briault, Sonia Davila, Lawrence W Stanton, Valere Cacheux
The cellular and molecular mechanisms underlying neurodevelopmental conditions such as autism spectrum disorders have been studied intensively for decades. The ability to generate patient-specific induced pluripotent stem cells (iPSCs) now offers a novel strategy for modelling human diseases. Recent studies have reported the derivation of iPSCs from patients with neurological disorders. The key challenge remains the demonstration of disease-related phenotypes and the ability to model the disease. Here we report a case study with signs of neurodevelopmental disorders (NDDs) harbouring chromosomal rearrangements that were sequenced using long-insert DNA paired-end tag (DNA-PET) sequencing approach...
January 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28359144/mind-bomb-binding-partner-ranbp9-plays-a-contributory-role-in-retinal-development
#11
Kyeong-Won Yoo, Maivannan Thiruvarangan, Yun-Mi Jeong, Mi-Sun Lee, Sateesh Maddirevula, Myungchull Rhee, Young-Ki Bae, Hyung-Goo Kim, Cheol-Hee Kim
Ran-binding protein family member, RanBP9 has been reported in various basic cellular mechanisms and neuropathological conditions including schizophrenia. Previous studies have reported that RanBP9 is highly expressed in the mammalian brain and retina; however, the role of RanBP9 in retinal development is largely unknown. Here, we present the novel and regulatory roles of RanBP9 in retinal development of a vertebrate animal model, zebrafish. Zebrafish embryos exhibited abundant expression of ranbp9 in developing brain tissues as well as in the developing retina...
April 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28251519/non-human-primate-models-for-brain-disorders-towards-genetic-manipulations-via-innovative-technology
#12
REVIEW
Zilong Qiu, Xiao Li
Modeling brain disorders has always been one of the key tasks in neurobiological studies. A wide range of organisms including worms, fruit flies, zebrafish, and rodents have been used for modeling brain disorders. However, whether complicated neurological and psychiatric symptoms can be faithfully mimicked in animals is still debatable. In this review, we discuss key findings using non-human primates to address the neural mechanisms underlying stress and anxiety behaviors, as well as technical advances for establishing genetically-engineered non-human primate models of autism spectrum disorders and other disorders...
April 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28163161/zebrafish-models-of-autism-spectrum-disorder
#13
REVIEW
Daria A Meshalkina, Marina N Kizlyk, Elana V Kysil, Adam D Collier, David J Echevarria, Murilo S Abreu, Leonardo J G Barcellos, Cai Song, Jason E Warnick, Evan J Kyzar, Allan V Kalueff
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by motor, social and cognitive deficits that develop early during childhood. The pathogenesis of ASD is not well characterized and involves a multifaceted interaction between genetic, neurobiological and environmental factors. Animal (experimental) models possess evolutionarily conserved behaviors and molecular pathways that are highly relevant for studying ASD. The zebrafish (Danio rerio) is a relatively new animal model with promise for understanding the pathogenesis of complex brain disorders and discovering novel treatments...
February 3, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/27802373/innate-color-preference-of-zebrafish-and-its-use-in-behavioral-analyses
#14
Jong-Su Park, Jae-Ho Ryu, Tae-Ik Choi, Young-Ki Bae, Suman Lee, Hae Jin Kang, Cheol-Hee Kim
Although innate color preference of motile organisms may provide clues to behavioral biases, it has remained a longstanding question. In this study, we investigated innate color preference of zebrafish larvae. A cross maze with different color sleeves around each arm was used for the color preference test (R; red, G; green, B; blue, Y; yellow). The findings showed that 5 dpf zebrafish larvae preferred blue over other colors (B > R > G > Y). To study innate color recognition further, tyrosinase mutants were generated using CRISPR/Cas9 system...
October 2016: Molecules and Cells
https://www.readbyqxmd.com/read/27785454/zebrafish-embryos-as-in-vivo-test-tubes-to-unravel-cell-specific-mechanisms-of-neurogenesis-during-neurodevelopment-and-in-diseases
#15
Éric Samarut
Zebrafish has become a model of choice for developmental studies in particular for studying neural development and related mechanisms involved in diseases. Indeed, zebrafish provides a fast, handy and accurate model to perform functional genomics on a gene or network of genes of interest. Recently, we successfully purified neural stem cells (NSCs) by fluorescence-activated cell sorting (FACS) from whole embryos in order to analyze cell-specific transcriptomic effects by RNA sequencing. As a result, our work sheds light on signaling pathways that are more likely to be involved in our morpholino-induced neurogenesis phenotype...
2016: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/27677466/gain-of-function-defects-of-astrocytic-kir4-1-channels-in-children-with-autism-spectrum-disorders-and-epilepsy
#16
Federico Sicca, Elena Ambrosini, Maria Marchese, Luigi Sforna, Ilenio Servettini, Giulia Valvo, Maria Stefania Brignone, Angela Lanciotti, Francesca Moro, Alessandro Grottesi, Luigi Catacuzzeno, Sara Baldini, Sonia Hasan, Maria Cristina D'Adamo, Fabio Franciolini, Paola Molinari, Filippo M Santorelli, Mauro Pessia
Dysfunction of the inwardly-rectifying potassium channels Kir4.1 (KCNJ10) represents a pathogenic mechanism contributing to Autism-Epilepsy comorbidity. To define the role of Kir4.1 variants in the disorder, we sequenced KCNJ10 in a sample of affected individuals, and performed genotype-phenotype correlations. The effects of mutations on channel activity, protein trafficking, and astrocyte function were investigated in Xenopus laevis oocytes, and in human astrocytoma cell lines. An in vivo model of the disorder was also explored through generation of kcnj10a morphant zebrafish overexpressing the mutated human KCNJ10...
September 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27573365/maternal-exposure-to-the-water-soluble-fraction-of-crude-oil-lead-and-their-mixture-induces-autism-like-behavioral-deficits-in-zebrafish-danio-rerio-larvae
#17
Yuanchuan Wang, Hongxiu Zhong, Chonggang Wang, Dongxu Gao, Yulin Zhou, Zhenghong Zuo
Autism spectrum disorder (ASD) is a serious debilitating mental illness with complex symptoms and multi-factorial pathogenesis. Although the pathogenesis of ASD remains unclear, etiology is thought to involve complex, multigenic interactions and possible environmental contributions. In the present study, we used zebrafish (Danio rerio) as a model to investigate whether maternal exposure to the water soluble fraction of crude oil (WSF, 5μg/L), lead (Pb, 20μg/L) and their mixture (5 μg/L WSF+20 μg/L Pb) could induce autism-like behavior in larvae...
August 26, 2016: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/27562614/developmental-profiling-of-asd-related-shank3-transcripts-and-their-differential-regulation-by-valproic-acid-in-zebrafish
#18
Chun-Xue Liu, Xiao-Lan Peng, Chun-Chun Hu, Chun-Yang Li, Qiang Li, Xiu Xu
SHANK3 is a scaffolding protein that binds to various synaptic proteins at the postsynaptic density (PSD) of excitatory glutamatergic synapses. SHANK3 is not only strongly implicated in autism spectrum disorders (ASD) but also plays a critical role in human Phelan-McDermid syndrome (22q13.3 deletion syndrome). Accumulated experimental evidence demonstrates that the zebrafish model system is useful for studying the functions of ASD-related gene during early development. However, many basic features of shank3 transcript expression in zebrafish remain poorly understood...
November 2016: Development Genes and Evolution
https://www.readbyqxmd.com/read/27458342/function-over-form-modeling-groups-of-inherited-neurological-conditions-in-zebrafish
#19
REVIEW
Robert A Kozol, Alexander J Abrams, David M James, Elena Buglo, Qing Yan, Julia E Dallman
Zebrafish are a unique cell to behavior model for studying the basic biology of human inherited neurological conditions. Conserved vertebrate genetics and optical transparency provide in vivo access to the developing nervous system as well as high-throughput approaches for drug screens. Here we review zebrafish modeling for two broad groups of inherited conditions that each share genetic and molecular pathways and overlap phenotypically: neurodevelopmental disorders such as Autism Spectrum Disorders (ASD), Intellectual Disability (ID) and Schizophrenia (SCZ), and neurodegenerative diseases, such as Cerebellar Ataxia (CATX), Hereditary Spastic Paraplegia (HSP) and Charcot-Marie Tooth Disease (CMT)...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27247142/oxytocin-reversed-mk-801-induced-social-interaction-and-aggression-deficits-in-zebrafish
#20
Fernanda Francine Zimmermann, Karina Vidarte Gaspary, Anna Maria Siebel, Carla Denise Bonan
Changes in social behavior occur in several neuropsychiatric disorders such as schizophrenia and autism. The interaction between individuals is an essential aspect and an adaptive response of several species, among them the zebrafish. Oxytocin is a neuroendocrine hormone associated with social behavior. The aim of the present study was to investigate the effects of MK-801, a non-competitive antagonist of glutamate NMDA receptors, on social interaction and aggression in zebrafish. We also examined the modulation of those effects by oxytocin, the oxytocin receptor agonist carbetocin and the oxytocin receptor antagonist L-368,899...
September 15, 2016: Behavioural Brain Research
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