New Zebrafish Models of Neurodegeneration

Martín-Jiménez, Rebeca; Campanella, Michelangelo; Russell, Claire

doi:10.1007/s11910-015-0555-z

Cited by 32 publications

(26 citation statements)

References 28 publications

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“…Zebrafish have been increasingly used as a system to model neurodegeneration and for the study of human eye disorders, since it has similarities to the mammalian nervous system, and has emerged as a vertebrate model organism to combine in vitro and in vivo assays. 32 , 33 Previous data confirm that in zebrafish, hdac6 is expressed in the larval eye during maturation of visual function, 19 and specifically in cone photoreceptors as determined by microarray analysis of cone-enriched transcripts from adult zebrafish. 34 The data are deposited in the NCBI Gene Expression Omnibus (GEO) database, under accession number GSE86155.…”

Section: Resultsmentioning

confidence: 76%

HDAC6 inhibition by tubastatin A is protective against oxidative stress in a photoreceptor cell line and restores visual function in a zebrafish model of inherited blindness

et al. 2017

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Retinal diseases, such as hereditary retinitis pigmentosa and age-related macular degeneration, are characterized by the progressive loss of photoreceptors. Histone deacetylase 6 (HDAC6) is considered as a stress surveillance factor and a potential target for neuroprotection and regeneration. Overexpression of HDAC6 has been connected to neurodegenerative disorders, and its suppression may provide protection. Here we show that HDAC6 is constitutively present in the mouse retina, and in the cone-like mouse cell line 661W. In 661W cells HDAC6 inhibition by the specific inhibitor tubastatin A (TST) led to the acetylation of α-tubulin, which is a major substrate for HDAC6. After oxidative stress, exerted by hydrogen peroxide, TST promoted cell survival and the upregulation of heat-shock proteins HSP70 and HSP25 by activation of heat-shock transcription factor 1. Furthermore, in response to oxidative stress the redox regulatory protein peroxiredoxin 1 (Prx1) was modulated in 661W cells by HDAC6 inhibition. The peroxide reducing activity of Prx1 is dependent on its acetylation, which is mediated by HDAC6. Pre-incubation with TST prevented the inactivation of Prx1 and its preserved activity may exert protective effects in photoreceptor cells. To determine whether TST treatment has a therapeutic effect on visual function, the dyeucd6 zebrafish model of inherited sight loss was utilized. Zebrafish have developed as a suitable model system for pharmacological testing. In vivo application of TST caused the hyperacetylation of α-tubulin, indicating that HDAC6 is active in this model. Furthermore, TST was sufficient to rescue visual function and retinal morphology. Hence, HDAC6 inhibition and the regulation of peroxiredoxin activity may play a significant role in protecting retinal cells and in particular photoreceptors, which are exposed to high levels of reactive oxygen species derived from oxidative stress-induced injuries.

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Section: Resultsmentioning

confidence: 76%

HDAC6 inhibition by tubastatin A is protective against oxidative stress in a photoreceptor cell line and restores visual function in a zebrafish model of inherited blindness

et al. 2017

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“…Zebrafish is an increasingly useful model of human neurodegenerative diseases including PD [17] . Loss of dopaminergic neurons and motor deficits, as observed in PD, can be replicated at the larvae stage of zebrafish exposed to oxidative stressors [18] , [19] , [20] , [21] .…”

Section: Introductionmentioning

confidence: 99%

Astroglial DJ-1 over-expression up-regulates proteins involved in redox regulation and is neuroprotective in vivo

et al. 2018

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DJ-1, a Parkinson's disease-associated protein, is strongly up-regulated in reactive astrocytes in Parkinson's disease. This is proposed to represent a neuronal protective response, although the mechanism has not yet been identified. We have generated a transgenic zebrafish line with increased astroglial DJ-1 expression driven by regulatory elements from the zebrafish GFAP gene. Larvae from this transgenic line are protected from oxidative stress-induced injuries as caused by MPP+, a mitochondrial complex I inhibitor shown to induce dopaminergic cells death. In a global label-free proteomics analysis of wild type and transgenic larvae exposed to MPP+, 3418 proteins were identified, in which 366 proteins were differentially regulated. In particular, we identified enzymes belonging to primary metabolism to be among proteins affected by MPP+ in wild type animals, but not affected in the transgenic line. Moreover, by performing protein profiling on isolated astrocytes we showed that an increase in astrocytic DJ-1 expression up-regulated a large group of proteins associated with redox regulation, inflammation and mitochondrial respiration. The majority of these proteins have also been shown to be regulated by Nrf2. These findings provide a mechanistic insight into the protective role of astroglial up-regulation of DJ-1 and show that our transgenic zebrafish line with astrocytic DJ-1 over-expression can serve as a useful animal model to understand astrocyte-regulated neuroprotection associated with oxidative stress-related neurodegenerative disease.

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“…Over the last ten years zebrafish has become an interesting model organism to study the molecular and cell biology of the vertebrate brain [ 54 , 55 ] and has emerged as a model species for translational research in various neuroscience areas, such as depressive disorders [ 56 ], neurodegeneration [ 57 ], motor neuron disease [ 58 ], autism spectrum disorders [ 59 ] and Alzheimer’s disease [ 60 ]. In addition, compared to mammals, the brain of adult zebrafish exhibits a high number of proliferative areas distributed along the ventricles of the telencephalon, diencephalon and mesencephalon [ 61 – 65 ], a feature tightly linked to the persistence of radial glial progenitors [ 61 ].…”

Section: Introductionmentioning

confidence: 99%

BDNF Expression in Larval and Adult Zebrafish Brain: Distribution and Cell Identification

Cacialli¹,

Guéguen²,

Coumailleau³

et al. 2016

PLoS ONE

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Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, has emerged as an active mediator in many essential functions in the central nervous system of mammals. BDNF plays significant roles in neurogenesis, neuronal maturation and/or synaptic plasticity and is involved in cognitive functions such as learning and memory. Despite the vast literature present in mammals, studies devoted to BDNF in the brain of other animal models are scarse. Zebrafish is a teleost fish widely known for developmental genetic studies and is emerging as model for translational neuroscience research. In addition, its brain shows many sites of adult neurogenesis allowing higher regenerative properties after traumatic injuries. To add further knowledge on neurotrophic factors in vertebrate brain models, we decided to determine the distribution of bdnf mRNAs in the larval and adult zebrafish brain and to characterize the phenotype of cells expressing bdnf mRNAs by means of double staining studies. Our results showed that bdnf mRNAs were widely expressed in the brain of 7 days old larvae and throughout the whole brain of mature female and male zebrafish. In adults, bdnf mRNAs were mainly observed in the dorsal telencephalon, preoptic area, dorsal thalamus, posterior tuberculum, hypothalamus, synencephalon, optic tectum and medulla oblongata. By combining immunohistochemistry with in situ hybridization, we showed that bdnf mRNAs were never expressed by radial glial cells or proliferating cells. By contrast, bdnf transcripts were expressed in cells with neuronal phenotype in all brain regions investigated. Our results provide the first demonstration that the brain of zebrafish expresses bdnf mRNAs in neurons and open new fields of research on the role of the BDNF factor in brain mechanisms in normal and brain repairs situations.

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New Zebrafish Models of Neurodegeneration

Cited by 32 publications

References 28 publications

HDAC6 inhibition by tubastatin A is protective against oxidative stress in a photoreceptor cell line and restores visual function in a zebrafish model of inherited blindness

HDAC6 inhibition by tubastatin A is protective against oxidative stress in a photoreceptor cell line and restores visual function in a zebrafish model of inherited blindness

Astroglial DJ-1 over-expression up-regulates proteins involved in redox regulation and is neuroprotective in vivo

BDNF Expression in Larval and Adult Zebrafish Brain: Distribution and Cell Identification

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