Beyond the Rat Models of Human Neurodegenerative Disorders

Bugos, Ondrej; Bhide, Mangesh; Žilka, Norbert

doi:10.1007/s10571-009-9367-5

Cited by 30 publications

(24 citation statements)

References 103 publications

(89 reference statements)

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“…This rodent exhibits many physiological and morphological characteristics similar to those of humans. Historically, neuroscientists have preferred rats to mice as model systems and, indeed, many aspects of rat pharmacology and physiology are regarded as more relevant to humans and easier to observe than in mice (Abbott 2004;Bugos et al 2009). Furthermore, rats generally exhibit a more robust capacity for learning in behavioral tasks.…”

Section: Animal Transgenic Systemsmentioning

confidence: 99%

“…Presence of nuclear staining and microaggregates early in the course of the disease. Early overt behavioral changes seen and strength of the phenotype generally correlated with the number of CAG repeats (-200) (Heng et al 2009;Levine et al 2004;Lin et al 2001;Raymond et al 2011;Shelbourne et al 1999;Wheeler et al 2000;White et al 1997 (Bugos et al 2009;Clarke et al 2007;Echeverria et al 2004;Agca et al 2008;Flood et al 2009;Folkesson et al 2007;Liu et al 2008a;Ruiz-Opazo et al 2004 of A 3-42 after cleavage (Link 1995). Expression of this human A 42 minigene in muscle cells resulted in progressive paralysis and staining of muscle cells with a human A 42 speciWc antibody revealed A 42 deposits that reacted with Congo red and thioXavin S. Ultrastructural studies, however, revealed that the deposits were intracytoplasmic rather than extracellular as are amyloid plaques found in AD (Ewald and Li 2010).…”

Section: Knock-in Mutant Htt Using Homologous Recombination In Es Cellsmentioning

confidence: 99%

“…Yet despite the lack of a plaque and tangle pathology presenilin FAD mutant mice exhibit a wide range of anatomic, electrophysiological and biochemical changes that mimic many of the features of AD (Elder et al 2010b). Rat models while becoming more available appear to suVer the same limitations as models in the mouse requiring high-level expression of an APP FAD mutation to induce signiWcant plaque pathology (Table 1; Bugos et al 2009;Clarke et al 2007;Echeverria et al 2004;Agca et al 2008;Flood et al 2009;Folkesson et al 2007;Leon et al 2010;Liu et al 2008a;Ruiz-Opazo et al 2004). …”

Section: Knock-in Mutant Htt Using Homologous Recombination In Es Cellsmentioning

confidence: 99%

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Modeling human neurodegenerative diseases in transgenic systems

2011

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Transgenic systems are widely used to study the cellular and molecular basis of human neurodegenerative diseases. A wide variety of model organisms have been utilized, including bacteria (Escherichia coli), plants (Arabidopsis thaliana), nematodes (Caenorhabditis elegans), arthropods (Drosophila melanogaster), fish (zebrafish, Danio rerio), rodents (mouse, Mus musculus and rat, Rattus norvegicus) as well as non-human primates (rhesus monkey, Macaca mulatta). These transgenic systems have enormous value for understanding the pathophysiological basis of these disorders and have, in some cases, been instrumental in the development of therapeutic approaches to treat these conditions. In this review, we discuss the most commonly used model organisms and the methodologies available for the preparation of transgenic organisms. Moreover, we provide selected examples of the use of these technologies for the preparation of transgenic animal models of neurodegenerative diseases, including Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and Parkinson's disease (PD) and discuss the application of these technologies to AD as an example of how transgenic modeling has affected the study of human neurodegenerative diseases.

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Section: Animal Transgenic Systemsmentioning

confidence: 99%

Section: Knock-in Mutant Htt Using Homologous Recombination In Es Cellsmentioning

confidence: 99%

Section: Knock-in Mutant Htt Using Homologous Recombination In Es Cellsmentioning

confidence: 99%

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Modeling human neurodegenerative diseases in transgenic systems

2011

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“…Animal models represent a suitable model for in vivo and in vitro studies since there are physiological characteristics similar to those of human (Bugos, Bhide and Zilka, 2009).…”

Section: Literature Reviewmentioning

confidence: 99%

Stem Cell’s Behavioral Effects in Rats in a Model of Alzheimer’s Disease

Bertuzzi¹,

Rosa²,

Ourique³

et al. 2014

ASC

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Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder related to aging and central nervous system dysfunctions. Besides compromising the memory, AD is responsible for deficits in attention, orientation, organization, the capacity of planning and judging, among other cognitive functions, leading to the inability of living independently. The pharmacological treatment is only palliative. Thus, researches on stem cells implants emerge as promising prospects for the cure of central nervous system's disorders. The aim of this study was to investigate the effects of stem cells implants from human dental pulp, human adipose tissue and mice renal tissue on the behavior of rats in a model for AD. To this purpose, male adult rats of Wistar strain underwent stereotactic surgery for lesions of the nucleus basalis magnocellularis with unilateral AMPA infusions. Twenty one days from surgery for lesions, In the elevated T-maze, the significant mean was identified in the inhibitory avoidance (p= 0.028). Implants of stem cells demonstrated an improvement in the performance of implanted animals compared to the non-implanted group.

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“…As far as neurodegenerative diseases are concerned, the potential of murine models is limited because of their small-sized brain and difficulty in behavioral testing [16]. On the contrary, pig models exhibit physiological and anatomical characteristics similar to human ones and particular emphasis has been placed on swine potential for modeling symptoms and phenomena of neuropsychiatric diseases [17].…”

Section: Introductionmentioning

confidence: 99%

Modeling Amyotrophic Lateral Sclerosis in hSOD1G93A Transgenic Swine

et al. 2013

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that occurs in two clinically indistinguishable forms: sporadic (SALS) and familial (FALS), the latter linked to several gene mutations, mostly inheritable in a dominant manner. Nearly 20% of FALS forms are linked to mutations in the Cu/Zn superoxide dismutase (SOD1) gene. Research on ALS relies on transgenic models and particularly on mice carrying a glycine-to-alanine conversion at the 93rd codon (G93A) of the hSOD1 gene. Although G93A transgenic mice have been widely employed in clinical trials and basic research, doubts have been recently raised from numerous reliable sources about their suitability to faithfully reproduce human disease. Besides, the scientific community has already foreseen swine as an attractive and alternative model to nonhuman primates for modeling human diseases due to closer anatomical, physiological and biochemical features of swine rather than rodents to humans. On this basis, we have produced the first swine ALS model by in vitro transfection of cultured somatic cells combined with somatic cell nuclear transfer (SCNT). To achieve this goal we developed a SOD1^G93A (superoxide dismutase 1 mutated in Gly93-Ala) vector, capable of promoting a high and stable transgene expression in primary porcine adult male fibroblasts (PAF). After transfection, clonal selection and transgene expression level assessment, selected SOD1^G93A PAF colonies were used as nuclei donors in SCNT procedures. SOD1^G93A embryos were transferred in recipient sows, and pregnancies developed to term. A total of 5 piglets survived artificial hand raising and weaning and developed normally, reaching adulthood. Preliminary analysis revealed transgene integration and hSOD1^G93A expression in swine tissues and 360° phenotypical characterization is ongoing. We believe that our SOD1^G93A swine would provide an essential bridge between the fundamental work done in rodent models and the reality of treating ALS.

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Beyond the Rat Models of Human Neurodegenerative Disorders

Cited by 30 publications

References 103 publications

Modeling human neurodegenerative diseases in transgenic systems

Modeling human neurodegenerative diseases in transgenic systems

Stem Cell’s Behavioral Effects in Rats in a Model of Alzheimer’s Disease

Modeling Amyotrophic Lateral Sclerosis in hSOD1G93A Transgenic Swine

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