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‣ Insights into Alzheimer disease pathogenesis from studies in transgenic animal models

SCHAEFFER, Evelin L.; FIGUEIRO, Micheli; GATTAZ, Wagner F.
Fonte: Faculdade de Medicina / USP Publicador: Faculdade de Medicina / USP
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
659.452%
Alzheimer disease is the most common cause of dementia among the elderly, accounting for ~60-70% of all cases of dementia. The neuropathological hallmarks of Alzheimer disease are senile plaques (mainly containing p-amyloid peptide derived from amyloid precursor protein) and neurofibrillary tangles (containing hyperphosphorylated Tau protein), along with neuronal loss. At present there is no effective treatment for Alzheimer disease. Given the prevalence and poor prognosis of the disease, the development of animal models has been a research priority to understand pathogenic mechanisms and to test therapeutic strategies. Most cases of Alzheimer disease occur sporadically in people over 65 years old, and are not genetically inherited. Roughly 5% of patients with Alzheimer disease have familial Alzheimer disease-that is, related to a genetic predisposition, including mutations in the amyloid precursor protein, presenilin 1, and presenilin 2 genes. The discovery of genes for familial Alzheimer disease has allowed transgenic models to be generated through the overexpression of the amyloid precursor protein and/or presenilins harboring one or several mutations found in familial Alzheimer disease. Although none of these models fully replicates the human disease...

‣ Animal models for genetic neuromuscular diseases

VAINZOF, Mariz; AYUB-GUERRIERI, Danielle; ONOFRE, Paula C. G.; MARTINS, Poliana C. M.; LOPES, Vanessa F.; ZILBERZTAJN, Dinorah; MAIA, Lucas S.; SELL, Karen; YAMAMOTO, Lydia U.
Fonte: HUMANA PRESS INC Publicador: HUMANA PRESS INC
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
665.3692%
The neuromuscular disorders are a heterogeneous group of genetic diseases, caused by mutations in genes coding sarcolemmal, sarcomeric, and citosolic muscle proteins. Deficiencies or loss of function of these proteins leads to variable degree of progressive loss of motor ability. Several animal models, manifesting phenotypes observed in neuromuscular diseases, have been identified in nature or generated in laboratory. These models generally present physiological alterations observed in human patients and can be used as important tools for genetic, clinic, and histopathological studies. The mdx mouse is the most widely used animal model for Duchenne muscular dystrophy (DMD). Although it is a good genetic and biochemical model, presenting total deficiency of the protein dystrophin in the muscle, this mouse is not useful for clinical trials because of its very mild phenotype. The canine golden retriever MD model represents a more clinically similar model of DMD due to its larger size and significant muscle weakness. Autosomal recessive limb-girdle MD forms models include the SJL/J mice, which develop a spontaneous myopathy resulting from a mutation in the Dysferlin gene, being a model for LGMD2B. For the human sarcoglycanopahties (SG)...

‣ Validating animal models for preclinical research: a scientific and ethical discussion

Varga, Orsolya E.; Hansen, Axel K.; Sandøe, Peter; Olsson, I. Anna S.
Fonte: Fund for the Replacement of Animals in Medical Experiments Publicador: Fund for the Replacement of Animals in Medical Experiments
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
664.98414%
The use of animals to model humans in biomedical research relies on the notion that basic processes are sufficiently similar across species to allow extrapolation. Animal model validity is discussed in terms of the similarity between the model and human condition it is intended to model, but no formal validation of models is applied. There is a stark contrast here with non-animal alternatives in toxicology and safety studies, for which an extensive validation is required. In the present paper we discuss the potential and limitations of validating preclinical animal models for proof-of-concept studies using an approach similar to that applied to alternative non-animal methods in toxicology and safety testing. A major challenge in devising a validation system for animal models is the lack of a clear gold standard to compare results with. While a complete adoption of the validation approach for alternative methods is probably inappropriate for research animal models, key feature such as making data available for external validation and defining a strategy to run experiments in a way that permits meaningful retrospective analysis remain relevant.

‣ Use of perfusion bioreactors and large animal models for long bone tissue engineering

Gardel, Leandro S.; Serra, L. A.; Reis, R. L.; Gomes, Manuela E.
Fonte: Mary Ann Liebert, Inc. Publicador: Mary Ann Liebert, Inc.
Tipo: Artigo de Revista Científica
Publicado em //2014 Português
Relevância na Pesquisa
658.5377%
Tissue engineering and regenerative medicine (TERM) strategies for generation of new bone tissue includes the combined use of autologous or heterologous mesenchymal stem cells (MSC) and three-dimensional (3D) scaffold materials serving as structural support for the cells, that develop into tissue-like substitutes under appropriate in vitro culture conditions. This approach is very important due to the limitations and risks associated with autologous, as well as allogenic bone grafiting procedures currently used. However, the cultivation of osteoprogenitor cells in 3D scaffolds presents several challenges, such as the efficient transport of nutrient and oxygen and removal of waste products from the cells in the interior of the scaffold. In this context, perfusion bioreactor systems are key components for bone TERM, as many recent studies have shown that such systems can provide dynamic environments with enhanced diffusion of nutrients and therefore, perfusion can be used to generate grafts of clinically relevant sizes and shapes. Nevertheless, to determine whether a developed tissue-like substitute conforms to the requirements of biocompatibility, mechanical stability and safety, it must undergo rigorous testing both in vitro and in vivo. Results from in vitro studies can be difficult to extrapolate to the in vivo situation...

‣ Animal models of anxiety: an ethological perspective

Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/03/1997 Português
Relevância na Pesquisa
660.6413%
In the field of anxiety research, animal models are used as screening tools in the search for compounds with therapeutic potential and as simulations for research on mechanisms underlying emotional behaviour. However, a solely pharmacological approach to the validation of such tests has resulted in distinct problems with their applicability to systems other than those involving the benzodiazepine/GABAA receptor complex. In this context, recent developments in our understanding of mammalian defensive behaviour have not only prompted the development of new models but also attempts to refine existing ones. The present review focuses on the application of ethological techniques to one of the most widely used animal models of anxiety, the elevated plus-maze paradigm. This fresh approach to an established test has revealed a hitherto unrecognized multidimensionality to plus-maze behaviour and, as it yields comprehensive behavioural profiles, has many advantages over conventional methodology. This assertion is supported by reference to recent work on the effects of diverse manipulations including psychosocial stress, benzodiazepines, GABA receptor ligands, neurosteroids, 5-HT1A receptor ligands, and panicolytic/panicogenic agents. On the basis of this review...

‣ The brain decade in debate: II. Panic or anxiety? From animal models to a neurobiological basis

Andreatini,R.; Blanchard,C.; Blanchard,R.; Brandão,M.L.; Carobrez,A.P.; Griebel,G.; Guimarães,F.S.; Handley,S.L.; Jenck,F.; Leite,J.R.; Rodgers,J.; Schenberg,L.C.; Da Cunha,C.; Graeff,F.G.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/02/2001 Português
Relevância na Pesquisa
663.41586%
This article is a transcription of an electronic symposium sponsored by the Brazilian Society of Neuroscience and Behavior (SBNeC). Invited researchers from the European Union, North America and Brazil discussed two issues on anxiety, namely whether panic is a very intense anxiety or something else, and what aspects of clinical anxiety are reproduced by animal models. Concerning the first issue, most participants agreed that generalized anxiety and panic disorder are different on the basis of clinical manifestations, drug response and animal models. Also, underlying brain structures, neurotransmitter modulation and hormonal changes seem to involve important differences. It is also common knowledge that existing animal models generate different types of fear/anxiety. A challenge for future research is to establish a good correlation between animal models and nosological classification.

‣ A critical overview of animal models of psychiatric disorders: challenges and perspectives

Salgado,Joao Vinicius; Sandner,Guy
Fonte: Associação Brasileira de Psiquiatria - ABP Publicador: Associação Brasileira de Psiquiatria - ABP
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2013 Português
Relevância na Pesquisa
659.75914%
Animal models of psychiatric disorders are a challenging but highly relevant issue. Most psychiatric disorders are very heterogeneous syndromes, resulting from multiple and varied causal factors and characterized by symptoms that can only be inferred with significant limitations in non-human models. As constructing a model that reproduces a whole psychiatric syndrome seems virtually impossible, researchers have tried to focus on endophenotypes, i.e., discrete traits that are more proximal to predisposing genes than the whole syndrome. These can be explored in a wide range of approaches, such as in pharmacological, lesion, and environmental models. Another challenge is to understand how genes interact with environmental factors over time to result in the syndromic phenotype. A better understanding of the subcellular mechanisms that enhance or allow brain resistance to environmental influences is required, as is a global thesis compatible with the diversity of diseases sharing similar behavioral and biological traits. With an experimental inventory of the possible causes of minor developmental failures, we may systematically explore their consequences in the adult animal and be able to decide if this will enlighten the understanding of one or another psychiatric disease.

‣ Animal models of anxiety disorders and stress

Campos,Alline C.; Fogaca,Manoela V.; Aguiar,Daniele C.; Guimaraes,Francisco S.
Fonte: Associação Brasileira de Psiquiatria - ABP Publicador: Associação Brasileira de Psiquiatria - ABP
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2013 Português
Relevância na Pesquisa
661.3083%
Anxiety and stress-related disorders are severe psychiatric conditions that affect performance in daily tasks and represent a high cost to public health. The initial observation of Charles Darwin that animals and human beings share similar characteristics in the expression of emotion raise the possibility of studying the mechanisms of psychiatric disorders in other mammals (mainly rodents). The development of animal models of anxiety and stress has helped to identify the pharmacological mechanisms and potential clinical effects of several drugs. Animal models of anxiety are based on conflict situations that can generate opposite motivational states induced by approach-avoidance situations. The present review revisited the main rodent models of anxiety and stress responses used worldwide. Here we defined as “ethological” the tests that assess unlearned/unpunished responses (such as the elevated plus maze, light-dark box, and open field), whereas models that involve learned/punished responses are referred to as “conditioned operant conflict tests” (such as the Vogel conflict test). We also discussed models that involve mainly classical conditioning tests (fear conditioning). Finally, we addressed the main protocols used to induce stress responses in rodents...

‣ Animal models for predicting the efficacy and side effects of antipsychotic drugs

Gobira,Pedro H.; Ropke,Jivago; Aguiar,Daniele C.; Crippa,Jose A.S.; Moreira,Fabricio A.
Fonte: Associação Brasileira de Psiquiatria - ABP Publicador: Associação Brasileira de Psiquiatria - ABP
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2013 Português
Relevância na Pesquisa
660.6413%
The use of antipsychotic drugs represents an important approach for the treatment of schizophrenia. However, their efficacy is limited to certain symptoms of this disorder, and they induce serious side effects. As a result, there is a strong demand for the development of new drugs, which depends on reliable animal models for pharmacological characterization. The present review discusses the face, construct, and predictive validity of classical animal models for studying the efficacy and side effects of compounds for the treatment of schizophrenia. These models are based on the properties of antipsychotics to impair the conditioned avoidance response and reverse certain behavioral changes induced by psychotomimetic drugs, such as stereotypies, hyperlocomotion, and deficit in prepulse inhibition of the startle response. Other tests, which are not specific to schizophrenia, may predict drug effects on negative and cognitive symptoms, such as deficits in social interaction and memory impairment. Regarding motor side effects, the catalepsy test predicts the liability of a drug to induce Parkinson-like syndrome, whereas vacuous chewing movements predict the liability to induce dyskinesia after chronic treatment. Despite certain limitations...

‣ Insights into Alzheimer disease pathogenesis from studies in transgenic animal models

Schaeffer,Evelin L.; Figueiro,Micheli; Gattaz,Wagner F.
Fonte: Faculdade de Medicina / USP Publicador: Faculdade de Medicina / USP
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2011 Português
Relevância na Pesquisa
659.452%
Alzheimer disease is the most common cause of dementia among the elderly, accounting for ~60-70% of all cases of dementia. The neuropathological hallmarks of Alzheimer disease are senile plaques (mainly containing p-amyloid peptide derived from amyloid precursor protein) and neurofibrillary tangles (containing hyperphosphorylated Tau protein), along with neuronal loss. At present there is no effective treatment for Alzheimer disease. Given the prevalence and poor prognosis of the disease, the development of animal models has been a research priority to understand pathogenic mechanisms and to test therapeutic strategies. Most cases of Alzheimer disease occur sporadically in people over 65 years old, and are not genetically inherited. Roughly 5% of patients with Alzheimer disease have familial Alzheimer disease-that is, related to a genetic predisposition, including mutations in the amyloid precursor protein, presenilin 1, and presenilin 2 genes. The discovery of genes for familial Alzheimer disease has allowed transgenic models to be generated through the overexpression of the amyloid precursor protein and/or presenilins harboring one or several mutations found in familial Alzheimer disease. Although none of these models fully replicates the human disease...

‣ Animal models of acute lung injury

Matute-Bello, Gustavo; Frevert, Charles W.; Martin, Thomas R.
Fonte: American Physiological Society Publicador: American Physiological Society
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
662.25234%
Acute lung injury in humans is characterized histopathologically by neutrophilic alveolitis, injury of the alveolar epithelium and endothelium, hyaline membrane formation, and microvascular thrombi. Different animal models of experimental lung injury have been used to investigate mechanisms of lung injury. Most are based on reproducing in animals known risk factors for ARDS, such as sepsis, lipid embolism secondary to bone fracture, acid aspiration, ischemia-reperfusion of pulmonary or distal vascular beds, and other clinical risks. However, none of these models fully reproduces the features of human lung injury. The goal of this review is to summarize the strengths and weaknesses of existing models of lung injury. We review the specific features of human ARDS that should be modeled in experimental lung injury and then discuss specific characteristics of animal species that may affect the pulmonary host response to noxious stimuli. We emphasize those models of lung injury that are based on reproducing risk factors for human ARDS in animals and discuss the advantages and disadvantages of each model and the extent to which each model reproduces human ARDS. The present review will help guide investigators in the design and interpretation of animal studies of acute lung injury.

‣ What causes type 1 diabetes? Lessons from animal models

Buschard, Karsten
Fonte: Blackwell Publishing Ltd Publicador: Blackwell Publishing Ltd
Tipo: Artigo de Revista Científica
Publicado em /07/2011 Português
Relevância na Pesquisa
663.41586%
To study type 1 diabetes (T1D), excellent animal models exist, both spontaneously diabetic and virus-induced. Based on knowledge from these, this review focuses on the environmental factors leading to T1D, concentrated into four areas which are: (1) The thymus-dependent immune system: T1D is a T cell driven disease and the beta cells are destroyed in an inflammatory insulitis process. Autoimmunity is breakdown of self-tolerance and the balance between regulator T cells and aggressive effector T cells is disturbed. Inhibition of the T cells (by e.g. anti-CD3 antibody or cyclosporine) will stop the T1D process, even if initiated by virus. Theoretically, the risk from immunotherapy elicits a higher frequency of malignancy. (2) The activity of the beta cells: Resting beta cells display less antigenicity and are less sensitive to immune destruction. Beta-cell rest can be induced by giving insulin externally in metabolic doses or by administering potassium-channel openers. Both procedures prevent T1D in animal models, whereas no good human data exist due to the risk of hypoglycemia. (3) NKT cells: According to the hygiene hypothesis, stimulation of NKT cells by non-pathogen microbes gives rise to less T cell reaction and less autoimmunity. Glycolipids presented by CD1 molecules are central in this stimulation. (4) Importance of the intestine and gliadin intake: Gluten-free diet dramatically inhibits T1D in animal models...

‣ Focus On: The Use of Animal Models for the Study of Fetal Alcohol Spectrum Disorders

Wilson, Shannon E.; Cudd, Timothy A.
Fonte: National Institute on Alcohol Abuse and Alcoholism Publicador: National Institute on Alcohol Abuse and Alcoholism
Tipo: Artigo de Revista Científica
Publicado em //2011 Português
Relevância na Pesquisa
660.1488%
Considerable efforts to educate women not to abuse alcohol during pregnancy have failed to reduce the incidence of fetal alcohol syndrome. Therefore, other approaches to limit the effects of prenatal alcohol exposure are under consideration, including the development of prevention programs and interventions. For these strategies to be as successful as possible, it also is important to improve methods for identifying affected children. The use of animal models in prenatal alcohol exposure research is critical because of the practical and ethical limitations of using human subjects for such studies. This article reviews the use of animal models in three areas of research: addressing basic questions about alcohol exposure during development; improving the identification of affected individuals; and developing approaches to reduce the impact of prenatal alcohol exposure. The various animal-model systems that have been used to study fetal alcohol spectrum disorders, each with their own specific strengths, have provided new findings that have been successfully extrapolated to human subjects, resulting in advancement of the research field and our understanding of fetal alcohol spectrum disorders.

‣ The Role of Animal Models for Research on Severe Malaria

Craig, Alister G.; Grau, Georges E.; Janse, Chris; Kazura, James W.; Milner, Danny Arnold; Barnwell, John W.; Turner, Gareth; Langhorne, Jean
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
661.3702%
In light of the recent controversies over the role of animal models for research into the development of new treatments for severe malaria, particularly cerebral disease, a group of scientists came together to discuss the relative merits of a range of animal models and their overlap with the complex clinical syndromes of human disease. While it was not possible to fully resolve differences over the utility of the Plasmodium berghei ANKA model of experimental cerebral malaria, the meeting did bring the two research communities closer together to identify further work to provide information needed to validate the model and revitalise the development of other animal models displaying features of human pathology. The driving force behind this was the desire to ensure better translation of experimental findings into effective treatments for severe malaria.

‣ Are underlying assumptions of current animal models of human stroke correct: From STAIRs to high hurdles?

Turner, R.; Jickling, G.; Sharp, F.
Fonte: Springer New York LLC Publicador: Springer New York LLC
Tipo: Artigo de Revista Científica
Publicado em //2011 Português
Relevância na Pesquisa
664.98414%
Animal models of acute ischemic stroke have been criticized for failing to translate to human stroke. Nevertheless, animal models are necessary to improve our understanding of stroke pathophysiology and to guide the development of new stroke therapies. The rabbit embolic clot model is one animal model that has led to an effective therapy in human acute ischemic stroke, namely tissue plasminogen activator (tPA). We propose that potential compounds that demonstrate efficacy in non-rabbit animal models of acute ischemic stroke should also be tested in the rabbit embolic blood clot model and, where appropriate, compared to tPA prior to investigation in humans. Furthermore, the use of anesthesia needs to be considered as a major confounder in animal models of acute ischemic stroke, and death should be included as an outcome measure in animal stroke studies. These steps, along with the current STAIRs recommendations, may improve the successful translation of experimental therapies to clinical stroke treatments.; Renée J. Turner, Glen C. Jickling, Frank R. Sharp

‣ Animal models of neurodegenerative diseases

Ribeiro,Fabiola Mara; Camargos,Elizabeth Ribeiro da Silva; Souza,Leonardo Cruz de; Teixeira,Antonio Lucio
Fonte: Associação Brasileira de Psiquiatria - ABP Publicador: Associação Brasileira de Psiquiatria - ABP
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2013 Português
Relevância na Pesquisa
659.75914%
The prevalence of neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), increases with age, and the number of affected patients is expected to increase worldwide in the next decades. Accurately understanding the etiopathogenic mechanisms of these diseases is a crucial step for developing disease-modifying drugs able to preclude their emergence or at least slow their progression. Animal models contribute to increase the knowledge on the pathophysiology of neurodegenerative diseases. These models reproduce different aspects of a given disease, as well as the histopathological lesions and its main symptoms. The purpose of this review is to present the main animal models for AD, PD, and Huntington's disease.

‣ Periodontal ligament-derived cells for periodontal regeneration in animal models: a systematic review

Bright, R.; Hynes, K.; Gronthos, S.; Bartold, P.M.
Fonte: Wiley Publicador: Wiley
Tipo: Artigo de Revista Científica
Publicado em //2015 Português
Relevância na Pesquisa
662.88055%
BACKGROUND AND OBJECTIVE: Implantation of periodontal ligament stem cells is emerging as a potential periodontal regenerative procedure. This systematic review considers the evidence from animal models investigating the use of periodontal ligament stem cells for successful periodontal regeneration. MATERIAL AND METHODS: PubMed, Embase, MEDLINE and Google Scholar were searched to December 2013 for quantitative studies examining the outcome of implanting periodontal ligament stem cells into experimental periodontal defects in animals. Inclusion criteria were: implantation of periodontal ligament stem cells into surgically created periodontal defects for periodontal regeneration; animal models only; source of cells either human or animal; and published in English. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: From the literature search, 43 studies met the inclusion criteria. A wide variety of surgical defects were created in four species of animal (dog, rat, pig and sheep). Owing to wide variability in defect type, cell source and cell scaffold, no meta-analysis was possible. Outcome measures included new bone, new cementum and new connective tissue formation. In 70.5% of the results...

‣ Cardiovascular imaging: what have we learned from animal models?

Santos, Arnoldo; Fernández-Friera, Leticia; Villalba, María; López-Melgar, Beatriz; España, Samuel; Mateo, Jesús; Mota, Ruben A.; Jiménez-Borreguero, Jesús; Ruiz-Cabello, Jesús
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
664.96266%
Cardiovascular imaging has become an indispensable tool for patient diagnosis and follow up. Probably the wide clinical applications of imaging are due to the possibility of a detailed and high quality description and quantification of cardiovascular system structure and function. Also phenomena that involve complex physiological mechanisms and biochemical pathways, such as inflammation and ischemia, can be visualized in a non-destructive way. The widespread use and evolution of imaging would not have been possible without animal studies. Animal models have allowed for instance, (i) the technical development of different imaging tools, (ii) to test hypothesis generated from human studies and finally, (iii) to evaluate the translational relevance assessment of in vitro and ex-vivo results. In this review, we will critically describe the contribution of animal models to the use of biomedical imaging in cardiovascular medicine. We will discuss the characteristics of the most frequent models used in/for imaging studies. We will cover the major findings of animal studies focused in the cardiovascular use of the repeatedly used imaging techniques in clinical practice and experimental studies. We will also describe the physiological findings and/or learning processes for imaging applications coming from models of the most common cardiovascular diseases. In these diseases...

‣ Modelos experimentais para o estudo do diabetes tipo 1; Animal models for type 1 diabetes studies

Kirsten, Vanessa R.; Sesterheim, Patrícia; Saitovitch, David
Fonte: Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto Publicador: Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; ; Formato: application/pdf
Publicado em 30/03/2010 Português
Relevância na Pesquisa
666.1731%
Os modelos animais de diabetes têm sido usados extensivamente na obtenção do esclarecimentosobre esta doença. O objetivo deste estudo foi realizar uma revisão bibliográfica sobre os principaismodelos experimentais para o estudo do diabetes mellitus. Dentre os modelos experimentais para oestudo do diabetes, existem os modelos induzidos quimicamente por aloxana e streptozotocina, sendoque a dose utilizada depende da espécie do animal e do seu peso. Além disso, existem dois excelentesmodelos de diabetes espontâneo: os ratos BB (Biobreading) e os camundongos NOD (Non ObeseDiabetic). Os camundongos NOD são o modelo mais estudado de doença espontânea auto-imuneórgão-específico em todo o mundo. As razões para a preferência deste modelo incluem um genomabem definido, maior quantidade de reagentes monoclonais para a análise de componentes do sistemaimune e um custo razoavelmente baixo, comparado com a utilização de ratos. Estes camundongosexibem autoimunidade espontânea com destruição das ilhotas pancreáticas, de forma semelhante àobservada em humanos. A destruição auto-imune é caracterizada por insulite e infiltrado leucocitárionas ilhotas pancreáticas. Esta infiltração é composta predominantemente por células dendríticas...

‣ Insights into Alzheimer disease pathogenesis from studies in transgenic animal models

Schaeffer, Evelin L.; Figueiro, Micheli; Gattaz, Wagner F.
Fonte: Universidade de São Paulo. Faculdade de Medicina Publicador: Universidade de São Paulo. Faculdade de Medicina
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; ; ; ; ; Formato: application/pdf
Publicado em 01/01/2011 Português
Relevância na Pesquisa
659.452%
Alzheimer disease is the most common cause of dementia among the elderly, accounting for ~60-70% of all cases of dementia. The neuropathological hallmarks of Alzheimer disease are senile plaques (mainly containing p-amyloid peptide derived from amyloid precursor protein) and neurofibrillary tangles (containing hyperphosphorylated Tau protein), along with neuronal loss. At present there is no effective treatment for Alzheimer disease. Given the prevalence and poor prognosis of the disease, the development of animal models has been a research priority to understand pathogenic mechanisms and to test therapeutic strategies. Most cases of Alzheimer disease occur sporadically in people over 65 years old, and are not genetically inherited. Roughly 5% of patients with Alzheimer disease have familial Alzheimer disease-that is, related to a genetic predisposition, including mutations in the amyloid precursor protein, presenilin 1, and presenilin 2 genes. The discovery of genes for familial Alzheimer disease has allowed transgenic models to be generated through the overexpression of the amyloid precursor protein and/or presenilins harboring one or several mutations found in familial Alzheimer disease. Although none of these models fully replicates the human disease...