WorldWideScience

Sample records for animal disease models

  1. Animal models for human diseases.

    Science.gov (United States)

    Rust, J H

    1982-01-01

    The use of animal models for the study of human disease is, for the most part, a recent development. This discussion of the use of animal models for human diseases directs attention to the sterile period, early advances, some personal experiences, the human as the model, biological oddities among common laboratory animals, malignancies in laboratory animals, problems created by federal regulations, cancer tests with animals, and what the future holds in terms of the use of animal models as an aid to understanding human disease. In terms of early use of animal models, there was a school of rabbis, some of whom were also physicians, in Babylon who studied and wrote extensively on ritual slaughter and the suitability of birds and beasts for food. Considerable detailed information on animal pathology, physiology, anatomy, and medicine in general can be found in the Soncino Babylonian Talmudic Translations. The 1906 edition of the "Jewish Encyclopedia," has been a rich resource. Although it has not been possible to establish what diseases of animals were studied and their relationship to the diseases of humans, there are fascinating clues to pursue, despite the fact that these were sterile years for research in medicine. The quotation from the Talmud is of interest: "The medical knowledge of the Talmudist was based upon tradition, the dissection of human bodies, observation of disease and experiments upon animals." A bright light in the lackluster years of medical research was provided by Galen, considered the originator of research in physiology and anatomy. His dissection of animals and work on apes and other lower animals were models for human anatomy and physiology and the bases for many treatises. Yet, Galen never seemed to suggest that animals could serve as models for human diseases. Most early physicians who can be considered to have been students of disease developed their medical knowledge by observing the sick under their care. 1 early medical investigator

  2. Animal Models of Allergic Diseases

    Directory of Open Access Journals (Sweden)

    Domenico Santoro

    2014-12-01

    Full Text Available Allergic diseases have great impact on the quality of life of both people and domestic animals. They are increasing in prevalence in both animals and humans, possibly due to the changed lifestyle conditions and the decreased exposure to beneficial microorganisms. Dogs, in particular, suffer from environmental skin allergies and develop a clinical presentation which is very similar to the one of children with eczema. Thus, dogs are a very useful species to improve our understanding on the mechanisms involved in people’s allergies and a natural model to study eczema. Animal models are frequently used to elucidate mechanisms of disease and to control for confounding factors which are present in studies with patients with spontaneously occurring disease and to test new therapies that can be beneficial in both species. It has been found that drugs useful in one species can also have benefits in other species highlighting the importance of a comprehensive understanding of diseases across species and the value of comparative studies. The purpose of the current article is to review allergic diseases across species and to focus on how these diseases compare to the counterpart in people.

  3. Engineering large animal models of human disease

    OpenAIRE

    Whitelaw, C. Bruce A.; Timothy P Sheets; Lillico, Simon G; Telugu, Bhanu P.

    2015-01-01

    Abstract The recent development of gene editing tools and methodology for use in livestock enables the production of new animal disease models. These tools facilitate site‐specific mutation of the genome, allowing animals carrying known human disease mutations to be produced. In this review, we describe the various gene editing tools and how they can be used for a range of large animal models of diseases. This genomic technology is in its infancy but the expectation is that through the use of...

  4. Limitations of Animal Models of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    J. A. Potashkin

    2011-01-01

    Full Text Available Most cases of Parkinson's disease (PD are sporadic. When choosing an animal model for idiopathic PD, one must consider the extent of similarity or divergence between the physiology, anatomy, behavior, and regulation of gene expression between humans and the animal. Rodents and nonhuman primates are used most frequently in PD research because when a Parkinsonian state is induced, they mimic many aspects of idiopathic PD. These models have been useful in our understanding of the etiology of the disease and provide a means for testing new treatments. However, the current animal models often fall short in replicating the true pathophysiology occurring in idiopathic PD, and thus results from animal models often do not translate to the clinic. In this paper we will explain the limitations of animal models of PD and why their use is inappropriate for the study of some aspects of PD.

  5. Animal models for diseases of respiratory system

    Directory of Open Access Journals (Sweden)

    R. Adil

    2012-07-01

    Full Text Available Latest trends in understanding of respiratory diseases in human beings can be derived from thorough clinical studies of these diseases occurring in man, but conducting such studies in man is difficult in terms of experimental manipulation. In the last 2 decades, various types of experimental respiratory disease models has been developed and utilized by investigators, which have contributed a lot to the understanding of respiratory diseases in man, but only little investigation has been done on the naturally occurring pulmonary diseases of animals as potential models which could have added to our knowledge. There are certain selected examples of spontaneous pulmonary disease in animals that may serve as exploitable models for human chronic bronchitis, bronchiectasis, emphysema, interstitial lung disease, hypersensitivity pneumonitis, hyaline membrane disease, and bronchial asthma.

  6. Animal and cellular models of human disease

    OpenAIRE

    Arends, Mark; White, Eric; Whitelaw, Christopher

    2016-01-01

    In this eighteenth (2016) Annual Review Issue of The Journal of Pathology, we present a collection of 19 invited review articles that cover different aspects of cellular and animal models of disease. These include genetically-engineered models, chemically-induced models, naturally-occurring models, and combinations thereof, with the focus on recent methodological and conceptual developments across a wide range of human diseases.

  7. Limitations of Animal Models of Parkinson's Disease

    OpenAIRE

    J. A. Potashkin; Blume, S. R.; Runkle, N. K.

    2011-01-01

    Most cases of Parkinson's disease (PD) are sporadic. When choosing an animal model for idiopathic PD, one must consider the extent of similarity or divergence between the physiology, anatomy, behavior, and regulation of gene expression between humans and the animal. Rodents and nonhuman primates are used most frequently in PD research because when a Parkinsonian state is induced, they mimic many aspects of idiopathic PD. These models have been useful in our understanding of the etiology of t...

  8. Animal models for Gaucher disease research

    Directory of Open Access Journals (Sweden)

    Tamar Farfel-Becker

    2011-11-01

    Full Text Available Gaucher disease (GD, the most common lysosomal storage disorder (LSD, is caused by the defective activity of the lysosomal hydrolase glucocerebrosidase, which is encoded by the GBA gene. Generation of animal models that faithfully recapitulate the three clinical subtypes of GD has proved to be more of a challenge than first anticipated. The first mouse to be produced died within hours after birth owing to skin permeability problems, and mice with point mutations in Gba did not display symptoms correlating with human disease and also died soon after birth. Recently, conditional knockout mice that mimic some features of the human disease have become available. Here, we review the contribution of all currently available animal models to examining pathological pathways underlying GD and to testing the efficacy of new treatment modalities, and propose a number of criteria for the generation of more appropriate animal models of GD.

  9. Animal Models of Calcific Aortic Valve Disease

    OpenAIRE

    Sider, Krista L.; Blaser, Mark C.; Simmons, Craig A.

    2011-01-01

    Calcific aortic valve disease (CAVD), once thought to be a degenerative disease, is now recognized to be an active pathobiological process, with chronic inflammation emerging as a predominant, and possibly driving, factor. However, many details of the pathobiological mechanisms of CAVD remain to be described, and new approaches to treat CAVD need to be identified. Animal models are emerging as vital tools to this end, facilitated by the advent of new models and improved understanding of the u...

  10. Large genetic animal models of Huntington's Disease.

    Science.gov (United States)

    Morton, A Jennifer; Howland, David S

    2013-01-01

    The dominant nature of the Huntington's disease gene mutation has allowed genetic models to be developed in multiple species, with the mutation causing an abnormal neurological phenotype in all animals in which it is expressed. Many different rodent models have been generated. The most widely used of these, the transgenic R6/2 mouse, carries the mutation in a fragment of the human huntingtin gene and has a rapidly progressive and fatal neurological phenotype with many relevant pathological changes. Nevertheless, their rapid decline has been frequently questioned in the context of a disease that takes years to manifest in humans, and strenuous efforts have been made to make rodent models that are genetically more 'relevant' to the human condition, including full length huntingtin gene transgenic and knock-in mice. While there is no doubt that we have learned, and continue to learn much from rodent models, their usefulness is limited by two species constraints. First, the brains of rodents differ significantly from humans in both their small size and their neuroanatomical organization. Second, rodents have much shorter lifespans than humans. Here, we review new approaches taken to these challenges in the development of models of Huntington's disease in large brained, long-lived animals. We discuss the need for such models, and how they might be used to fill specific niches in preclinical Huntington's disease research, particularly in testing gene-based therapeutics. We discuss the advantages and disadvantages of animals in which the prodromal period of disease extends over a long time span. We suggest that there is considerable 'value added' for large animal models in preclinical Huntington's disease research. PMID:25063426

  11. Animal models for genetic neuromuscular diseases.

    Science.gov (United States)

    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

    2008-03-01

    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), the BIO14.6 hamster is the spontaneous animal model for delta-SG deficiency, whereas some canine models with deficiency of SG proteins have also been identified. More recently, using the homologous recombination technique in embryonic stem cell, several mouse models have been developed with null mutations in each one of the four SG genes. All sarcoglycan-null animals display a progressive muscular dystrophy of variable severity and share the property of a significant secondary reduction in the expression of the other members of the sarcoglycan subcomplex and other components of the Dystrophin-glycoprotein complex. Mouse models for congenital MD include the dy/dy (dystrophia-muscularis) mouse and the allelic mutant dy(2J)/dy(2J) mouse

  12. Animal models for Gaucher disease research

    OpenAIRE

    Tamar Farfel-Becker; Vitner, Einat B.; Futerman, Anthony H.

    2011-01-01

    Gaucher disease (GD), the most common lysosomal storage disorder (LSD), is caused by the defective activity of the lysosomal hydrolase glucocerebrosidase, which is encoded by the GBA gene. Generation of animal models that faithfully recapitulate the three clinical subtypes of GD has proved to be more of a challenge than first anticipated. The first mouse to be produced died within hours after birth owing to skin permeability problems, and mice with point mutations in Gba did not display sympt...

  13. Animal Models of Cardiac Disease and Stem Cell Therapy

    OpenAIRE

    Ou, Lailiang; Li, Wenzhong; Liu, Yi; Zhang, Yue(Walter Burke Institute for Theoretical Physics, California Institute of Technology, Pasadena, CA, 91125, U.S.A.); Jie, Shen; Kong, Deling; Steinhoff, Gustav; Ma, Nan

    2010-01-01

    Animal models that mimic cardiovascular diseases are indispensable tools for understanding the mechanisms underlying the diseases at the cellular and molecular level. This review focuses on various methods in preclinical research to create small animal models of cardiac diseases, such as myocardial infarction, dilated cardiomyopathy, heart failure, myocarditis and cardiac hypertrophy, and the related stem cell treatment for these diseases.

  14. Animal Models of Human Granulocyte Diseases

    OpenAIRE

    Schäffer, Alejandro A.; Klein, Christoph

    2012-01-01

    In vivo animal models have proven very useful to understand basic biological pathways of the immune system, a prerequisite for the development of innovate therapies. This manuscript addresses currently available models for defined human monogenetic defects of neutrophil granulocytes, including murine, zebrafish and larger mammalian species. Strengths and weaknesses of each system are summarized, and clinical investigators may thus be inspired to develop further lines of research to improve di...

  15. Infectious diseases among animals : combining models with data

    OpenAIRE

    de Koeijer, A.A.

    2003-01-01

    To eradicate or control the spread of infectious diseases, knowledge on the spread of the infection between (groups of) animals is necessary. Models can include such information and can subsequently be used to observe the efficacy of various control measures in fighting the infection. However, the availability of information and data to build and quantify these models is essential for applying such models in real life. In this thesis, models on the spread of infectious diseases in animals are...

  16. The rat as an animal model of Alzheimer's disease

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Kloskowska, Ewa; Winblad, Bengt

    2009-01-01

    As a disease model, the laboratory rat has contributed enormously to neuroscience research over the years. It has also been a popular animal model for Alzheimer's disease but its popularity has diminished during the last decade, as techniques for genetic manipulation in rats have lagged behind that...... of mice. In recent years, the rat has been making a comeback as an Alzheimer's disease model and the appearance of increasing numbers of transgenic rats will be a welcome and valuable complement to the existing mouse models. This review summarizes the contributions and current status of the rat as an...... animal model of Alzheimer's disease....

  17. Research progress on animal models of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Wen DONG

    2015-08-01

    Full Text Available Alzheimer's disease (AD is a degenerative disease of the central nervous system, and its pathogenesis is complex. Animal models play an important role in study on pathogenesis and treatment of AD. This paper summarized methods of building models, observation on animal models and evaluation index in recent years, so as to provide related evidence for basic and clinical research in future. DOI: 10.3969/j.issn.1672-6731.2015.08.003

  18. Research progress on animal models of Alzheimer's disease

    OpenAIRE

    Dong, Wen; Wang, Rong

    2015-01-01

    Alzheimer's disease (AD) is a degenerative disease of the central nervous system, and its pathogenesis is complex. Animal models play an important role in study on pathogenesis and treatment of AD. This paper summarized methods of building models, observation on animal models and evaluation index in recent years, so as to provide related evidence for basic and clinical research in future. DOI: 10.3969/j.issn.1672-6731.2015.08.003

  19. Animal models for Alzheimer's disease and frontotemporal dementia: a perspective

    OpenAIRE

    Jürgen Götz; Naeman N Götz

    2009-01-01

    In dementia research, animal models have become indispensable tools. They not only model aspects of the human condition, but also simulate processes that occur in humans and hence provide insight into how disease is initiated and propagated. The present review discusses two prominent human neurodegenerative disorders, Alzheimer's disease and frontotemporal dementia. It discusses what we would like to model in animals and highlights some of the more recent achievements using species as ...

  20. Engineering Large Animal Species to Model Human Diseases.

    Science.gov (United States)

    Rogers, Christopher S

    2016-01-01

    Animal models are an important resource for studying human diseases. Genetically engineered mice are the most commonly used species and have made significant contributions to our understanding of basic biology, disease mechanisms, and drug development. However, they often fail to recreate important aspects of human diseases and thus can have limited utility as translational research tools. Developing disease models in species more similar to humans may provide a better setting in which to study disease pathogenesis and test new treatments. This unit provides an overview of the history of genetically engineered large animals and the techniques that have made their development possible. Factors to consider when planning a large animal model, including choice of species, type of modification and methodology, characterization, production methods, and regulatory compliance, are also covered. © 2016 by John Wiley & Sons, Inc. PMID:27367161

  1. Animal models of primary myocardial diseases.

    OpenAIRE

    Liu, S. K.; Tilley, L. P.

    1980-01-01

    Feline and canine cardiomyopathies (primary myocardial diseases) were reviewed and divided into three groups based on the clinical, hemodynamic, angiocardiographic, and pathologic findings: (1) feline and canine hypertrophic cardiomyopathy, (2) feline and canine congestive (dilated) cardiomyopathy, and (3) feline restrictive cardiomyopathy. All three groups consisted predominantly of mature adult male cats and dogs. Cardiomyopathy in the hamster and turkey was also reviewed. The most common p...

  2. Animal models of human respiratory syncytial virus disease

    NARCIS (Netherlands)

    R.A. Bem; J.B. Domachowske; H.F. Rosenberg

    2011-01-01

    Infection with the human pneumovirus pathogen, respiratory syncytial virus (hRSV), causes a wide spectrum of respiratory disease, notably among infants and the elderly. Laboratory animal studies permit detailed experimental modeling of hRSV disease and are therefore indispensable in the search for n

  3. Critical Behavior in a Cellular Automata Animal Disease Transmission Model

    CERN Document Server

    Morley, P D; Chang, Julius

    2003-01-01

    Using a cellular automata model, we simulate the British Government Policy (BGP) in the 2001 foot and mouth epidemic in Great Britain. When clinical symptoms of the disease appeared on a farm, there is mandatory slaughter (culling) of all livestock on an infected premise (IP). Those farms that neighbor an IP (contiguous premise, CP), are also culled, aka nearest neighbor interaction. Farms where the disease may be prevalent from animal, human, vehicle or airborne transmission (dangerous contact, DC), are additionally culled, aka next-to-nearest neighbor iteractions and lightning factor. The resulting mathematical model possesses a phase transition, whereupon if the physical disease transmission kernel exceeds a critical value, catastrophic loss of animals ensues. The non-local disease transport probability can be as low as .01% per day and the disease can still be in the high mortality phase. We show that the fundamental equation for sustainable disease transport is the criticality equation for neutron fissio...

  4. Small animal model for HIV-1 Disease

    Institute of Scientific and Technical Information of China (English)

    Yoshio; Koyanagi

    2005-01-01

    Development of a viral infection model of the humanimmune systemusingsmall animalsis animportant goal in biomedi-cal research,especiallyinstudiesof HIV-1infection.Thisis particularlyimportant since susceptibilityto HIV-1islimit-edto humans.The C.B-17-scid/scid-mouselacks mature Tand Bcells dueto a defective rearrangement of the Tcell re-ceptor andimmunoglobulin genes.Twotypes of humanlymphoid chimeras have been establishedin scid-mice.The firstsuccess withthe human mouse chimera was achieved.Human fetal liv...

  5. New Methods for Integrated Models of Animal Disease Control

    OpenAIRE

    Rich, Karl M.

    2007-01-01

    Accurate assessments of the epidemiological and economic impacts of an animal disease require the incorporation of feedbacks between disease spread and production incentives. This paper motivates a new modeling framework that is sensitive to the dynamics of disease, production decisions and incentives, different livestock production systems, and their interaction through the use of an integrated system dynamics framework. Preliminary simulation results are provided to demonstrate proof-of-con...

  6. Concise Review: Stem Cell Trials Using Companion Animal Disease Models.

    Science.gov (United States)

    Hoffman, Andrew M; Dow, Steven W

    2016-07-01

    Studies to evaluate the therapeutic potential of stem cells in humans would benefit from more realistic animal models. In veterinary medicine, companion animals naturally develop many diseases that resemble human conditions, therefore, representing a novel source of preclinical models. To understand how companion animal disease models are being studied for this purpose, we reviewed the literature between 2008 and 2015 for reports on stem cell therapies in dogs and cats, excluding laboratory animals, induced disease models, cancer, and case reports. Disease models included osteoarthritis, intervertebral disc degeneration, dilated cardiomyopathy, inflammatory bowel diseases, Crohn's fistulas, meningoencephalomyelitis (multiple sclerosis-like), keratoconjunctivitis sicca (Sjogren's syndrome-like), atopic dermatitis, and chronic (end-stage) kidney disease. Stem cells evaluated in these studies included mesenchymal stem-stromal cells (MSC, 17/19 trials), olfactory ensheathing cells (OEC, 1 trial), or neural lineage cells derived from bone marrow MSC (1 trial), and 16/19 studies were performed in dogs. The MSC studies (13/17) used adipose tissue-derived MSC from either allogeneic (8/13) or autologous (5/13) sources. The majority of studies were open label, uncontrolled studies. Endpoints and protocols were feasible, and the stem cell therapies were reportedly safe and elicited beneficial patient responses in all but two of the trials. In conclusion, companion animals with naturally occurring diseases analogous to human conditions can be recruited into clinical trials and provide realistic insight into feasibility, safety, and biologic activity of novel stem cell therapies. However, improvements in the rigor of manufacturing, study design, and regulatory compliance will be needed to better utilize these models. Stem Cells 2016;34:1709-1729. PMID:27066769

  7. Animal models for Alzheimer's disease and frontotemporal dementia: a perspective

    Directory of Open Access Journals (Sweden)

    Jürgen Götz

    2009-11-01

    Full Text Available In dementia research, animal models have become indispensable tools. They not only model aspects of the human condition, but also simulate processes that occur in humans and hence provide insight into how disease is initiated and propagated. The present review discusses two prominent human neurodegenerative disorders, Alzheimer's disease and frontotemporal dementia. It discusses what we would like to model in animals and highlights some of the more recent achievements using species as diverse as mice, fish, flies and worms. Advances in imaging and therapy are explored. We also discuss some anticipated new models and developments. These will reveal how key players in the pathogenesis of Alzheimer's disease and frontotemporal dementia, such as the peptide Aβ (amyloid β and the protein tau, cause neuronal dysfunction and eventually, neuronal demise. Understanding these processes fully will lead to early diagnosis and therapy.

  8. Animal models

    DEFF Research Database (Denmark)

    Gøtze, Jens Peter; Krentz, Andrew

    2014-01-01

    In this issue of Cardiovascular Endocrinology, we are proud to present a broad and dedicated spectrum of reviews on animal models in cardiovascular disease. The reviews cover most aspects of animal models in science from basic differences and similarities between small animals and the human...

  9. Infectious diseases among animals : combining models with data

    NARCIS (Netherlands)

    Koeijer, A.A. de

    2003-01-01

    To eradicate or control the spread of infectious diseases, knowledge on the spread of the infection between (groups of) animals is necessary. Models can include such information and can subsequently be used to observe the efficacy of various control measures in fighting the infection. However, the a

  10. Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

    Institute of Scientific and Technical Information of China (English)

    Yoshihisa Takahashi; Yurie Soejima; Toshio Fukusato

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse.Nonalcoholic steatohepatitis (NASH),a severe form of NAFLD,can progress to liver cirrhosis and hepatocellular carcinoma.NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity,type 2 diabetes,and hyperlipemia.Animal models of NAFLD/NASH give crucial information,not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents.An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH.Animal models of NAFLD/NASH are divided into genetic,dietary,and combination models.In this paper,we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages.

  11. Large Animal Models for Batten Disease: A Review

    OpenAIRE

    Weber, Krystal; Pearce, David A.

    2013-01-01

    The neuronal ceroid lipofuscinoses, collectively referred to as Batten disease, make up a group of inherited childhood disorders that result in blindness, motor and cognitive regression, brain atrophy, and seizures, ultimately leading to premature death. So far more than 10 genes have been implicated in different forms of the neuronal ceroid lipofuscinoses. Most related research has involved mouse models, but several naturally occurring large animal models have recently been discovered. In th...

  12. ANIMAL MODELS FOR HUNTINGTON’S DISEASES: A REVIEW

    Directory of Open Access Journals (Sweden)

    Sharma Manisha

    2012-10-01

    Full Text Available Huntington's disease (HD is an inherited autosomal, progressive neurodegenerative disorder associated with involuntary abnormal movements (chorea, cognitive impairments and psychiatric disturbances. HD is caused by an abnormal expansion of a CAG region located in exon 1 of the gene encoding the huntingtin protein (Htt and is the causative factor in the pathogenesis of HD Animal models of HD have provided insight into disease pathology and the outcomes of thera- peutic strategies. Earlier studies of HD most often used toxin-induced models to study mitochondrial impairment and excitotoxicity-induced cell death, which are both mechanisms of degeneration seen in the HD brain. These models, based on 3-nitropropionic acid and quinolinic acid, respectively, are still often used in HD studies. The discovery in 1993 of the huntingtin mutation led to the creation of newer models that incorporate a similar genetic defect. These models, which include transgenic and knock-in rodents, are more representative of the HD progression and pathology. An even more recent model that uses a ovine transgenic model (sheep model,fly models ,cell cultures models for better understanding of gene mutation in and in mammalian and nonhuman primates, as it is difficult to produce genetic models in these species. This article examines the aforementioned models and describes their use in HD research, including aspects of the creation, de- livery, pathology, and tested therapies for each model.

  13. MeCP2-Related Diseases and Animal Models

    Directory of Open Access Journals (Sweden)

    Chinelo D. Ezeonwuka

    2014-01-01

    Full Text Available The role of epigenetics in human disease has become an area of increased research interest. Collaborative efforts from scientists and clinicians have led to a better understanding of the molecular mechanisms by which epigenetic regulation is involved in the pathogenesis of many human diseases. Several neurological and non-neurological disorders are associated with mutations in genes that encode for epigenetic factors. One of the most studied proteins that impacts human disease and is associated with deregulation of epigenetic processes is Methyl CpG binding protein 2 (MeCP2. MeCP2 is an epigenetic regulator that modulates gene expression by translating epigenetic DNA methylation marks into appropriate cellular responses. In order to highlight the importance of epigenetics to development and disease, we will discuss how MeCP2 emerges as a key epigenetic player in human neurodevelopmental, neurological, and non-neurological disorders. We will review our current knowledge on MeCP2-related diseases, including Rett Syndrome, Angelman Syndrome, Fetal Alcohol Spectrum Disorder, Hirschsprung disease, and Cancer. Additionally, we will briefly discuss about the existing MeCP2 animal models that have been generated for a better understanding of how MeCP2 impacts certain human diseases.

  14. Animal models of gastrointestinal and liver diseases. Animal models of infant short bowel syndrome

    DEFF Research Database (Denmark)

    Sangild, Per Torp; Ney, Denise M; Sigalet, David L;

    2014-01-01

    enterocolitis, atresia, gastroschisis, volvulus and aganglionosis. Patient outcomes have improved, but there is a need to develop new therapies for SBS and to understand intestinal adaptation after different diseases, resection types, nutritional interventions and growth factor therapies. Animal studies may...... hormone, insulin-like growth factor 1, epidermal growth factor, keratinocyte growth factor). The greater size of rats, and especially young pigs, is an advantage for testing surgical procedures and nutritional interventions (e.g. PN, milk diets, long/short chain lipids, pre- and probiotics). Conversely......, newborn pigs and weanling rats represent a translational advantage for infant SBS due to their immature intestine. A balance among practical, economical, experimental and ethical constraints determines the choice of SBS model for each clinical or basic research question....

  15. Toxin-Induced and Genetic Animal Models of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Shin Hisahara

    2011-01-01

    Full Text Available Parkinson's disease (PD is a common progressive neurodegenerative disorder. The major pathological hallmarks of PD are the selective loss of nigrostriatal dopaminergic neurons and the presence of intraneuronal aggregates termed Lewy bodies (LBs, but the pathophysiological mechanisms are not fully understood. Epidemiologically, environmental neurotoxins such as pesticides are promising candidates for causative factors of PD. Oxidative stress and mitochondrial dysfunction induced by these toxins could contribute to the progression of PD. While most cases of PD are sporadic, specific mutations in genes that cause familial forms of PD have led to provide new insights into its pathogenesis. This paper focuses on animal models of both toxin-induced and genetically determined PD that have provided significant insight for understanding this disease. We also discuss the validity, benefits, and limitations of representative models.

  16. Large animal models of rare genetic disorders: sheep as phenotypically relevant models of human genetic disease

    OpenAIRE

    Pinnapureddy, Ashish R.; Stayner, Cherie; McEwan, John; Baddeley, Olivia; Forman, John; Eccles, Michael R

    2015-01-01

    Animals that accurately model human disease are invaluable in medical research, allowing a critical understanding of disease mechanisms, and the opportunity to evaluate the effect of therapeutic compounds in pre-clinical studies. Many types of animal models are used world-wide, with the most common being small laboratory animals, such as mice. However, rodents often do not faithfully replicate human disease, despite their predominant use in research. This discordancy is due in part to physiol...

  17. Defective membrane remodeling in neuromuscular diseases: insights from animal models.

    Directory of Open Access Journals (Sweden)

    Belinda S Cowling

    Full Text Available Proteins involved in membrane remodeling play an essential role in a plethora of cell functions including endocytosis and intracellular transport. Defects in several of them lead to human diseases. Myotubularins, amphiphysins, and dynamins are all proteins implicated in membrane trafficking and/or remodeling. Mutations in myotubularin, amphiphysin 2 (BIN1, and dynamin 2 lead to different forms of centronuclear myopathy, while mutations in myotubularin-related proteins cause Charcot-Marie-Tooth neuropathies. In addition to centronuclear myopathy, dynamin 2 is also mutated in a dominant form of Charcot-Marie-Tooth neuropathy. While several proteins from these different families are implicated in similar diseases, mutations in close homologues or in the same protein in the case of dynamin 2 lead to diseases affecting different tissues. This suggests (1 a common molecular pathway underlying these different neuromuscular diseases, and (2 tissue-specific regulation of these proteins. This review discusses the pathophysiology of the related neuromuscular diseases on the basis of animal models developed for proteins of the myotubularin, amphiphysin, and dynamin families. A better understanding of the common mechanisms between these neuromuscular disorders will lead to more specific health care and therapeutic approaches.

  18. Transgenic animals modelling polyamine metabolism-related diseases.

    Science.gov (United States)

    Alhonen, Leena; Uimari, Anne; Pietilä, Marko; Hyvönen, Mervi T; Pirinen, Eija; Keinänen, Tuomo A

    2009-01-01

    Cloning of genes related to polyamine metabolism has enabled the generation of genetically modified mice and rats overproducing or devoid of proteins encoded by these genes. Our first transgenic mice overexpressing ODC (ornithine decarboxylase) were generated in 1991 and, thereafter, most genes involved in polyamine metabolism have been used for overproduction of the respective proteins, either ubiquitously or in a tissue-specific fashion in transgenic animals. Phenotypic characterization of these animals has revealed a multitude of changes, many of which could not have been predicted based on the previous knowledge of the polyamine requirements and functions. Animals that overexpress the genes encoding the inducible key enzymes of biosynthesis and catabolism, ODC and SSAT (spermidine/spermine N1-acetyltransferase) respectively, appear to possess the most pleiotropic phenotypes. Mice overexpressing ODC have particularly been used as cancer research models. Transgenic mice and rats with enhanced polyamine catabolism have revealed an association of rapidly depleted polyamine pools and accelerated metabolic cycle with development of acute pancreatitis and a fatless phenotype respectively. The latter phenotype with improved glucose tolerance and insulin sensitivity is useful in uncovering the mechanisms that lead to the opposite phenotype in humans, Type 2 diabetes. Disruption of the ODC or AdoMetDC [AdoMet (S-adenosylmethionine) decarboxylase] gene is not compatible with mouse embryogenesis, whereas mice with a disrupted SSAT gene are viable and show no harmful phenotypic changes, except insulin resistance at a late age. Ultimately, the mice with genetically altered polyamine metabolism can be used to develop targeted means to treat human disease conditions that they relevantly model. PMID:20095974

  19. Miniature pig as a large animal model of Huntington disease

    Czech Academy of Sciences Publication Activity Database

    Juhás, Štefan; Hruška-Plocháň, Marian; Juhásová, Jana; Vodička, Petr; Pavlok, Antonín; Baxa, Monika; Miyanohara, A.; Marsala, M.; Motlík, Jan

    Liběchov : Institute of Animal Physiology and Genetics AS CR, v.v ,, 2010. s. 48-48. [Czech-Japan Joint Symposium for Animal Reproduction. 20.09.2010-21.09.2010, Liblice] R&D Projects: GA MŠk 1M0538 Institutional research plan: CEZ:AV0Z50450515 Keywords : miniature pig * Huntington disease Subject RIV: EB - Genetics ; Molecular Biology

  20. Early synaptic dysfunction in Parkinson's disease: Insights from animal models.

    Science.gov (United States)

    Schirinzi, Tommaso; Madeo, Graziella; Martella, Giuseppina; Maltese, Marta; Picconi, Barbara; Calabresi, Paolo; Pisani, Antonio

    2016-06-01

    The appearance of motor manifestations in Parkinson's disease (PD) is invariably linked to degeneration of nigral dopaminergic neurons of the substantia nigra pars compacta. Traditional views on PD neuropathology have been grounded in the assumption that the prime event of neurodegeneration involves neuronal cell bodies with the accumulation of metabolic products. However, this view has recently been challenged by both clinical and experimental evidence. Neuropathological studies in human brain samples and both in vivo and in vitro models support the hypothesis that nigrostriatal synapses may indeed be affected at the earliest stages of the neurodegenerative process. The mechanisms leading to either structural or functional synaptic dysfunction are starting to be elucidated and include dysregulation of axonal transport, impairment of the exocytosis and endocytosis machinery, altered intracellular trafficking, and loss of corticostriatal synaptic plasticity. The aim of this review is to try to integrate different lines of evidence from both pathogenic and genetic animal models that, to different extents, suggest that early synaptic impairment may represent the key event in PD pathogenesis. Understanding the molecular and cellular events underlying such synaptopathy is a fundamental step toward developing specific biomarkers of early dopaminergic dysfunction and, more importantly, designing novel therapies targeting the synaptic apparatus of selective, vulnerable synapses. © 2016 International Parkinson and Movement Disorder Society. PMID:27193205

  1. Ovarian autoimmune disease: clinical concepts and animal models

    OpenAIRE

    Warren, Bryce D; Kinsey, William K; McGinnis, Lynda K; Christenson, Lane K.; Jasti, Susmita; Stevens, Anne M.; Petroff, Brian K.; Petroff, Margaret G.

    2014-01-01

    The ovary is not an immunologically privileged organ, but a breakdown in tolerogenic mechanisms for ovary-specific antigens has disastrous consequences on fertility in women, and this is replicated in murine models of autoimmune disease. Isolated ovarian autoimmune disease is rare in women, likely due to the severity of the disease and the inability to transmit genetic information conferring the ovarian disease across generations. Nonetheless, autoimmune oophoritis is often observed in associ...

  2. A cross-species analysis method to analyze animal models' similarity to human's disease state

    OpenAIRE

    Yu Shuhao; Zheng Lulu; Li Yun; Li Chunyan; Ma Chenchen; Li Yixue; Li Xuan; Hao Pei

    2012-01-01

    Abstract Background Animal models are indispensable tools in studying the cause of human diseases and searching for the treatments. The scientific value of an animal model depends on the accurate mimicry of human diseases. The primary goal of the current study was to develop a cross-species method by using the animal models' expression data to evaluate the similarity to human diseases' and assess drug molecules' efficiency in drug research. Therefore, we hoped to reveal that it is feasible an...

  3. Therapeutic study of proton beam in vascular disease animal models

    International Nuclear Information System (INIS)

    Proton beam radiation therapy is difficult to apply to animal model. When the cells with DNA damage in the irradiated zebrafish were stained with acridine orange, green fluorescent cell death spots were increased in trunk regions compared to non-irradiated control embryos. From this study, we found that proton radiation therapy can inhibit the blood vessel growth, which is probably induced in vivo in zebrafish embryos, and vascular endothelial cell proliferation.

  4. Animal Models of Helicobacter-Induced Disease: Methods to Successfully Infect the Mouse [chapter

    OpenAIRE

    James G Fox

    2012-01-01

    Animal models of microbial diseases in humans are an essential component for determining fulfillment of Koch’s postulates and determining how the organism causes disease, host response(s), disease prevention, and treatment. In the case of Helicobacter pylori, establishing an animal model to fulfill Koch’s postulates initially proved so challenging that out of frustration a human volunteer undertook an experiment to become infected with H. pylori and to monitor disease progression in order to ...

  5. Animal Models for imaging

    OpenAIRE

    Croft, Barbara Y.

    2002-01-01

    Animal models can be used in the study of disease. This chapter discusses imaging animal models to elucidate the process of human disease. The mouse is used as the primary model. Though this choice simplifies many research choices, it necessitates compromises for in vivo imaging. In the future, we can expect improvements in both animal models and imaging techniques.

  6. A knowledge based approach to matching human neurodegenerative disease and animal models

    OpenAIRE

    Martone, Maryann E.; Mungall, Christopher J.

    2013-01-01

    Neurodegenerative diseases present a wide and complex range of biological and clinical features. Animal models are key to translational research, yet typically only exhibit a subset of disease features rather than being precise replicas of the disease. Consequently, connecting animal to human conditions using direct data-mining strategies has proven challenging, particularly for diseases of the nervous system, with its complicated anatomy and physiology. To address this challenge we have expl...

  7. Animal Models of Inflammatory Bowel Diseases: Illuminating the Pathogenesis of Colitis, Ileitis and Cancer

    OpenAIRE

    Neurath, Markus F

    2014-01-01

    Background/Aims: Inflammatory bowel diseases (IBD) are chronic relapsing diseases of unknown origin. In spite of improved options for therapy, many patients with IBD have an impaired quality of life and require hospitalization or surgery. Animal models of IBD might help to obtain new insights into the pathogenesis of these diseases and may be used to test innovative approaches for therapy. Methods: Review of the literature using PubMed. Results: Numerous new animal mod...

  8. Correlated Inflammatory Responses and Neurodegeneration in Peptide-Injected Animal Models of Alzheimer’s Disease

    OpenAIRE

    McLarnon, James G

    2014-01-01

    Animal models of Alzheimer's disease (AD) which emphasize activation of microglia may have particular utility in correlating proinflammatory activity with neurodegeneration. This paper reviews injection of amyloid- β (A β ) into rat brain as an alternative AD animal model to the use of transgenic animals. In particular, intrahippocampal injection of Aβ 1-42 peptide demonstrates prominent microglial mobilization and activation accompanied by a significant loss of granule cell neurons. Furtherm...

  9. Influence of Species Differences on the Neuropathology of Transgenic Huntington's Disease Animal Models

    Institute of Scientific and Technical Information of China (English)

    Xiao-Jiang Li; Shihua Li

    2012-01-01

    Transgenic animal models have revealed much about the pathogenesis of age-dependent neurodegenerative diseases and proved to be a useful tool for uncovering therapeutic targets.Huntington's disease is a well-characterized neurodegenerative disorder that is caused by expansion of a CAG repeat,which results in expansion of a polyglutamine tract in the N-terminal region of huntingtin (HTT).Similar CAG/glutamine expansions are also found to cause eight other neurodegenerative diseases that affect distinct brain regions in an agedependent manner.Identification of this CAG/glutamine expansion has led to the generation of a variety of transgenic animal models.Of these different animal models,transgenic mice have been investigated extensively,and they show similar neuropathology and phenotypes as seen in their respective diseases.The common pathological hallmark of age-dependent neurodegeneration is the formation of aggregates or inclusions consisting of misfolded proteins in the affected brain regions; however,overt or striking neurodegeneration and apoptosis have not been reported in most transgenic mouse models for age-dependent diseases,including HD.By comparing the neuropathology of transgenic HD mouse,pig,and monkey models,we found that mutant HTT is more toxic to larger animals than mice,and larger animals also show neuropathology that has not been uncovered by transgenic mouse models.This review will discuss the importancc of transgenic large animal models for analyzing the pathogenesis of neurodegenerative diseases and developing effective treatments.

  10. How To Become a Top Model: Impact of Animal Experimentation on Human Salmonella Disease Research ▿

    OpenAIRE

    Tsolis, Renée M.; Xavier, Mariana N.; Santos, Renato L; Bäumler, Andreas J.

    2011-01-01

    Salmonella serotypes are a major cause of human morbidity and mortality worldwide. Over the past decades, a series of animal models have been developed to advance vaccine development, provide insights into immunity to infection, and study the pathogenesis of human Salmonella disease. The successive introduction of new animal models, each suited to interrogate previously neglected aspects of Salmonella disease, has ushered in important conceptual advances that continue to have a strong and sus...

  11. Sleep disturbances in the rotenone animal model of Parkinson disease.

    Science.gov (United States)

    García-García, Fabio; Ponce, Sonia; Brown, Richard; Cussen, Victoria; Krueger, James M

    2005-05-01

    Parkinson disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) and the presence of intracytoplasmatic inclusions known as Lewy bodies. Chronic administration of rotenone (RT) produces Parkinson's-like symptoms in rats. Because PD patients have disrupted sleep patterns, we determined if chronic RT administration produces similar changes in rat sleep. RT was administered for 28 days to rats. Basal and vehicle (VH) rats received saline or dimethyl sulfoxide and polyethylene glycol (1:1), respectively. VH infusion induced a progressive decrease in non-rapid eye movement sleep (NREMS) during the 4-week period of VH infusion and REMS was reduced in the third and fourth week of VH infusion. VH infusion did not induce dopaminergic cell degeneration. Rats receiving RT infusion also showed decreased NREMS during the treatment. REMS was dramatically reduced on day 7 although subsequently on days 13 and 20 REMS was similar to basal values. After 4 weeks of RT infusion, time in REMS was decreased again. In RT-treated rats, progressive dopaminergic cell degeneration occurred in the SNc. After 4 weeks of daily injections of L-dopa in RT-infused rats, NREMS values remained similar to those values obtained after RT alone. L-dopa therapy did, however, induce a recovery of REMS in weeks 3 and 4 of RT infusion. Dopaminergic cell damage persisted in the L-dopa-RT-infused rats. We conclude that the RT-PD rat model is associated with large long-term sleep disruption, however, the vehicle, DMSO/PEG had as large an effect as RT on sleep, thus changes in sleep cannot be ascribed to loss of dopaminergic cells. Such results question the validity of the RT-PD rat model. PMID:15854587

  12. New developments in animal models of Alzheimer's disease.

    Science.gov (United States)

    Janus, C; Phinney, A L; Chishti, M A; Westaway, D

    2001-09-01

    Alzheimer's disease (AD) is characterized by deterioration in mental function leading to dementia, deposition of amyloid plaques and neurofibrillary tangles (NFTs), and neuronal loss. The major component of plaques is the amyloid-beta peptide (A beta), whereas NFTs are assemblies of hyperphosphorylated forms of the microtubule-associated protein tau. Electron microscopy of NFTs reveals structures known as paired helical filaments (PHFs). In familial AD (FAD), mutations in three distinct genes drive A beta synthesis by favoring endoproteolytic secretase cleavages that liberate A beta from the Alzheimer beta-amyloid precursor protein (APP). This suggests that excess A beta initiates a pathogenic cascade in humans that culminates in all the pathologic and cellular hallmarks of AD. Building upon the knowledge of FAD mutations, incremental technical advances have now allowed reproduceable creation of APP transgenic mice that exhibit AD-like amyloid pathology and A beta burdens. These transgenic mouse lines also exhibit deficits in spatial reference and working memory, with immunization against A beta abrogating both AD-associated phenotypes. Besides establishing a proof of principle for A beta-directed therapies, these findings suggest a potential to identify individual elements in the pathogenic pathway that lead to cognitive dysfunction. Furthermore, transgenic APP mice with potent amyloid deposition will likely form a beach-head to capture the final elements of AD neuropathology--cell loss and NFTs composed of PHFs--that are missing from current transgenic models. PMID:11898556

  13. Mesenchymal stem cells in the treatment of inflammatoryand autoimmune diseases in experimental animal models

    Institute of Scientific and Technical Information of China (English)

    Matthew W Klinker; Cheng-Hong Wei

    2015-01-01

    Multipotent mesenchymal stromal cells [also known asmesenchymal stem cells (MSCs)] are currently beingstudied as a cell-based treatment for inflammatorydisorders. Experimental animal models of humanimmune-mediated diseases have been instrumental inestablishing their immunosuppressive properties. Inthis review, we summarize recent studies examiningthe effectiveness of MSCs as immunotherapy in severalwidely-studied animal models, including type 1 diabetes,experimental autoimmune arthritis, experimentalautoimmune encephalomyelitis, inflammatory boweldisease, graft-vs -host disease, and systemic lupuserythematosus. In addition, we discuss mechanismsidentified by which MSCs mediate immune suppressionin specific disease models, and potential sources offunctional variability of MSCs between studies.

  14. MicroRNAs are potential therapeutic targets in fibrosing kidney disease: lessons from animal models

    OpenAIRE

    Duffield, Jeremy S.; Grafals, Monica; Portilla, Didier

    2012-01-01

    Chronic disease of the kidneys has reached epidemic proportions in industrialized nations. New therapies are urgently sought. Using a combination of animal models of kidney disease and human biopsy samples, a pattern of dysregulated microRNA expression has emerged which is common to chronic diseases. A number of these dysregulated microRNA have recently been shown to have functional consequences for the disease process and therefore may be potential therapeutic targets. We highlight microRNA-...

  15. Large animal induced pluripotent stem cells as pre-clinical models for studying human disease

    OpenAIRE

    Jordan R Plews; Gu, Mingxia; Longaker, Michael T.; Joseph C. Wu

    2012-01-01

    Abstract The derivation of human embryonic stem cells and subsequently human induced pluripotent stem cells (iPSCs) has energized regenerative medicine research and enabled seemingly limitless applications. Although small animal models, such as mouse models, have played an important role in the progression of the field, typically, they are poor representations of the human disease phenotype. As an alternative, large animal models should be explored as a potentially better approach for clinica...

  16. A SPATIAL MODEL OF ANIMAL DISEASE CONTROL IN LIVESTOCK: EMPIRICAL ANALYSIS OF FOOT AND MOUTH DISEASE IN THE SOUTHERN CONE

    OpenAIRE

    Rich, Karl M.; Winter-Nelson, Alex

    2004-01-01

    This paper presents a multi-market model of animal disease control that extends the current literature by accounting for spatial and inter-temporal relations in both epidemiological and economic variables. The model is applied to Foot and Mouth Disease control in Argentina, Uruguay and Paraguay, but it is broadly generalizable.

  17. Toxin-Induced and Genetic Animal Models of Parkinson's Disease

    OpenAIRE

    Shun Shimohama; Shin Hisahara

    2010-01-01

    Parkinson's disease (PD) is a common progressive neurodegenerative disorder. The major pathological hallmarks of PD are the selective loss of nigrostriatal dopaminergic neurons and the presence of intraneuronal aggregates termed Lewy bodies (LBs), but the pathophysiological mechanisms are not fully understood. Epidemiologically, environmental neurotoxins such as pesticides are promising candidates for causative factors of PD. Oxidative stress and mitochondrial dysfunction induced by these tox...

  18. Animal models of dementia

    DEFF Research Database (Denmark)

    Olsson, I. Anna S.; Sandøe, Peter

    2011-01-01

    are here distinguished. These serve as points of orientation in the following discussion of four more specific ethical questions: Does animal species matter? How effective is disease modelling in delivering the benefits claimed for it? What can be done to minimize potential harm to animals in research? Who......This chapter aims to encourage scientists and others interested in the use of animal models of disease – specifically, in the study of dementia – to engage in ethical reflection. It opens with a general discussion of the moral acceptability of animal use in research. Three ethical approaches...... bears responsibility for the use of animals in disease models?...

  19. Ocular Manifestations of Alzheimer's Disease in Animal Models

    OpenAIRE

    Francesca Cordeiro, M.; Mohamed Abdi; Miles Parnell; Li Guo

    2012-01-01

    Alzheimer’s disease (AD) is the most common form of dementia, and the pathological changes of senile plaques (SPs) and neurofibrillary tangles (NFTs) in AD brains are well described. Clinically, a diagnosis remains a postmortem one, hampering both accurate and early diagnosis as well as research into potential new treatments. Visual deficits have long been noted in AD patients, and it is becoming increasingly apparent that histopathological changes already noted in the brain also occur in an ...

  20. Alzheimer’s disease and epilepsy: insight from animal models

    OpenAIRE

    Scharfman, Helen E.

    2012-01-01

    Alzheimer’s disease (AD) and epilepsy are separated in the medical community, but seizures occur in some patients with AD, and AD is a risk factor for epilepsy. Furthermore, memory impairment is common in patients with epilepsy. The relationship between AD and epilepsy remains an important question because ideas for therapeutic approaches could be shared between AD and epilepsy research laboratories if AD and epilepsy were related. Here we focus on one of the many types of epilepsy, temporal ...

  1. PARKINSON’S DISEASE: ANIMAL MODELS AND DOPAMINERGIC CELL VULNERABILITY

    OpenAIRE

    Javier Blesa

    2014-01-01

    Parkinson’s disease (PD) is a neurodegenerative disorder that affects about 1.5% of the global population over 65 years of age. A hallmark feature of PD is the degeneration of the dopamine (DA) neurons in the substantia nigra pars compacta (SNc) and the consequent striatal DA deficiency. Yet, the pathogenesis of PD remains unclear. Despite tremendous growth in recent years in our knowledge of the molecular basis of PD and the molecular pathways of cell death, important questions remain, such ...

  2. Progress of GAITRite testing in different large animal models of neurodegenerative diseases

    Czech Academy of Sciences Publication Activity Database

    Hölzner, E.; Marcegaglia, M.; Skillings, L.; Baxa, Monika; Morton, J.; Reilmann, R.

    Mělník: IAPG, 2013. [Large Animal Models of Neurodegenerative Diseases /2./. 17.11.2013-19.11.2013, Liblice] Institutional support: RVO:67985904 Keywords : GAITRite * phenotyping * Huntington´s disease * minipig Subject RIV: EB - Genetics ; Molecular Biology

  3. An everlasting role of animal models in understanding human disease

    Institute of Scientific and Technical Information of China (English)

    Xiao Yang; Chonglin Yang

    2010-01-01

    Model organisms have been widely used to dissect important biological phenomena, as well as to explore potential causes and treatments for human disorders. Much of our knowledge on molecular mechanisms underlying the he?redity, development as well as physiology is largely derived from the researches of model organisms.We have witnessed an explosive increase in the development and application of genetic modified model organisms in the last decade.

  4. Life Cycle Heterogeneity in Animal Models of Human Papillomavirus-Associated Disease

    OpenAIRE

    Peh, Woei Ling; Middleton, Kate; Christensen, Neil; Nicholls, Philip; Egawa, Kiyofumi; Sotlar, Karl; Brandsma, Janet; Percival, Alan; Lewis, Jon; Liu, Wen Jun; Doorbar, John

    2002-01-01

    Animal papillomaviruses are widely used as models to study papillomavirus infection in humans despite differences in genome organization and tissue tropism. Here, we have investigated the extent to which animal models of papillomavirus infection resemble human disease by comparing the life cycles of 10 different papillomavirus types. Three phases in the life cycles of all viruses were apparent using antibodies that distinguish between early events, the onset of viral genome amplification, and...

  5. Evaluation and validation of new animal and behavioural models for the study of Alzheimer's disease

    OpenAIRE

    Goricanec, Irena

    2004-01-01

    The incidence of suffering from Alzheimer's disease (AD) increases steadily with augmenting life expectancy in humans, generating an enormous burden for patients, their families and the national health system. Models used in previous publications covered only parts of the AD pathology. The work presented here combines transgenic technology and selective invasive methods to identify an improved animal model for the study of AD. The suitability of animals to acquire task demands of behaviour...

  6. Reduced animal use in efficacy testing in disease models with use of sequential experimental designs.

    OpenAIRE

    Waterton JC, Middleton BJ, Pickford R, Allott CP, Checkley D, Keith RA.

    2000-01-01

    Although the use of animals in efficacy tests has declined substantially, there remains a small number of well-documented disease models which provide essential information about the efficacy of new compounds. Such models are typically used after extensive in vitro testing, to evaluate small numbers of compounds and to select the most promising agents for clinical trial in humans. The aim of this study was to reduce the number of animals required to achieve valid results, without compromising...

  7. a Simplified Bayesian Network Model Applied in Crop or Animal Disease Diagnosis

    Science.gov (United States)

    Yu, Helong; Chen, Guifen; Liu, Dayou

    Bayesian network is a powerful tool to represent and deal with uncertain knowledge. There exists much uncertainty in crop or animal disease. The construction of Bayesian network need much data and knowledge. But when data is scarce, some methods should be adopted to construct an effective Bayesian network. This paper introduces a disease diagnosis model based on Bayesian network, which is two-layered and obeys noisy-or assumption. Based on the two-layered structure, the relationship between nodes is obtained by domain knowledge. Based on the noisy-model, the conditional probability table is elicited by three methods, which are parameter learning, domain expert and the existing certainty factor model. In order to implement this model, a Bayesian network tool is developed. Finally, an example about cow disease diagnosis was implemented, which proved that the model discussed in this paper is an effective tool for some simple disease diagnosis in crop or animal field.

  8. Understanding disease processes in multiple sclerosis through magnetic resonance imaging studies in animal models

    Directory of Open Access Journals (Sweden)

    Nabeela Nathoo

    2014-01-01

    Full Text Available There are exciting new advances in multiple sclerosis (MS resulting in a growing understanding of both the complexity of the disorder and the relative involvement of grey matter, white matter and inflammation. Increasing need for preclinical imaging is anticipated, as animal models provide insights into the pathophysiology of the disease. Magnetic resonance (MR is the key imaging tool used to diagnose and to monitor disease progression in MS, and thus will be a cornerstone for future research. Although gadolinium-enhancing and T2 lesions on MRI have been useful for detecting MS pathology, they are not correlative of disability. Therefore, new MRI methods are needed. Such methods require validation in animal models. The increasing necessity for MRI of animal models makes it critical and timely to understand what research has been conducted in this area and what potential there is for use of MRI in preclinical models of MS. Here, we provide a review of MRI and magnetic resonance spectroscopy (MRS studies that have been carried out in animal models of MS that focus on pathology. We compare the MRI phenotypes of animals and patients and provide advice on how best to use animal MR studies to increase our understanding of the linkages between MR and pathology in patients. This review describes how MRI studies of animal models have been, and will continue to be, used in the ongoing effort to understand MS.

  9. Outline for an integrated modelling approach concerning risks and economic consequences of contagious animal diseases.

    NARCIS (Netherlands)

    Horst, H.S.; Dijkhuizen, A.A.; Huirne, R.B.M.

    1996-01-01

    Management decisions on control of major infectious animal diseases may have a large impact, but are usually based on scarce and unreliable information. An integrated model which combines the various aspects of outbreaks and risks with economic consequences has yet to be developed. A flexible model

  10. A branching model for the spread of infectious animal diseases in varying environments

    OpenAIRE

    Trapman, Pieter; Meester, R; Heesterbeek, J A P

    2004-01-01

    This paper is concerned with a stochastic model, describing outbreaks of infectious diseases that have potentially great animal or human health consequences, and which can result in such severe economic losses that immediate sets of measures need to be taken to curb the spread. During an outbreak of such a disease, the environment that the infectious agent experiences is therefore changing due to the subsequent control measures taken. In our model, we introduce a general branching process in ...

  11. ERAIZDA: a model for holistic annotation of animal infectious and zoonotic diseases.

    Science.gov (United States)

    Buza, Teresia M; Jack, Sherman W; Kirunda, Halid; Khaitsa, Margaret L; Lawrence, Mark L; Pruett, Stephen; Peterson, Daniel G

    2015-01-01

    There is an urgent need for a unified resource that integrates trans-disciplinary annotations of emerging and reemerging animal infectious and zoonotic diseases. Such data integration will provide wonderful opportunity for epidemiologists, researchers and health policy makers to make data-driven decisions designed to improve animal health. Integrating emerging and reemerging animal infectious and zoonotic disease data from a large variety of sources into a unified open-access resource provides more plausible arguments to achieve better understanding of infectious and zoonotic diseases. We have developed a model for interlinking annotations of these diseases. These diseases are of particular interest because of the threats they pose to animal health, human health and global health security. We demonstrated the application of this model using brucellosis, an infectious and zoonotic disease. Preliminary annotations were deposited into VetBioBase database (http://vetbiobase.igbb.msstate.edu). This database is associated with user-friendly tools to facilitate searching, retrieving and downloading of disease-related information. Database URL: http://vetbiobase.igbb.msstate.edu. PMID:26581408

  12. Porcine models of digestive disease: the future of large animal translational research.

    Science.gov (United States)

    Gonzalez, Liara M; Moeser, Adam J; Blikslager, Anthony T

    2015-07-01

    There is increasing interest in nonrodent translational models for the study of human disease. The pig, in particular, serves as a useful animal model for the study of pathophysiological conditions relevant to the human intestine. This review assesses currently used porcine models of gastrointestinal physiology and disease and provides a rationale for the use of these models for future translational studies. The pig has proven its utility for the study of fundamental disease conditions such as ischemia-reperfusion injury, stress-induced intestinal dysfunction, and short bowel syndrome. Pigs have also shown great promise for the study of intestinal barrier function, surgical tissue manipulation and intervention, as well as biomaterial implantation and tissue transplantation. Advantages of pig models highlighted by these studies include the physiological similarity to human intestine and mechanisms of human disease. Emerging future directions for porcine models of human disease include the fields of transgenics and stem cell biology, with exciting implications for regenerative medicine. PMID:25655839

  13. The rat as an animal model of Alzheimer’s disease

    OpenAIRE

    Benedikz, Eirikur; Kloskowska, Ewa; Winblad, Bengt

    2009-01-01

    As a disease model, the laboratory rat has contributed enormously to neuroscience research over the years. It has also been a popular animal model for Alzheimer’s disease but its popularity has diminished during the last decade, as techniques for genetic manipulation in rats have lagged behind that of mice. In recent years, the rat has been making a comeback as an Alzheimer’s disease model and the appearance of increasing numbers of transgenic rats will be a welcome and valuable complement to...

  14. Metallothionein-I and -III expression in animal models of Alzheimer disease

    DEFF Research Database (Denmark)

    Carrasco, J; Adlard, P; Cotman, C;

    2006-01-01

    Previous studies have described altered expression of metallothioneins (MTs) in neurodegenerative diseases like multiple sclerosis (MS), Down syndrome, and Alzheimer's disease (AD). In order to gain insight into the possible role of MTs in neurodegenerative processes and especially in human...... diseases, the use of animal models is a valuable tool. Several transgenic mouse models of AD amyloid deposits are currently available. These models express human beta-amyloid precursor protein (AbetaPP) carrying different mutations that subsequently result in a varied pattern of beta-amyloid (Abeta...

  15. Transgenic animal models for study of the pathogenesis of Huntington’s disease and therapy

    Directory of Open Access Journals (Sweden)

    Chang RB

    2015-04-01

    Full Text Available Renbao Chang,1 Xudong Liu,1 Shihua Li,2 Xiao-Jiang Li1,2 1State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, People’s Republic of China; 2Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA Abstract: Huntington’s disease (HD is caused by a genetic mutation that results in polyglutamine expansion in the N-terminal regions of huntingtin. As a result, this polyQ expansion leads to the misfolding and aggregation of mutant huntingtin as well as age-dependent neurodegeneration. The genetic mutation in HD allows for generating a variety of animal models that express different forms of mutant huntingtin and show differential pathology. Studies of these animal models have provided an important insight into the pathogenesis of HD. Mouse models of HD include transgenic mice, which express N-terminal or full-length mutant huntingtin ubiquitously or selectively in different cell types, and knock-in mice that express full-length mutant Htt at the endogenous level. Large animals, such as pig, sheep, and monkeys, have also been used to generate animal HD models. This review focuses on the different features of commonly used transgenic HD mouse models as well as transgenic large animal models of HD, and also discusses how to use them to identify potential therapeutics. Since HD shares many pathological features with other neurodegenerative diseases, identification of therapies for HD would also help to develop effective treatment for different neurodegenerative diseases that are also caused by protein misfolding and occur in an age-dependent manner. Keywords: transgenic animal models, Huntington’s disease, pathogenesis, therapy

  16. Correlated Inflammatory Responses and Neurodegeneration in Peptide-Injected Animal Models of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    James G. McLarnon

    2014-01-01

    Full Text Available Animal models of Alzheimer’s disease (AD which emphasize activation of microglia may have particular utility in correlating proinflammatory activity with neurodegeneration. This paper reviews injection of amyloid-β (Aβ into rat brain as an alternative AD animal model to the use of transgenic animals. In particular, intrahippocampal injection of Aβ1-42 peptide demonstrates prominent microglial mobilization and activation accompanied by a significant loss of granule cell neurons. Furthermore, pharmacological inhibition of inflammatory reactivity is demonstrated by a broad spectrum of drugs with a common endpoint in conferring neuroprotection in peptide-injected animals. Peptide-injection models provide a focus on glial cell responses to direct peptide injection in rat brain and offer advantages in the study of the mechanisms underlying neuroinflammation in AD brain.

  17. From animal models to human disease: a genetic approach for personalized medicine in ALS.

    Science.gov (United States)

    Picher-Martel, Vincent; Valdmanis, Paul N; Gould, Peter V; Julien, Jean-Pierre; Dupré, Nicolas

    2016-01-01

    Amyotrophic Lateral Sclerosis (ALS) is the most frequent motor neuron disease in adults. Classical ALS is characterized by the death of upper and lower motor neurons leading to progressive paralysis. Approximately 10 % of ALS patients have familial form of the disease. Numerous different gene mutations have been found in familial cases of ALS, such as mutations in superoxide dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP-43), fused in sarcoma (FUS), C9ORF72, ubiquilin-2 (UBQLN2), optineurin (OPTN) and others. Multiple animal models were generated to mimic the disease and to test future treatments. However, no animal model fully replicates the spectrum of phenotypes in the human disease and it is difficult to assess how a therapeutic effect in disease models can predict efficacy in humans. Importantly, the genetic and phenotypic heterogeneity of ALS leads to a variety of responses to similar treatment regimens. From this has emerged the concept of personalized medicine (PM), which is a medical scheme that combines study of genetic, environmental and clinical diagnostic testing, including biomarkers, to individualized patient care. In this perspective, we used subgroups of specific ALS-linked gene mutations to go through existing animal models and to provide a comprehensive profile of the differences and similarities between animal models of disease and human disease. Finally, we reviewed application of biomarkers and gene therapies relevant in personalized medicine approach. For instance, this includes viral delivering of antisense oligonucleotide and small interfering RNA in SOD1, TDP-43 and C9orf72 mice models. Promising gene therapies raised possibilities for treating differently the major mutations in familial ALS cases. PMID:27400686

  18. Understanding disease processes in multiple sclerosis through magnetic resonance imaging studies in animal models

    OpenAIRE

    Nabeela Nathoo; V Wee Yong; Dunn, Jeff F.

    2014-01-01

    There are exciting new advances in multiple sclerosis (MS) resulting in a growing understanding of both the complexity of the disorder and the relative involvement of grey matter, white matter and inflammation. Increasing need for preclinical imaging is anticipated, as animal models provide insights into the pathophysiology of the disease. Magnetic resonance (MR) is the key imaging tool used to diagnose and to monitor disease progression in MS, and thus will be a cornerstone for future resear...

  19. Grunting in genetically modified minipig animal model for Huntington ´s disease - a pilot experiment

    Czech Academy of Sciences Publication Activity Database

    Tykalová, T.; Hlavnička, J.; Mačáková, Monika; Baxa, Monika; Cmejla, R.; Motlík, Jan; Klempíř, J.; Rusz, J.

    2015-01-01

    Roč. 78, Suppl 2 (2015), s. 12-13. ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : Huntington´s disease * mitochondria * DNA damage Subject RIV: FH - Neurology

  20. Needs for animal models of human diseases of the respiratory system.

    OpenAIRE

    Reid, L. M.

    1980-01-01

    Animal models are of two types those that occur spontaneously and those that the scientist produces by artefact. One value of spontaneously occurring models is that if pathogenetic mechanisms are identified, they give new leads for the study of human disease. There is a need for spontaneously occurring examples of so-called primary or idiopathic pulmonary fibrosis, pulmonary hypertension (arterial or venous), and emphysema. Acquired or artefactual models of each of these conditions are availa...

  1. Animal models of gastrointestinal and liver diseases. Animal models of infant short bowel syndrome: translational relevance and challenges.

    Science.gov (United States)

    Sangild, Per T; Ney, Denise M; Sigalet, David L; Vegge, Andreas; Burrin, Douglas

    2014-12-15

    Intestinal failure (IF), due to short bowel syndrome (SBS), results from surgical resection of a major portion of the intestine, leading to reduced nutrient absorption and need for parenteral nutrition (PN). The incidence is highest in infants and relates to preterm birth, necrotizing enterocolitis, atresia, gastroschisis, volvulus, and aganglionosis. Patient outcomes have improved, but there is a need to develop new therapies for SBS and to understand intestinal adaptation after different diseases, resection types, and nutritional and pharmacological interventions. Animal studies are needed to carefully evaluate the cellular mechanisms, safety, and translational relevance of new procedures. Distal intestinal resection, without a functioning colon, results in the most severe complications and adaptation may depend on the age at resection (preterm, term, young, adult). Clinically relevant therapies have recently been suggested from studies in preterm and term PN-dependent SBS piglets, with or without a functional colon. Studies in rats and mice have specifically addressed the fundamental physiological processes underlying adaptation at the cellular level, such as regulation of mucosal proliferation, apoptosis, transport, and digestive enzyme expression, and easily allow exogenous or genetic manipulation of growth factors and their receptors (e.g., glucagon-like peptide 2, growth hormone, insulin-like growth factor 1, epidermal growth factor, keratinocyte growth factor). The greater size of rats, and especially young pigs, is an advantage for testing surgical procedures and nutritional interventions (e.g., PN, milk diets, long-/short-chain lipids, pre- and probiotics). Conversely, newborn pigs (preterm or term) and weanling rats provide better insights into the developmental aspects of treatment for SBS in infants owing to their immature intestines. The review shows that a balance among practical, economical, experimental, and ethical constraints will determine the

  2. Neurodegeneration in an animal model of Parkinson's disease is exacerbated by a high-fat diet

    OpenAIRE

    Morris, Jill K.; Bomhoff, Gregory L.; Stanford, John A.; Geiger, Paige C.

    2010-01-01

    Despite numerous clinical studies supporting a link between type 2 diabetes (T2D) and Parkinson's disease (PD), the clinical literature remains equivocal. We, therefore, sought to address the relationship between insulin resistance and nigrostriatal dopamine (DA) in a preclinical animal model. High-fat feeding in rodents is an established model of insulin resistance, characterized by increased adiposity, systemic oxidative stress, and hyperglycemia. We subjected rats to a normal chow or high-...

  3. Challenges in animal modelling of mesenchymal stromal cell therapy for inflammatory bowel disease

    Science.gov (United States)

    Chinnadurai, Raghavan; Ng, Spencer; Velu, Vijayakumar; Galipeau, Jacques

    2015-01-01

    Utilization of mesenchymal stromal cells (MSCs) for the treatment of Crohn’s disease and ulcerative colitis is of translational interest. Safety of MSC therapy has been well demonstrated in early phase clinical trials but efficacy in randomized clinical trials needs to be demonstrated. Understanding MSC mechanisms of action to reduce gut injury and inflammation is necessary to improve current ongoing and future clinical trials. However, two major hurdles impede the direct translation of data derived from animal experiments to the clinical situation: (1) limitations of the currently available animal models of colitis that reflect human inflammatory bowel diseases (IBD). The etiology and progression of human IBD are multifactorial and hence a challenge to mimic in animal models; and (2) Species specific differences in the functionality of MSCs derived from mice versus humans. MSCs derived from mice and humans are not identical in their mechanisms of action in suppressing inflammation. Thus, preclinical animal studies with murine derived MSCs cannot be considered as an exact replica of human MSC based clinical trials. In the present review, we discuss the therapeutic properties of MSCs in preclinical and clinical studies of IBD. We also discuss the challenges and approaches of using appropriate animal models of colitis, not only to study putative MSC therapeutic efficacy and their mechanisms of action, but also the suitability of translating findings derived from such studies to the clinic. PMID:25944991

  4. Animal models of asthma

    OpenAIRE

    Bates, Jason H.T.; Rincon, Mercedes; Irvin, Charles G.

    2009-01-01

    Studies in animal models form the basis for much of our current understanding of the pathophysiology of asthma, and are central to the preclinical development of drug therapies. No animal model completely recapitulates all features of the human disease, however. Research has focused primarily on ways to generate allergic inflammation by sensitizing and challenging animals with a variety of foreign proteins, leading to an increased understanding of the immunological factors that mediate the in...

  5. Animal Models of Fibromyalgia

    OpenAIRE

    Nagakura, Yukinori; Ito, Hiroyuki; Shimizu, Yasuaki

    2012-01-01

    Animal models of disease states are valuable tools for developing new treatments and investigating underlying mechanisms. They should mimic the symptoms and pathology of the disease and importantly be predictive of effective treatments. Fibromyalgia is characterized by chronic widespread pain with associated co-morbid symptoms that include fatigue, depression, anxiety and sleep dysfunction. In this review, we present different animal models that mimic the signs and symptoms of fibromyalgia. T...

  6. Diabetes Mellitus Induces Alzheimer’s Disease Pathology: Histopathological Evidence from Animal Models

    Directory of Open Access Journals (Sweden)

    Nobuyuki Kimura

    2016-04-01

    Full Text Available Alzheimer’s disease (AD is the major causative disease of dementia and is characterized pathologically by the accumulation of senile plaques (SPs and neurofibrillary tangles (NFTs in the brain. Although genetic studies show that β-amyloid protein (Aβ, the major component of SPs, is the key factor underlying AD pathogenesis, it remains unclear why advanced age often leads to AD. Interestingly, several epidemiological and clinical studies show that type II diabetes mellitus (DM patients are more likely to exhibit increased susceptibility to AD. Moreover, growing evidence suggests that there are several connections between the neuropathology that underlies AD and DM, and there is evidence that the experimental induction of DM can cause cognitive dysfunction, even in rodent animal models. This mini-review summarizes histopathological evidence that DM induces AD pathology in animal models and discusses the possibility that aberrant insulin signaling is a key factor in the induction of AD pathology.

  7. Opportunities and challenges in developing relevant animal models for Alzheimer's disease.

    Science.gov (United States)

    De Felice, Fernanda G; Munoz, Douglas P

    2016-03-01

    A major impediment to the development of safe and effective therapeutics in Alzheimer's disease (AD) lies in difficulties in translating research findings across species: therapies that work in rodents often do not translate to humans. A route to bridge the gap between promising rodent research and the human clinical condition consists in using non-human primates (NHPs), which are phylogenetically much closer to humans. In this article, we discuss the importance of investigating disease mechanisms from cell culture, through different animal models of disease. We highlight that developing a viable, validated NHP AD model will likely be a key step toward understanding AD-relevant pathogenic mechanisms and for developing therapies that will effectively translate to the human disease condition. PMID:26829469

  8. Morphological changes of glutamatergic synapses in animal models of Parkinson’s disease

    OpenAIRE

    Villalba, Rosa M.; Yoland Smith

    2015-01-01

    The striatum and the subthalamic nucleus are the main entry doors for extrinsic inputs to reach the basal ganglia circuitry. The cerebral cortex, thalamus and brainstem are the key sources of glutamatergic inputs to these nuclei. There is functional and neurochemical evidence that glutamatergic neurotransmission is altered in the striatum and subthalamic nucleus of animal models of Parkinson’s disease, and that these changes may contribute to aberrant network neuronal activity in the basal ga...

  9. Induction of animal model of Graves' disease in BALB/c mice

    Institute of Scientific and Technical Information of China (English)

    Zhu-fang Tian; Bing-yin Shi; Xiao-yan Wu; Li Xu

    2009-01-01

    Objective To construct an animal model of Graves' disease (GD) by immunizing BALB/c mice with hM12 cells co-expressing major histocompatibility complex (MHC) class Ⅱ molecules and human thyrotropin receptor (TSHR) molecules. Methods BALB/c mice in experimental group (H-2d) were immunized with hM12 cells Intraper-itoncally every 2 weeks for six times, while mice in control group were immunized with M12 cells. Five weeks later, the thyroids were histologically examined, and serum samples were tested for thyroid-stimulating antibodies (TSAb) and thyroid hormone levels. Results One BALB/c mouse in experimental group developed Graves'-like disease. Total T4 and T3 levels in this mouse were above the upper limit of normal, TSAb activity was displayed in its serum. The thyroid histologically showed the features of thyroid hyperactivity including thyrocyte hypercellularity and colloid absorption.None of control mice developed Graves'-like disease. Conclusion An animal model with some characteristics of human Graves' disease was successfully induced and the model will facilitate studies aimed directly at understanding the patho-genesis of autoimmunity in Graves' disease.

  10. Studying human respiratory disease in animals--role of induced and naturally occurring models.

    Science.gov (United States)

    Williams, Kurt; Roman, Jesse

    2016-01-01

    Respiratory disorders like asthma, emphysema, and pulmonary fibrosis affect millions of Americans and many more worldwide. Despite advancements in medical research that have led to improved understanding of the pathophysiology of these conditions and sometimes to new therapeutic interventions, these disorders are for the most part chronic and progressive; current interventions are not curative and do not halt disease progression. A major obstacle to further advancements relates to the absence of animal models that exactly resemble the human condition, which delays the elucidation of relevant mechanisms of action, the unveiling of biomarkers of disease progression, and identification of new targets for intervention in patients. There are currently many induced animal models of human respiratory disease available for study, and even though they mimic features of human disease, discoveries in these models have not always translated into safe and effective treatments in humans. A major obstacle relates to the genetic, anatomical, and functional variations amongst species, which represents the major challenge to overcome when searching for appropriate models of respiratory disease. Nevertheless, rodents, in particular mice, have become the most common species used for experimentation, due to their relatively low cost, size, and adequate understanding of murine genetics, among other advantages. Less well known is the fact that domestic animals also suffer from respiratory illnesses similar to those found in humans. Asthma, bronchitis, pneumonia, and pulmonary fibrosis are among the many disorders occurring naturally in dogs, cats, and horses, among other species. These models might better resemble the human condition and are emphasized here, but further investigations are needed to determine their relevance. PMID:26467890

  11. Derivation of neural stem cells from an animal model of psychiatric disease.

    Science.gov (United States)

    de Koning, A; Walton, N M; Shin, R; Chen, Q; Miyake, S; Tajinda, K; Gross, A K; Kogan, J H; Heusner, C L; Tamura, K; Matsumoto, M

    2013-01-01

    Several psychiatric and neurological diseases are associated with altered hippocampal neurogenesis, suggesting differing neural stem cell (NSC) function may play a critical role in these diseases. To investigate the role of resident NSCs in a murine model of psychiatric disease, we sought to isolate and characterize NSCs from alpha-calcium-/calmodulin-dependent protein kinase II heterozygous knockout (CaMK2α-hKO) mice, a model of schizophrenia/bipolar disorder. These mice display altered neurogenesis, impaired neuronal development and are part of a larger family possessing phenotypic and behavioral correlates of schizophrenia/bipolar disorder and a shared pathology referred to as the immature dentate gyrus (iDG). The extent to which NSCs contribute to iDG pathophysiology remains unclear. To address this, we established heterogeneous cultures of NSCs isolated from the hippocampal neuropoietic niche. When induced to differentiate, CaMK2α-hKO-derived NSCs recapitulate organotypic hippocampal neurogenesis, but generate larger numbers of immature neurons than wild-type (WT) littermates. Furthermore, mutant neurons fail to assume mature phenotypes (including morphology and MAP2/calbindin expression) at the same rate observed in WT counterparts. The increased production of immature neurons which fail to mature indicates that this reductionist model retains key animal- and iDG-specific maturational deficits observed in animal models and human patients. This is doubly significant, as these stem cells lack several developmental inputs present in vivo. Interestingly, NSCs were isolated from animals prior to the emergence of overt iDG pathophysiology, suggesting mutant NSCs may possess lasting intrinsic alterations and that altered NSC function may contribute to iDG pathophysiology in adult animals. PMID:24193728

  12. Animal models of Huntington's disease: implications in uncovering pathogenic mechanisms and developing therapies

    Institute of Scientific and Technical Information of China (English)

    Lin-hui WANG; Zheng-hong QIN

    2006-01-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder, which is caused by an abnormal expansion of Cytosine Adenine Guanine (CAG) trinucleotide repeat in the gene making huntingtin (Htt). Despite intensive research efforts devoted to investigate molecular mechanisms of pathogenesis, effective therapy for this devastating disease is still not available at present. The development of various animal models of HD has offered alternative approaches in the study of HD molecular pathology. Many HD models, including chemical-induced models and genetic models, mimic some aspects of HD symptoms and pathology. To date, however, there is no ideal model which replicates all of the essential features of neuropathology and progressive motor and cognitive impairments of human HD. As a result, our understanding of molecular mechanisms of pathogenesis in HD is still limited. A new model is needed in order to uncover the pathogenesis and to develop novel therapies for HD. In this review we discussed usefulness and limitations of various animal and cellular models of HD in uncovering molecular mechanisms of pathogenesis and developing novel therapies for HD.

  13. Continuity of Business Plans for Animal Disease Outbreaks: Using a Logic Model Approach to Protect Animal Health, Public Health, and Our Food Supply

    Directory of Open Access Journals (Sweden)

    Heather Allen

    2013-04-01

    Full Text Available Foreign animal diseases can have a devastating impact on the American economy and agriculture system, while significantly disrupting the food supply chain, and affecting animal health and public health. Continuity of business during an animal disease outbreak aims to mitigate these agriculture-related losses by facilitating normal business operations through the managed movement of non-infected animals and non-contaminated animal products. During a foreign animal disease outbreak, there are competing objectives of trying to control and contain the outbreak while allowing non-infected premises to continue normal business operations to the greatest extent possible. Using a logic model approach, this article discusses the importance of continuity of business planning during an animal disease outbreak, providing a detailed and transparent theoretical framework for continuity of business planning for animal agriculture stakeholders. The logic model provides a basis for continuity of business planning, which is rapidly gaining focus and interest in the animal emergency management community. This unique logic model offers a framework for effective planning and subsequent evaluation of continuity of business plans and processes, by identifying explicit stakeholders, inputs, and activities, alongside the desired outputs and outcomes of such planning.

  14. Modeling HCV Disease in Animals: Virology, Immunology and Pathogenesis of HCV and GBV-B Infections

    Directory of Open Access Journals (Sweden)

    Cordelia eManickam

    2014-12-01

    Full Text Available Hepatitis C virus (HCV infection has become a global public health burden costing billions of dollars in health care annually. Even with rapidly advancing scientific technologies, this disease still looms large due to a lack of vaccines and affordable treatment options. The immune correlates of protection and predisposing factors towards chronicity remain major obstacles to development of HCV vaccines and immunotherapeutics due, at least in part, to lack of a tangible infection animal model. This review discusses the currently available animal models for HCV disease, with a primary focus on GB virus B (GBV-B infection of New World primates that recapitulates the dual hepacivirus phenotypes of acute viral clearance and chronic pathologic disease. HCV and GBV-B are also closely phylogenetically related, and advances in characterization of the immune systems of New World primates have already led to the use of this model for drug testing and vaccine trials. Herein, we discuss the benefits and caveats of the GBV-B infection model and discuss potential avenues for future development of novel vaccines and immunotherapies.

  15. Effects of Low-Dose-Gamma Rays on the Immune System of Different Animal Models of Disease

    OpenAIRE

    Shimura, Noriko; Kojima, Shuji

    2014-01-01

    We reviewed the beneficial or harmful effects of low-dose ionizing radiation on several diseases based on a search of the literature. The attenuation of autoimmune manifestations in animal disease models irradiated with low-dose γ-rays was previously reported by several research groups, whereas the exacerbation of allergic manifestations was described by others. Based on a detailed examination of the literature, we divided animal disease models into two groups: one group consisting of collage...

  16. Animal Models in Autoimmune Diseases: Lessons Learned from Mouse Models for Sjögren’s Syndrome

    OpenAIRE

    Lee, Byung Ha; Gauna, Adrienne E.; Pauley, Kaleb M; Park, Yun-Jong; Cha, Seunghee

    2012-01-01

    The mouse model is the one of the most frequently used and well-established animal models, and is currently used in many research areas. To date, various mouse models have been utilized to elucidate underlying causes of multi-factorial autoimmune conditions, including pathological immune components and specific signaling pathways. This review summarizes the more recent mouse models for Sjögren’s syndrome, a systemic autoimmune disease characterized by lymphocytic infiltration in the exocrine ...

  17. A branching model for the spread of infectious animal diseases in varying environments.

    Science.gov (United States)

    Trapman, Pieter; Meester, Ronald; Heesterbeek, Hans

    2004-12-01

    This paper is concerned with a stochastic model, describing outbreaks of infectious diseases that have potentially great animal or human health consequences, and which can result in such severe economic losses that immediate sets of measures need to be taken to curb the spread. During an outbreak of such a disease, the environment that the infectious agent experiences is therefore changing due to the subsequent control measures taken. In our model, we introduce a general branching process in a changing (but not random) environment. With this branching process, we estimate the probability of extinction and the expected number of infected individuals for different control measures. We also use this branching process to calculate the generating function of the number of infected individuals at any given moment. The model and methods are designed using important infections of farmed animals, such as classical swine fever, foot-and-mouth disease and avian influenza as motivating examples, but have a wider application, for example to emerging human infections that lead to strict quarantine of cases and suspected cases (e.g. SARS) and contact and movement restrictions. PMID:15565446

  18. Morphological changes of glutamatergic synapses in animal models of Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Rosa M Villalba

    2015-09-01

    Full Text Available The striatum and the subthalamic nucleus are the main entry doors for extrinsic inputs to reach the basal ganglia circuitry. The cerebral cortex, thalamus and brainstem are the key sources of glutamatergic inputs to these nuclei. There is functional and neurochemical evidence that glutamatergic neurotransmission is altered in the striatum and subthalamic nucleus of animal models of Parkinson’s disease, and that these changes may contribute to aberrant network neuronal activity in the basal ganglia-thalamocortical circuitry. Postmortem studies of animal models and PD patients have revealed significant pathology of glutamatergic synapses, dendritic spines and microcircuits in the striatum of parkinsonians. More recent findings have also demonstrated a significant breakdown of the glutamatergic corticosubthalamic system in parkinsonian monkeys. In this review, we will discuss evidence for synaptic glutamatergic dysfunction and pathology of cortical and thalamic inputs to the striatum and subthalamic nucleus in models of Parkinson’s disease. The potential functional implication of these alterations on synaptic integration, processing and transmission of extrinsic information through the basal ganglia circuits will be considered. Finally, the significance of these pathological changes in the pathophysiology of motor and non-motor symptoms in Parkinson’s disease will be examined.

  19. ERAIZDA: a model for holistic annotation of animal infectious and zoonotic diseases

    OpenAIRE

    Buza, Teresia M.; Jack, Sherman W.; Kirunda, Halid; Khaitsa, Margaret L.; Lawrence, Mark L.; Pruett, Stephen; Peterson, Daniel G.

    2015-01-01

    There is an urgent need for a unified resource that integrates trans-disciplinary annotations of emerging and reemerging animal infectious and zoonotic diseases. Such data integration will provide wonderful opportunity for epidemiologists, researchers and health policy makers to make data-driven decisions designed to improve animal health. Integrating emerging and reemerging animal infectious and zoonotic disease data from a large variety of sources into a unified open-access resource provide...

  20. Induction of animal model of Graves disease in BALB/c mice

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To construct an animal model of Graves' disease(GD)by immunizing BALB/c mice with hM12 cells co-expressing major histocompatibility complex(MHC)class II molecules and human thyrotropin receptor(TSHR)molecules.Methods BALB/c mice in experimental group(H-2d)were immunized with hM12 cells intraperitoneally every 2 weeks for six times,while mice in control group were immunized with M12 cells.Five weeks later,the thyroids were histologically examined,and serum samples were tested for thyroid-stimulatin...

  1. [Application of CRISPR-Cas9 genome editing for constructing animal models of human diseases].

    Science.gov (United States)

    Ou, Zhanhui; Sun, Xiaofang

    2016-08-10

    The CRISPR-Cas9 system is a new targeted nuclease for genome editing, which can directly introduce modifications at the targeted genomic locus. The system utilizes a short single guide RNA (sgRNA) to direct the endonuclease Cas9 in the genome. Upon targeting, Cas9 can generate DNA double-strand breaks (DSBs). As such DSBs are repaired by non-homologous end joining (NHEJ) or homology directed repair (HDR), therefore facilitates introduction of random or specific mutations, repair of endogenous mutations, or insertion of DNA elements. The system has been successfully used to generate gene targeted cell lines including those of human, animals and plants. This article reviews recent advances made in this rapidly evolving technique for the generation of animal models for human diseases. PMID:27455021

  2. Imaging of Small Animal Peripheral Artery Disease Models: Recent Advancements and Translational Potential

    Directory of Open Access Journals (Sweden)

    Jenny B. Lin

    2015-05-01

    Full Text Available Peripheral artery disease (PAD is a broad disorder encompassing multiple forms of arterial disease outside of the heart. As such, PAD development is a multifactorial process with a variety of manifestations. For example, aneurysms are pathological expansions of an artery that can lead to rupture, while ischemic atherosclerosis reduces blood flow, increasing the risk of claudication, poor wound healing, limb amputation, and stroke. Current PAD treatment is often ineffective or associated with serious risks, largely because these disorders are commonly undiagnosed or misdiagnosed. Active areas of research are focused on detecting and characterizing deleterious arterial changes at early stages using non-invasive imaging strategies, such as ultrasound, as well as emerging technologies like photoacoustic imaging. Earlier disease detection and characterization could improve interventional strategies, leading to better prognosis in PAD patients. While rodents are being used to investigate PAD pathophysiology, imaging of these animal models has been underutilized. This review focuses on structural and molecular information and disease progression revealed by recent imaging efforts of aortic, cerebral, and peripheral vascular disease models in mice, rats, and rabbits. Effective translation to humans involves better understanding of underlying PAD pathophysiology to develop novel therapeutics and apply non-invasive imaging techniques in the clinic.

  3. Animal experimental model of Peyronie’s disease: A pilot study

    Directory of Open Access Journals (Sweden)

    Maria Angela Cerruto

    2013-04-01

    Full Text Available Objective: The Peyronie's disease (PD is an idiopathic disorder of connective tissue of the penis, that involves the tunica albuginea of the corpora cavernosa and the adjacent areolar space. It is a growing clinical evidence to support the therapeutic potential of mesenchymal stem cells and histological findings has assumed a possible application of lipofilling technique in patients with PD. The objective of this experimental study is the creation of a murine experimental model of PD, evaluating with MRI the penis of the rats (feasibility study, in order to plane the application of lipofilling technique in an animal model. Methods: Four male Wistar rats were anesthetized, fixed in prone position and subjected to MRI. The animals underwent, subsequently, an injection of thrombin in the tunica albuginea and MRI images were acquired at 7 and 21 days after injection with incision of the dartos. Results: The MRI acquisitions, both in coronal and axial projection, showed an adequate visibility of the anatomical structures. At 7 days after thrombin injection with the dartos incision it was evident an oedematous portion, visible as a hyperintense area, located at the injection area. At 21 days after injection, oedema was partially resolved: the injection part of the hyperintense area remains unchanged, while the remaining area appears to be part of a re-absorption and re-organization process. Conclusions: Since none of the various treatment modalities currently available for the management of PD is able to bring healing, the researchers’ attention is increasingly directed towards innovative treatment programs, such as the use of stem cells of mesenchymal origin. At the present time, the research in PD is hampered by the lack of universally accepted animal model and this is likely attributed to the limited insight into PD mechanisms and the difficulties faced by current animal models to truly represent the complexity.

  4. Modeling vector-borne disease risk in migratory animals under climate change.

    Science.gov (United States)

    Hall, Richard J; Brown, Leone M; Altizer, Sonia

    2016-08-01

    Recent theory suggests that animals that migrate to breed at higher latitudes may benefit from reduced pressure from natural enemies, including pathogens ("migratory escape"), and that migration itself weeds out infected individuals and lowers infection prevalence ("migratory culling"). The distribution and activity period of arthropod disease vectors in temperate regions is expected to respond rapidly to climate change, which could reduce the potential for migratory escape. However, climate change could have the opposite effect of reducing transmission if differential responses in the phenology and distribution of migrants and disease vectors reduce their overlap in space and time. Here we outline a simple modeling framework for exploring the influence of climate change on vector-borne disease dynamics in a migratory host. We investigate two scenarios under which pathogen transmission dynamics might be mediated by climate change: (1) vectors respond more rapidly than migrants to advancing phenology at temperate breeding sites, causing peak susceptible host density and vector emergence to diverge ("migratory mismatch") and (2) reduced migratory propensity allows increased nonbreeding survival of infected hosts and larger breeding-site epidemics (loss of migratory culling, here referred to as "sedentary amplification"). Our results highlight the need for continued surveillance of climate-induced changes to migratory behavior and vector activity to predict pathogen prevalence and its impacts on migratory animals. PMID:27252225

  5. Linking human diseases to animal models using ontology-based phenotype annotation.

    Directory of Open Access Journals (Sweden)

    Nicole L Washington

    2009-11-01

    gene candidates and animal models of human disease, which may shorten the lengthy path to identification and understanding of the genetic basis of human disease.

  6. Hepatitis C virus infection and related liver disease: the quest for the best animal model

    Directory of Open Access Journals (Sweden)

    Laurent eMailly

    2013-07-01

    Full Text Available Hepatitis C virus (HCV is a major cause of cirrhosis and hepatocellular carcinoma (HCC making the virus the most common cause of liver failure and transplantation. HCV is estimated to chronically affect 130 million individuals and to lead to more than 350,000 deaths per year worldwide. A vaccine is currently not available. The recently developed direct acting antivirals (DAAs have markedly increased the efficacy of the standard of care but are not efficient enough to completely cure all chronically infected patients and their toxicity limits their use in patients with advanced liver disease, co-morbidity or transplant recipients. Because of the host restriction, which is limited to humans and non-human primates, in vivo study of HCV infection has been hampered since its discovery more than 20 years ago. The chimpanzee remains the most physiological model to study the innate and adaptive immune responses, but its use is ethically difficult and is now very restricted and regulated. The development of a small animal model that allows robust HCV infection has been achieved using chimeric liver immunodeficient mice, which are therefore not suitable for studying the adaptive immune responses. Nevertheless, these models allowed to go deeply in the comprehension of virus-host interactions and to assess different therapeutic approaches. The immunocompetent mouse models that were recently established by genetic humanization have shown an interesting improvement concerning the study of the immune responses but are still limited by the absence of the complete robust life cycle of the virus. In this review, we will focus on the relevant available animal models of HCV infection and their usefulness for deciphering the HCV life cycle and virus-induced liver disease, as well as for the development and evaluation of new therapeutics. We will also discuss the perspectives on future immunocompetent mouse models and the hurdles to their development.

  7. Neuroprotective effects of protocatechuic aldehyde against neurotoxin-induced cellular and animal models of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Xin Zhao

    Full Text Available Protocatechuic aldehyde (PAL has been reported to bind to DJ-1, a key protein involved in Parkinson's disease (PD, and exerts potential neuroprotective effects via DJ-1 in SH-SY5Y cells. In this study, we investigated the neuroprotective pharmacological effects of PAL against neurotoxin-induced cell and animal models of PD. In cellular models of PD, PAL markedly increased cell viability rates, mitochondrial oxidation-reduction activity and mitochondrial membrane potential, and reduced intracellular ROS levels to prevent neurotoxicity in PC12 cells. In animal models of PD, PAL reduced the apomorphine injection, caused turning in 6-OHDA treated rats, and increased the motor coordination and stride decreases in MPTP treated mice. Meanwhile, in an MPTP mouse model, PAL prevented a decrease of the contents of dopamine (DA and its metabolites in the striatum and TH-positive dopaminergic neuron loss in the substantia nigra (SN. In addition, PAL increased the protein expression of DJ-1 and reduced the level of α-synuclein in the SN of MPTP lesioned mice. PAL also increased the spine density in hippocampal CA1 neurons. The current study demonstrates that PAL can efficiently protect dopaminergic neurons against neurotoxin injury in vitro and in vivo, and that the potential mechanisms may be related to its effects in increasing DJ-1, decreasing α-synuclein and its growth-promoting effect on spine density.

  8. Aminochrome induces dopaminergic neuronal dysfunction: a new animal model for Parkinson's disease.

    Science.gov (United States)

    Herrera, Andrea; Muñoz, Patricia; Paris, Irmgard; Díaz-Veliz, Gabriela; Mora, Sergio; Inzunza, Jose; Hultenby, Kjell; Cardenas, Cesar; Jaña, Fabián; Raisman-Vozari, Rita; Gysling, Katia; Abarca, Jorge; Steinbusch, Harry W M; Segura-Aguilar, Juan

    2016-09-01

    L-Dopa continues to be the gold drug in Parkinson's disease (PD) treatment from 1967. The failure to translate successful results from preclinical to clinical studies can be explained by the use of preclinical models which do not reflect what happens in the disease since these induce a rapid and extensive degeneration; for example, MPTP induces a severe Parkinsonism in only 3 days in humans contrasting with the slow degeneration and progression of PD. This study presents a new anatomy and develops preclinical model based on aminochrome which induces a slow and progressive dysfunction of dopaminergic neurons. The unilateral injection of aminochrome into rat striatum resulted in (1) contralateral rotation when the animals are stimulated with apomorphine; (2) absence of significant loss of tyrosine hydroxylase-positive neuronal elements both in substantia nigra and striatum; (3) cell shrinkage; (4) significant reduction of dopamine release; (5) significant increase in GABA release; (6) significant decrease in the number of monoaminergic presynaptic vesicles; (7) significant increase of dopamine concentration inside of monoaminergic vesicles; (8) significant increase of damaged mitochondria; (9) significant decrease of ATP level in the striatum (10) significant decrease in basal and maximal mitochondrial respiration. These results suggest that aminochrome induces dysfunction of dopaminergic neurons where the contralateral behavior can be explained by aminochrome-induced ATP decrease required both for anterograde transport of synaptic vesicles and dopamine release. Aminochrome could be implemented as a new model neurotoxin to study Parkinson's disease. PMID:27001668

  9. [Animal models of human retinal and optic nerve diseases analysed using electroretinography].

    Science.gov (United States)

    Kondo, Mineo

    2010-03-01

    Investigations of animal models with diseases found in humans are important to the understanding of their pathophysiology and for developing new treatments. Both naturally occurring and genetically-manipulated animal models of human retinal and optic nerve diseases have been studied in this manner. Electroretinography (ERG) is valuable for the evaluation of the visual function of animal models, because a layer-by-layer assessment of the retina can be done objectively. We used ERGs to analyze the visual functions of animal models of human retinal and and optic nerve diseases. To investigate the contribution of the cone ON- and OFF-pathways to the mouse photopic ERGs, we studied the properties of the photopic ERGs of metabotropic glutamate receptor subtype 6-deficient mice. The results of the ERG and the effect of an intravitreous injection of cis-2,3 piperidine dicarboxylic acid (PDA) in these mice suggest that the contribution of the post-synaptic ON-pathway to the photopic ERG of mice is larger than that of the OFF-pathway. The ERGs of pikachurin-deficient mice had normal a-waves with severely delayed b-waves, indicating that the signal transmission from the photoreceptors to the bipolar cells was impaired in these mutant mice. We also generated a rabbit model of retinitis pigmentosa (RP), the rhodopsin P347L transgenic (Tg) rabbit, by using bacterial artificial chromosome (BAC) transgenesis. These rabbits showed a rod-dominant, progressive retinal degeneration with marked regional variations in the loss of photoreceptors. All ERG components of the Tg rabbits decreased progressively with the a-waves more affected than the b-waves, and with the oscillatory potentials (OPs) the best preserved. Interestingly, the OP amplitudes of young Tg rabbits were significantly larger than those of wild-type rabbits. Pharmacological experiments showed that the significantly larger OPs in young Tg rabbits resulted from secondary alterations in the inner retinal function. This type

  10. MicroRNAs are potential therapeutic targets in fibrosing kidney disease: lessons from animal models

    Science.gov (United States)

    Duffield, Jeremy S; Grafals, Monica; Portilla, Didier

    2012-01-01

    Chronic disease of the kidneys has reached epidemic proportions in industrialized nations. New therapies are urgently sought. Using a combination of animal models of kidney disease and human biopsy samples, a pattern of dysregulated microRNA expression has emerged which is common to chronic diseases. A number of these dysregulated microRNA have recently been shown to have functional consequences for the disease process and therefore may be potential therapeutic targets. We highlight microRNA-21, the most comprehensively studied microRNA in the kidney so far. MicroRNA-21 is expressed widely in healthy kidney but studies from knockout mice indicate it is largely inert. Although microRNA-21 is upregulated in many cell compartments including leukocytes, epithelial cells and myofibroblasts, the inert microRNA-21 also appears to become activated, by unclear mechanisms. Mice lacking microRNA-21 are protected from kidney injury and fibrosis in several distinct models of kidney disease, and systemically administered oligonucleotides that specifically bind to the active site in microRNA-21, inhibiting its function, recapitulate the genetic deletion of microRNA-21, suggesting inhibitory oligonucleotides may have therapeutic potential. Recent studies of microRNA-21 targets in kidney indicate that it normally functions to silence metabolic pathways including fatty acid metabolism and pathways that prevent Reactive Oxygen Species generation in peroxisomes and mitochondria in epithelial cells and myofibroblasts. Targeting specific pathogenic microRNAs in a specific manner is feasible in vivo and may be a new therapeutic target in disease of the kidney PMID:25018773

  11. Current Understanding of Dysbiosis in Disease in Human and Animal Models.

    Science.gov (United States)

    DeGruttola, Arianna K; Low, Daren; Mizoguchi, Atsushi; Mizoguchi, Emiko

    2016-05-01

    Inflammatory bowel disease (IBD) is an intestinal inflammatory condition that affects more than 2 million people in the United States. Although the etiology and pathogenesis of IBD are still largely unknown, dysregulated host/enteric microbial interactions are requisite for the development of IBD. So far, many researchers have tried to identify a precise relationship between IBD and an imbalance of the intestinal microbiota, termed "dysbiosis." Despite extensive efforts, it is still largely unknown about the interplay among microbes, their hosts, and their environments, and whether dysbiosis is a causal factor or an effect of IBD. Recently, deep-sequencing analyses of the microbiota in patients with IBD patients have been instrumental in characterizing the strong association between dysbiosis and IBD development, although it is still unable to identify specific-associated species level changes in most cases. Based on many recent reports, dysbiosis of the commensal microbiota is implicated in the pathogenesis of several diseases, including IBD, obesity, and allergic disorders, in both human and animal models. In this review article, the authors have focused on explaining the multiple types of dysbiosis, as well as dysbiosis-related diseases and potential treatments to apply this knowledge to understand a possible cause and potentially find therapeutic strategies for IBD as well as the other dysbiosis-related diseases. PMID:27070911

  12. Animal Models of Narcolepsy

    OpenAIRE

    Chen, Lichao; Brown, Ritchie E.; McKenna, James T.; McCARLEY, ROBERT W.

    2009-01-01

    Narcolepsy is a debilitating sleep disorder with excessive daytime sleepiness and cataplexy as its two major symptoms. Although this disease was first described about one century ago, an animal model was not available until the 1970s. With the establishment of the Stanford canine narcolepsy colony, researchers were able to conduct multiple neurochemical studies to explore the pathophysiology of this disease. It was concluded that there was an imbalance between monoaminergic and cholinergic sy...

  13. Models for Correlating the Composition of the Gut Microbiota with Inflammatory Disease Parameters Using Animal Models

    DEFF Research Database (Denmark)

    Krych, Lukasz

    animal models. In order to evaluate the usefulness of a murine model for accomplishing this venture, a meta-analysis comparing GM consortia between humans and laboratory mice strains was conducted. More than 1.5 million high quality tag-encoded partial 16S rRNA gene sequences determined with pyro...... experimental model. An additional task of this thesis was to develop a fast screening method and to investigate the distribution of two bacterial species namely: Akkermansia muciniphila and Candidatus Savagella in detail. These two members of the gut microbial community were previously reported, including our...... changes in relative distribution of bacterial taxa in both groups, with the dominance of A. muciniphila to up to 90%. However, only neonatally treated mice had a significantly lower cumulative diabetes incidence.We also tested how a gluten-free diet, known to protect against T1D, modulated the bacterial...

  14. Protective effects of a dimeric derivative of ferulic acid in animal models of Alzheimer's disease.

    Science.gov (United States)

    Jung, Jun-Sub; Yan, Ji-Jing; Li, Hong-Mei; Sultan, Md Tipu; Yu, Jaehoon; Lee, Hee-Sul; Shin, Kye-Jung; Song, Dong-Keun

    2016-07-01

    Ferulic acid is a compound with potent anti-oxidant and anti-inflammatory activities. We previously reported the protective effects of ferulic acid administration against two animal models of Alzheimer's disease (AD): intracerebroventricular (i.c.v.) injection of Aß1-42 in mice and APP/PS1 mutant transgenic mice. In this study using the same AD animal models, we examined the effect of KMS4001, one of dimeric derivatives of ferulic acid. Intragastric pretreatment of mice with KMS4001 (30mg/kg/day) for 5 days significantly attenuated the Aß1-42 (i.c.v.)-induced memory impairment both in passive avoidance test and in Y-maze test. APP/PS1 mutant transgenic mice at KMS4001 doses of 3 and 30mg/kg/day via drinking water showed the significantly enhanced novel-object recognition memory at both 1.5 and 3 months after the start of KMS4001 treatment. Treatment of APP/PS1 mutant transgenic mice with KMS4001 for 3 months at the doses of 3 and 30mg/kg/day markedly decreased Aβ1-40 and Aβ1-42 levels in the frontal cortex. The KMS4001 dose-response relationships for Aβ decrease and for improvement in novel-object recognition test corresponded to each other. Taken together, these results suggest that KMS4001 could be an effective drug candidate against AD. PMID:27118174

  15. Follicular Helper CD4+ T Cells in Human Neuroautoimmune Diseases and Their Animal Models

    Directory of Open Access Journals (Sweden)

    Xueli Fan

    2015-01-01

    Full Text Available Follicular helper CD4+ T (TFH cells play a fundamental role in humoral immunity deriving from their ability to provide help for germinal center (GC formation, B cell differentiation into plasma cells and memory cells, and antibody production in secondary lymphoid tissues. TFH cells can be identified by a combination of markers, including the chemokine receptor CXCR5, costimulatory molecules ICOS and PD-1, transcription repressor Bcl-6, and cytokine IL-21. It is difficult and impossible to get access to secondary lymphoid tissues in humans, so studies are usually performed with human peripheral blood samples as circulating counterparts of tissue TFH cells. A balance of TFH cell generation and function is critical for protective antibody response, whereas overactivation of TFH cells or overexpression of TFH-associated molecules may result in autoimmune diseases. Emerging data have shown that TFH cells and TFH-associated molecules may be involved in the pathogenesis of neuroautoimmune diseases including multiple sclerosis (MS, neuromyelitis optica (NMO/neuromyelitis optica spectrum disorders (NMOSD, and myasthenia gravis (MG. This review summarizes the features of TFH cells, including their development, function, and roles as well as TFH-associated molecules in neuroautoimmune diseases and their animal models.

  16. Animal models of gastrointestinal and liver diseases. Animal models of necrotizing enterocolitis: pathophysiology, translational relevance, and challenges

    OpenAIRE

    Lu, Peng; Sodhi, Chhinder P.; Jia, Hongpeng; Shaffiey, Shahab; Good, Misty; Branca, Maria F.; Hackam, David J.

    2014-01-01

    Necrotizing enterocolitis is the leading cause of morbidity and mortality from gastrointestinal disease in premature infants and is characterized by initial feeding intolerance and abdominal distention followed by the rapid progression to coagulation necrosis of the intestine and death in many cases. Although the risk factors for NEC development remain well accepted, namely premature birth and formula feeding, the underlying mechanisms remain incompletely understood. Current thinking indicate...

  17. Animal Models of Atherosclerosis

    OpenAIRE

    Godfrey S Getz; Reardon, Catherine A

    2012-01-01

    Atherosclerosis is a chronic inflammatory disorder that is the underlying cause of most cardiovascular disease. Both cells of the vessel wall and cells of the immune system participate in atherogenesis. This process is heavily influenced by plasma lipoproteins, genetics and the hemodynamics of the blood flow in the artery. A variety of small and large animal models have been used to study the atherogenic process. No model is ideal as each has its own advantages and limitations with respect to...

  18. Animals: Disease Risks for People

    Science.gov (United States)

    ... the Knowledge Base Browse AVMA Policies Browse by Animal/Species Browse by Topic Browse by Discipline Resources ... Your Veterinarian Pet Care Currently selected Emergency Care Animal Welfare Veterinary Careers Public Health Disease Risks for ...

  19. Cognitive Dysfunction in Major Depressive Disorder. A Translational Review in Animal Models of the Disease

    Directory of Open Access Journals (Sweden)

    Flavie Darcet

    2016-02-01

    Full Text Available Major Depressive Disorder (MDD is the most common psychiatric disease, affecting millions of people worldwide. In addition to the well-defined depressive symptoms, patients suffering from MDD consistently complain about cognitive disturbances, significantly exacerbating the burden of this illness. Among cognitive symptoms, impairments in attention, working memory, learning and memory or executive functions are often reported. However, available data about the heterogeneity of MDD patients and magnitude of cognitive symptoms through the different phases of MDD remain difficult to summarize. Thus, the first part of this review briefly overviewed clinical studies, focusing on the cognitive dysfunctions depending on the MDD type. As animal models are essential translational tools for underpinning the mechanisms of cognitive deficits in MDD, the second part of this review synthetized preclinical studies observing cognitive deficits in different rodent models of anxiety/depression. For each cognitive domain, we determined whether deficits could be shared across models. Particularly, we established whether specific stress-related procedures or unspecific criteria (such as species, sex or age could segregate common cognitive alteration across models. Finally, the role of adult hippocampal neurogenesis in rodents in cognitive dysfunctions during MDD state was also discussed.

  20. Mitoapocynin Treatment Protects Against Neuroinflammation and Dopaminergic Neurodegeneration in a Preclinical Animal Model of Parkinson's Disease.

    Science.gov (United States)

    Ghosh, Anamitra; Langley, Monica R; Harischandra, Dilshan S; Neal, Matthew L; Jin, Huajun; Anantharam, Vellareddy; Joseph, Joy; Brenza, Timothy; Narasimhan, Balaji; Kanthasamy, Arthi; Kalyanaraman, Balaraman; Kanthasamy, Anumantha G

    2016-06-01

    Mitochondrial dysfunction, oxidative stress and neuroinflammation have been implicated as key mediators contributing to the progressive degeneration of dopaminergic neurons in Parkinson's disease (PD). Currently, we lack a pharmacological agent that can intervene in all key pathological mechanisms, which would offer better neuroprotective efficacy than a compound that targets a single degenerative mechanism. Herein, we investigated whether mito-apocynin (Mito-Apo), a newly-synthesized and orally available derivative of apocynin that targets mitochondria, protects against oxidative damage, glial-mediated inflammation and nigrostriatal neurodegeneration in cellular and animal models of PD. Mito-Apo treatment in primary mesencephalic cultures significantly attenuated the 1-methyl-4-phenylpyridinium (MPP(+))-induced loss of tyrosine hydroxylase (TH)-positive neuronal cells and neurites. Mito-Apo also diminished MPP(+)-induced increases in glial cell activation and inducible nitric oxide synthase (iNOS) expression. Additionally, Mito-Apo decreased nitrotyrosine (3-NT) and 4-hydroxynonenol (4-HNE) levels in primary mesencephalic cultures. Importantly, we assessed the neuroprotective property of Mito-Apo in the MPTP mouse model of PD, wherein it restored the behavioral performance of MPTP-treated mice. Immunohistological analysis of nigral dopaminergic neurons and monoamine measurement further confirmed the neuroprotective effect of Mito-Apo against MPTP-induced nigrostriatal dopaminergic neuronal loss. Mito-Apo showed excellent brain bioavailability and also markedly attenuated MPTP-induced oxidative markers in the substantia nigra (SN). Furthermore, oral administration of Mito-Apo significantly suppressed MPTP-induced glial cell activation, upregulation of proinflammatory cytokines, iNOS and gp91phox in IBA1-positive cells of SN. Collectively, these results demonstrate that the novel mitochondria-targeted compound Mito-Apo exhibits profound neuroprotective effects in

  1. From Bedside to Bench and Back Again: Research Issues in Animal Models of Human Disease

    OpenAIRE

    Tkacs, Nancy C.; Thompson, Hilaire J.

    2006-01-01

    To improve outcomes for patients with many serious clinical problems, multifactorial research approaches by nurse scientists, including the use of animal models, are necessary. Animal models serve as analogies for clinical problems seen in humans and must meet certain criteria, including validity and reliability, to be useful in moving research efforts forward. This article describes research considerations in the development of rodent models. As the standard of diabetes care evolves to empha...

  2. A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer

    Science.gov (United States)

    Asgharpour, Amon; Cazanave, Sophie C.; Pacana, Tommy; Seneshaw, Mulugeta; Vincent, Robert; Banini, Bubu A.; Kumar, Divya Prasanna; Daita, Kalyani; Min, Hae-Ki; Mirshahi, Faridoddin; Bedossa, Pierre; Sun, Xiaochen; Hoshida, Yujin; Koduru, Srinivas V.; Contaifer, Daniel; Warncke, Urszula Osinska; Wijesinghe, Dayanjan S.; Sanyal, Arun J.

    2016-01-01

    Background & Aims The lack of a preclinical model of progressive non-alcoholic steatohepatitis (NASH) that recapitulates human disease is a barrier to therapeutic development. Methods A stable isogenic cross between C57BL/6J (B6) and 129S1/SvImJ (S129) mice were fed a high fat diet with ad libitum consumption of glucose and fructose in physiologically relevant concentrations and compared to mice fed a chow diet and also to both parent strains. Results Following initiation of the obesogenic diet, B6/129 mice developed obesity, insulin resistance, hypertriglyceridemia and increased LDL-cholesterol. They sequentially also developed steatosis (4–8 weeks), steatohepatitis (16–24 weeks), progressive fibrosis (16 weeks onwards) and spontaneous hepatocellular cancer (HCC). There was a strong concordance between the pattern of pathway activation at a transcriptomic level between humans and mice with similar histological phenotypes (FDR 0.02 for early and 0.08 for late time points). Lipogenic, inflammatory and apoptotic signaling pathways activated in human NASH were also activated in these mice. The HCC gene signature resembled the S1 and S2 human subclasses of HCC (FDR 0.01 for both). Only the B6/129 mouse but not the parent strains recapitulated all of these aspects of human NAFLD. Conclusions We here describe a diet-induced animal model of non-alcoholic fatty liver disease (DIAMOND) that recapitulates the key physiological, metabolic, histologic, transcriptomic and cell-signaling changes seen in humans with progressive NASH. Lay summary We have developed a diet-induced mouse model of non-alcoholic steatohepatitis (NASH) and hepatic cancers in a cross between two mouse strains (129S1/SvImJ and C57Bl/6J). This model mimics all the physiological, metabolic, histological, transcriptomic gene signature and clinical endpoints of human NASH and can facilitate preclinical development of therapeutic targets for NASH. PMID:27261415

  3. Arthritis, a complex connective and synovial joint destructive autoimmune disease: animal models of arthritis with varied etiopathology and their significance.

    Science.gov (United States)

    Naik, S R; Wala, S M

    2014-01-01

    Animal models play a vital role in simplifying the complexity of pathogenesis and understanding the indefinable processes and diverse mechanisms involved in the progression of disease, and in providing new knowledge that may facilitate the drug development program. Selection of the animal models has to be carefully done, so that there is morphologic similarity to human arthritic conditions that may predict as well as augment the effective screening of novel antiarthritic agents. The review describes exclusively animal models of rheumatoid arthritis (RA) and osteoarthritis (OA). The development of RA has been vividly described using a wide variety of animal models with diverse insults (viz. collagen, Freund's adjuvant, proteoglycan, pristane, avridine, formaldehyde, etc.) that are able to simulate/trigger the cellular, biochemical, immunological, and histologic alterations, which perhaps mimic, to a great extent, the pathologic conditions of human RA. Similarly, numerous methods of inducing animal models with OA have also been described (such as spontaneous, surgical, chemical, and physical methods including genetically manipulated animals) which may give an insight into the events of alteration in connective tissues and their metabolism (synovial membrane/tissues along with cartilage) and bone erosion. The development of such arthritic animal models may throw light for better understanding of the etiopathogenic mechanisms of human arthritis and give new impetus for the drug development program on arthritis, a crippling disease. PMID:25121375

  4. Arthritis, a complex connective and synovial joint destructive autoimmune disease: Animal models of arthritis with varied etiopathology and their significance

    Directory of Open Access Journals (Sweden)

    S R Naik

    2014-01-01

    Full Text Available Animal models play a vital role in simplifying the complexity of pathogenesis and understanding the indefinable processes and diverse mechanisms involved in the progression of disease, and in providing new knowledge that may facilitate the drug development program. Selection of the animal models has to be carefully done, so that there is morphologic similarity to human arthritic conditions that may predict as well as augment the effective screening of novel antiarthritic agents. The review describes exclusively animal models of rheumatoid arthritis (RA and osteoarthritis (OA. The development of RA has been vividly described using a wide variety of animal models with diverse insults (viz. collagen, Freund′s adjuvant, proteoglycan, pristane, avridine, formaldehyde, etc. that are able to simulate/trigger the cellular, biochemical, immunological, and histologic alterations, which perhaps mimic, to a great extent, the pathologic conditions of human RA. Similarly, numerous methods of inducing animal models with OA have also been described (such as spontaneous, surgical, chemical, and physical methods including genetically manipulated animals which may give an insight into the events of alteration in connective tissues and their metabolism (synovial membrane/tissues along with cartilage and bone erosion. The development of such arthritic animal models may throw light for better understanding of the etiopathogenic mechanisms of human arthritis and give new impetus for the drug development program on arthritis, a crippling disease.

  5. Research progress in animal models and stem cell therapy for Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Han F

    2014-12-01

    Full Text Available Fabin Han,1,2 Wei Wang1, Chao Chen1 1Centre for Stem Cells and Regenerative Medicine, 2Department of Neurology, Liaocheng People’s Hospital/The Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People’s Republic of China Abstract: Alzheimer’s disease (AD causes degeneration of brain neurons and leads to memory loss and cognitive impairment. Since current therapeutic strategies cannot cure the disease, stem cell therapy represents a powerful tool for the treatment of AD. We first review the advances in molecular pathogenesis and animal models of AD and then discuss recent clinical studies using small molecules and immunoglobulins to target amyloid-beta plaques for AD therapy. Finally, we discuss stem cell therapy for AD using neural stem cells, olfactory ensheathing cells, embryonic stem cells, and mesenchymal stem cell from bone marrow, umbilical cord, and umbilical cord blood. In particular, patient-specific induced pluripotent stem cells are proposed as a future treatment for AD. Keywords: amyloid-beta plaque, neurofibrillary tangle, neural stem cell, olfactory ensheathing cell, mesenchymal stem cell, induced pluripotent stem cell

  6. Neuroprotection of pramipexole in UPS impairment induced animal model of Parkinson's disease.

    Science.gov (United States)

    Li, Chao; Guo, Yuan; Xie, Wenjie; Li, Xingang; Janokovic, Joseph; Le, Weidong

    2010-10-01

    Pramipexole (PPX), a dopamine (DA) receptor D3 preferring agonist, has been used as monotherapy or adjunct therapy to treat Parkinson's disease (PD) for many years. Several in vitro and in vivo studies in neurotoxin-induced DA neuron injury models have reported that PPX may possess neuroprotective properties. The present study is to evaluate the neuroprotection of PPX in a sustained DA neuron degeneration model of PD induced by ubiquitin-proteasome system (UPS) impairment. Adult C57BL/6 mice were treated with PPX (low dose 0.1 mg/kg or high dose 0.5 mg/kg, i.p, twice a day) started 7 days before, and continued after microinjection of proteasome inhibitor lactacystin in the medial forebrain bundle for a total 4 weeks. Animal behavior observation, and pathological and biochemical assays were conducted to determine the neuroprotective effects of PPX. We report here that PPX treatment significantly improves rotarod performance, attenuates DA neuron loss and striatal DA reduction, and alleviates proteasomal inhibition and microglial activation in the substantia nigra of lactacystin-lesioned mice. PPX can increase the levels of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor and induce an activation of autophagy. Furthermore, pretreatment with D3 receptor antagonist U99194 can significantly block the PPX-mediated neuroprotection. These results suggest that multiple molecular pathways may be attributed to the neuroprotective effects of PPX in the UPS impairment model of PD. PMID:20635141

  7. The multifactorial role of the 3Rs in shifting the harm-benefit analysis in animal models of disease.

    Science.gov (United States)

    Graham, Melanie L; Prescott, Mark J

    2015-07-15

    Ethics on animal use in science in Western society is based on utilitarianism, weighing the harms and benefits to the animals involved against those of the intended human beneficiaries. The 3Rs concept (Replacement, Reduction, Refinement) is both a robust framework for minimizing animal use and suffering (addressing the harms to animals) and a means of supporting high quality science and translation (addressing the benefits). The ambiguity of basic research performed early in the research continuum can sometimes make harm-benefit analysis more difficult since anticipated benefit is often an incremental contribution to a field of knowledge. On the other hand, benefit is much more evident in translational research aimed at developing treatments for direct application in humans or animals suffering from disease. Though benefit may be easier to define, it should certainly not be considered automatic. Issues related to model validity seriously compromise experiments and have been implicated as a major impediment in translation, especially in complex disease models where harms to animals can be intensified. Increased investment and activity in the 3Rs is delivering new research models, tools and approaches with reduced reliance on animal use, improved animal welfare, and improved scientific and predictive value. PMID:25823812

  8. Nasal Administration of Quercetin Liposomes Improves Memory Impairment and Neurodegeneration in Animal Model of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Terdthai Tong-un

    2010-01-01

    Full Text Available Problem statement: At present, the development of protective strategy against Alzheimer’s Disease (AD is increasing its importance due to the high prevalence of AD, a limitation of therapeutic efficacy and its high impacts on economic and social aspects. The development of the preventive and therapeutic strategy to protect against the path physiology induced by free radicals in AD from antioxidant has gained very much concentration. Quercetin, one of the flavonoids in fruits and vegetables, has a powerful antioxidant activity both in vitro and in vivo. However, poor absorption, rapid metabolism and limited ability to cross the blood-brain-barrier are obstacles to its use for treatment of AD. Liposome’s have been used as an effective delivery system to the brain. Advantages associated with the nasal administration over oral route include higher bioavailability due to no first pass hepatic metabolism and rapid absorption leading to shorter time to onset of effect. Based on all these points, the possible effects of quercetin liposomes via nasal route on improving cognitive behavior and neurodegeneration in animal model of Alzheimer’s disease were investigated. Approach: Male Wistar rats were pretreated with quercetin liposome’s, containing 0.5 mg of quercetin in 20 μL (dose = 20 μg, via intranasal route once daily continually for 2 weeks before and 1 week after AF64A administration. Learning and memory was evaluated using the Morris water maze test at 7 days after the AF64A administration and then the rats were sacrificed for determining the density of neurons and cholinergic neurons in hippocampus using histological and immunohistochemical techniques. Results: Nasal administration of quercetin liposome’s significantly prevented changes of spatial memory of AF64A treated rats. The cognitive enhancement of quercetin liposome’s was found to be related to its ability to inhibit the degeneration of neurons and cholinergic neurons in hippocampus

  9. Hormonal Influences on Lung Function and Response to Environmental Agents: Lessons from Animal Models of Respiratory Disease

    OpenAIRE

    Card, Jeffrey W.; Zeldin, Darryl C

    2009-01-01

    Numerous studies in humans and experimental animals have identified considerable sex differences in respiratory physiology and in the response of the lung to environmental agents. These differences appear to be mediated, at least in part, by sex hormones and their nuclear receptors. Moreover, animal models are increasingly used to study pathogenic mechanisms and test potential therapies for a variety of human lung diseases, many of which appear to be influenced by sex and sex hormones. In thi...

  10. Fumarylacetoacetate hydrolase deficient pigs are a novel large animal model of metabolic liver disease

    Directory of Open Access Journals (Sweden)

    Raymond D. Hickey

    2014-07-01

    FAH-deficiency produced a lethal defect in utero that was corrected by administration of 2-(2-nitro-4-trifluoromethylbenzoyl-1,3 cyclohexanedione (NTBC throughout pregnancy. Animals on NTBC were phenotypically normal at birth; however, the animals were euthanized approximately four weeks after withdrawal of NTBC due to clinical decline and physical examination findings of severe liver injury and encephalopathy consistent with acute liver failure. Biochemical and histological analyses, characterized by diffuse and severe hepatocellular damage, confirmed the diagnosis of severe liver injury. FAH−/− pigs provide the first genetically engineered large animal model of a metabolic liver disorder. Future applications of FAH−/− pigs include discovery research as a large animal model of HT1 and spontaneous acute liver failure, and preclinical testing of the efficacy of liver cell therapies, including transplantation of hepatocytes, liver stem cells, and pluripotent stem cell-derived hepatocytes.

  11. The Y-Box Binding Protein 1 Suppresses Alzheimer's Disease Progression in Two Animal Models.

    Directory of Open Access Journals (Sweden)

    N V Bobkova

    Full Text Available The Y-box binding protein 1 (YB-1 is a member of the family of DNA- and RNA binding proteins. It is involved in a wide variety of DNA/RNA-dependent events including cell proliferation and differentiation, stress response, and malignant cell transformation. Previously, YB-1 was detected in neurons of the neocortex and hippocampus, but its precise role in the brain remains undefined. Here we show that subchronic intranasal injections of recombinant YB-1, as well as its fragment YB-11-219, suppress impairment of spatial memory in olfactory bulbectomized (OBX mice with Alzheimer's type degeneration and improve learning in transgenic 5XFAD mice used as a model of cerebral amyloidosis. YB-1-treated OBX and 5XFAD mice showed a decreased level of brain β-amyloid. In OBX animals, an improved morphological state of neurons was revealed in the neocortex and hippocampus; in 5XFAD mice, a delay in amyloid plaque progression was observed. Intranasally administered YB-1 penetrated into the brain and could enter neurons. In vitro co-incubation of YB-1 with monomeric β-amyloid (1-42 inhibited formation of β-amyloid fibrils, as confirmed by electron microscopy. This suggests that YB-1 interaction with β-amyloid prevents formation of filaments that are responsible for neurotoxicity and neuronal death. Our data are the first evidence for a potential therapeutic benefit of YB-1 for treatment of Alzheimer's disease.

  12. Derivation of neural stem cells from an animal model of psychiatric disease

    OpenAIRE

    Koning, A.; Walton, N M; Shin, R.; Q. Chen; Miyake, S.; Tajinda, K; Gross, A K; Kogan, J H; Heusner, C L; Tamura, K.; Matsumoto, M.

    2013-01-01

    Several psychiatric and neurological diseases are associated with altered hippocampal neurogenesis, suggesting differing neural stem cell (NSC) function may play a critical role in these diseases. To investigate the role of resident NSCs in a murine model of psychiatric disease, we sought to isolate and characterize NSCs from alpha-calcium-/calmodulin-dependent protein kinase II heterozygous knockout (CaMK2α-hKO) mice, a model of schizophrenia/bipolar disorder. These mice display altered neur...

  13. Animal Models of Allergic Airways Disease: Where Are We and Where to Next?

    OpenAIRE

    Chapman, David G.; Tully, Jane E.; Nolin, James D.; Jansen-Heininger, Yvonne M; Irvin, Charles G.

    2014-01-01

    In a complex inflammatory airways disease such as asthma, abnormalities in a plethora of molecular and cellular pathways ultimately culminate in characteristic impairments in respiratory function. The ability to study disease pathophysiology in the setting of a functioning immune and respiratory system therefore makes mouse models an invaluable tool in translational research. Despite the vast understanding of inflammatory airways diseases gained from mouse models to date, concern over the val...

  14. Animal models for the study of hepatitis C virus infection and related liver disease

    DEFF Research Database (Denmark)

    Bukh, Jens

    2012-01-01

    HCV research and development of drugs and vaccines. Chimpanzees are the best model for studies of HCV infection and related innate and adaptive host immune responses. They can be used in immunogenicity and efficacy studies of HCV vaccines. The only small animal models of robust HCV infection are T...

  15. Grunting in a Genetically Modified Minipig Animal Model for Huntington’s Disease –  
Pilot Experiments


    Czech Academy of Sciences Publication Activity Database

    Tykalová, T.; Hlavnička, J.; Mačáková, Monika; Baxa, Monika; Cmejla, R.; Motlík, Jan; Klempíř, J.; Rusz, J.

    2015-01-01

    Roč. 78, Suppl 2 (2015), s. 61-65. ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. Liblice, 08.11.2015-10.11.2015] R&D Projects: GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : Huntington’s disease * grunting * transgenic pigs Subject RIV: ED - Physiology Impact factor: 0.165, year: 2014

  16. General view in animal model of inflammatory bowel disease%炎症性肠病动物模型的研究概况

    Institute of Scientific and Technical Information of China (English)

    兰雷; 陈垦; 王晖

    2004-01-01

    The etiology and pathogenesis of inflammatory bowel disease are up to now still not clear and definite. Establishing the ideal animal model to study its cause and pathogenesis of this disease is very important. The ideal animal model should have the same manifestation with human inflammatory bowel disease on clinical and pathologic feature etc. In this article, the method, the pathologic character isfics and concerning pathogenesis, of a few common useful experiment animal models are discussed.

  17. Chemical and biomechanical characterization of hyperhomocysteinemic bone disease in an animal model

    Directory of Open Access Journals (Sweden)

    Howell David S

    2003-02-01

    Full Text Available Abstract Background Classical homocystinuria is an autosomal recessive disorder caused by cystathionine β-synthase (CBS deficiency and characterized by distinctive alterations of bone growth and skeletal development. Skeletal changes include a reduction in bone density, making it a potentially attractive model for the study of idiopathic osteoporosis. Methods To investigate this aspect of hyperhomocysteinemia, we supplemented developing chicks (n = 8 with 0.6% dl-homocysteine (hCySH for the first 8 weeks of life in comparison to controls (n = 10, and studied biochemical, biomechanical and morphologic effects of this nutritional intervention. Results hCySH-fed animals grew faster and had longer tibiae at the end of the study. Plasma levels of hCySH, methionine, cystathionine, and inorganic sulfate were higher, but calcium, phosphate, and other indices of osteoblast metabolism were not different. Radiographs of the lower limbs showed generalized osteopenia and accelerated epiphyseal ossification with distinct metaphyseal and suprametaphyseal lucencies similar to those found in human homocystinurics. Although biomechanical testing of the tibiae, including maximal load to failure and bone stiffness, indicated stronger bone, strength was proportional to the increased length and cortical thickness in the hCySH-supplemented group. Bone ash weights and IR-spectroscopy of cortical bone showed no difference in mineral content, but there were higher Ca2+/PO43- and lower Ca2+/CO32- molar ratios than in controls. Mineral crystallization was unchanged. Conclusion In this chick model, hyperhomocysteinemia causes greater radial and longitudinal bone growth, despite normal indices of bone formation. Although there is also evidence for an abnormal matrix and altered bone composition, our finding of normal biomechanical bone strength, once corrected for altered morphometry, suggests that any increase in the risk of long bone fracture in human hyperhomocysteinemic

  18. Copper balance and ceruloplasmin in chronic hepatitis in a Wilson disease animal model, LEC rats

    Energy Technology Data Exchange (ETDEWEB)

    Komatsu, Yutaka; Ogra, Yasumitsu; Suzuki, Kazuo T. [Graduate School of Pharmaceutical Sciences, Chiba University, Inage, Chiba 263-8522 (Japan)

    2002-09-01

    In an animal model of Wilson disease, Long-Evans rats with cinnamon-colored coat (LEC rats), copper (Cu) accumulates in the liver with age up to the onset of acute hepatitis owing to a hereditary defective transporter for the efflux of Cu, ATP7B. The plasma Cu concentration is low in LEC rats because of the excretion of apo-ceruloplasmin (apo-Cp). However, toward and after the onset of chronic hepatitis, plasma Cu concentration increases in the form of holo-Cp, while the liver Cu concentration is maintained at a constant level without the occurrence of fulminant hepatitis. In the present study, the material balance of Cu was studied in LEC rats with chronic hepatitis in order to elucidate the mechanisms underlying the increase of holo-Cp in plasma and the maintenance of Cu at a constant level in the liver. The relationship between the Cu concentration and ferroxidase activity of Cp was analyzed in the plasma of LEC rats of different ages and of Wistar rats fed a Cu-deficient diet for different durations. Cu was suggested to be delivered to Cp in an all-or-nothing manner, resulting in the excretion of fully Cu-occupied holo-Cp (Cu{sub 6}-Cp) or totally Cu-unoccupied Cu{sub 0}-Cp (apo-Cp), but not partially Cu-occupied Cu{sub n}-Cp (where n=1-5). The increase of holo-Cp in acute and chronic hepatitis in LEC rats was explained by the delivery of Cu, accumulating in the non-metallothionein-bound form, to Cp outside the Golgi apparatus of the liver. The plasma Cu concentration and ferroxidase activity were proposed to be specific indicators of the appearance of non-metallothionein-bound Cu in the liver of LEC rats. (orig.)

  19. Early astrocytic atrophy in the entorhinal cortex of a triple transgenic animal model of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Chia‑Yu Yeh

    2011-12-01

    Full Text Available The EC (entorhinal cortex is fundamental for cognitive and mnesic functions. Thus damage to this area appears as a key element in the progression of AD (Alzheimer's disease, resulting in memory deficits arising from neuronal and synaptic alterations as well as glial malfunction. In this paper, we have performed an in-depth analysis of astroglial morphology in the EC by measuring the surface and volume of the GFAP (glial fibrillary acidic protein profiles in a triple transgenic mouse model of AD [3xTg-AD (triple transgenic mice of AD]. We found significant reduction in both the surface and volume of GFAP-labelled profiles in 3xTg-AD animals from very early ages (1 month when compared with non-Tg (non-transgenic controls (48 and 54%, reduction respectively, which was sustained for up to 12 months (33 and 45% reduction respectively. The appearance of Aβ (amyloid β-peptide depositions at 12 months of age did not trigger astroglial hypertrophy; nor did it result in the close association of astrocytes with senile plaques. Our results suggest that the AD progressive cognitive deterioration can be associated with an early reduction of astrocytic arborization and shrinkage of the astroglial domain, which may affect synaptic connectivity within the EC and between the EC and other brain regions. In addition, the EC seems to be particularly vulnerable to AD pathology because of the absence of evident astrogliosis in response to Aβ accumulation. Thus we can consider that targeting astroglial atrophy may represent a therapeutic strategy which might slow down the progression of AD.

  20. Raloxifene improves skeletal properties in an animal model of cystic chronic kidney disease.

    Science.gov (United States)

    Newman, Christopher L; Creecy, Amy; Granke, Mathilde; Nyman, Jeffry S; Tian, Nannan; Hammond, Max A; Wallace, Joseph M; Brown, Drew M; Chen, Neal; Moe, Sharon M; Allen, Matthew R

    2016-01-01

    Patients with chronic kidney disease (CKD) have an increased risk of fracture. Raloxifene is a mild antiresorptive agent that reduces fracture risk in the general population. Here we assessed the impact of raloxifene on the skeletal properties of animals with progressive CKD. Male Cy/+ rats that develop autosomal dominant cystic kidney disease were treated with either vehicle or raloxifene for five weeks. They were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole-bone mechanics, and material properties). Their normal littermates served as controls. Animals with CKD had significantly higher parathyroid hormone levels compared with normal controls, as well as inferior structural and mechanical skeletal properties. Raloxifene treatment resulted in lower bone remodeling rates and higher cancellous bone volume in the rats with CKD. Although it had little effect on cortical bone geometry, it resulted in higher energy to fracture and modulus of toughness values than vehicle-treated rats with CKD, achieving levels equivalent to normal controls. Animals treated with raloxifene had superior tissue-level mechanical properties as assessed by nanoindentation, and higher collagen D-periodic spacing as assessed by atomic force microscopy. Thus, raloxifene can positively impact whole-bone mechanical properties in CKD through its impact on skeletal material properties. PMID:26489025

  1. A Flexible Spatial Framework for Modeling Spread of Pathogens in Animals with Biosurveillance and Disease Control Applications

    Directory of Open Access Journals (Sweden)

    Montiago X. LaBute

    2014-05-01

    Full Text Available Biosurveillance activities focus on acquiring and analyzing epidemiological and biological data to interpret unfolding events and predict outcomes in infectious disease outbreaks. We describe a mathematical modeling framework based on geographically aligned data sources and with appropriate flexibility that partitions the modeling of disease spread into two distinct but coupled levels. A top-level stochastic simulation is defined on a network with nodes representing user-configurable geospatial “patches”. Intra-patch disease spread is treated with differential equations that assume uniform mixing within the patch. We use U.S. county-level aggregated data on animal populations and parameters from the literature to simulate epidemic spread of two strikingly different animal diseases agents: foot-and-mouth disease and highly pathogenic avian influenza. Results demonstrate the capability of this framework to leverage low-fidelity data while producing meaningful output to inform biosurveillance and disease control measures. For example, we show that the possible magnitude of an outbreak is sensitive to the starting location of the outbreak, highlighting the strong geographic dependence of livestock and poultry infectious disease epidemics and the usefulness of effective biosurveillance policy. The ability to compare different diseases and host populations across the geographic landscape is important for decision support applications and for assessing the impact of surveillance, detection, and mitigation protocols.

  2. Lavandula angustifolia extract improves deteriorated synaptic plasticity in an animal model of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Masoud Soheili

    2015-11-01

    Full Text Available Objective(s:Neurodegenerative Alzheimer’s disease (AD is associated with profound deficits in synaptic transmission and synaptic plasticity. Long-term potentiation (LTP, an experimental form of synaptic plasticity, is intensively examined in hippocampus. In this study we evaluated the effect of aqueous extract of lavender (Lavandula angustifolia on induction of LTP in the CA1 area of hippocampus. In response to stimulation of the Schaffer collaterals the baseline or tetanized field extracellular postsynaptic potentials (fEPSPs were recorded in the CA1 area. Materials and Methods: The electrophysiological recordings were carried out in four groups of rats; two control groups including the vehicle (CON and lavender (CE treated rats and two Alzheimeric groups including the vehicle (ALZ and lavender (AE treated animals. Results: The extract inefficiently affected the baseline responses in the four testing groups. While the fEPSPs displayed a considerable LTP in the CON animals, no potentiation was evident in the tetanized responses in the ALZ rats. The herbal medicine effectively restored LTP in the AE group and further potentiated fEPSPs in the CE group. Conclusion:The positive effect of the lavender extract on the plasticity of synaptic transmission supports its previously reported behavioral effects on improvement of impaired spatial memory in the Alzheimeric animals.

  3. Alzheimer’s disease biomarkers in animal models: closing the translational gap

    OpenAIRE

    Sabbagh, Jonathan J.; Kinney, Jefferson W.; Cummings, Jeffrey L.

    2013-01-01

    The rising prevalence of Alzheimer’s disease (AD) is rapidly becoming one of the largest health and economic challenges in the world. There is a growing need for the development and implementation of reliable biomarkers for AD that can be used to assist in diagnosis, inform disease progression, and monitor therapeutic efficacy. Preclinical models permit the evaluation of candidate biomarkers and assessment of pipeline agents before clinical trials are initiated and provide a translational opp...

  4. The Effect of Treadmill Running on Passive Avoidance Learning in Animal Model of Alzheimer Disease

    OpenAIRE

    Nasrin Hosseini; Hojjatallah Alaei; Parham Reisi; Maryam Radahmadi

    2013-01-01

    Background : Alzheimer′s disease was known as a progressive neurodegenerative disorder in the elderly and is characterized by dementia and severe neuronal loss in the some regions of brain such as nucleus basalis magnocellularis. It plays an important role in the brain functions such as learning and memory. Loss of cholinergic neurons of nucleus basalis magnocellularis by ibotenic acid can commonly be regarded as a suitable model of Alzheimer′s disease. Previous studies reported that exercise...

  5. Animal welfare and the refinement of neuroscience research methods--a case study of Huntington's disease models.

    Science.gov (United States)

    Olsson, I Anna S; Hansen, Axel K; Sandøe, Peter

    2008-07-01

    The use of animals in biomedical and other research presents an ethical dilemma: we do not want to lose scientific benefits, nor do we want to cause laboratory animals to suffer. Scientists often refer to the potential human benefits of animal models to justify their use. However, even if this is accepted, it still needs to be argued that the same benefits could not have been achieved with a mitigated impact on animal welfare. Reducing the adverse effects of scientific protocols ('refinement') is therefore crucial in animal-based research. It is especially important that researchers share knowledge on how to avoid causing unnecessary suffering. We have previously demonstrated that even in studies in which animal use leads to spontaneous death, scientists often fail to report measures to minimize animal distress (Olsson et al. 2007). In this paper, we present the full results of a case study examining reports, published in peer-reviewed journals between 2003 and 2004, of experiments employing animal models to study the neurodegenerative disorder Huntington's disease. In 51 references, experiments in which animals were expected to develop motor deficits so severe that they would have difficulty eating and drinking normally were conducted, yet only three references were made to housing adaptation to facilitate food and water intake. Experiments including end-stages of the disease were reported in 14 papers, yet of these only six referred to the euthanasia of moribund animals. If the reference in scientific publications reflects the actual application of refinement, researchers do not follow the 3Rs (replacement, reduction, refinement) principle. While in some cases, it is clear that less-than-optimal techniques were used, we recognize that scientists may apply refinement without referring to it; however, if they do not include such information in publications, it suggests they find it less relevant. Journal publishing policy could play an important role: first, in

  6. Successful therapies for Alzheimer’s disease: why so many in animal models and none in humans?

    OpenAIRE

    RafaelFranco; AngelCedazo-Minguez

    2014-01-01

    Peering into the field of Alzheimer's disease (AD) the outsider realizes that many of the therapeutic strategies tested (in animal models) have been successful. One also may notice that there is a deficit in translational research, i.e. to take a successful drug in mice and translate it to the patient. Efforts are still focused on novel projects to expand the therapeutic arsenal to "cure mice". Scientific reasons behind so many successful strategies are not obvious. This article aims to revie...

  7. Animal Models of Colorectal Cancer

    Science.gov (United States)

    Johnson, Robert L.; Fleet, James C.

    2012-01-01

    Colorectal cancer is a heterogeneous disease that afflicts a large number of people in the United States. The use of animal models has the potential to increase our understanding of carcinogenesis, tumor biology, and the impact of specific molecular events on colon biology. In addition, animal models with features of specific human colorectal cancers can be used to test strategies for cancer prevention and treatment. In this review we provide an overview of the mechanisms driving human cancer, we discuss the approaches one can take to model colon cancer in animals, and we describe a number of specific animal models that have been developed for the study of colon cancer. We believe that there are many valuable animal models to study various aspects of human colorectal cancer. However, opportunities for improving upon these models exist. PMID:23076650

  8. Small animal disease surveillance: respiratory disease

    OpenAIRE

    Sánchez-Vizcaíno, Fernando; Daly, Janet M.; Philip H Jones; Dawson, Susan; Gaskell, Rosalind; Menacere, Tarek; Heayns, Bethaney; Wardeh, Maya; Newman, Jenny; Everitt, Sally; Day, Michael J.; McConnell, Katie; Noble, Peter J.M.; Radford, Alan D

    2016-01-01

    This second Small Animal Disease Surveillance report focuses on syndromic surveillance of i) respiratory disease in veterinary practice and ii) feline calicivirus (FCV) based on laboratory diagnosis, in a large veterinary-visiting pet population of the UK between January 2014 and December 2015. Presentation for respiratory disease comprised 1.7%, 2.3% and 2.5% of canine, feline and rabbit consultations, respectively. In dogs, the most frequent respiratory sign reported was coughing (71.1% of ...

  9. Animal Model of Dermatophytosis

    OpenAIRE

    Tsuyoshi Shimamura; Nobuo Kubota; Kazutoshi Shibuya

    2012-01-01

    Dermatophytosis is superficial fungal infection caused by dermatophytes that invade the keratinized tissue of humans and animals. Lesions from dermatophytosis exhibit an inflammatory reaction induced to eliminate the invading fungi by using the host’s normal immune function. Many scientists have attempted to establish an experimental animal model to elucidate the pathogenesis of human dermatophytosis and evaluate drug efficacy. However, current animal models have several issues. In the presen...

  10. Animal Diseases and Your Health

    Science.gov (United States)

    ... cause Lyme disease. Some wild animals may carry rabies. Enjoy wildlife from a distance. Pets can also make you sick. Reptiles pose a particular risk. Turtles, snakes and iguanas can transmit Salmonella bacteria to their owners. You can get rabies from an infected dog or toxoplasmosis from handling ...

  11. The effect of mGlu8 deficiency in animal models of psychiatric diseases.

    Science.gov (United States)

    Fendt, M; Bürki, H; Imobersteg, S; van der Putten, H; McAllister, K; Leslie, J C; Shaw, D; Hölscher, C

    2010-02-01

    The metabotropic glutamate receptor subtype 8 (mGlu(8)) is presynaptically located and regulates the release of the transmitter. Dysfunctions of this mechanism are involved in the pathophysiology of different psychiatric disorders. mGlu(8) deficient mice have been previously investigated in a range of studies, but the results are contradictory and there are still many open questions. Therefore, we tested mGlu(8)-deficient animals in different behavioral tasks that are commonly used in neuropsychiatric research. Our results show a robust contextual fear deficit in mGlu(8)-deficient mice. Furthermore, novel object recognition, chlordiazepoxide-facilitated extinction of operant conditioning and the acoustic startle response were attenuated by mGlu(8) deficiency. We found no changes in sensory processing, locomotor activity, prepulse inhibition, phencyclidine-induced changes in locomotion or prepulse inhibition, operant conditioning, conditioned fear to a discrete cue or in animal models of innate fear and post-traumatic stress disorder. We conclude that mGlu(8) might be a potential target for disorders with pathophysiological changes in brain areas where mGlu(8) modulates glutamate and gamma-amino butyric acid (GABA) transmission. Our data especially point to anxiety disorders involving exaggerated contextual fear, such as generalized anxiety disorders, and to conditions with disturbed declarative memory. PMID:19740090

  12. In vivo tracking of stem cells labeled with a nanoparticle in Alzheimer's disease animal model

    Science.gov (United States)

    Ha, Sungji; Suh, Yoo-Hun; Chang, Keun-A.

    2013-05-01

    Stem cell therapy is a promising tool for the treatment of diverse conditions including neurodegenerative diseases. To understand transplanted stem cell biology, in vivo imaging is necessary. Nano material has great potential for in vivo imaging and several noninvasive methods are used such as magnetic resonance imaging (MRI), positron emission tomography (PET), Fluorescence imaging (FI) and Near-infrared fluorescence imaging (NIRFI). However, each method has limitations for in vivo imaging. To overcome these limitations, multimodal nanoprobes have been developed. In the present study, we intravenously injected human adipose derived stem cells (hASCs) that labeled with multimodal nano particle, LEO-LIVETM-Magnoxide 797 or 675, into the Tg2576 mice, Alzheimer's disease (AD) mouse model. Sequential in vivo tracking was performed with mice injected with hASCs. We could found fluorescence signals until 10 days after injection.

  13. ANIMAL MODELS FOR FOOD ALLERGY

    Science.gov (United States)

    Animal models have been used to provide insight into the complex immunological and pathophysioligical mechanisms of human Type 1 allergic diseases. Research efforts that include mechanistic studies in search of new therapies and screening models for hazard identification of potential allergens in a...

  14. In vivo imaging of human adipose-derived stem cells in Alzheimer's disease animal model

    Science.gov (United States)

    Ha, Sungji; Ahn, Sangzin; Kim, Saeromi; Joo, Yuyoung; Chong, Young Hae; Suh, Yoo-Hun; Chang, Keun-A.

    2014-05-01

    Stem cell therapy is a promising tool for the treatment of diverse conditions, including neurodegenerative diseases such as Alzheimer's disease (AD). To understand transplanted stem cell biology, in vivo imaging is necessary. Nanomaterial has great potential for in vivo imaging and several noninvasive methods are used, such as magnetic resonance imaging, positron emission tomography, fluorescence imaging (FI) and near-infrared FI. However, each method has limitations for in vivo imaging. To overcome these limitations, multimodal nanoprobes have been developed. In the present study, we intravenously injected human adipose-derived stem cells (hASCs) that were labeled with a multimodal nanoparticle, LEO-LIVE™-Magnoxide 675 or 797 (BITERIALS, Seoul, Korea), into Tg2576 mice, an AD mouse model. After sequential in vivo tracking using Maestro Imaging System, we found fluorescence signals up to 10 days after injection. We also found strong signals in the brains extracted from hASC-transplanted Tg2576 mice up to 12 days after injection. With these results, we suggest that in vivo imaging with this multimodal nanoparticle may provide a useful tool for stem cell tracking and understanding stem cell biology in other neurodegenerative diseases.

  15. Animal models of cerebral ischemia

    Science.gov (United States)

    Khodanovich, M. Yu.; Kisel, A. A.

    2015-11-01

    Cerebral ischemia remains one of the most frequent causes of death and disability worldwide. Animal models are necessary to understand complex molecular mechanisms of brain damage as well as for the development of new therapies for stroke. This review considers a certain range of animal models of cerebral ischemia, including several types of focal and global ischemia. Since animal models vary in specificity for the human disease which they reproduce, the complexity of surgery, infarct size, reliability of reproduction for statistical analysis, and adequate models need to be chosen according to the aim of a study. The reproduction of a particular animal model needs to be evaluated using appropriate tools, including the behavioral assessment of injury and non-invasive and post-mortem control of brain damage. These problems also have been summarized in the review.

  16. Animal models in peritoneal dialysis

    Science.gov (United States)

    Nikitidou, Olga; Peppa, Vasiliki I.; Leivaditis, Konstantinos; Eleftheriadis, Theodoros; Zarogiannis, Sotirios G.; Liakopoulos, Vassilios

    2015-01-01

    Peritoneal dialysis (PD) has been extensively used over the past years as a method of kidney replacement therapy for patients with end stage renal disease (ESRD). In an attempt to better understand the properties of the peritoneal membrane and the mechanisms involved in major complications associated with PD, such as inflammation, peritonitis and peritoneal injury, both in vivo and ex vivo animal models have been used. The aim of the present review is to briefly describe the animal models that have been used, and comment on the main problems encountered while working with these models. Moreover, the differences characterizing these animal models, as well as, the differences with humans are highlighted. Finally, it is suggested that the use of standardized protocols is a necessity in order to take full advantage of animal models, extrapolate their results in humans, overcome the problems related to PD and help promote its use. PMID:26388781

  17. Animal Models in Peritoneal Dialysis

    Directory of Open Access Journals (Sweden)

    OLGA eNIKITIDOU

    2015-09-01

    Full Text Available Peritoneal dialysis (PD has been extensively used over the past years as a method of kidney replacement therapy for patients with end stage renal disease. In an attempt to better understand the properties of the peritoneal membrane and the mechanisms involved in major complications associated with PD, such as inflammation, peritonitis and peritoneal injury, both in vivo and ex vivo animal models have been used. The aim of the present review is to briefly describe the animal models that have been used, and comment on the main problems encountered while working with these models. Moreover, the differences characterizing these animal models, as well as, the differences with humans are highlighted. Finally, it is suggested that the use of standardized protocols is a necessity in order to take full advantage of animal models, extrapolate their results in humans, overcome the problems related to PD and help promote its use.

  18. Experimental Animal Models of Pancreatic Carcinogenesis for Prevention Studies and Their Relevance to Human Disease

    International Nuclear Information System (INIS)

    Pancreatic cancer is difficult to cure, so its prevention is very important. For this purpose, animal model studies are necessary to develop effective methods. Injection of N-nitrosobis(2-oxopropyl)amine (BOP) into Syrian golden hamsters is known to induce pancreatic ductal adenocarcinomas, the histology of which is similar to human tumors. Moreover, K-ras activation by point mutations and p16 inactivation by aberrant methylation of 5′ CpG islands or by homozygous deletions have been frequently observed in common in both the hamster and humans. Thus, this chemical carcinogenesis model has an advantage of histopathological and genetic similarity to human pancreatic cancer, and it is useful to study promotive and suppressive factors. Syrian golden hamsters are in a hyperlipidemic state even under normal dietary conditions, and a ligand of peroxizome proliferator-activated receptor gamma was found to improve the hyperlipidemia and suppress pancreatic carcinogenesis. Chronic inflammation is a known important risk factor, and selective inhibitors of inducible nitric oxide synthase and cyclooxygenase-2 also have protective effects against pancreatic cancer development. Anti-inflammatory and anti-hyperlipidemic agents can thus be considered candidate chemopreventive agents deserving more attention

  19. Experimental Animal Models of Pancreatic Carcinogenesis for Prevention Studies and Their Relevance to Human Disease

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Mami, E-mail: mtakahas@ncc.go.jp; Hori, Mika; Mutoh, Michihiro [Division of Cancer Development System, Carcinogenesis Research Group, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045 (Japan); Wakabayashi, Keiji [Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Yada 52-1, Suruga-ku, Shizuoka 422-8526 (Japan); Nakagama, Hitoshi [Division of Cancer Development System, Carcinogenesis Research Group, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045 (Japan)

    2011-02-09

    Pancreatic cancer is difficult to cure, so its prevention is very important. For this purpose, animal model studies are necessary to develop effective methods. Injection of N-nitrosobis(2-oxopropyl)amine (BOP) into Syrian golden hamsters is known to induce pancreatic ductal adenocarcinomas, the histology of which is similar to human tumors. Moreover, K-ras activation by point mutations and p16 inactivation by aberrant methylation of 5′ CpG islands or by homozygous deletions have been frequently observed in common in both the hamster and humans. Thus, this chemical carcinogenesis model has an advantage of histopathological and genetic similarity to human pancreatic cancer, and it is useful to study promotive and suppressive factors. Syrian golden hamsters are in a hyperlipidemic state even under normal dietary conditions, and a ligand of peroxizome proliferator-activated receptor gamma was found to improve the hyperlipidemia and suppress pancreatic carcinogenesis. Chronic inflammation is a known important risk factor, and selective inhibitors of inducible nitric oxide synthase and cyclooxygenase-2 also have protective effects against pancreatic cancer development. Anti-inflammatory and anti-hyperlipidemic agents can thus be considered candidate chemopreventive agents deserving more attention.

  20. In vitro validation of bioluminescent monitoring of disease progression and therapeutic response in leukaemia model animals

    International Nuclear Information System (INIS)

    The application of in vivo bioluminescence imaging to non-invasive, quantitative monitoring of tumour models relies on a positive correlation between the intensity of bioluminescence and the tumour burden. We conducted cell culture studies to investigate the relationship between bioluminescent signal intensity and viable cell numbers in murine leukaemia model cells. Interleukin-3 (IL-3)-dependent murine pro-B cell line Ba/F3 was transduced with firefly luciferase to generate cells expressing luciferase stably under the control of a retroviral long terminal repeat. The luciferase-expressing cells were transduced with p190 BCR-ABL to give factor-independent proliferation. The cells were cultured under various conditions, and bioluminescent signal intensity was compared with viable cell numbers and the cell cycle stage. The Ba/F3 cells showed autonomous growth as well as stable luciferase expression following transduction with both luciferase and p190 BCR-ABL, and in vivo bioluminescence imaging permitted external detection of these cells implanted into mice. The bioluminescence intensities tended to reflect cell proliferation and responses to imatinib in cell culture studies. However, the luminescence per viable cell was influenced by the IL-3 concentration in factor-dependent cells and by the stage of proliferation and imatinib concentration in factor-independent cells, thereby impairing the proportionality between viable cell number and bioluminescent signal intensity. Luminescence per cell tended to vary in association with the fraction of proliferating cells. Although in vivo bioluminescence imaging would allow non-invasive monitoring of leukaemia model animals, environmental factors and therapeutic interventions may cause some discrepancies between tumour burden and bioluminescence intensity. (orig.)

  1. In vitro validation of bioluminescent monitoring of disease progression and therapeutic response in leukaemia model animals

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Yusuke; Okubo, Toshiyuki [University of Tokyo, Department of Radiology, Institute of Medical Science, Tokyo (Japan); Tojo, Arinobu; Sekine, Rieko; Soda, Yasushi; Kobayashi, Seiichiro; Nomura, Akiko; Izawa, Kiyoko [University of Tokyo, Division of Molecular Therapy, Advanced Clinical Research Centre, Tokyo (Japan); Kitamura, Toshio [University of Tokyo, Division of Cellular Therapy, Advanced Clinical Research Centre, Tokyo (Japan); Ohtomo, Kuni [University of Tokyo, Department of Radiology, Graduate School of Medicine, Tokyo (Japan)

    2006-05-15

    The application of in vivo bioluminescence imaging to non-invasive, quantitative monitoring of tumour models relies on a positive correlation between the intensity of bioluminescence and the tumour burden. We conducted cell culture studies to investigate the relationship between bioluminescent signal intensity and viable cell numbers in murine leukaemia model cells. Interleukin-3 (IL-3)-dependent murine pro-B cell line Ba/F3 was transduced with firefly luciferase to generate cells expressing luciferase stably under the control of a retroviral long terminal repeat. The luciferase-expressing cells were transduced with p190 BCR-ABL to give factor-independent proliferation. The cells were cultured under various conditions, and bioluminescent signal intensity was compared with viable cell numbers and the cell cycle stage. The Ba/F3 cells showed autonomous growth as well as stable luciferase expression following transduction with both luciferase and p190 BCR-ABL, and in vivo bioluminescence imaging permitted external detection of these cells implanted into mice. The bioluminescence intensities tended to reflect cell proliferation and responses to imatinib in cell culture studies. However, the luminescence per viable cell was influenced by the IL-3 concentration in factor-dependent cells and by the stage of proliferation and imatinib concentration in factor-independent cells, thereby impairing the proportionality between viable cell number and bioluminescent signal intensity. Luminescence per cell tended to vary in association with the fraction of proliferating cells. Although in vivo bioluminescence imaging would allow non-invasive monitoring of leukaemia model animals, environmental factors and therapeutic interventions may cause some discrepancies between tumour burden and bioluminescence intensity. (orig.)

  2. Animal models of schizophrenia

    OpenAIRE

    Jones, CA; Watson, DJG; Fone, KCF

    2011-01-01

    Developing reliable, predictive animal models for complex psychiatric disorders, such as schizophrenia, is essential to increase our understanding of the neurobiological basis of the disorder and for the development of novel drugs with improved therapeutic efficacy. All available animal models of schizophrenia fit into four different induction categories: developmental, drug-induced, lesion or genetic manipulation, and the best characterized examples of each type are reviewed herein. Most rod...

  3. Mitochondrial Dysfunction Contributes to Hypertensive Target Organ Damage: Lessons from an Animal Model of Human Disease

    Science.gov (United States)

    Stanzione, Rosita; Volpe, Massimo

    2016-01-01

    Mechanisms underlying hypertensive target organ damage (TOD) are not completely understood. The pathophysiological role of mitochondrial oxidative stress, resulting from mitochondrial dysfunction, in development of TOD is unclear. The stroke-prone spontaneously hypertensive rat (SHRSP) is a suitable model of human hypertension and of its vascular consequences. Pathogenesis of TOD in SHRSP is multifactorial, being determined by high blood pressure levels, high salt/low potassium diet, and genetic factors. Accumulating evidence points to a key role of mitochondrial dysfunction in increased susceptibility to TOD development of SHRSP. Mitochondrial abnormalities were described in both heart and brain of SHRSP. Pharmacological compounds able to protect mitochondrial function exerted a significant protective effect on TOD development, independently of blood pressure levels. Through our research efforts, we discovered that two genes encoding mitochondrial proteins, one (Ndufc2) involved in OXPHOS complex I assembly and activity and the second one (UCP2) involved in clearance of mitochondrial ROS, are responsible, when dysregulated, for vascular damage in SHRSP. The suitability of SHRSP as a model of human disease represents a promising background for future translation of the experimental findings to human hypertension. Novel therapeutic strategies toward mitochondrial molecular targets may become a valuable tool for prevention and treatment of TOD in human hypertension. PMID:27594970

  4. Renal depletion of myo-inositol is associated with its increased degradation in animal models of metabolic disease.

    Science.gov (United States)

    Chang, H-H; Chao, H-N; Walker, C S; Choong, S-Y; Phillips, A; Loomes, K M

    2015-11-01

    Renal depletion of myo-inositol (MI) is associated with the pathogenesis of diabetic nephropathy in animal models, but the underlying mechanisms involved are unclear. We hypothesized that MI depletion was due to changes in inositol metabolism and therefore examined the expression of genes regulating de novo biosynthesis, reabsorption, and catabolism of MI. We also extended the analyses from diabetes mellitus to animal models of dietary-induced obesity and hypertension. We found that renal MI depletion was pervasive across these three distinct disease states in the relative order: hypertension (-51%)>diabetes mellitus (-35%)>dietary-induced obesity (-19%). In 4-wk diabetic kidneys and in kidneys derived from insulin-resistant and hypertensive rats, MI depletion was correlated with activity of the MI-degrading enzyme myo-inositol oxygenase (MIOX). By contrast, there was decreased MIOX expression in 8-wk diabetic kidneys. Immunohistochemistry localized the MI-degrading pathway comprising MIOX and the glucuronate-xylulose (GX) pathway to the proximal tubules within the renal cortex. These findings indicate that MI depletion could reflect increased catabolism through MIOX and the GX pathway and implicate a common pathological mechanism contributing to renal oxidative stress in metabolic disease. PMID:26311112

  5. Animal models of tinnitus.

    Science.gov (United States)

    Brozoski, Thomas J; Bauer, Carol A

    2016-08-01

    Presented is a thematic review of animal tinnitus models from a functional perspective. Chronic tinnitus is a persistent subjective sound sensation, emergent typically after hearing loss. Although the sensation is experientially simple, it appears to have central a nervous system substrate of unexpected complexity that includes areas outside of those classically defined as auditory. Over the past 27 years animal models have significantly contributed to understanding tinnitus' complex neurophysiology. In that time, a diversity of models have been developed, each with its own strengths and limitations. None has clearly become a standard. Animal models trace their origin to the 1988 experiments of Jastreboff and colleagues. All subsequent models derive some of their features from those experiments. Common features include behavior-dependent psychophysical determination, acoustic conditions that contrast objective sound and silence, and inclusion of at least one normal-hearing control group. In the present review, animal models have been categorized as either interrogative or reflexive. Interrogative models use emitted behavior under voluntary control to indicate hearing. An example would be pressing a lever to obtain food in the presence of a particular sound. In this type of model animals are interrogated about their auditory sensations, analogous to asking a patient, "What do you hear?" These models require at least some training and motivation management, and reflect the perception of tinnitus. Reflexive models, in contrast, employ acoustic modulation of an auditory reflex, such as the acoustic startle response. An unexpected loud sound will elicit a reflexive motor response from many species, including humans. Although involuntary, acoustic startle can be modified by a lower-level preceding event, including a silent sound gap. Sound-gap modulation of acoustic startle appears to discriminate tinnitus in animals as well as humans, and requires no training or

  6. Animal models of ADHD.

    Science.gov (United States)

    Bari, A; Robbins, T W

    2011-01-01

    Studies employing animal models of attention-deficit/hyperactivity disorder (ADHD) present clear inherent advantages over human studies. Animal models are invaluable tools for the study of underlying neurochemical, neuropathological and genetic alterations that cause ADHD, because they allow relatively fast, rigorous hypothesis testing and invasive manipulations as well as selective breeding. Moreover, especially for ADHD, animal models with good predictive validity would allow the assessment of potential new therapeutics. In this chapter, we describe and comment on the most frequently used animal models of ADHD that have been created by genetic, neurochemical and physical alterations in rodents. We then discuss that an emerging and promising direction of the field is the analysis of individual behavioural differences among a normal population of animals. Subjects presenting extreme characteristics related to ADHD can be studied, thereby avoiding some of the problems that are found in other models, such as functional recovery and unnecessary assumptions about aetiology. This approach is justified by the theoretical need to consider human ADHD as the extreme part of a spectrum of characteristics that are distributed normally in the general population, as opposed to the predominant view of ADHD as a separate pathological category. PMID:21287324

  7. Concomitant Astroglial Atrophy and Astrogliosis in a Triple Transgenic Animal Model of Alzheimer's Disease

    Czech Academy of Sciences Publication Activity Database

    Olabarria, M.; Noristani, H. N.; Verkhratsky, Alexei; Rodríguez Arellano, Jose Julio

    2010-01-01

    Roč. 58, č. 7 (2010), s. 831-838. ISSN 0894-1491 Institutional research plan: CEZ:AV0Z50390703 Keywords : astroglia * Alzheimer's disease * hippocampus Subject RIV: FH - Neurology Impact factor: 5.186, year: 2010

  8. Dental Disease and Bisphosphonates Induce Osteonecrosis of the Jaws in Animal Models

    OpenAIRE

    Kang, Benjamin

    2012-01-01

    Bisphosphonates (BPs) have been used clinically for over 30 years to treat postmenopausal osteoporosis, hypercalcemia of malignancy and metabolic bone diseases. Although the use of BPs have been beneficial for these pathologies, several recent reports have linked BP usage to osteonecrosis of the jaw. A common factor amongst these case reports suggests a significant link of dental disease and bisphosphonate treatment in the development of bisphosphonate related osteonecrosis of the jaw (BRONJ...

  9. Inhibition of fatty acid metabolism ameliorates disease activity in an animal model of multiple sclerosis

    OpenAIRE

    Shriver, Leah P.; Manchester, Marianne

    2011-01-01

    Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system and a leading cause of neurological disability. The complex immunopathology and variable disease course of multiple sclerosis have limited effective treatment of all patients. Altering the metabolism of immune cells may be an attractive strategy to modify their function during autoimmunity. We examined the effect of inhibiting fatty acid metabolism in experimental autoimmune encephalomyelitis (EAE), a mo...

  10. Research progress in animal models and stem cell therapy for Alzheimer’s disease

    OpenAIRE

    Han F; Wang W.; Chen C

    2014-01-01

    Fabin Han,1,2 Wei Wang1, Chao Chen1 1Centre for Stem Cells and Regenerative Medicine, 2Department of Neurology, Liaocheng People’s Hospital/The Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People’s Republic of China Abstract: Alzheimer’s disease (AD) causes degeneration of brain neurons and leads to memory loss and cognitive impairment. Since current therapeutic strategies cannot cure the disease, stem cell therapy represents a powerful tool for the ...

  11. Animal models of cardiac cachexia.

    Science.gov (United States)

    Molinari, Francesca; Malara, Natalia; Mollace, Vincenzo; Rosano, Giuseppe; Ferraro, Elisabetta

    2016-09-15

    Cachexia is the loss of body weight associated with several chronic diseases including chronic heart failure (CHF). The cachectic condition is mainly due to loss of skeletal muscle mass and adipose tissue depletion. The majority of experimental in vivo studies on cachexia rely on animal models of cancer cachexia while a reliable and appropriate model for cardiac cachexia has not yet been established. A critical issue in generating a cardiac cachexia model is that genetic modifications or pharmacological treatments impairing the heart functionality and used to obtain the heart failure model might likely impair the skeletal muscle, this also being a striated muscle and sharing with the myocardium several molecular and physiological mechanisms. On the other hand, often, the induction of heart damage in the several existing models of heart failure does not necessarily lead to skeletal muscle loss and cachexia. Here we describe the main features of cardiac cachexia and illustrate some animal models proposed for cardiac cachexia studies; they include the genetic calsequestrin and Dahl salt-sensitive models, the monocrotaline model and the surgical models obtained by left anterior descending (LAD) ligation, transverse aortic constriction (TAC) and ascending aortic banding. The availability of a specific animal model for cardiac cachexia is a crucial issue since, besides the common aspects of cachexia in the different syndromes, each disease has some peculiarities in its etiology and pathophysiology leading to cachexia. Such peculiarities need to be unraveled in order to find new targets for effective therapies. PMID:27317993

  12. Cytokines and Cytokine Profiles in Human Autoimmune Diseases and Animal Models of Autoimmunity

    Directory of Open Access Journals (Sweden)

    Manfred Kunz

    2009-01-01

    Full Text Available The precise pathomechanisms of human autoimmune diseases are still poorly understood. However, a deepened understanding of these is urgently needed to improve disease prevention and early detection and guide more specific treatment approaches. In recent years, many new genes and signalling pathways involved in autoimmunity with often overlapping patterns between different disease entities have been detected. Major contributions were made by experiments using DNA microarray technology, which has been used for the analysis of gene expression patterns in chronic inflammatory and autoimmune diseases, among which were rheumatoid arthritis, systemic lupus erythematosus, psoriasis, systemic sclerosis, multiple sclerosis, and type-1 diabetes. In systemic lupus erythematosus, a so-called interferon signature has been identified. In psoriasis, researchers found a particular immune signalling cluster. Moreover the identification of a new subset of inflammatory T cells, so-called Th17 T cells, secreting interleukin (IL-17 as one of their major cytokines and the identification of the IL-23/IL-17 axis of inflammation regulation, have significantly improved our understanding of autoimmune diseases. Since a plethora of new treatment approaches using antibodies or small molecule inhibitors specifically targeting cytokines, cellular receptors, or signalling mechanisms has emerged in recent years, more individualized treatment for affected patients may be within reach in the future.

  13. First Siena International Conference on Animal Models of Chronic Obstructive Pulmonary Disease, Certosa di Pontignano, University of Siena, Italy, September 30-October 2, 2001

    OpenAIRE

    Hele David

    2002-01-01

    Abstract The meeting proved of great interest to those developing an animal model of chronic obstructive pulmonary disease (COPD). COPD is caused by cigarette smoking, evidenced by deterioration in lung function. Lung function is only rarely assessed in animal models. A cigarette smoke driven pathology should provide the best in vivo model for COPD. However, as lesions produced this way take 8–12 months to develop other strategies have to be employed. Emphysematous lesions were also ...

  14. Detecting inflammation and fibrosis in bowel wall with photoacoustic imaging in a Crohn's disease animal model

    Science.gov (United States)

    Xu, Guan; Johnson, Laura A.; Hu, Jack; Dillman, Jonathan R.; Higgins, Peter D. R.; Wang, Xueding

    2015-03-01

    Crohn's disease (CD) is an autoimmune disease affecting 700,000 people in the United States. This condition may cause obstructing intestinal narrowings (strictures) due to inflammation, fibrosis (deposition of collagen), or a combination of both. Utilizing the unique strong optical absorption of hemoglobin at 532 nm and collagen at 1370 nm, this study investigated the feasibility of non-invasively characterizing intestinal strictures using photoacoustic imaging (PAI). Three normal controls, ten pure inflammation and 9 inflammation plus fibrosis rat bowel wall samples were imaged. Statistical analysis of the PA measurements has shown the capability of discriminating the purely inflammatory from mixed inflammatory and fibrotic strictures.

  15. Successful therapies for Alzheimer’s disease: Why so many in animal models and none in humans?

    Directory of Open Access Journals (Sweden)

    Rafael eFranco

    2014-06-01

    Full Text Available Peering into the field of Alzheimer's disease (AD the outsider realizes that many of the therapeutic strategies tested (in animal models have been successful. One also may notice that there is a deficit in translational research, i.e. to take a successful drug in mice and translate it to the patient. Efforts are still focused on novel projects to expand the therapeutic arsenal to cure mice. Scientific reasons behind so many successful strategies are not obvious. This article aims to review the current approaches to combat AD, and to open a debate on common mechanisms of cognitive enhancement and neuroprotection. In short, either the rodent models are not good and should be discontinued, or we should extract only the most useful information from those models. An example of a question that may be debated for the advancement in AD therapy is: In addition to reducing amyloid and tau pathologies, would it be necessary to boost synaptic strength and cognition? The debate would provide helpful information that could turn around the current negative output in generating effective drugs for patients. Furthermore, discovery of biomarkers in human body fluids, and a clear distinction between cognitive enhancers and disease modifying strategies, should be instrumental for advancing in anti-AD drug discovery.

  16. Minipig as a large animal model for Huntington´s disease study

    Czech Academy of Sciences Publication Activity Database

    Juhás, Štefan; Juhásová, Jana; Vochozková, Petra; Klíma, Jiří; Bohuslavová, Božena; Recek, L.; Howland, D. S.; Motlík, Jan

    Milan : FENS, 2014. s. 1463-1463. [FENS Forum of Neuroscience /9./. 05.07.2014-09.07.2014, Milan] R&D Projects: GA TA ČR(CZ) TA01011466; GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : Huntington ´s disease Subject RIV: FH - Neurology

  17. Animal models of asthma

    OpenAIRE

    Akkoç, Tunç

    2014-01-01

    ABSTRACT: Allergic disease such as asthma, rhinitis, and eczema are increasing prevelanceand affect up to 15% of population in Westernized countries. Among them, asthma is achronic inflammatory disease of airways and the underlying physiological and immunologicalprocesses are not fully understood. Mouse models of asthma dupicates many featuresof human asthma, including airway hyperreactivity, andairway inflammation. Therefore, relevantmodels for asthma are important to understand the mechanis...

  18. Defining the potential for cell therapy for vascular disease using animal models

    OpenAIRE

    Gulati, Rajiv; Simari, Robert D.

    2009-01-01

    Cell-based therapeutics are currently being developed for a wide array of unmet medical needs. As obstructive vascular disease is the major cause of mortality in the world, cell-based strategies aimed at developing novel therapies or improving current therapies are currently under study. These studies are based on the evolving understanding of the biology of vascular progenitor cells, which has in turn led to the availability of well-defined sources of vascular cells for delivery. Crucial to ...

  19. Lavandula angustifolia extract improves deteriorated synaptic plasticity in an animal model of Alzheimer’s disease

    OpenAIRE

    Masoud Soheili; Mostafa Rezaei Tavirany; Mahmoud Salami

    2015-01-01

    Objective(s): Neurodegenerative Alzheimer’s disease (AD) is associated with profound deficits in synaptic transmission and synaptic plasticity. Long-term potentiation (LTP), an experimental form of synaptic plasticity, is intensively examined in hippocampus. In this study we evaluated the effect of aqueous extract of lavender (Lavandula angustifolia) on induction of LTP in the CA1 area of hippocampus. In response to stimulation of the Schaffer collaterals the baseline or tetanized field extra...

  20. Proteomic Profiling of Animal Models of Myotonia and Motor Neuron Disease

    OpenAIRE

    STAUNTON, LISA

    2011-01-01

    Skeletal muscle provides an organism with a means of reacting to its environments. It is a complex and versatile tissue that is capable of change under a variety of conditions. For example extensive literature has shown muscle transformation from slow-to-fast by decreased motor nerve activity, hypogravity, physical inactivity and in diseased states. Similarly muscle transformation from fast-to-slow can be evoked by increased muscle nerve activity or exercise. The multitude of protein changes ...

  1. Spinal Cord Stimulation Restores Locomotion in Animal Models of Parkinson’s disease1

    OpenAIRE

    Fuentes, Romulo; Petersson, Per; Siesser, William B.; Caron, Marc G.; Nicolelis, Miguel A. L.

    2009-01-01

    Dopamine replacement therapy is useful for treating motor symptoms in the early phase of Parkinson’s disease, but is less effective in the long-term. Electrical deep-brain stimulation is a valuable complement to pharmacological treatment but involves a highly invasive surgical procedure. We found that epidural electrical stimulation of the dorsal columns in the spinal cord restores locomotion in both acute pharmacologically induced dopamine-depleted mice and in chronic 6-hydroxydopamine lesio...

  2. Gene Therapy for Lysosomal Storage Diseases (LSDs) in Large Animal Models

    OpenAIRE

    Haskins, Mark

    2009-01-01

    Lysosomal storage diseases (LSDs) are inherited metabolic disorders caused by deficient activity of a single lysosomal enzyme or other defects resulting in deficient catabolism of large substrates in lysosomes. There are more than 40 forms of inherited LSDs known to occur in humans, with an aggregate incidence estimated at 1 in 7,000 live births. Clinical signs result from the inability of lysosomes to degrade large substrates; because most lysosomal enzymes are ubiquitously expressed, a defi...

  3. Early astrocytic atrophy in the entorhinal cortex of a triple transgenic animal model of Alzheimer's disease.

    Czech Academy of Sciences Publication Activity Database

    Yeh, C. Y.; Vadhwana, B.; Verkhratsky, Alexei; Rodríguez Arellano, Jose Julio

    2011-01-01

    Roč. 3, č. 5 (2011), e00071. ISSN 1759-0914 R&D Projects: GA ČR GA309/09/1696; GA ČR(CZ) GAP304/11/0184; GA ČR GA305/08/1384; GA ČR GA309/08/1381 Institutional research plan: CEZ:AV0Z50390703 Keywords : Alzheimer's disease * astrocyte * dementia Subject RIV: FH - Neurology Impact factor: 3.750, year: 2011

  4. Design of an advanced positron emission tomography detector system and algorithms for imaging small animal models of human disease

    Science.gov (United States)

    Foudray, Angela Marie Klohs

    Detecting, quantifying and visualizing biochemical mechanism in a living system without perturbing function is the goal of the instrument and algorithms designed in this thesis. Biochemical mechanisms of cells have long been known to be dependent on the signals they receive from their environment. Studying biological processes of cells in-vitro can vastly distort their function, since you are removing them from their natural chemical signaling environment. Mice have become the biological system of choice for various areas of biomedical research due to their genetic and physiological similarities with humans, the relatively low cost of their care, and their quick breeding cycle. Drug development and efficacy assessment along with disease detection, management, and mechanism research all have benefited from the use of small animal models of human disease. A high resolution, high sensitivity, three-dimensional (3D) positioning positron emission tomography (PET) detector system was designed through device characterization and Monte Carlo simulation. Position-sensitive avalanche photodiodes (PSAPDs) were characterized in various packaging configurations; coupled to various configurations of lutetium oxyorthosilicate (LSO) scintillation crystals. Forty novelly packaged final design devices were constructed and characterized, each providing characteristics superior to commercially available scintillation detectors used in small animal imaging systems: ˜1mm crystal identification, 14-15% of 511 keV energy resolution, and averaging 1.9 to 5.6 ns coincidence time resolution. A closed-cornered box-shaped detector configuration was found to provide optimal photon sensitivity (˜10.5% in the central plane) using dual LSO-PSAPD scintillation detector modules and Monte Carlo simulation. Standard figures of merit were used to determine optimal system acquisition parameters. A realistic model for constituent devices was developed for understanding the signals reported by the

  5. Animal models of disease: classification and etiology of diabetes in dogs and cats

    OpenAIRE

    R. W. Nelson; Reusch, C.E.

    2014-01-01

    Diabetes mellitus is a common disease in dogs and cats. The most common form of diabetes in dogs resembles type 1 diabetes in humans. Studies suggest that genetics, an immune-mediated component, and environmental factors are involved in the development of diabetes in dogs. A variant of gestational diabetes also occurs in dogs. The most common form of diabetes in cats resembles type 2 diabetes in humans. A major risk factor in cats is obesity. Obese cats have altered expression of several insu...

  6. Genetic animal models for evaluating the role of autophagy in etiopathogenesis of Parkinson disease.

    Science.gov (United States)

    Lachenmayer, M Lenard; Yue, Zhenyu

    2012-12-01

    Parkinson disease (PD) is the most common neurodegenerative movement disorder and is characterized pathologically by the formation of ubiquitin and SNCA/α-synuclein-containing inclusions (Lewy bodies), dystrophic midbrain dopaminergic (DAergic) terminals, and degeneration of midbrain DAergic neurons. The vast majority of PD occurs sporadically, while approximately 5% of all PD cases are inherited. Genetic mutations of a few genes have been identified as causes of familiar PD, i.e., mutations in SNCA, PARK2/parkin, UCHL1, PARK7/DJ1, PINK1 and LRRK2, leading to DAergic cell death, but variable pathological changes. The evidence supports the hypothesis that several pathogenic mechanisms are likely involved at initial stages of the disease, and eventually they merge to cause parkinsonism. The current challenge facing PD research is to unravel the components in these pathways that contribute to the pathogenesis of PD. Accumulating evidence has implicated dysfunctional autophagy, a regulated lysosomal pathway with a capacity for clearing protein aggregates and cellular organelles, as one of the pathogenic systems contributing to the development of idiopathic PD. PMID:22931754

  7. Mitoapocynin Treatment Protects Against Neuroinflammation and Dopaminergic Neurodegeneration in a Preclinical Animal Model of Parkinson’s Disease

    Science.gov (United States)

    Ghosh, Anamitra; Langley, Monica R; Harischandra, Dilshan; Neal, Matthew L; Jin, Huajun; Anantharam, Vellareddy; Joseph, Joy; Brenza, Timothy; Narasimhan, Balaji; Kanthasamy, Arthi; Kalyanaraman, Balaraman; Kanthasamy, Anumantha G.

    2016-01-01

    Mitochondrial dysfunction, oxidative stress and neuroinflammation have been implicated as key mediators contributing to the progressive degeneration of dopaminergic neurons in Parkinson’s disease (PD). Currently, we lack a pharmacological agent that can intervene in all key pathological mechanisms, which would offer better neuroprotective efficacy than a compound that targets a single degenerative mechanism. Herein, we investigated whether mito-apocynin (Mito-Apo), a newly-synthesized and orally available derivative of apocynin that targets mitochondria, protects against oxidative damage, glial-mediated inflammation and nigrostriatal neurodegeneration in cellular and animal models of PD. Mito-Apo treatment in primary mesencephalic cultures significantly attenuated the 1-methyl-4-phenylpyridinium (MPP+)-induced loss of tyrosine hydroxylase (TH)-positive neuronal cells and neurites. Mito-Apo also diminished MPP+-induced increases in glial cell activation and inducible nitric oxide synthase (iNOS) expression. Additionally, Mito-Apo decreased nitrotyrosine (3-NT) and 4-hydroxynonenol (4-HNE) levels in primary mesencephalic cultures. Importantly, we assessed the neuroprotective property of Mito-Apo in the MPTP mouse model of PD, wherein it restored the behavioral performance of MPTP-treated mice. Immunohistological analysis of nigral dopaminergic neurons and monoamine measurement further confirmed the neuroprotective effect of Mito-Apo against MPTP-induced nigrostriatal dopaminergic neuronal loss. Mito-Apo showed excellent brain bioavailability and also markedly attenuated MPTP-induced oxidative markers in the substantia nigra (SN). Furthermore, oral administration of Mito-Apo significantly suppressed MPTP-induced glial cell activation, upregulation of proinflammatory cytokines, iNOS and gp91phox in IBA1-positive cells of SN. Collectively, these results demonstrate that the novel mitochondria-targeted compound Mito-Apo exhibits profound neuroprotective effects in

  8. Animal models of sepsis

    OpenAIRE

    Fink, Mitchell P.

    2013-01-01

    Sepsis remains a common, serious, and heterogeneous clinical entity that is difficult to define adequately. Despite its importance as a public health problem, efforts to develop and gain regulatory approval for a specific therapeutic agent for the adjuvant treatment of sepsis have been remarkably unsuccessful. One step in the critical pathway for the development of a new agent for adjuvant treatment of sepsis is evaluation in an appropriate animal model of the human condition. Unfortunately, ...

  9. Ligustrazine phosphate ethosomes for treatment of Alzheimer's disease, in vitro and in animal model studies.

    Science.gov (United States)

    Shi, Jun; Wang, Yiming; Luo, Guoan

    2012-06-01

    In the present study, we have investigated transdermal administration of ligustrazine phosphate (LP), as an antioxidant, for the treatment of Alzheimer's disease (AD). The LP transdermal ethosomal system was designed and characterized. Franz-type diffusion cells and confocal laser scanning microscopy were used for the in vitro permeation studies. Furthermore, the effect of LP transdermal ethosomal system on AD was evaluated in the scopolamine-induced amnesia rats by evaluating the behavioral performance in the Morris water maze test. The activities of the antioxidant enzymes and the levels of the lipid peroxidation product malondialdehyde (MDA) in the brain of rats were also determined. The results showed that both the penetration ability and the drug deposition in skin of the LP ethosomal system were significantly higher than the aqueous one. The LP transdermal ethosomal system could recover the activities of the antioxidant enzymes and the levels of MDA in the brain of the amnesic rats to the similar status of the normal rats, which was also indirectly reflected by the improvement in the behavioral performance. In conclusion, LP might offer a potential alternative therapeutic drug in the fight against AD, and ethosomes could be vesicles of choice for transdermal delivery of LP. PMID:22415639

  10. Animal Models for Vascular Tissue-Engineering

    OpenAIRE

    Swartz, Daniel D.; Andreadis, Stelios T.

    2013-01-01

    Due to rise in cardiovascular disease throughout the world, there is increasing demand for small diameter blood vessels as replacement grafts. The present review focuses on the animal models that have been used to test small-diameter TEVs with emphasis on the attributes of each model. Small animal models are used to test short-term patency and address mechanistic hypotheses; and large, pre-clinical animal models are employed to test long-term patency, remodeling and function in an environment...

  11. The implications of oxidative stress and antioxidant therapies in Inflammatory Bowel Disease: Clinical aspects and animal models

    Directory of Open Access Journals (Sweden)

    Ioana Miruna Balmus

    2016-01-01

    Full Text Available Inflammatory bowel disease (IBD, including Crohn′s disease (CD and ulcerative colitis (UC, is a chronic inflammatory disorder characterized by alternating phases of clinical relapse and remission. The etiology of IBD remains largely unknown, although a combination of patient′s immune response, genetics, microbiome, and environment plays an important role in disturbing intestinal homeostasis, leading to development and perpetuation of the inflammatory cascade in IBD. As chronic intestinal inflammation is associated with the formation of reactive oxygen and reactive nitrogen species (ROS and RNS, oxidative and nitrosative stress has been proposed as one of the major contributing factor in the IBD development. Substantial evidence suggests that IBD is associated with an imbalance between increased ROS and decreased antioxidant activity, which may explain, at least in part, many of the clinical pathophysiological features of both CD and UC patients. Hereby, we review the presently known oxidant and antioxidant mechanisms involved in IBD-specific events, the animal models used to determine these specific features, and also the antioxidant therapies proposed in IBD patients.

  12. Inflammatory Animal Model for Parkinson's Disease: The Intranigral Injection of LPS Induced the Inflammatory Process along with the Selective Degeneration of Nigrostriatal Dopaminergic Neurons

    OpenAIRE

    Machado, A.; A. J. Herrera; J. L. Venero; Santiago, M; De Pablos, R. M.; R. F. Villarán; Espinosa-Oliva, A. M.; S. Argüelles; Sarmiento, M.; M. J. Delgado-Cortés; R. Mauriño; Cano, J.

    2011-01-01

    We have developed an animal model of degeneration of the nigrostriatal dopaminergic neurons, the neuronal system involved in Parkinson's disease (PD). The implication of neuroinflammation on this disease was originally established in 1988, when the presence of activated microglia in the substantia nigra (SN) of parkinsonians was reported by McGeer et al. Neuroinflammation could be involved in the progression of the disease or even has more direct implications. We injected 2 μg of the potent p...

  13. Modeling animal landscapes.

    Science.gov (United States)

    Porter, W P; Ostrowski, S; Williams, J B

    2010-01-01

    There is an increasing need to assess the effects of climate and land-use change on habitat quality, ideally from a mechanistic basis. The symposium "Molecules to Migration: Pressures of Life" at the Fourth International Conference in Africa for Comparative Physiology and Biochemistry, Maasai Mara National Reserve, Kenya, 2008, illustrated how the principles of biophysical ecology can capture the mechanistic links between organisms, climate, and other habitat features. These principles provide spatially explicit assessments of habitat quality from a physiological perspective (i.e., "animal landscapes") that can be validated independently of the data used to derive and parameterize them. The contents of this symposium showcased how the modeling of animal landscapes can be used to assess key issues in applied and theoretical ecology. The presentations included applications to amphibians, reptiles, birds, and mammals. The rare Arabian oryx on the Arabian Peninsula is used as an example for energetic calculations and their implications for behavior on the landscape. PMID:20670170

  14. Investigation of proteolytic enzymes expression in brain tissue and cultivated retinal pigment epithelial cells at transgenic animal model of Hintington´s disease

    Czech Academy of Sciences Publication Activity Database

    Ardan, Taras; Kocurová, Gabriela; Motlík, Jan

    2015-01-01

    Roč. 78, Suppl 2 (2015), s. 12-12. ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : Huntington´s disease * transgenic porcine model * proteolytic enzymes Subject RIV: EB - Genetics ; Molecular Biology

  15. Animal models of CNS disorders.

    Science.gov (United States)

    McGonigle, Paul

    2014-01-01

    There is intense interest in the development and application of animal models of CNS disorders to explore pathology and molecular mechanisms, identify potential biomarkers, and to assess the therapeutic utility, estimate safety margins and establish pharmacodynamic and pharmacokinetic parameters of new chemical entities (NCEs). This is a daunting undertaking, due to the complex and heterogeneous nature of these disorders, the subjective and sometimes contradictory nature of the clinical endpoints and the paucity of information regarding underlying molecular mechanisms. Historically, these models have been invaluable in the discovery of therapeutics for a range of disorders including anxiety, depression, schizophrenia, and Parkinson's disease. Recently, however, they have been increasingly criticized in the wake of numerous clinical trial failures of NCEs with promising preclinical profiles. These failures have resulted from a number of factors including inherent limitations of the models, over-interpretation of preclinical results and the complex nature of clinical trials for CNS disorders. This review discusses the rationale, strengths, weaknesses and predictive validity of the most commonly used models for psychiatric, neurodegenerative and neurological disorders as well as critical factors that affect the variability and reproducibility of these models. It also addresses how progress in molecular genetics and the development of transgenic animals has fundamentally changed the approach to neurodegenerative disorder research. To date, transgenic animal models\\have not been the panacea for drug discovery that many had hoped for. However continual refinement of these models is leading to steady progress with the promise of eventual therapeutic breakthroughs. PMID:23811310

  16. Interactions between infections and immune-inflammatory cells in type 1 diabetes mellitus and inflammatory bowel diseases: evidences from animal models

    DEFF Research Database (Denmark)

    Claesson, M H; Nicoletti, F; Stosic-Grujicic, S;

    2008-01-01

    models which resemble the phenotype of the human disease they mimic, can be very useful to identify important pathogenetic mechanisms, as well as therapeutical targets to treat the disease. This review is focused on the immune inflammatory pathways which are considered to be associated with the......Type 1 diabetes mellitus (T1D) and inflammatory bowel diseases (IBD) are multifactorial disorders of autoimmune origin.Several microbial agents have been reported to be associated with the development of type 1 diabetes and inflammatory bowel diseases in animal models by different mechanisms. These...

  17. An overview of animal prion diseases.

    Science.gov (United States)

    Imran, Muhammad; Mahmood, Saqib

    2011-01-01

    Prion diseases are transmissible neurodegenerative conditions affecting human and a wide range of animal species. The pathogenesis of prion diseases is associated with the accumulation of aggregates of misfolded conformers of host-encoded cellular prion protein (PrPC). Animal prion diseases include scrapie of sheep and goats, bovine spongiform encephalopathy (BSE) or mad cow disease, transmissible mink encephalopathy, feline spongiform encephalopathy, exotic ungulate spongiform encephalopathy, chronic wasting disease of cervids and spongiform encephalopathy of primates. Although some cases of sporadic atypical scrapie and BSE have also been reported, animal prion diseases have basically occurred via the acquisition of infection from contaminated feed or via the exposure to contaminated environment. Scrapie and chronic wasting disease are naturally sustaining epidemics. The transmission of BSE to human has caused more than 200 cases of variant Cruetzfeldt-Jacob disease and has raised serious public health concerns. The present review discusses the epidemiology, clinical neuropathology, transmissibility and genetics of animal prion diseases. PMID:22044871

  18. Animal models of tuberculosis for vaccine development.

    Science.gov (United States)

    Gupta, U D; Katoch, V M

    2009-01-01

    Animal models for testing different vaccine candidates have been developed since a long time for studying tuberculosis. Mice, guinea pigs and rabbits are animals most frequently used. Each model has its own merits for studying human tuberculosis, and none completely mimics the human disease. Different animal models are being used depending upon the availability of the space, trained manpower as well as other resources. Efforts should continue to develop a vaccine which can replace/outperform the presently available vaccine BCG. PMID:19287053

  19. Development of osteoporosis animal model using micropigs

    OpenAIRE

    Kim, Sang-Woo; Kim, Kyoung-Shim; Solis, Chester D.; Lee, Myeong-Seop; Hyun, Byung-Hwa

    2013-01-01

    Osteoporosis is a known major health problem and a serious disease of the bone, there has been a great need to develop more and newer animal models for this disease. Among animal models used for testing drug efficacy, the minipig model has become useful and effective due to its close similarity with humans (validity), particularly with the pharmacokinetics of compounds via subcutaneous administration, the structure and function of the organs, the morphology of bone and the overall metabolic n...

  20. An overview of animal prion diseases

    OpenAIRE

    Imran Muhammad; Mahmood Saqib

    2011-01-01

    Abstract Prion diseases are transmissible neurodegenerative conditions affecting human and a wide range of animal species. The pathogenesis of prion diseases is associated with the accumulation of aggregates of misfolded conformers of host-encoded cellular prion protein (PrPC). Animal prion diseases include scrapie of sheep and goats, bovine spongiform encephalopathy (BSE) or mad cow disease, transmissible mink encephalopathy, feline spongiform encephalopathy, exotic ungulate spongiform encep...

  1. Animal health: foot-and-mouth disease

    Science.gov (United States)

    Foot-and-mouth disease (FMD) is one of the most contagious viral diseases that can affect cloven-hoofed livestock and wild animals. Outbreaks of FMD have caused devastating economic losses and the slaughter of millions of animals in many regions of the world affecting the food chain and global devel...

  2. The enduring importance of animal modelsin understanding periodontal disease

    OpenAIRE

    Hajishengallis, George; Lamont, Richard J.; Graves, Dana T.

    2015-01-01

    Whereas no single animal model can reproduce the complexity of periodontitis, different aspects of the disease can be addressed by distinct models. Despite their limitations, animal models are essential for testing the biological significance of in vitro findings and for establishing cause-and-effect relationships relevant to clinical observations, which are typically correlative. We provide evidence that animal-based studies have generated a durable framework for dissecting the mechanistic b...

  3. Application of new therapies in Graves' disease and thyroid-associated ophthalmopathy: animal models and translation to human clinical trials

    DEFF Research Database (Denmark)

    Banga, J Paul; Nielsen, Claus H; Gilbert, Jacqueline A;

    2008-01-01

    immunosuppression. The recent development of an induced model of experimental Graves' disease, although incomplete as it lacks the extrathyroidal manifestations, provided opportunities to investigate immune intervention strategies, including influence upon the autoreactive B and T cell players in the autoimmune...... process. These major advances are generating new possibilities for therapeutic interventions for patients with Graves' disease and TAO....

  4. Generalized cerebral atrophy seen on MRI in a naturally exposed animal model for creutzfeldt-jakob disease

    Directory of Open Access Journals (Sweden)

    Dasanu Constantin A

    2010-11-01

    Full Text Available Abstract Background Magnetic resonance imaging has been used in the diagnosis of human prion diseases such as sCJD and vCJD, but patients are scanned only when clinical signs appear, often at the late stage of disease. This study attempts to answer the questions "Could MRI detect prion diseases before clinical symptoms appear?, and if so, with what confidence?" Methods Scrapie, the prion disease of sheep, was chosen for the study because sheep can fit into a human sized MRI scanner (and there were no large animal MRI scanners at the time of this study, and because the USDA had, at the time of the study, a sizeable sample of scrapie exposed sheep, which we were able to use for this purpose. 111 genetically susceptible sheep that were naturally exposed to scrapie were used in this study. Results Our MRI findings revealed no clear, consistent hyperintense or hypointense signal changes in the brain on either clinically affected or asymptomatic positive animals on any sequence. However, in all 37 PrPSc positive sheep (28 asymptomatic and 9 symptomatic, there was a greater ventricle to cerebrum area ratio on MRI compared to 74 PrPSc negative sheep from the scrapie exposed flock and 6 control sheep from certified scrapie free flocks as defined by immunohistochemistry (IHC. Conclusions Our findings indicate that MRI imaging can detect diffuse cerebral atrophy in asymptomatic and symptomatic sheep infected with scrapie. Nine of these 37 positive sheep, including 2 one-year old animals, were PrPSc positive only in lymph tissues but PrPSc negative in the brain. This suggests either 1 that the cerebral atrophy/neuronal loss is not directly related to the accumulation of PrPSc within the brain or 2 that the amount of PrPSc in the brain is below the detectable limits of the utilized immunohistochemistry assay. The significance of these findings remains to be confirmed in human subjects with CJD.

  5. A REVIEW ON ANIMAL MODELS OF DEPRESSION

    OpenAIRE

    Madhu Devi* and Ramica Sharma

    2013-01-01

    As described by the world health organization (WHO), depression is the most common and serious disorder leading to suicide. Numbers of synthetic drugs are available for the treatment of this fatal disease, but are associated with serious complications. A wide diversity of animal models has been used to examine antidepressant activity. These range from relatively simple models sensitive to acute treatment, to highly sophisticated models. The number of validated animal models for affective diso...

  6. A Brief History of Animal Modeling

    OpenAIRE

    Ericsson, Aaron C.; Crim, Marcus J; Franklin, Craig L.

    2013-01-01

    Comparative medicine is founded on the concept that other animal species share physiological, behavioral, or other characteristics with humans. Over 2,400 years ago it was recognized that by studying animals, we could learn much about ourselves. This technique has now developed to the point that animal models are employed in virtually all fields of biomedical research including, but not limited to, basic biology, immunology and infectious disease, oncology, and behavior.

  7. Animal Models in Studying Cerebral Arteriovenous Malformation

    OpenAIRE

    Ming Xu; Hongzhi Xu; Zhiyong Qin

    2015-01-01

    Brain arteriovenous malformation (AVM) is an important cause of hemorrhagic stroke. The etiology is largely unknown and the therapeutics are controversial. A review of AVM-associated animal models may be helpful in order to understand the up-to-date knowledge and promote further research about the disease. We searched PubMed till December 31, 2014, with the term “arteriovenous malformation,” limiting results to animals and English language. Publications that described creations of AVM animal ...

  8. Stochastic modelling of animal movement

    OpenAIRE

    Smouse, Peter E.; Focardi, Stefano; Moorcroft, Paul R.; Kie, John G.; Forester, James D.; Morales, Juan M.

    2010-01-01

    Modern animal movement modelling derives from two traditions. Lagrangian models, based on random walk behaviour, are useful for multi-step trajectories of single animals. Continuous Eulerian models describe expected behaviour, averaged over stochastic realizations, and are usefully applied to ensembles of individuals. We illustrate three modern research arenas. (i) Models of home-range formation describe the process of an animal ‘settling down’, accomplished by including one or more focal poi...

  9. LARGE ANIMAL PARKINSONS DISEASE MODELS USING VIRAL VECTORS AND INOCULATION OF PREFORMED FIBRILS TO MEDIATE ALPHA-SYNUCLEIN OVEREXPRESSION AND MISFOLDING IN THE GOTTINGEN MINIPIG CNS

    DEFF Research Database (Denmark)

    Glud, Andreas Nørgaard; Landau, A.M.; Johnsen, Erik Lisbjerg; Bjarkam, C.R.; Brooks, David; Kirik, Deniz; Sørensen, Jens Christian Hedemann

    2015-01-01

    Animal models towards understanding and treating Parkinson’s disease (PD) are important translational steps toward clinical applications. The Göttingen minipig(GM), fits progressional neurological models due to an relative low adult weight between 20-40 kg, and has a large gyrencephalic brain (6x 5...... quantified by neurological tests (behavior, scoring and gait), conventional and preclinical PET scanning modalities, autoradiography and post mortem histological evaluation. Results: Studies are still ongoing and data is being collected. First results from LV methods shoved "prove of concept" on gait and...... as antiaggreganttreatment, induced pluripotent stem cells or immunotherapy and development of novel radioligands for early diagnosis and assess disease progression....

  10. Animal Models of Dengue Virus Infection

    OpenAIRE

    Eva Harris; Simona Zompi

    2012-01-01

    The development of animal models of dengue virus (DENV) infection and disease has been challenging, as epidemic DENV does not naturally infect non-human species. Non-human primates (NHPs) can sustain viral replication in relevant cell types and develop a robust immune response, but they do not develop overt disease. In contrast, certain immunodeficient mouse models infected with mouse-adapted DENV strains show signs of severe disease similar to the ‘vascular-leak’ syndrome seen in severe deng...

  11. Animal Models of Neuropsychiatric Disorders

    OpenAIRE

    Nestler, Eric J.; Steven E Hyman

    2010-01-01

    Modeling of human neuropsychiatric disorders in animals is extremely challenging given the subjective nature of many key symptoms, the lack of biomarkers and objective diagnostic tests, and the early state of the relevant neurobiology and genetics. Nonetheless, progress in understanding pathophysiology and in treatment development would benefit greatly from improved animal models. Here we review the current state of animal models of mental illness, with a focus on schizophrenia, depression, a...

  12. An overview of animal prion diseases

    Directory of Open Access Journals (Sweden)

    Imran Muhammad

    2011-11-01

    Full Text Available Abstract Prion diseases are transmissible neurodegenerative conditions affecting human and a wide range of animal species. The pathogenesis of prion diseases is associated with the accumulation of aggregates of misfolded conformers of host-encoded cellular prion protein (PrPC. Animal prion diseases include scrapie of sheep and goats, bovine spongiform encephalopathy (BSE or mad cow disease, transmissible mink encephalopathy, feline spongiform encephalopathy, exotic ungulate spongiform encephalopathy, chronic wasting disease of cervids and spongiform encephalopathy of primates. Although some cases of sporadic atypical scrapie and BSE have also been reported, animal prion diseases have basically occurred via the acquisition of infection from contaminated feed or via the exposure to contaminated environment. Scrapie and chronic wasting disease are naturally sustaining epidemics. The transmission of BSE to human has caused more than 200 cases of variant Cruetzfeldt-Jacob disease and has raised serious public health concerns. The present review discusses the epidemiology, clinical neuropathology, transmissibility and genetics of animal prion diseases.

  13. Effects of SR141716A on Cognitive and Depression-Related Behavior in an Animal Model of Premotor Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    M. T. Tadaiesky

    2010-01-01

    Full Text Available A previous study from our laboratory revealed that moderate nigral dopaminergic degeneration caused emotional and cognitive deficits in rats, paralleling early signs of Parkinson's disease. Recent evidence suggests that the blockade of cannabinoid CB1 receptors might be beneficial to alleviate motor inhibition typical of Parkinson's disease. Here, we investigated whether antagonism of CB1 receptors would improve emotional and cognitive deficits in a rat model of premotor Parkinson's disease. Depression-like behavior and cognition were assessed with the forced swim test and the social recognition test, respectively. Confirming our previous study, rats injected with 6-hydroxydopamine in striatum presented emotional and cognitive alterations which were improved by acute injection of SR141716A. HPLC analysis of monoamine levels demonstrated alterations in the striatum and prefrontal cortex after SR141716A injection. These findings suggest a role for CB1 receptors in the early symptoms caused by degeneration of dopaminergic neurons in the striatum, as observed in Parkinson's disease.

  14. Effects of SR141716A on Cognitive and Depression-Related Behavior in an Animal Model of Premotor Parkinson's Disease

    Science.gov (United States)

    Tadaiesky, M. T.; Dombrowski, P. A.; Da Cunha, C.; Takahashi, R. N.

    2010-01-01

    A previous study from our laboratory revealed that moderate nigral dopaminergic degeneration caused emotional and cognitive deficits in rats, paralleling early signs of Parkinson's disease. Recent evidence suggests that the blockade of cannabinoid CB1 receptors might be beneficial to alleviate motor inhibition typical of Parkinson's disease. Here, we investigated whether antagonism of CB1 receptors would improve emotional and cognitive deficits in a rat model of premotor Parkinson's disease. Depression-like behavior and cognition were assessed with the forced swim test and the social recognition test, respectively. Confirming our previous study, rats injected with 6-hydroxydopamine in striatum presented emotional and cognitive alterations which were improved by acute injection of SR141716A. HPLC analysis of monoamine levels demonstrated alterations in the striatum and prefrontal cortex after SR141716A injection. These findings suggest a role for CB1 receptors in the early symptoms caused by degeneration of dopaminergic neurons in the striatum, as observed in Parkinson's disease. PMID:20976080

  15. Cost-benefit analysis in animal disease control

    International Nuclear Information System (INIS)

    Animal health economics is a relatively new discipline which is progressively developing a solid framework of concepts, procedures and data to support the decision making process in optimizing animal health management. Research in this field deals primarily with three interrelated aspects: (1) quantifying the financial effects of animal diseases, (2) developing methods for optimizing decisions when individual animals, herds or populations are affected, and (3) determining the costs and benefits of disease control measures. In the paper the four most common economic modelling techniques in animal health economics (i.e. partial budgeting, cost-benefit analysis, decision analysis, and systems simulation) are described and applied on three levels of veterinary decision making: the animal, herd and national level. Outcomes so far are summarized, and shortcomings indicated and discussed. The importance of a close link between economics and epidemiology is stressed for future development, as well as the need for, and possibilities of, an international exchange of models and procedures. (author)

  16. Animal Models for the Study of Osteomyelitis

    OpenAIRE

    Patel, Mitul; Rojavin, Yuri; Jamali, Amir A.; Wasielewski, Samantha J.; Salgado, Christopher J.

    2009-01-01

    Osteomyelitis is an acute or chronic inflammatory process of the bone and its related structures secondary to an infection with pyogenic organisms. Because of the variety in disease presentations and pathophysiology of osteomyelitis, it is very difficult to evaluate in clinical studies. Therefore, animal models have been created for in vivo experimentation. A PubMed and OVID search was performed on March 31, 2008, using keywords osteomyelitis, animal model (rabbit, rat, mouse, avian, dog, she...

  17. ANIMAL MODELS OF CANCER: A REVIEW

    OpenAIRE

    Archana M Navale

    2013-01-01

    Cancer is the second leading cause of death worldwide. In USA three persons out of five will develop some type of cancer. Beyond these statistics of mortality, the morbidity due to cancer presents a real scary picture. Last 50 years of research has rendered some types of cancer curable, but still the major fear factor associated with this disease is unchanged. Animal models are classified according to the method of induction of cancer in the animal. Spontaneous tumor models are the most primi...

  18. Use of animal models in musculoskeletal research.

    OpenAIRE

    Neyt, J. G.; Buckwalter, J. A.; Carroll, N. C.

    1998-01-01

    Understanding of the human musculoskeletal system and common clinical disorders of bones, joints and soft tissues has been enhanced by the use of experimental animal models. Articles reporting on the results of these biomedical experiments frequently include conclusions that are based on the assumption that the biology of the animal model is similar to that of a human being for the disease process under investigation. The purpose of this investigation was to study the criteria and the conside...

  19. Animal models of osteoporosis - necessity and limitations

    OpenAIRE

    Turner A. Simon

    2001-01-01

    There is a great need to further characterise the available animal models for postmenopausal osteoporosis, for the understanding of the pathogenesis of the disease, investigation of new therapies (e.g. selective estrogen receptor modulators (SERMs)) and evaluation of prosthetic devices in osteoporotic bone. Animal models that have been used in the past include non-human primates, dogs, cats, rodents, rabbits, guinea pigs and minipigs, all of which have advantages and disadvantages. Sheep ar...

  20. Animal Models in Studying Cerebral Arteriovenous Malformation

    Directory of Open Access Journals (Sweden)

    Ming Xu

    2015-01-01

    Full Text Available Brain arteriovenous malformation (AVM is an important cause of hemorrhagic stroke. The etiology is largely unknown and the therapeutics are controversial. A review of AVM-associated animal models may be helpful in order to understand the up-to-date knowledge and promote further research about the disease. We searched PubMed till December 31, 2014, with the term “arteriovenous malformation,” limiting results to animals and English language. Publications that described creations of AVM animal models or investigated AVM-related mechanisms and treatments using these models were reviewed. More than 100 articles fulfilling our inclusion criteria were identified, and from them eight different types of the original models were summarized. The backgrounds and procedures of these models, their applications, and research findings were demonstrated. Animal models are useful in studying the pathogenesis of AVM formation, growth, and rupture, as well as in developing and testing new treatments. Creations of preferable models are expected.

  1. Refining Animal Models to Enhance Animal Welfare

    Institute of Scientific and Technical Information of China (English)

    Patricia V.Turner

    2012-01-01

    The use of animals in research will be necessary for scientific advances in the basic and biomedical sciences for the foreseeable future.As we learn more about the ability of animals to experience pain,suffering,and distress,and particularly for mammals,it becomes the responsibility of scientists,institutions,animal caregivers,and veterinarians to seek ways to improve the lives of research animals and refine their care and use.Refinement is one of the three R's emphasized by Russell and Burch,and refers to modification of procedures to minimise the potential for pain,suffering and distress. It may also refer to procedures used to enhance animal comfort. This paper summarizes considerations for refinements in research animal.

  2. Small animal disease surveillance: respiratory disease.

    Science.gov (United States)

    Sánchez-Vizcaíno, Fernando; Daly, Janet M; Jones, Philip H; Dawson, Susan; Gaskell, Rosalind; Menacere, Tarek; Heayns, Bethaney; Wardeh, Maya; Newman, Jenny; Everitt, Sally; Day, Michael J; McConnell, Katie; Noble, Peter J M; Radford, Alan D

    2016-04-01

    Presentation for respiratory disease comprised 1.7 per cent, 2.3 per cent and 2.5 per cent of canine, feline and rabbit consultations, respectively, between January 2014 and December 2015Coughing was the most frequent respiratory sign reported in dogs (71.1 per cent of consultations); in cats it was sneezing (42.6 per cent)Mean percentage of samples testing positive for feline calicivirus (FCV) was 30.1 per cent in 2014 and 27.9 per cent in 2015January was the month with the highest percentage of FCV-positive samples in both 2014 and 2015. PMID:27056810

  3. Animal models used to examine the role of the environment in the development of autoimmune disease: findings from an NIEHS Expert Panel Workshop.

    Science.gov (United States)

    Germolec, Dori; Kono, Dwight H; Pfau, Jean C; Pollard, K Michael

    2012-12-01

    Autoimmunity is thought to result from a combination of genetics, environmental triggers, and stochastic events. Environmental factors, such as chemicals, drugs or infectious agents, have been implicated in the expression of autoimmune disease, yet human studies are extremely limited in their ability to test isolated exposures to demonstrate causation or to assess pathogenic mechanisms. In this review we examine the research literature on the ability of chemical, physical and biological agents to induce and/or exacerbate autoimmunity in a variety of animal models. There is no single animal model capable of mimicking the features of human autoimmune disease, particularly as related to environmental exposures. An objective, therefore, was to assess the types of information that can be gleaned from the use of animal models, and how well that information can be used to translate back to human health. Our review notes the importance of genetic background to the types and severity of the autoimmune response following exposure to environmental factors, and emphasizes literature where animal model studies have led to increased confidence about environmental factors that affect expression of autoimmunity. A high level of confidence was reached if there were multiple studies from different laboratories confirming the same findings. Examples include mercury, pristane, and infection with Streptococcus or Coxsackie B virus. A second level of consensus identified those exposures likely to influence autoimmunity but requiring further confirmation. To fit into this category, there needed to be significant supporting data, perhaps by multiple studies from a single laboratory, or repetition of some but not all findings in multiple laboratories. Examples include silica, gold, TCE, TCDD, UV radiation, and Theiler's murine encephalomyelitis virus. With the caveat that researchers must keep in mind the limitations and appropriate applications of the various approaches, animal models are

  4. Evaluation of Surrogate Animal Models of Melioidosis

    OpenAIRE

    Warawa, Jonathan Mark

    2010-01-01

    Burkholderia pseudomallei is the Gram-negative bacterial pathogen responsible for the disease melioidosis. B. pseudomallei establishes disease in susceptible individuals through multiple routes of infection, all of which may proceed to a septicemic disease associated with a high mortality rate. B. pseudomallei opportunistically infects humans and a wide range of animals directly from the environment, and modeling of experimental melioidosis has been conducted in numerous biologically relevant...

  5. Cystamine/cysteamine rescues the dopaminergic system and shows neurorestorative properties in an animal model of Parkinson's disease.

    Science.gov (United States)

    Cisbani, G; Drouin-Ouellet, J; Gibrat, C; Saint-Pierre, M; Lagacé, M; Badrinarayanan, S; Lavallée-Bourget, M H; Charest, J; Chabrat, A; Boivin, L; Lebel, M; Bousquet, M; Lévesque, M; Cicchetti, F

    2015-10-01

    The neuroprotective properties of cystamine identified in pre-clinical studies have fast-tracked this compound to clinical trials in Huntington's disease, showing tolerability and benefits on motor symptoms. We tested whether cystamine could have such properties in a Parkinson's disease murine model and now provide evidence that it can not only prevent the neurodegenerative process but also can reverse motor impairments created by a 6-hydroxydopamine lesion 3 weeks post-surgery. Importantly, we report that cystamine has neurorestorative properties 5 weeks post-lesion as seen on the number of nigral dopaminergic neurons which is comparable with treatments of cysteamine, the reduced form of cystamine used in the clinic, as well as rasagiline, increasingly prescribed in early parkinsonism. All three compounds induced neurite arborization of the remaining dopaminergic cells which was further confirmed in ex vivo dopaminergic explants derived from Pitx3-GFP mice. The disease-modifying effects displayed by cystamine/cysteamine would encourage clinical testing. PMID:26232588

  6. Potential Large Animal Models for Gene Therapy of Human Genetic Diseases of Immune and Blood Cell Systems

    OpenAIRE

    Bauer, Thomas R.; Adler, Rima L.; Hickstein, Dennis D.

    2009-01-01

    Genetic mutations involving the cellular components of the hematopoietic system—red blood cells, white blood cells, and platelets—manifest clinically as anemia, infection, and bleeding. Although gene targeting has recapitulated many of these diseases in mice, these murine homologues are limited as translational models by their small size and brief life span as well as the fact that mutations induced by gene targeting do not always faithfully reflect the clinical manifestations of such mutatio...

  7. ANIMAL MODELS OF CANCER: A REVIEW

    Directory of Open Access Journals (Sweden)

    Archana M. Navale

    2013-01-01

    Full Text Available Cancer is the second leading cause of death worldwide. In USA three persons out of five will develop some type of cancer. Beyond these statistics of mortality, the morbidity due to cancer presents a real scary picture. Last 50 years of research has rendered some types of cancer curable, but still the major fear factor associated with this disease is unchanged. Animal models are classified according to the method of induction of cancer in the animal. Spontaneous tumor models are the most primitive models. Although these models show good resemblance to the natural disease in humans, they were not capable of keeping pace with developing experimental therapeutics programs. It has therefore been necessary to take a further step towards artificiality, away from the clinical problem in the search for satisfactory testing method. From this step, the journey of artificially induced tumor models started. It is possible to induce cancer reproducibly in animals by exposing them to various agents and now, by transplanting tumor cells or tissue. The development of Genetically Engineered Animal models has provided a great help in knowing the disease. This article takes a review of present animal models used in anti-cancer drug discovery.

  8. A Comparison of the Pathogenesis of Marburg Virus Disease in Humans and Nonhuman Primates and Evaluation of the Suitability of These Animal Models for Predicting Clinical Efficacy under the 'Animal Rule'.

    Science.gov (United States)

    Glaze, Elizabeth R; Roy, Michael J; Dalrymple, Lonnie W; Lanning, Lynda L

    2015-06-01

    Marburg virus outbreaks are sporadic, infrequent, brief, and relatively small in terms of numbers of subjects affected. In addition, outbreaks most likely will occur in remote regions where clinical trials are not feasible; therefore, definitive, well-controlled human efficacy studies to test the effectiveness of a drug or biologic product are not feasible. Healthy human volunteers cannot ethically be deliberately exposed to a lethal agent such as Marburg virus in order to test the efficacy of a therapy or preventive prior to licensure. When human efficacy studies are neither ethical nor feasible, the US Food and Drug Administration may grant marketing approval of a drug or biologic product under the 'Animal Rule,' through which demonstration of the efficacy of a product can be 'based on adequate and well-controlled animal efficacy studies when the results of those studies establish that the drug is reasonably likely to produce clinical benefit in humans.' This process requires that the pathogenic determinants of the disease in the animal model are similar to those that have been identified in humans. After reviewing primarily English-language, peer-reviewed journal articles, we here summarize the clinical manifestations of Marburg virus disease and the results of studies in NHP showing the characteristics and progression of the disease. We also include a detailed comparison of the characteristics of the human disease relative to those for NHP. This review reveals that the disease characteristics of Marburg virus disease are generally similar for humans and 3 NHP species: cynomolgus macaques (Macaca fascicularis), rhesus macaques (Macaca mulatta), and African green monkeys (Chlorocebus aethiops). PMID:26141449

  9. Symptomatic animal models for dystonia

    OpenAIRE

    Wilson, Bethany K.; Hess, Ellen J.

    2013-01-01

    Symptomatic animal models have clinical features consistent with human disorders and are often used to identify the anatomical and physiological processes involved in the expression of symptoms and to experimentally demonstrate causality where it would be infeasible in the patient population. Rodent and primate models of dystonia have identified basal ganglia abnormalities, including alterations in striatal GABAergic and dopaminergic transmission. Symptomatic animal models have also establish...

  10. 9 CFR 95.3 - Byproducts from diseased animals prohibited.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Byproducts from diseased animals prohibited. 95.3 Section 95.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EXPORTATION AND IMPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL...

  11. Animal models of osteoporosis - necessity and limitations

    Directory of Open Access Journals (Sweden)

    Turner A. Simon

    2001-06-01

    Full Text Available There is a great need to further characterise the available animal models for postmenopausal osteoporosis, for the understanding of the pathogenesis of the disease, investigation of new therapies (e.g. selective estrogen receptor modulators (SERMs and evaluation of prosthetic devices in osteoporotic bone. Animal models that have been used in the past include non-human primates, dogs, cats, rodents, rabbits, guinea pigs and minipigs, all of which have advantages and disadvantages. Sheep are a promising model for various reasons: they are docile, easy to handle and house, relatively inexpensive, available in large numbers, spontaneously ovulate, and the sheep's bones are large enough to evaluate orthopaedic implants. Most animal models have used females and osteoporosis in the male has been largely ignored. Recently, interest in development of appropriate prosthetic devices which would stimulate osseointegration into osteoporotic, appendicular, axial and mandibular bone has intensified. Augmentation of osteopenic lumbar vertebrae with bioactive ceramics (vertebroplasty is another area that will require testing in the appropriate animal model. Using experimental animal models for the study of these different facets of osteoporosis minimizes some of the difficulties associated with studying the disease in humans, namely time and behavioral variability among test subjects. New experimental drug therapies and orthopaedic implants can potentially be tested on large numbers of animals subjected to a level of experimental control impossible in human clinical research.

  12. The multifactorial role of the 3Rs in shifting the harm-benefit analysis in animal models of disease

    OpenAIRE

    Graham, Melanie L; Prescott, Mark J

    2015-01-01

    Ethics on animal use in science in Western society is based on utilitarianism, weighing the harms and benefits to the animals involved against those of the intended human beneficiaries. The 3Rs concept (Replacement, Reduction, Refinement) is both a robust framework for minimizing animal use and suffering (addressing the harms to animals) and a means of supporting high quality science and translation (addressing the benefits). The ambiguity of basic research performed early in the research con...

  13. Overview of Neurotoxin Induced Animal Models of Parkinson's Disease%神经毒素诱导帕金森病动物模型的概述

    Institute of Scientific and Technical Information of China (English)

    史肖锦; 屈洪党

    2015-01-01

    帕金森病(Parkinson's disease,PD)是一种常见的神经系统退行性疾病,其主要的病理改变为黑质多巴胺能神经元的进行性丢失、纹状体多巴胺的耗竭和残留的神经元胞浆中路易小体的形成,但其确切病因仍未明确。目前对帕金森病病因和病理生理机制的认知,主要来源于对PD动物模型的深入研究。为进一步研究PD,该文对目前常用的神经毒素诱导的PD动物模型进行概述,为相关研究者选择合适的动物模型提供一定依据。%Parkinson's disease (PD) is a common neurodegenerative disease, the main pathological is progressive losing of dopaminergic neurons, depletion of striatal dopamine and formation of Lewy bodies in residual neuronal cytoplasm, but the exact cause is not clear. At present, the etiology and pathophysiology of Parkinson's disease are mainly derived from the PD animal model. For further study of PD, the paper aims to survey the animal model of PD induced by neurotoxin, and the purpose is to pro-vide the basis of selecting suitable animal model.

  14. Infectious disease in animal metapopulations: the importance of environmental transmission

    OpenAIRE

    Park, Andrew W.

    2012-01-01

    Motivated by an array of infectious diseases that threaten wildlife populations, a simple metapopulation model (subpopulations connected by animal movement) is developed, which allows for both movement-based and environmental transmission. The model demonstrates that for a range of plausible parameterizations of environmental transmission, increased movement rate of animals between discrete habitats can lead to a decrease in the overall proportion of sites that are occupied. This can limit th...

  15. Animal Models of Depression: Molecular Perspectives

    OpenAIRE

    Krishnan, Vaishnav; Nestler, Eric J.

    2011-01-01

    Much of the current understanding about the pathogenesis of altered mood, impaired concentration and neurovegetative symptoms in major depression has come from animal models. However, because of the unique and complex features of human depression, the generation of valid and insightful depression models has been less straightforward than modeling other disabling diseases like cancer or autoimmune conditions. Today’s popular depression models creatively merge ethologically valid behavioral ass...

  16. Animal Models of Ricin Toxicosis

    OpenAIRE

    Roy, Chad J; Song, Kejing; Sivasubramani, Satheesh K.; Gardner, Donald J.; Seth H Pincus

    2012-01-01

    Animal models of ricin toxicosis are necessary for testing the efficacy of therapeutic measures, as well studying the mechanisms by which ricin exerts its toxicity in intact animals. Because ricin can serve as a particularly well-characterized model of tissue damage, and the host response to that damage, studies of the mechanisms of ricin toxicity may have more general applicability. For example, our studies of the molecular mechanisms underlying the development of ricin-induced hypoglycemia ...

  17. Peptide hormone exendin-4 stimulates subventricular zone neurogenesis in the adult rodent brain and induces recovery in an animal model of Parkinson's disease.

    Science.gov (United States)

    Bertilsson, Göran; Patrone, Cesare; Zachrisson, Olof; Andersson, Annica; Dannaeus, Karin; Heidrich, Jessica; Kortesmaa, Jarkko; Mercer, Alex; Nielsen, Elisabet; Rönnholm, Harriet; Wikström, Lilian

    2008-02-01

    We investigated the effects of exendin-4 on neural stem/progenitor cells in the subventricular zone of the adult rodent brain and its functional effects in an animal model of Parkinson's disease. Our results showed expression of GLP-1 receptor mRNA or protein in the subventricular zone and cultured neural stem/progenitor cells isolated from this region. In vitro, exendin-4 increased the number of neural stem/progenitor cells, and the number of cells expressing the neuronal markers microtubule-associated protein 2, beta-III-tubulin, and neuron-specific enolase. When exendin-4 was given intraperitoneally to naïve rodents together with bromodeoxyuridine, a marker for DNA synthesis, both the number of bromodeoxyuridine-positive cells and the number of neuronal precursor cells expressing doublecortin were increased. Exendin-4 was tested in the 6-hydroxydopamine model of Parkinson's disease to investigate its possible functional effects in an animal model with neuronal loss. After unilateral lesion and a 5-week stabilization period, the rats were treated for 3 weeks with exendin-4. We found a reduction of amphetamine-induced rotations in animals receiving exendin-4 that persisted for several weeks after drug administration had been terminated. Histological analysis showed that exendin-4 significantly increased the number of both tyrosine hydroxylase- and vesicular monoamine transporter 2-positive neurons in the substantia nigra. In conclusion, our results show that exendin-4 is able to promote adult neurogenesis in vitro and in vivo, normalize dopamine imbalance, and increase the number of cells positive for markers of dopaminergic neurons in the substantia nigra in a model of Parkinson's disease. PMID:17803225

  18. Animal models of portal hypertension

    Institute of Scientific and Technical Information of China (English)

    Juan G Abraldes; Marcos Pasarín; Juan Carlos; García-Pagán

    2006-01-01

    Animal models have allowed detailed study of hemodynamic alterations typical of portal hypertension and the molecular mechanisms involved in abnormalities in splanchnic and systemic circulation associated with this syndrome. Models of prehepatic portal hypertension can be used to study alterations in the splanchnic circulation and the pathophysiology of the hyperdynamic circulation. Models of cirrhosis allow study of the alterations in intrahepatic microcirculation that lead to increased resistance to portal flow. This review summarizes the currently available literature on animal models of portal hypertension and analyzes their relative utility. The criteria for choosing a particular model,depending on the specific objectives of the study, are also discussed.

  19. Animal Models for Candidiasis

    OpenAIRE

    Conti, Heather R.; Huppler, Anna R.; Whibley, Natasha; Gaffen, Sarah L

    2014-01-01

    Multiple forms of candidiasis are clinically important in humans. Established murine models of disseminated, oropharyngeal, vaginal, and cutaneous candidiasis caused by Candida albicans are described in this unit. Detailed materials and methods for C. albicans growth and detection are also described.

  20. Animal models in myopia research.

    Science.gov (United States)

    Schaeffel, Frank; Feldkaemper, Marita

    2015-11-01

    Our current understanding of the development of refractive errors, in particular myopia, would be substantially limited had Wiesel and Raviola not discovered by accident that monkeys develop axial myopia as a result of deprivation of form vision. Similarly, if Josh Wallman and colleagues had not found that simple plastic goggles attached to the chicken eye generate large amounts of myopia, the chicken model would perhaps not have become such an important animal model. Contrary to previous assumptions about the mechanisms of myopia, these animal models suggested that eye growth is visually controlled locally by the retina, that an afferent connection to the brain is not essential and that emmetropisation uses more sophisticated cues than just the magnitude of retinal blur. While animal models have shown that the retina can determine the sign of defocus, the underlying mechanism is still not entirely clear. Animal models have also provided knowledge about the biochemical nature of the signal cascade converting the output of retinal image processing to changes in choroidal thickness and scleral growth; however, a critical question was, and still is, can the results from animal models be applied to myopia in children? While the basic findings from chickens appear applicable to monkeys, some fundamental questions remain. If eye growth is guided by visual feedback, why is myopic development not self-limiting? Why does undercorrection not arrest myopic progression even though positive lenses induce myopic defocus, which leads to the development of hyperopia in emmetropic animals? Why do some spectacle or contact lens designs reduce myopic progression and others not? It appears that some major differences exist between animals reared with imposed defocus and children treated with various optical corrections, although without the basic knowledge obtained from animal models, we would be lost in an abundance of untestable hypotheses concerning human myopia. PMID:26769177

  1. Gene transfer in rodents and primates as a new tool for modeling diseases in animals and assessing functions by in vivo imaging

    International Nuclear Information System (INIS)

    The identification of disease-causing genes in familial forms of neuro-degenerative disorders and the development of genetic models closely replicating human CNS pathologies have drastically changed our understanding of the molecular events leading to neuronal cell death. If these achievements open new opportunities of therapeutic interventions efficient delivery systems taking into account the specificity of the central nervous system are required to administer therapeutic candidates. In addition, there is a need to develop 1) genetic models in large animals that replicate late stages of the diseases and 2) imaging techniques suitable for longitudinal, quantitative and non-invasive evaluation of disease progression and the evaluation of new therapeutic strategies. Over the last few years, we have investigated the potential of lentiviral vectors as tool to model and treat CNS disorders. The use of lentiviral vectors to create animal model of these pathologies holds various advantages compared to classical transgenic approaches. Viral vectors are versatile, highly flexible tools to perform in vivo studies. Multiple genetic models can be created in a short period of time. High transduction efficiencies as well as robust and sustained trans-gene expression lead to the rapid appearance of functional and behavioral abnormalities and severe neuro-degeneration. Targeted injections in different brain areas can be used to investigate the regional specificity of the neuro-pathology and eliminate potential side effects associated with a widespread over-expression of the trans-gene. Finally, models can be established in different mammalian species including non-human primates, thereby providing an opportunity to assess complex behavioral changes and perform longitudinal follow-up of neuro-pathological alterations by imaging. We have demonstrated the proof of principle of this approach for Huntington's disease. We have shown that the intratriatal injection of lentiviral vector

  2. Comparative dual-tracer studies of carbon-14 tryptophan and iodine-131 HIPDM in animal models of pancreatic diseases

    International Nuclear Information System (INIS)

    Our previous studies have shown that a significant amount of the diamine derivative 131I-N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3- propanediamine (HIPDM) is taken up and retained by the normal pancreas. Therefore, we studied the uptake of [131I]HIPDM in various pathophysiological models in mice (chronic alcoholism, diabetes with beta-cell atrophy and obesity with beta-cell hypertrophy) and compared to 14C-L-Tryptophan (TRY) distribution in order to determine the factors influencing their pancreatic uptake. In normal animals, the pancreas uptake of TRY was generally higher than HIPDM. In diabetes, the relative concentration of both compounds was higher over the controls; however, in obesity, TRY showed lower accumulation than in controls while HIPDM showed no significant difference. Chronic ethanol (20%) ingestion increased TRY uptake in the pancreas compared to controls (36.88 ± 3.21 vs. 30.03 ± 4.17% ID/g; p less than 0.01) after 5 wk study period, but it decreased by 10 wk (22.36 ± 0.95% ID/g; p less than 0.005). There were no significant changes in [131I]HIPDM distribution in alcoholics as compared to the controls. Radioiodinated HIPDM has potential advantages over [11C]TRY for pancreatic imaging since conventional imaging techniques can be employed. Our data, however, suggest that 11C-L-TRY is a more sensitive indicator of various pancreatic disorders

  3. An Animal Model for the Juvenile Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis

    Science.gov (United States)

    Marin, Veronica; Rosso, Natalia; Dal Ben, Matteo; Raseni, Alan; Boschelle, Manuela; Degrassi, Cristina; Nemeckova, Ivana; Nachtigal, Petr; Avellini, Claudio; Tiribelli, Claudio; Gazzin, Silvia

    2016-01-01

    Non Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) are the hepatic manifestations of the metabolic syndrome; worrisome is the booming increase in pediatric age. To recreate the full spectrum of juvenile liver pathology and investigate the gender impact, male and female C57Bl/6 mice were fed with high fat diet plus fructose in the drinking water (HFHC) immediately after weaning (equal to 3-years old human), and disease progression followed for 16 weeks, until adults (equal to 30-years old human). 100% of subjects of both genders on HFHC diet developed steatosis in 4weeks, and some degree of fibrosis in 8weeks, with the 86% of males and 15% of females presenting a stage 2 fibrosis at 16weeks. Despite a similar final liver damage both groups, a sex difference in the pathology progression was observed. Alterations in glucose homeostasis, dyslipidemia, hepatomegaly and obese phenotype were evident from the very beginning in males with an increased hepatic inflammatory activity. Conversely, such alterations were present in females only at the end of the HFHC diet (with the exception of insulin resistance and the hepatic inflammatory state). Interestingly, only females showed an altered hepatic redox state. This juvenile model appears a good platform to unravel the underlying gender dependent mechanisms in the progression from NAFLD to NASH, and to characterize novel therapeutic approaches. PMID:27391242

  4. Orally administrated cinnamon extract reduces β-amyloid oligomerization and corrects cognitive impairment in Alzheimer's disease animal models.

    Directory of Open Access Journals (Sweden)

    Anat Frydman-Marom

    Full Text Available An increasing body of evidence indicates that accumulation of soluble oligomeric assemblies of β-amyloid polypeptide (Aβ play a key role in Alzheimer's disease (AD pathology. Specifically, 56 kDa oligomeric species were shown to be correlated with impaired cognitive function in AD model mice. Several reports have documented the inhibition of Aβ plaque formation by compounds from natural sources. Yet, evidence for the ability of common edible elements to modulate Aβ oligomerization remains an unmet challenge. Here we identify a natural substance, based on cinnamon extract (CEppt, which markedly inhibits the formation of toxic Aβ oligomers and prevents the toxicity of Aβ on neuronal PC12 cells. When administered to an AD fly model, CEppt rectified their reduced longevity, fully recovered their locomotion defects and totally abolished tetrameric species of Aβ in their brain. Furthermore, oral administration of CEppt to an aggressive AD transgenic mice model led to marked decrease in 56 kDa Aβ oligomers, reduction of plaques and improvement in cognitive behavior. Our results present a novel prophylactic approach for inhibition of toxic oligomeric Aβ species formation in AD through the utilization of a compound that is currently in use in human diet.

  5. Orally administrated cinnamon extract reduces β-amyloid oligomerization and corrects cognitive impairment in Alzheimer's disease animal models.

    Science.gov (United States)

    Frydman-Marom, Anat; Levin, Aviad; Farfara, Dorit; Benromano, Tali; Scherzer-Attali, Roni; Peled, Sivan; Vassar, Robert; Segal, Daniel; Gazit, Ehud; Frenkel, Dan; Ovadia, Michael

    2011-01-01

    An increasing body of evidence indicates that accumulation of soluble oligomeric assemblies of β-amyloid polypeptide (Aβ) play a key role in Alzheimer's disease (AD) pathology. Specifically, 56 kDa oligomeric species were shown to be correlated with impaired cognitive function in AD model mice. Several reports have documented the inhibition of Aβ plaque formation by compounds from natural sources. Yet, evidence for the ability of common edible elements to modulate Aβ oligomerization remains an unmet challenge. Here we identify a natural substance, based on cinnamon extract (CEppt), which markedly inhibits the formation of toxic Aβ oligomers and prevents the toxicity of Aβ on neuronal PC12 cells. When administered to an AD fly model, CEppt rectified their reduced longevity, fully recovered their locomotion defects and totally abolished tetrameric species of Aβ in their brain. Furthermore, oral administration of CEppt to an aggressive AD transgenic mice model led to marked decrease in 56 kDa Aβ oligomers, reduction of plaques and improvement in cognitive behavior. Our results present a novel prophylactic approach for inhibition of toxic oligomeric Aβ species formation in AD through the utilization of a compound that is currently in use in human diet. PMID:21305046

  6. XX. Animal models of pneumocystosis

    DEFF Research Database (Denmark)

    Dei-Cas, E.; Brun-Pascaud, M.; Bille-Hansen, Vivi;

    1998-01-01

    As in vitro culture systems allowing to isolate Pneumocystis samples from patients or other mammal hosts are still not available, animal models have critical importance in Pneumocystis research. The parasite was reported in numerous mammals but P. carinii pneumonia (PCP) experimental models were...... source of parasites taxonomically related to P. carinii sp. f hominis. Moreover, primates might be used as experimental hosts to human Pneumocystis. A marked variability of parasite levels among corticosteroid-treated animals and the fact that the origin of the parasite strain remains unknown, are...... important drawbacks of the corticosteroid-treated models. For these reasons, inoculated animal models of PCP were developed. The intratracheal inoculation of lung homogenates containing viable parasites in corticosteroid-treated non-latently infected rats resulted in extensive, reproducible Pneumocystis...

  7. Modelling group dynamic animal movement

    DEFF Research Database (Denmark)

    Langrock, Roland; Hopcraft, J. Grant C.; Blackwell, Paul G.;

    2014-01-01

    , to date, practical statistical methods which can include group dynamics in animal movement models have been lacking. We consider a flexible modelling framework that distinguishes a group-level model, describing the movement of the group's centre, and an individual-level model, such that each individual...... makes its movement decisions relative to the group centroid. The basic idea is framed within the flexible class of hidden Markov models, extending previous work on modelling animal movement by means of multi-state random walks. While in simulation experiments parameter estimators exhibit some bias...... in an encamped state. Though the attraction to the group centroid is relatively weak, our model successfully captures group-influenced movement dynamics. Specifically, as compared to a regular mixture of correlated random walks, the group dynamic model more accurately predicts the non-diffusive behaviour...

  8. Simulation of between-farm transmission of porcine reproductive and respiratory syndrome virus in Ontario, Canada using the North American Animal Disease Spread Model.

    Science.gov (United States)

    Thakur, Krishna K; Revie, Crawford W; Hurnik, Daniel; Poljak, Zvonimir; Sanchez, Javier

    2015-03-01

    Porcine reproductive and respiratory syndrome (PRRS), a viral disease of swine, has major economic impacts on the swine industry. The North American Animal Disease Spread Model (NAADSM) is a spatial, stochastic, farm level state-transition modeling framework originally developed to simulate highly contagious and foreign livestock diseases. The objectives of this study were to develop a model to simulate between-farm spread of a homologous strain of PRRS virus in Ontario swine farms via direct (animal movement) and indirect (sharing of trucks between farms) contacts using the NAADSM and to compare the patterns and extent of outbreak under different simulated conditions. A total of 2552 swine farms in Ontario province were allocated to each census division of Ontario and geo-locations of the farms were randomly generated within the agriculture land of each Census Division. Contact rates among different production types were obtained using pig movement information from four regions in Canada. A total of 24 scenarios were developed involving various direct (movement of infected animals) and indirect (pig transportation trucks) contact parameters in combination with alternating the production type of the farm in which the infection was seeded. Outbreaks were simulated for one year with 1000 replications. The median number of farms infected, proportion of farms with multiple outbreaks and time to reach the peak epidemic were used to compare the size, progression and extent of outbreaks. Scenarios involving spread only by direct contact between farms resulted in outbreaks where the median percentage of infected farms ranged from 31.5 to 37% of all farms. In scenarios with both direct and indirect contact, the median percentage of infected farms increased to a range from 41.6 to 48.6%. Furthermore, scenarios with both direct and indirect contact resulted in a 44% increase in median epidemic size when compared to the direct contact scenarios. Incorporation of both animal

  9. Animal models of preeclampsia; uses and limitations.

    LENUS (Irish Health Repository)

    McCarthy, F P

    2012-01-31

    Preeclampsia remains a leading cause of maternal and fetal morbidity and mortality and has an unknown etiology. The limited progress made regarding new treatments to reduce the incidence and severity of preeclampsia has been attributed to the difficulties faced in the development of suitable animal models for the mechanistic research of this disease. In addition, animal models need hypotheses on which to be based and the slow development of testable hypotheses has also contributed to this poor progress. The past decade has seen significant advances in our understanding of preeclampsia and the development of viable reproducible animal models has contributed significantly to these advances. Although many of these models have features of preeclampsia, they are still poor overall models of the human disease and limited due to lack of reproducibility and because they do not include the complete spectrum of pathophysiological changes associated with preeclampsia. This review aims to provide a succinct and comprehensive assessment of current animal models of preeclampsia, their uses and limitations with particular attention paid to the best validated and most comprehensive models, in addition to those models which have been utilized to investigate potential therapeutic interventions for the treatment or prevention of preeclampsia.

  10. Evaluation of surrogate animal models of melioidosis

    Directory of Open Access Journals (Sweden)

    Jonathan Mark Warawa

    2010-12-01

    Full Text Available Burkholderia pseudomallei is the Gram-negative bacterial pathogen responsible for the disease melioidosis. B. pseudomallei establishes disease in susceptible individuals through multiple routes of infection, all of which may proceed to a septicemic disease associated with a high mortality rate. B. pseudomallei opportunistically infects humans and a wide range of animals directly from the environment, and modeling of experimental melioidosis has been conducted in numerous biologically relevant models including mammalian and invertebrate hosts. This review seeks to summarize published findings related to established animal models of melioidosis, with an aim to compare and contrast the virulence of B. pseudomallei in these models. The effect of the route of delivery on disease is also discussed for intravenous, intraperitoneal, subcutaneous, intranasal, aerosol, oral, and intratracheal infection methodologies, with a particular focus on how they relate to modeling clinical melioidosis. The importance of the translational validity of the animal models used in B. pseudomallei research is highlighted as these studies have become increasingly therapeutic in nature.

  11. Maintaining a vigilance for foreign animal diseases.

    Science.gov (United States)

    Waldrup, Kenneth A; Conger, Terry H

    2002-11-01

    The incursion of foot-and-mouth disease (FMD) into the United Kingdom in February 2001 served as a wakeup call for North American agriculture. As the livestock health crisis in the United Kingdom progressed, it became increasingly evident that the United States, Canada, and Mexico were also susceptible to an incursion of a foreign animal disease. The terrorist attacks of September 11, 2001, and the subsequent anthrax mailings reaffirmed the fact that the United States is vulnerable to an infectious assault, regardless of whether it is intentional or accidental. PMID:12442572

  12. Phaeohyphomycoses, Emerging Opportunistic Diseases in Animals

    OpenAIRE

    Seyedmousavi, S.; Guillot, J; Hoog, de, G.S.

    2013-01-01

    Emerging fungal diseases due to black yeasts and relatives in domestic or wild animals and in invertebrates or cold- and warm-blooded vertebrates are continually being reported, either as novel pathogens or as familiar pathogens affecting new species of hosts. Different epidemiological situations can be distinguished, i.e., occurrence as single infections or as zoonoses, and infection may occur sporadically in otherwise healthy hosts. Such infections are found mostly in mammals but also in co...

  13. The big bang of genome editing technology: development and application of the CRISPR/Cas9 system in disease animal models.

    Science.gov (United States)

    Shao, Ming; Xu, Tian-Rui; Chen, Ce-Shi

    2016-07-18

    Targeted genome editing technology has been widely used in biomedical studies. The CRISPR-associated RNA-guided endonuclease Cas9 has become a versatile genome editing tool. The CRISPR/Cas9 system is useful for studying gene function through efficient knock-out, knock-in or chromatin modification of the targeted gene loci in various cell types and organisms. It can be applied in a number of fields, such as genetic breeding, disease treatment and gene functional investigation. In this review, we introduce the most recent developments and applications, the challenges, and future directions of Cas9 in generating disease animal model. Derived from the CRISPR adaptive immune system of bacteria, the development trend of Cas9 will inevitably fuel the vital applications from basic research to biotechnology and bio-medicine. PMID:27469250

  14. The big bang of genome editing technology: development and application of the CRISPR/Cas9 system in disease animal models

    Science.gov (United States)

    SHAO, Ming; XU, Tian-Rui; CHEN, Ce-Shi

    2016-01-01

    Targeted genome editing technology has been widely used in biomedical studies. The CRISPR-associated RNA-guided endonuclease Cas9 has become a versatile genome editing tool. The CRISPR/Cas9 system is useful for studying gene function through efficient knock-out, knock-in or chromatin modification of the targeted gene loci in various cell types and organisms. It can be applied in a number of fields, such as genetic breeding, disease treatment and gene functional investigation. In this review, we introduce the most recent developments and applications, the challenges, and future directions of Cas9 in generating disease animal model. Derived from the CRISPR adaptive immune system of bacteria, the development trend of Cas9 will inevitably fuel the vital applications from basic research to biotechnology and biomedicine. PMID:27469250

  15. 7.0T nuclear magnetic resonance evaluation of the amyloid beta (1-40) animal model of Alzheimer’s disease:comparison of cytology veriifcation

    Institute of Scientific and Technical Information of China (English)

    Lei Zhang; Shuai Dong; Guixiang Zhao; Yu Ma

    2014-01-01

    3.0T magnetic resonance spectroscopic imaging is a commonly used method in the research of brain function in Alzheimer’s disease. However, the role of 7.0T high-ifeld magnetic resonance spectroscopic imaging in brain function of Alzheimer’s disease remains unclear. In this study, 7.0T magnetic resonance spectroscopy showed that in the hippocampus of Alzheimer’s disease rats, the N-acetylaspartate wave crest was reduced, and the creatine and choline wave crest was elevated. This ifnding was further supported by hematoxylin-eosin staining, which showed a loss of hippocampal neurons and more glial cells. Moreover, electron microscopy showed neuronal shrinkage and mitochondrial rupture, and scanning electron microscopy revealed small size hippocampal synaptic vesicles, incomplete synaptic structure, and reduced number. Overall, the results revealed that 7.0T high-ifeld nuclear magnetic resonance spectroscopy detected the lesions and functional changes in hippocampal neurons of Alzheimer’s disease rats in vivo, allowing the possibility for assessing the success rate and grading of the amyloid beta (1-40) animal model of Alzheimer’s disease.

  16. Foreign animal disease outbreaks, the animal welfare implications for Canada: Risks apparent from international experience

    OpenAIRE

    Whiting, Terry L.

    2003-01-01

    Any outbreak of an Office International des Épizooties List A disease, such as classical swine fever or foot and mouth disease, has severe consequences for animal welfare, livestock production, exports of animals and animal products, and the environment. The public concern with the animal welfare effects of methods of disease eradication that result in the destruction of large numbers of uninfected animals has initiated a reconsideration of disease eradication policy in Europe. In many recent...

  17. Modelling group dynamic animal movement

    OpenAIRE

    Langrock, Roland; Hopcraft, Grant; Blackwell, Paul; Goodall, Victoria; King, Ruth; Niu, Mu; Patterson, Toby; Pedersen, Martin; Skarin, Anna; Schick, Robert Schilling

    2013-01-01

    1). Group dynamics are a fundamental aspect of many species' movements. The need to adequately model individuals' interactions with other group members has been recognized, particularly in order to differentiate the role of social forces in individual movement from environmental factors. However, to date, practical statistical methods, which can include group dynamics in animal movement models, have been lacking. 2). We consider a flexible modelling framework that distinguishes a group-level ...

  18. Information Learned from Animal Models of Atrial Fibrillation

    OpenAIRE

    Finet, J. Emanuel; Rosenbaum, David S.; Donahue, J. Kevin

    2009-01-01

    Animal models of atrial fibrillation have taught us about mechanisms of this common disease. A variety of animal models exist, including models of lone atrial fibrillation and models of atrial fibrillation in the setting of heart failure, aging or pericardial inflammation. This chapter reviews these various models.

  19. Animal models of age related macular degeneration

    OpenAIRE

    Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

    2012-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the ...

  20. Aspects of animal models for major neuropsychiatric disorders

    OpenAIRE

    Lefter Radu; Cojocaru Dumitru; Ciobica Alin; Paulet Manuel Ioan; Serban Lacramioara Ionela; Anton Emil

    2014-01-01

    We will review the main animal models for the major neuropsychiatric disorders, focusing on schizophrenia, Alzheimer’s disease, Parkinson’s disease, depression, anxiety and autism. Although these mental disorders are specifically human pathologies and therefore impossible to perfectly replicate in animals, the use of experimental animals is based on the physiological and anatomical similarities between humans and animals such as the rat, and mouse, and on t...

  1. Challenges for risk management related to emerging animal diseases

    OpenAIRE

    Aaltonen, Taina

    2010-01-01

    The uncertainties related to climate change and its effects on the spreading of animal diseases causes the most difficulties for the risk management. Preparedness and contingency planning for serious animal diseases in EU has mainly focused on conventional animal diseases, like foot- and-mouth-disease, classical swine fever and avian influenza.

  2. Effect of serotonin transporter blockade on L-DOPA-induced dyskinesia in animal models of Parkinson's disease.

    Science.gov (United States)

    Fidalgo, C; Ko, W K D; Tronci, E; Li, Q; Stancampiano, R; Chuan, Q; Bezard, E; Carta, M

    2015-07-01

    Serotonin transporter blockade with selective serotonin reuptake inhibitors (SSRIs) was recently shown to counteract L-DOPA-induced dyskinesia in 6-hydroxydopamine (6-OHDA)-lesioned rats. However, this effect has never been described in Parkinson's disease (PD) patients, despite that they often receive SSRIs for the treatment of depression. In the present study, we investigated the efficacy of the SSRI citalopram against dyskinesia in two experimental models of PD, the 6-OHDA-lesioned rat and 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)-treated macaque. First, we studied the acute and chronic effect of citalopram, given at different time points before L-DOPA, in L-DOPA-primed parkinsonian rats. Moreover, the acute effect of citalopram was also evaluated in dyskinetic MPTP-treated macaques. In L-DOPA-primed rats, a significant and long-lasting reduction of L-DOPA-induced dyskinesia (LID) was observed only when citalopram was given 30 min before L-DOPA, suggesting that the time of injection relative to L-DOPA is a key factor for the efficacy of the treatment. Interestingly, an acute challenge with the 5-HT1A/1B receptor agonist eltoprazine, given at the end of the chronic study, was equally effective in reducing LID in rats previously chronically treated with L-DOPA or L-DOPA plus citalopram, suggesting that no auto-receptor desensitization was induced by chronic citalopram treatment. In MPTP-treated macaques, citalopram produced a striking suppression of LID but at the expense of L-DOPA therapeutic efficacy, which represents a concern for possible clinical application. PMID:25907446

  3. Animal Models of Williams Syndrome

    OpenAIRE

    Osborne, Lucy R.

    2010-01-01

    In recent years, researchers have generated a variety of mouse models in an attempt to dissect the contribution of individual genes to the complex phenotype associated with Williams syndrome (WS). The mouse genome is easily manipulated to produce animals that are copies of humans with genetic conditions, be it with null mutations, hypomorphic mutations, point mutations, or even large deletions encompassing many genes. The existing mouse models certainly seem to implicate hemizygosity for ELN,...

  4. Animal Models Utilized in HTLV-1 Research

    OpenAIRE

    Panfil, Amanda R.; Al-Saleem, Jacob J; Green, Patrick L

    2013-01-01

    Since the isolation and discovery of human T-cell leukemia virus type 1 (HTLV-1) over 30 years ago, researchers have utilized animal models to study HTLV-1 transmission, viral persistence, virus-elicited immune responses, and HTLV-1-associated disease development (ATL, HAM/TSP). Non-human primates, rabbits, rats, and mice have all been used to help understand HTLV-1 biology and disease progression. Non-human primates offer a model system that is phylogenetically similar to humans for examinin...

  5. Application of new therapies in Graves' disease and thyroid-associated ophthalmopathy: animal models and translation to human clinical trials

    DEFF Research Database (Denmark)

    Banga, J Paul; Nielsen, Claus H; Gilbert, Jacqueline A; El Fassi, Daniel; Hegedus, Laszlo

    2008-01-01

    Most current approaches for treating Graves' disease are based essentially upon regimes developed nearly 50 years ago. Moreover, therapeutic approaches for complications such as thyroid-associated ophthalmopathy (TAO) and dermopathy are singularly dependent on conventional approaches of nonspecif...

  6. Polycystic Kidney Rat Is a Novel Animal Model of Caroli’s Disease Associated with Congenital Hepatic Fibrosis

    OpenAIRE

    Sanzen, Takahiro; Harada, Kenichi; Yasoshima, Mitsue; Kawamura, Yasuhito; Ishibashi, Masahiko; Nakanuma, Yasuni

    2001-01-01

    Caroli’s disease (congenital intrahepatic biliary dilatation) associated with congenital hepatic fibrosis is an autosomal recessive polycystic kidney disease. Recently, the polycystic kidney (PCK) rat, a spontaneous mutant derived from a colony of Crj:CD rats with polycystic lesions in the liver and an autosomal recessive mode of inheritance, was reported. In the present study, the pathology of the hepatobiliary system and the biliary cell-kinetics were evaluated in fetuses (day 18 to 21 of g...

  7. Henipavirus Infections: Lessons from Animal Models

    Directory of Open Access Journals (Sweden)

    Kévin P. Dhondt

    2013-04-01

    Full Text Available The Henipavirus genus contains two highly lethal viruses, the Hendra and Nipah viruses and one, recently discovered, apparently nonpathogenic member; Cedar virus. These three, negative-sense single-stranded RNA viruses, are hosted by fruit bats and use EphrinB2 receptors for entry into cells. The Hendra and Nipah viruses are zoonotic pathogens that emerged in the middle of 90s and have caused severe, and often fatal, neurologic and/or respiratory diseases in both humans and different animals; including spillover into equine and porcine species. Development of relevant models is critical for a better understanding of viral pathogenesis, generating new diagnostic tools, and assessing anti-viral therapeutics and vaccines. This review summarizes available data on several animal models where natural and/or experimental infection has been demonstrated; including pteroid bats, horses, pigs, cats, hamsters, guinea pigs, ferrets, and nonhuman primates. It recapitulates the principal features of viral pathogenesis in these animals and current knowledge on anti-viral immune responses. Lastly it describes the recently characterized murine animal model, which provides the possibility to use numerous and powerful tools available for mice to further decipher henipaviruses immunopathogenesis, prophylaxis, and treatment. The utility of different models to analyze important aspects of henipaviruses-induced disease in humans, potential routes of transmission, and therapeutic approaches are equally discussed.

  8. Henipavirus infections: lessons from animal models.

    Science.gov (United States)

    Dhondt, Kévin P; Horvat, Branka

    2013-01-01

    The Henipavirus genus contains two highly lethal viruses, the Hendra and Nipah viruses and one, recently discovered, apparently nonpathogenic member; Cedar virus. These three, negative-sense single-stranded RNA viruses, are hosted by fruit bats and use EphrinB2 receptors for entry into cells. The Hendra and Nipah viruses are zoonotic pathogens that emerged in the middle of 90s and have caused severe, and often fatal, neurologic and/or respiratory diseases in both humans and different animals; including spillover into equine and porcine species. Development of relevant models is critical for a better understanding of viral pathogenesis, generating new diagnostic tools, and assessing anti-viral therapeutics and vaccines. This review summarizes available data on several animal models where natural and/or experimental infection has been demonstrated; including pteroid bats, horses, pigs, cats, hamsters, guinea pigs, ferrets, and nonhuman primates. It recapitulates the principal features of viral pathogenesis in these animals and current knowledge on anti-viral immune responses. Lastly it describes the recently characterized murine animal model, which provides the possibility to use numerous and powerful tools available for mice to further decipher henipaviruses immunopathogenesis, prophylaxis, and treatment. The utility of different models to analyze important aspects of henipaviruses-induced disease in humans, potential routes of transmission, and therapeutic approaches are equally discussed. PMID:25437037

  9. Closing the gap between clinic and cage: sensori-motor and cognitive behavioural testing regimens in neurotoxin-induced animal models of Parkinson's disease.

    Science.gov (United States)

    Pienaar, Ilse S; Lu, Bingwei; Schallert, Timothy

    2012-11-01

    Animal models that make use of chemical toxins to adversely affect the nigrostriatal dopaminergic pathway of rodents and primates have contributed significantly towards the development of symptomatic therapies for Parkinson's disease (PD) patients. Although their use in developing neuro-therapeutic and -regenerative compounds remains to be ascertained, toxin-based mammalian and a range of non-mammalian models of PD are important tools in the identification and validation of candidate biomarkers for earlier diagnosis, as well as in the development of novel treatments that are currently working their way into the clinic. Toxin models of PD have and continue to be important models to use for understanding the consequences of nigrostriatal dopamine cell loss. Functional assessment of these models is also a critical component for eventual translational success. Sensitive behavioural testing regimens for assessing the extent of dysfunction exhibited in the toxin models, the degree of protection or improvement afforded by potential treatment modalities, and the correlation of these findings with what is observed clinically in PD patients, ultimately determines whether a potential treatment moves to clinical trials. Here, we review existing published work that describes the use of such behavioural outcome measures associated with toxin models of parkinsonism. In particular, we focus on tests assessing sensorimotor and cognitive function, both of which are significantly and progressively impaired in PD. PMID:22910679

  10. 人类疾病模型动物的管理要点%Scientific management of animal models of human diseases

    Institute of Scientific and Technical Information of China (English)

    周淑佩; 郑振辉; 贾光

    2012-01-01

    近年来,国内、国外人类疾病模型动物品种、品系繁多,遗传背景各异.国内基因修饰动物模型发展也很快,这些模型动物既有我们自己研发的,也有从国外引进的.建立动物模型的上游科研工作成绩突出,但宝贵的动物模型建立或引进后,由于种种原因导致动物断种、失去原有生物学特性的案例却屡见不鲜.从人类疾病模型动物的引种、保种、检疫隔离、饲养管理的特殊性等方面加强管理,可有效地控制和避免突变系出现自身修复,转基因动物的基因丢失,敲除基因动物基因复位等问题,从而达到保持其固有生物学特性的目的.%In recent years,many kinds of animal models of human diseases with different genetic background were developed.Some were established in China,others were imported from abroad.Precious were these animal models,their biological features could be lost for various reasons,for instance,reverse from mutation,lost of modified or constructed gene,etc.This study provided some suggestions for scientific management of the animal models to in terms of quarantine inspection,specific feeding method and methods to maintain gene stability,so as to preserve their biological features.

  11. ANIMAL BEHAVIORAL MODELS OF TINNITUS

    Institute of Scientific and Technical Information of China (English)

    ZHANG Chao; WANG Qiuju; SUN Wei

    2014-01-01

    The pathophysiology of tinnitus is poorly understood and treatments are often unsuccessful. A number of animal models have been developed in order to gain a better understanding of tinnitus. A great deal has been learned from these models re-garding the electrophysiological and neuroanatomical correlates of tinnitus following exposure to noise or ototoxic drugs. Re-liable behavioral data is important for determining whether such electrophysiological or neuroanatomical changes are indeed related to tinnitus. Of the many documented tinnitus animal behavioral paradigms, the acoustic startle reflex had been pro-posed as a simple method to identify the presence or absence of tinnitus. Several behavioral models based on conditioned re-sponse suppression paradigms have also been developed. In addition to determining the presence or absence of tinnitus, some of the behavioral paradigms have provided signs of the onset, frequency, and intensity of tinnitus in animals. Although none of these behavioral models have been proved to be a perfect model, these studies provide useful information on understanding the neural mechanisms underlying tinnitus.

  12. Laser Acupuncture at HT7 Acupoint Improves Cognitive Deficit, Neuronal Loss, Oxidative Stress, and Functions of Cholinergic and Dopaminergic Systems in Animal Model of Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Jintanaporn Wattanathorn

    2014-01-01

    Full Text Available To date, the therapeutic strategy against cognitive impairment in Parkinson’s disease (PD is still not in satisfaction level and requires novel effective intervention. Based the oxidative stress reduction and cognitive enhancement induced by laser acupuncture at HT7, the beneficial effect of laser acupuncture at HT7 against cognitive impairment in PD has been focused. In this study, we aimed to determine the effect of laser acupuncture at HT7 on memory impairment, oxidative stress status, and the functions of both cholinergic and dopaminergic systems in hippocampus of animal model of PD. Male Wistar rats, weighing 180–220 g, were induced unilateral lesion at right substantianigra by 6-OHDA and were treated with laser acupuncture continuously at a period of 14 days. The results showed that laser acupuncture at HT7 enhanced memory and neuron density in CA3 and dentate gyrus. The decreased AChE, MAO-B, and MDA together with increased GSH-Px in hippocampus of a 6-OHDA lesion rats were also observed. In conclusion, laser acupuncture at HT7 can improve neuron degeneration and memory impairment in animal model of PD partly via the decreased oxidative stress and the improved cholinergic and dopaminergic functions. More researches concerning effect of treatment duration are still required.

  13. Inhibition of high-mobility group box 1 as therapeutic option in autoimmune disease : lessons from animal models

    NARCIS (Netherlands)

    Schaper, Fleur; Heeringa, Peter; Bijl, Marc; Westra, Johanna

    2013-01-01

    Purpose of review High-mobility group box 1 (HMGB1) is a molecule that has gained much attention in the last couple of years as an important player in innate immune responses and modulating factor in several (auto) immune diseases. Furthermore, advancements have been made in identifying the diverse

  14. Animal models of human herpesvirus 6 infection

    OpenAIRE

    Joséphine eReynaud; Branka eHorvat

    2013-01-01

    Human herpesvirus (HHV)-6A and HHV-6B are two enveloped DNA viruses of β-herpesvirus family, infecting over 90% of the population and associated with several diseases, including exanthema subitum (for HHV-6B), multiple sclerosis and encephalitis, particularly in immunosuppressed patients. Animal models are highly important to better understand the pathogenesis of viral infections. Naturally developed neutralizing antibodies to HHV-6 or a related virus were found in different species of monkey...

  15. The wobbler mouse, an ALS animal model

    OpenAIRE

    Moser, Jakob Maximilian; Bigini, Paolo; Schmitt-John, Thomas

    2013-01-01

    This review article is focused on the research progress made utilizing the wobbler mouse as animal model for human motor neuron diseases, especially the amyotrophic lateral sclerosis (ALS). The wobbler mouse develops progressive degeneration of upper and lower motor neurons and shows striking similarities to ALS. The cellular effects of the wobbler mutation, cellular transport defects, neurofilament aggregation, neuronal hyperexcitability and neuroinflammation closely resemble human ALS. Now,...

  16. 骨关节疾病病证结合模型的构建与评价研究进展%Evaluation and Prospects of Integration of Disease and Syndrome Animal Models of Bone and Joint Diseases

    Institute of Scientific and Technical Information of China (English)

    夏炳江; 童培建; 肖鲁伟; 谢健; 金红婷

    2013-01-01

    从骨关节疾病病证结合动物模型的构建和评价两方面来对该类模型的研究进展进行综述.对骨关节疾病病证结合动物模型的研究意义、模型构建模式等环节及模型的评价方法和标准等方面分别进行阐述.同时指出骨关节疾病病证结合模型研究中存在的问题,并提出相应建议.%This article summarized the study progress in establishment and evaluation methods of integration of disease and syndrome animal models of bone and joint diseases. The significance of the research of integration of disease and syndrome animal models and the facts for making models manifest the methods and standards for evaluating the models. Meanwhile it pointed out the problems and gave some ideas on the research direction in the future.

  17. Making the animal model for AIDS research more precise: the impact of major histocompatibility complex (MHC) genes on pathogenesis and disease progression in SIV-infected monkeys.

    Science.gov (United States)

    Sauermann, U

    2001-09-01

    Experimentally infected rhesus monkeys serve as an indispensable animal model to assess the pathogenesis, to validate therapy approaches and to develop vaccination strategies against viral diseases such as AIDS threatening the human population. Upon infection with simian immunodeficiency virus (SIV), a retrovirus closely related to the human immunodeficiency virus (HIV), macaques develop clinical manifestations similar to those of HIV-infected humans. As in humans, the disease course is variable. Polymorphic genes of the major histocompatibility complex (MHC) are required for the initiation and regulation of a specific immune response and represent a major host factor accounting for the differential outcome of infection. During the last few years, our understanding of the structure and function of the rhesus macaque MHC has increased substantially. Functional studies have led to the identification of specific SIV and HIV peptide epitopes presented by rhesus macaque MHC molecules. The subsequent development of MHC class I tetramers has allowed further insight into the cellular immune response following SIV-infection. Detailed studies demonstrated that viral escape mutants are generated during the acute and chronic phase of infection and explain why control of viral replication ultimately fails. Furthermore, particular MHC haplotypes which influence disease progression have been discovered. Thus, MHC-typing can have a prognostic potential. The further elucidation of the rhesus macaque MHC and the search for other relevant genes will remain an important task for future research and will stimulate all immunologically-related investigations in macaques. PMID:11899095

  18. Ligustrazine Phosphate Ethosomes for Treatment of Alzheimer’s Disease, In Vitro and in Animal Model Studies

    OpenAIRE

    Shi, Jun; Wang, Yiming; Luo, Guoan

    2012-01-01

    In the present study, we have investigated transdermal administration of ligustrazine phosphate (LP), as an antioxidant, for the treatment of Alzheimer’s disease (AD). The LP transdermal ethosomal system was designed and characterized. Franz-type diffusion cells and confocal laser scanning microscopy were used for the in vitro permeation studies. Furthermore, the effect of LP transdermal ethosomal system on AD was evaluated in the scopolamine-induced amnesia rats by evaluating the behavioral ...

  19. Bridging Animal and Human Models

    OpenAIRE

    Barkley-Levenson, Amanda M.; Crabbe, John C.

    2012-01-01

    Genetics play an important role in the development and course of alcohol abuse, and understanding genetic contributions to this disorder may lead to improved preventative and therapeutic strategies in the future. Studies both in humans and in animal models are necessary to fully understand the neurobiology of alcoholism from the molecular to the cognitive level. By dissecting the complex facets of alcoholism into discrete, well-defined phenotypes that are measurable in both human populations ...

  20. Animal models of eating disorders

    OpenAIRE

    Kim, Sangwon F.

    2012-01-01

    Feeding is a fundamental process for basic survival, and is influenced by genetics and environmental stressors. Recent advances in our understanding of behavioral genetics have provided a profound insight on several components regulating eating patterns. However, our understanding of eating disorders such as anorexia nervosa, bulimia nervosa, and binge eating is still poor. The animal model is an essential tool in the investigation of eating behaviors and their pathological forms, yet develop...

  1. Modeling Autistic Features in Animals

    OpenAIRE

    Patterson, Paul H.

    2011-01-01

    A variety of features of autism can be simulated in rodents, including the core behavioral hallmarks of stereotyped and repetitive behaviors, and deficits in social interaction and communication. Other behaviors frequently found in autism spectrum disorders (ASD) such as neophobia, enhanced anxiety, abnormal pain sensitivity and eye blink conditioning, disturbed sleep patterns, seizures, and deficits in sensorimotor gating are also present in some of the animal models. Neuropathology and some...

  2. Animal Models in Burn Research

    OpenAIRE

    Abdullahi, A.; Amini-Nik, S.; Jeschke, M.G

    2014-01-01

    Burn injury is a severe form of trauma affecting more than two million people in North America each year. Burn trauma is not a single pathophysiological event but a devastating injury that causes structural and functional deficits in numerous organ systems. Due to its complexity and the involvement of multiple organs, in vitro experiments cannot capture this complexity nor address the pathophysiology. In the past two decades, a number of burn animal models have been developed to replicate the...

  3. Animal models for microbicide studies

    OpenAIRE

    Veazey, Ronald S.; Shattock, Robin J.; Klasse, Per Johan; Moore, John P.

    2012-01-01

    There have been encouraging recent successes in the development of safe and effective topical microbicides to prevent vaginal or rectal HIV-1 transmission, based on the use of anti-retroviral drugs. However, much work remains to be accomplished before a microbicide becomes a standard element of prevention science strategies. Animal models should continue to play an important role in pre-clinical testing, with emphasis on safety, pharmacokinetic and efficacy testing.

  4. Animal modelling for inherited central vision loss.

    Science.gov (United States)

    Kostic, Corinne; Arsenijevic, Yvan

    2016-01-01

    Disease-causing variants of a large number of genes trigger inherited retinal degeneration leading to photoreceptor loss. Because cones are essential for daylight and central vision such as reading, mobility, and face recognition, this review focuses on a variety of animal models for cone diseases. The pertinence of using these models to reveal genotype/phenotype correlations and to evaluate new therapeutic strategies is discussed. Interestingly, several large animal models recapitulate human diseases and can serve as a strong base from which to study the biology of disease and to assess the scale-up of new therapies. Examples of innovative approaches will be presented such as lentiviral-based transgenesis in pigs and adeno-associated virus (AAV)-gene transfer into the monkey eye to investigate the neural circuitry plasticity of the visual system. The models reported herein permit the exploration of common mechanisms that exist between different species and the identification and highlighting of pathways that may be specific to primates, including humans. PMID:26387748

  5. NIH Researchers Find Resveratrol Helps Protect against Cardiovascular Disease in Animal Study

    Science.gov (United States)

    ... find Resveratrol helps protect against cardiovascular disease in animal study June 3, 2014 Resveratrol, a compound found ... translatable to humans. Multiple studies on resveratrol in animal models, however, have presented ample evidence to support ...

  6. Haemolysis and perturbations in the systemic iron metabolism of suckling, copper-deficient mosaic mutant mice - an animal model of Menkes disease.

    Directory of Open Access Journals (Sweden)

    Małgorzata Lenartowicz

    Full Text Available The biological interaction between copper and iron is best exemplified by the decreased activity of multicopper ferroxidases under conditions of copper deficiency that limits the availability of iron for erythropoiesis. However, little is known about how copper deficiency affects iron homeostasis through alteration of the activity of other copper-containing proteins, not directly connected with iron metabolism, such as superoxide dismutase 1 (SOD1. This antioxidant enzyme scavenges the superoxide anion, a reactive oxygen species contributing to the toxicity of iron via the Fenton reaction. Here, we analyzed changes in the systemic iron metabolism using an animal model of Menkes disease: copper-deficient mosaic mutant mice with dysfunction of the ATP7A copper transporter. We found that the erythrocytes of these mutants are copper-deficient, display decreased SOD1 activity/expression and have cell membrane abnormalities. In consequence, the mosaic mice show evidence of haemolysis accompanied by haptoglobin-dependent elimination of haemoglobin (Hb from the circulation, as well as the induction of haem oxygenase 1 (HO1 in the liver and kidney. Moreover, the hepcidin-ferroportin regulatory axis is strongly affected in mosaic mice. These findings indicate that haemolysis is an additional pathogenic factor in a mouse model of Menkes diseases and provides evidence of a new indirect connection between copper deficiency and iron metabolism.

  7. The wobbler mouse, an ALS animal model

    DEFF Research Database (Denmark)

    Moser, Jakob Maximilian; Bigini, Paolo; Schmitt-John, Thomas

    2013-01-01

    This review article is focused on the research progress made utilizing the wobbler mouse as animal model for human motor neuron diseases, especially the amyotrophic lateral sclerosis (ALS). The wobbler mouse develops progressive degeneration of upper and lower motor neurons and shows striking...... disease mechanism and testing various therapeutic approaches and discuss the relevance of these advances for human ALS. The identification of the causative mutation linking the wobbler mutation to a vesicle transport factor and the research focussed on the cellular basis and the therapeutic treatment of...

  8. Potential role of some nutraceuticals in the regression of Alzheimer’s disease in an experimental animal model

    OpenAIRE

    AHMED, Hanna Hamdy; SHOUSHA, Wafaa Ghoneim; HUSSIEN, Rehab Mahmoud; FARRAG, Abdel Razik Hussein

    2011-01-01

    The goal of this study was to evaluate the potential role of some nutraceuticals, coenzyme Q10, vitamin B complex, and lecithin against aluminum-induced neurodegeneration characteristic of Alzheimer's disease. Materials and methods: Ninety-six male and female Sprague Dawley rats were divided into 2 main groups, namely female and male. Each group was divided into 6 subgroups. Group 1 served as control group. Group 2 was administered AlCl3 for 4 months. Groups 3, 4, 5, and 6 were adminis...

  9. On the surveillance for animal diseases in small herds

    DEFF Research Database (Denmark)

    Greiner, Matthias; Dekker, Aldo

    2005-01-01

    Small herds may present a problem in surveillance for infectious animal diseases because typical levels of a within-herd design prevalence are not directly applicable. We suggest a definition of small herds as those smaller than 2/(within-herd design prevalence) on the basis that such herds would...... be expected to have less than two (i.e. only one) infected animals. Consequently, the probability of detecting small herds cannot be improved by choosing a larger sample size within the herd. We derive necessary sample sizes of herds and the probability ("confidence") of detecting disease within a stratum...... of small herds, given the among-herd design prevalence and test diagnostic sensitivity. Both a binomial model and a Poisson model can be used to establish the confidence for a given sample size of herds (and vice versa). The results of a simulation study suggest that the Poisson model provides more...

  10. Animal Migraine Models for Drug Development

    DEFF Research Database (Denmark)

    Jansen-Olesen, Inger; Tfelt-Hansen, Peer; Olesen, Jes

    2013-01-01

    Migraine is number seven in WHO's list of all diseases causing disability and the third most costly neurological disorder in Europe. Acute attacks are treatable by highly selective drugs such as the triptans but there is still a huge unmet therapeutic need. Unfortunately, drug development for...... headache has almost come to a standstill partly because of a lack of valid animal models. Here we review previous models with emphasis on optimal characteristics of a future model. In addition to selection of animal species, the method of induction of migraine-like changes and the method of recording...... responses elicited by such measures are crucial. The most naturalistic way of inducing attacks is by infusion of endogenous signaling molecules that are known to cause migraine in patients. The most valid response is recording of neural activity in the trigeminal system. The most useful headache related...

  11. Exploring the Validity of Valproic Acid Animal Model of Autism

    OpenAIRE

    Darine Froy N. Mabunga; Gonzales, Edson Luck T.; Kim, Ji-Woon; Kim, Ki Chan; Shin, Chan Young

    2015-01-01

    The valproic acid (VPA) animal model of autism spectrum disorder (ASD) is one of the most widely used animal model in the field. Like any other disease models, it can't model the totality of the features seen in autism. Then, is it valid to model autism? This model demonstrates many of the structural and behavioral features that can be observed in individuals with autism. These similarities enable the model to define relevant pathways of developmental dysregulation resulting from environmenta...

  12. Regulatory T Cells and Their Role in Animal Disease.

    Science.gov (United States)

    Veiga-Parga, T

    2016-07-01

    In humans and mouse models, Foxp3(+) regulatory T cells are known to control all aspects of immune responses. However, only limited information exists on these cells' role in diseases of other animals. In this review, we cover the most important features and different types of regulatory T cells, which include those that are thymus-derived and peripherally induced, the mechanisms by which they control immune responses by targeting effector T cells and antigen-presenting cells, and most important, their role in animal health and diseases including cancer, infections, and other conditions such as hypersensitivities and autoimmunity. Although the literature regarding regulatory T cells in domestic animal species is still limited, multiple articles have recently emerged and are discussed. Moreover, we also discuss the evidence suggesting that regulatory T cells might limit the magnitude of effector responses, which can have either a positive or negative result, depending on the context of animal and human disease. In addition, the issue of plasticity is discussed because plasticity in regulatory T cells can result in the loss of their protective function in some microenvironments during disease. Lastly, the manipulation of regulatory T cells is discussed in assessing the possibility of their use as a treatment in the future. PMID:26945003

  13. Novel therapeutic targets in osteoarthritis: Narrative review on knock-out genes involved in disease development in mouse animal models.

    Science.gov (United States)

    Veronesi, Francesca; Della Bella, Elena; Cepollaro, Simona; Brogini, Silvia; Martini, Lucia; Fini, Milena

    2016-05-01

    Osteoarthritis (OA) can affect every joint, especially the knee. Given the complexity of this pathology, OA is difficult to treat with current therapies, which only relieve pain and inflammation and are not capable of restoring tissues once OA has started. Currently, researchers focus on finding a therapeutic strategy that may help to arrest disease progression. The present narrative review gives an overview of the genes involved in the development and progression of OA, assessing in vivo studies performed in knock-out mice affected by OA, to suggest new therapeutic strategies. The article search was performed on the PubMed database and www.webofknowledge.com website with the following keywords: "knee osteoarthritis" AND "knockout mice". The included studies were in English and published from 2005 to 2015. Additional papers were found within the references of the selected articles. In the 55 analyzed in vivo studies, genes mainly affected chondrocyte homeostasis, inflammatory processes, extracellular matrix and the relationship between obesity and OA. Genes are defined as inducing, preventing and not influencing OA. This review shows that joint homeostasis depends on a variety of genetic factors, and preventing or restoring the loss of a gene encoding for protective proteins, or inhibiting the expression of proteins that induce OA, might be a potential therapeutic approach. However, conclusions cannot be drawn because of the wide variability concerning the technique used for OA induction, the role of the genes, the method for tissue evaluations and the lack of assessments of all joint tissues. PMID:27059198

  14. Animal Models of Dengue Virus Infection

    Directory of Open Access Journals (Sweden)

    Eva Harris

    2012-01-01

    Full Text Available The development of animal models of dengue virus (DENV infection and disease has been challenging, as epidemic DENV does not naturally infect non-human species. Non-human primates (NHPs can sustain viral replication in relevant cell types and develop a robust immune response, but they do not develop overt disease. In contrast, certain immunodeficient mouse models infected with mouse-adapted DENV strains show signs of severe disease similar to the ‘vascular-leak’ syndrome seen in severe dengue in humans. Humanized mouse models can sustain DENV replication and show some signs of disease, but further development is needed to validate the immune response. Classically, immunocompetent mice infected with DENV do not manifest disease or else develop paralysis when inoculated intracranially; however, a new model using high doses of DENV has recently been shown to develop hemorrhagic signs after infection. Overall, each model has its advantages and disadvantages and is differentially suited for studies of dengue pathogenesis and immunopathogenesis and/or pre-clinical testing of antiviral drugs and vaccines.

  15. Experimental Diabetes Mellitus in Different Animal Models.

    Science.gov (United States)

    Al-Awar, Amin; Kupai, Krisztina; Veszelka, Médea; Szűcs, Gergő; Attieh, Zouhair; Murlasits, Zsolt; Török, Szilvia; Pósa, Anikó; Varga, Csaba

    2016-01-01

    Animal models have historically played a critical role in the exploration and characterization of disease pathophysiology and target identification and in the evaluation of novel therapeutic agents and treatments in vivo. Diabetes mellitus disease, commonly known as diabetes, is a group of metabolic disorders characterized by high blood glucose levels for a prolonged time. To avoid late complications of diabetes and related costs, primary prevention and early treatment are therefore necessary. Due to its chronic symptoms, new treatment strategies need to be developed, because of the limited effectiveness of the current therapies. We overviewed the pathophysiological features of diabetes in relation to its complications in type 1 and type 2 mice along with rat models, including Zucker Diabetic Fatty (ZDF) rats, BB rats, LEW 1AR1/-iddm rats, Goto-Kakizaki rats, chemically induced diabetic models, and Nonobese Diabetic mouse, and Akita mice model. The advantages and disadvantages that these models comprise were also addressed in this review. This paper briefly reviews the wide pathophysiological and molecular mechanisms associated with type 1 and type 2 diabetes, particularly focusing on the challenges associated with the evaluation and predictive validation of these models as ideal animal models for preclinical assessments and discovering new drugs and therapeutic agents for translational application in humans. PMID:27595114

  16. Satureja bachtiarica ameliorate beta-amyloid induced memory impairment, oxidative stress and cholinergic deficit in animal model of Alzheimer's disease.

    Science.gov (United States)

    Soodi, Maliheh; Saeidnia, Soodabeh; Sharifzadeh, Mohammad; Hajimehdipoor, Homa; Dashti, Abolfazl; Sepand, Mohammad Reza; Moradi, Shahla

    2016-04-01

    Extracellular deposition of Beta-amyloid peptide (Aβ) is the main finding in the pathophysiology of Alzheimer's disease (AD), which damages cholinergic neurons through oxidative stress and reduces the cholinergic neurotransmission. Satureja bachtiarica is a medicinal plant from the Lamiaceae family which was widely used in Iranian traditional medicine. The aim of the present study was to investigate possible protective effects of S. bachtiarica methanolic extract on Aβ induced spatial memory impairment in Morris Water Maze (MWM), oxidative stress and cholinergic neuron degeneration. Pre- aggregated Aβ was injected into the hippocampus of each rat bilaterally (10 μg/rat) and MWM task was performed 14 days later to evaluate learning and memory function. Methanolic extract of S.bachtiarica (10, 50 and 100 mg/Kg) was injected intraperitoneally for 19 consecutive days, after Aβ injection. After the probe test the brain tissue were collected and lipid peroxidation, Acetylcholinesterase (AChE) activity and Cholin Acetyl Transferees (ChAT) immunorectivity were measured in the hippocampus. Intrahipocampal injection of Aβ impaired learning and memory in MWM in training days and probe trail. Methanolic extract of S. bachtiarica (50 and 100 mg/Kg) could attenuate Aβ-induced memory deficit. ChAT immunostaining revealed that cholinergic neurons were loss in Aβ- injected group and S. bachtiarica (100 mg/Kg) could ameliorate Aβ- induced ChAT reduction in the hippocampus. Also S. bachtiarica could ameliorate Aβ-induced lipid peroxidation and AChE activity increase in the hippocampus. In conclusion our study represent that S.bachtiarica methanolic extract can improve Aβ-induced memory impairment and cholinergic loss then we recommended this extract as a candidate for further investigation in treatment of AD. PMID:26638718

  17. Aspects of animal models for major neuropsychiatric disorders

    Directory of Open Access Journals (Sweden)

    Lefter Radu

    2014-01-01

    Full Text Available We will review the main animal models for the major neuropsychiatric disorders, focusing on schizophrenia, Alzheimer’s disease, Parkinson’s disease, depression, anxiety and autism. Although these mental disorders are specifically human pathologies and therefore impossible to perfectly replicate in animals, the use of experimental animals is based on the physiological and anatomical similarities between humans and animals such as the rat, and mouse, and on the fact that 99% of human and murine genomes are shared. Pathological conditions in animals can be assessed by manipulating the metabolism of neurotransmitters, through various behavioral tests, and by determining biochemical parameters that can serve as important markers of disorders.

  18. Proliferative retinopathies: animal models and therapeutic opportunities.

    Science.gov (United States)

    Villacampa, Pilar; Haurigot, Virginia; Bosch, Fatima

    2015-01-01

    Proliferative retinopathies are the leading causes of blindness in Western societies. The development of new, more efficacious treatments that take advantage of recent advances in the fields of gene and cell therapy requires further investigations on the mechanisms underlying disease onset and progression, and adequate animal models that recapitulate the pathogenesis of human proliferative retinopathy and allow evaluation of the long-term therapeutic benefits that these therapies can offer. Unfortunately, most models of retinal neovascularization have short-term evolution and diabetic rodents show a very mild retinal phenotype, limited to non-proliferative changes, and do not develop proliferative retinopathy at all. Transgenic mice overexpressing Insulin-like Growth Factor-I (IGF-I) in the retina (TgIGF-I) constitute the only rodent model currently available that develops most of the retinal alterations observed in diabetic eyes, with a temporal evolution that resembles that of the human disease. TgIGF-I have retinal vascular alterations that progress as animals age from non-proliferative to proliferative disease, making these mice an excellent model of proliferative retinopathy that, due to its slow progression, allows long-term evaluation of novel antiangiogenic therapies. At the molecular level, transgenic retinas recapitulate a variety of changes that are also observed in diabetic retinas, which reinforces the validity of this model. In addition to vascular and glial alterations, Tg-IGF-I mice show progressive neurodegeneration that leads to blindness in old animals. Thus, TgIGF-I are a useful model for testing the long-term efficacy and safety of innovative antiangiogenic, glial-modulating and neuroprotective therapies for the treatment of diabetic retinopathy and other retinal proliferative disorders. PMID:25760215

  19. Evaluation of animal models of neurobehavioral disorders

    OpenAIRE

    Nordquist Rebecca E; Arndt Saskia S; van der Staay F Josef

    2009-01-01

    Abstract Animal models play a central role in all areas of biomedical research. The process of animal model building, development and evaluation has rarely been addressed systematically, despite the long history of using animal models in the investigation of neuropsychiatric disorders and behavioral dysfunctions. An iterative, multi-stage trajectory for developing animal models and assessing their quality is proposed. The process starts with defining the purpose(s) of the model, preferentiall...

  20. An animal model of fetishism.

    Science.gov (United States)

    Köksal, Falih; Domjan, Michael; Kurt, Adnan; Sertel, Ozlem; Orüng, Sabiha; Bowers, Rob; Kumru, Gulsen

    2004-12-01

    An animal model of sexual fetishism was developed with male Japanese quail based on persistence of conditioned sexual responding during extinction to an inanimate object made of terrycloth (Experiments 1 and 3). This persistent responding occurred only in subjects that came to copulate with the terrycloth object, suggesting that the copulatory behavior served to maintain the fetishistic behavior. Sexual conditioning was carried out by pairing a conditioned stimulus (CS) with the opportunity to copulate with a female (the unconditioned stimulus or US). Copulation with the CS object and persistent responding did not develop if the CS was a light (Experiment 1) or if conditioning was carried out with a food US (Experiment 2). In addition, subjects that showed persistence in responding to the terrycloth CS did not persist in their responding to a light CS (Experiment 3). The results are consistent with the hypothesis that conditioned copulatory behavior creates a form of self-maintenance that leads to persistent responding to an inanimate object. The development of an animal model of such fetishistic behavior should facilitate experimental analysis of the phenomenon. PMID:15500813

  1. Animal models of bronchopulmonary dysplasia. The preterm baboon models

    OpenAIRE

    Yoder, Bradley A.; Coalson, Jacqueline J.

    2014-01-01

    Much of the progress in improved neonatal care, particularly management of underdeveloped preterm lungs, has been aided by investigations of multiple animal models, including the neonatal baboon (Papio species). In this article we highlight how the preterm baboon model at both 140 and 125 days gestation (term equivalent 185 days) has advanced our understanding and management of the immature human infant with neonatal lung disease. Not only is the 125-day baboon model extremely relevant to the...

  2. Infectious disease in animal metapopulations: the importance of environmental transmission.

    Science.gov (United States)

    Park, Andrew W

    2012-07-01

    Motivated by an array of infectious diseases that threaten wildlife populations, a simple metapopulation model (subpopulations connected by animal movement) is developed, which allows for both movement-based and environmental transmission. The model demonstrates that for a range of plausible parameterizations of environmental transmission, increased movement rate of animals between discrete habitats can lead to a decrease in the overall proportion of sites that are occupied. This can limit the ability of the rescue effect to ensure locally extinct populations become recolonized and can drive metapopulations down in size so that extinction by mechanisms other than disease may become more likely. It further highlights that, in the context of environmental transmission, the environmental persistence time of pathogens and the probability of acquiring infection by environmental transmission can affect host metapopulations both qualitatively and quantitatively. Additional spillover sources of infection from alternate reservoir hosts are also included in the model and a synthesis of all three types of transmission, acting alone or in combination, is performed revealing that movement-based transmission is the only necessary condition for a decline in the proportion of occupied sites with increasing movement rate, but that the presence of other types of transmission can reverse this qualitative result. By including the previously neglected role of environmental transmission, this work contributes to the general discussion of when dispersal by wild animals is beneficial or detrimental to populations experiencing infectious disease. PMID:22957148

  3. Animal models and conserved processes

    Directory of Open Access Journals (Sweden)

    Greek Ray

    2012-09-01

    Full Text Available Abstract Background The concept of conserved processes presents unique opportunities for using nonhuman animal models in biomedical research. However, the concept must be examined in the context that humans and nonhuman animals are evolved, complex, adaptive systems. Given that nonhuman animals are examples of living systems that are differently complex from humans, what does the existence of a conserved gene or process imply for inter-species extrapolation? Methods We surveyed the literature including philosophy of science, biological complexity, conserved processes, evolutionary biology, comparative medicine, anti-neoplastic agents, inhalational anesthetics, and drug development journals in order to determine the value of nonhuman animal models when studying conserved processes. Results Evolution through natural selection has employed components and processes both to produce the same outcomes among species but also to generate different functions and traits. Many genes and processes are conserved, but new combinations of these processes or different regulation of the genes involved in these processes have resulted in unique organisms. Further, there is a hierarchy of organization in complex living systems. At some levels, the components are simple systems that can be analyzed by mathematics or the physical sciences, while at other levels the system cannot be fully analyzed by reducing it to a physical system. The study of complex living systems must alternate between focusing on the parts and examining the intact whole organism while taking into account the connections between the two. Systems biology aims for this holism. We examined the actions of inhalational anesthetic agents and anti-neoplastic agents in order to address what the characteristics of complex living systems imply for inter-species extrapolation of traits and responses related to conserved processes. Conclusion We conclude that even the presence of conserved processes is

  4. Animal behavioral assessments in current research of Parkinson's disease.

    Science.gov (United States)

    Asakawa, Tetsuya; Fang, Huan; Sugiyama, Kenji; Nozaki, Takao; Hong, Zhen; Yang, Yilin; Hua, Fei; Ding, Guanghong; Chao, Dongman; Fenoy, Albert J; Villarreal, Sebastian J; Onoe, Hirotaka; Suzuki, Katsuaki; Mori, Norio; Namba, Hiroki; Xia, Ying

    2016-06-01

    Parkinson's disease (PD), a neurodegenerative disorder, is traditionally classified as a movement disorder. Patients typically suffer from many motor dysfunctions. Presently, clinicians and scientists recognize that many non-motor symptoms are associated with PD. There is an increasing interest in both motor and non-motor symptoms in clinical studies on PD patients and laboratory research on animal models that imitate the pathophysiologic features and symptoms of PD patients. Therefore, appropriate behavioral assessments are extremely crucial for correctly understanding the mechanisms of PD and accurately evaluating the efficacy and safety of novel therapies. This article systematically reviews the behavioral assessments, for both motor and non-motor symptoms, in various animal models involved in current PD research. We addressed the strengths and weaknesses of these behavioral tests and their appropriate applications. Moreover, we discussed potential mechanisms behind these behavioral tests and cautioned readers against potential experimental bias. Since most of the behavioral assessments currently used for non-motor symptoms are not particularly designed for animals with PD, it is of the utmost importance to greatly improve experimental design and evaluation in PD research with animal models. Indeed, it is essential to develop specific assessments for non-motor symptoms in PD animals based on their characteristics. We concluded with a prospective view for behavioral assessments with real-time assessment with mobile internet and wearable device in future PD research. PMID:27026638

  5. Modeling alcohol's effects on organs in animal models.

    Science.gov (United States)

    Ponnappa, B C; Rubin, E

    2000-01-01

    Researchers have developed numerous animal models to investigate the development of various alcohol-related diseases. Such models have provided insights into the mechanism through which alcohol can induce liver damage. Animal models also have helped researchers explore the mechanisms by which both short-term (e.g., binge) and long-term drinking can interfere with the function of the heart, a condition referred to as alcoholic cardiomyopathy. Furthermore, animal models have provided substantial information on the causes of fetal alcohol syndrome. Such models have demonstrated that exposure to alcohol during gestation can lead to prenatal and postnatal growth retardation, characteristic facial malformations, immune system deficiencies, and alterations in the central nervous system. PMID:11199283

  6. Evaluation of nigrostriatal damage and its change over weeks in a rat model of Parkinson's disease: small animal positron emission tomography studies with [11C]β-CFT

    International Nuclear Information System (INIS)

    Introduction: The cardinal pathological feature of Parkinson's disease (PD) is progressive loss of dopaminergic neurons. Since dopamine transporter (DAT) is a protein located presynaptically on dopaminergic nerve terminals, radioligands that bind to these sites are promising radiopharmaceuticals for evaluation of the integrity of the dopamine system. This study using positron emission tomography (PET) tracers, [11C]-2β-carbomethoxy-3β-(4-fluorophenyl)-tropane ([11C]β-CFT, radioligand for DAT), was aimed at evaluating the degree of nigrostriatal damage and its change over weeks in a rat model of PD. Methods: The brains of these rats were unilaterally lesioned by mechanical transection of the nigrostriatal dopamine pathway at the medial forebrain bundle (MFB). Behavioral studies were carried out by apomorphine (APO) challenge prior to and 1, 2 and 4 weeks after MFB axotomy. Small animal PET scans were performed 2 days after the behavioral test. Immunohistochemistry was conducted 4 days after the last PET scan. Results: Compared with the contralateral intact side, a progressively decreased [11C]β-CFT binding was observed on the lesioned side which correlated inversely with the APO-induced rotations. Postmortem immunohistochemical studies confirmed the loss of both striatal dopamine fibers and nigral neurons on the lesioned side. Conclusion: These findings not only demonstrate that the neuronal degeneration in this model is relatively slow, but also suggest [11C]β-CFT is a sensitive marker to monitor the degree of nigrostriatal damage and its change over weeks. This marker can be used prospectively to study the progression of the disease, thereby making detection of early phases of PD possible.

  7. A physically-modified saline suppresses neuronal apoptosis, attenuates tau phosphorylation and protects memory in an animal model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Khushbu K Modi

    Full Text Available Alzheimer's disease (AD, the leading cause of dementia in the aging population, is characterized by the presence of neuritic plaques, neurofibrillary tangles and extensive neuronal apoptosis. Neuritic plaques are mainly composed of aggregates of amyloid-β (Aβ protein while neurofibrillary tangles are composed of the hyperphosphorylated tau protein. Despite intense investigations, no effective therapy is currently available to halt the progression of this disease. Here, we have undertaken a novel approach to attenuate apoptosis and tau phosphorylation in cultured neuronal cells and in a transgenic animal model of AD. RNS60 is a 0.9% saline solution containing oxygenated nanobubbles that is generated by subjecting normal saline to Taylor-Couette-Poiseuille (TCP flow under elevated oxygen pressure. In our experiments, fibrillar Aβ1-42, but not the reverse peptide Aβ42-1, induced apoptosis and cell death in human SHSY5Y neuronal cells. RNS60, but not NS (normal saline, RNS10.3 (TCP-modified saline without excess oxygen or PNS60 (saline containing excess oxygen without TCP modification, attenuated Aβ(1-42-induced cell death. RNS60 inhibited neuronal cell death via activation of the type 1A phosphatidylinositol-3 (PI-3 kinase-Akt-BAD pathway. Furthermore, RNS60 also decreased Aβ(1-42-induced tau phosphorylation via (PI-3 kinase-Akt-mediated inhibition of GSK-3β. Similarly, RNS60 treatment suppressed neuronal apoptosis, attenuated Tau phosphorylation, inhibited glial activation, and reduced the burden of Aβ in the hippocampus and protected memory and learning in 5XFAD transgenic mouse model of AD. Therefore, RNS60 may be a promising pharmaceutical candidate in halting or delaying the progression of AD.

  8. Animal models of recurrent or bipolar depression.

    Science.gov (United States)

    Kato, T; Kasahara, T; Kubota-Sakashita, M; Kato, T M; Nakajima, K

    2016-05-01

    Animal models of mental disorders should ideally have construct, face, and predictive validity, but current animal models do not always satisfy these validity criteria. Additionally, animal models of depression rely mainly on stress-induced behavioral changes. These stress-induced models have limited validity, because stress is not a risk factor specific to depression, and the models do not recapitulate the recurrent and spontaneous nature of depressive episodes. Although animal models exhibiting recurrent depressive episodes or bipolar depression have not yet been established, several researchers are trying to generate such animals by modeling clinical risk factors as well as by manipulating a specific neural circuit using emerging techniques. PMID:26265551

  9. Lessons Learned from Animal Models of Inherited Bleeding Disorders

    OpenAIRE

    Nichols, Timothy C.

    2014-01-01

    Advances in treatment of hemophilia and von Willebrand disease (VWD) depend heavily on the availability of well-characterized animal models. These animals faithfully recapitulate the severe bleeding phenotype that occurs in humans with these inherited bleeding disorders. Research in these animal models represents important early and intermediate steps of translational research aimed at addressing current limitations in treatment such as the development of inhibitory antibodies to coagulation ...

  10. Progress in animal model of radiation-induced heart disease%放射性心脏损伤动物模型的研究进展

    Institute of Scientific and Technical Information of China (English)

    张洪明; 李险峰

    2014-01-01

    The incidence of cancer has surpassed the cardiovascular disease as the first one in China.With the improvement and development of surgical techniques and chemo-radiotherapy,the patient's survival time has been prolonged greatly.On the contrary,long-term and recent complications caused during the tumors treatment process have become one of the main factors which severely influence the quality of life of the patients.Cardiovascular recent and long-term adverse reaction caused by radiation has become the major cause of death in cancer patients especially for thoracic,chest wall and mediastinal tumor (such as Hodgkin's lymphoma,breast cancer,etc.).And stable animal model is the basis of clinical research of radioactive heart damage which can provide a large number of experiments for the prevention and treatment of radioactive heart damage.For this purpose,the article reviewed the animal model of radioactive heart damage and its characteristics,the improvement and development of the modelling methods,and the concrete application of the model.%目前我国肿瘤发病率已超越心血管疾病跃居第一位,随着外科及放化疗技术的提升与发展,肿瘤患者的生存周期已得到大幅度提高.与之相反的是肿瘤在治疗过程中所引起的近期和远期并发症却已成为影响患者生存质量的主要因素,尤其是胸廓、胸壁及纵隔肿瘤(如霍奇金淋巴瘤、乳腺癌等)在进行放疗时所引起的心脏的近期及远期不良反应,成为该类肿瘤患者死亡的重要原因之一.而稳定的动物模型是临床前研究放射性心脏损伤的基础,为放射性心脏损伤的预防和治疗提供大量实验依据.为此该文对历年来研究者常用建立放射性心脏损伤模型的造模动物及其特点、造模方法的改进与发展、模型的具体应用进行综述.

  11. Biology of Obesity: Lessons from Animal Models of Obesity

    OpenAIRE

    Keizo Kanasaki; Daisuke Koya

    2011-01-01

    Obesity is an epidemic problem in the world and is associated with several health problems, including diabetes, cardiovascular disease, respiratory failure, muscle weakness, and cancer. The precise molecular mechanisms by which obesity induces these health problems are not yet clear. To better understand the pathomechanisms of human disease, good animal models are essential. In this paper, we will analyze animal models of obesity and their use in the research of obesity-associated human he...

  12. Towards an animal model of food addiction.

    Science.gov (United States)

    de Jong, Johannes W; Vanderschuren, Louk J M J; Adan, Roger A H

    2012-01-01

    The dramatically increasing prevalence of obesity, associated with potentially life-threatening health problems, including cardiovascular diseases and type II diabetes, poses an enormous public health problem. It has been proposed that the obesity epidemic can be explained by the concept of 'food addiction'. In this review we focus on possible similarities between binge eating disorder (BED), which is highly prevalent in the obese population, and drug addiction. Indeed, both behavioral and neural similarities between addiction and BED have been demonstrated. Behavioral similarities are reflected in the overlap in DSM-IV criteria for drug addiction with the (suggested) criteria for BED and by food addiction-like behavior in animals after prolonged intermittent access to palatable food. Neural similarities include the overlap in brain regions involved in food and drug craving. Decreased dopamine D2 receptor availability in the striatum has been found in animal models of binge eating, after cocaine self-administration in animals as well as in drug addiction and obesity in humans. To further explore the neurobiological basis of food addiction, it is essential to have an animal model to test the addictive potential of palatable food. A recently developed animal model for drug addiction involves three behavioral characteristics that are based on the DSM-IV criteria: i) extremely high motivation to obtain the drug, ii) difficulty in limiting drug seeking even in periods of explicit non-availability, iii) continuation of drug-seeking despite negative consequences. Indeed, it has been shown that a subgroup of rats, after prolonged cocaine self-administration, scores positive on these three criteria. If food possesses addictive properties, then food-addicted rats should also meet these criteria while searching for and consuming food. In this review we discuss evidence from literature regarding food addiction-like behavior. We also suggest future experiments that could

  13. Impact of thoracic surgery on cardiac morphology and function in small animal models of heart disease: a cardiac MRI study in rats.

    Directory of Open Access Journals (Sweden)

    Peter Nordbeck

    Full Text Available BACKGROUND: Surgical procedures in small animal models of heart disease might evoke alterations in cardiac morphology and function. The aim of this study was to reveal and quantify such potential artificial early or long term effects in vivo, which might account for a significant bias in basic cardiovascular research, and, therefore, could potentially question the meaning of respective studies. METHODS: Female Wistar rats (n = 6 per group were matched for weight and assorted for sham left coronary artery ligation or control. Cardiac morphology and function was then investigated in vivo by cine magnetic resonance imaging at 7 Tesla 1 and 8 weeks after the surgical procedure. The time course of metabolic and inflammatory blood parameters was determined in addition. RESULTS: Compared to healthy controls, rats after sham surgery showed a lower body weight both 1 week (267.5±10.6 vs. 317.0±11.3 g, n<0.05 and 8 weeks (317.0±21.1 vs. 358.7±22.4 g, n<0.05 after the intervention. Left and right ventricular morphology and function were not different in absolute measures in both groups 1 week after surgery. However, there was a confined difference in several cardiac parameters normalized to the body weight (bw, such as myocardial mass (2.19±0.30/0.83±0.13 vs. 1.85±0.22/0.70±0.07 mg left/right per g bw, p<0.05, or enddiastolic ventricular volume (1.31±0.36/1.21±0.31 vs. 1.14±0.20/1.07±0.17 µl left/right per g bw, p<0.05. Vice versa, after 8 weeks, cardiac masses, volumes, and output showed a trend for lower values in sham operated rats compared to controls in absolute measures (782.2±57.2/260.2±33.2 vs. 805.9±84.8/310.4±48.5 mg, p<0.05 for left/right ventricular mass, but not normalized to body weight. Matching these findings, blood testing revealed only minor inflammatory but prolonged metabolic changes after surgery not related to cardiac disease. CONCLUSION: Cardio-thoracic surgical procedures in experimental myocardial infarction

  14. Animal models of extracranial pediatric solid tumors

    OpenAIRE

    Seitz, Guido; Armeanu-Ebinger, Sorin; WARMANN, STEVEN; Fuchs, Jörg

    2012-01-01

    Animal models, including xenografts, models of metastatic invasion, syngeneic models and transgenic models, are important tools for basic research in solid pediatric tumors, while humanized animal models are useful for novel immunotherapeutical approaches. Optical and molecular imaging techniques are used for in vivo imaging and may be used in conjunction with alternative treatment approaches, including photodynamic therapy. The aim of this review is to highlight the various animal models tha...

  15. Effects of Bacillus subtilis 'PB6' (ATCC - PTA 6737 on Clostridium difficile Associated Diarrhea (CDAD and Inflammatory Bowel Disease (IBD in Animal Models

    Directory of Open Access Journals (Sweden)

    Eric Peys

    2007-01-01

    Full Text Available The administration of probiotic bacteria is emerging as a potential means of preventing the onset or recurrence of Clostridium difficile associated diarrhea (CDAD and of attenuating inflammatory activity and preventing relapses in inflammatory bowel disease (IBD. We evaluated the efficacy of Bacillus subtilis ‘PB6’ (ATCC – PTA 6737 in a hamster model of antibiotic-induced CDAD and in a rat model of IBD. CDAD was induced in male Golden Syrian hamsters using C. difficile and clindamycin. These hamsters received either nothing or, by gavage, vancomycin (5 days or PB6 (low, middle and high dose, 6 days. Diarrhea, body weight loss and mortality were observed in all groups in which CDAD was induced. Intensity of diarrhea and body weight loss was least in the groups treated with vancomycin or with the highest dose of PB6. At the end of the treatment period, vancomycin and the highest dose of PB6 were equally efficient in preventing mortality in this hamster model of CDAD. No adverse effects of PB6 treatment were observed in healthy animals. In male Wistar rats, colitis was induced using a single intrarectal administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS. Treatments consisted of PB6 (low, middle and high dose, Saccharomyces boulardii, mesalazine, infliximab, or no treatment. A possible benefit of the prophylactic use of PB6 was also tested. At the end of the treatment period significant differences in body weight gain, in colon inflammatory edema and in gross morphology of the colon intestinal lining were observed between groups. The groups treated with high dose PB6 could not be distincted from the colitis-free negative control group nor from the group treated with mesalazine. The data presented are suggestive of possible therapeutic effectiveness of PB6 in CDAD and IBD in humans.

  16. Models of breast cancer: quo vadis, animal modeling?

    International Nuclear Information System (INIS)

    Rodent models for breast cancer have for many decades provided unparalleled insights into cellular and molecular aspects of neoplastic transformation and tumorigenesis. Despite recent improvements in the fidelity of genetically engineered mice, rodent models are still being criticized by many colleagues for not being 'authentic' enough to the human disease. Motives for this criticism are manifold and range from a very general antipathy against the rodent model system to well-founded arguments that highlight physiological variations between species. Newly proposed differences in genetic pathways that cause cancer in humans and mice invigorated the ongoing discussion about the legitimacy of the murine system to model the human disease. The present commentary intends to stimulate a debate on this subject by providing the background about new developments in animal modeling, by disputing suggested limitations of genetically engineered mice, and by discussing improvements but also ambiguous expectations on the authenticity of xenograft models to faithfully mimic the human disease

  17. The methods of inducing polymyositis animal model

    International Nuclear Information System (INIS)

    Objective: To investigate the methods of inducing polymyosistis(PM) animal model. Methods: In order to develope a induce PM animal model in purified guinea pia muscle myosin mixed with complete Freund adjuvant was injected subcutaneously to SD rats many times and the results of the clinical finding, the EMG, the pathologic changes and the musclar MRI changes in SD rats was assessed. Results: The PM animal models were similar to the human in clinical findings, the EMG, the pathologic changes, the musclar MRI changes and so on. Conclusion: The animal model is similar to the human PM, it is an ideal animal model to investigate PM. (authors)

  18. Animal models of GM2 gangliosidosis: utility and limitations

    Directory of Open Access Journals (Sweden)

    Lawson CA

    2016-07-01

    Full Text Available Cheryl A Lawson,1,2 Douglas R Martin2,3 1Department of Pathobiology, 2Scott-Ritchey Research Center, 3Department of Anatomy, Physiology and Pharmacology, Auburn University College of Veterinary Medicine, Auburn, AL, USA Abstract: GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay–Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay–Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described. Keywords: GM2 gangliosidosis, Tay–Sachs disease, Sandhoff disease, lysosomal storage disorder, sphingolipidosis, brain disease

  19. Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer’s disease

    OpenAIRE

    Zhang, Xueli; Tian, Yanli; Zhang, Can; Tian, Xiaoyu; Ross, Alana W.; Moir, Robert D.; Sun, Hongbin; Tanzi, Rudolph E.; Moore, Anna; Ran, Chongzhao

    2015-01-01

    Drug development for Alzheimer’s disease (AD) has been largely unsuccessful to date. Although numerous agents are reportedly effective in vitro, only an inadequate number of them have been tested in vivo, partially because of the lack of reliable and cost-efficient imaging methods to monitor their in vivo therapeutic effectiveness. Several amyloid beta (Aβ)-specific PET tracers have been used for clinical studies. However, their application for monitoring drug treatment in small animals is li...

  20. Potency of Animal Models in KANSEI Engineering

    Science.gov (United States)

    Ozaki, Shigeru; Hisano, Setsuji; Iwamoto, Yoshiki

    Various species of animals have been used as animal models for neuroscience and provided critical information about the brain functions. Although it seems difficult to elucidate a highly advanced function of the human brain, animal models have potency to clarify the fundamental mechanisms of emotion, decision-making and social behavior. In this review, we will pick up common animal models and point to both the merits and demerits caused by the characteristics. We will also mention that wide-ranging approaches from animal models are advantageous to understand KANSEI as well as mind in humans.

  1. Cinnamon and Its Metabolite Sodium Benzoate Attenuate the Activation of p21rac and Protect Memory and Learning in an Animal Model of Alzheimer's Disease.

    Science.gov (United States)

    Modi, Khushbu K; Roy, Avik; Brahmachari, Saurabh; Rangasamy, Suresh B; Pahan, Kalipada

    2015-01-01

    This study underlines the importance of cinnamon, a commonly used natural spice and flavoring material, and its metabolite sodium benzoate (NaB) in attenuating oxidative stress and protecting memory and learning in an animal model of Alzheimer's disease (AD). NaB, but not sodium formate, was found to inhibit LPS-induced production of reactive oxygen species (ROS) in mouse microglial cells. Similarly, NaB also inhibited fibrillar amyloid beta (Aβ)- and 1-methyl-4-phenylpyridinium(+)-induced microglial production of ROS. Although NaB reduced the level of cholesterol in vivo in mice, reversal of the inhibitory effect of NaB on ROS production by mevalonate, and geranylgeranyl pyrophosphate, but not cholesterol, suggests that depletion of intermediates, but not end products, of the mevalonate pathway is involved in the antioxidant effect of NaB. Furthermore, we demonstrate that an inhibitor of p21rac geranylgeranyl protein transferase suppressed the production of ROS and that NaB suppressed the activation of p21rac in microglia. As expected, marked activation of p21rac was observed in the hippocampus of subjects with AD and 5XFAD transgenic (Tg) mouse model of AD. However, oral feeding of cinnamon (Cinnamonum verum) powder and NaB suppressed the activation of p21rac and attenuated oxidative stress in the hippocampus of Tg mice as evident by decreased dihydroethidium (DHE) and nitrotyrosine staining, reduced homocysteine level and increased level of reduced glutathione. This was accompanied by suppression of neuronal apoptosis, inhibition of glial activation, and reduction of Aβ burden in the hippocampus and protection of memory and learning in transgenic mice. Therefore, cinnamon powder may be a promising natural supplement in halting or delaying the progression of AD. PMID:26102198

  2. Cinnamon and Its Metabolite Sodium Benzoate Attenuate the Activation of p21rac and Protect Memory and Learning in an Animal Model of Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Khushbu K Modi

    Full Text Available This study underlines the importance of cinnamon, a commonly used natural spice and flavoring material, and its metabolite sodium benzoate (NaB in attenuating oxidative stress and protecting memory and learning in an animal model of Alzheimer's disease (AD. NaB, but not sodium formate, was found to inhibit LPS-induced production of reactive oxygen species (ROS in mouse microglial cells. Similarly, NaB also inhibited fibrillar amyloid beta (Aβ- and 1-methyl-4-phenylpyridinium(+-induced microglial production of ROS. Although NaB reduced the level of cholesterol in vivo in mice, reversal of the inhibitory effect of NaB on ROS production by mevalonate, and geranylgeranyl pyrophosphate, but not cholesterol, suggests that depletion of intermediates, but not end products, of the mevalonate pathway is involved in the antioxidant effect of NaB. Furthermore, we demonstrate that an inhibitor of p21rac geranylgeranyl protein transferase suppressed the production of ROS and that NaB suppressed the activation of p21rac in microglia. As expected, marked activation of p21rac was observed in the hippocampus of subjects with AD and 5XFAD transgenic (Tg mouse model of AD. However, oral feeding of cinnamon (Cinnamonum verum powder and NaB suppressed the activation of p21rac and attenuated oxidative stress in the hippocampus of Tg mice as evident by decreased dihydroethidium (DHE and nitrotyrosine staining, reduced homocysteine level and increased level of reduced glutathione. This was accompanied by suppression of neuronal apoptosis, inhibition of glial activation, and reduction of Aβ burden in the hippocampus and protection of memory and learning in transgenic mice. Therefore, cinnamon powder may be a promising natural supplement in halting or delaying the progression of AD.

  3. Mobile technologies for disease surveillance in humans and animals.

    Science.gov (United States)

    Mwabukusi, Mpoki; Karimuribo, Esron D; Rweyemamu, Mark M; Beda, Eric

    2014-01-01

    A paper-based disease reporting system has been associated with a number of challenges. These include difficulties to submit hard copies of the disease surveillance forms because of poor road infrastructure, weather conditions or challenging terrain, particularly in the developing countries. The system demands re-entry of the data at data processing and analysis points, thus making it prone to introduction of errors during this process. All these challenges contribute to delayed acquisition, processing and response to disease events occurring in remote hard to reach areas. Our study piloted the use of mobile phones in order to transmit near to real-time data from remote districts in Tanzania (Ngorongoro and Ngara), Burundi (Muyinga) and Zambia (Kazungula and Sesheke). Two technologies namely, digital and short messaging services were used to capture and transmit disease event data in the animal and human health sectors in the study areas based on a server-client model. Smart phones running the Android operating system (minimum required version: Android 1.6), and which supported open source application, Epicollect, as well as the Open Data Kit application, were used in the study. These phones allowed collection of geo-tagged data, with the opportunity of including static and moving images related to disease events. The project supported routine disease surveillance systems in the ministries responsible for animal and human health in Burundi, Tanzania and Zambia, as well as data collection for researchers at the Sokoine University of Agriculture, Tanzania. During the project implementation period between 2011 and 2013, a total number of 1651 diseases event-related forms were submitted, which allowed reporters to include GPS coordinates and photographs related to the events captured. It was concluded that the new technology-based surveillance system is useful in providing near to real-time data, with potential for enhancing timely response in rural remote areas of

  4. Clinical relevance of animal models of schizophrenia.

    Science.gov (United States)

    Koch, Michael

    2013-01-01

    Animal models and endophenotypes of mental disorders are regarded as preclinical heuristic approaches aiming at understanding the etiopathogenesis of these diseases, and at developing drug treatment strategies. A frequently used translational model of sensorimotor gating and its deficits in some neuropsychiatric disorders is prepulse inhibition (PPI) of startle. PPI is reduced in schizophrenia patients, but the exact relationship between symptoms and reduced PPI is still unclear. Recent findings suggest that the levels of PPI in humans and animals may be predictive of certain cognitive functions. Hence, this simple measure of reflex suppression may be of use for clinical research. PPI is the reduction of the acoustic startle response that occurs when a weak prestimulus is presented shortly prior to a startling noise pulse. It is considered a measure of sensorimotor gating and is regulated by a cortico-limbic striato-pallidal circuit. However, PPI does not only occur in the domain of startle. PPI of alpha, gamma, and theta oscillations at frontal and central locations has been found, suggesting a relationship between PPI and cognitive processes. In fact, levels of PPI in healthy subjects and in animals predict their performance in cognitive tasks mainly mediated by the frontal cortex. Taken together, PPI might reflect a more general filtering performance leading to gating of intrusive sensory, motor, and cognitive input, thereby improving cognitive function. Hence, PPI might be used in clinical settings to predict the impact of drugs or psychotherapy on cognitive performance in neuropsychiatric patients. PMID:24053035

  5. Directed animals and Gas Models Revisited

    OpenAIRE

    Le Borgne, Yvan; Marckert, Jean-François

    2007-01-01

    In this paper, we revisit the enumeration of directed animals using gas models. We show that there exists a natural construction of random directed animals on any directed graph together with a particle system that explains at the level of objects the formal link known between the density of the gas model and the generating function of directed animals counted according to the area. This provides some new methods to compute the generating function of directed animals counted according to area...

  6. Animal models of glucocorticoid-induced glaucoma.

    Science.gov (United States)

    Overby, Darryl R; Clark, Abbot F

    2015-12-01

    Glucocorticoid (GC) therapy is widely used to treat a variety of inflammatory diseases and conditions. While unmatched in their anti-inflammatory and immunosuppressive activities, GC therapy is often associated with the significant ocular side effect of GC-induced ocular hypertension (OHT) and iatrogenic open-angle glaucoma. Investigators have generated GC-induced OHT and glaucoma in at least 8 different species besides man. These models mimic many features of this condition in man and provide morphologic and molecular insights into the pathogenesis of GC-OHT. In addition, there are many clinical, morphological, and molecular similarities between GC-induced glaucoma and primary open-angle glaucoma (POAG), making animals models of GC-induced OHT and glaucoma attractive models in which to study specific aspects of POAG. PMID:26051991

  7. Animal models for mucopolysaccharidosis disorders and their clinical relevance

    OpenAIRE

    Haskins, Mark E.

    2007-01-01

    Progress in understanding how a particular genotype produces the phenotype of an inborn error of metabolism, such as a mucopolysaccharidosis, in human patients has been facilitated by the study of animals with mutations in the orthologous genes. These are not just animal models, but true orthologues of the human genetic disease, with defects involving the same evolutionarily conserved genes and the same molecular, biochemical, and anatomic lesions as in human patients. These animals are often...

  8. Animal models for protein respiratory sensitizers.

    Science.gov (United States)

    Ward, Marsha D W; Selgrade, Maryjane K

    2007-01-01

    Protein induced respiratory hypersensitivity, particularly atopic disease in general, and allergic asthma in particular, has increased dramatically over the last several decades in the US and other industrialized nations as a result of ill-defined changes in living conditions in modern western society. In addition, work-related asthma has become the most frequently diagnosed occupational respiratory illness. Animal models have demonstrated great utility in developing an understanding of the etiology and mechanisms of many diseases. A few models been developed as predictive models to identify a protein as an allergen or to characterize its potency. Here we describe animal models that have been used to investigate and identify protein respiratory sensitizers. In addition to prototypical experimental design, methods for exposure route, sample collection, and endpoint assessment are described. Some of the most relevant endpoints in assessing the potential for a given protein to induce atopic or allergic asthma respiratory hypersensitivity are the development of cytotropic antibodies (IgE, IgG1), eosinophil influx into the lung, and airway hyperresponsiveness to the sensitizing protein and/or to non-antigenic stimuli (Mch). The utility of technologies such as PCR and multiplexing assay systems is also described. These models and methods have been used to elucidate the potential for protein sources to induce allergy, identify environmental conditions (pollutants) to impact allergy responsiveness, and establish safe exposure limits. As an example, data are presented from an experiment designed to compare the allergenicity of a fungal biopesticide Metarhizium anisopliae (MACA) crude extract with the one of its components, conidia (CON) extract. PMID:17161304

  9. Risk and economic consequences of contagious animal disease introduction.

    OpenAIRE

    Horst, H.S.

    1998-01-01

    IntroductionWithin the European Union, epidemics of contagious animal diseases such as Classical Swine Fever (CSF) and Foot-and-Mouth Disease (FMD) are to be eradicated according to strict EU- prescriptions including stamping-out of infected herds, establishment of control and surveillance zones with complete standstill of animals and possible export bans on live animals. Epidemics clearly have a serious impact, in particular on countries with a high farm density and an export- oriented produ...

  10. Animal models for the study of arterial hypertension

    Indian Academy of Sciences (India)

    Waleska C Dornas; Marcelo E Silva

    2011-09-01

    Hypertension is one of the leading causes of disability or death due to stroke, heart attack and kidney failure. Because the etiology of essential hypertension is not known and may be multifactorial, the use of experimental animal models has provided valuable information regarding many aspects of the disease, which include etiology, pathophysiology, complications and treatment. The models of hypertension are various, and in this review, we provide a brief overview of the most widely used animal models, their features and their importance.

  11. Joint diseases in animal paleopathology: Veterinary approach

    OpenAIRE

    Oliver Stevanović,; Maciej Janeczek,; Aleksander Chrószcz; Nemanja Marković

    2015-01-01

    Animal paleopathology is not a very well known scientific discipline within veterinary science, but it has great importance for historical and archaeological investigations. In this paper, authors attention is focused on the description of one of the most common findings on the skeletal remains of animals - osteoarthropathies. This review particularly emphasizes the description and classification of the most common pathological changes in synovial joints. The authors have provided their obser...

  12. Small-Animal PET Imaging of Amyloid-Beta Plaques with [11C]PiB and Its Multi-Modal Validation in an APP/PS1 Mouse Model of Alzheimer's Disease

    OpenAIRE

    Manook, André; Yousefi, Behrooz H.; Willuweit, Antje; Platzer, Stefan; Reder, Sybille; Voss, Andreas; Huisman, Marc; Settles, Markus; Neff, Frauke; Velden, Joachim; Schoor, Michael; von der Kammer, Heinz; Wester, Hans-Jürgen; Schwaiger, Markus; Henriksen, Gjermund

    2012-01-01

    In vivo imaging and quantification of amyloid-β plaque (Aβ) burden in small-animal models of Alzheimer's disease (AD) is a valuable tool for translational research such as developing specific imaging markers and monitoring new therapy approaches. Methodological constraints such as image resolution of positron emission tomography (PET) and lack of suitable AD models have limited the feasibility of PET in mice. In this study, we evaluated a feasible protocol for PET imaging of Aβ in mouse brain...

  13. Animal models for investigating chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Aghdassi Alexander A

    2011-12-01

    Full Text Available Abstract Chronic pancreatitis is defined as a continuous or recurrent inflammatory disease of the pancreas characterized by progressive and irreversible morphological changes. It typically causes pain and permanent impairment of pancreatic function. In chronic pancreatitis areas of focal necrosis are followed by perilobular and intralobular fibrosis of the parenchyma, by stone formation in the pancreatic duct, calcifications in the parenchyma as well as the formation of pseudocysts. Late in the course of the disease a progressive loss of endocrine and exocrine function occurs. Despite advances in understanding the pathogenesis no causal treatment for chronic pancreatitis is presently available. Thus, there is a need for well characterized animal models for further investigations that allow translation to the human situation. This review summarizes existing experimental models and distinguishes them according to the type of pathological stimulus used for induction of pancreatitis. There is a special focus on pancreatic duct ligation, repetitive overstimulation with caerulein and chronic alcohol feeding. Secondly, attention is drawn to genetic models that have recently been generated and which mimic features of chronic pancreatitis in man. Each technique will be supplemented with data on the pathophysiological background of the model and their limitations will be discussed.

  14. Animal models for investigating chronic pancreatitis.

    Science.gov (United States)

    Aghdassi, Alexander A; Mayerle, Julia; Christochowitz, Sandra; Weiss, Frank U; Sendler, Matthias; Lerch, Markus M

    2011-01-01

    Chronic pancreatitis is defined as a continuous or recurrent inflammatory disease of the pancreas characterized by progressive and irreversible morphological changes. It typically causes pain and permanent impairment of pancreatic function. In chronic pancreatitis areas of focal necrosis are followed by perilobular and intralobular fibrosis of the parenchyma, by stone formation in the pancreatic duct, calcifications in the parenchyma as well as the formation of pseudocysts. Late in the course of the disease a progressive loss of endocrine and exocrine function occurs. Despite advances in understanding the pathogenesis no causal treatment for chronic pancreatitis is presently available. Thus, there is a need for well characterized animal models for further investigations that allow translation to the human situation. This review summarizes existing experimental models and distinguishes them according to the type of pathological stimulus used for induction of pancreatitis. There is a special focus on pancreatic duct ligation, repetitive overstimulation with caerulein and chronic alcohol feeding. Secondly, attention is drawn to genetic models that have recently been generated and which mimic features of chronic pancreatitis in man. Each technique will be supplemented with data on the pathophysiological background of the model and their limitations will be discussed. PMID:22133269

  15. Minireview: Epigenetic programming of diabetes and obesity: animal models.

    Science.gov (United States)

    Seki, Yoshinori; Williams, Lyda; Vuguin, Patricia M; Charron, Maureen J

    2012-03-01

    A growing body of evidence suggests that the intrauterine (IU) environment has a significant and lasting effect on the long-term health of the growing fetus and the development of metabolic disease in later life as put forth in the fetal origins of disease hypothesis. Metabolic diseases have been associated with alterations in the epigenome that occur without changes in the DNA sequence, such as cytosine methylation of DNA, histone posttranslational modifications, and micro-RNA. Animal models of epigenetic modifications secondary to an altered IU milieu are an invaluable tool to study the mechanisms that determine the development of metabolic diseases, such as diabetes and obesity. Rodent and nonlitter bearing animals are good models for the study of disease, because they have similar embryology, anatomy, and physiology to humans. Thus, it is feasible to monitor and modify the IU environment of animal models in order to gain insight into the molecular basis of human metabolic disease pathogenesis. In this review, the database of PubMed was searched for articles published between 1999 and 2011. Key words included epigenetic modifications, IU growth retardation, small for gestational age, animal models, metabolic disease, and obesity. The inclusion criteria used to select studies included animal models of epigenetic modifications during fetal and neonatal development associated with adult metabolic syndrome. Experimental manipulations included: changes in the nutritional status of the pregnant female (calorie-restricted, high-fat, or low-protein diets during pregnancy), as well as the father; interference with placenta function, or uterine blood flow, environmental toxin exposure during pregnancy, as well as dietary modifications during the neonatal (lactation) as well as pubertal period. This review article is focused solely on studies in animal models that demonstrate epigenetic changes that are correlated with manifestation of metabolic disease, including diabetes

  16. Animal models of GM2 gangliosidosis: utility and limitations.

    Science.gov (United States)

    Lawson, Cheryl A; Martin, Douglas R

    2016-01-01

    GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay-Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay-Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described. PMID:27499644

  17. Experimental Animal Models in Periodontology: A Review

    OpenAIRE

    Struillou, Xavier; Boutigny, Hervé; Soueidan, Assem; Layrolle, Pierre

    2010-01-01

    In periodontal research, animal studies are complementary to in vitro experiments prior to testing new treatments. Animal models should make possible the validation of hypotheses and prove the safety and efficacy of new regenerating approaches using biomaterials, growth factors or stem cells. A review of the literature was carried out by using electronic databases (PubMed, ISI Web of Science). Numerous animal models in different species such as rats, hamsters, rabbits, ferrets, canines and pr...

  18. Towards a reliable animal model of migraine

    DEFF Research Database (Denmark)

    Olesen, Jes; Jansen-Olesen, Inger

    2012-01-01

    The pharmaceutical industry shows a decreasing interest in the development of drugs for migraine. One of the reasons for this could be the lack of reliable animal models for studying the effect of acute and prophylactic migraine drugs. The infusion of glyceryl trinitrate (GTN) is the best validated...... and most studied human migraine model. Several attempts have been made to transfer this model to animals. The different variants of this model are discussed as well as other recent models....

  19. Animal Models in Cardiovascular Research: Hypertension and Atherosclerosis

    OpenAIRE

    Xin-Fang Leong; Chun-Yi Ng; Kamsiah Jaarin

    2015-01-01

    Hypertension and atherosclerosis are among the most common causes of mortality in both developed and developing countries. Experimental animal models of hypertension and atherosclerosis have become a valuable tool for providing information on etiology, pathophysiology, and complications of the disease and on the efficacy and mechanism of action of various drugs and compounds used in treatment. An animal model has been developed to study hypertension and atherosclerosis for several reasons. Co...

  20. Promise and Pitfalls of Animal Models of Schizophrenia

    OpenAIRE

    Feifel, David; Shilling, Paul D.

    2010-01-01

    Animal models are indispensible tools for advancing understanding of the cause of any given disease and developing new treatments. Developing animal models for schizophrenia presents formidable challenges owing to the distinctively human nature of the symptoms that define it and the thus-far-obscured underlying biological mechanisms. Nevertheless, progress has been and continues to be made in this important field of endeavor. This article discusses the challenges facing investigators who seek...

  1. What Constitutes a Relevant Animal Model of the Ketogenic Diet?

    OpenAIRE

    Gregory L Holmes

    2008-01-01

    Animal models of human disease have been enormously important in improving our understanding of the pathophysiological basis and the development of novel therapies. In epilepsy, modeling using both in vivo and in vitro preparations has provided insight into fundamental neuronal mechanisms. Indeed, much of our understanding of seizure mechanisms comes from animal studies. The conceptual advances in understanding basic mechanisms of epilepsies have been largely validated in humans, attesting to...

  2. The Use of Animal Models for Stroke Research: A Review

    OpenAIRE

    Juliana B Casals; Pieri, Naira CG; Feitosa, Matheus LT; Ercolin, Anna CM; Roballo, Kelly CS; Barreto, Rodrigo SN; Bressan, Fabiana F; Daniele S. Martins; Maria A. Miglino; Carlos E. Ambrósio

    2011-01-01

    Stroke has been identified as the second leading cause of death worldwide. Stroke is a focal neurologic deficit caused by a change in cerebral circulation. The use of animal models in recent years has improved our understanding of the physiopathology of this disease. Rats and mice are the most commonly used stroke models, but the demand for larger models, such as rabbits and even nonhuman primates, is increasing so as to better understand the disease and its treatment. Although the basic mech...

  3. Large Animal Models of Neurological Disorders for Gene Therapy

    OpenAIRE

    Gagliardi, Christine; Bunnell, Bruce A.

    2009-01-01

    The development of therapeutic interventions for genetic disorders and diseases that affect the central nervous system (CNS) has proven challenging. There has been significant progress in the development of gene therapy strategies in murine models of human disease, but gene therapy outcomes in these models do not always translate to the human setting. Therefore, large animal models are crucial to the development of diagnostics, treatments, and eventual cures for debilitating neurological diso...

  4. Disease protection vs animal protection--synergisms and contradictions.

    Science.gov (United States)

    Dimander, S O

    Health is an important part of animal welfare. This implies that measures for the protection against disease will also affect animal protection. In most instances, efforts to improve disease protection act synergistically with efforts to promote animal protection, and vice versa. In the context of farm animal transport, however, infectious disease protection and animal protection may not always be mutually beneficial. Examples of contradictions are: Logistic perturbations; Current farm animal production is increasingly sensitive to logistic perturbations. Control and prevention of epizootic diseases involve extraordinary transport precautions that rapidly result in overcrowded stables. Transhumance; The practise of transhumance is compromised when control measures are taken to prevent spread of epizootic diseases. Travel sickness; Travel sickness is a problem particularly in pigs. Starvation before transport prevents vomiting but result in hungry animals. Lack of experience; Animals that are kept under conditions estranged from situations associated with transport alike are more prone to transport induced stress. Flooring; A non-slip flooring is a prerequisite for firm footing but demand more careful cleaning and disinfection to prevent spread of infectious agents. PMID:16429802

  5. Evaluation of spinal cord injury animal models

    Institute of Scientific and Technical Information of China (English)

    Ning Zhang; Marong Fang; Haohao Chen; Fangming Gou; Mingxing Ding

    2014-01-01

    Because there is no curative treatment for spinal cord injury, establishing an ideal animal model is important to identify injury mechanisms and develop therapies for individuals suffering from spinal cord injuries. In this article, we systematically review and analyze various kinds of animal models of spinal cord injury and assess their advantages and disadvantages for further studies.

  6. Modeling dopamine system dysfunction in experimental animals

    International Nuclear Information System (INIS)

    Quite a substantial number of human disorders have been associated with a primary or a secondary impairment of one or several of the dopaminergic pathways. Among disorders associated with a primary impairment of dopaminergic transmission are Parkinson's disease, striatonigral degeneration, progressive supranuclear palsy, and possibly schizophrenia. Diseases of secondary dopamine dysfunction are chiefly represented by Huntington's disease in which dopaminergic transmission is being interrupted by progressive loss of the striatal neurons bearing the postsynaptic D1- and D2-dopamine receptors. Central dopaminergic systems have anatomical as well as organizational properties that render them unique by comparison to other neurotransmission systems, making them able to play a pivotal role in the modulation of various important brain functions such as locomotor activity, attention, and some cognitive abilities. These properties of dopamine neurons have obviously several implications in the clinical expression of human disorders involving dopamine neuron dysfunction. In addition, they can greatly influence the clinical/behavioral consequences of experimental lesions in animal models of dopamine dysfunctions

  7. Animal models of polymicrobial pneumonia

    OpenAIRE

    Hraiech S; Papazian L.; Rolain JM; Bregeon F

    2015-01-01

    Sami Hraiech,1,2 Laurent Papazian,1,2 Jean-Marc Rolain,1 Fabienne Bregeon1,3IHU Méditerranée Infection, URMITE CNRS IRD INSERM UMR 7278, Marseille, France; 2Réanimation – Détresses respiratoires et Infections Sévères, APHM, CHU Nord, Marseille, France; 3Service d’Explorations Fonctionnelles Respiratoires, APHM, CHU Nord, Marseille, FranceAbstract: Pneumonia is one of the leading causes of severe and occasion...

  8. Animal Models of Subjective Tinnitus

    OpenAIRE

    2014-01-01

    Tinnitus is one of the major audiological diseases, affecting a significant portion of the ageing society. Despite its huge personal and presumed economic impact there are only limited therapeutic options available. The reason for this deficiency lies in the very nature of the disease as it is deeply connected to elementary plasticity of auditory processing in the central nervous system. Understanding these mechanisms is essential for developing a therapy that reverses the plastic changes und...

  9. Modeling Infectious Diseases

    Science.gov (United States)

    ... Background Information > Modeling Infectious Diseases Fact Sheet Modeling Infectious Diseases Fact Sheet Tagline (Optional) Using computers to prepare ... Content Area Predicting the potential spread of an infectious disease requires much more than simply connecting cities on ...

  10. Animal Models of Cystic Fibrosis Pathology: Phenotypic Parallels and Divergences

    Science.gov (United States)

    McElvaney, Noel G.

    2016-01-01

    Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The resultant characteristic ion transport defect results in decreased mucociliary clearance, bacterial colonisation, and chronic neutrophil-dominated inflammation. Much knowledge surrounding the pathophysiology of the disease has been gained through the generation of animal models, despite inherent limitations in each. The failure of certain mouse models to recapitulate the phenotypic manifestations of human disease has initiated the generation of larger animals in which to study CF, including the pig and the ferret. This review will summarise the basic phenotypes of three animal models and describe the contributions of such animal studies to our current understanding of CF. PMID:27340661

  11. Animal Models of Cystic Fibrosis Pathology: Phenotypic Parallels and Divergences

    Directory of Open Access Journals (Sweden)

    Gillian M. Lavelle

    2016-01-01

    Full Text Available Cystic fibrosis (CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR gene. The resultant characteristic ion transport defect results in decreased mucociliary clearance, bacterial colonisation, and chronic neutrophil-dominated inflammation. Much knowledge surrounding the pathophysiology of the disease has been gained through the generation of animal models, despite inherent limitations in each. The failure of certain mouse models to recapitulate the phenotypic manifestations of human disease has initiated the generation of larger animals in which to study CF, including the pig and the ferret. This review will summarise the basic phenotypes of three animal models and describe the contributions of such animal studies to our current understanding of CF.

  12. Zoonotic disease concerns in animal-assisted therapy and animal visitation programs

    OpenAIRE

    Waltner-Toews, David

    1993-01-01

    A survey was done of 150 systematically selected United States animal care agencies and 74 Canadian humane societies to determine the prevalence of animal assisted therapy (AAT) programs; concerns about, and experience with, zoonotic diseases; and precautions taken to prevent zoonotic disease transmission. Of the 69 US agencies and 49 Canadian societies that reported having AAT programs, 94% used dogs and/or cats in their programs, 28% used rabbits, 15% used “pocket pets” (hamsters, gerbils, ...

  13. TSUNAMI: an antisense method to phenocopy splicing-associated diseases in animals

    OpenAIRE

    Sahashi, Kentaro; Hua, Yimin; Ling, Karen K Y; Hung, Gene; Rigo, Frank; Horev, Guy; Katsuno, Masahisa; Sobue, Gen; Ko, Chien-Ping; Bennett, C. Frank; Krainer, Adrian R.

    2012-01-01

    This study presents an antisense oligonucleotide methodology to phenocopy a disease—in this case, the motor neuron disease spinal muscular atrophy in mice. Sahashi et al. show that it is possible to fine-tune disease severity through dose-dependent effects on RNA splicing, making this a novel animal model for monitoring disease onset and progression as well as testing candidate therapeutics.

  14. Humane killing of animals for disease control purposes.

    Science.gov (United States)

    Thornber, P M; Rubira, R J; Styles, D K

    2014-04-01

    Killing for disease control purposes is an emotional issue for everyone concerned. Large-scale euthanasia or depopulation of animals may be necessary for the emergency control or eradication of animal diseases, to remove animals from a compromised situation (e.g. following flood, storm, fire, drought or a feed contamination event), to effect welfare depopulation when there is an oversupply due to a dysfunctional or closed marketing channel, or to depopulate and dispose of animals with minimal handling to decrease the risk of a zoonotic disease infecting humans. The World Organisation for Animal Health (OIE) developed international standards to provide advice on humane killing for various species and situations. Some fundamental issues are defined, such as competency of animal handling and implementation of humane killing techniques. Some of these methods have been used for many years, but novel approaches for the mass killing of particular species are being explored. Novel vaccines and new diagnostic techniques that differentiate between vaccinated and infected animals will save many animals from being killed as part of biosecurity response measures. Unfortunately, the destruction of affected livestock will still be required to control diseases whilst vaccination programmes are activated or where effective vaccines are not available. This paper reviews the principles of humane destruction and depopulation and explores available techniques with their associated advantages and disadvantages. It also identifies some current issues that merit consideration, such as legislative conflicts (emergency disease legislation versus animal welfare legislation, occupational health and safety), media issues, opinions on the future approaches to killing for disease control, and animal welfare. PMID:25000803

  15. Mobile technologies for disease surveillance in humans and animals

    Directory of Open Access Journals (Sweden)

    Mpoki Mwabukusi

    2014-04-01

    Full Text Available A paper-based disease reporting system has been associated with a number of challenges. These include difficulties to submit hard copies of the disease surveillance forms because of poor road infrastructure, weather conditions or challenging terrain, particularly in the developing countries. The system demands re-entry of the data at data processing and analysis points, thus making it prone to introduction of errors during this process. All these challenges contribute to delayed acquisition, processing and response to disease events occurring in remote hard to reach areas. Our study piloted the use of mobile phones in order to transmit near to real-time data from remote districts in Tanzania (Ngorongoro and Ngara, Burundi (Muyinga and Zambia (Kazungula and Sesheke. Two technologies namely, digital and short messaging services were used to capture and transmit disease event data in the animal and human health sectors in the study areas based on a server–client model. Smart phones running the Android operating system (minimum required version: Android 1.6, and which supported open source application, Epicollect, as well as the Open Data Kit application, were used in the study. These phones allowed collection of geo-tagged data, with the opportunity of including static and moving images related to disease events. The project supported routine disease surveillance systems in the ministries responsible for animal and human health in Burundi, Tanzania and Zambia, as well as data collection for researchers at the Sokoine University of Agriculture, Tanzania. During the project implementation period between 2011 and 2013, a total number of 1651 diseases event-related forms were submitted, which allowed reporters to include GPS coordinates and photographs related to the events captured. It was concluded that the new technology-based surveillance system is useful in providing near to real-time data, with potential for enhancing

  16. Accelerating drug discovery for Alzheimer's disease: best practices for preclinical animal studies

    OpenAIRE

    Shineman, Diana W; Basi, Guriqbal S.; Bizon, Jennifer L.; Colton, Carol A.; Greenberg, Barry D.; Hollister, Beth A; Lincecum, John; Leblanc, Gabrielle G.; Lee, Linda H; Luo, Feng; Morgan, Dave; Morse, Iva; Refolo, Lorenzo M; Riddell, David R; Scearce-Levie, Kimberly

    2011-01-01

    Animal models have contributed significantly to our understanding of the underlying biological mechanisms of Alzheimer's disease (AD). As a result, over 300 interventions have been investigated and reported to mitigate pathological phenotypes or improve behavior in AD animal models or both. To date, however, very few of these findings have resulted in target validation in humans or successful translation to disease-modifying therapies. Challenges in translating preclinical studies to clinical...

  17. Transmission and Epidemiology of Zoonotic Protozoal Diseases of Companion Animals

    OpenAIRE

    Esch, Kevin J.; Petersen, Christine A.

    2013-01-01

    Over 77 million dogs and 93 million cats share our households in the United States. Multiple studies have demonstrated the importance of pets in their owners' physical and mental health. Given the large number of companion animals in the United States and the proximity and bond of these animals with their owners, understanding and preventing the diseases that these companions bring with them are of paramount importance. Zoonotic protozoal parasites, including toxoplasmosis, Chagas' disease, b...

  18. Laboratory Animal Models for Brucellosis Research

    OpenAIRE

    Silva, Teane M. A.; Erica A Costa; Tatiane A. Paixão; Renée M. Tsolis; Santos, Renato L

    2011-01-01

    Brucellosis is a chronic infectious disease caused by Brucella spp., a Gram-negative facultative intracellular pathogen that affects humans and animals, leading to significant impact on public health and animal industry. Human brucellosis is considered the most prevalent bacterial zoonosis in the world and is characterized by fever, weight loss, depression, hepato/splenomegaly, osteoarticular, and genital infections. Relevant aspects of Brucella pathogenesis have been intensively investigated...

  19. Animal diseases of public health importance.

    OpenAIRE

    Orriss, G. D.

    1997-01-01

    The Food and Agriculture Organization's (FAO) interest in emerging diseases caused by foodborne pathogens derives from its role as the leading United Nations agency with a mandate for food quality and safety matters. The Food Quality and Standards Service of FAO's Food and Nutrition Division is active in all areas related to food safety and implements the FAO/World Health Organization Food Standards Program. Its activities include providing assistance to FAO's member nations in addressing pro...

  20. Animal models of systemic sclerosis: their utility and limitations

    OpenAIRE

    Artlett, Carol

    2014-01-01

    Carol M Artlett Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA Abstract: Without doubt, animal models have provided significant insights into our understanding of the rheumatological diseases; however, no model has accurately replicated all aspects of any autoimmune disease. Recent years have seen a plethora of knockouts and transgenics that have contributed to our knowledge of the initiating events of systemic sclerosis, an autoimmune...

  1. Animal models as tools to study the pathophysiology of depression

    OpenAIRE

    Abelaira, Helena M.; Gislaine Z. Reus; Joao Quevedo

    2013-01-01

    The incidence of depressive illness is high worldwide, and the inadequacy of currently available drug treatments contributes to the significant health burden associated with depression. A basic understanding of the underlying disease processes in depression is lacking; therefore, recreating the disease in animal models is not possible. Popular current models of depression creatively merge ethologically valid behavioral assays with the latest technological advances in molecular biology. Within...

  2. 3-D Human Modeling and Animation

    CERN Document Server

    Ratner, Peter

    2012-01-01

    3-D Human Modeling and Animation Third Edition All the tools and techniques you need to bring human figures to 3-D life Thanks to today's remarkable technology, artists can create and animate realistic, three-dimensional human figures that were not possible just a few years ago. This easy-to-follow book guides you through all the necessary steps to adapt your own artistic skill in figure drawing, painting, and sculpture to this exciting digital canvas. 3-D Human Modeling and Animation, Third Edition starts you off with simple modeling, then prepares you for more advanced techniques for crea

  3. Evaluation of animal models of neurobehavioral disorders

    Directory of Open Access Journals (Sweden)

    Nordquist Rebecca E

    2009-02-01

    Full Text Available Abstract Animal models play a central role in all areas of biomedical research. The process of animal model building, development and evaluation has rarely been addressed systematically, despite the long history of using animal models in the investigation of neuropsychiatric disorders and behavioral dysfunctions. An iterative, multi-stage trajectory for developing animal models and assessing their quality is proposed. The process starts with defining the purpose(s of the model, preferentially based on hypotheses about brain-behavior relationships. Then, the model is developed and tested. The evaluation of the model takes scientific and ethical criteria into consideration. Model development requires a multidisciplinary approach. Preclinical and clinical experts should establish a set of scientific criteria, which a model must meet. The scientific evaluation consists of assessing the replicability/reliability, predictive, construct and external validity/generalizability, and relevance of the model. We emphasize the role of (systematic and extended replications in the course of the validation process. One may apply a multiple-tiered 'replication battery' to estimate the reliability/replicability, validity, and generalizability of result. Compromised welfare is inherent in many deficiency models in animals. Unfortunately, 'animal welfare' is a vaguely defined concept, making it difficult to establish exact evaluation criteria. Weighing the animal's welfare and considerations as to whether action is indicated to reduce the discomfort must accompany the scientific evaluation at any stage of the model building and evaluation process. Animal model building should be discontinued if the model does not meet the preset scientific criteria, or when animal welfare is severely compromised. The application of the evaluation procedure is exemplified using the rat with neonatal hippocampal lesion as a proposed model of schizophrenia. In a manner congruent to

  4. Exploring the Validity of Valproic Acid Animal Model of Autism.

    Science.gov (United States)

    Mabunga, Darine Froy N; Gonzales, Edson Luck T; Kim, Ji-Woon; Kim, Ki Chan; Shin, Chan Young

    2015-12-01

    The valproic acid (VPA) animal model of autism spectrum disorder (ASD) is one of the most widely used animal model in the field. Like any other disease models, it can't model the totality of the features seen in autism. Then, is it valid to model autism? This model demonstrates many of the structural and behavioral features that can be observed in individuals with autism. These similarities enable the model to define relevant pathways of developmental dysregulation resulting from environmental manipulation. The uncovering of these complex pathways resulted to the growing pool of potential therapeutic candidates addressing the core symptoms of ASD. Here, we summarize the validity points of VPA that may or may not qualify it as a valid animal model of ASD. PMID:26713077

  5. Animal model of Mycoplasma fermentans respiratory infection

    Directory of Open Access Journals (Sweden)

    Yáñez Antonio

    2013-01-01

    Full Text Available Abstract Background Mycoplasma fermentans has been associated with respiratory, genitourinary tract infections and rheumatoid diseases but its role as pathogen is controversial. The purpose of this study was to probe that Mycoplasma fermentans is able to produce respiratory tract infection and migrate to several organs on an experimental infection model in hamsters. One hundred and twenty six hamsters were divided in six groups (A-F of 21 hamsters each. Animals of groups A, B, C were intratracheally injected with one of the mycoplasma strains: Mycoplasma fermentans P 140 (wild strain, Mycoplasma fermentans PG 18 (type strain or Mycoplasma pneumoniae Eaton strain. Groups D, E, F were the negative, media, and sham controls. Fragments of trachea, lungs, kidney, heart, brain and spleen were cultured and used for the histopathological study. U frequency test was used to compare recovery of mycoplasmas from organs. Results Mycoplasmas were detected by culture and PCR. The three mycoplasma strains induced an interstitial pneumonia; they also migrated to several organs and persisted there for at least 50 days. Mycoplasma fermentans P 140 induced a more severe damage in lungs than Mycoplasma fermentans PG 18. Mycoplasma pneumoniae produced severe damage in lungs and renal damage. Conclusions Mycoplasma fermentans induced a respiratory tract infection and persisted in different organs for several weeks in hamsters. This finding may help to explain the ability of Mycoplasma fermentans to induce pneumonia and chronic infectious diseases in humans.

  6. Animal Models of Nonalcoholic Steatohepatitis: Eat, Delete, and Inflame.

    Science.gov (United States)

    Ibrahim, Samar H; Hirsova, Petra; Malhi, Harmeet; Gores, Gregory J

    2016-05-01

    With the obesity epidemic, nonalcoholic fatty liver disease (NAFLD) has become a public health problem with increasing prevalence. The mechanism of disease progression remains obscure and effective therapy is lacking. Therefore, there is a need to understand the pathogenic mechanisms responsible for disease development and progression in order to develop innovative therapies. To accomplish this goal, experimental animal models that recapitulate the human disease are necessary, especially, since causative mechanistic studies of NAFLD are more difficult or unethical to perform in humans. A large number of studies regarding the pathophysiology and treatment of nonalcoholic steatohepatitis (NASH) have been undertaken in mice to model human NAFLD and NASH. This review discusses the known dietary, genetic, and inflammation-based animal models of NASH described in recent years, with a focus on the major advances made in this field. PMID:26626909

  7. Instrumental and ethical aspects of experimental research with animal models

    Directory of Open Access Journals (Sweden)

    Mirian Watanabe

    2014-02-01

    Full Text Available Experimental animal models offer possibilities of physiology knowledge, pathogenesis of disease and action of drugs that are directly related to quality nursing care. This integrative review describes the current state of the instrumental and ethical aspects of experimental research with animal models, including the main recommendations of ethics committees that focus on animal welfare and raises questions about the impact of their findings in nursing care. Data show that, in Brazil, the progress in ethics for the use of animals for scientific purposes was consolidated with Law No. 11.794/2008 establishing ethical procedures, attending health, genetic and experimental parameters. The application of ethics in handling of animals for scientific and educational purposes and obtaining consistent and quality data brings unquestionable contributions to the nurse, as they offer subsidies to relate pathophysiological mechanisms and the clinical aspect on the patient.

  8. Risk and economic consequences of contagious animal disease introduction.

    NARCIS (Netherlands)

    Horst, H.S.

    1998-01-01

    IntroductionWithin the European Union, epidemics of contagious animal diseases such as Classical Swine Fever (CSF) and Foot-and-Mouth Disease (FMD) are to be eradicated according to strict EU- prescriptions including stamping-out of infected herds, establishment of control and surve

  9. Animal models for HCV and HBV studies

    Directory of Open Access Journals (Sweden)

    Isabelle Chemin

    2007-02-01

    Full Text Available

    The narrow host range of infection and lack of suitable tissue culture systems for the propagation of hepatitis B and C viruses are limitations that have prevented a more thorough understanding of persistent infection and the pathogenesis of chronic liver disease.

    Despite decades of intensive research and significant progresses in understanding of viral hepatitis, many basic questions and clinical problems still await to be resolved. For example, the HBV cellular receptor and related mechanisms of viral entry have not yet been identified. Little is also known about the function of certain non-structural viral products, such as the hepatitis B e antigen and the X protein, or about the role of excess hepadnavirus subviral particles circulating in the blood stream during infection. Furthermore, the molecular mechanisms involved in the development of hepatocellular carcinoma and the role of the immune system in determining the fate of infection are not fully understood.

    The reason for these drawbacks is essentially due to the lack of reliable cell-based in vitro infection systems and, most importantly, convenient animal models.

    This lack of knowledge has been partially overcome for hepatitis B virus (HBV, by the discovery and characterization of HBV-like viruses in wild animals while for hepatitis C virus (HCV, related flaviviruses have been used as surrogate systems.

    Other laboratories have developed transgenic mice that express virus gene products and/or support virus replication. Some HBV transgenic mouse models

  10. Animal Models of Human Disease is the Research Frontier of Medical Innovation%人类疾病动物模型是医药创新研究的前沿

    Institute of Scientific and Technical Information of China (English)

    秦川

    2011-01-01

    Animal models of human disease play an essential role in supporting medical research and are the basic tool for medical research. The present paper summarized the function of animal models in medical research, as well as the contributions of animal models to the progress if medical research in history. Then, the application prospects of animal models in research frontier of medical innovation were previewed.%人类疾病动物模型对医药研究起着支撑作用,是进行医药研究的必备工具之一.本文阐述了人类疾病动物模型在医药研究中所能发挥的作用,以及在医药研究的历史中所做出的贡献.最后,对疾病动物模型在医药创新研究中应用的前沿进行了展望.

  11. Transmission and epidemiology of zoonotic protozoal diseases of companion animals.

    Science.gov (United States)

    Esch, Kevin J; Petersen, Christine A

    2013-01-01

    Over 77 million dogs and 93 million cats share our households in the United States. Multiple studies have demonstrated the importance of pets in their owners' physical and mental health. Given the large number of companion animals in the United States and the proximity and bond of these animals with their owners, understanding and preventing the diseases that these companions bring with them are of paramount importance. Zoonotic protozoal parasites, including toxoplasmosis, Chagas' disease, babesiosis, giardiasis, and leishmaniasis, can cause insidious infections, with asymptomatic animals being capable of transmitting disease. Giardia and Toxoplasma gondii, endemic to the United States, have high prevalences in companion animals. Leishmania and Trypanosoma cruzi are found regionally within the United States. These diseases have lower prevalences but are significant sources of human disease globally and are expanding their companion animal distribution. Thankfully, healthy individuals in the United States are protected by intact immune systems and bolstered by good nutrition, sanitation, and hygiene. Immunocompromised individuals, including the growing number of obese and/or diabetic people, are at a much higher risk of developing zoonoses. Awareness of these often neglected diseases in all health communities is important for protecting pets and owners. To provide this awareness, this review is focused on zoonotic protozoal mechanisms of virulence, epidemiology, and the transmission of pathogens of consequence to pet owners in the United States. PMID:23297259

  12. The social and political impact of animal diseases.

    Science.gov (United States)

    Evans, B

    2006-01-01

    The twenty-first century is characterised by 'epidemiological globalisation' on an unprecedented scale with resulting impacts at the interface of economic, scientific, social and political forces arising from the emergence and re-emergence of animal diseases. Throughout history, animals have served as a source to humankind of food, transportation, medicines, entertainment, clothing, fuel, military advantage and financial security. It is therefore not at all surprising that animal diseases have resulted in significant social and political impacts that have shaped and continue to shape the course of national and international events. The social impacts can be expressed as indirect health consequences or behavioural changes, changes in societal values and changes in social standing and can be felt at the individual, family or community level. The political impact of major disease outbreaks can include loss of public and consumer confidence, resistance to investments in disease surveillance, reluctance to report disease detections in a timely or transparent manner, failure to implement science-based international standards for safe trade (which protect animal, human and ecosystem health) and the removal of government officials. The magnitude of these impacts would support that social and political impacts warrant their inclusion in the consequence assessment of a robust animal disease risk analysis framework. PMID:20429074

  13. Animal models of human disease. Pathology and molecular biology of spontaneous neoplasms occurring in transgenic mice carrying and expressing activated cellular oncogenes.

    OpenAIRE

    Pattengale, P K; Stewart, T A; Leder, A; Sinn, E; Muller, W.; Tepler, I; Schmidt, E.; Leder, P

    1989-01-01

    This present review focuses on spontaneous neoplasms occurring in transgenic mice carrying and expressing activated cellular oncogenes. The historical development of transgenic mice as in vivo disease models is briefly traced, followed by a brief description of the actual technology in such systems. Additional emphasis is placed on the concept of targeting activated cellular oncogenes to specific tissues in transgenic mice. Cumulative experience with activated (Vmyc, ras, and neu (erb-B2] onc...

  14. An updated overview of animal models in neuropsychiatry.

    Science.gov (United States)

    Razafsha, M; Behforuzi, H; Harati, H; Wafai, R Al; Khaku, A; Mondello, S; Gold, M S; Kobeissy, F H

    2013-06-14

    Animal models are vital tools to study the genetic, molecular, cellular, and environmental parameters involved in several neuropsychiatric disorders. Over the years, these models have expanded our understanding of the pathogenesis of many neuropsychiatric disorders and neurodegenerative diseases. Although animal models have been widely used in psychiatry, and despite several years of extensive research with these models, their validity is still being investigated and presents a challenge to both investigators and clinicians as well. In this concise review, we will describe the most common animal models utilized in neuropsychiatry, including animal models of depression, anxiety, and psychosis. In addition, we will also discuss the validity and reliability of these models and current challenges in this domain. Furthermore, this work will discuss the role of gene-environment interaction as an additional contributing factor that modulates neuropsychological outcome and its implication on animal models. This overview will give a succinct summary of animal models in psychiatry which will be useful both to the seasoned researcher, as well as novices in the field. PMID:23473749

  15. Animal models for the study of tendinopathy

    OpenAIRE

    Warden, S. J.

    2006-01-01

    Tendinopathy is a common and significant clinical problem characterised by activity‐related pain, focal tendon tenderness and intratendinous imaging changes. Recent histopathological studies have indicated the underlying pathology to be one of tendinosis (degeneration) as opposed to tendinitis (inflammation). Relatively little is known about tendinosis and its pathogenesis. Contributing to this is an absence of validated animal models of the pathology. Animal models of tendinosis represent po...

  16. Animal Models of Stress Urinary Incontinence

    OpenAIRE

    Jiang, Hai-Hong; Damaser, Margot S.

    2011-01-01

    Stress urinary incontinence (SUI) is a common health problem significantly affecting the quality of life of women worldwide. Animal models that simulate SUI enable the assessment of the mechanism of risk factors for SUI in a controlled fashion, including childbirth injuries, and enable preclinical testing of new treatments and therapies for SUI. Animal models that simulate childbirth are presently being utilized to determine the mechanisms of the maternal injuries of childbirth that lead to S...

  17. A cognitive model's view of animal cognition

    OpenAIRE

    Sidney D'MELLO, Stan FRANKLIN

    2011-01-01

    Although it is a relatively new field of study, the animal cognition literature is quite extensive and difficult to synthesize. This paper explores the contributions a comprehensive, computational, cognitive model can make toward organizing and assimilating this literature, as well as toward identifying important concepts and their interrelations. Using the LIDA model as an example, a framework is described within which to integrate the diverse research in animal cognition. Such a framework c...

  18. Contemporary Animal Models For Human Gene Therapy Applications.

    Science.gov (United States)

    Gopinath, Chitra; Nathar, Trupti Job; Ghosh, Arkasubhra; Hickstein, Dennis Durand; Remington Nelson, Everette Jacob

    2015-01-01

    Over the past three decades, gene therapy has been making considerable progress as an alternative strategy in the treatment of many diseases. Since 2009, several studies have been reported in humans on the successful treatment of various diseases. Animal models mimicking human disease conditions are very essential at the preclinical stage before embarking on a clinical trial. In gene therapy, for instance, they are useful in the assessment of variables related to the use of viral vectors such as safety, efficacy, dosage and localization of transgene expression. However, choosing a suitable disease-specific model is of paramount importance for successful clinical translation. This review focuses on the animal models that are most commonly used in gene therapy studies, such as murine, canine, non-human primates, rabbits, porcine, and a more recently developed humanized mice. Though small and large animals both have their own pros and cons as disease-specific models, the choice is made largely based on the type and length of study performed. While small animals with a shorter life span could be well-suited for degenerative/aging studies, large animals with longer life span could suit longitudinal studies and also help with dosage adjustments to maximize therapeutic benefit. Recently, humanized mice or mouse-human chimaeras have gained interest in the study of human tissues or cells, thereby providing a more reliable understanding of therapeutic interventions. Thus, animal models are of great importance with regard to testing new vector technologies in vivo for assessing safety and efficacy prior to a gene therapy clinical trial. PMID:26415576

  19. A cognitive model's view of animal cognition

    Directory of Open Access Journals (Sweden)

    Sidney D'MELLO, Stan FRANKLIN

    2011-08-01

    Full Text Available Although it is a relatively new field of study, the animal cognition literature is quite extensive and difficult to synthesize. This paper explores the contributions a comprehensive, computational, cognitive model can make toward organizing and assimilating this literature, as well as toward identifying important concepts and their interrelations. Using the LIDA model as an example, a framework is described within which to integrate the diverse research in animal cognition. Such a framework can provide both an ontology of concepts and their relations, and a working model of an animal’s cognitive processes that can compliment active empirical research. In addition to helping to account for a broad range of cognitive processes, such a model can help to comparatively assess the cognitive capabilities of different animal species. After deriving an ontology for animal cognition from the LIDA model, we apply it to develop the beginnings of a database that maps the cognitive facilities of a variety of animal species. We conclude by discussing future avenues of research, particularly the use of computational models of animal cognition as valuable tools for hypotheses generation and testing [Current Zoology 57 (4: 499–513, 2011].

  20. Review of Animal Models of Prostate Cancer Bone Metastasis

    Directory of Open Access Journals (Sweden)

    Jessica K. Simmons

    2014-06-01

    Full Text Available Prostate cancer bone metastases are associated with a poor prognosis and are considered incurable. Insight into the formation and growth of prostate cancer bone metastasis is required for development of new imaging and therapeutic strategies to combat this devastating disease. Animal models are indispensable in investigating cancer pathogenesis and evaluating therapeutics. Multiple animal models of prostate cancer bone metastasis have been developed, but few effectively model prostatic neoplasms and osteoblastic bone metastases as they occur in men. This review discusses the animal models that have been developed to investigate prostate cancer bone metastasis, with a focus on canine models and also includes human xenograft and rodent models. Adult dogs spontaneously develop benign prostatic hyperplasia and prostate cancer with osteoblastic bone metastases. Large animal models, such as dogs, are needed to develop new molecular imaging tools and effective focal intraprostatic therapy. None of the available models fully reflect the metastatic disease seen in men, although the various models have provided important insight into the metastatic process. As additional models are developed and knowledge from the different models is combined, the molecular mechanisms of prostate cancer bone metastasis can be deciphered and targeted for development of novel therapies and molecular diagnostic imaging.

  1. RASopathies: unraveling mechanisms with animal models

    Directory of Open Access Journals (Sweden)

    Granton A. Jindal

    2015-08-01

    Full Text Available RASopathies are developmental disorders caused by germline mutations in the Ras-MAPK pathway, and are characterized by a broad spectrum of functional and morphological abnormalities. The high incidence of these disorders (∼1/1000 births motivates the development of systematic approaches for their efficient diagnosis and potential treatment. Recent advances in genome sequencing have greatly facilitated the genotyping and discovery of mutations in affected individuals, but establishing the causal relationships between molecules and disease phenotypes is non-trivial and presents both technical and conceptual challenges. Here, we discuss how these challenges could be addressed using genetically modified model organisms that have been instrumental in delineating the Ras-MAPK pathway and its roles during development. Focusing on studies in mice, zebrafish and Drosophila, we provide an up-to-date review of animal models of RASopathies at the molecular and functional level. We also discuss how increasingly sophisticated techniques of genetic engineering can be used to rigorously connect changes in specific components of the Ras-MAPK pathway with observed functional and morphological phenotypes. Establishing these connections is essential for advancing our understanding of RASopathies and for devising rational strategies for their management and treatment.

  2. RASopathies: unraveling mechanisms with animal models.

    Science.gov (United States)

    Jindal, Granton A; Goyal, Yogesh; Burdine, Rebecca D; Rauen, Katherine A; Shvartsman, Stanislav Y

    2015-08-01

    RASopathies are developmental disorders caused by germline mutations in the Ras-MAPK pathway, and are characterized by a broad spectrum of functional and morphological abnormalities. The high incidence of these disorders (∼1/1000 births) motivates the development of systematic approaches for their efficient diagnosis and potential treatment. Recent advances in genome sequencing have greatly facilitated the genotyping and discovery of mutations in affected individuals, but establishing the causal relationships between molecules and disease phenotypes is non-trivial and presents both technical and conceptual challenges. Here, we discuss how these challenges could be addressed using genetically modified model organisms that have been instrumental in delineating the Ras-MAPK pathway and its roles during development. Focusing on studies in mice, zebrafish and Drosophila, we provide an up-to-date review of animal models of RASopathies at the molecular and functional level. We also discuss how increasingly sophisticated techniques of genetic engineering can be used to rigorously connect changes in specific components of the Ras-MAPK pathway with observed functional and morphological phenotypes. Establishing these connections is essential for advancing our understanding of RASopathies and for devising rational strategies for their management and treatment. PMID:26203125

  3. Comparative study of the neuroprotective and nootropic activities of the carboxylate and amide forms of the HLDF-6 peptide in animal models of Alzheimer's disease.

    Science.gov (United States)

    Bogachouk, Anna P; Storozheva, Zinaida I; Solovjeva, Olga A; Sherstnev, Vyacheslav V; Zolotarev, Yury A; Azev, Vyacheslav N; Rodionov, Igor L; Surina, Elena A; Lipkin, Valery M

    2016-01-01

    A comparative study of the neuroprotective and nootropic activities of two pharmaceutical substances, the HLDF-6 peptide (HLDF-6-OH) and its amide form (HLDF-6-NH2), was conducted. The study was performed in male rats using two models of a neurodegenerative disorder. Cognitive deficit in rats was induced by injection of the beta-amyloid fragment 25-35 (βA 25-35) into the giant-cell nucleus basalis of Meynert or by coinjection of βA 25-35 and ibotenic acid into the hippocampus. To evaluate cognitive functions in animals, three tests were used: the novel object recognition test, the conditioned passive avoidance task and the Morris maze. Comparative analysis of the data demonstrated that the neuroprotective activity of HLDF-6-NH2, evaluated by improvement of cognitive functions in animals, surpassed that of the native HLDF-6-OH peptide. The greater cognitive/ behavioral effects can be attributed to improved kinetic properties of the amide form of the peptide, such as the character of biodegradation and the half-life time. The effects of HLDF-6-NH2 are comparable to, or exceed, those of the reference compounds. Importantly, HLDF-6-NH2 exerts its effects at much lower doses than the reference compounds. PMID:26628555

  4. Progress With Nonhuman Animal Models of Addiction.

    Science.gov (United States)

    Crabbe, John C

    2016-09-01

    Nonhuman animals have been major contributors to the science of the genetics of addiction. Given the explosion of interest in genetics, it is fair to ask, are we making reasonable progress toward our goals with animal models? I will argue that our goals are changing and that overall progress has been steady and seems likely to continue apace. Genetics tools have developed almost incredibly rapidly, enabling both more reductionist and more synthetic or integrative approaches. I believe that these approaches to making progress have been unbalanced in biomedical science, favoring reductionism, particularly in animal genetics. I argue that substantial, novel progress is also likely to come in the other direction, toward synthesis and abstraction. Another area in which future progress with genetic animal models seems poised to contribute more is the reconciliation of human and animal phenotypes, or consilience. The inherent power of the genetic animal models could be more profitably exploited. In the end, animal research has continued to provide novel insights about how genes influence individual differences in addiction risk and consequences. The rules of the genetics game are changing so fast that it is hard to remember how comparatively little we knew even a generation ago. Rather than worry about whether we have been wasting time and resources asking the questions we have been, we should look to the future and see if we can come up with some new ones. The valuable findings from the past will endure, and the sidetracks will be forgotten. PMID:27588527

  5. Animal models in motion sickness research

    Science.gov (United States)

    Daunton, Nancy G.

    1990-01-01

    Practical information on candidate animal models for motion sickness research and on methods used to elicit and detect motion sickness in these models is provided. Four good potential models for use in motion sickness experiments include the dog, cat, squirrel monkey, and rat. It is concluded that the appropriate use of the animal models, combined with exploitation of state-of-the-art biomedical techniques, should generate a great step forward in the understanding of motion sickness mechanisms and in the development of efficient and effective approaches to its prevention and treatment in humans.

  6. A Review of Translational Animal Models for Knee Osteoarthritis

    OpenAIRE

    Gregory, Martin H.; Nicholas Capito; Keiichi Kuroki; Aaron M. Stoker; Cook, James L.; Sherman, Seth L.

    2012-01-01

    Knee osteoarthritis remains a tremendous public health concern, both in terms of health-related quality of life and financial burden of disease. Translational research is a critical step towards understanding and mitigating the long-term effects of this disease process. Animal models provide practical and clinically relevant ways to study both the natural history and response to treatment of knee osteoarthritis. Many factors including size, cost, and method of inducing osteoarthritis are impo...

  7. Naturally Occurring Animal Models with Outer Retina Phenotypes

    OpenAIRE

    Baehr, Wolfgang; Frederick, Jeanne M.

    2009-01-01

    Naturally occurring and laboratory generated animal models serve as powerful tools with which to investigate the etiology of human retinal degenerations, especially retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), cone dystrophies (CD) and macular degeneration (MD). Much progress has been made in elucidating gene defects underlying disease, in understanding mechanisms leading to disease, and in designing molecules for translational research and gene-based therapy to interfere with...

  8. Animal models and brain circuits in drug addiction.

    Science.gov (United States)

    Kalivas, Peter W; Peters, Jamie; Knackstedt, Lori

    2006-12-01

    Animal models in the field of addiction are considered to be among the best available models of neuropsychiatric disease. These models have undergone a number of refinements that allow deeper understanding of the circuitry involved in initiating drug seeking and relapse. Notably, the demonstrable involvement of classic corticostriatal habit circuitry and the engagement of prefrontal cortical circuits in extinction training may have relevance to the therapeutic modulation of habit circuitry and drug addiction in humans. PMID:17200461

  9. Final model of multicriterionevaluation of animal welfare

    DEFF Research Database (Denmark)

    Bonde, Marianne; Botreau, R; Bracke, MBM;

    One major objective of Welfare Quality® is to propose harmonized methods for the overall assessment of animal welfare on farm and at slaughter that are science based and meet societal concerns. Welfare is a multidimensional concept and its assessment requires measures of different aspects. Welfare...... Quality® proposes a formal evaluation model whereby the data on animals or their environment are transformed into value scores that reflect compliance with 12 subcriteria and 4 criteria of good welfare. Each animal unit is then allocated to one of four categories: excellent welfare, enhanced welfare......, acceptable welfare and not classified. This evaluation model is tuned according to the views of experts from animal and social sciences, and stakeholders....

  10. Animal models of anxiety disorders and stress

    OpenAIRE

    Campos, Alline C; Manoela V. Fogaca; Daniele C. Aguiar; Guimaraes, Francisco S.

    2013-01-01

    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 mecha...

  11. Animal models of contraception: utility and limitations

    OpenAIRE

    Liechty ER; Bergin IL; Bell JD

    2015-01-01

    Emma R Liechty,1 Ingrid L Bergin,1 Jason D Bell2 1Unit for Laboratory Animal Medicine, 2Program on Women's Health Care Effectiveness Research, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA Abstract: Appropriate animal modeling is vital for the successful development of novel contraceptive devices. Advances in reproductive biology have identified novel pathways for contraceptive intervention. Here we review species-specific anatomic and physiologic co...

  12. Animal models of contraception: utility and limitations

    OpenAIRE

    Bell, Jason

    2015-01-01

    Emma R Liechty,1 Ingrid L Bergin,1 Jason D Bell2 1Unit for Laboratory Animal Medicine, 2Program on Women's Health Care Effectiveness Research, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA Abstract: Appropriate animal modeling is vital for the successful development of novel contraceptive devices. Advances in reproductive biology have identified novel pathways for contraceptive intervention. Here we review species-specific anatomic and physiologi...

  13. Animal models to study the pathogenesis of human and animal Clostridium perfringens infections.

    Science.gov (United States)

    Uzal, Francisco A; McClane, Bruce A; Cheung, Jackie K; Theoret, James; Garcia, Jorge P; Moore, Robert J; Rood, Julian I

    2015-08-31

    The most common animal models used to study Clostridium perfringens infections in humans and animals are reviewed here. The classical C. perfringens-mediated histotoxic disease of humans is clostridial myonecrosis or gas gangrene and the use of a mouse myonecrosis model coupled with genetic studies has contributed greatly to our understanding of disease pathogenesis. Similarly, the use of a chicken model has enhanced our understanding of type A-mediated necrotic enteritis in poultry and has led to the identification of NetB as the primary toxin involved in disease. C. perfringens type A food poisoning is a highly prevalent bacterial illness in the USA and elsewhere. Rabbits and mice are the species most commonly used to study the action of enterotoxin, the causative toxin. Other animal models used to study the effect of this toxin are rats, non-human primates, sheep and cattle. In rabbits and mice, CPE produces severe necrosis of the small intestinal epithelium along with fluid accumulation. C. perfringens type D infection has been studied by inoculating epsilon toxin (ETX) intravenously into mice, rats, sheep, goats and cattle, and by intraduodenal inoculation of whole cultures of this microorganism in mice, sheep, goats and cattle. Molecular Koch's postulates have been fulfilled for enterotoxigenic C. perfringens type A in rabbits and mice, for C. perfringens type A necrotic enteritis and gas gangrene in chickens and mice, respectively, for C. perfringens type C in mice, rabbits and goats, and for C. perfringens type D in mice, sheep and goats. PMID:25770894

  14. Thirteen challenges in modelling plant diseases

    OpenAIRE

    Cunniffe, Nik J.; Britt Koskella; C. Jessica E. Metcalf; Stephen Parnell; Tim R Gottwald; Gilligan, Christopher A.

    2015-01-01

    The underlying structure of epidemiological models, and the questions that models can be used to address, do not necessarily depend on the host organism in question. This means that certain preoccupations of plant disease modellers are similar to those of modellers of diseases in human, livestock and wild animal populations. However, a number of aspects of plant epidemiology are very distinctive, and this leads to specific challenges in modelling plant diseases, which in turn sets a certain a...

  15. Pharmacokinetic modeling in aquatic animals. 1. Models and concepts

    Science.gov (United States)

    Barron, M.G.; Stehly, Guy R.; Hayton, W.L.

    1990-01-01

    While clinical and toxicological applications of pharmacokinetics have continued to evolve both conceptually and experimentally, pharmacokinetics modeling in aquatic animals has not progressed accordingly. In this paper we present methods and concepts of pharmacokinetic modeling in aquatic animals using multicompartmental, clearance-based, non-compartmental and physiologically-based pharmacokinetic models. These models should be considered as alternatives to traditional approaches, which assume that the animal acts as a single homogeneous compartment based on apparent monoexponential elimination.

  16. Control and eradication of animal diseases in New Zealand.

    Science.gov (United States)

    Davidson, R M

    2002-01-01

    New Zealand is free from all the major epidemic (Office International des Epizooties List A) diseases of animals and other important diseases, such as rabies and the transmissible spongiform encephalopathies. The once endemic conditions of sheep scab (Psoroptes ovis), bovine brucellosis (Brucella abortus), hydatids (Echinococcus granulosus) and Aujeszky's disease have been eradicated. Anthrax (Bacillus anthracis) is no longer considered endemic and Pullorum disease (Salmonella Pullorum) has effectively been eradicated from commercial poultry flocks. There are current control programmes for bovine tuberculosis (Mycobacterium bovis), enzootic bovine leucosis in dairy cattle, infectious bursal disease, ovine epididymitis (Brucella ovis), and caprine arthritis encephalitis. Historically, incursions by three important non-endemic diseases, contagious bovine pleuropneumonia, classical swine fever and scrapie, have been successfully eliminated. Any new occurrence of a serious exotic disease would be dealt with swiftly using powerful legislative authorities available for the purpose. PMID:16032229

  17. Comparison of animal models of hyperlipidemia

    OpenAIRE

    Xue-mei LIU

    2004-01-01

    Objective: To select the proper experimental animal model for research on prevention and treatment of hyperlipidemia. Method: Hyperlipidemia models of mouse, rat, golden hamster, guinea pig, rabbit, pigeon and quail often used in the last ten years were compared. Results: Golden hamster and guinea pig models are similar to human beings in lipid metabolism and have unique superiority in experimental study, while the models of rat, mouse, pigeon and quail have significant difference as compared...

  18. Phenotyping animal models of diabetic neuropathy

    DEFF Research Database (Denmark)

    Biessels, G J; Bril, V; Calcutt, N A;

    2014-01-01

    NIDDK, JDRF, and the Diabetic Neuropathy Study Group of EASD sponsored a meeting to explore the current status of animal models of diabetic peripheral neuropathy. The goal of the workshop was to develop a set of consensus criteria for the phenotyping of rodent models of diabetic neuropathy. The...

  19. Animal Models for HIV Cure Research

    OpenAIRE

    Benjamin B Policicchio; Pandrea, Ivona; Apetrei, Cristian

    2016-01-01

    The HIV-1/AIDS pandemic continues to spread unabated worldwide, and no vaccine exists within our grasp. Effective antiretroviral therapy (ART) has been developed, but ART cannot clear the virus from the infected patient. A cure for HIV-1 is badly needed to stop both the spread of the virus in human populations and disease progression in infected individuals. A safe and effective cure strategy for human immunodeficiency virus (HIV) infection will require multiple tools, and appropriate animal ...

  20. Diabetic cardiac autonomic neuropathy: insights from animal models.

    Science.gov (United States)

    Stables, Catherine L; Glasser, Rebecca L; Feldman, Eva L

    2013-10-01

    Cardiac autonomic neuropathy (CAN) is a relatively common and often devastating complication of diabetes. The major clinical signs are tachycardia, exercise intolerance, and orthostatic hypotension, but the most severe aspects of this complication are high rates of cardiac events and mortality. One of the earliest manifestations of CAN is reduced heart rate variability, and detection of this, along with abnormal results in postural blood pressure testing and/or the Valsalva maneuver, are central to diagnosis of the disease. The treatment options for CAN, beyond glycemic control, are extremely limited and lack evidence of efficacy. The underlying molecular mechanisms are also poorly understood. Thus, CAN is associated with a poor prognosis and there is a compelling need for research to understand, prevent, and reverse CAN. In this review of the literature we examine the use and usefulness of animal models of CAN in diabetes. Compared to other diabetic complications, the number of animal studies of CAN is very low. The published studies range across a variety of species, methods of inducing diabetes, and timescales examined, leading to high variability in study outcomes. The lack of well-characterized animal models makes it difficult to judge the relevance of these models to the human disease. One major advantage of animal studies is the ability to probe underlying molecular mechanisms, and the limited numbers of mechanistic studies conducted to date are outlined. Thus, while animal models of CAN in diabetes are crucial to better understanding and development of therapies, they are currently under-used. PMID:23562143

  1. Clinical Forms and Animal Models of Hypophosphatasia.

    Science.gov (United States)

    Salles, Jean Pierre

    2015-01-01

    Hypophosphatasia (HPP) is due to mutations of the tissue non-specific alkaline phosphatase (TNAP) gene expressed in the liver, kidney, and bone. TNAP substrates include inorganic pyrophosphate cleaved into inorganic phosphate (Pi) in bone, pyridoxal-5'-phosphate (PLP), the circulating form of vitamin B6, and phosphoethanolamine (PEA). As an autosomal recessive or dominant disease, HPP results in a range of clinical forms. Its hallmarks are low alkaline phosphatase (AP) and elevated PLP and PEA levels. Perinatal HPP may cause early death with respiratory insufficiency and hypomineralization resulting in deformed limbs and sometimes near-absence of bones and skull. Infantile HPP is diagnosed before 6 months of life. Respiratory failure, rib fractures and seizures due to vitamin B6 deficiency in the brain indicate poor prognosis. Craniosynostosis is frequent. Unlike in other forms of rickets, calcium and phosphorus are not decreased, resulting in hypercalciuria and nephrocalcinosis. Hypercalcemic crisis may occur. Failure to thrive and growth retardation are concerns. In infantile and adult forms of HPP, non-traumatic fractures may be the prominent manifestation, with otherwise unexplained chronic pain. Progressive myopathy has been described. Dental manifestations with early loss of teeth are usual in HPP and in a specific form, odontohypophosphatasia. HPP has been studied in knock-out mice models which mimic its severe form. Animal models have made a major contribution to the development of an original enzyme therapy for human infantile HPP, which is however essentially targeted at mineralized tissues. Better knowledge of its extraskeletal manifestations, including pain and neurological symptoms, is therefore required. PMID:26219704

  2. Differential Paradigms in Animal Models of Sepsis.

    Science.gov (United States)

    Kingsley, S Manoj Kumar; Bhat, B Vishnu

    2016-09-01

    Sepsis is a serious clinical problem involving complex mechanisms which requires better understanding and insight. Animal models of sepsis have played a major role in providing insight into the complex pathophysiology of sepsis. There have been various animal models of sepsis with different paradigms. Endotoxin, bacterial infusion, cecal ligation and puncture, and colon ascendens stent peritonitis models are the commonly practiced methods at present. Each of these models has their own advantages and also confounding factors. We have discussed the underlying mechanisms regulating each of these models along with possible reasons why each model failed to translate into the clinic. In animal models, the timing of development of the hemodynamic phases and the varied cytokine patterns could not accurately resemble the progression of clinical sepsis. More often, the exuberant and transient pro-inflammatory cytokine response is only focused in most models. Immunosuppression and apoptosis in the later phase of sepsis have been found to cause more damage than the initial acute phase of sepsis. Likewise, better understanding of the existing models of sepsis could help us create a more relevant model which could provide solution to the currently failed clinical trials in sepsis. PMID:27432263

  3. Impact of animal diseases on livestock productivity and economic losses

    International Nuclear Information System (INIS)

    The most serious impact of animal disease on livestock productivity in developing countries derives from its effect on overall livestock production and trade development rather than from the direct losses it causes. The global importance of major infectious diseases such as foot and mouth disease, rinderpest and African swine fever is reviewed. The impact of major livestock diseases in tropical Africa on livestock productivity and economic losses is analysed, and the importance of in-depth analysis of the disease impact on livestock and rural development is stressed. Lack of diagnosis facilities that are needed to acquire reliable information on the distribution of disease is often a major constraint to cost-benefit analysis of control options. However, enough evidence exists to substantiate the fact that improved disease control is a prerequisite for progress towards increased productivity based on the adoption of more intensive production systems and use of animals of improved genotype. Veterinary services in developing countries are at various stages of development, and the priority order of infra-structure, manpower and technological development for disease control programmes should be carefully planned and be based on socio-economic, cost-benefit and feasibility studies. (author)

  4. Novel Animal Models of Pediatric Epilepsy

    OpenAIRE

    Auvin, Stéphane; Pineda, Eduardo; Shin, Don; Gressens, Pierre; Mazarati, Andrey

    2012-01-01

    When mimicking epileptic processes in a laboratory setting, it is important to understand the differences between experimental models of seizures and epilepsy. Because human epilepsy is defined by the appearance of multiple spontaneous recurrent seizures, the induction of a single acute seizure without recurrence does not constitute an adequate epilepsy model. Animal models of epilepsy might be useful for various tasks. They allow for the investigation of pathophysiological mechanisms of the ...

  5. Animal models of focal brain ischemia

    OpenAIRE

    Sicard Kenneth M; Fisher Marc

    2009-01-01

    Abstract Stroke is a leading cause of disability and death in many countries. Understanding the pathophysiology of ischemic injury and developing therapies is an important endeavor that requires much additional research. Animal stroke models provide an important mechanism for these activities. A large number of stroke models have been developed and are currently used in laboratories around the world. These models are overviewed as are approaches for measuring infarct size and functional outcome.

  6. Monkeypox Virus Infections in Small Animal Models for Evaluation of Anti-Poxvirus Agents

    OpenAIRE

    Inger K Damon; Christina L Hutson

    2010-01-01

    An ideal animal model for the study of a human disease is one which utilizes a route of infection that mimics the natural transmission of the pathogen; the ability to obtain disease with an infectious dose equivalent to that causing disease in humans; as well having a disease course, morbidity and mortality similar to that seen with human disease. Additionally, the animal model should have a mode(s) of transmission that mimics human cases. The development of small animal models for the study ...

  7. Animal models of gene-nutrient interactions.

    Science.gov (United States)

    Reed, Danielle R

    2008-12-01

    Food intake of humans is governed by the food's nutritional value and pleasing taste, but also by other factors such as food cost and availability, cultural imperatives, and social status. The biological determinants of human food intake are not easily parsed from these other factors, making them hard to study against the whirligig aspects of human life in a modern age. The study of animals provides a useful alternative. Humans have a history of studying animal food intake, for agricultural reasons (e.g., pigs and cows), and for personal reasons (e.g., dogs and cats), and these practical concerns have been joined with the appreciation that other models can teach us the principles of behavior, genetics, and nutrition. Thus there is a steady use of the traditional animal models in this type of research, as well as growth in the use of other systems such as worms and flies. Rats and mice occupy a special niche as animal models for two reasons; first, they share with humans a love of the same types of food, and second, they are the target of a number of well-developed genetic tools. The available genetic tools that make mice a popular model include a well-annotated genome (Mouse Build 37), profiles of RNA expression from many tissues, a diverse panel of inbred strains, and the ability to manipulate genes in the whole animal, including removing a gene only in specific tissues (e.g., Cre-lox system). Mice have been harnessed to find genotypes that contribute to sweet-liking, and other studies are underway to understand how genetic variation might at least partially explain other puzzles of human appetites. Animal models provide a way to study the genetic determinants of food selection with experimental rigor and therefore complement human genetics studies. PMID:19037208

  8. Tissue and Animal Models of Sudden Cardiac Death

    OpenAIRE

    Sallam, Karim; Li, Yingxin; Sager, Philip T.; Steven R. Houser; Wu, Joseph C.

    2015-01-01

    Sudden Cardiac Death (SCD) is a common cause of death in patients with structural heart disease, genetic mutations or acquired disorders affecting cardiac ion channels. A wide range of platforms exist to model and study disorders associated with SCD. Human clinical studies are cumbersome and are thwarted by the extent of investigation that can be performed on human subjects. Animal models are limited by their degree of homology to human cardiac electrophysiology including ion channel expressi...

  9. Animal models for studying penile hemodynamics

    Institute of Scientific and Technical Information of China (English)

    HiroyaMizusawa; OsamuIshizuka

    2002-01-01

    Animal models for the study of erectile function monitoring the changes in intracavernous pressure(ICP)during penile erection was reviewed.The development of new modwls using small commercially-available experimen-tal animals,rats and mice,in the last edcade facilitated in vivo investigation of erectile physiology.The technique enabled to evaluate even subtle erectile responses by analyzing ICPand systemic blood pressure,Moreover,the method has been well improved and studies using conscious animal models without the influence of any drug or anesthesia are more appropriate in exploring the precise physiological and pharmacological mechanisms in erection.Also,more natural and physiological sexual arousal instead of electrical or pharmacological stimulation is desirable in most of the studies.This article reviewed the development of ICPstudies in rats and mice.

  10. Teaching Neurophysiology, Neuropharmacology, and Experimental Design Using Animal Models of Psychiatric and Neurological Disorders

    Science.gov (United States)

    Morsink, Maarten C.; Dukers, Danny F.

    2009-01-01

    Animal models have been widely used for studying the physiology and pharmacology of psychiatric and neurological diseases. The concepts of face, construct, and predictive validity are used as indicators to estimate the extent to which the animal model mimics the disease. Currently, we used these three concepts to design a theoretical assignment to…

  11. Animal models for Ebola and Marburg virus infections

    Directory of Open Access Journals (Sweden)

    Eri eNakayama

    2013-09-01

    Full Text Available Ebola and Marburg hemorrhagic fevers (EHF and MHF are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus, respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4 pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using nonhuman primates (NHPs and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics.

  12. Animal Models of Middle Ear Cholesteatoma

    OpenAIRE

    Tomomi Yamamoto-Fukuda; Haruo Takahashi; Takehiko Koji

    2011-01-01

    Middle ear acquired cholesteatoma is a pathological condition associated with otitis media, which may be associated with temporal bone resorption, otorrhea and hearing loss, and occasionally various other complications. Cholesteatoma is characterized by the enhanced proliferation of epithelial cells with aberrant morphologic characteristics. Unfortunately, our understanding of the mechanism underlying its pathogenesis is limited. To investigate its pathogenesis, different animal models have b...

  13. Translational In Vivo Models for Cardiovascular Diseases.

    Science.gov (United States)

    Fliegner, Daniela; Gerdes, Christoph; Meding, Jörg; Stasch, Johannes-Peter

    2016-01-01

    Cardiovascular diseases are still the first leading cause of death and morbidity in developed countries. Experimental cardiology research and preclinical drug development in cardiology call for appropriate and especially clinically relevant in vitro and in vivo studies. The use of animal models has contributed to expand our knowledge and our understanding of the underlying mechanisms and accordingly provided new approaches focused on the improvement of diagnostic and treatment strategies of various cardiac pathologies.Numerous animal models in different species as well as in small and large animals have been developed to address cardiovascular complications, including heart failure, pulmonary hypertension, and thrombotic diseases. However, a perfect model of heart failure or other indications that reproduces every aspect of the natural disease does not exist. The complexity and heterogeneity of cardiac diseases plus the influence of genetic and environmental factors limit to mirror a particular disease with a single experimental model.Thus, drug development in the field of cardiology is not only very challenging but also inspiring; therefore animal models should be selected that reflect as best as possible the disease being investigated. Given the wide range of animal models, reflecting critical features of the human pathophysiology available nowadays increases the likelihood of the translation to the patients. Furthermore, this knowledge and the increase of the predictive value of preclinical models help us to find more efficient and reliable solutions as well as better and innovative treatment strategies for cardiovascular diseases. PMID:26552402

  14. Animal models for meniscus repair and regeneration.

    Science.gov (United States)

    Deponti, Daniela; Di Giancamillo, Alessia; Scotti, Celeste; Peretti, Giuseppe M; Martin, Ivan

    2015-05-01

    The meniscus plays an important role in knee function and mechanics. Meniscal lesions, however, are common phenomena and this tissue is not able to achieve spontaneous successful repair, particularly in the inner avascular zone. Several animal models have been studied and proposed for testing different reparative approaches, as well as for studying regenerative methods aiming to restore the original shape and function of this structure. This review summarizes the gross anatomy, function, ultrastructure and biochemical composition of the knee meniscus in several animal models in comparison with the human meniscus. The relevance of the models is discussed from the point of view of basic research as well as of clinical translation for meniscal repair, substitution and regeneration. Finally, the advantages and disadvantages of each model for various research directions are critically discussed. PMID:23712959

  15. Genetically Modified Pig Models for Human Diseases

    Institute of Scientific and Technical Information of China (English)

    Nana Fan; Liangxue Lai

    2013-01-01

    Genetically modified animal models are important for understanding the pathogenesis of human disease and developing therapeutic strategies.Although genetically modified mice have been widely used to model human diseases,some of these mouse models do not replicate important disease symptoms or pathology.Pigs are more similar to humans than mice in anatomy,physiology,and genome.Thus,pigs are considered to be better animal models to mimic some human diseases.This review describes genetically modified pigs that have been used to model various diseases including neurological,cardiovascular,and diabetic disorders.We also discuss the development in gene modification technology that can facilitate the generation of transgenic pig models for human diseases.

  16. Update on Animal Models for HIV Research

    OpenAIRE

    Haigwood, Nancy L.

    2009-01-01

    Animal models for HIV research have been indispensible in fulfilling Koch’s postulate and in exploring issues of viral infectivity and pathogenesis, sequence divergence, route(s) of acquisition, tissue distribution and tropism, immunogenicity and protection capacity of vaccine candidates, escape from adaptive immunity, and more. Did they fail to predict the efficacy of T cell vaccines in humans? This article summarizes progress and status of models to inform and complement clinical work.

  17. Translational value of animal models of asthma: Challenges and promises.

    Science.gov (United States)

    Sagar, Seil; Akbarshahi, Hamid; Uller, Lena

    2015-07-15

    Asthma is a heterogeneous disease in which various environmental stimuli as well as different genes, cell types, cytokines and mediators are implicated. This chronic inflammatory disorder of the airways is estimated to affect as many as 300 million people worldwide. Animal models of asthma, despite their limitations, have contributed greatly to our understanding of disease pathology and the identification of key processes, cells and mediators in asthma. However, it is less likely to develop an animal model of asthma that takes into account all aspects of human disease. The focus in current asthma research is increasingly on severe asthma because this group of patients is not well treated today. Recent advances in studies of asthma exacerbation are thus considered. We therefore need to develop translational model systems for pharmacological evaluation and molecular target discovery of severe asthma and asthma exacerbations. In this review we attempted to discuss the different animal models of asthma, with special emphasis on ovalbumin and house dust mite models, their merits and their limitations. PMID:25823808

  18. 7-nitroindazole attenuates 6-hydroxydopamine-induced spatial learning deficits and dopamine neuron loss in a presymptomatic animal model of Parkinson's disease.

    Science.gov (United States)

    Haik, Kristi L; Shear, Deborah A; Hargrove, Chad; Patton, Jared; Mazei-Robison, Michelle; Sandstrom, Michael I; Dunbar, Gary L

    2008-04-01

    Parkinson's disease (PD) is a neurodegenerative disorder in which loss of dopaminergic (DA) neurons (>50%) in the substantia nigra (SN) precedes most of the overt motor symptoms, making early diagnosis and treatment interventions difficult. Because PD has been associated with free radicals generated by nitric oxide, this study tested whether treatments of 7-nitroindazole (7NI), a nitric-oxide-synthase inhibitor, could reduce cognitive deficits that often emerge before overt motor symptoms in a presymptomatic rat model of PD. Rats were given intraperitoneal injections of 50 mg/kg 7NI (or vehicle) just before receiving bilateral, intrastriatal injections of the DA-toxin, 6-hydroxydopamine (6-OHDA). The rats were then given a battery of motor tasks, and their learning ability was assessed using a spatial reversal task in a water-T maze. Results indicate that 7NI treatments attenuate 6-OHDA-induced spatial learning deficits and protect against DA cell loss in the SN, suggesting that 7NI may have potential as an early, presymptomatic pharmacotherapy for PD. PMID:18489022

  19. Animal models of cerebral ischemia for evaluation of drugs.

    Science.gov (United States)

    Gupta, Y K; Briyal, Seema

    2004-10-01

    Stroke is a major cause of death and disability worldwide. The resulting burden on the society continues to grow, with increase in the incidence of stroke. Brain attack is a term introduced to describe the acute presentation of stroke, which emphasizes the need for urgent action to remedy the situation. Though a large number of therapeutic agents like thrombolytics, NMDA receptor antagonists, calcium channel blockers and antioxidants, have been used or being evaluated, there remains a large gap between the benefits by these agents and properties an ideal drug for stroke should offer. In recent years much attention is being paid towards the exploration of herbal preparation, antioxidant agents and combination therapies including COX-2 inhibitors in experimental model of stroke. For better evaluation of the drugs and enhancement of their predictability from animal experimentation to clinical settings, it has been realized that the selection of animal models, the parameters to be evaluated should be critically assessed. Focal and global cerebral ischemia represents diseases that are common in the human population. Understanding the mechanisms of injury and neuroprotection in these diseases is important to learn new target sites to treat ischemia. There are many animal models available to investigate injury mechanisms and neuroprotective strategies. In this article we attempted to summarize commonly explored animal models of focal and global cerebral ischemia and evaluate their advantages and limitations. PMID:15907047

  20. The hypoxia imaging agent CuII(atsm) is neuroprotective and improves motor and cognitive functions in multiple animal models of Parkinson’s disease

    OpenAIRE

    Hung, Lin W.; Victor L Villemagne; Cheng, Lesley; Nicki A. Sherratt; Ayton, Scott; White, Anthony R.; Peter J Crouch; Lim, SinChun; Leong, Su Ling; Wilkins, Simon; George, Jessica; Blaine R. Roberts; Chi L L Pham; Liu, Xiang(Research Center for Hadron and CSR Physics, Lanzhou University and Institute of Modern Physics of CAS, 730000, Lanzhou , China); Chiu, Francis C. K.

    2012-01-01

    Parkinson’s disease (PD) is a progressive, chronic disease characterized by dyskinesia, rigidity, instability, and tremors. The disease is defined by the presence of Lewy bodies, which primarily consist of aggregated α-synuclein protein, and is accompanied by the loss of monoaminergic neurons. Current therapeutic strategies only give symptomatic relief of motor impairment and do not address the underlying neurodegeneration. Hence, we have identified CuII(atsm) as a potential therapeutic for P...

  1. Helium ventilation in obstructive respiratory diseases : evaluation of ventilation/perfusion relationships with the MIGET : from the animal model to the clinical application

    OpenAIRE

    Watremez, Christine

    2010-01-01

    To briefly guide the reader along this thesis on the contribution of helium ventilation in bronchospastic diseases, we provide a short outline in five steps as following: - First, we will review briefly the basis of asthma disease and COPD. - Second, we will describe some respiratory measurements we have at one’s disposal to evaluate the level of the disease and the extent of therapy effect. - Third, we will make a recall of measurement of the ventilation-perfusion relationships by t...

  2. Reproduction of post-weaning multi-systemic wasting syndrome in an animal disease model as a tool for vaccine testing under controlled conditions.

    Science.gov (United States)

    McKillen, John; McNair, Irene; Lagan, Paula; McKay, Karen; McClintock, Julie; Casement, Veronica; Charreyre, Catherine; Allan, Gordon

    2016-04-01

    Snatch farrowed, colostrum deprived piglets were inoculated with different combinations of porcine circovirus 2, porcine parvovirus and Erysipelothrix rhusiopathiae candidate vaccines. 10 piglets were mock-vaccinated. Following virus challenge with a combined porcine circovirus 2/porcine parvovirus inoculum, all animals were monitored and samples taken for serology, immunohistochemistry and qPCR. At 24dpc all non-vaccinated animals remaining were exhibiting signs of post-weaning multi-systemic wasting syndrome which was confirmed by laboratory analysis. Details of the study, analysis of samples and performance of the candidate vaccines are described. PMID:27033924

  3. Fantastic animals as an experimental model to teach animal adaptation

    Directory of Open Access Journals (Sweden)

    Veronesi Paola

    2007-08-01

    Full Text Available Abstract Background Science curricula and teachers should emphasize evolution in a manner commensurate with its importance as a unifying concept in science. The concept of adaptation represents a first step to understand the results of natural selection. We settled an experimental project of alternative didactic to improve knowledge of organism adaptation. Students were involved and stimulated in learning processes by creative activities. To set adaptation in a historic frame, fossil records as evidence of past life and evolution were considered. Results The experimental project is schematized in nine phases: review of previous knowledge; lesson on fossils; lesson on fantastic animals; planning an imaginary world; creation of an imaginary animal; revision of the imaginary animals; adaptations of real animals; adaptations of fossil animals; and public exposition. A rubric to evaluate the student's performances is reported. The project involved professors and students of the University of Modena and Reggio Emilia and of the "G. Marconi" Secondary School of First Degree (Modena, Italy. Conclusion The educational objectives of the project are in line with the National Indications of the Italian Ministry of Public Instruction: knowledge of the characteristics of living beings, the meanings of the term "adaptation", the meaning of fossils, the definition of ecosystem, and the particularity of the different biomes. At the end of the project, students will be able to grasp particular adaptations of real organisms and to deduce information about the environment in which the organism evolved. This project allows students to review previous knowledge and to form their personalities.

  4. Animal models of contraception: utility and limitations

    Directory of Open Access Journals (Sweden)

    Liechty ER

    2015-04-01

    Full Text Available Emma R Liechty,1 Ingrid L Bergin,1 Jason D Bell2 1Unit for Laboratory Animal Medicine, 2Program on Women's Health Care Effectiveness Research, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA Abstract: Appropriate animal modeling is vital for the successful development of novel contraceptive devices. Advances in reproductive biology have identified novel pathways for contraceptive intervention. Here we review species-specific anatomic and physiologic considerations impacting preclinical contraceptive testing, including efficacy testing, mechanistic studies, device design, and modeling off-target effects. Emphasis is placed on the use of nonhuman primate models in contraceptive device development. Keywords: nonhuman primate, preclinical, in vivo, contraceptive devices

  5. The use of animal models in multiple myeloma.

    Science.gov (United States)

    Libouban, H

    2015-06-01

    In myeloma, the understanding of the tissular, cellular and molecular mechanisms of the interactions between tumor plasma cells and bone cells have progressed from in vitro and in vivo studies. However none of the known animal models of myeloma reproduce exactly the human form of the disease. There are currently three types of animal models: (1) injection of pristane oil in BALB/c mice leads to intraperitoneal plasmacytomas but without bone marrow colonization and osteolysis; (2) injection of malignant plasma cell lines in immunodeficient mice SCID or NOD/SCID; the use of the SCID-hu or SCID-rab model allows the use of fresh plasma cells obtained from MM patients; (3) injection of allogeneic malignant plasma cells (5T2MM, 5T33) in the C57BL/KalwRij mouse induces bone marrow proliferation and osteolytic lesions. These cells did not grow in vitro and can be propagated by injection of plasma cells isolated from bone marrow of a mouse at end stage of the disease into young recipient mice. The 5TGM1 is a subclone of 5T33MM cells and can grow in vitro. Among the different models, the 5TMM models and SCID-hu/SCID-rab models were extensively used to test pathophysiological hypotheses and to assess anti-osteoclastic, anti-osteoblastic or anti-tumor therapies in myeloma. In the present review, we report the different types of animal models of MM and describe their interests and limitations. PMID:25898798

  6. Animal models of anxiety disorders and stress

    Directory of Open Access Journals (Sweden)

    Alline C. Campos

    2013-01-01

    Full Text Available 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, including psychosocial (social defeat and neonatal isolation stress, physical (restraint stress, and chronic unpredictable stress.

  7. WHAT WE ARE LEARNING ON HTLV-1 PATHOGENESISFROM ANIMAL MODELS

    Directory of Open Access Journals (Sweden)

    Madeleine eDuc Dodon

    2012-08-01

    Full Text Available Isolated and identified more than 30 years ago, Human T-cell Leukemia Virus type 1 (HTLV-1 is the etiological agent of adult T-cell leukemia/lymphoma (ATL, an aggressive lymphoproliferative disease of activated CD4+ T cells, and other inflammatory disorders such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. A variety of animal models have contributed to the fundamental knowledge of HTLV-1 transmission, pathogenesis and to the design of novel therapies to treat HTLV-1 associated diseases. Small animal models (rabbits, rats, mice as well as large animal models (monkeys have been utilized to significantly advance characterization of the viral proteins and of virus-infected cells in the early steps of infection, as well as in the development of leukemogenic and immunopathogenic processes. Over the past two decades, the creation of new immuno-compromised mouse strains that are robustly reconstituted with a functional human immune system (HIS after being transplanted with human tissues or progenitor cells has revolutionized the in vivo investigation of viral infection and pathogenesis. Recent observations obtained in HTLV-1-infected humanized HIS mice that develop lymphomas provide the opportunity to study the evolution of the proviral clonality in human T cells present in different lymphoid organs. Current progress in the improvement of those humanized models will favor the testing of drugs and the development of targeted therapies against HTLV-1-associated diseases.

  8. Behavioral impairments in animal models for zinc deficiency

    Directory of Open Access Journals (Sweden)

    Simone eHagmeyer

    2015-01-01

    Full Text Available Apart from teratogenic and pathological effects of zinc deficiency such as the occurrence of skin lesions, anorexia, growth retardation, depressed wound healing, altered immune function, impaired night vision, and alterations in taste and smell acuity, characteristic behavioral changes in animal models and human patients suffering from zinc deficiency have been observed. Given that it is estimated that about 17% of the worldwide population are at risk for zinc deficiency and that zinc deficiency is associated with a variety of brain disorders and disease states in humans, it is of major interest to investigate, how these behavioral changes will affect the individual and a putative course of a disease. Thus, here, we provide a state of the art overview about the behavioral phenotypes observed in various models of zinc deficiency, among them environmentally produced zinc deficient animals as well as animal models based on a genetic alteration of a particular zinc homeostasis gene. Finally, we compare the behavioral phenotypes to the human condition of mild to severe zinc deficiency and provide a model, how zinc deficiency that is associated with many neurodegenerative and neuropsychological disorders might modify the disease pathologies.

  9. Experimental autoimmune uveitis and other animal models of uveitis: An update

    OpenAIRE

    Svati Bansal; Barathi, Veluchamy A.; Daiju Iwata; Rupesh Agrawal

    2015-01-01

    Over the past several decades, animal models of autoimmune uveitis directed at eye-specific antigens (Ags) have been developed. These have allowed researchers to understand the basic mechanisms that lead to these diseases and also recently helped the researchers in translational research for therapeutic interventions. Experimental autoimmune uveitis (EAU) is an animal disease model of human endogenous uveitis and can be induced in susceptible animals by immunization with retinal Ags. Ever sin...

  10. Animal models of epilepsy: use and limitations

    Directory of Open Access Journals (Sweden)

    Kandratavicius L

    2014-09-01

    Full Text Available Ludmyla Kandratavicius,1 Priscila Alves Balista,1 Cleiton Lopes-Aguiar,1 Rafael Naime Ruggiero,1 Eduardo Henrique Umeoka,2 Norberto Garcia-Cairasco,2 Lezio Soares Bueno-Junior,1 Joao Pereira Leite11Department of Neurosciences and Behavior, 2Department of Physiology, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, BrazilAbstract: Epilepsy is a chronic neurological condition characterized by recurrent seizures that affects millions of people worldwide. Comprehension of the complex mechanisms underlying epileptogenesis and seizure generation in temporal lobe epilepsy and other forms of epilepsy cannot be fully acquired in clinical studies with humans. As a result, the use of appropriate animal models is essential. Some of these models replicate the natural history of symptomatic focal epilepsy with an initial epileptogenic insult, which is followed by an apparent latent period and by a subsequent period of chronic spontaneous seizures. Seizures are a combination of electrical and behavioral events that are able to induce chemical, molecular, and anatomic alterations. In this review, we summarize the most frequently used models of chronic epilepsy and models of acute seizures induced by chemoconvulsants, traumatic brain injury, and electrical or sound stimuli. Genetic models of absence seizures and models of seizures and status epilepticus in the immature brain were also examined. Major uses and limitations were highlighted, and neuropathological, behavioral, and neurophysiological similarities and differences between the model and the human equivalent were considered. The quest for seizure mechanisms can provide insights into overall brain functions and consciousness, and animal models of epilepsy will continue to promote the progress of both epilepsy and neurophysiology research.Keywords: epilepsy, animal model, pilocarpine, kindling, neurodevelopment

  11. Overview on available animal models for application in leukemia research

    International Nuclear Information System (INIS)

    The term ''leukemia'' encompasses a group of diseases with a variable clinical and pathological presentation. Its cellular origin, its biology and the underlying molecular genetic alterations determine the very variable and individual disease phenotype. The focus of this review is to discuss the most important guidelines to be taken into account when we aim at developing an ''ideal'' animal model to study leukemia. The animal model should mimic all the clinical, histological and molecular genetic characteristics of the human phenotype and should be applicable as a clinically predictive model. It should achieve all the requirements to be used as a standardized model adaptive to basic research as well as to pharmaceutical practice. Furthermore it should fulfill all the criteria to investigate environmental risk factors, the role of genomic mutations and be applicable for therapeutic testing. These constraints limit the usefulness of some existing animal models, which are however very valuable for basic research. Hence in this review we will primarily focus on genetically engineered mouse models (GEMMs) to study the most frequent types of childhood leukemia. GEMMs are robust models with relatively low site specific variability and which can, with the help of the latest gene modulating tools be adapted to individual clinical and research questions. Moreover they offer the possibility to restrict oncogene expression to a defined target population and regulate its expression level as well as its timely activity. Until recently it was only possible in individual cases to develop a murin model, which fulfills the above mentioned requirements. Hence the development of new regulatory elements to control targeted oncogene expression should be priority. Tightly controlled and cell specific oncogene expression can then be combined with a knock-in approach and will depict a robust murine model, which enables almost physiologic oncogene

  12. Noninvasive Assessment of Tumor Cell Proliferation in Animal Models

    Directory of Open Access Journals (Sweden)

    Matthias Edinger

    1999-10-01

    Full Text Available Revealing the mechanisms of neoplastic disease and enhancing our ability to intervene in these processes requires an increased understanding of cellular and molecular changes as they occur in intact living animal models. We have begun to address these needs by developing a method of labeling tumor cells through constitutive expression of an optical reporter gene, noninvasively monitoring cellular proliferation in vivo using a sensitive photon detection system. A stable line of HeLa cells that expressed a modified firefly luciferase gene was generated, proliferation of these cells in irradiated severe combined immunodeficiency (SCID mice was monitored. Tumor cells were introduced into animals via subcutaneous, intraperitoneal and intravenous inoculation and whole body images, that revealed tumor location and growth kinetics, were obtained. The number of photons that were emitted from the labeled tumor cells and transmitted through murine tissues was sufficient to detect 1×103 cells in the peritoneal cavity, 1×104 cells at subcutaneous sites and 1×106 circulating cells immediately following injection. The kinetics of cell proliferation, as measured by photon emission, was exponential in the peritoneal cavity and at subcutaneous sites. Intravenous inoculation resulted in detectable colonies of tumor cells in animals receiving more than 1×103 cells. Our demonstrated ability to detect small numbers of tumor cells in living animals noninvasively suggests that therapies designed to treat minimal disease states, as occur early in the disease course and after elimination of the tumor mass, may be monitored using this approach. Moreover, it may be possible to monitor micrometastases and evaluate the molecular steps in the metastatic process. Spatiotemporal analyses of neoplasia will improve the predictability of animal models of human disease as study groups can be followed over time, this method will accelerate development of novel therapeutic

  13. Is Epilepsy a Preventable Disorder? New Evidence from Animal Models

    OpenAIRE

    Giblin, Kathryn A.; Blumenfeld, Hal

    2010-01-01

    Epilepsy accounts for 0.5% of the global burden of disease, and primary prevention of epilepsy represents one of the three 2007 NINDS Epilepsy Research Benchmarks. In the past decade, efforts to understand and intervene in the process of epileptogenesis have yielded fruitful preventative strategies in animal models. This article reviews the current understanding of epileptogenesis, introduces the concept of a “critical period” for epileptogenesis, and examines strategies for epilepsy preventi...

  14. The search for animal models for Lassa fever vaccine development

    OpenAIRE

    Lukashevich, Igor S.

    2013-01-01

    Lassa virus (LASV) is the most prevalent arenavirus in West Africa and is responsible for several hundred thousand infections and thousands of deaths annually. The sizeable disease burden, numerous imported cases of Lassa fever (LF) and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Currently there is no licensed LF vaccine and research and devlopment is hampered by the high cost of nonhuman primate animal models and by bioc...

  15. Animal models of alcohol and drug dependence

    Directory of Open Access Journals (Sweden)

    Cleopatra S. Planeta

    2013-01-01

    Full Text Available Drug addiction has serious health and social consequences. In the last 50 years, a wide range of techniques have been developed to model specific aspects of drug-taking behaviors and have greatly contributed to the understanding of the neurobiological basis of drug abuse and addiction. In the last two decades, new models have been proposed in an attempt to capture the more genuine aspects of addiction-like behaviors in laboratory animals. The goal of the present review is to provide an overview of the preclinical procedures used to study drug abuse and dependence and describe recent progress that has been made in studying more specific aspects of addictive behavior in animals.

  16. Deformation Models Tracking, Animation and Applications

    CERN Document Server

    Torres, Arnau; Gómez, Javier

    2013-01-01

    The computational modelling of deformations has been actively studied for the last thirty years. This is mainly due to its large range of applications that include computer animation, medical imaging, shape estimation, face deformation as well as other parts of the human body, and object tracking. In addition, these advances have been supported by the evolution of computer processing capabilities, enabling realism in a more sophisticated way. This book encompasses relevant works of expert researchers in the field of deformation models and their applications.  The book is divided into two main parts. The first part presents recent object deformation techniques from the point of view of computer graphics and computer animation. The second part of this book presents six works that study deformations from a computer vision point of view with a common characteristic: deformations are applied in real world applications. The primary audience for this work are researchers from different multidisciplinary fields, s...

  17. A Physically-Modified Saline Suppresses Neuronal Apoptosis, Attenuates Tau Phosphorylation and Protects Memory in an Animal Model of Alzheimer's Disease

    OpenAIRE

    Modi, Khushbu K.; Jana, Arundhati; Ghosh, Supurna; Watson, Richard; Pahan, Kalipada

    2014-01-01

    Alzheimer's disease (AD), the leading cause of dementia in the aging population, is characterized by the presence of neuritic plaques, neurofibrillary tangles and extensive neuronal apoptosis. Neuritic plaques are mainly composed of aggregates of amyloid-β (Aβ) protein while neurofibrillary tangles are composed of the hyperphosphorylated tau protein. Despite intense investigations, no effective therapy is currently available to halt the progression of this disease. Here, we have undertaken a ...

  18. Penile autotransplantation in rats: An animal model

    OpenAIRE

    Seyam, Raouf M.; Said A Kattan; Assad, Lina W.; Raafat M El-Sayed; Falah H Almohanna

    2013-01-01

    Context: Penile allotransplantation might be a viable option for patients who need penile reconstruction. Aims: A successful autotransplantation rat model is the first step toward proceeding for allotransplantation. We herein evaluate autotransplantation following transaction of the rat penis just distal to the urethral bulb. Settings and Design: Experimental animal study. Materials and Methods: Five Sprague-Dawely rats weighing 520 g (SD 19) were used. Utilizing a magnification o...

  19. Animal Models of Typical Heterotopic Ossification

    OpenAIRE

    Lixin Kan; Kessler, John A.

    2010-01-01

    Heterotopic ossification (HO) is the formation of marrow-containing bone outside of the normal skeleton. Acquired HO following traumatic events is a common and costly clinical complication. In contrast, hereditary HO is rarer, progressive, and life-threatening. Substantial effort has been directed towards understanding the mechanisms underlying HO and finding efficient treatments. However, one crucial limiting factor has been the lack of relevant animal models. This article reviews the major ...

  20. Large animal models for stem cell therapy

    OpenAIRE

    Harding, John; Roberts, R. Michael; Mirochnitchenko, Oleg

    2013-01-01

    The field of regenerative medicine is approaching translation to clinical practice, and significant safety concerns and knowledge gaps have become clear as clinical practitioners are considering the potential risks and benefits of cell-based therapy. It is necessary to understand the full spectrum of stem cell actions and preclinical evidence for safety and therapeutic efficacy. The role of animal models for gaining this information has increased substantially. There is an urgent need for nov...

  1. Diabetic Retinopathy: Animal Models, Therapies, and Perspectives

    OpenAIRE

    Xue Cai; McGinnis, James F.

    2016-01-01

    Diabetic retinopathy (DR) is one of the major complications of diabetes. Although great efforts have been made to uncover the mechanisms underlying the pathology of DR, the exact causes of DR remain largely unknown. Because of multifactor involvement in DR etiology, currently no effective therapeutic treatments for DR are available. In this paper, we review the pathology of DR, commonly used animal models, and novel therapeutic approaches. Perspectives and future directions for DR treatment a...

  2. Animal models of enterovirus 71 infection: applications and limitations.

    Science.gov (United States)

    Wang, Ya-Fang; Yu, Chun-Keung

    2014-01-01

    Human enterovirus 71 (EV71) has emerged as a neuroinvasive virus that is responsible for several outbreaks in the Asia-Pacific region over the past 15 years. Appropriate animal models are needed to understand EV71 neuropathogenesis better and to facilitate the development of effective vaccines and drugs. Non-human primate models have been used to characterize and evaluate the neurovirulence of EV71 after the early outbreaks in late 1990s. However, these models were not suitable for assessing the neurovirulence level of the virus and were associated with ethical and economic difficulties in terms of broad application. Several strategies have been applied to develop mouse models of EV71 infection, including strategies that employ virus adaption and immunodeficient hosts. Although these mouse models do not closely mimic human disease, they have been applied to determine the pathogenesis of and treatment and prevention of the disease. EV71 receptor-transgenic mouse models have recently been developed and have significantly advanced our understanding of the biological features of the virus and the host-parasite interactions. Overall, each of these models has advantages and disadvantages, and these models are differentially suited for studies of EV71 pathogenesis and/or the pre-clinical testing of antiviral drugs and vaccines. In this paper, we review the characteristics, applications and limitation of these EV71 animal models, including non-human primate and mouse models. PMID:24742252

  3. Animal Models of Varicella Zoster Virus Infection

    Directory of Open Access Journals (Sweden)

    Ilhem Messaoudi

    2013-05-01

    Full Text Available Primary infection with varicella zoster virus (VZV results in varicella (chickenpox followed by the establishment of latency in sensory ganglia. Declining T cell immunity due to aging or immune suppressive treatments can lead to VZV reactivation and the development of herpes zoster (HZ, shingles. HZ is often associated with significant morbidity and occasionally mortality in elderly and immune compromised patients. There are currently two FDA-approved vaccines for the prevention of VZV: Varivax® (for varicella and Zostavax® (for HZ. Both vaccines contain the live-attenuated Oka strain of VZV. Although highly immunogenic, a two-dose regimen is required to achieve a 99% seroconversion rate. Zostavax vaccination reduces the incidence of HZ by 51% within a 3-year period, but a significant reduction in vaccine-induced immunity is observed within the first year after vaccination. Developing more efficacious vaccines and therapeutics requires a better understanding of the host response to VZV. These studies have been hampered by the scarcity of animal models that recapitulate all aspects of VZV infections in humans. In this review, we describe different animal models of VZV infection as well as an alternative animal model that leverages the infection of Old World macaques with the highly related simian varicella virus (SVV and discuss their contributions to our understanding of pathogenesis and immunity during VZV infection.

  4. Neuroteratology and Animal Modeling of Brain Disorders.

    Science.gov (United States)

    Archer, Trevor; Kostrzewa, Richard M

    2016-01-01

    Over the past 60 years, a large number of selective neurotoxins were discovered and developed, making it possible to animal-model a broad range of human neuropsychiatric and neurodevelopmental disorders. In this paper, we highlight those neurotoxins that are most commonly used as neuroteratologic agents, to either produce lifelong destruction of neurons of a particular phenotype, or a group of neurons linked by a specific class of transporter proteins (i.e., dopamine transporter) or body of receptors for a specific neurotransmitter (i.e., NMDA class of glutamate receptors). Actions of a range of neurotoxins are described: 6-hydroxydopamine (6-OHDA), 6-hydroxydopa, DSP-4, MPTP, methamphetamine, IgG-saporin, domoate, NMDA receptor antagonists, and valproate. Their neuroteratologic features are outlined, as well as those of nerve growth factor, epidermal growth factor, and that of stress. The value of each of these neurotoxins in animal modeling of human neurologic, neurodegenerative, and neuropsychiatric disorders is discussed in terms of the respective value as well as limitations of the derived animal model. Neuroteratologic agents have proven to be of immense importance for understanding how associated neural systems in human neural disorders may be better targeted by new therapeutic agents. PMID:26857462

  5. Animal Models of Compulsive Eating Behavior

    Directory of Open Access Journals (Sweden)

    Matteo Di Segni

    2014-10-01

    Full Text Available Eating disorders are multifactorial conditions that can involve a combination of genetic, metabolic, environmental, and behavioral factors. Studies in humans and laboratory animals show that eating can also be regulated by factors unrelated to metabolic control. Several studies suggest a link between stress, access to highly palatable food, and eating disorders. Eating “comfort foods” in response to a negative emotional state, for example, suggests that some individuals overeat to self-medicate. Clinical data suggest that some individuals may develop addiction-like behaviors from consuming palatable foods. Based on this observation, “food addiction” has emerged as an area of intense scientific research. A growing body of evidence suggests that some aspects of food addiction, such as compulsive eating behavior, can be modeled in animals. Moreover, several areas of the brain, including various neurotransmitter systems, are involved in the reinforcement effects of both food and drugs, suggesting that natural and pharmacological stimuli activate similar neural systems. In addition, several recent studies have identified a putative connection between neural circuits activated in the seeking and intake of both palatable food and drugs. The development of well-characterized animal models will increase our understanding of the etiological factors of food addiction and will help identify the neural substrates involved in eating disorders such as compulsive overeating. Such models will facilitate the development and validation of targeted pharmacological therapies.

  6. Animal models of compulsive eating behavior.

    Science.gov (United States)

    Di Segni, Matteo; Patrono, Enrico; Patella, Loris; Puglisi-Allegra, Stefano; Ventura, Rossella

    2014-10-01

    Eating disorders are multifactorial conditions that can involve a combination of genetic, metabolic, environmental, and behavioral factors. Studies in humans and laboratory animals show that eating can also be regulated by factors unrelated to metabolic control. Several studies suggest a link between stress, access to highly palatable food, and eating disorders. Eating "comfort foods" in response to a negative emotional state, for example, suggests that some individuals overeat to self-medicate. Clinical data suggest that some individuals may develop addiction-like behaviors from consuming palatable foods. Based on this observation, "food addiction" has emerged as an area of intense scientific research. A growing body of evidence suggests that some aspects of food addiction, such as compulsive eating behavior, can be modeled in animals. Moreover, several areas of the brain, including various neurotransmitter systems, are involved in the reinforcement effects of both food and drugs, suggesting that natural and pharmacological stimuli activate similar neural systems. In addition, several recent studies have identified a putative connection between neural circuits activated in the seeking and intake of both palatable food and drugs. The development of well-characterized animal models will increase our understanding of the etiological factors of food addiction and will help identify the neural substrates involved in eating disorders such as compulsive overeating. Such models will facilitate the development and validation of targeted pharmacological therapies. PMID:25340369

  7. Establishing of the Transplanted Animal Models for Human Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Xingli Zhang; Jinchang Wu

    2009-01-01

    Lung cancer is the leading cause of cancer mortality worldwide.Even with the applications of excision,radiotherapy,chemotherapy,and gene therapy,the 5 year survival rate is only 15% in the USA.Clinically relevant laboratory animal models of the disease could greatly facilitate understanding of the pathogenesis of lung cancer,its progression,invasion and metastasis.Transplanted lung cancer models are of special interest and are widely used today.Such models are essential tools in accelerating development of new therapies for lung cancer.In this communication we will present a brief overview of the hosts,sites and pathways used to establish transplanted animal lung tumor models.

  8. REVIEW ON IMPORTANT HELMINTHIC DISEASES IN ANIMAL IN INDONESIA

    Directory of Open Access Journals (Sweden)

    I.G. P. Suweta

    2012-09-01

    Full Text Available Helminthic diseases are widely spread throughout the world. In Indonesia, the cases in animals are primarily associated with the condition of the field, although the intensity of the infestations are also affected by various factors inside the body of the host. In general, the tropical and humid conditions in Indonesia, optimally support the development and spreading of the parasites, so that the prevalence of the infestations are usually high except in the very dry areas. In Indonesia, important helminthic diseases found in livestock are mostly caused by nematodes and trematodes, and there is a lack of information regarding cestode infestations, except infestation by immature stages of the worm such as cysticercosis in ruminants and swine. On the other hand, dogs and cats are usually infested by cestodes and nematodes. Here, the negative influence of helminthic infestation on live stock is mostiy shown by failure of growth, decrease of body weight and body resistance, damage of organs infested by the parasites, but it is not rare that the disease cause death of the infested animals such as haemonchiasis in sheep, ascariasis in young swine and calves, etc. The integrated system of farming combined with periodic anthelminthic treatments were favourable in the effort of controlling the disease.

  9. Animal models of alcohol and drug dependence

    OpenAIRE

    Planeta, Cleopatra S.

    2013-01-01

    Drug addiction has serious health and social consequences. In the last 50 years, a wide range of techniques have been developed to model specific aspects of drug-taking behaviors and have greatly contributed to the understanding of the neurobiological basis of drug abuse and addiction. In the last two decades, new models have been proposed in an attempt to capture the more genuine aspects of addiction-like behaviors in laboratory animals. The goal of the present review is to provide an overvi...

  10. Physically based modeling and animation of tornado

    Institute of Scientific and Technical Information of China (English)

    LIU Shi-guang; WANG Zhang-ye; GONG Zheng; CHEN Fei-fei; PENG Qun-sheng

    2006-01-01

    Realistic modeling and rendering of dynamic tornado scene is recognized as a challenging task for researchers of computer graphics. In this paper a new physically based method for simulating and animating tornado scene is presented. We first propose a Two-Fluid model based on the physical theory of tornado, then we simulate the flow of tornado and its interaction with surrounding objects such as debris, etc. Taking the scattering and absorption of light by the participating media into account, the illumination effects of the tornado scene can be generated realistically. With the support of graphics hardware, various kinds of dynamic tornado scenes can be rendered at interactive rates.

  11. Making animals alcoholic: shifting laboratory models of addiction.

    Science.gov (United States)

    Ramsden, Edmund

    2015-01-01

    The use of animals as experimental organisms has been critical to the development of addiction research from the nineteenth century. They have been used as a means of generating reliable data regarding the processes of addiction that was not available from the study of human subjects. Their use, however, has been far from straightforward. Through focusing on the study of alcoholism, where the nonhuman animal proved a most reluctant collaborator, this paper will analyze the ways in which scientists attempted to deal with its determined sobriety and account for their consistent failure to replicate the volitional consumption of ethanol to the point of physical dependency. In doing so, we will see how the animal model not only served as a means of interrogating a complex pathology, but also came to embody competing definitions of alcoholism as a disease process, and alternative visions for the very structure and purpose of a research field. PMID:25740698

  12. Animal models of depression: are there any?

    Science.gov (United States)

    O'Neil, Michael F; Moore, Nicholas A

    2003-06-01

    Simple tests for antidepressant-like activity, such as 5-HTP-induced syndrome or reserpine-induced hypomotility, are often mechanism-based tests, pharmacologically specific for certain known classes of therapeutically successful antidepressant agents. Many of these behavioural assays have been superseded by neurochemical techniques such as in vivo microdialysis. In contrast to these mechanistic-based models, investigators have also endeavoured to reproduce in the laboratory, factors that are believed to precipitate depression in people. It is a strong assumption in this approach that depression is a response to stress. This strategy profiles the consequences of chronic stress particularly psychosocial stress or early life events, in order to reproduce in animals the behavioural signs and pathologies associated with depression. The advances in the social psychological, clinical pathological and new areas such as neuroimaging research offer the possibility of establishing more sophisticated models for depression in animals with a broader range of biomarkers from the immunological and endocrinological to neurochemical and behavioural. Combining these novel insights with more traditional tests of depression may not only increase our understanding of the neurobiology of depression but also afford more precise and predictive preclinical models of depression. The responsiveness of different strains or genetically modified animals to stress is likely to be a key area of study. Furthermore we must look to individual differences in subjects, even within the same strain, to more fully understand why some individuals show pathological responses to stress whereas others appear unaffected. Conversely in validating our models using currently available treatments we must include the concept of non-responders so as not to disregard models that may extend therapeutic possibilities in these patients. PMID:12766928

  13. 慢性缺氧模型与病证相关性的研究进展%Advances on Correlation between Chronic Hypoxic Animal Models and Diseases and Syndromes

    Institute of Scientific and Technical Information of China (English)

    张洁琼; 柴程芝; 寇俊萍; 余伯阳

    2012-01-01

    Prolonged or repeated hypoxia can affect the normal oxygen supply for tissues and organs and normal physiological function of the cardiovascular, respiratory and nervous systems. Multi-system injuries bring serious harm to human health. Along with the modern life style and dietary structure change, deficiency of aerobic exercise and the worsening earth pollution and destruction make human in a chronic hypoxic environment imperceptibly. Therefore, it is of importance to pay more attention to the harm of chronic hypoxia and take corresponding prevention measures. Scholars at home and abroad largely explored constructing animal models to simulate different diseases and syndromes through observing macro and micro indications, including performance and physiological or biochemical indexes. And different oxygen cycles and different hypoxia intensities were used. Various animal models of chronic hypoxia have been commonly used to investigate the various physiological or pathological processes of hypoxia-related diseases including obstructive sleep apnea syndrome, pulmonary artery hypertension, cardiovascular diseases, neurodegenerative disease and Deficiency of both Qi and Yin syndrome, Stagnation of Qi and blood stasis. In this paper, the recent studies on relationship of chronic hypoxia model and the related diseases and syndromes were reviewed. It is inclined to provide some clues not only for selecting reasonable animal models simulating the clinical features of diseases and syndrome but also for evaluating the characters of drug action reasonably.%长期或反复处于缺氧状态,可以影响机体组织器官的正常供氧,使心血管、呼吸和神经等系统功能紊乱,从而诱导机体多系统损伤,严重危害人体健康.随着现代人生活方式以及饮食结构的改变,生活中有氧运动不足再加上地球污染与破坏逐年加剧,人类不知不觉地处在一个慢性缺氧的环境中.因此,了解并重视慢性缺氧对生理功能的

  14. Eight challenges in modelling infectious livestock diseases

    Directory of Open Access Journals (Sweden)

    E. Brooks-Pollock

    2015-03-01

    Full Text Available The transmission of infectious diseases of livestock does not differ in principle from disease transmission in any other animals, apart from that the aim of control is ultimately economic, with the influence of social, political and welfare constraints often poorly defined. Modelling of livestock diseases suffers simultaneously from a wealth and a lack of data. On the one hand, the ability to conduct transmission experiments, detailed within-host studies and track individual animals between geocoded locations make livestock diseases a particularly rich potential source of realistic data for illuminating biological mechanisms of transmission and conducting explicit analyses of contact networks. On the other hand, scarcity of funding, as compared to human diseases, often results in incomplete and partial data for many livestock diseases and regions of the world. In this overview of challenges in livestock disease modelling, we highlight eight areas unique to livestock that, if addressed, would mark major progress in the area.

  15. Large Animal Models for Foamy Virus Vector Gene Therapy

    Directory of Open Access Journals (Sweden)

    Peter A. Horn

    2012-12-01

    Full Text Available Foamy virus (FV vectors have shown great promise for hematopoietic stem cell (HSC gene therapy. Their ability to efficiently deliver transgenes to multi-lineage long-term repopulating cells in large animal models suggests they will be effective for several human hematopoietic diseases. Here, we review FV vector studies in large animal models, including the use of FV vectors with the mutant O6-methylguanine-DNA methyltransferase, MGMTP140K to increase the number of genetically modified cells after transplantation. In these studies, FV vectors have mediated efficient gene transfer to polyclonal repopulating cells using short ex vivo transduction protocols designed to minimize the negative effects of ex vivo culture on stem cell engraftment. In this regard, FV vectors appear superior to gammaretroviral vectors, which require longer ex vivo culture to effect efficient transduction. FV vectors have also compared favorably with lentiviral vectors when directly compared in the dog model. FV vectors have corrected leukocyte adhesion deficiency and pyruvate kinase deficiency in the dog large animal model. FV vectors also appear safer than gammaretroviral vectors based on a reduced frequency of integrants near promoters and also near proto-oncogenes in canine repopulating cells. Together, these studies suggest that FV vectors should be highly effective for several human hematopoietic diseases, including those that will require relatively high percentages of gene-modified cells to achieve clinical benefit.

  16. Eight challenges in modelling infectious livestock diseases

    NARCIS (Netherlands)

    Brooks-Pollock, E; de Jong, M C M; Keeling, M J; Klinkenberg, D; Wood, J L N

    2015-01-01

    The transmission of infectious diseases of livestock does not differ in principle from disease transmission in any other animals, apart from that the aim of control is ultimately economic, with the influence of social, political and welfare constraints often poorly defined. Modelling of livestock di

  17. Impulsive prion disease model

    Directory of Open Access Journals (Sweden)

    Lakmeche Abdelkader

    2015-01-01

    Full Text Available A model of prion diseases with impulse effects is studied in this work. First we transform the model to a system of three differential equations with impulse effects in order to study the stability of periodic solution. After that we study the general model by the mean of evolution semi group in order to find conditions of existence of mild solution.

  18. Animal models of craving for ethanol.

    Science.gov (United States)

    Koob, G F

    2000-08-01

    Craving has various meanings but can be defined generally in terms of a desire for the previously experienced effects of ethanol. Animal models provide a means by which to study the underlying mechanisms associated with craving and are most useful when they fulfill the requirements for predictive validity and reliability. Craving is a key part of the process of addiction that can lead to relapse and is conceptualized as having at least three components: preoccupation/anticipation, binge/intoxication and withdrawal/negative affect. Animal models of craving are hypothesized at this time to involve three domains of motivation to take drugs: excessive drinking, negative affective states and conditioned reinforcement. Excessive drinking includes the alcohol deprivation effect, drinking during withdrawal and drinking after a history of dependence. Models of the negative affective state include increases in brain reward thresholds, and conditioned reinforcement models include cue-induced resistance to extinction or cue-induced reinstatement. Experimental psychology is a rich resource of sensitive behavioral techniques by which to measure hypothetical constructs associated with the motivation to drink ethanol. Rigorous tests of predictive validity and reliability will be necessary to make them useful for understanding the neurobiology of craving and for the development of new medications for treating craving. PMID:11002904

  19. Animal models of anxiety: an ethological perspective

    Directory of Open Access Journals (Sweden)

    R.J. Rodgers

    1997-03-01

    Full Text Available 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, it is suggested that other models of anxiety may well benefit from greater attention to behavioural detail

  20. Bifunctional RNAs Targeting the Intronic Splicing Silencer N1 Increase SMN Levels and Reduce Disease Severity in an Animal Model of Spinal Muscular Atrophy

    OpenAIRE

    Osman, Erkan Y; Yen, Pei-Fen; Lorson, Christian L.

    2011-01-01

    Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by loss of survival motor neuron-1 (SMN1). A nearly identical copy gene, SMN2, is present in all SMA patients. Although the SMN2 coding sequence has the potential to produce full-length SMN, nearly 90% of SMN2-derived transcripts are alternatively spliced and encode a truncated protein. SMN2, however, is an excellent therapeutic target. Previously, we developed antisense-based oligonucleotides (bifunctional RNAs) that specifi...

  1. The Effect of HIV Protease Inhibitors on Amyloid-β Peptide Degradation and Synthesis in Human Cells and Alzheimer’s Disease Animal Model

    OpenAIRE

    Lan, Xiqian; Kiyota, Tomomi; Hanamsagar, Richa; Huang, Yunlong; Andrews, Scott; Peng, Hui; Zheng, Jialin C.; Swindells, Susan; Carlson, George A.; Ikezu, Tsuneya

    2011-01-01

    Combined antiretroviral therapy (ART) tremendously improved the lifespan and symptoms associated with AIDS-defining illness in affected individuals. However, chronic ART-treated patients frequently develop age-dependent complications, including dementia, diabetes, and hyperlipidemia: all risk factors of Alzheimer’s disease. Importantly, the effect of ART compounds on amyloid generation and clearance has never been systematically examined. Nine prescribed HIV protease inhibitors were tested fo...

  2. Regulation of the NMDA Receptor-mediated Synaptic Response by Acetylcholinesterase Inhibitors and its Impairment in an Animal Model of Alzheimer’s Disease

    OpenAIRE

    Chen, Guojun; Chen, Paul; Tan, Huibing; Ma, Da; Dou, Fei; FENG, JIAN; Yan, Zhen

    2007-01-01

    The cholinergic system is crucial for cognitive processes and the deficient acetylcholine (ACh) function has been implicated in Alzheimer’s disease (AD). Inhibitors of acetylcholinesterase (AChE), which act to enhance cholinergic function by prolonging the action of endogenously released ACh, have been used as the major therapy of AD. To understand the functional roles of cholinergic enhancement in prefrontal cortex (PFC), a key brain region for cognition, we examined the impact of AChE inhib...

  3. Animal models of neurological deficits: how relevant is the rat?

    Science.gov (United States)

    Cenci, M Angela; Whishaw, Ian Q; Schallert, Timothy

    2002-07-01

    Animal models of neurological deficits are essential for the assessment of new therapeutic options. It has been suggested that rats are not as appropriate as primates for the symptomatic modelling of disease, but a large body of data argues against this view. Comparative analyses of movements in rats and primates show homology of many motor patterns across species. Advances have been made in identifying rat equivalents of akinesia, tremor, postural deficits and dyskinesia, which are relevant to Parkinson's disease. Rat models of hemiplegia, neglect and tactile extinction are useful in assessing the outcome of ischaemic or traumatic brain injury, and in monitoring the effects of therapeutic interventions. Studies in rodents that emphasize careful behavioural analysis should continue to be developed as effective and inexpensive models that complement studies in primates. PMID:12094213

  4. Animal models of henipavirus infection: a review.

    Science.gov (United States)

    Weingartl, Hana M; Berhane, Yohannes; Czub, Markus

    2009-09-01

    Hendra virus (HeV) and Nipah virus (NiV) form a separate genus Henipavirus within the family Paramyxoviridae, and are classified as biosafety level four pathogens due to their high case fatality rate following human infection and because of the lack of effective vaccines or therapy. Both viruses emerged from their natural reservoir during the last decade of the 20th century, causing severe disease in humans, horses and swine, and infecting a number of other mammalian species. The current review summarises current published data relating to experimental infection of small and large animals, including the natural reservoir species, the Pteropus bat, with HeV or NiV. Susceptibility to infection and virus distribution in the individual species is discussed, along with the pathogenesis, pathological changes, and potential routes of transmission. PMID:19084436

  5. Management of Ocular Diseases Using Lutein and Zeaxanthin: What Have We Learned from Experimental Animal Studies?

    Directory of Open Access Journals (Sweden)

    Chunyan Xue

    2015-01-01

    Full Text Available Zeaxanthin and lutein are two carotenoid pigments that concentrated in the retina, especially in the macula. The effects of lutein and zeaxanthin on the prevention and treatment of various eye diseases, including age-related macular degeneration, diabetic retinopathy and cataract, ischemic/hypoxia induced retinopathy, light damage of the retina, retinitis pigmentosa, retinal detachment, and uveitis, have been studied in different experimental animal models. In these animal models, lutein and zeaxanthin have been reported to have beneficial effects in protecting ocular tissues and cells (especially the retinal neurons against damage caused by different etiological factors. The mechanisms responsible for these effects of lutein and zeaxanthin include prevention of phototoxic damage by absorption of blue light, reduction of oxidative stress through antioxidant activity and free radical scavenging, and their anti-inflammatory and antiangiogenic properties. The results of these experimental animal studies may provide new preventive and therapeutic procedures for clinical management of various vision-threatening diseases.

  6. Development of a Large Animal Model of Osteochondritis Dissecans of the Knee

    OpenAIRE

    Pfeifer, Christian G.; Kinsella, Stuart D.; Milby, Andrew H.; Fisher, Matthew B.; Belkin, Nicole S.; Mauck, Robert L.; Carey, James L.

    2015-01-01

    Background: Treatment of osteochondritis dissecans (OCD) of the knee is challenging, and evidence for stage-dependent treatment options is lacking. Basic science approaches utilizing animal models have provided insight into the etiology of OCD but have yet to produce a reliable and reproducible large animal model of the disease on which to test new surgical strategies. Purpose/Hypotheses: The purpose of this study was to develop an animal model featuring an OCD-like lesion in terms of size, l...

  7. Animal genomics and infectious disease resistance in poultry.

    Science.gov (United States)

    Smith, J; Gheyas, A; Burt, D W

    2016-04-01

    Avian pathogens are responsible for major costs to society, both in terms of huge economic losses to the poultry industry and their implications for human health. The health and welfare of millions of birds is under continued threat from many infectious diseases, some of which are increasing in virulence and thus becoming harder to control, such as Marek's disease virus and avian influenza viruses. The current era in animal genomics has seen huge developments in both technologies and resources, which means that researchers have never been in a better position to investigate the genetics of disease resistance and determine the underlying genes/mutations which make birds susceptible or resistant to infection. Avian genomics has reached a point where the biological mechanisms of infectious diseases can be investigated and understood in poultry and other avian species. Knowledge of genes conferring disease resistance can be used in selective breeding programmes or to develop vaccines which help to control the effects of these pathogens, which have such a major impact on birds and humans alike. PMID:27217172

  8. Ideal Experimental Rat Models for Liver Diseases.

    Science.gov (United States)

    Lee, Sang Woo; Kim, Sung Hoon; Min, Seon Ok; Kim, Kyung Sik

    2011-05-01

    There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and diverse clinical symptoms, adverse reactions, and complications due to the pathological physiology. Also, it is not easy to reproduce identically various clinical situations in animal models. Recently, the Guide for the Care and Use of Laboratory Animals has tightened up the regulations, and therefore it is advisable to select the appropriate animals and decide upon the appropriate quantities through scientific and systemic considerations before conducting animal testing. Therefore, in this review article the authors examined various white rat animal testing models and determined the appropriate usable rat model, and the pros and cons of its application in liver disease research. The authors believe that this review will be beneficial in selecting proper laboratory animals for research purposes. PMID:26421020

  9. Pulmonary abnormalities in animal models due to Niemann-Pick type C1 (NPC1 or C2 (NPC2 disease.

    Directory of Open Access Journals (Sweden)

    Blair R Roszell

    Full Text Available Niemann-Pick C (NPC disease is due to loss of NPC1 or NPC2 protein function that is required for unesterified cholesterol transport from the endosomal/lysosomal compartment. Though lung involvement is a recognized characteristic of Niemann-Pick type C disease, the pathological features are not well understood. We investigated components of the surfactant system in both NPC1 mutant mice and felines and in NPC2 mutant mice near the end of their expected life span. Histological analysis of the NPC mutant mice demonstrated thickened septae and foamy macrophages/leukocytes. At the level of electron microscopy, NPC1-mutant type II cells had uncharacteristically larger lamellar bodies (LB, mean area 2-fold larger, while NPC2-mutant cells had predominantly smaller lamellar bodies (mean area 50% of normal than wild type. Bronchoalveolar lavage from NPC1 and NPC2 mutant mice had an approx. 4-fold and 2.5-fold enrichment in phospholipid, respectively, and an approx. 9-fold and 35-fold enrichment in cholesterol, consistent with alveolar lipidosis. Phospholipid and cholesterol also were elevated in type II cell LBs and lung tissue while phospholipid degradation was reduced. Enrichment of surfactant protein-A in the lung and surfactant of the mutant mice was found. Immunocytochemical results showed that cholesterol accumulated in the LBs of the type II cells isolated from the affected mice. Alveolar macrophages from the NPC1 and NPC2 mutant mice were enlarged compared to those from wild type mice and were enriched in phospholipid and cholesterol. Pulmonary features of NPC1 mutant felines reflected the disease described in NPC1 mutant mice. Thus, with the exception of lamellar body size, the lung phenotype seen in the NPC1 and NPC2 mutant mice were similar. The lack of NPC1 and NPC2 proteins resulted in a disruption of the type II cell surfactant system contributing to pulmonary abnormalities.

  10. Animal Models of Human Placentation - A Review

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2007-01-01

    This review examines the strengths and weaknesses of animal models of human placentation and pays particular attention to the mouse and non-human primates. Analogies can be drawn between mouse and human in placental cell types and genes controlling placental development. There are, however...... is no trophoblast invasion of uterine vessels, and the immunology of pregnancy may be quite different. We conclude that continued research on non-human primates is needed to clarify embryonic-endometrial interactions. The interstitial implantation of human is unusual, but the initial interaction...... and delivers poorly developed young. Guinea pig is a good alternative rodent model and among the few species known to develop pregnancy toxaemia. The sheep is well established as a model in fetal physiology but is of limited value for placental research. The ovine placenta is epitheliochorial, there...

  11. Lattice animal model of chromosome organization

    Science.gov (United States)

    Iyer, Balaji V. S.; Arya, Gaurav

    2012-07-01

    Polymer models tied together by constraints of looping and confinement have been used to explain many of the observed organizational characteristics of interphase chromosomes. Here we introduce a simple lattice animal representation of interphase chromosomes that combines the features of looping and confinement constraints into a single framework. We show through Monte Carlo simulations that this model qualitatively captures both the leveling off in the spatial distance between genomic markers observed in fluorescent in situ hybridization experiments and the inverse decay in the looping probability as a function of genomic separation observed in chromosome conformation capture experiments. The model also suggests that the collapsed state of chromosomes and their segregation into territories with distinct looping activities might be a natural consequence of confinement.

  12. Transient neuromotor phenotype in transgenic spastic mice expressing low levels of glycine receptor β-subunit: an animal model of startle disease

    OpenAIRE

    Becker, Lore; Hartenstein, Bettina; Schenkel, Johannes; Kuhse, Jochen; Betz, Heinrich; Weiher, Hans

    2000-01-01

    Startle disease or hereditary hyperekplexia has been shown to result from mutations in the α1-subunit gene of the inhibitory glycine receptor (GlyR). In hyperekplexia patients, neuromotor symptoms generally become apparent at birth, improve with age, and often disappear in adulthood. Loss-of-function mutations of GlyR α or β-subunits in mice show rather severe neuromotor phenotypes. Here, we generated mutant mice with a transient neuromotor deficiency by introducing a GlyR β transgene into th...

  13. Detrended Fluctuation Analysis on Cardiac Pulses in Both, Animal Models and Humans: A Computation for an Early Prognosis of Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Toru Yazawa

    2008-04-01

    Full Text Available We analyzed the heartbeat interval by the detrended fluctuation analysis (DFA in models and humans. In models, the myocardium of the healthy heart contracted regularly. The deteriorated heart model, however, showed alternating beats so-called "alternans." The DFA revealed that if the heart is having "alternans" exhibited there is a declined scaling exponent (~0.5. In humans, the heart that had "alternans" also showed a low scaling exponent (~0.6. We consider that the coexistence of "alternans" and a low scaling exponent can be a risk marker in predictive and preventative diagnosis, supporting the idea that "alternans" can be a harbinger of sudden death.

  14. Ideal Experimental Rat Models for Liver Diseases

    OpenAIRE

    Lee, Sang Woo; Kim, Sung Hoon; Min, Seon Ok; Kim, Kyung Sik

    2011-01-01

    There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and dive...

  15. Turbulent dispersivity under conditions relevant to airborne disease transmission between laboratory animals

    Science.gov (United States)

    Halloran, Siobhan; Wexler, Anthony; Ristenpart, William

    2014-11-01

    Virologists and other researchers who test pathogens for airborne disease transmissibility often place a test animal downstream from an inoculated animal and later determine whether the test animal became infected. Despite the crucial role of the airflow in modulating the pathogen transmission, to date the infectious disease community has paid little attention to the effect of airspeed or turbulence intensity on the probability of transmission. Here we present measurements of the turbulent dispersivity under conditions relevant to experimental tests of airborne disease transmissibility between laboratory animals. We used time lapse photography to visualize the downstream transport and turbulent dispersion of smoke particulates released from a point source downstream of a standard axial fan, thus mimicking the release and transport of expiratory aerosols exhaled by an inoculated animal. We demonstrate that the fan speed counterintuitively has no effect on the downstream plume width, a result replicated with a variety of different fan types and configurations. The results point toward a useful simplification in modeling of airborne disease transmission via fan-generated flows.

  16. To Your Health: NLM update transcript - Preventing disease spillover from animals to humans

    Science.gov (United States)

    ... Health: NLM update Transcript Preventing disease spillover from animals to humans : 07/11/2016 To use the ... weekly topics. The prevention of disease transmission from animals to humans begins by careful surveillance of the ...

  17. A systematic review of animal models for experimental neuroma.

    Science.gov (United States)

    Toia, Francesca; Giesen, Thomas; Giovanoli, Pietro; Calcagni, Maurizio

    2015-10-01

    Peripheral neuromas can result in an unbearable neuropathic pain and functional impairment. Their treatment is still challenging, and their optimal management is to be defined. Experimental research still plays a major role, but - although numerous neuroma models have been proposed on different animals - there is still no single model recognised as being the reference. Several models show advantages over the others in specific aspects of neuroma physiopathology, prevention or treatment, making it unlikely that a single model could be of reference. A reproducible and standardised model of peripheral neuroma would allow better comparison of results from different studies. We present a systematic review of the literature on experimental in vivo models, analysing advantages and disadvantages, specific features and indications, with the goal of providing suggestions to help their standardisation. Published models greatly differ in the animal and the nerve employed, the mechanisms of nerve injury and the evaluation methods. Specific experimental models exist for terminal neuromas and neuromas in continuity (NIC). The rat is the most widely employed animal, the rabbit being the second most popular model. NIC models are more actively researched, but it is more difficult to generate such studies in a reproducible manner. Nerve transection is considered the best method to cause terminal neuromas, whereas partial transection is the best method to cause NIC. Traditional histomorphology is the historical gold-standard evaluation method, but immunolabelling, reverse transcriptase-polymerase chain reaction (RT-PCR) and proteomics are gaining increasing popularity. Computerised gait analysis is the gold standard for motor-recovery evaluation, whereas mechanical testing of allodynia and hyperalgesia reproducibly assesses sensory recovery. This review summarises current knowledge on experimental neuroma models, and it provides a useful tool for defining experimental protocols

  18. Diagnosis and epidemiology of animal diseases in Latin America

    International Nuclear Information System (INIS)

    Support for scientists and their endeavours in developing countries by the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture is provided through FAO/IAEA Co-ordinated Research Projects (CRP) and IAEA Technical Co-operation Projects (TCPs). Using these mechanisms the Animal Production and Health Section of the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agricultural aims to encourage and improve the capacity of national institutions in developing countries to identify and resolve problems connected with improving livestock productivity and health. In 1986, the Section introduced and animal health component into its Project. The initial support was for five years but in 1991 this was extended for a further three years and linked with the support available from the IAEA's Technical Co-operation Project through national and regional TCPs and ARCAL activities in Latin America dealing with diagnosis of animal diseases. Central to this overall project ws the use of ELISA for the diagnosis and control of livestock diseases. FAO/IAEA CRPs are developed around a well defined research topic on which between 15 and 20 national institutes collaborate - the topic itself being defined through consultation with national authorities in developing and developed countries and international agricultural research centers and organizations. The primary role of the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture in such programmes is to ensure that the inputs and efforts under these programmes are co-ordinated and that the results are published. The studies being reported in this IAEA TECDOC were initiated in 1991 and whilst the focus was on three major disease affecting livestock in the region (foot-and-mouth disease (FMD), brucellosis and babesiosis) the approach taken by individual Research Control holders was different and thus in some cases research concentrated on assay validation whilst in other cases the focus was on the

  19. ANIMAL MODELS TO EVALUATE THE CAUSE BEHIND GASTRIC ULCERS

    Directory of Open Access Journals (Sweden)

    Saini Amita

    2012-08-01

    Full Text Available Peptic ulcer is the major cause of mortality and morbidity in developing countries, characterised by imbalance between aggressive gastric luminal factor and defensive mucosal barrier. This disease is mainly associated with increase in gastric acid secretion. Numerous factors like diet, smoking, drugs like aspirin and infection are responsible for augmentation of ulcers. Still, no therapeutic intervention has been found successful. So, this review has been designed to explore various animal models to find out a suitable medication. Various synthetic Omeprazole, cemitidine and herbal drugs like tulsi, Areca catechu are employed in the management of the ulcers but still no curative treatment is available due to unknown mechanism behind ulceration. So this review has been designed to explore various animal models that depict the signalling pathway involved in ulcers and have open vista for the development of the new drugs.

  20. The search for animal models for Lassa fever vaccine development.

    Science.gov (United States)

    Lukashevich, Igor S

    2013-01-01

    Lassa virus (LASV) is the most prevalent arenavirus in West Africa and is responsible for several hundred thousand infections and thousands of deaths annually. The sizeable disease burden, numerous imported cases of Lassa fever (LF) and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Currently there is no licensed LF vaccine and research and devlopment is hampered by the high cost of nonhuman primate animal models and by biocontainment requirements (BSL-4). In addition, a successful LF vaccine has to induce a strong cell-mediated cross-protective immunity against different LASV lineages. All of these challenges will be addressed in this review in the context of available and novel animal models recently described for evaluation of LF vaccine candidates. PMID:23256740

  1. The search for animal models for Lassa fever vaccine development

    Science.gov (United States)

    Lukashevich, Igor S

    2013-01-01

    Lassa virus (LASV) is the most prevalent arenavirus in West Africa and is responsible for several hundred thousand infections and thousands of deaths annually. The sizeable disease burden, numerous imported cases of Lassa fever (LF) and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Currently there is no licensed LF vaccine and research and devlopment is hampered by the high cost of nonhuman primate animal models and by biocontainment requirements (BSL-4). In addition, a successful LF vaccine has to induce a strong cell-mediated cross-protective immunity against different LASV lineages. All of these challenges will be addressed in this review in the context of available and novel animal models recently described for evaluation of LF vaccine candidates. PMID:23256740

  2. Impaired auditory sensorimotor gating: An animal model of schizophrenia

    Institute of Scientific and Technical Information of China (English)

    LI Liang; SHAO Feng

    2003-01-01

    Establishment of animal models of schizophrenia is critical for both understanding the mechanisms underlying this severe mental disease and developing new antipsychotics. This paper starts from the theoretical root of sensory gating, the "protection-of-processing" theory, then thoroughly describes the representative studies over the past decade on the mechanism underlying prepulse inhibition and on those underlying modulation of prepulse inhibition, which is the normal startle suppression caused by the weak stimulus preceding the intense startling stimulus. The main methods for inducing prepulse inhibition deficits in experimental animals include: i ) modulations of neuro- transmission that are closely associated with schizophrenia; ii )focal lesions or pharmacological manipulations of brain structures in the cortico-striato-pallido-pontine circuit; and iii) maternal deprivation or social isolation. Six essential topics for studies in modeling schizophrenia are suggested at the last part of this review.

  3. Animal models of social anxiety disorder and their validity criteria.

    Science.gov (United States)

    Réus, Gislaine Z; Dos Santos, Maria Augusta B; Abelaira, Helena M; Quevedo, João

    2014-09-26

    Anxiety disorders pose one of the largest threats to global mental health, and they predominantly emerge early in life. Social anxiety disorder, also known as social phobia, is the most common of all anxiety disorders. Moreover, it has severe consequences and is a disabling disorder that can cause an individual to be unable to perform the tasks of daily life. Social anxiety disorder is associated with the subsequent development of major depression and other mental diseases, as well as increased substance abuse. Although some neurobiological alterations have been found to be associated with social anxiety disorder, little is known about this disorder. Animal models are useful tools for the investigation of this disorder, as well as for finding new pharmacological targets for treatment. Thus, this review will highlight the main animal models of anxiety associated with social phobia. PMID:25132362

  4. Cardiovascular Changes in Animal Models of Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Alexandre M. Lehnen

    2013-01-01

    Full Text Available Metabolic syndrome has been defined as a group of risk factors that directly contribute to the development of cardiovascular disease and/or type 2 diabetes. Insulin resistance seems to have a fundamental role in the genesis of this syndrome. Over the past years to the present day, basic and translational research has used small animal models to explore the pathophysiology of metabolic syndrome and to develop novel therapies that might slow the progression of this prevalent condition. In this paper we discuss the animal models used for the study of metabolic syndrome, with particular focus on cardiovascular changes, since they are the main cause of death associated with the condition in humans.

  5. 9 CFR 80.3 - Movement of domestic animals that are positive to an official Johne's disease test.

    Science.gov (United States)

    2010-01-01

    ... positive to an official Johne's disease test. 80.3 Section 80.3 Animals and Animal Products ANIMAL AND... (INCLUDING POULTRY) AND ANIMAL PRODUCTS JOHNE'S DISEASE IN DOMESTIC ANIMALS § 80.3 Movement of domestic animals that are positive to an official Johne's disease test. (a) Movement of domestic animals...

  6. Mefenamic Acid Induced Nephrotoxicity: An Animal Model

    Directory of Open Access Journals (Sweden)

    Muhammad Nazrul Somchit

    2014-12-01

    Full Text Available Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs are used for the treatment of many joint disorders, inflammation and to control pain. Numerous reports have indicated that NSAIDs are capable of producing nephrotoxicity in human. Therefore, the objective of this study was to evaluate mefenamic acid, a NSAID nephrotoxicity in an animal model. Methods: Mice were dosed intraperitoneally with mefenamic acid either as a single dose (100 or 200 mg/kg in 10% Dimethyl sulfoxide/Palm oil or as single daily doses for 14 days (50 or 100 mg/kg in 10% Dimethyl sulfoxide/Palm oil per day. Venous blood samples from mice during the dosing period were taken prior to and 14 days post-dosing from cardiac puncture into heparinized vials. Plasma blood urea nitrogen (BUN and creatinine activities were measured. Results: Single dose of mefenamic acid induced mild alteration of kidney histology mainly mild glomerular necrosis and tubular atrophy. Interestingly, chronic doses induced a dose dependent glomerular necrosis, massive degeneration, inflammation and tubular atrophy. Plasma blood urea nitrogen was statistically elevated in mice treated with mefenamic acid for 14 days similar to plasma creatinine. Conclusion: Results from this study suggest that mefenamic acid as with other NSAIDs capable of producing nephrotoxicity. Therefore, the study of the exact mechanism of mefenamic acid induced severe nephrotoxicity can be done in this animal model.

  7. Disease risk assessments involving companion animals: an overview for 15 selected pathogens taking a European perspective

    OpenAIRE

    Rijks, J. M.; Cito, F.; Cunningham, A. A.; Rantsios, A. T.; Givannini, A.

    2015-01-01

    Prioritization of companion animal transmissible diseases was performed by the Companion Animals multisectoriaL interprofessionaL Interdisciplinary Strategic Think tank On zoonoses (CALLISTO) project. The project considered diseases occurring in domesticated species commonly kept as pets, such as dogs and cats, but also included diseases occurring in captive wild animals and production animal species. The prioritization process led to the selection of 15 diseases of prime public health releva...

  8. Humans, Other Animals and Disease: a comparative approach towards the development of a standardised recording protocol for animal palaeopathology

    Directory of Open Access Journals (Sweden)

    Stephanie Vann

    2006-11-01

    Full Text Available In recent years the impact of animal disease on human societies has had an extremely high profile, with the spread of diseases such as Bovine Spongiform Encephalopathy (BSE and foot and mouth among animal populations, as well as the transmission of diseases such as Human Immunodeficiency Virus (HIV, Ebola and Severe Acute Respiratory Syndrome (SARS from animal to human populations. The social and economic impact of such illnesses has been profound. However, studies on the effect of animal disease in past human populations have been widely neglected. This is partly due to the inconsistent manner in which instances of animal disease (palaeopathology are recorded, diagnosed and interpreted which, together with the typically low incidence of specimens per site, has precluded detailed studies of regional or temporal trends. This article outlines the archaeological rationale behind developing a generic methodology to enable the consistent recognition, recording and description of animal palaeopathological data. Furthermore, the experience of palaeopathologists concerned with human populations has been drawn upon to develop a downloadable, stand-alone recording system to facilitate the recording of animal palaeopathological data and enable questions concerning past animal health and disease to be better explored in future.

  9. Animal Models of Interferon Signature Positive Lupus.

    Science.gov (United States)

    Zhuang, Haoyang; Szeto, Christopher; Han, Shuhong; Yang, Lijun; Reeves, Westley H

    2015-01-01

    Human lupus is strongly associated with a gene expression signature characterized by over-expression of Type I interferon-regulated genes. A strong interferon signature generally is not seen in the standard mouse models of lupus, despite considerable evidence for the involvement of toll-like receptor-driven interferon production. In contrast, pristane-induced lupus exhibits a prominent TLR7-dependent interferon signature. Importantly, genetic disorders with dysregulated interferon production in both human beings and mice cause severe autoinflammatory diseases but not the typical manifestations of lupus, suggesting that interferon over-production is insufficient to cause systemic lupus erythematosus itself. Single-gene models in mice suggest that lupus-like disease may result from abnormalities in B-cell activation and the clearance of dead cells. Pristane may mimic human systemic lupus erythematosus by causing synergistic abnormalities in interferon production along with defective clearance of apoptotic cells and over-active B-cell signaling. PMID:26097482

  10. Prioritizing Zoonotic Diseases: Differences in Perspectives Between Human and Animal Health Professionals in North America.

    Science.gov (United States)

    Ng, V; Sargeant, J M

    2016-05-01

    Zoonoses pose a significant burden of illness in North America. Zoonoses represent an additional threat to public health because the natural reservoirs are often animals, particularly wildlife, thus eluding control efforts such as quarantine, vaccination and social distancing. As there are limited resources available, it is necessary to prioritize diseases in order to allocate resources to those posing the greatest public health threat. Many studies have attempted to prioritize zoonoses, but challenges exist. This study uses a quantitative approach, conjoint analysis (CA), to overcome some limitations of traditional disease prioritization exercises. We used CA to conduct a zoonoses prioritization study involving a range of human and animal health professionals across North America; these included epidemiologists, public health practitioners, research scientists, physicians, veterinarians, laboratory technicians and nurses. A total of 699 human health professionals (HHP) and 585 animal health professionals (AHP) participated in this study. We used CA to prioritize 62 zoonotic diseases using 21 criteria. Our findings suggest CA can be used to produce reasonable criteria scores for disease prioritization. The fitted models were satisfactory for both groups with a slightly better fit for AHP compared to HHP (84.4% certainty fit versus 83.6%). Human-related criteria were more influential for HHP in their decision to prioritize zoonoses, while animal-related criteria were more influential for AHP resulting in different disease priority lists. While the differences were not statistically significant, a difference of one or two ranks could be considered important for some individuals. A potential solution to address the varying opinions is discussed. The scientific framework for disease prioritization presented can be revised on a regular basis by updating disease criteria to reflect diseases as they evolve over time; such a framework is of value allowing diseases of

  11. Animal models as tools to study the pathophysiology of depression

    Directory of Open Access Journals (Sweden)

    Helena M. Abelaira

    2013-01-01

    Full Text Available The incidence of depressive illness is high worldwide, and the inadequacy of currently available drug treatments contributes to the significant health burden associated with depression. A basic understanding of the underlying disease processes in depression is lacking; therefore, recreating the disease in animal models is not possible. Popular current models of depression creatively merge ethologically valid behavioral assays with the latest technological advances in molecular biology. Within this context, this study aims to evaluate animal models of depression and determine which has the best face, construct, and predictive validity. These models differ in the degree to which they produce features that resemble a depressive-like state, and models that include stress exposure are widely used. Paradigms that employ acute or sub-chronic stress exposure include learned helplessness, the forced swimming test, the tail suspension test, maternal deprivation, chronic mild stress, and sleep deprivation, to name but a few, all of which employ relatively short-term exposure to inescapable or uncontrollable stress and can reliably detect antidepressant drug response.

  12. Animal models as tools to study the pathophysiology of depression.

    Science.gov (United States)

    Abelaira, Helena M; Réus, Gislaine Z; Quevedo, João

    2013-01-01

    The incidence of depressive illness is high worldwide, and the inadequacy of currently available drug treatments contributes to the significant health burden associated with depression. A basic understanding of the underlying disease processes in depression is lacking; therefore, recreating the disease in animal models is not possible. Popular current models of depression creatively merge ethologically valid behavioral assays with the latest technological advances in molecular biology. Within this context, this study aims to evaluate animal models of depression and determine which has the best face, construct, and predictive validity. These models differ in the degree to which they produce features that resemble a depressive-like state, and models that include stress exposure are widely used. Paradigms that employ acute or sub-chronic stress exposure include learned helplessness, the forced swimming test, the tail suspension test, maternal deprivation, chronic mild stress, and sleep deprivation, to name but a few, all of which employ relatively short-term exposure to inescapable or uncontrollable stress and can reliably detect antidepressant drug response. PMID:24271223

  13. Genetic animal models of dystonia: common features and diversities.

    Science.gov (United States)

    Richter, Franziska; Richter, Angelika

    2014-10-01

    Animal models are pivotal for studies of pathogenesis and treatment of disorders of the central nervous system which in its complexity cannot yet be modeled in vitro or using computer simulations. The choice of a specific model to test novel therapeutic strategies for a human disease should be based on validity of the model for the approach: does the model reflect symptoms, pathogenesis and treatment response present in human patients? In the movement disorder dystonia, prior to the availability of genetically engineered mice, spontaneous mutants were chosen based on expression of dystonic features, including abnormal muscle contraction, movements and postures. Recent discovery of a number of genes and gene products involved in dystonia initiated research on pathogenesis of the disorder, and the creation of novel models based on gene mutations. Here we present a review of current models of dystonia, with a focus on genetic rodent models, which will likely be first choice in the future either for pathophysiological or for preclinical drug testing or both. In order to help selection of a model depending on expression of a specific feature of dystonia, this review is organized by symptoms and current knowledge of pathogenesis of dystonia. We conclude that albeit there is increasing need for research on pathogenesis of the disease and development of improved models, current models do replicate features of dystonia and are useful tools to develop urgently demanded treatment for this debilitating disorder. PMID:25034123

  14. 9 CFR 80.4 - Segregation of animals positive to an official Johne's disease test during interstate movement.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Segregation of animals positive to an official Johne's disease test during interstate movement. 80.4 Section 80.4 Animals and Animal Products... ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS JOHNE'S DISEASE IN DOMESTIC ANIMALS § 80.4 Segregation...

  15. Deep brain stimulation of the subthalamic nucleus preferentially alters the translational profile of striatopallidal neurons in an animal model of Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Iman Kamali Sarvestani

    2015-06-01

    Full Text Available Deep brain stimulation targeting the subthalamic nucleus (STN-DBS is an effective surgical treatment for the motor symptoms of Parkinson’s disease (PD, the precise neuronal mechanisms of which both at molecular and network levels remain a topic of debate. Here we employ two transgenic mouse lines, combining translating ribosomal affinity purification (TRAP with bacterial artificial chromosome expression (Bac, to selectively identify changes in translational gene expression in either Drd1a-expressing striatonigral or Drd2-expressing striatopallidal medium spiny neurons (MSNs of the striatum following STN-DBS. 6-hydroxydopamine lesioned mice received either 5 days stimulation via a DBS electrode implanted in the ipsilateral STN or 5 days sham treatment (no stimulation. Striatal polyribosomal RNA was selectively purified from either Drd2 or Drd1a MSNs using the TRAP method and gene expression profiling performed. We identified 8 significantly altered genes in Drd2 MSNs (Vps33b, Ppp1r3c, Mapk4, Sorcs2, Neto1, Abca1, Penk1 and Gapdh and 2 overlapping genes in Drd1a MSNs (Penk1 and Ppp1r3c implicated in the molecular mechanisms of STN-DBS. A detailed functional analysis, using a further 728 probes implicated in STN-DBS, suggested an increased ability to receive excitation (mediated by increased dendritic spines, increased calcium influx and enhanced excitatory post synaptic potentials accompanied by processes that would hamper the initiation of action potentials, transport of neurotransmitters from soma to axon terminals and vesicular release in Drd2-expressing MSNs. Finally, changes in expression of several genes involved in apoptosis as well as cholesterol and fatty acid metabolism were also identified. This increased understanding of the molecular mechanisms induced by STN-DBS may reveal novel targets for future non-surgical therapies for PD.

  16. The effect of HIV protease inhibitors on amyloid-β peptide degradation and synthesis in human cells and Alzheimer's disease animal model.

    Science.gov (United States)

    Lan, Xiqian; Kiyota, Tomomi; Hanamsagar, Richa; Huang, Yunlong; Andrews, Scott; Peng, Hui; Zheng, Jialin C; Swindells, Susan; Carlson, George A; Ikezu, Tsuneya

    2012-06-01

    Combined antiretroviral therapy (ART) tremendously improved the lifespan and symptoms associated with AIDS-defining illness in affected individuals. However, chronic ART-treated patients frequently develop age-dependent complications, including dementia, diabetes, and hyperlipidemia: all risk factors of Alzheimer's disease. Importantly, the effect of ART compounds on amyloid generation and clearance has never been systematically examined. Nine prescribed HIV protease inhibitors were tested for their effect on amyloid-β peptide (Aβ) clearance in primary cultured human monocyte-derived macrophages. Atazanavir, ritonavir, and saquinavir modestly inhibited of Aβ degradation, while lopinavir, nelfinavir, and ritonavir enhanced secretion of undigested Aβ after phagocytosis. Lopinavir, nelfinavir, ritonavir, and saquinavir inhibited endogenous Aβ40 production from primary cultured human cortical neurons, which were associated with reduction in Beta-site APP Converting Enzyme 1 (BACE1) and γ-secretase enzyme activities. However, ART compounds showed little inhibition of purified BACE1 activity in vitro, suggesting the indirect effect of ART compounds on BACE1 activity in neurons. Finally, nefinavir or lopinavir/ritonavir (Kaletra) were orally administered for 30 days into APP SCID mice expressing a double mutant form of APP 695 (KM670/671NL + V717F) in homozygosity for the scid allele of Prkdc. There was no difference in beta-amyloidosis by ART drug administration as determined by both immunohistochemistry and ELISA measurements although the therapeutic doses of the ART compounds was present in the brain. These data demonstrated that ART drugs can inhibit Aβ clearance in macrophages and Aβ production in neurons, but these effects did not significantly alter Aβ accumulation in the mouse brain. PMID:21826404

  17. Melittin restores proteasome function in an animal model of ALS

    Directory of Open Access Journals (Sweden)

    Lee Sang Min

    2011-06-01

    Full Text Available Abstract Amyotrophic lateral sclerosis (ALS is a paralyzing disorder characterized by the progressive degeneration and death of motor neurons and occurs both as a sporadic and familial disease. Mutant SOD1 (mtSOD1 in motor neurons induces vulnerability to the disease through protein misfolding, mitochondrial dysfunction, oxidative damage, cytoskeletal abnormalities, defective axonal transport- and growth factor signaling, excitotoxicity, and neuro-inflammation. Melittin is a 26 amino acid protein and is one of the components of bee venom which is used in traditional Chinese medicine to inhibit of cancer cell proliferation and is known to have anti-inflammatory and anti-arthritic effects. The purpose of the present study was to determine if melittin could suppress motor neuron loss and protein misfolding in the hSOD1G93A mouse, which is commonly used as a model for inherited ALS. Meltittin was injected at the 'ZuSanLi' (ST36 acupuncture point in the hSOD1G93A animal model. Melittin-treated animals showed a decrease in the number of microglia and in the expression level of phospho-p38 in the spinal cord and brainstem. Interestingly, melittin treatment in symptomatic ALS animals improved motor function and reduced the level of neuron death in the spinal cord when compared to the control group. Furthermore, we found increased of α-synuclein modifications, such as phosphorylation or nitration, in both the brainstem and spinal cord in hSOD1G93A mice. However, melittin treatment reduced α-synuclein misfolding and restored the proteasomal activity in the brainstem and spinal cord of symptomatic hSOD1G93A transgenic mice. Our research suggests a potential functional link between melittin and the inhibition of neuroinflammation in an ALS animal model.

  18. The utility of animal models to evaluate novel anti-obesity agents

    OpenAIRE

    Vickers, Steven P; Jackson, Helen C; Cheetham, Sharon C

    2011-01-01

    The global incidence of obesity continues to rise and is a major driver of morbidity and mortality through cardiovascular and cerebrovascular diseases. Animal models used in the discovery of novel treatments for obesity range from straightforward measures of food intake in lean rodents to long-term studies in animals exhibiting obesity due to the continuous access to diets high in fat. The utility of these animal models can be extended to determine, for example, that weight loss is due to fat...

  19. ANIMAL MODELS: A REVIEW FROM THREE TESTS USED IN ANXIETY

    OpenAIRE

    Manuel Eduardo Góngora; Cristina Vargas-Irwin; Lady Andrea Polanco

    2011-01-01

    The aim of this paper is to present a review of commonly used animal models tostudy anxiety, looking to make a presentation of three instruments used in thelaboratory. It describes the importance of using animal models for understandinghuman behavior; there are two groups of animal models and the most representativetests for each of these.

  20. Computational Prediction of Alzheimer's and Parkinson's Disease MicroRNAs in Domestic Animals.

    Science.gov (United States)

    Wang, Hai Yang; Lin, Zi Li; Yu, Xian Feng; Bao, Yuan; Cui, Xiang-Shun; Kim, Nam-Hyung

    2016-06-01

    As the most common neurodegenerative diseases, Alzheimer's disease (AD) and Parkinson's disease (PD) are two of the main health concerns for the elderly population. Recently, microRNAs (miRNAs) have been used as biomarkers of infectious, genetic, and metabolic diseases in humans but they have not been well studied in domestic animals. Here we describe a computational biology study in which human AD- and PD-associated miRNAs (ADM and PDM) were utilized to predict orthologous miRNAs in the following domestic animal species: dog, cow, pig, horse, and chicken. In this study, a total of 121 and 70 published human ADM and PDM were identified, respectively. Thirty-seven miRNAs were co-regulated in AD and PD. We identified a total of 105 unrepeated human ADM and PDM that had at least one 100% identical animal homolog, among which 81 and 54 showed 100% sequence identity with 241 and 161 domestic animal miRNAs, respectively. Over 20% of the total mature horse miRNAs (92) showed perfect matches to AD/PD-associated miRNAs. Pigs, dogs, and cows have similar numbers of AD/PD-associated miRNAs (63, 62, and 59). Chickens had the least number of perfect matches (34). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses suggested that humans and dogs are relatively similar in the functional pathways of the five selected highly conserved miRNAs. Taken together, our study provides the first evidence for better understanding the miRNA-AD/PD associations in domestic animals, and provides guidance to generate domestic animal models of AD/PD to replace the current rodent models. PMID:26954182