Stress and Schizophrenia

2020 ◽  
pp. 225-266
Author(s):  
Richard McCarty
Keyword(s):  
Animal Models ◽  
Neuronal Development ◽  
Early Adulthood ◽  
Laboratory Mice ◽  
Dopaminergic Drugs ◽  
Risk Genes ◽  
Recent Approach ◽  
Hippocampal Lesions ◽  
Stressful Stimulation ◽  
Neurodevelopmental Hypothesis

Developing animal models of schizophrenia is challenging because of the uniquely human nature of some of the classic symptoms of the disorder (e.g., hallucinations, delusions, disordered thought). Several efforts have been guided by the neurodevelopmental hypothesis of schizophrenia and have included exposure of animals to stressful stimulation. Other animal models have involved prenatal exposure to maternal immune activation or drugs that disrupt neuronal development, followed by stress during adolescence or in early adulthood to unmask vulnerabilities. Neonatal hippocampal lesions have been employed in other animal models of schizophrenia. Another profitable approach has been to selectively breed laboratory mice or rats for their susceptibility to dopaminergic drugs. A more recent approach has been to develop laboratory mice with targeted alterations in risk genes for schizophrenia that were previously identified in clinical studies. In many cases, the effects of these risk genes are unmasked by exposure of animals to stressful stimulation during specific stages of postnatal development.

Inflammational Animal Models for Schizophrenia

2015 ◽  
Vol 223 (3) ◽  
pp. 157-164 ◽  
Author(s):  
Georg Juckel
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Immune Activation ◽  
Microglial Activation ◽  
Treatment Options ◽  
Early Adulthood ◽  
Brain Regions ◽  
Synaptic Connections ◽  
Preventive Interventions ◽  
Immunological System

Abstract. Inflammational-immunological processes within the pathophysiology of schizophrenia seem to play an important role. Early signals of neurobiological changes in the embryonal phase of brain in later patients with schizophrenia might lead to activation of the immunological system, for example, of cytokines and microglial cells. Microglia then induces – via the neurotoxic activities of these cells as an overreaction – a rarification of synaptic connections in frontal and temporal brain regions, that is, reduction of the neuropil. Promising inflammational animal models for schizophrenia with high validity can be used today to mimic behavioral as well as neurobiological findings in patients, for example, the well-known neurochemical alterations of dopaminergic, glutamatergic, serotonergic, and other neurotransmitter systems. Also the microglial activation can be modeled well within one of this models, that is, the inflammational PolyI:C animal model of schizophrenia, showing a time peak in late adolescence/early adulthood. The exact mechanism, by which activated microglia cells then triggers further neurodegeneration, must now be investigated in broader detail. Thus, these animal models can be used to understand the pathophysiology of schizophrenia better especially concerning the interaction of immune activation, inflammation, and neurodegeneration. This could also lead to the development of anti-inflammational treatment options and of preventive interventions.

Animal Models of Down Syndrome

2021 ◽  
Author(s):  
Anna J. Moyer ◽  
Roger H. Reeves
Keyword(s):  
Down Syndrome ◽  
Cognitive Impairment ◽  
Intellectual Disability ◽  
Animal Models ◽  
Brain Regions ◽  
Laboratory Mice ◽  
Tremendous Progress ◽  
New Treatments ◽  
And Function ◽  
Early Developmental

Is intellectual disability a treatable feature of persons with Down syndrome? Researchers have made tremendous progress in the last 30 years, from creating the first mouse model of Down syndrome to completing the first major clinical trial for cognitive impairment in people with Down syndrome. Until recently, normalizing brain development and function seemed too lofty a goal, and indeed, even proposing a candidate therapy requires answering a number of difficult questions. How does trisomy 21, a molecular diagnosis, cause the clinical phenotypes of Down syndrome? When, where, and how do trisomic genes act to disrupt normal development and which genes are involved with which outcomes? Which brain regions and behaviors are most impaired? Is there an early developmental window of time during which treatments are most effective? This article discusses how animal models such as laboratory mice can be used to understand intellectual disability and to develop new treatments for cognitive impairment.

scholarly journals An Update on Animal Models for Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Countermeasure Development

2021 ◽  
Vol 12 ◽  
Author(s):  
Liang Zhang ◽  
Shuaiyin Chen ◽  
Weiguo Zhang ◽  
Haiyan Yang ◽  
Yuefei Jin ◽  
...  
Keyword(s):  
Animal Models ◽  
Severe Acute Respiratory Syndrome ◽  
Research Progress ◽  
Laboratory Mice ◽  
Disease Manifestation ◽  
Highly Pathogenic ◽  
The World ◽  
Coronavirus Infection ◽  
Different Levels ◽  
Critical Aspects

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic since March 2020 and led to significant challenges to over 200 countries and regions all over the world. The establishment of highly pathogenic coronavirus animal model is beneficial for the study of vaccines and pathogenic mechanism of the virus. Laboratory mice, Syrian hamsters, Non-human primates and Ferrets have been used to establish animal models of emerging coronavirus infection. Different animal models can reproduce clinical infection symptoms at different levels. Appropriate animal models are of great significance for the pathogenesis of COVID-19 and the research progress related to vaccines. This review aims to introduce the current progress about experimental animal models for SARS-CoV-2, and collectively generalize critical aspects of disease manifestation in humans and increase their usefulness in research into COVID-19 pathogenesis and developing new preventions and treatments.

scholarly journals Thogoto Virus Lacking Interferon-Antagonistic Protein ML Is Strongly Attenuated in Newborn Mx1-Positive but Not Mx1-Negative Mice

2004 ◽  
Vol 78 (20) ◽  
pp. 11422-11424 ◽  
Author(s):  
Andreas Pichlmair ◽  
Johanna Buse ◽  
Stephanie Jennings ◽  
Otto Haller ◽  
Georg Kochs ◽  
...  
Keyword(s):  
Animal Models ◽  
Standard Laboratory ◽  
Laboratory Mice ◽  
Highly Pathogenic ◽  
Wild Mice ◽  
Effector Molecules ◽  
Conventional Animal ◽  
Infected Cells ◽  
Virus Mutant ◽  
Interferon Antagonists

ABSTRACT The Thogoto virus ML protein suppresses interferon synthesis in infected cells. Nevertheless, a virus mutant lacking ML remained highly pathogenic in standard laboratory mice. It was strongly attenuated, however, in mice carrying the interferon-responsive Mx1 gene found in wild mice, demonstrating that enhanced interferon synthesis is protective only if appropriate antiviral effector molecules are present. Our study shows that the virulence-enhancing effects of some viral interferon antagonists may escape detection in conventional animal models.

scholarly journals Animal Models of GWAS-Identified Type 2 Diabetes Genes

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Gabriela da Silva Xavier ◽  
Elisa A. Bellomo ◽  
James A. McGinty ◽  
Paul M. French ◽  
Guy A. Rutter
Keyword(s):  
Type 2 Diabetes ◽  
Animal Models ◽  
Mouse Models ◽  
Human Genetics ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Risk Genes ◽  
Genome Wide ◽  
Increased Risk

More than 65loci, encoding up to 500 different genes, have been implicated by genome-wide association studies (GWAS) as conferring an increased risk of developing type 2 diabetes (T2D). Whilst mouse models have in the past been central to understanding the mechanisms through which more penetrant risk genes for T2D, for example, those responsible for neonatal or maturity-onset diabetes of the young, only a few of those identified by GWAS, notablyTCF7L2andZnT8/SLC30A8, have to date been examined in mouse models. We discuss here the animal models available for the latter genes and provide perspectives for future, higher throughput approaches towards efficiently mining the information provided by human genetics.

scholarly journals Effect of postnatal intermittent hypoxia on locomotor activity and neuronal development in rats tested in early adulthood.

2014 ◽  
Vol 7 (2) ◽  
pp. 125-130
Author(s):  
Karen Y. Yamada ◽  
Susan Y. Satake ◽  
Juliana C. Perry ◽  
Karina O. Garcia ◽  
Vânia D'Almeida ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Intermittent Hypoxia ◽  
Neuronal Development ◽  
Early Adulthood

Can animals develop depression? An overview and assessment of ‘depression-like’ states

Behaviour ◽  
2021 ◽  
pp. 1-51
Author(s):  
Aileen MacLellan ◽  
Carole Fureix ◽  
Andrea Polanco ◽  
Georgia Mason
Keyword(s):  
Animal Models ◽  
Clinical Depression ◽  
Laboratory Mice ◽  
Clinical Disorder ◽  
Ethical Implications ◽  
Animal Models Of Depression ◽  
Dsm V ◽  
Icd 10 ◽  
Low Activity ◽  
Poor Welfare

Abstract Describing certain animal behaviours as ‘depression-like’ or ‘depressive’ has become common across several fields of research. These typically involve unusually low activity or unresponsiveness and/or reduced interest in pleasure (anhedonia). While the term ‘depression-like’ carefully avoids directly claiming that animals are depressed, this narrative review asks whether stronger conclusions can be legitimate, with animals developing the clinical disorder as seen in humans (cf., DSM-V/ICD-10). Here, we examine evidence from animal models of depression (especially chronically stressed rats) and animals experiencing poor welfare in conventional captive conditions (e.g., laboratory mice and production pigs in barren environments). We find troubling evidence that animals are indeed capable of experiencing clinical depression, but demonstrate that a true diagnosis has yet to be confirmed in any case. We thus highlight the importance of investigating the co-occurrence of depressive criteria and discuss the potential welfare and ethical implications of animal depression.

Animal Models in Psychiatry

2020 ◽  
pp. 167-192
Author(s):  
Richard McCarty
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Learned Helplessness ◽  
Molecular Targets ◽  
Essential Element ◽  
Inbred Strains ◽  
Behavioral Tests ◽  
Single Animal ◽  
Stressful Stimulation ◽  
Helplessness Model

Darwin made a compelling case that studies of animals could provide insights into the behavior of humans. Early studies by Pavlov and Harlow paved the way for further developments of animal models of psychiatric disorders. Seligman and Maier’s learned helplessness model continues to be employed in laboratory studies of stress and depression. It has become clear that no single animal model can possibly reproduce all of the critical facets of a mental disorder in humans. However, animal models do provide an essential element in attempts to understand the mechanisms that underlie mental disorders and to reveal molecular targets for the development of new drug therapies. Concerns have been raised about the reproducibility of laboratory experiments with inbred strains of laboratory mice and rats. Any animal model should be evaluated based upon a battery of behavioral tests and the parameters of stressful stimulation employed in experiments should be chosen with care.

scholarly journals Significance of different animal species in experimental models for in vivo investigations of hematopoiesis

2004 ◽  
Vol 58 (1-2) ◽  
pp. 55-66
Author(s):  
Milica Kovacevic-Filipovic ◽  
Tatjana Bozic ◽  
Jelka Stevanovic
Keyword(s):  
Stem Cells ◽  
Animal Models ◽  
Animal Species ◽  
Experimental Models ◽  
Biologically Active ◽  
Laboratory Mice ◽  
Hematopoietic System ◽  
General Rules ◽  
Experimental Hematology

Numerous discoveries in medicine are results of experiments on different animal species. The most frequently used animals in hematopoiesis investigations are laboratory mice and rats, but so-called big animals, such as pigs, sheep, cats, dogs, and monkeys, evolution-wise closer to humans have a place in experimental hematology as well. The specific problematics of a certain animal specie can lead to fundamental knowledge on certain aspects of the process of hematopoiesis end the biology of stem cells in hematopoiesis. Furthermore, comparative investigations of certain phenomena in different species help in the recognition of the general rules in the living world. In the area f preclinicalinvesti- gations, animal models are an inevitable step in studies of transplantation biology of stem cells in hematopoiesis, as well as in studies of biologically active molecules which have an effect on the hematopoietic system. Knowledge acquired on animal models is applied in both human and veterinary medicine.

Neurodevelopmental Mechanisms for Psychotic Disorders

2017 ◽  
Author(s):  
Nao J. Gamo ◽  
Takeshi Sakurai ◽  
Hanna Jaaro-Peled ◽  
Akira Sawa
Keyword(s):  
Animal Models ◽  
Psychotic Disorders ◽  
Accurate Diagnosis ◽  
Developmental Trajectory ◽  
Behavioral Changes ◽  
Biological Mechanisms ◽  
Dimensional Approach ◽  
Diagnosis And Prognosis ◽  
Neurodevelopmental Hypothesis ◽  
Experimental Strategies

The current understanding of the mechanisms underlying psychotic disorders, including schizophrenia, is far from satisfactory and has hampered the establishment of effective treatments, as well as accurate diagnosis and prognosis in patients. A prevailing hypothesis that attempts to understand these mechanisms is the “neurodevelopmental hypothesis.” In this chapter, we address experimental strategies to characterize the biological mechanisms underlying psychotic disorders, including a complementary combination of human cell and animal models that pays attention to the developmental trajectory, in particular key neural circuitries that may underlie behavioral changes relevant to psychotic disorders. In addition, we discuss a “dimensional” approach to understanding psychiatric disorders to more easily translate findings between animal models and human applications.

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