What's New @ ILAR e-Newsletter -- Spring 2013

ILAR Journal

Volume 53, Issues 3-4
Epigenetics
Scientific Editor: Dana C. Dolinoy

 

Changes in the epigenome induced by the environment have been documented in diverse animal phyla, ranging from insects to rodents to humans. These include chromatin remodeling, histone tail modifications, and DNA methylation, and more recently the list has expanded to encompass noncoding RNA and microRNA gene regulation (Matzke and Birchler 2005). Thus, it is increasingly recognized that exposure to chemical, nutritional, behavioral, and physical factors alters gene expression and affects health and disease not only through mutation of but also through modification of the epigenome. Moreover, such exposures have been directly linked with subsequent disease formation through deregulation of epigenetic mechanisms. Unlike genetic mutations, these epigenetic changes are potentially reversible, providing a unique avenue to improve human health. Consequently research in epigenetics has increased dramatically in the last few years.

 

The term "epigenetics" was popularized in the early 1940s by developmental biologist Conrad Waddington (1940) to explain "the interactions of genes with their environment, which bring the phenotype into being." In the 1970s, Holliday and Pugh (1975) fi rst proposed covalent chemical DNA modifications, including methylation of cytosine-guanine (CpG) dinucleotides, as the molecular mechanism to explainWaddington's hypothesis. The revelations several decades later that X inactivation in mammals and genomic imprinting are regulated by complex and multifactorial mechanisms (Monk 1988; Willard et al. 1993) resulted in an updated definition, describing epigenetics as heritable changes in gene expression that occur without a change in DNA sequence, including the modification of DNA methylation and chromatin remodeling (Wolfe and Matzke 1999). The genomics revolution inspired the investigation of genome-wide rather than local gene analyses, and the term "epigenomics" was coined as the study of the "effects of chromatin structure including the higher order of chromatin folding and attachment to the nuclear matrix, packaging of DNA around nucleosomes, covalent modifications of histone tails (acetylation, methylation, phosphorylation, ubiquitination), and DNA methylation" (Murrell et al. 2005). Finally, evidence that demonstrated the resistance of certain gene loci to methylation reprogramming during embryogenesis revealed that epigenetic modifications can be inherited not only mitotically but also transgenerationally (Lane et al. 2003; Morgan et al. 1999; Rakyan et al. 2003).


Contents:

  • Introduction: The Use of Animals Models to Advance Epigenetic Science
  • Recruitment and Biological Consequences of Histone Modification of H3K27me3 and H3K9me3
  • Developmental Epigenetics of the Murine Secondary Palate
  • Sexually Selected Traits: A Fundamental Framework for Studies on Behavioral Epigenetics
  • Nutritional Epigenetics
  • Epigenetic Influence of Stress and the Social Environment
  • Environmental Epigenetics and Its Implication on Disease Risk and Health Outcomes
  • Early Origins of Adult Disease: Approaches for Investigating the Programmable Epigenome in Humans, Nonhuman Primates, and Rodents
  • Gene–Environment Interactions and Epigenetic Pathways in Autism: The Importance of One-Carbon Metabolism
  • The Human Imprintome: Regulatory Mechanisms, Methods of Ascertainment, and Roles in Disease Susceptibility
  • Cancer Epigenetics: A Brief Review
  • Animal Models in Epigenetic Research: Institutional Animal Care and Use Committee Considerations across the Lifespan

Recent Issues

Volume 53, Issue 2
Zebrafish Health and Husbandry
Scientific Editors: Michael Kent Zoltán Varga

 

The scientific community is rapidly realizing the benefits of using zebrafish (Danio rerio) as a model in research related to human health. The field was initially led by investigations in developmental genetics, but now adult zebrafish are also extensively used as model organisms in infectious disease and immune system function work and in the study of aging, toxicology, oncology, and behavior.

Given the increasing importance of these animals in biomedical research, it is essential to produce and maintain healthy and pathogen-free adults. Both husbandry and underlying health status can significantly affect research outcomes. Improper water quality, nutrition, and pathogen infections can profoundly affect fecundity, growth, immunity, neoplasia, and other responses. These in turn can distort experimental results, an important concern with any animal model. This issue features reviews of the major husbandry issues and diseases of importance to zebrafish in the research setting.

Contents:

  • Introduction: Use of Zebrafish in Research and Importance of Health and Husbandry
  • Mycobacteriosis in Zebrafish Colonies
  • Microsporidiosis in Zebrafish Research Facilities
  • Neoplasia and Neoplasm-Associated Lesions in Laboratory Colonies of Zebrafish Emphasizing Key Influences of Diet and Aquaculture System Design
  • Documented and Potential Research Impacts of Subclinical Diseases in Zebrafish
  • Viral Diseases in Zebrafish: What is Known and Unknown
  • Fundamental Approaches to the Study of Zebrafish Nutrition
  • Zebrafish Breeding in the Laboratory Environment
  • Aspects of Larval Rearing
  • Zebrafish Housing Systems: A Review of Basic Operating Principles and Considerations for Design and Functionality
  • Anesthesia and Euthanasia in Zebrafish
  • IACUC Issues Associated with Zebrafish
  • Zebrafish Resources on the Internet

 

Volume 53, Issue 1
Neurobiology of Addiction-like Behaviors
Scientific Editors: Elisabeth J. Van Bockstaele

 

As one of society’s major public health problems, addiction poses a tremendous threat to the health and welfare of individuals, families, communities, and nations. Despite the significant new information that scientists have gained over the past two decades from preclinical and clinical studies, a great deal remains unknown about addiction-like behaviors. Even as scientists learn more about the neurobiological underpinnings of addiction, new categories of addictions are being defined and include addictions to prescription medication, food, the Internet, gambling, sex, and shopping.

Scientists have gained significant insight into the neurobiological adaptations that underlie addiction-like behaviors from convergent evidence in the fields of neuroscience, genetics, and psychiatry. Many of the articles in the issue deal with animal models for the study of the neurobiology of addiction-like behaviors. The issue concludes with important recommendations for members of institutional animal care and use committees (IACUCs) as they consider the multiple facets involved in investigations into the neurobiology of addiction-like behaviors.

Contents:

  • Introduction: The Neurobiology of Addiction-like Behaviors
  • Advancing Addiction Treatment: What Can We Learn from Animal Studies?
  • Influence of Sex Differences and Gonadal Hormones on Cocaine Addiction
  • Rodent Models of Binge Eating: Are They Models of Addiction?
  • Neurobiology of Consummatory Behavior: Mechanisms Underlying Overeating and Drug Use
  • Translational Neuroimaging in Drug Addiction and Obesity
  • IACUC Considerations Specific to the Use of Animal Models in Studies on the Neurobiology of Addictive Behaviors

 

Volume 52, Issue 3
Animal Models of Drug Addictions: High Hopes for Therapeutic Treatments
Scientific Editors: Kimberlei A. Richardson and Gabrielle L. McLemore

 

Addictions to a variety of substances both licit (e.g., alcohol, nicotine) and illicit (e.g., marijuana, cocaine) are a pervasive national and international social and economic challenge, accounting for as much as $600 billion annually in cumulative losses in the United States (cited in Nicholson and Ator 2011). The treatment of addictions and addictive behaviors is thus an important public health concern. Basic animal studies have greatly contributed to progress in this area and will surely continue to yield significant insights into the neuroanatomical circuitry, neurophysiological function, neurochemical changes, and behavioral processes underlying addiction.

Current clinical neurobiological methods such as brain imaging have expanded knowledge and provided novel insights into the most complex human brain-behavior interactions. The science of addiction is revealing that alterations of brain-behavioral processes can have a complex mixture of intrinsic and extrinsic causes. A better understanding of the etiology and brain mechanisms directly involved will provide more effective addiction prevention and treatment approaches.

The topic is critically important and broad enough to warrant two issues, in which experts review efforts both to understand a variety of substance dependences and to develop therapeutic treatments for them. In this issue the authors address addictions to alcohol, nicotine, marijuana, opiates, cocaine, methamphetamine, and ketamine.

Contents:

  • Introduction: Animal Models of Drug Addiction in Support of Novel Therapeutic Strategies
  • Translational Models of Interactions between Stress and Alcohol Consumption: Strengths and Limitations
  • Effects of Pre- and Neonatal Nicotine Exposure in Rodents: Inconsistent Evidence
  • Marijuana Dependence: Not Just Smoke and Mirrors
  • Cracking the Molecular Code of Cocaine Addiction
  • Mediating the Effects of Drug Abuse: The Role of Narp in Synaptic Plasticity
  • Changing Mechanisms of Opiate Tolerance and Withdrawal during Early Development: Animal Models of the Human Experience
  • Opioid Dependence and NMDA Receptors
  • Nucleus Accumbens Invulnerability to Methamphetamine Neurotoxicity
  • The Neurobehavioral Pharmacology of Ketamine: Implications for Drug Abuse, Addiction, and Psychiatric Disorders
  • IACUC Perspective on Drug Addiction Research
  • Workshop Summary: Neotropical Primates in Biomedical Research
  • Harmonizing Veterinary Training and Qualifications in Laboratory Animal Medicine: A Global Perspective

Future Issue Topics*

Vol 54(3): Animal Models of Peripheral Neuropathy

Vol 54(2): Nonhuman Primate Genetics and Genomics

Vol 54(1): Ethical and IACUC Considerations of Field Biology Studies

* Topics and titles are subject to change

 

 


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Recently Published



Guide for the Care and Use of Laboratory Animals: Eighth Edition (2011)

This seventh update to the Guide for the Care and Use of Laboratory Animals integrates recently published data, scientific principles, and expert opinion to recommend practices for the humane care and use of animals in research, testing, and teaching. The Guide is an internationally accepted primary reference on animal care for the scientific community. Previous editions have served as the basis for accreditation of institutions worldwide by the Association for Assessment and Accreditation of Laboratory Animal Care International. Also, use of previous editions has been required for researchers supported by the National Institutes of Health who adhere to the Public Health Service policy. Additions to this eighth edition of the Guide include expanded coverage of the ethics of laboratory animal use; components of effective Animal Care and Use Programs; new guidelines for the housing, environment, and enrichment of terrestrial and aquatic animals; updated information on veterinary and clinical care, and discussion of animal biosecurity.

 


Animal Research in a Global Environment (2011)

To identify and promote better understanding of the challenges of conducting animal research across country boundaries, the Institute for Laboratory Animal Research (ILAR) convened a workshop on Animal Research in a Global Environment: Meeting the Challenges, drawing on the expertise and perspectives of 200 participants from 17 countries. The public workshop featured invited presentations and discussions that focused on new information published since the last workshop in 2003, in part to inform the continuing development of guidelines (including an update of the 1996 Guide for the Care and Use of Laboratory Animals).

 

 

Animal Models for Assessing Countermeasures to Bioterrorism Agents (2011)

In response to a request by the Department of Defense, this report addresses the challenges stemming from developing and testing medical countermeasures in animal models. The report makes the principal point that a comprehensive strategy to improve data gathering and data sharing from animal models (or their alternatives) would significantly increase the efficiency and productivity of research into countermeasures while improving the humane use of laboratory animals in accordance with the principles of the Three Rs.

 

Guidance for the Description of Animal Research in Scientific Publications (2011)

This a short report aimed at editors of Journals that publish animal studies. The report outlines the information that should be included in scientific papers regarding such studies to ensure that the studies can be replicated. Necessary information includes conditions of housing and husbandry, genetic nomenclature, microbial status, detailed experimental manipulations, and handling and use of pharmaceuticals.

 

International Animal Research Regulations: Impact on Neuroscience Research (2012)

Animals are widely use in neuroscience research to explore biological mechanisms of nervous system function, to identify the genetic basis of disease states, and to provide models of human disorders and diseases for the development of new treatments. To ensure the humane care and use of animals, numerous laws, policies, and regulations are in place governing the use of animals in research, and certain animal regulations have implications specific to neuroscience research. This report summarizes the workshop “U.S. and European Animal Research Regulations” convened by the Institute of Medicine Forum on Neuroscience and Nervous System Disorders, in collaboration with the National Research Council Committee on Science, Technology, and Law, and the Institute for Laboratory Animal Research, held in the UK on July 26-27, 2011.

 


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