Environmental Factors in Neurodevelopmental and Neurodegenerative Disorders

1st Edition - June 18, 2015
Editors: Michael Aschner, Lucio G. Costa
Language: English
Hardback ISBN:
9 7 8 - 0 - 1 2 - 8 0 0 2 2 8 - 5
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 0 0 4 0 7 - 4

Environmental Factors in Neurodevelopmental and Neurodegenerative Disorders presents a state-of-the-art review of the effects of environmental contaminants on the developme… Read more

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Environmental Factors in Neurodevelopmental and Neurodegenerative Disorders presents a state-of-the-art review of the effects of environmental contaminants on the development and degeneration of the human nervous system, brought together by world-leading experts in the field.

Part One describes the adverse effects that the environment can have on neurological development, and how these effects may exhibit. Specific contaminants and their possible consequences of exposure are addressed (lead, methylmercury, alcohol), as well as specific disorders and the environmental factors associated with them, such as the effect of diet on attention deficit and hyperactivity disorders. Part Two tackles neurodegenerative disorders, specifically addressing their potential neurotoxic origins, and discussing the increasing interest in the effects that early exposure may have in later life.

Environmental Factors in Neurodevelopmental and Neurodegenerative Disorders is an invaluable reference for those professionals working in the fields of toxicology, environmental health and neuroscience.

Preface
Foreword
SECTION I. Neurodevelopmental Disorders
- Chapter 1. Overview of the Role of Environmental Factors in Neurodevelopmental Disorders
  - Introduction
  - Evidence Implicating Environmental Factors
  - Environmental Factors Associated with Increased Risk for Neurodevelopmental Disorders
  - Mechanisms by Which Environmental Factors Influence Risk of Neurodevelopmental Disorders
  - Conclusions
- Chapter 2. Genetic Factors in Environmentally Induced Disease
  - Introduction
  - Parkinson’s Disease
  - Amyotrophic Lateral Sclerosis
  - Alzheimer’s Disease
  - Conclusions and Future Directions
- Chapter 3. Fetal Alcohol Spectrum Disorders: Effects and Mechanisms of Ethanol on the Developing Brain
  - Introduction
  - Fetal Alcohol Spectrum Disorders (FASD)
  - FASD Prevalence
  - Neurobehavioral Deficits in FASD
  - FASD and Brain Structures
  - Animal Models for FASD
  - Mechanisms Involved in FASD
  - Experimental Treatments for FASD
- Chapter 4. Prenatal Infection: Setting the Course of Brain Aging and Alzheimer’s Disease?
  - Introduction
  - What Characterizes Alzheimer’s Disease?
  - Toward a Novel Animal Model of Sporadic Alzheimer’s Disease
  - Chronic Neuroinflammation—Impact on Basic Cellular Functions
  - From Axonal Varicosities to Axonal Degeneration
  - Conclusions
- Chapter 5. Neurobehavioral Effects of Air Pollution in Children
  - Introduction
  - Evidence from Epidemiological Research
  - Evidence from Animal Research
  - Biological Pathways
  - Evaluation of the Evidence and Future Research Directions
  - Conclusions
- Chapter 6. The Role of Methylmercury Exposure in Neurodevelopmental and Neurodegenerative Disorders
  - Introduction
  - Fetal Minamata Disease and Associated Disorders
  - Environmental Epidemiology Studies of Low-Level MeHg Exposure: Improving Measurements and Methods
  - The Delicate Balance Between the Risks and Benefits of Maternal Fish Consumption for Childhood Outcomes
  - Insights on Neurobehavioral Effects of MeHg From Animal Model Studies
  - Cross-Species Comparisons of MeHg Neurodevelopmental Effects
  - Mechanisms Underlying MeHg-Mediated Neurotoxicity
  - Effects on Mitochondria, Including Reduced Cellular Energetics, Altered Ca²⁺ Homeostasis, and Production of Reactive Oxygen Species
  - Effects of MeHg on Microtubules as a Mechanism Underlying Developmental Neuropathology
  - Effects of MeHg on Astrocytes and Microglia
  - Mechanisms of MeHg at Low Doses: Effects on Neuronal Signaling
  - Delayed Neurotoxicity, Neurodegenerative Disease, and Intergenerational Effects
  - The Societal and Human Costs of MeHg Exposure
- Chapter 7. Developmental Exposure to Lead: Overview and Integration of Neurobehavioral Consequences and Mediation
  - Introduction and Focus
  - History of Lead as an Environmental and Occupational Contaminant
  - The Persistent Question of whether Elevated Lead Exposure Reduces IQ
  - What Does an IQ Reduction Mean Behaviorally: Changes in Learning
  - Do Attention Deficits and/or Hearing Loss Serve as Behavioral Mechanisms of Lead-Induced Learning and IQ Deficits?
  - Persistence of Developmental Lead Neurotoxicity
  - En Route to More Relevant Evaluations of Lead Exposure and Public Health Protection
  - An Integrated Summary and Hypothesized Relationships of the Consequences of Developmental Lead Exposure
- Chapter 8. Thyroid-Disrupting Chemicals as Developmental Neurotoxicants
  - Introduction
  - Regulation of TH Action
  - Representative TDCs and Mechanisms of Disruption
  - Disruption of TH Action in the Developing Brain
  - TH and Development of the Auditory System
  - Concluding Remarks
- Chapter 9. Environmental Factors in Neurodevelopmental Disorders: Summary and Perspectives
SECTION II. Neurodegenerative Disorders
- Chapter 10. Overview of Neurodegenerative Disorders and Susceptibility Factors in Neurodegenerative Processes
  - Classification
  - Mechanistic Clues
  - Complex Disorders
  - Lifestyle Modifiers of Neurodegenerative Disease Risk
  - Gene–Environment Interactions
  - Epigenetics
  - Conclusions
- Chapter 11. Environmental Neurotoxins Linked to a Prototypical Neurodegenerative Disease
  - Introduction
  - ALS-PDC: A Declining or Disappearing Environmental Disease
  - ALS-PDC: Links to Cycad Exposure
  - ALS-PDC: Links to Cycasin
  - ALS-PDC: Links to L-BMAA
  - ALS-PDC and Phytosterols
  - Biomedical Relevance beyond the Western Pacific Region
  - Summarizing the Evidence: ALS-PDC and Cycad Toxins
- Chapter 12. Environmental Exposures and Risks for Parkinson’s Disease
  - Introduction
  - Environmental Exposures
  - Discussion and Recommendations
- Chapter 13. Parkinson’s Disease: Mechanisms, Models, and Biological Plausibility
  - Description of Parkinson’s Disease
  - Genetic Etiology of PD
  - Environmental Contributors to PD
  - Classes of Environmental Toxicants Associated with PD
  - Animal Models Relevant to PD
  - Alternative Models
  - Emerging Frontiers and Future Directions
- Chapter 14. Genetic Models of Parkinson’s Disease: Behavior, Signaling, and Pathological Features
  - Introduction
  - Desirable Characteristics of an Animal Model for PD
  - Methods to Generate Genetic Models of Disease
  - Genetic Mouse Models for PD
  - Autosomal Recessive Mutations
  - Conclusions
- Chapter 15. Alzheimer’s Disease and the Search for Environmental Risk Factors
  - Introduction
  - History and Biological Context
  - Clinical and Study Design Considerations
  - Early Disease Recognition and Biomarkers Influence Study Design
  - Considering Risk Factors
  - Examples of Environmental Risk Factors
  - Conclusions
- Chapter 16. Environmental Factors and Amyotrophic Lateral Sclerosis: What Do We Know?
  - Introduction
  - Epidemiology and Challenges to the Study of Amyotrophic Lateral Sclerosis
  - Environmental Risk Factors for Amyotrophic Lateral Sclerosis
  - Antioxidants and Amyotrophic Lateral Sclerosis
  - Future Research Considerations
- Chapter 17. Gene–Environment Interactions in Huntington’s Disease
  - Huntington’s Disease: Onset, Genetics, Protein, and Models
  - Natural History of Huntington’s Disease and Related Disorders
  - Animal Models of Huntington’s Disease and the Study of Environmental Factors
  - Biological Functions of the Huntingtin Protein
  - Environmental Influences in Huntington’s Disease: Lifestyle Effects
  - Environmental Influences in Huntington’s Disease: Metals
  - Conclusions
- Chapter 18. Neuroinflammation in Neurological Dysfunction and Degeneration
  - Inflammation and Neurodegeneration: Clues from Epidemiological Studies
  - Direct and Indirect Induction of Chronic Neuroinflammation
  - Neuroinflammation and Neurological Dysfunction: Modulating Behavior
  - Neuroinflammation in Neurodegeneration: Recapitulating Progressive Neuronal Death
  - Therapeutic Implications: Breaking the Cycle
  - Conclusions
- Chapter 19. Late Neurological Effects of Early Environmental Exposures
  - Methodological Challenges
  - Early-Life Exposure and Later Cognitive Status
  - Early-Life Exposure and Later Psychiatric Status
  - Early-Life Exposures and Neuroimaging in Adolescence and Adulthood
  - Epigenetic Processes as a Mechanism of Developmental Programming
  - Early-Life Lead Exposure and AD
  - Epigenetic Markers as Biomarkers of Environmental Exposures
  - Conclusion
- Chapter 20. Environmental Factors in Neurodegenerative Disorders: Summary and Perspectives
Index

Michael Aschner

Dr. Aschner serves as the Harold and Muriel Block Chair in Molecular Pharmacology at Albert Einstein College of Medicine. He served on numerous toxicology panels (Institute of Medicine, US Environmental Protection Agency, Center for Disease Control), and is a member of the Neurotoxicology and Alcohol study section (NIH). Research in our lab focuses on the following topics: (1) Modulation of C. elegans genes (aat, skn-1, daf-16) that are homologous to mammalian regulators of MeHg uptake and cellular resistance will modify dopaminergic neurodegeneration in response to MeHg exposure. (2) Under conditions of MeHg-induced oxidative stress, Nrf2 (a master regulator of antioxidant responses) coordinates the upregulation of cytoprotective genes that combat MeHg-induced oxidative injury, and that genetic and biochemical changes that negatively impact upon Nrf2 function increase MeHg’s neurotoxicity. (3) PARK2, a strong PD genetic risk factor, alters neuronal vulnerability to modifiers of cellular Mn status, particularly at the level of mitochondrial dysfunction and oxidative stress. Our studies are designed to (1) shed novel mechanistic insight into metal-induced neurodegeneration; (2) identify targets for genetic or pharmacologic modulation of neurodegenerative disorders; (3) increase knowledge of the pathway involved in oxidative stress; (4) develop improved research models for human disease using knowledge of environmental sciences.

Affiliations and expertise

Professor, Department of Molecular Pharmacology, Albert Einstein College of Medicine, NY, USA

Lucio G. Costa

Dr. Lucio G. Costa is Professor of Toxicology at the University of Washington in Seattle, and of Pharmacology/Toxicology at the University of Parma Medical School. He received a doctorate in Pharmacology from the University of Milano in 1977, and was a postdoctoral fellow at the University of Texas at Houston. He is a member of several national and international professional organizations, a Fellow of the Academy of Toxicological Sciences, and a European Certified Toxicologist. He received various award for his scientific accomplishments, including the Achievement Award from the Society of Toxicology. He serves in various editorial capacities for several toxicology journals, and is an active manuscript and grant reviewer. Dr. Costa has been the member of dozens of panels and committees at the national and international level dealing with toxicology and risk assessment issues. He has chaired and/or organized symposia at scientific meetings in the United States and internationally. He has been teaching classes in the area of toxicology, neurotoxicology and pharmacology to graduate and medical students for 30 years. He keeps an active research program in the area of neurotoxicology.

Affiliations and expertise

Professor of Toxicology, University of Washington, Seattle, WA, USA

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