Front Cover

Linking Environmental Exposure to Neurodevelopmental Disorders

Copyright

Contents

Contributors

Preface

Chapter One: The Neurodevelopmental Toxicity of Lead: History, Epidemiology, and Public Health Implications

1. Neuropsychological Function

1.1. Other Neuropsychological Endpoints

2. Academic Achievement

3. ADHD

4. Anti-Social Behavior

5. Neuroimaging

6. Potential Effect Modifiers of Lead Neurotoxicity

7. Developmental Origins of Neurodegenerative Disease

8. Critical Windows of Vulnerability

9. Conclusion

References

Further Reading

Chapter Two: Neurodevelopmental Effects of Mercury

1. Introduction

2. Inorganic Elemental Mercury

3. Ionic Inorganic Mercury

4. Organic Mercury

5. Neurodevelopmental Toxicity: Hg Versus ASD

6. Potential Molecular Target of Hg and Mechanism of Neurotoxicity

6.1. Thiol (-SH) and Selenol (-SeH) Groups

6.2. Hg and Other Neurotoxicants: Additive Effect?

7. Concluding Remarks

Acknowledgments

References

Further Reading

Chapter Three: Connections Between Manganese Neurotoxicity and Neurological Disease

1. Introduction

2. Established Roles of Mn in Neurological Dysfunction

2.1. Role of Mn in Neurodegenerative Disease

2.2. Connections Between Mn Neurotoxicity to DA Neural Dysfunction

2.3. Role of Mn Neurotoxicity in Neurodevelopment Disorders

3. Evidence to Support a Link Between Mn and Other Neurological Disorders

3.1. Restless Legs Syndrome

3.1.1. Genetic Contribution to RLS

3.1.2. RLS and Role of Iron

3.1.3. Co-regulation of Fe and Mn Brain Transport

3.1.3.1. Divalent Metal Transporter 1

3.1.3.2. Transferrin and Transferrin Receptor

3.1.3.3. Ferroportin as an Exporter

3.1.4. Dopaminergic Alterations in RLS

3.1.5. Summary of the Putative Role of Mn Neurotoxicity in RLS

3.2. Attention Deficit Hyperactive Disorder

3.3. Tourette Syndrome

4. Conclusions

References

Chapter Four: Developmental Neurotoxicity of Alcohol: Effects and Mechanisms of Ethanol on the Developing Brain

1. Introduction

2. Fetal Alcohol Spectrum Disorders

2.1. Fetal Alcohol Syndrome

2.2. Partial (p)FAS

2.3. Alcohol-Related Neurodevelopmental Disorders

2.4. Alcohol-Related Birth Defects

3. Neurobehavioral Deficits in FASD

4. FASD and Brain Structure

5. Animal Models for FASD

6. Mechanisms Involved in FASD

6.1. Genetics and Early Development Gene Expression

6.2. Cell-Cell Interaction

6.3. Neuronal Apoptosis

6.4. Glial Cells

6.5. Neuronal Plasticity

6.6. Epigenetics

6.7. Oxidative Stress

7. FASD Treatments

Acknowledgments

References

Chapter Five: Possible Mechanisms of Developmental Neurotoxicity of Organophosphate Insecticides

1. Effects on DNA

2. Free Radical Formation

3. Neurite Outgrowth and Effects on the Cytoskeleton

4. Need for in vitro Studies to Include Astrocytes

5. Altering the Morphogenetic Action of AChE

6. Monoamine Neurotransmitter Systems

7. Endocannabinoid System

8. Disruption of Emotional/Social Behavior

9. Conclusions

References

Chapter Six: Chronic Nicotine Effects on Memory and Nicotine Self-Administration: Age of Exposure is Key

1. Introduction

2. Prenatal Nicotine Exposure

3. Adolescent Nicotine Exposure

4. Adult Nicotine Exposure

5. Nicotine Exposure During Aging

6. Conclusions

Acknowledgments

References

Chapter Seven: Developmental Neurotoxicity of Endocrine Disruptor Chemicals: A Challenge for Behavioral Toxicology

1. The Developing Brain: Plasticity and Vulnerability

2. Impact of Endogenous Hormones in Brain and Behavior Development

3. Developmental Neurotoxicity of Low-Dose Chemicals

4. Fifty Years of EDC Research: From Avian Eggshell Thinning to Child NDDs

4.1. Key Uncertainties and Hot Issues in the Debate on EDCs

5. The Developing Brain as a Target of BPA

5.1. Neurobehavioral Effects of BPA in Children

5.2. Behavioral Toxicology of BPA in Rodent Models

5.3. BPA Effects on Brain and Behavior: Are They Mediated by its Estrogen-Like Activity?

6. Chlorpyrifos as a Neuroendocrine Disruptor

6.1. Neurobehavioral Effects of CPF in Children

6.2. Neurobehavioral Toxicology of CPF in Rodent Models

6.3. CPF Effects on Brain and Behavior are Also Mediated by Hormones?

7. Conclusions

Acknowledgments

References

Chapter Eight: Neurodevelopment: Inflammation Matters

1. Introduction

2. Key Stages of Neurodevelopment

3. Glia: Roles in Neurodevelopment and Neuroimmune Function

3.1. Microglia

3.1.1. Role of Microglia in Neurogenesis

3.1.2. Role of Microglia in Synaptic Pruning

3.1.3. Role of Microglia in Myelination

3.1.4. Role of Microglia in Angiogenesis

3.2. Astrocytes

3.2.1. Role of Astrocytes in Neuronal Survival

3.2.2. Role of Astrocytes in Axonal Guidance

3.2.3. Role of Astrocytes in Synaptic Pruning

3.2.4. Role of Astrocytes in Synaptogenesis

3.2.5. Role of Astrocytes in Angiogenesis

3.3. Oligodendrocytes

4. Clinical Evidence for the Detrimental Impact of Inflammation on Neurodevelopment

4.1. Cerebral Palsy

4.2. Autism Spectrum Disorders

4.3. Schizophrenia

5. Preclinical Models of Inflammation and Neurodevelopment

5.1. Maternal Inflammation

5.1.1. LPS

5.1.2. Poly(I:C)

5.2. Postnatal Inflammation

5.2.1. LPS

5.2.2. Cytomegalovirus

5.2.3. Hypoxia-Ischemia

5.2.4. Intraventricular Hemorrhage

5.3. Therapeutic Strategies

5.3.1. NAC

5.3.2. Minocycline

5.3.3. 7,8-Dihydrooxyflavone

5.3.4. Melatonin

5.3.5. Paliperidone

5.3.6. Hyaluronidase

6. Conclusions

References

Chapter Nine: Enduring Behavioral and Brain Impacts of Prenatal Stress and Childhood Adversity and Their Potential Multig ...

1. Introduction

2. Defining Stress

3. Biological Mediation of Stress

4. Considerations for Stress Research

4.1. Demographic Features of Stress

4.2. Not All Stress is Bad: Pathology vs. Resilience as an Outcome

5. Not all Stressors are Equal

5.1. Acute vs. Chronic Stressor Presentation and Habituation/Adaptation

5.2. Types of Stressor

5.3. Sex Differences in Stress Outcomes and Mechanisms

5.4. Implications

5.5. Enduring Consequences of Developmental Stress

5.6. Prenatal Stress

5.7. Childhood Adversity

6. Cumulative Effects of Stress

7. Multigenerational and Transgenerational Effects of Developmental Stress

8. Mechanisms of Biological Programming of Prenatal Stress and Childhood Adversity

8.1. Changes in HPA Axis Function

8.2. Catecholamine Changes

8.3. Maternal Immunity

8.4. Oxidative Stress and Reactive Oxygen Species

8.5. Neuroactive Steroids

8.6. Tryptophan and Serotonin

8.7. Gut-Brain Axis

8.8. Epigenetic Changes and Transgenerational Effects

9. Conclusions and Research Needs

References

Back Cover