Handbook of Developmental Neurotoxicology

William Slikker Jr., Louis W. Chang, William Slikker, Jr.

• Publisher: Academic Press
• Year: 1998
• eBook ISBN: 9780080533438
• Topic: Biological Sciences
• Subtopic: Neuroscience
• Index: Biological Sciences

The Handbook of Developmental Neurotoxicology provides a comprehensive account of the impacts, mechanisms, and clinical relevances of chemicals on the development of the nervous system. The book is written by internationally recognized experts on developmental neurotoxicology, covering subjects from basic neuro-development to toxic syndromes induced by various chemicals. It is an important text for both students and professionals who are interested in developmental neurobiology and neurotoxicology.- Written by internationally recognized experts on developmental neurotoxicology- Includes extensive references- Well illustrated with diagrams, charts and tables- Provides coverage of basic neurobiology as well as neurotoxicology

Part I

Cellular and Molecular Morphogenesis of the Nervous System

Introduction

Louis W. Chang

Developmental neurotoxicology involves the study of adverse effects on the developing nervous system induced by biological, chemical, or physical agents. It is therefore important to understand the various stages and factors that are critical in the morphogenic development of the nervous system, such as neuronal differentiation, neuronal migration, cell-cell interactions, neuritic developments, synaptogenesis, and myelinogenesis. The cellular events in the maturation and cytoarchitectural development of the central nervous system (CNS) are underlied by a series of molecular elements and processes such as cytoskeletal elements, adhesion molecules, signal transductions, and so on. The role of these elements and processes in both normal and chemically intoxicated brains is presented and discussed in Part I.

The developing CNS is a constantly remodeling organ with active neuronal differentation, migration, synaptogenesis, and circuitry establishments. Chapter 1 by Karl F. Jensen introduces and discusses all these basic processes of morphogenesis of the brain. Factors such as hormonal and nutritional homeostasis, xenobiotic metabolism, and the development of the blood–brain barrier that influence the development of the brain are also presented. The normal development and function of the nervous system can only be achieved if all these critical processes and stages of development remain intact. Obviously, any disturbance or disruption of these processes by exogenous chemicals will result in pathologic and functional (neurobehavioral) changes of the brain.

The CNS is uniquely different from other organ systems by having a complex circuitry of communication network between various nervous cells, neuronal groups, and the glial elements. The abilities of developing nerve cells and glial elements to migrate to their proper and “predestined” positions, recognition of the target cells, and signaling are largely influenced and directed by cad-herins, a family of calcium-dependent cell adhesion molecules. In Chapter 2, Gerald B. Grunwald provides a detailed presentation and discussion on the cadherin adhesion molecules and their critical roles in the development of both the CNS and the PNS. An informative account on the structural and functional diversity of the cadherin molecules, the regulations and expressions of these molecules in relation to neural development, nuclear and ganglionic organization, axonal growth, and fiber tract development is provided and discussed.

Another characteristic feature of nerve cells, different from other cell types, is the existence of neuronal processes or neurites for the establishment of the communicative network (circuitry) among the nerve cells. The neuritic development is critically controlled by the cytoskeletal components. The fundamental structures and roles of cytoskeleton in developing neurites (dendrites and axons) is presented and discussed in Chapter 3 by Gerald Audesirk and Teresa Audesirk. The regulation of cytoskeleton by intracellular calcium and by protein phosphorylation, the relationship between cytoskeleton and growth cone formation, and the roles of adhesion, attraction, and repulsion in pathfinding of the growth cones are also discussed in conjunction with neuritic initiation and elongation. Various neurotoxicants such as lead, mercury, and ethanol are known to affect neuritic development. These toxicants and their toxic actions on the developing neurites are provided to illustrate chemical impact on the developing nervous system.

One of the most fundamental functions of the nervous system is impulse transmission along the axons of the neurons. The myelin sheath surrounding the axons serves as an insulator and facilitates such impulse transmission. Development of the myelin is most active at an early neonatal age. In Chapter 4 by G. Jean Harry and Arrel D. Toews, the basic structures, morphogenesis, and chemistry of myelin are presented. Molecular aspects of myelin assembly, axon-glial interactions, myelin disorders, and dysmyelination-demyelination induced by toxic chemicals are also discussed.

It is obvious that a single neurotoxicant (e.g., lead, mercury) can exert its toxic influence and action on one or combinations of developmental parimeters (e.g., cadherin adhesion molecules, cytoskeleton, cell migration, neuritic development, synaptogenesis, myelina- tion). Investigators must avoid the “tunnel vision” mentality, but approach the problem or issue with a broad view and the understanding that neural development involves multiple factors, processes and stages. Any given developmental neurotoxicant can affect multiple factors and events at the same time. Neurotoxicology is a complex issue, this complexity is even more so in the situation of developmental neurotoxicology.

Chapter 1

Brain Morphogenesis and Developmental Neurotoxicology

Karl F. Jensen Neurotoxicology Division, National Health and Environmental Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711

Susan M. Catalano Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720

I. Introduction

II. Instructive and Selective Processes Shape Brain Morphogenesis

A. Intercellular Signals Organize the Brain Primordium

B. Time and Place of Origin of a Neuron in the Germinal Neuroepithelium Is Predictive of Its Adult Location

C. Axonal Pathfinding Involves Attractive and Repulsive Cues

D. Cell Death and Collateral Loss Refine Connectivity

E. Dendritic Form Is Shaped by Afferent Innervation

F. Activity Patterns Synaptic Connections

G. Neurotransmitters and Hormones Regulate Morphogenetic Events

H. Astrocytes Induce Expression of the Blood–Brain Barrier in Endothelial Cells

III. Developmental Neurobehavioral Disorders Result from the Disruption of Morphogenesis

A. Mental Retardation Results from the Disruption of Diverse Morphogenetic Signals

B. Schizophrenia Is Associated with Structural Alterations Indicative of Alterations in Development

C. Predominance of Structural and Functional Alterations May Be a Reflection of the Relative Disruption of Instructive and Selective Morphogenetic Processes

IV Convergence of Genetic and Environmental Influences May Increase the Severity and Incidence of Developmental Neurobehavioral Disorders

A. Developmental Neurotoxicants Disrupt Morphogenetic Signals

B. Homeostatic Processes Protect the Developing Brain from Xenobiotic Insult

C. Interactions between Genetic and Environmental Factors Influence Homeostatic and Morphogenetic Processes

V. Summary

Abbreviations:

APP amyloid precursor protein

BMP bone morphogenetic proteins

Ci Cubitus Interuptus

Dix distalless

DS Down syndrome

Emx empty spiracles

EN engrailed

FGF fibroblast growth factor

HASAS hydrocephalus as a result of stenosis of the Aqueduct of Sylvius

Mad Mothers against decaptaplegic

MAP2 microtubule-associated protein 2

MAPK mitogen-activated protein kinase

MASA mental retardation, aphasia, shuffling gaits and adducted thumbs

NMD A N-methyl-d-aspartate

NRC National Research Council

Otx orthodenticle

PCB polychlorinated biphenyls

PKC protein kinase C

ptc patched

Shh Sonic hedgehog

smo smothered

T3 triiodothyrione

T4 thyroxine

TGF-β transforming growth factor β

VEGF vascular endothelial growth factor

Wnt wingless.

I Introduction

A postulate of developmental neurotoxicology is that particular toxicants can cause mo...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright page
• Dedication
• Contributors
• Foreword
• Preface
• Part I: Cellular and Molecular Morphogenesis of the Nervous System
• Part II: Developmental Biology/Toxicology
• Part III: Synaptogenesis and Neurotransmission
• Part IV: Nutrient and Chemical Disposition
• Part V: Behavioral Assessment
• Part VI: Clinical Assessment and Epidemiology
• Part VII: Specific Neurotoxic Syndromes
• Part VIII: Risk Assessment
• Index