The Role of Glia in Neurotoxicity, Second Edition

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ISBN: 9780849317941 | 0849317940
Cover: Hardcover
Copyright: 12/28/2004

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Presenting the latest research in glial cell function gleaned from new techniques in imaging and molecular biology, this second edition covers multiple aspects of glial cells, including morphology, physiology, pharmacology, biochemistry, pathology, and their involvement in the pathophysiology of neurological diseases. The book examines the interactions between glial cells and neurons during development, adulthood, and senescence, followed by specific examples of directly mediated glial neurotoxicity. It includes coverage of miscellaneous topics in glial physiology/biochemistry and advances in current knowledge and understanding of glial physiology and biochemistry.

Neural Precursor Cells and Toxicant Action: Addressing the Analysis of Low-Level Toxicant Exposure

(28)

Mark Noble

Indroduction

(1)

General Concepts: Purified Populations and Clonal Analyses

(1)

Current Knowledge of CNS Precursor Cell Biology Allows a Detailed Analysis of Neurotoxicity of Toxicants

(6)

Overview

(2)

The GRP Cell as an Ancestor of the O-2A/OPC

(1)

Regional Differences in Precursor Cell Biology

(1)

Cortical O-2A/OPCs Appear to Be Specialized to Undergo Extended Self-Renewal

(1)

Cortex-Derived O-2A/OPCs Exhibit Reduced Responsiveness to Inducers of Oligodendrocyte Generation

(1)

Cortex-Derived O-2A/OPCs Appear to Be Intrinsically Different from Cells from Optic Nerve or Chiasm

(1)

Developmental Relevance of Regional and Age-Related Differences of O-2A/OPCs

(1)

Intracellular Redox State as a Modulator of Precursor Cell Function

(1)

The Importance of Sublethal Changes in Precursor Cell Function in Developmental Maladies

(1)

Toxicant Exposure and the Developing CNS

(4)

Alcohol and Nicotine

(1)

Toxicant Exposure

(3)

Mercury Toxicity for Precursor Cells Occurs with Exposure Levels as Low as 4--5 Parts per Billion

(1)

Challenges for the Toxicology of the Future: Analysis of Low-Dose Exposure and Combinatorial Insults

(13)

References

(12)

The Role of Microglia in Neurotoxicity

(12)

Wolfgang J. Streit

Introduction

(1)

Historical Overview

(1)

Current Questions

(6)

Microglial Responses to Neuronal Injury

(1)

Axotomy of Motor Neurons

(1)

Cerebral Ischemia

(1)

Neurotoxic Injury

(1)

Ricinus communis Agglutinin (RCA60)

(1)

Kainic Acid

(1)

Trimethyltin (TMT)

(1)

Significance of Microglial Reaction

(1)

Microglial Neurotoxicity

(1)

Conclusions and Future Directions

(4)

Acknowledgments

(1)

List of Abbreviations

(1)

References

(4)

Schwann Cell Neurotoxicity

(20)

Arrel D. Toews

G. Jean Harry

Pierre Morell

Introduction

(1)

Ontogenic Development and Differentiation of Schwann Cells

(2)

PNS Myelin Formation

(2)

Myelin Composition and Metabolism

(1)

Generalized Responses of Schwann Cells to Injury

(1)

Perturbations Involving PNS Myelin and Schwann Cells

(1)

Classification of Neurotoxic Insults to Schwann Cells and Myelin

(1)

Survey of Selected Schwann Cell/Myelin Toxicants

(1)

Tellurium Neuropathy as Model for Primary Toxicant-Induced Demyelination

(2)

The Future

(9)

References

(8)

Function of Astrocyte Cytochrome P450 in Control of Xenobiotic Metabolism

(12)

Ralf Peter Meyer

Benedikt Volk

Rolf Knoth

Introduction

(1)

CYP in the Brain---An Overview

(1)

Localization of CYP-Containing Astrocytes In Vivo

(4)

CYP in Astrocytes of Brain Border Lines

(1)

Blood--Brain Barrier

(1)

Cerebrospinal Fluid-Brain Barrier

(3)

Glial CYPs in Parenchymal Structures of the Brain: Cortex and Cerebellum

(1)

Functional Aspects of CYPs in Astrocytes

(2)

Induction of Specific CYP Isoforms

(1)

Metabolic Activity of CYPs

(1)

Conclusions

(4)

Acknowledgments

(1)

References

(4)

The Reactive Astrocyte

(20)

Michael D. Norenberg

Introduction

(1)

Morphologic Findings

(3)

General Aspects of Astrogliosis

(2)

Timing

(1)

Age of Subject

(1)

Location

(1)

Proliferation

(1)

Migration

(1)

Heterogeneity of Reactive Astrocytes

(1)

Reversion to an Immature Phenotype

(1)

Origin/Sources of Reactive Astrocytes

(1)

Special Features of Reactive Astrocytes

(1)

Gap Junctions

(1)

Ion Channels

(1)

Glutamate Transport

(1)

Glucose Transport

(1)

Factors Produced by Reactive Astrocytes

(1)

Regulators of Reactive Astrocytes

(1)

Signal Transduction Pathways

(2)

Significance of Astrogliosis

(1)

Perspectives

(10)

Acknowledgments

(1)

References

(9)

Molecular Mechanisms of Glutamate and Glutamine Transport in Astrocytes

(18)

Stefan Broer

The Concept of the Glutamate/Glutamine Cycle

(1)

Glutamate Uptake

(3)

EAAT1 (GLAST), EAAT2 (GLT-1) (System XAG)

(1)

Molecular Characteristics

(1)

Localization

(1)

Mechanism

(1)

Physiological Role

(1)

4F2hc/xCT (System x-c)

(1)

Molecular Characteristics and Localization

(1)

Mechanism

(1)

Physiological Function

(1)

Transport of Glutamine

(8)

Principles of Glutamine Transport

(1)

ASCT2 (System ASC)

(1)

Molecular Characteristics

(1)

Localization

(1)

Mechanism

(1)

Physiological Role

(1)

LAT1, LAT2 (System L)

(1)

Molecular Characteristics and Localization

(1)

Mechanism

(1)

Physiological Role

100

(1)

SNAT1, SNAT2 (ATA1, ATA2)* (System A)

100

(1)

Molecular Characteristics

100

(1)

Localization

100

(1)

Mechanism

100

(1)

Physiological Role

101

(1)

SNAT3, SNAT5 (SN1, SN2)* (System N)

101

(1)

Molecular Characteristics

101

(1)

Localization

101

(1)

Mechanism

102

(1)

Physiological Role

103

(1)

4F2hc/y+LAT2 (System y+L)

103

(1)

Molecular Characteristics

103

(1)

Mechanism

103

(1)

Physiological Role

103

(2)

Transporters Not Yet Defined at the Molecular Level

105

(1)

Summary

105

(6)

List of Abbreviations

105

(1)

References

105

(6)

Neuronal--Astrocytic Interactions (TCA Cycling)

111

(14)

Ursula Sonnewald

Arne Schousboe

Helle S. Waagepetersen

Compartmentation of Brain Metabolism

111

(2)

The Glutamate--Glutamine Cycle

113

(1)

The GABA--Glutamate--Glutamine Cycle

113

(1)

The Intracellular Compartmentation Concept

114

(1)

Metabolic Interactions in Brain Studied by 13C NMRS

114

(1)

13C NMRS Analyses of Neuronal--Glial Interactions in Animal Models of Epilepsy

115

(1)

Metabolism Studied by 13C NMRS in Brain Cell Culture

116

(1)

Pyruvate Recycling

116

(1)

13C NMRS Analysis of the Effects of Thiopental on Brain Cells in Culture

117

(1)

Glutamate Uptake and Release

117

(1)

Glutamate Metabolism

117

(1)

Concluding Remarks

118

(7)

Acknowledgment

118

(1)

List of Abbreviations

118

(1)

References

118

(7)

Cytokines in Neuronal--Glial Interaction

125

(16)

Barbara Viviani

Marina Marinovich

Introduction

125

(3)

Cytokines that Contribute to Neurodegeneration and Neurotoxicity

128

(3)

IL-1β and ``Its Family''

128

(1)

Molecular Mechanisms Involved in IL-1β-Induced Neuronal Damage

128

(1)

Regulation of IL-1 Bioavailability and Bioactivity

129

(1)

Tumor Necrosis Factor-α

129

(1)

Chemokines

130

(1)

Cytokines with Ambiguous Behavior

131

(1)

Interleukin-6 (IL-6)

131

(1)

Regulation of IL-6 Bioactivity and Intracellular Signaling

132

(1)

Cytokines that Support Neuroprotection

132

(2)

Interleukin-10 (IL-10)

132

(1)

Transforming Growth Factor-β (TGF-β)

132

(1)

Control of TGF-β Bioactivity and Intracellular Signaling

133

(1)

Erythropoietin (EPO)

133

(1)

Molecular Mechanisms Involved in EPO Effect

134

(1)

Conclusions

134

(7)

List of Abbreviations

134

(1)

References

135

(6)

Signaling Mechanisms Underlying Toxicant-Induced Gliosis

141

(32)

Krishnan Sriram

James P. O'Callaghan

Introduction

141

(1)

Reactive Gliosis Is Associated with Several Forms of Neural Injury and Neurodegeneration: Astroglial and Microglial Responses

142

(3)

GFAP Expression as an Index of Astrogliosis

145

(3)

The GFAP Gene

145

(2)

Regulation of GFAP Gene Expression

147

(1)

Signal Transduction Pathways Associated with Gliosis

148

(7)

Protein Phosphorylation Cascades and Gliosis

148

(1)

Use of Focused Microwave Irradiation to Preserve In Vivo Steady-State Protein Phosphorylation

148

(1)

The MAPK Pathway: Its Involvement in Neuronal and Glial Response to Injury

149

(3)

The JAK/STAT Pathway: Its Involvement in Neuronal and Glial Response to Injury

152

(1)

Phosphorylation of JAK2/STAT3 as a Key Signaling Pathway for Astrogliosis

153

(2)

Applying Genomic, Proteomic, and Protein Phosphorylation Analyses to Identify Potential Ligands Activating Signaling Pathways Associated with Reactive Astrogliosis

155

(5)

Conclusion

160

(13)

References

160

(13)

Astrocyte Cellular Swelling: Mechanisms and Relevance to Brain Edema

173

(18)

Herminia Pasantes-Morales

Rodrigo Franco

Introduction

173

(1)

Astrocyte Swelling in Ischemia, Trauma, and Epilepsies

174

(5)

Extracellular K+ Clearance and Astrocyte Swelling

175

(1)

Glutamate-Induced Astrocyte Swelling

175

(2)

Lactacidosis

177

(1)

Arachidonic Acid and Generation of Reactive Oxygen Species

178

(1)

Mechanical Stress

179

(1)

The Role of Gap Junctions in Astrocyte Swelling

179

(1)

Astrocyte Swelling in Hepatic Encephalopathy

180

(2)

Hyposmotic Astrocyte Swelling and Regulatory Volume Decrease

182

(2)

Volume Regulatory Mechanisms Do Not Operate in Cytotoxic Edema

184

(1)

Aquaporins and Astrocyte Swelling

185

(1)

Consequences of Astrocyte Swelling

186

(1)

Why Do Astrocytes Swell More than Neurons?

187

(4)

Acknowledgments

187

(1)

References

187

(4)

Astrocyte Metallothioneins and Physiological and Pathological Consequences to Brain Injury

191

(16)

Juan Hidalgo

Introduction

191

(1)

Central Nervous System Metallothioneins Are Differentially Expressed

192

(1)

Metallothionein-I&II Are Preferentially Expressed in Reactive Astrocytes

192

(1)

Expression of Metallothionein-III in the Central Nervous System

192

(1)

Transgenic Mice Demonstrate Important Roles of Metallothioneins in the Central Nervous System

193

(14)

Metallothionein-I&II Are Essential Proteins for Coping with Brain Damage

193

(2)

Metallothionein-III Shows Different Functions

195

(1)

Acknowledgments

196

(1)

List of Abbreviations

196

(1)

References

197

(10)

Peripheral Benzodiazepine Receptor Imaging in Glial Cells: Molecular Sensors of Brain Pathology

207

(14)

Tomas R. Guilarte

Introduction

207

(1)

Central and Peripheral Benzodiazepine Receptors

208

(1)

Peripheral Benzodiazepine Receptors: Pharmacology, Cellular Localization, and Molecular Composition

209

(1)

Function of the Peripheral Benzodiazepine Receptor

210

(1)

Peripheral Benzodiazepine Receptors as Molecular Sensors of Brain Pathology

210

(1)

Cellular Contributions to Increased PBR Levels in Brain Injury

211

(1)

Peripheral Benzodiazepine Receptor Imaging In Vitro and In Vivo to Assess Brain Pathology

212

(2)

In Vitro Imaging

212

(1)

In Vivo PBR Imaging Using Position Emission Tomography

213

(1)

Potential Use of PBR Ligands for Therapeutic Interventions

214

(7)

Acknowledgments

214

(1)

References

214

(7)

Astrocyte--Neuronal Interaction and Oxidative Injury: Role of Glia in Neurotoxicity

221

(16)

Valerie Chock

Rona Giffard

Introduction

222

(1)

Generation, Interconversion, and Scavenging of Reactive Oxygen Species

222

(2)

Superoxide

222

(1)

Hydrogen Peroxide

222

(1)

Nitric Oxide

223

(1)

Low-Molecular-Weight Antioxidants: Glutathione (GSH), Ascorbic Acid, and α-Tocopherol

223

(1)

Oxidative Stress, Astrocytes, and Mechanisms of Ischemic Brain Injury

224

(2)

Astrocytes Are Central to Brain Antioxidant Defense

224

(1)

Astrocytes Bolster Neuronal Antioxidant Defenses

225

(1)

Oxidative Stress and Apoptosis

225

(1)

Oxidative Stress and Gene Expression

225

(1)

Astrocytes Protect by Production of Neurotrophic Factors

226

(1)

Astrocyte Glutamate Uptake Is Impaired by Oxidative Stress

226

(1)

Direct Contribution of Astrocytes to Neurotoxicity

226

(1)

Glia Can Promote Inflammation

226

(1)

Astrocytes as a Source of Toxic NO

227

(1)

Neuroprotective Strategies that Include Reducing Oxidative Stress

227

(3)

Antioxidant Enzymes

227

(1)

Antiapoptotic Proteins

228

(1)

Heat-Shock Proteins

228

(2)

Common Themes in Neurodegeneration: A Role for Astrocytes in Oxidative Injury

230

(1)

Alzheimer's Disease

230

(1)

Amyotrophic Lateral Sclerosis (ALS)

230

(1)

Parkinson's Disease

230

(1)

Conclusion

231

(6)

References

231

(6)

Astrocytes in Acute Energy Deprivation Syndromes

237

(14)

E. Spencer Williams

Amanda D. Phelka

David E. Ray

Martin A. Philbert

Introduction

237

(2)

Acute Energy Deprivation Syndromes

237

(1)

Pathology

238

(1)

Astrocytes

238

(1)

Clinical Syndromes

239

(1)

mtDNA Disorders

239

(1)

Leigh's Syndrome

239

(1)

MELAS/MERRF

239

(1)

Wernicke's/Thiamine Deficiency

240

(1)

Experimental Models of AEDS

240

(2)

Chlorosugars

240

(1)

6-Aminonicotinamide

240

(1)

Nitroaromatic Chemicals (Misonidazol/Metronidazol/m-Dinitrobenzene)

240

(2)

Molecular Mechanisms of Astrocyte Cell Death

242

(3)

Mitochondrial Dysfunction

242

(1)

Lactic Acidosis

242

(1)

SDH Inhibition

242

(1)

ATP Loss

243

(1)

ROS/Oxidative Stress

244

(1)

Mitochondrial Permeability Transition

244

(1)

Bcl-2 Proteins

245

(1)

Summary

245

(6)

References

246

(5)

The Role of Multiple Drug Resistance in Neuroglial Survival: Lessons from Human Epileptic Brain

251

(12)

Kerri L. Hallene

Kelly M. Kight

Gabriele Dini

Damir Janigro

Blood--Brain Barrier

251

(1)

Astroglia and Its Role in Neurotoxicity

252

(2)

p53 and p21

254

(1)

Multiple Drug Resistance Protein

254

(1)

Multiple Drug Resistance Gene and Protein Expression in Human Epileptic Brain

255

(1)

p53, MDR, and Epilepsy

256

(1)

p53 and Brain Tumors

256

(1)

Antiepileptic Drugs and Apoptosis

257

(1)

Current Questions

257

(1)

Conclusions and Perspectives

258

(5)

Acknowledgments

258

(1)

References

258

(5)

Pathogenesis of HIV-Associated Dementia and Multiple Sclerosis: Role of Microglia and Astrocytes

263

(16)

Alireza Minagar

Paul Shapshak

J. Steven Alexander

Introduction

263

(1)

Macrophage/Microglia (MØ)

264

(1)

HIV-1-Associated Dementia

264

(1)

MØ and Astrocyte Activation in HAD

265

(3)

Multiple Sclerosis

268

(1)

MØ versus Astrocytes: Their Effects on the Th1/Th2 Cells and Their Interactions in Pathogenesis of MS

269

(2)

Conclusions

271

(8)

Acknowledgments

271

(1)

List of Abbreviations

271

(1)

References

272

(7)

Possible Detrimental Role of Astrocytic Activation during the Subacute Phase of Permanent Focal Cerebral Ischemia in the Rat

279

(20)

Takao Asano

Narito Tateishi

Takashi Mori

Introduction

280

(1)

Alterations in the Infarct Volume after pMCAO in the Rat

280

(2)

Properties and Cytotoxicity of S100B

282

(1)

Results of Experiments Using the Rat pMCAO Model

283

(4)

The Number of TUNEL-Positive Cells in the Peri-Infarct Area

283

(1)

Determination of the S100B Levels in the CSF and the Brain Tissue in the Peri-Infarct Area

283

(1)

Immunohistochemical Study

284

(1)

Expression of iNOS in Reactive Astrocytes

285

(2)

Properties and In Vitro and In Vivo Effects of ONO-2506

287

(4)

Effects of ONO-2506 on the Infarct Volume after pMCAO

288

(1)

Effects of ONO-2506 on the Neurological Deficits

288

(1)

Effects of ONO-2506 on the Extracellular Levels of Glutamate after tMCAO in the Rat

289

(1)

Effects of Astrocytic Proteins on Cognitive Functions and Neuronal Survival

290

(1)

Chronic Neurodegeneration in Remote Areas after tMCAO or pMCAO in the Rat

291

(1)

Increased Vulnerability to Focal Ischemia in Human Apolipoprotein E4 Knock-In Mice

292

(1)

Concluding Remarks

293

(6)

References

294

(5)

Role of Microglia and Astrocytes in Alzheimer's Disease

299

(14)

Peter Schubert

Stefano Ferroni

Introduction

299

(1)

Reactive Microglia: Neurotoxic versus Beneficial Effects

300

(1)

Signaling Underlying the Escalating Glia Reactions

301

(2)

Role of Astrocytes

303

(1)

Possible Pathomechanisms of Neuronal Death

304

(3)

β-Amyloid-Mediated Neurotoxicity

304

(1)

Oxidative Neuronal Damage

305

(1)

Excitotoxic Neuronal Damage

305

(2)

Summary and Conclusions

307

(6)

References

308

(5)

Developmental Effects of Xenobiotics on Thyroid Hormone Regulation in the CNS with Emphasis on Glial Function

313

(16)

Offie P. Soldin

Introduction

314

(1)

The Effects of Thyroid Hormone and Its Deficits on Neurodevelopment

315

(1)

Thyroid Hormone Regulation at the Nuclear Level

315

(1)

Thyroid Hormone Coordinates Maturational Processes in a Regional and Temporal Pattern

316

(1)

Thyroid Hormone Deficiency Affects Glial Function---The Rat Model

316

(1)

Glia Mediate Thyroid Hormone Action

316

(2)

The Role of Glia Thyroid Hormone Receptors

317

(1)

Thyroid Hormone Increases Glial Cell Proliferation and Maturation

317

(1)

Nongenomic Transcriptional Regulation of Cell Structure Proteins by Thyroid Hormones

318

(1)

Deiodinases in Glia and Control of Brain T3 Concentrations

318

(2)

Deiodinases in the Brain

318

(1)

DII in Tanycytes

319

(1)

DII in Astrocytes

319

(1)

The Timing of Oligodendrocyte Development Is Regulated by Thyroid Hormones

319

(1)

Thyroid Hormone Gene Regulation

319

(1)

Alterations in Thyroid Hormone Regulation

320

(2)

The Role of Iodine

320

(1)

The Effects of Iodine Deficiency

321

(1)

Goitrogens

321

(1)

Dietary Goitrogens

321

(1)

Environmental and Other Goitrogens

321

(1)

Polychlorinated Biphenyls

322

(1)

Summary

322

(7)

Acknowledgments

323

(1)

References

323

(6)

Astrocytes in Ammonia Neurotoxicity: A Target, a Mediator, and a Shield

329

(14)

Jan Albrecht

Introduction

329

(1)

Ammonia in Neurological Disorders: Epidemiology and Symptoms

330

(1)

Astrocyte as a Metabolic Target of Ammonia

331

(2)

Glutamine Synthesis in Astrocytes and the Glutamine--Glutamate Cycle: A Key Route of Ammonia Metabolism in the Brain

331

(1)

Bioenergetic Failure

332

(1)

Oxidative and Nitrosative Stress

332

(1)

Peripheral Benzodiazepine Receptor: Mediator of Ammonia-Induced Oxidative Stress and Mitochondrial Dysfunction in Astrocytes

333

(1)

Mechanisms of Ammonia-Induced Astrocytic Swelling

333

(1)

Contribution of Astrocytes to the Ammonia-Induced Changes in Neural Transmission

334

(1)

Glutaminergic Transmission

334

(1)

GABAergic Transmission

335

(1)

Ammonia and Astroglia-Derived Neuromodulators: Focus on Neuroprotection

335

(1)

Taurine

335

(1)

Kynurenic Acid

336

(1)

Conclusions and Forthcoming Issues

336

(7)

References

337

(6)

Alcohol and Glia in the Developing Brain

343

(12)

Lucio G. Costa

Kevin Yagle

Annabella Vitalone

Marina Guizzetti

Introduction

343

(1)

Ethanol and Glial Cell Proliferation

344

(3)

Ethanol and Glial Cell Death

347

(1)

Relevance of Ethanol--Glia Interactions in Fetal Alcohol Syndrome

348

(7)

Acknowledgments

349

(1)

References

349

(6)

Zinc Homeostatic Proteins and Glia

355

(12)

William F. Silverman

Free Zinc in the CNS

355

(2)

Metallothioneins

357

(1)

Zinc Transporters

357

(1)

Zinc, Zinc Homeostatic Proteins, and Glia

358

(9)

Acknowledgments

361

(1)

References

361

(6)

Iron and Glial Toxicity

367

(12)

James R. Connor

Xuesheng Zhang

Poonlarp Cheepsunthorn

Introduction

367

(1)

Brain Injury and Iron Accumulation in Glia

368

(1)

Oligodendrocytes and Iron

368

(2)

What Role Does Iron Play in the Vulnerability of Oligodendrocytes to Physiological Stresses?

369

(1)

Evidence that Cytokine-Mediated Toxicity in Oligodendrocytes Is Iron Mediated

369

(1)

A Relationship between Iron, Microglia, and Oligodendrocytes

370

(1)

Iron and Microglia

370

(1)

Iron and Astrocytes

371

(2)

Iron, Oxidative Stress, and Excitotoxicity in Astrocytes

372

(1)

Conclusion

373

(6)

References

373

(6)

Astroglia and Methylmercury Neurotoxicity

379

(16)

Gouri Shanker

Tore Syversen

Judy L. Aschner

Michael Aschner

Introduction

379

(1)

Astrocytes, MeHg, and GSH

380

(2)

MeHg and Astrocytes

380

(1)

GSH Biosynthesis in Brain and Its Role in the Maintenance of Redox Homeostasis

380

(1)

Association between MeHg Neurotoxicity and GSH Levels

381

(1)

Inhibitory Effects of MeHg on EAA, Cystine, and Cysteine Transport

382

(1)

EAA Uptake Inhibition

382

(1)

Cystine Uptake Inhibition

382

(1)

Cysteine Uptake Inhibition

383

(1)

Role of cPLA2 in MeHg Neurotoxicity

383

(1)

Role of ROS in MeHg Neurotoxicity

384

(4)

Biochemical Studies

384

(1)

Confocal Microscopic Studies

384

(4)

Conclusions

388

(7)

Acknowledgments

389

(1)

References

389

(6)

Manganese Dynamics, Distribution, and Neurotoxicity

395

(22)

Vanessa A. Fitsanakis

Stephanie J. Garcia

Michael Aschner

Introduction

395

(1)

Current Questions

396

(8)

At and Across the Blood--Brain Barrier

396

(2)

Mn Levels in the Brain

398

(1)

Dynamics and Distribution in Glia

399

(2)

Manganese Interactions with Glutamine Synthetase

401

(1)

Neurochemical Components

402

(1)

Dopamine

403

(1)

Glutamate

403

(1)

GABA

404

(1)

Manganese, Mitochondrial Inhibition, and Reactive Oxygen Species Production

404

(2)

Manganese and Magnetic Resonance Studies

406

(1)

Conclusions and Future Directions

407

(10)

Acknowledgments

407

(1)

Abbreviations

407

(1)

References

408

(9)

Astroglia and Lead Neurotoxicity

417

(22)

Evelyn Tiffany-Castiglioni

Yongchang Qian

Introduction

417

(7)

Effects of Lead on Gene and Protein Expression

424

(9)

Regulation of Gene Expression

424

(2)

Genes in Development

426

(1)

Glutamine Synthetase (GS)

427

(1)

Glial Fibrillary Acidic Protein (GFAP)

428

(1)

Stress-Responsive Genes

429

(1)

Glucose-Regulated Protein 78 (GRP78)

430

(1)

Tumor Necrosis Factor-α (TNF-α)

431

(2)

Conclusions and Future Directions

433

(6)

Acknowledgments

433

(1)

References

433

(6)

Role of Glia in MPTP Toxicity and Parkinson's Disease

439

(6)

Lucio G. Costa

Michael Aschner

Introduction

439

(1)

MPTP and Astrocytes

439

(3)

Glia and Parkinson's Disease

442

(3)

References

442

(3)

Index

445

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The Role of Glia in Neurotoxicity, Second Edition

Summary

Table of Contents

Supplemental Materials