The Role of Glia in Neurotoxicity, Second Edition

1794fm.pdf......Page 1
The Role of Glia in Neurotoxicity, Second Edition......Page 2
Preface......Page 4
Pierre Morell Tribute for The Role of Glia in Neurotoxicology......Page 6
Editors......Page 9
Contributors......Page 10
Contents......Page 14
CONTENTS......Page 17
Table of Contents......Page 0
1.1 INTRODUCTION......Page 18
1.2 GENERAL CONCEPTS: PURIFIED POPULATIONS AND CLONAL ANALYSES......Page 19
1.3.1 Overview......Page 20
1.3.2 The GRP Cell as an Ancestor of the O-2A/OPC......Page 22
1.3.3.1 Cortical O-2A/OPCs Appear to Be Specialized to Undergo Extended Self-Renewal......Page 23
1.3.3.2 Cortex-Derived O-2A/OPCs Exhibit Reduced Responsiveness to Inducers of Oligodendrocyte Generation......Page 24
1.3.3.4 Developmental Relevance of Regional and Age-Related Differences of O-2A/OPCs......Page 25
1.4 INTRACELLULAR REDOX STATE AS A MODULATOR OF PRECURSOR CELL FUNCTION......Page 26
1.5 THE IMPORTANCE OF SUBLETHAL CHANGES IN PRECURSOR CELL FUNCTION IN DEVELOPMENTAL MALADIES......Page 27
1.6.2 Toxicant Exposure......Page 28
1.6.3 Mercury Toxicity for Precursor Cells Occurs with Exposure Levels as Low as 4–5 Parts per Billion......Page 31
1.7 CHALLENGES FOR THE TOXICOLOGY OF THE FUTURE: ANALYSIS OF LOW-DOSE EXPOSURE AND COMBINATORIAL INSULTS......Page 32
REFERENCES......Page 33
2.1 INTRODUCTION......Page 44
2.2 HISTORICAL OVERVIEW......Page 45
2.3.1.1 Axotomy of Motor Neurons......Page 46
2.3.1.3.1 Ricinus communis Agglutinin (RCA60)......Page 47
2.3.1.3.2 Kainic Acid......Page 48
2.3.1.3.3 Trimethyltin (TMT)......Page 49
2.3.1.4 Significance of Microglial Reaction......Page 50
2.3.2 Microglial Neurotoxicity......Page 51
REFERENCES......Page 52
3.1 INTRODUCTION......Page 56
3.2 ONTOGENIC DEVELOPMENT AND DIFFERENTIATION OF SCHWANN CELLS......Page 57
3.3 PNS MYELIN FORMATION......Page 59
3.4 MYELIN COMPOSITION AND METABOLISM......Page 61
3.6 PERTURBATIONS INVOLVING PNS MYELIN AND SCHWANN CELLS......Page 62
3.7 CLASSIFICATION OF NEUROTOXIC INSULTS TO SCHWANN CELLS AND MYELIN......Page 63
3.8 SURVEY OF SELECTED SCHWANN CELL/MYELIN TOXICANTS......Page 64
3.9 TELLURIUM NEUROPATHY AS MODEL FOR PRIMARY TOXICANT-INDUCED DEMYELINATION......Page 65
3.10 THE FUTURE......Page 67
REFERENCES......Page 68
4.1 INTRODUCTION......Page 75
4.2 CYP IN THE BRAIN—AN OVERVIEW......Page 76
4.3.1.2 Cerebrospinal Fluid–Brain Barrier......Page 77
4.3.2 Glial CYPs in Parenchymal Structures of the Brain: Cortex and Cerebellum......Page 80
4.4.1 Induction of Specific CYP Isoforms......Page 81
4.4.2 Metabolic Activity of CYPs......Page 82
REFERENCES......Page 83
5.1 INTRODUCTION......Page 87
5.2 MORPHOLOGIC FINDINGS......Page 88
5.3.6 Heterogeneity of Reactive Astrocytes......Page 91
5.3.8 Origin/Sources of Reactive Astrocytes......Page 92
5.5 FACTORS PRODUCED BY REACTIVE ASTROCYTES......Page 93
5.7 SIGNAL TRANSDUCTION PATHWAYS......Page 95
5.8 SIGNIFICANCE OF ASTROGLIOSIS......Page 96
5.9 PERSPECTIVES......Page 97
REFERENCES......Page 98
CONTENTS......Page 107
6.2.1.1 Molecular Characteristics......Page 108
6.2.1.3 Mechanism......Page 109
6.2.1.4 Physiological Role......Page 110
6.3.1 Principles of Glutamine Transport......Page 111
6.3.2.3 Mechanism......Page 112
6.3.3.2 Mechanism......Page 113
6.3.4.3 Mechanism......Page 114
6.3.5.2 Localization......Page 115
6.3.5.3 Mechanism......Page 116
6.3.6.3 Physiological Role......Page 117
REFERENCES......Page 119
7.1 COMPARTMENTATION OF BRAIN METABOLISM......Page 124
7.3 THE GABA–GLUTAMATE–GLUTAMINE CYCLE......Page 126
7.5 METABOLIC INTERACTIONS IN BRAIN STUDIED BY 13C NMRS......Page 127
7.6 13C NMRS ANALYSES OF NEURONAL–GLIAL INTERACTIONS IN ANIMAL MODELS OF EPILEPSY......Page 128
7.8 PYRUVATE RECYCLING......Page 129
7.9.2 Glutamate Metabolism......Page 130
REFERENCES......Page 131
8.1 INTRODUCTION......Page 137
8.2.1.1 Molecular Mechanisms Involved in IL-1beta–Induced Neuronal Damage......Page 140
8.2.2 Tumor Necrosis Factor-alfha......Page 141
8.2.3 Chemokines......Page 142
8.3.1 Interleukin-6 (IL-6)......Page 143
8.4.2 Transforming Growth Factor-beta (TGF-beta)......Page 144
8.4.3 Erythropoietin (EPO)......Page 145
LIST OF ABBREVIATIONS......Page 146
REFERENCES......Page 147
9.1 INTRODUCTION......Page 153
9.2 REACTIVE GLIOSIS IS ASSOCIATED WITH SEVERAL FORMS OF NEURAL INJURY AND NEURODEGENERATION: ASTROGLIAL AND MICROGLIAL RESPONSES......Page 154
9.3.1 The GFAP Gene......Page 157
9.3.2 Regulation of GFAP Gene Expression......Page 159
9.4.2 Use of Focused Microwave Irradiation to Preserve In Vivo Steady-State Protein Phosphorylation......Page 160
9.4.3 The MAPK Pathway: Its Involvement in Neuronal and Glial Response to Injury......Page 161
9.4.4 The JAK/STAT Pathway: Its Involvement in Neuronal and Glial Response to Injury......Page 164
9.4.5 Phosphorylation of JAK2/STAT3 as a Key Signaling Pathway for Astrogliosis......Page 165
9.5 APPLYING GENOMIC, PROTEOMIC, AND PROTEIN PHOSPHORYLATION ANALYSES TO IDENTIFY POTENTIAL LIGANDS ACTIVATING SIGNALING PATHWAYS ASSOCIATED WITH REACTIVE ASTROGLIOSIS......Page 167
REFERENCES......Page 172
10.1 INTRODUCTION......Page 184
10.2 ASTROCYTE SWELLING IN ISCHEMIA, TRAUMA, AND EPILEPSIES......Page 185
10.2.2 Glutamate-Induced Astrocyte Swelling......Page 186
10.2.3 Lactacidosis......Page 188
10.2.4 Arachidonic Acid and Generation of Reactive Oxygen Species......Page 189
10.3 THE ROLE OF GAP JUNCTIONS IN ASTROCYTE SWELLING......Page 190
10.4 ASTROCYTE SWELLING IN HEPATIC ENCEPHALOPATHY......Page 191
10.5 HYPOSMOTIC ASTROCYTE SWELLING AND REGULATORY VOLUME DECREASE......Page 193
10.6 VOLUME REGULATORY MECHANISMS DO NOT OPERATE IN CYTOTOXIC EDEMA......Page 195
10.7 AQUAPORINS AND ASTROCYTE SWELLING......Page 196
10.8 CONSEQUENCES OF ASTROCYTE SWELLING......Page 197
REFERENCES......Page 198
11.1 INTRODUCTION......Page 202
11.2.2 Expression of Metallothionein-III in the Central Nervous System......Page 203
11.3.1 Metallothionein-I&II Are Essential Proteins for Coping with Brain Damage......Page 204
11.3.2 Metallothionein-III Shows Different Functions......Page 206
LIST OF ABBREVIATIONS......Page 207
REFERENCES......Page 208
12.1 INTRODUCTION......Page 217
12.2 CENTRAL AND PERIPHERAL BENZODIAZEPINE RECEPTORS......Page 218
12.3 PERIPHERAL BENZODIAZEPINE RECEPTORS: PHARMACOLOGY, CELLULAR LOCALIZATION, AND MOLECULAR COMPOSITION......Page 219
12.5 PERIPHERAL BENZODIAZEPINE RECEPTORS AS MOLECULAR SENSORS OF BRAIN PATHOLOGY......Page 220
12.6 CELLULAR CONTRIBUTIONS TO INCREASED PBR LEVELS IN BRAIN INJURY......Page 221
12.7.1 In Vitro Imaging......Page 222
12.7.2 In Vivo PBR Imaging Using Positron Emission Tomography......Page 223
REFERENCES......Page 224
CONTENTS......Page 230
13.2.2 Hydrogen Peroxide......Page 231
13.2.4 Low-Molecular-Weight Antioxidants: Glutathione (GSH), Ascorbic Acid, and alpha-Tocopherol......Page 232
13.3.1 Astrocytes Are Central to Brain Antioxidant Defense......Page 233
13.3.5 Astrocytes Protect by Production of Neurotrophic Factors......Page 234
13.4.1 Glia Can Promote Inflammation......Page 235
13.5.1 Antioxidant Enzymes......Page 236
13.5.3 Heat-Shock Proteins......Page 237
13.6.3 Parkinson’s Disease......Page 239
REFERENCES......Page 240
14.1.1 Acute Energy Deprivation Syndromes......Page 257
14.1.3 Astrocytes......Page 258
14.2.1.2 MELAS/MERRF......Page 259
14.3.3 Nitroaromatic Chemicals (Misonidazol/Metronidazol/m-Dinitrobenzene)......Page 260
14.4.1.2 SDH Inhibition......Page 262
14.4.1.3 ATP Loss......Page 263
14.4.1.5 Mitochondrial Permeability Transition......Page 264
14.5 SUMMARY......Page 265
REFERENCES......Page 266
15.1 BLOOD–BRAIN BARRIER......Page 270
15.2 ASTROGLIA AND ITS ROLE IN NEUROTOXICITY......Page 271
15.4 MULTIPLE DRUG RESISTANCE PROTEIN......Page 273
15.5 MULTIPLE DRUG RESISTANCE GENE AND PROTEIN EXPRESSION IN HUMAN EPILEPTIC BRAIN......Page 274
15.7 p53 AND BRAIN TUMORS......Page 275
15.9 CURRENT QUESTIONS......Page 276
REFERENCES......Page 277
16.1 INTRODUCTION......Page 281
16.3 HIV-1-ASSOCIATED DEMENTIA......Page 282
16.4 MØ AND ASTROCYTE ACTIVATION IN HAD......Page 283
16.5 MULTIPLE SCLEROSIS......Page 286
16.6 MØ VERSUS ASTROCYTES: THEIR EFFECTS ON THE TH1/TH2 CELLS AND THEIR INTERACTIONS IN PATHOGENESIS OF MS......Page 287
LIST OF ABBREVIATIONS......Page 289
REFERENCES......Page 290
CONTENTS......Page 296
17.2 ALTERATIONS IN THE INFARCT VOLUME AFTER pMCAO IN THE RAT......Page 297
17.3 PROPERTIES AND CYTOTOXICITY OF S100B......Page 299
17.4.2 Determination of the S100B Levels in the CSF and the Brain Tissue in the Peri-Infarct Area......Page 300
17.4.3 Immunohistochemical Study......Page 301
17.4.4 Expression of iNOS in Reactive Astrocytes......Page 302
17.5 PROPERTIES AND IN VITRO AND IN VIVO EFFECTS OF ONO-2506......Page 304
17.5.2 Effects of ONO-2506 on the Neurological Deficits......Page 305
17.5.3 Effects of ONO-2506 on the Extracellular Levels of Glutamate after tMCAO in the Rat......Page 306
17.5.4 Effects of Astrocytic Proteins on Cognitive Functions and Neuronal Survival......Page 307
17.6 CHRONIC NEURODEGENERATION IN REMOTE AREAS AFTER tMCAO OR pMCAO IN THE RAT......Page 308
17.7 INCREASED VULNERABILITY TO FOCAL ISCHEMIA IN HUMAN APOLIPOPROTEIN E4 KNOCK-IN MICE......Page 309
17.8 CONCLUDING REMARKS......Page 310
REFERENCES......Page 311
18.1 INTRODUCTION......Page 316
18.2 REACTIVE MICROGLIA: NEUROTOXIC VERSUS BENEFICIAL EFFECTS......Page 317
18.3 SIGNALING UNDERLYING THE ESCALATING GLIA REACTIONS......Page 318
18.4 ROLE OF ASTROCYTES......Page 320
18.5.1 beta-Amyloid–Mediated Neurotoxicity......Page 321
18.5.3 Excitotoxic Neuronal Damage......Page 322
18.6 SUMMARY AND CONCLUSIONS......Page 324
REFERENCES......Page 325
CONTENTS......Page 329
19.1 INTRODUCTION......Page 330
19.2.1 Thyroid Hormone Regulation at the Nuclear Level......Page 331
19.3 GLIA MEDIATE THYROID HORMONE ACTION......Page 332
19.3.2 Thyroid Hormone Increases Glial Cell Proliferation and Maturation......Page 333
19.4.1 Deiodinases in the Brain......Page 334
19.4.5 Thyroid Hormone Gene Regulation......Page 335
19.5.1 The Role of Iodine......Page 336
19.5.3.2 Environmental and Other Goitrogens......Page 337
19.6 SUMMARY......Page 338
REFERENCES......Page 339
20.1 INTRODUCTION......Page 344
20.2 AMMONIA IN NEUROLOGICAL DISORDERS: EPIDEMIOLOGY AND SYMPTOMS......Page 345
20.3.1 Glutamine Synthesis in Astrocytes and the Glutamine–Glutamate Cycle: A Key Route of Ammonia Metabolism in the Brain......Page 346
20.3.3 Oxidative and Nitrosative Stress......Page 347
20.4 MECHANISMS OF AMMONIA-INDUCED ASTROCYTIC SWELLING......Page 348
20.5.1 Glutaminergic Transmission......Page 349
20.6.1 Taurine......Page 350
20.7 CONCLUSIONS AND FORTHCOMING ISSUES......Page 351
REFERENCES......Page 352
21.1 INTRODUCTION......Page 358
21.2 ETHANOL AND GLIAL CELL PROLIFERATION......Page 359
21.3 ETHANOL AND GLIAL CELL DEATH......Page 362
21.4 RELEVANCE OF ETHANOL–GLIA INTERACTIONS IN FETAL ALCOHOL SYNDROME......Page 363
REFERENCES......Page 364
22.1 FREE ZINC IN THE CNS......Page 370
22.3 ZINC TRANSPORTERS......Page 372
22.4 ZINC, ZINC HOMEOSTATIC PROTEINS, AND GLIA......Page 373
REFERENCES......Page 377
23.1 INTRODUCTION......Page 381
23.3 OLIGODENDROCYTES AND IRON......Page 382
23.3.2 Evidence that Cytokine-Mediated Toxicity in Oligodendrocytes Is Iron Mediated......Page 383
23.4.1 Iron and Microglia......Page 384
23.5 IRON AND ASTROCYTES......Page 385
23.5.1 Iron, Oxidative Stress, and Excitotoxicity in Astrocytes......Page 386
REFERENCES......Page 387
24.1 INTRODUCTION......Page 392
24.2.2 GSH Biosynthesis in Brain and Its Role in the Maintenance of Redox Homeostasis......Page 393
24.2.3 Association between MeHg Neurotoxicity and GSH Levels......Page 394
24.3.2 Cystine Uptake Inhibition......Page 395
24.4 ROLE OF cPLA2 IN MeHg NEUROTOXICITY......Page 396
24.5.2 Confocal Microscopic Studies......Page 397
24.6 CONCLUSIONS......Page 401
REFERENCES......Page 402
25.1 INTRODUCTION......Page 407
25.2.1 At and Across the Blood–Brain Barrier......Page 408
25.2.2 Mn Levels in the Brain......Page 410
25.2.3 Dynamics and Distribution in Glia......Page 411
25.2.4 Manganese Interactions with Glutamine Synthetase......Page 413
25.2.5 Neurochemical Components......Page 414
25.2.5.2 Glutamate......Page 415
25.3 MANGANESE, MITOCHONDRIAL INHIBITION, AND REACTIVE OXYGEN SPECIES PRODUCTION......Page 416
25.4 MANGANESE AND MAGNETIC RESONANCE STUDIES......Page 418
ABBREVIATIONS......Page 419
REFERENCES......Page 420
26.1 INTRODUCTION......Page 428
26.2.1 Regulation of Gene Expression......Page 435
26.2.2 Genes in Development......Page 437
26.2.2.1 Glutamine Synthetase (GS)......Page 438
26.2.2.2 Glial Fibrillary Acidic Protein (GFAP)......Page 439
26.2.3 Stress-Responsive Genes......Page 440
26.2.3.1 Glucose-Regulated Protein 78 (GRP78)......Page 441
26.2.3.2 Tumor Necrosis Factor-alpha (TNF-alpha)......Page 442
REFERENCES......Page 444
27.2 MPTP AND ASTROCYTES......Page 450
REFERENCES......Page 453