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Life and Death in the Nervous System

Life and Death in the Nervous System

C. F. Ibanez | T. Hokfelt | L. Olson | K. Fuxe | H. Jornvall | D. Ottoson

(1995)

Additional Information

Abstract

Life and Death in the Nervous System

Table of Contents

Section Title Page Action Price
Front Cover Cover
Life and Death in the Nervous System: Role of Neurotrophic Factors and their\rReceptors iii
Copyright Page iv
Table of Contents v
Preface ix
A Memorial Symposium for Hakan Persson xiii
List of Contributors xvii
Part I: Structure-Function Relationships and Mechanismsof Action of Neurotrophic Factors 1
Chapter 1. Insights into Neurotrophic Factor Function from Structural Analyses 3
Introduction 3
Identification of New Structural Folds and Motifs 6
Identification of Functionally Important Features 9
Future Prospects and Challenges 13
Acknowledgements 13
References 14
Chapter 2. Functional Analysis of Receptor Binding Determinants in the Neurotrophin Family 19
Introduction 19
Determinants of Binding to p75LNGFR in BDNF, NT-3 and NT-4 21
Biological Activities of Mutant BDNF and NT-3 Deficient in Binding to p75LNGF 24
Disruption of Binding to p75LNGFR in NT-4 Reduces Responsiveness in Neuronal Cells Co-expressing TrkB and p75LNGF 28
Similarities and Differences in the Way Neurotrophins Interact with p75LNGFR 28
Role of p75LNGFR in Regulating Biological Responsiveness to NT-4 32
Acknowledgements 34
References 34
Chapter 3. Signal Transduction by Trk Receptors 37
Introduction 37
Acknowledgements 48
References 48
Chapter 4. On the Mechanisms by Which Neurotrophic Factors Regulate Neuronal Survival and Cell Death 55
Introduction 55
Experimental Systems 56
Neuronal Apoptosis 57
Prevention of Apoptotic Death by Neurotrophic Factors: A Post-translational Mechanism for PC12 Cells 57
Death After Withdrawal of Trophic Support: Contrasting Roles of Transcription/Translation In PC12 Cells and Neurons 58
The Cell Cycle/Apoptosis Hypothesis 58
Support for the Cell Cycle/Apoptosis Hypothesis in the Case of Non-Neuronal Cells 59
Concordance of PC1 2 Cell Behavior with the Cell Cycle/Apoptosis Hypothesis: Independence of Apoptosis from Transcription orTranslation Explained 60
Application of the Cell Cycle/Apoptosis Hypothesis to Sympathetic Neurons and Neuronally Differentiated PC12 Cells: Dependence of Apoptosis on Transcription and Translation Explained 61
Current Tests of the Cell Cycle/Apoptosis Hypothesis 62
Oxidative Stress and Trophic Factor Deprivation as a Cause of Neuronal Apoptosis: Convergence of Initially Independent Pathways 64
Conclusions and Perspectives 65
Acknowledgements 65
References 65
Part II: Neurotrophic Factor Receptors: Expression and Function 69
Chapter 5. The Interaction Between the Two Receptors for NGF, p75LNTR and TrkA 71
Introduction 71
The Two NGF Receptors 72
References 83
Chapter 6. Interactions Between NGF Receptors, TrkA and p75 87
Introduction 87
Results 88
Discussion 91
Acknowledgements 95
References 95
Chapter 7. Receptors and Signaling PathwaysUsed by the Neurotrophins, CNTF and a New Family of Neurotrophic Factors, the EFLs 99
Introduction 99
The Receptor System Used by the Neurotrophins 101
The Receptor System Used by CNTF and Implications for Other Cytokine Receptor Systems 103
Different Classes of Neurotrophic Factors can Collaborate 106
Mice with Disruptions in Genes for Neurotrophic Factors or their Receptors Provide Unexpected Insights into In Vivo Function 107
Identification and Cloning of a New Family of Factors that Utilize the EPH -related Receptor Tyrosine Kinases 108
Conclusions 109
References 111
Chapter 8. Embryonic Expression of Neurotrophin Trk Receptor mRNAsWithin Sensory Neurons: Chicken Development as a Model 113
Introduction 113
Results 115
Discussion 126
References 129
Part III: Development: Proliferation and Differentiation 131
Chapter 9. Brain-Derived Neurotrophic Factor and the Developing Chick Retina 133
Introduction 133
Results 135
Discussion 137
References 140
Chapter 10. Neurotrophins in the Developing Avian Visual System 143
Introduction 143
Detection of Neurotrophin mRNA Expression 144
Neurotrophin Expression in the Developing Retina 145
Neurotrophin Expression in Optic Tectum 149
Acknowledgements 151
References 151
Chapter 11. The Regulation and Function of NGFReceptors in Normal and Immortalized Sympathoadrenal Progenitor Cells 155
Introduction 155
The Function of NGF Receptors in Differentiating MAH Cells 159
Neurotrophins Regulate an Ontogenic Switch in Neurotrophin Responsiveness During Sympathetic Development 161
Conclusions 174
Acknowledgements 176
References 176
Chapter 12. Sequential Trophic Regulation of Sympathetic Neuroblast Development by NT-3 and NGF 181
Introduction 181
Results 182
Discussion 188
Acknowledgements 191
References 191
Chapter 13. Effects of Brain-Derived Neurotrophic Factor and Neurotrophin-4 on Embryonic Rat Sensory Neurons 193
Introduction 193
Results 196
Discussion 199
Acknowledgements 203
References 203
Chapter 14. Role of Neurotrophic Factors in Cerebellar Development 205
Introduction 205
Expression of Neurotrophins and Their Receptors in the Rodent Cerebellum 206
Regulation and Action of NT-3 in the Developing Rat Cerebellum 208
Effect of Different Neurotrophins on Survival of Cerebellar Granule Neurons 209
Possible Interactions of the Neurotrophins with Neurotransmitters in the Cerebellum 210
Multiple Neurotrophic Factors are Present in the Developing Cerebellum 211
Conclusions 212
References 212
Chapter 15. Neurotrophins, Depolarization and Second Messengers Interact to Control Serotonergic Neuronal Differentiation 217
Introduction 217
Results 219
Discussion 225
Acknowledgements 229
References 229
Part IV: Control of Neurotrophic Factor Synthesis and Release 233
Chapter 16. Structure and Regulation of BDNF and NT-4 Genes 235
Introduction 235
Structure and Regulation of the BDNF Gene 237
Structure and Regulation of the NT-4 Gene 247
Acknowledgements 255
References 255
Chapter 17. Neurotrophins as Mediators of Neuronal Plasticity 261
Introduction 261
Characterization of Constitutive and Activity-dependent NGF Release from Hippocampal Neurons 264
Localization of NGF Stores in Transfected Hippocampal Neurons in Culture 267
Site of Constitutive and Activity-Dependent NGF Secretion 268
Evidence for a Neurotrophin-Mediated Transmitter Release from Neurons Expressing the Corresponding Trk Receptors 270
Conclusions 272
References 273
Chapter 18. Stimulation of Neurotrophic Factor Expression: Links to Different Forms of Brain Plasticity 275
Introduction 275
Physiological Activity and Expression of Neurotrophic Factor mRNAs 277
Deafferentation and the Expression of Neurotrophic Factor mRNAs 285
Discussion 289
Acknowledgements 292
References 292
Chapter 19. Molecular Determinants of Neurotrophin Actions in the Brain 297
Synergistic Trophic Actions in the Basal Forebrain 297
Regulation of NGF Expression in Hippocampal Astrocytes 304
Summary 309
Acknowledgements 310
References 310
Part V: Gene Knock-Outs 313
Chapter 20. Neurotrophins: Essential Functions In Vivo Characterized by Targeted Gene Mutations 315
Introduction 315
Results 316
Discussion 325
Acknowledgements 330
References 331
Chapter 21. Requirement for Neurotrophin-3 in the Development of the Muscle Proprioceptive System 335
Introduction 335
Results and Discussion 336
Acknowledgements 342
References 342
Chapter 22. Life and Death in Mice Without Trk Neurotrophin Receptors 345
Introduction 345
Structural Features of the Trk Family of Receptors 346
trkA Expression 351
trkB Expression 351
trkC Expression 352
Genetic Analysis of Trk Receptor Function 354
Sensory and Sympathetic Defects in Mice Lacking TrkA Receptors 354
Neuronal Defects in frfcB-Targeted Mice 356
Proprioceptive Defects in Mice Lacking TrkC Receptors 357
References 358
Part VI: Neurotrophic Factor Function In Vivo: Degeneration and Regeneration 361
Chapter 23. Specificity, Synergy and Autocrine Roles of the Neurotrophins and CNTF 363
Introduction 363
Neurotrophin-3 Specificity for Proprioceptive Neurons: Biology and Clinical Implications 365
Synergy of BDNF and CNTF Towards Motor Neurons: Biology and Clinical Implications 368
A BDNF Autocrine Loop Maintains Survival of Adult Neurons 371
Conclusions 375
Acknowledgements 376
References 376
Chapter 24. Therapeutic Use of Neurotrophic Factors 379
Introduction 379
Peripheral Sensory Neuropat 380
Parkinson's Disease 384
Alzheimer's Disease 385
Huntington's Disease 385
Ischemic Stroke and Acute Brain Injury 386
Acknowledgements 387
References 388
Chapter 25. NGF-Dependent Regeneration of Adult Septal Cholinergic Axons into Denervated Hippocampus 391
Introduction 391
References 398
Chapter 26. Glial Cell Line-Derived Neurotrophic Factor Augments Midbrain Dopaminergic Circuits In Vivo 401
Introduction 401
Results 403
Discussion 409
References 413
Chapter 27. Neurotrophins in Kindling Epilepsy:Neuronal Protection or Induction of Sprouting and Epileptogenesis? 417
Introduction 417
Changes of Neurotrophin and Trk Levels after Kindled Seizures 418
Changes of Neurotrophin and Trk Levels After Other Brain Insults 422
Regulation of Neurotrophin and Trk Gene Expression after BrainInsults 426
Functional Effects of Seizure-Induced Neurotrophin Changes 428
Concluding Remarks 434
Acknowledgements 434
References 435
Concluding Remarks 439
Chapter 28. Future Directions and Clinical Prospects of Neurotrophic Factor Research 441
Introduction 441
New Neurotrophic Factors 442
Intracellular Pathways and Effects 443
Regulation of Synthesis 443
Release of Neurotrophic Factors 444
Trophic Factor Receptors 445
Signal Transduction Mechanisms 445
Sites of Action 446
Preclinical Considerations: Routes of Administration 447
Clinical Trials: Ongoing and Future Possibilities 449
Acknowledgements 450
References 450
Hâkan Persson Publication List 453
Subject Index 467
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