Astrocytes in (Patho)Physiology of the Nervous System (eBook)

Preface 6
Acknowledgment 7
Contents 8
Contributors 11
Astrocyte Heterogeneity or Homogeneity? 16
1.1 The Classification Problem 17
1.2 Neurons and Glia 20
1.3 Some Basic Principles of Astroglial Classification 21
1.4 Experiments Relevant to Heterogeneity or Non-Heterogeneity 24
1.5 Envoi 34
References 37
Abbreviations 40
Neural Stem Cells Disguised as Astrocytes 41
2.1 Identification of Neural Stem Cells in the Central Nervous System 41
2.2 Interactions Within the Stem-Cell Niche 47
2.3 Developmental Lineage of Neural Stem Cells 51
2.4 Conclusion 56
References 56
Abbreviations 61
Neurotransmitter Receptors in Astrocytes 62
3.1 Introduction 63
3.2 Glutamate Receptors 66
3.3 GABA Receptors 69
3.4 Purinoreceptors 70
3.5 Glycine Receptors 72
3.6 Cholinoreceptors 72
3.7 Adrenergic Receptors 73
3.8 Concluding Remarks 73
References 74
Abbreviations 80
Specialized Neurotransmitter Transporters in Astrocytes 81
4.1 Glutamate Transporters in the CNS 82
4.2 Sodium- and Chloride-Dependent Neurotransmitter Transporter Family SLC6 in Astrocytes 102
4.3 Concluding Remarks 107
References 108
Abbreviations 116
Connexin Expression (Gap Junctions and Hemichannels) in Astrocytes 118
5.1 Gap Junction Structure 119
5.2 Functions of Gap Junction Channels and Hemichannels 129
5.3 Gating of Gap Junction Channels and Hemichannels/ Pannexin Channels 137
5.4 Gap Junction Alteration in Neuropathology and Hereditary Disease 144
5.5 Regulation of Gene Expression by Glial Gap Junctions 148
References 148
Abbreviations 160
Regulation of Potassium by Glial Cells in the Central Nervous System 162
6.1 Potassium in the Extracellular Space of the Central Nervous System 163
6.2 Overview of K+ Regulatory Mechanisms 164
6.3 Net Uptake of K+ 166
6.4 Potassium Spatial Buffering 168
6.5 Evidence for K+ Spatial Buffering 169
6.6 Potassium Siphoning 171
6.7 Potassium Siphoning and the Regulation of Blood Flow 173
6.8 Relative Importance of K+ Regulatory Mechanisms 173
6.9 Glial Cells and K+ Channels 174
6.10 Kir-Channel Subtypes Expressed in Müller Cells 175
6.11 Kir-Channel Accessory Proteins in Müller Cells: Localization and Function 177
6.12 Impaired Potassium Regulation in Pathological Conditions 180
6.13 Conclusions 180
References 181
Abbreviations 186
Energy and Amino Acid Neurotransmitter Metabolism in Astrocytes 187
7.1 Introduction 187
7.2 Energy Metabolism 188
7.3 TCA Cycle-Related Metabolism and Compartmentation 193
7.4 Amino Acid Metabolism 199
References 202
Abbreviations 210
Calcium Ion Signaling in Astrocytes 211
8.1 Introduction 211
8.2 Modes and Mechanisms of Ca2+ Signaling 212
8.3 Spontaneous Ca2+ Transients and Oscillations 216
8.4 Propagation of Ca2+ Signals 218
8.5 Ca2+ Responses to Transmitters and Other Signaling Molecules 220
8.6 Ca2+ Responses to Neuronal Activity 221
8.7 Store-Operated Ca2+ Entry and Ca2+ Store Refilling 223
8.8 Ca2+-Induced Release of Gliotransmitters 225
8.9 Functional Significance of Ca2+ Signaling 226
8.10 Summary and Conclusion 227
References 228
Abbreviations 234
Astrocytes in Control of the Biophysical Properties of the Extracellular Space 235
9.1 Extracellular Space (ECS) and Extrasynaptic Transmission 235
9.2 Homeostatic Function of Glia 237
9.3 Diffusion in the ECS 238
9.4 Glia and ECS Diffusion Parameters 243
9.5 Conclusion 254
References 255
Abbreviations 260
Structural Association of Astrocytes with Neurons and Vasculature: Defining Territorial Boundaries 261
10.1 Introduction 261
10.2 The Ectodermal Player: Neurons: Polarized Cells with Several Specialized Compartments 262
10.3 The Mesodermal Player: Blood Vessels with Polarized Endothelial Cells and Pericytes 264
10.4 The Joint Player: Astrocytes Polarized Cells with Several Specialized Compartments 266
10.5 The Sites of Inter-Ectodermal Interplay: “Peripheral Astrocyte Processes” (PAPs) 268
10.6 The Sites of Mesodermal-Ectodermal Interplay: “Perivascular Astrocytic Endfeet” (PAE) 275
10.7 Individual Astrocytes Vs. Functional Astrocytic Syncytia: Gap Junctions 280
10.8 Functional Territories and Territorial Boundaries 283
10.9 Summary and Conclusions 290
References 291
Abbreviations 296
Synaptic Information Processing by Astrocytes 297
11.1 Introduction 297
11.2 Intracellular Ca2+ Variations are the Basis of the Astrocyte Excitability 298
11.3 Tripartite Synapse: Reciprocal Communication Between Neurons and Astrocytes 299
11.4 Astrocytes Discriminate the Activity of Different Synaptic Pathways 301
11.5 Astrocytes Integrate Synaptic Information 301
11.6 Astrocyte Ca2+ Signal Modulation is Specific of Some Neurotransmitters 303
11.7 The Modulation of the Astrocyte Ca2+ Signal Depends on the Level of Synaptic Activity 304
11.8 Ca2+ Signal Modulation is Present in Astrocytic Processes 305
11.9 Perspectives and Conclusions 305
References 307
Abbreviations 310
Mechanisms of Transmitter Release from Astrocytes 311
12.1 Amino Acids and Their Derivatives as Astrocytic Transmitters 312
12.2 Nucleotides and Nucleosides as Astrocytic Transmitters 333
12.3 Concluding Remarks 345
References 346
Abbreviations 359
Release of Trophic Factors and Immune Molecules from Astrocytes 361
13.1 The Effects of Astrocytes on Neurons 363
13.2 Molecules Produced by Astrocytes That Impact Neurons 363
13.3 The Identification of Molecules Responsible for Astrocyte Effects on Neurons 372
13.4 Astrocytes Are Heterogeneous 373
13.5 The Role of Astrocytes Changes with Development 374
13.6 The Function of Astrocytes Changes After Injury: The Role of Immune Molecules 375
13.7 Other Molecules That Regulate Astrocytes: Their Role During Injury 376
13.8 Concluding Remarks 379
References 380
Abbreviations 391
Molecular Approaches for Studying Astrocytes 392
14.1 Introduction 392
14.2 Transgenic Approaches 394
14.3 Studying Astrocytes Through Conditional Gene Knockout 404
14.4 Summary 410
References 411
Abbreviations 413
The Tripartite Synapse 415
15.1 What is Gliotransmission? 416
15.2 Gliotransmission Continuously and Dynamically Regulates Synaptic Transmission 417
15.3 Conclusions 421
References 421
Abbreviations 423
Glia-Derived d-Serine and Synaptic Plasticity 424
16.1 Introduction 424
16.2 Regional and Cellular Distributions of d-Serine in the Nervous System 425
16.3 De Novo Synthesis and Degradation of d-Serine in the Nervous System 428
16.4 Release and Clearance of d-Serine 433
16.5 Functions of d-Serine in the Nervous System 437
16.6 Future Directions 442
References 443
Abbreviations 447
Purinergic Signaling in Astrocyte Function and Interactions with Neurons 449
17.1 Intercellular ATP Signaling 450
17.2 ATP Receptors 452
17.3 ATP Release Mechanisms 456
17.4 Extracellular Degradation and Synthesis of ATP 456
17.5 Functional Significance of Purinergic Signaling in Astrocytes 457
17.6 Conclusions 460
References 461
Abbreviations 466
Astrocyte Control of Blood Flow 467
18.1 Functional Hyperemia 468
18.2 Astrocytes and Functional Hyperemia: Origins and Revisions 469
18.3 Astrocytic Characteristics for Cerebrovascular Control 470
18.4 Astrocytes Control Cerebrovascular Diameter 472
18.5 NO: An Important Modulator of Astrocyte-Mediated Cerebral Vessel Control 476
18.6 K+ and Vascular Control by Astrocytes 477
18.7 Astrocyte Ca2+ Signals: Functional Significance? 478
18.8 Norepinephrine and Astrocyte-Mediated Cerebrovascular Control 480
18.9 Astrocytes in Spreading Depression and Cerebrovascular Constriction 481
18.10 Astrocyte-Mediated Vasodilations or Vasoconstrictions? 481
18.11 Astrocytes in Brain Energetics and the Link to Blood Flow 482
18.12 New Players: Pericytes and Vasoactive Interneurons 484
18.13 Conclusion 485
References 486
Abbreviations 492
A Role for Glial Cells of the Neuroendocrine Brain in the Central Control of Female Sexual Development 493
19.1 Neuroendocrine Control of Sexual Development: General Aspects 494
19.2 Glial–neuronal Interactions in the Hypothalamus 495
19.3 Hypothalamic Astrocytes and Glutamate Metabolism 505
19.4 Neuron-to-Glia Communication in the Hypothalamus 506
19.5 Gonadal Steroids and Astrocyte Function 506
19.6 Conclusions 509
References 509
Abbreviations 516
Physiological and Pathological Roles of Astrocyte-mediated Neuronal Synchrony 518
20.1 Introduction 518
20.2 Non-synaptic Mechanisms of Neuronal Synchrony 519
20.3 Can Astrocytes be Considered “Non-neuronal Interneurons”? 523
20.4 Astrocyte and Epilepsy 525
20.5 Conclusions and Perspectives 527
References 528
Abbreviations 530
Role of Ion Channels and Amino-Acid Transporters in the Biology of Astrocytic Tumors 531
21.1 Gliomas 532
21.2 Ion Channels and Glioma Cell Invasion 540
References 545
Abbreviations 549
Connexins and Pannexins: Two Gap Junction Families Mediating Glioma Growth Control 551
22.1 Introduction 551
22.2 Overview of Gap Junctions 552
22.3 Gap Junctions and Cancer 554
22.4 Gap Junctions and Glioma 556
22.5 Summary 563
References 564
Abbreviations 570
The Impact of Astrocyte Mitochondrial Metabolism on Neuroprotection During Aging 572
23.1 Introduction 572
23.2 Astrocyte Bioenergetics 573
23.3 Physiological Changes in Astrocytes During Aging 574
23.4 G-Protein-Coupled Receptor Stimulated IP 578
-Mediated Ca2+ Release in Astrocytes Increases Neuroprotection 578
23.5 Summary 587
References 588
Abbreviations 592
Alexander Disease: A Genetic Disorder of Astrocytes 594
24.1 Introduction 595
24.2 Characteristics of Alexander Disease 595
24.3 GFAP Mutations 612
24.4 Disease Mechanisms 633
24.5 Treatment 641
24.6 Future Directions 642
24.7 Concluding Remarks 643
References 644
Abbreviations 651
Role of Astrocytes in Epilepsy 652
25.1 Introduction 652
25.2 Altered Astrocyte Morphology in Temporal Lobe Epilepsy 653
25.3 Astrocytic Glutamate Release in Epilepsy 654
25.4 Astrocyte Dysfunction in Temporal Lobe Epilepsy 655
25.5 Astrocyte Dysfunction in Other Epilepsy Syndromes 662
25.6 Conclusions and Perspectives 664
References 666
Abbreviations 674
Hepatic Encephalopathy: A Primary Astrocytopathy 675
26.1 Introduction 675
26.2 Astrocyte Pathology in HE 676
26.3 Astrocyte Metabolism in HE 678
26.4 Astrocyte Function in HE 679
26.5 Intercellular Signaling in HE 687
26.6 Inflammation and Proinflammatory Cytokines 688
26.7 Implications for Therapy 688
References 689
Abbreviations 694
Index 695
About the Editors 701