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Hormones in neurodegeneration, neuroprotection, and neurogenesis / edited by Achille G. Gravanis and Synthia H. Mellon. — Weinheim : Wiley-VCH, c2011. – (58.17436/H812) |
Contents
CONTENTS
Part I Estrogens， Progestins， Allopregnanolone and Neuroprotection 1
1 Interactions of Estradiol and Insulin-like Growth Factor-I in Neuroprotection: Implications for Brain Aging and Neurodegeneration 3
1.1 Introduction: Hormones， Brain Aging， and Neurodegeneration 3
1.2 Estradiol， IGF-I， Brain Aging， and Neuroprotection 4
1.3 Molecular Interactions of Estrogen Receptors and IGF-I Receptor in the Brain
1.4 Regulation of IGF-I Receptor Signaling by Estradiol in the Brain 5
1.5 Regulation of Estrogen Receptor Transcriptional Activity by IGF-I in Neural Cells 6
1.6 Implications of the Cross Talk between Estrogen Receptors and IGF-I Receptors for Brain Aging， and Neurodegeneration 6
Acknowledgment 8
References 8
2 Structure-Nongenomic Neuroprotection Relationship of Estrogens and Estrogen-Derived Compounds 13
2.1 Introduction 13
2.2 In vitro Assessments of Structure-Neuroprotective Activity Relationships 14
2.3 In vivo Assessment of Structure-Neuroprotective Activity Relationships 20
2.4 In vitro Assessment of Structure-Cell Signaling Relationships 20
2.5 Summary 24
Acknowledgment 24
References 24
3 Progestins and Neuroprotection: Why the Choice of Progestin Matters 29
3.1 Introduction 29
3.2 The Biology of Progesterone 30
3.3 Membrane-Associated Progesterone Receptors 31
3.4 Progesterone-Induced Protection 32
3.5 Mechanisms Underlying Progesterone's Protective Effects 33
3.6 Medroxyprogesterone Acetate 34
Acknowledgments 37
References 37
4 Endogenous and Synthetic Neurosteroids in the Treatment of Niemann-Pick Type C Disease 41
4.1 Introduction 41
4.2 Niemann-Pick Type C Disease as a Model of Disrupted Neurosteroidogenesis 43
4.3 Steroidogenesis and Neurosteroidogenesis in NP-C 44
4.4 Treatment of NP-C Mice with Allopregnanolone 45
4.5 Mechanism of Allopregnanolone Action: GABAA Receptor 46
4.6 Mechanism of Allopregnanolone Action: Pregnane-X Receptor 48
4.7 Mechanism of Allopregnanolone Action: Reduction of Cellular Oxidative Stress
4.8 Conclusions - Mechanisms of Allopregnanolone Action in Treatment of NP-C and Other Neurodegenerative Diseases 49
Acknowledgments 51
References 51
Part II Glucocorticoids， Dehydroepiandrosterone， Neuroprotection and Neuropathy
5 Glucocorticoids， Developmental "Programming，" and the Risk of Affective Dysfunction 63
5.1 Introduction to Programming 64
5.2 Programming 65
5.3 Glucocorticoids and Fetal Development 66
5.4 Glucocorticoids: the Endocrine Programming Factor 68
5.5 Fetal Tissue Glucocorticoid Sensitivity 72
5.6 Stress and Glucocorticoids: Key Programmers of the Brain 74
5.7 CNS Programming Mechanisms 76
5.8 Glucocorticoid Programming in Humans 78
5.9 Future Perspectives and Therapeutic Opportunities 82
5.10 Overview 83
References 84
6 Regulation of Structural Plasticity and Neurogenesis during Stress and Diabetes; Protective Effects of Glucocorticoid Receptor Antagonists 103
6.1 The Stress Response 103
6.2 HPA Axis and Glucocorticoids 104
6.3 Glucocorticoid Actions 104
6.4 Feedback Regulation 104
6.5 Stress and Depression 105
6.6 Stress-Induced Viability Changes in the Hippocampus: Effect on Function， Volume， Cell Number， and Apoptosis 106
6.7 Effects of Stress on Dendritic Atrophy， Spine， and Synaptic Changes 107
6.8 Adult Hippocampal Neurogenesis 107
6.9 Effect of Stress on Adult Hippocampal Neurogenesis 109
6.10 Normalization of the Effects of Stress on the Hippocampus by Means of GR Blockade 110
6.11 Normalization of Hippocampal Alterations during Diabetes Mellitus Using the GR Antagonist Mifepristone 113
6.12 Concluding Remarks 115
Acknowledgments 115
Disclosure 115
References 116
7 Neuroactive Steroids and Peripheral Neuropathy 121
7.1 Introduction 121
7.2 Regulation of Neuroactive Steroid Responsiveness in Peripheral Nerves 122
7.3 Schwann Cell Responses to Neuroactive Steroids 123
7.4 Sexually Dimorphic Changes of Neuroactive Steroid Levels Induced by Pathology in Peripheral Nerves 126
7.5 Neuroactive Steroids as Protective Agents in PNS 126
7.6 Chemotherapy-Induced Peripheral Neuropathy 128
7.7 Concluding Remarks 129
Acknowledgments 129
References 129
8 Neuroprotective and Neurogenic Properties of Dehydroepiandrosterone and its Synthetic Analogs 137
8.1 Introduction 137
8.2 Neuroprotective and Neurogenic Effects of DHEA in Hippocampal Neurons 138
8.3 Neuroprotective Effects of DHEA in Nigrostriatal Dopaminergic Neurons 140
8.4 Neuroprotective Effects of DHEA in Autoimmune Neurodegenerative Processes
8.5 Neuroprotective Effects of DHEA against Brain Ischemia and Trauma 142
8.6 Signaling Pathways Involved in the Effects of DHEA on Neuronal Cell Fate 144
8.7 Therapeutic Perspectives of DHEA and its Synthetic Analogs in Neurodegenerative Diseases 146
References 147
9 Neurosteroids and Pain 155
9.1 Introduction 155
9.2 General Background on Neurosteroids 155
9.3 Overview on Pain 156
9.4 Involvement of Endogenous Neurosteroids in the Control of Pain 157
9.5 Conclusion 164
Acknowledgments 164
References 164
Part III Polypeptide Hormones and Neuroprotection 171
10 The Insulin/IGF-1 System in Neurodegeneration and Neurovascular Disease 173
10.1 Introduction 173
10.2 Insulin and Insulin Growth Factors 174
10.3 Local versus Systemic Actions 174
10.4 Insulin/IGF Signaling Pathway 175
10.5 The Insulin/IGF Axis in the Brain 176
10.6 Insulin/IGF and Neuroprotection 176
10.7 Alzheimer's Disease 178
10.8 Parkinson's Disease 179
10.9 Vascular Dementia 179
10.10 Neurovascular Degeneration 180
10.11 Conclusion 182
References 182
11 Leptin Neuroprotection in the Central Nervous System 189
11.1 Introduction 189
11.2 Mutation of Leptin or Leptin Receptors 192
11.3 Neurotrophic Role of Leptin 193
11.4 Leptin Neuroprotection against Disorders of the Central Nervous System 193
11.5 Significance 199
References 199
12 Somatostatin and Neuroprotection in Retina 205
12.1 Introduction 205
12.2 Somatostatin and Related Peptides 206
12.3 Somatostatin Receptors and Signaling 206
12.4 Somatostatin and its Receptors in Retina 206
12.5 Localization of Somatostatin Receptors in Retinal Neurons 207
12.6 Somatostatin Receptor Function in Retinal Circuitry 209
12.7 Neuroprotection by Somatostatin Analogs 212
12.8 Mechanisms of SRIF's Neuroprotection 213
12.9 Therapeutic Potential of Somatostatin Agents 216
12.10 Conclusions 217
Acknowledgments 217
Abbreviations 218
References 218
13 Neurotrophic Effects of PACAP in the Cerebellar Cortex 227
13.1 Expression of PACAP and its Receptors in the Developing Cerebellum 227
13.2 Effects of PACAP on Granule Cell Proliferation 229
13.3 Effects of PACAP on Granule Cell Migration 229
13.4 Effects of PACAP on Granule Cell Survival 231
13.5 Effects of PACAP on Granule Cell Differentiation 231
13.6 Functional Relevance 233
Acknowledgments 234
References 234
14 The Corticotropin-Releasing Hormone in Neuroprotection 237
14.1 Introduction 237
14.2 The CRH Family of Proteins and Molecular Signal Transduction 238
14.3 From the Physiology to the Pathophysiology of CRH 239
14.4 CRH and Neurodegenerative Conditions 240
14.5 Protective Activities of CRH 240
14.6 Lessons from the Heart 244
14.7 Outlook 245
References 245
15 Neuroprotective and Neurogenic Effects of Erythropoietin 251
15.1 Introduction 251
15.2 EPO in Models of Neonatal Hypoxic-Ischemic Brain Injury 251
15.3 EPO in Models of Ischemic Stroke in Adults 253
15.4 EPO in Models of Traumatic Brain Injury and Spinal Cord Trauma 257
15.5 EPO in Experimental Autoimmune Encephalomyelitis 257
15.6 EPO in Models of Peripheral Neuropathy 258
15.7 Summary 260
References 260
Part IV Hormones and Neurogenesis 265
16 Thyroid Hormone Actions on Glioma Ceils 267
16.1 Introduction 267
16.2 Origins of Glioma 267
16.3 Glioma Cell Biology 268
16.4 Thyroid Hormone Analogs， Transport， and Metabolism 270
16.5 Thyroid Hormones and Brain Development 270
16.6 Nongenomic Actions of Thyroid Hormones 271
16.7 Hypothyroidism Suppresses Growth of Glioma in Patients 273
16.8 Molecular Mechanisms of Hypothyroidism-Induced Clinical Suppression of Glioma Progression 273
16.9 Future Perspectives 275
References 276
17 Gonadal Hormones， Neurosteroids， and Clinical Progestins as Neurogenic Regenerative Agents: Therapeutic Implications 281
17.1 Introduction 281
17.2 Gonadal Hormones， Neurosteroids， and Neurogenesis 282
17.3 Neurosteroid Regulation of Adult Neurogenesis 290
17.4 Gonadal Steroids， Clinical Progestins， and Neurosteroids as Neuroregenerative Therapeutics: Challenges and Strategies 292
References 295
18 Gonadotropins and Progestogens: Obligatory Developmental Functions during Early Embryogenesis and their Role in Adult Neurogenesis， Neuroregeneration and Neurodegeneration 305
18.1 Introduction 305
18.2 Hormonal Regulation of Human Embryogenesis 305
18.3 Progesterone: an Essential Neurotrophic Hormone during All Phases of Life
18.4 Age-Related Loss of Progesterone: Implications in the Pathophysiology of Neurodegenerative Diseases 314
18.5 Conclusion 318
References 319
19 Human Neural Progenitor Cells: Mitotic and Neurogenic Effects of Growth Factors， Neurosteroids， and Excitatory Amino Acids 331
19.1 Introduction 331
19.2 Neural Stem/Progenitor Cells as a Model of Human Cortical Development 331
19.3 Mitotic and Neurogenic Effects of a Neurosteroid: Dehydroepiandrosterone (DHEA) 332
19.4 Glutamate Enhances Proliferation and Neurogenesis in hNPCs 336
19.5 Increased Neurogenic "Radial Glial"-like Cells within Human Neurosphere Cultures 338
19.6 Conclusions 341
Acknowledgments 342
References 342
20 Corticosterone， Dehydroepiandrosterone， and Neurogenesis in the Adult Hippocampus 347
20.1 Background 347
20.2 Glucocorticoids and Neurogenesis in the Adult Hippocampus 348
20.3 Conclusion 360
Acknowledgments 360
References 360
Index 367
