Elsevier S & T

Neurosteroids and Brain Function

Bradley, Ronald J.

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Table of contents

Contentsv
Contributorsxiii
Prefacexvii
Chapter 1. Neurosteroids: Beginning of the Story1
I. Introduction2
II. Biosynthesis and Metabolism of Neurosteroids: Related Behavioral Effects7
III. Receptors and Related Activities of Neurosteroids13
IV. Conclusions25
References26
Chapter 2. Biosynthesis of Neurosteroids and Regulation of Their Synthesis33
I. What Is a Neurosteroid?34
II. Enzymes Involved in Neurosteroidogenesis: Biochemistry and Molecular Biology35
III. Enzymes Involved in Neurosteroidogenesis: Distribution in the Brain and Developmental Regulatio49
IV. Regulation of Neurosteroidogenic Enzymes61
V. Conclusions65
References66
Chapter 3. Neurosteroid 7-Hydroxylation Products in the Brain79
I. Neurosteroid Metabolism in the Brain79
II. 7α-Hydroxylation Studies in the Brain81
III. 7β-Hydroxylation Studies in the Brain83
IV. 7α-Hydroxy-DHEA and 7β-Hydroxy-DHEA as Native Anti-glucocorticoids84
V. The Brain and Other Organs88
VI. Sex Steroid Metabolism in the Brain90
VII. Conclusions92
References92
Chapter 4. Neurosteroid Analysis97
I. Introduction98
II. Analysis of Neurosteroids by Radioimmunoassay99
III. Analysis of Neurosteroids by High-Performance Liquid Chromatography Coupled with Gas Chromatogr99
IV. Analysis of Unconjugated Neurosteroids by Gas Chromatography–Mass Spectrometry100
V. Derivatization of Neurosteroids103
VI. Gas Chromatography Columns for Separation of Neurosteroid Derivatives106
VII. Isotopic Dilution for Quantitative Gas Chromatography–Mass Spectrometry107
VIII. Data Acquisition Modes in Mass Spectrometry107
IX. Mass Spectrometry/Mass Spectrometry108
X. Analysis of Neurosteroid Sulfates by Mass Spectrometry108
XI. Analysis of Sulfated Steroids by Soft Ionization Mass Spectrometry109
XII. Analysis of Steroid Sulfates by Atmospheric Pressure Chemical Ionization/Mass Spectrometry111
XIII. Thermospray Liquid Chromatography/Mass Spectrometry111
XIV. Future Analysis of Neurosteroid Sulfates111
XV. Conclusions112
References112
Chapter 5. Role of the Peripheral-Type Benzodiazepine Receptor in Adrenal and Brain Steroidogenesis117
I. Introduction118
II. Peripheral-Type Benzodiazepine Receptor118
III. Structure of the PBR Complex120
IV. Role of the PBR in Steroidogenesis124
V. The PBR in Adrenal Steroid Biosynthesis128
VI. Role of the PBR in Brain Neurosteroid Biosynthesis131
VII. Role of the PBR in Pathology134
VIII. Other Proteins Involved in the Acute Regulation of Steroidogenesis135
IX. Conclusions137
References137
Chapter 6. Formation and Effects of Neuroactive Steroids in the Central and Peripheral Nervous Syste145
I. Introduction146
II. 5α-Reductase and 3α-Hydroxysteroid Dehydrogenase System146
III. Effect of Glial–Neuronal Interactions on the Formation of Neuroactive Steroids153
IV. Effects of Neuroactive Steroids on Glial Cells of the Central Nervous System155
V. Formation of Neuroactive Steroids in the Peripheral Nervous System161
VI. Effects of Neuroactive Steroids on the Peripheral Nervous System162
VII. Conclusions170
References170
Chapter 7. Neurosteroid Modulation of Recombinant and Synaptic GABAA Receptors177
I. Introduction178
II. Transmitter-Gated Ion Channels and Neurosteroid Selectivity180
III. Influence of GABAA-Receptor Subunit Composition on Neurosteroid Action185
IV. Mechanism of Neurosteroid Modulation of GABAA Receptors188
V. Neurosteroid Modulation of Inhibitory Synaptic Transmission190
VI. Structure–Activity Relationships for Steroids at the GABAA Receptor194
VII. Multiple Steroid Binding Sites on the GABAA Receptor196
VIII. Conclusions197
References199
Chapter 8. GABAA-Receptor Plasticity during Long-Term Exposure to and Withdrawal from Progesterone207
I. Introduction208
II. Effects of Long-Term Exposure to PROG and GABAA-Receptor Gene Expression and Function in Vitro209
III. Effects of PROG Withdrawal on GABAA-Receptor Gene Expression and Function in Vitro216
IV. Effects of Long-Term Exposure to and Subsequent Withdrawal of PROG in Pseudo-pregnancy218
V. Effects of Long-Term Exposure to and Subsequent Withdrawal of PROG in Pregnancy220
VI. Oral Contraceptives and GABAA-Receptor Plasticity231
VII. Mechanism of the Effect of Long-Term PROG Exposure on GABAA-Receptor Plasticity234
VIII. Conclusions235
References235
Chapter 9. Stress and Neuroactive Steroids243
I. Stress and GABAA Receptors244
II. Effect of Stress on Brain Concentrations of Neuroactive Steroids246
III. Possible Mechanisms Underlying the Stress-Induced Changes in Brain Neurosteroid Concentrations261
IV. Conclusions263
References264
Chapter 10. Neurosteroids in Learning and Memory Processes273
I. Introduction274
II. Learning and Memory Processes and Animal Models275
III. Pharmacological Effects of Neurosteroids280
IV. Mechanisms of Action292
V. Physiological Significance301
VI. Conclusions and Future Perspectives309
References312
Chapter 11. Neurosteroids and Behavior321
I. Introduction321
II. Anxiety and Stress322
III. Cognition328
IV. Aggression333
V. Sleep, Feeding, and Reinforcement335
VI. Discriminative Stimulus Effects337
References342
Chapter 12. Ethanol and Neurosteroid Interactions in the Brain349
I. Introduction349
II. Role of 3α,5α-TH PROG in Ethanol Action351
III. Role of Neurosteroids in Alcohol Reinforcement359
IV. Role of Neurosteroids in Ethanol Tolerance361
V. Role of Neurosteroids in Ethanol Dependence364
VI. Conclusions and Future Directions369
References369
Chapter 13. Preclinical Development of Neurosteroids as Neuroprotective Agents for the Treatment of379
I. Neurosteroids and the Brain380
II. Synthesis of Central Nervous System Neurosteroids380
III. Receptor Signaling Pathways381
IV. Neurosteroids and Central Nervous System Plasticity384
V. Neurosteroids and Neuroprotection384
VI. Conclusions391
References391
Chapter 14. Clinical Implications of Circulating Neurosteroids399
I. Introduction399
II. Changes and Possible Role of Neurosteroids in Humans402
References414
Chapter 15. Neuroactive Steroids and Central Nervous System Disorders421
I. Neuroactive Steroids and the Central Nervous System422
II. Concentrations of Neuroactive Steroids in the Brain425
III. Sensory–Motor and Cognitive Function428
IV. Estrogen and Alzheimer’s Disease429
V. Neuroactive Steroids and Menstrual-Cycle-Linked Mood Changes430
VI. Side Effects of Oral Contraceptives435
VII. Neuroactive Steroids and Menopause436
VIII. Side Effects of Hormone Replacement Therapy439
IX. Neuroactive Steroids and Epilepsy441
References448
Chapter 16. Neuroactive Steroids in Neuropsychopharmacology461
I. Introduction462
II. Sources and Biosynthesis of Neuroactive Steroids463
III. Steroid Modulation of GABAA Receptors465
IV. Steroid Modulation of Other Neurotransmitter Receptors466
V. A Putative Specific Steroid-Binding Site on Ligand-Gated Ion Channels468
VI. Genomic Effects of Neuroactive Steroids469
VII. Neuropsychopharmacological Properties of Neuroactive Steroids470
VIII. Modulation of Endogenous Neuroactive Steroids as a Pharmacological Principle471
IX. Outlook472
References474
Chapter 17. Current Perspectives on the Role of Neurosteroids in PMS and Depression479
I. Introduction479
II. Premenstrual Syndrome or Premenstrual (Late Luteal) Dysphoric Disorder480
III. Allopregnanolone and Premenstrual Dysphoric Disorder481
IV. Biosynthesis of Allopregnanolone483
V. SSRIs in the Treatment of Premenstrual Dysphoric Disorder: Modulation of Neurosteroid Levels485
VI. SSRIs, Neurosteroids, and Depression487
VII. Conclusions489
References489
Index493

Book details

Vendor Elsevier S & T
SKU 9780123668462
ISBN-13 9780080544236
Author Bradley, Ronald J.
Category Medical
Subject Neuroscience

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International Review of Neurobiology, Volume 46 presents in-depth reviews on such ground-breaking topics as assembly and intracellular trafficking of GABA A receptors, D-1 dopamine receptors, and Alzheimer's disease. This series offers the most comprehensive and up-to-date information available and is a must for anyone in the field.

Includes a historical overview of neurosteroid research
Contains a chapter on neurosteroid biosynthesis and regulation
Presents current methods of neurosteroid measurement and analysis
Discusses neurosteroid function in both the normal and the pathological brain
Chapters address the function of neurosteroid in:
Stress
Receptor plasticity and function
Learning and Memory
Alcohol use
Depression

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