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Basic Neurochemistry had its origin in the Conference on Neurochemistry Curriculum initiated and organized by R. Wayne Albers, Robert Katzman and George J. Siegel under the sponsorship of the National Institute for Neurological Diseases and Stroke, June 19 and 20, 1969, Bronx, New York. At this conference, a group of 30 neuroscientists constructed a syllabus outline delineating the scope of a neurochemistry curriculum appropriate for medical, graduate and postgraduate neuroscience students. Out of this outline grew the first edition, edited by R. Wayne Albers, George J. Siegel, Robert Katzman and Bernard W. Agranoff. It was anticipated that the book would evolve with the emergence of the field and would stimulate continuing reappraisal of the scientific and educational aspects of neurochemistry.
Contents
- Acknowledgments
- Preface
- Part One. Cellular Neurochemistry and Neural Membranes
- Chapter 1. Neurocellular AnatomyCedric S Raine.
- Understanding Neuroanatomy is Necessary to Study Neurochemistry
- Characteristics of the Neuron
- Characteristics of Neuroglia
- Acknowledgments
- References
- Chapter 2. Cell Membrane Structures and FunctionsR Wayne Albers.
- Phospholipid Bilayers
- Membrane Proteins
- Membrane Dynamics
- References
- Chapter 3. LipidsBernard W Agranoff, Joyce A Benjamins, and Amiya K Hajra.
- Properties of Brain Lipids
- Complex Lipids
- Analysis of Brain Lipids
- Brain Lipid Biosynthesis
- Lipids in the Cellular Milieu
- References
- General References
- Chapter 4. Myelin Formation, Structure and BiochemistryPierre Morell and Richard H Quarles.
- The Myelin Sheath
- Characteristic Composition of Myelin
- Developmental Biology of Myelin
- Synthesis and Metabolism of Myelin
- Molecular Architecture of Myelin
- Acknowledgments
- References
- Chapter 5. Membrane TransportR Wayne Albers and George J Siegel.
- Transport Processes
- The ATP-Dependent Na+,K+ Pump
- ATP-Dependent Ca2+ Pumps
- Other P-Type Cation Transporters
- Mitochondrial and Vacuolar Atpases
- ATP-Binding Cassette Proteins
- Secondary Transport Systems
- Uncoupled Transporters
- References
- Chapter 6. Electrical Excitability and Ion ChannelsBertil Hille and William A Catterall.
- Electrical Phenomena in Excitable Cells
- The Ionic Hypothesis and Rules of Ionic Electricity
- Electrically Excitable Cells
- Functional Properties of Voltage-Gated Ion Channels
- Molecular Components of Voltage-Gated Ion Channels
- Other Channels
- Acknowledgments
- References
- Chapter 7. Cell Adhesion MoleculesDavid R Colman and Marie T Filbin.
- Overview
- The Immunoglobulin Gene Superfamily
- The Integrin Family
- The Cadherin Family
- Cell Adhesion Molecules and Axonal Outgrowth
- Cell Adhesion Molecules in Myelination
- Summary
- References
- Chapter 8. Cytoskeleton of Neurons and GliaLaura L Kirkpatrick and Scott T Brady.
- Molecular Components of the Neuronal Cytoskeleton
- Ultrastructure and Molecular Organization of Neurons and Glia
- Cytoskeletal Structures in the Neuron Have Complementary Distributions and Functions
- Conclusions
- References
- Chapter 9. Intracellular TraffickingThomas C Südhof.
- Intracellular Membrane Traffic
- The Synaptic Vesicle Cycle in the Nerve Terminal
- Composition of Synaptic Vesicles
- Characteristics of Synaptic Vesicle Exocytosis
- Proteins that Function in Synaptic Vesicle Exocytosis
- Characteristics and Proteins of Synaptic Vesicle Endocytosis
- Implications for Intracellular Trafficking
- References
- Chapter 1. Neurocellular Anatomy
- Part Two. Intercellular Signaling
- Chapter 10. Synaptic Transmission and Cellular Signaling: An OverviewRonald W Holz and Stephen K Fisher.
- Synaptic Transmission
- Cellular Signaling Mechanisms
- Acknowledgments
- References
- Chapter 11. AcetylcholinePalmer Taylor and Joan Heller Brown.
- Chemistry of Acetylcholine
- Organization of the Cholinergic Nervous System
- Functional Aspects of Cholinergic Neurotransmission
- Synthesis, Storage and Release of Acetylcholine
- Acetylcholinesterase and the Termination of Acetylcholine Action
- Nicotinic Receptors
- Muscarinic Receptors
- References
- Chapter 12. CatecholaminesMichael J Kuhar, Pastor R Couceyro, and Philip D Lambert.
- Biosynthesis of Catecholamines
- Storage and Release of Catecholamines
- Anatomy of Catecholaminergic Systems
- Catecholamine Receptors
- Dopamine Receptors
- α- and β-Adrenergic Receptors
- Dynamics of Catecholamine Receptors
- Acknowledgments
- References
- Chapter 13. SerotoninAlan Frazer and Julie G Hensler.
- Serotonin
- Serotonin Receptors
- Serotonin Involvement in Physiological Function and Behavior
- Serotonin Neurons and Receptors as Drug Targets
- References
- Chapter 14. HistamineLindsay B Hough.
- Histamine: A Messenger Molecule Within and Outside of the Nervous System
- Histaminergic Cells of the Central Nervous System: Anatomy and Morphology
- Dynamics of Histamine in the Brain
- Molecular Sites of Histamine Action
- Histamine Actions in the Central Nervous System
- Significance of Brain Histamine for Drug Action
- Acknowledgments
- References
- Chapter 15. Glutamate and AspartateRaymond Dingledine and Chris J McBain.
- Three Classes of Ionotropic Glutamate Receptor
- Metabotropic Receptors Modulate Synaptic Transmission
- Glutamate and Aspartate Are the Major Excitatory Transmitters in the Brain
- Glutamate Transporters
- Excessive Glutamate Receptor Activation and Neurological Disorders
- Future Prospects
- References
- Chapter 16. GABA and GlycineRichard W Olsen and Timothy M DeLorey.
- GABA Synthesis, Uptake and Release
- GABA Receptor Physiology and Pharmacology
- Cloning GABA Receptors
- Glycine Receptors
- Glycine Receptor Physiology and Pharmacology
- Cloning Glycine Receptors
- GABA and Glycine are the Major Rapidly Acting Inhibitory Neurotransmitters in Brain
- References
- Chapter 17. Purinergic SystemsJoel M Linden.
- Purine Release and Metabolism
- Purinergic Receptors
- Effects of Purines in the Nervous System
- References
- Chapter 18. PeptidesRichard E Mains and Betty A Eipper.
- The Neuropeptides
- Neuropeptide Receptors
- Neuropeptide Functions and Regulation
- Peptidergic Systems in Disease
- References
- Chapter 19. Growth FactorsGary E Landreth.
- Growth Factors Are Essential for Nervous System Development and Function
- Classes of Growth Factors Acting in the Nervous System
- Growth Factors Act Combinatorially and Sequentially to Regulate Nervous System Development
- References
- Chapter 10. Synaptic Transmission and Cellular Signaling: An Overview
- Part Three. Intracellular Signaling
- Chapter 20. G ProteinsEric J Nestler and Ronald S Duman.
- Heterotrimeric G Proteins
- Small G Proteins
- Other Features of G Proteins
- References
- Chapter 21. PhosphoinositidesStephen K Fisher and Bernard W Agranoff.
- Background
- Chemistry of the Inositol Lipids and Phosphates
- The Inositol Phosphates
- Diacylglycerol
- Functional Correlates of Phosphoinositide-Linked Receptors in the Nervous System
- Acknowledgments
- References
- Chapter 22. Cyclic NucleotidesRonald S Duman and Eric J Nestler.
- The Second-Messenger Hypothesis
- Adenylyl Cyclases
- Guanylyl Cyclase
- Cyclic Nucleotide Phosphodiesterases
- Functional Roles for cAMP and cGMP
- Future Perspectives
- References
- Chapter 23. CalciumJames W Putney Jr.
- The Concept of Ca2+ as a Cellular Signal
- Measurement of Cellular Ca2+ Concentrations and Movements
- Ca2+ Regulation at the Plasma Membrane
- Ca2+ Stores and Ca2+ Pools
- Ca2+ Signaling
- Ca2+-Regulated Processes
- References
- Chapter 24. Serine and Threonine PhosphorylationEric J Nestler and Paul Greengard.
- Protein Phosphorylation is of Fundamental Importance in Biological Regulation
- Protein Serine-Threonine Kinases
- Protein Serine-Threonine Phosphatases
- Neuronal Phosphoproteins
- Cellular Signals Converge at the Level of Protein Phosphorylation Pathways
- Protein Phosphorylation Mechanisms in Disease
- References
- Chapter 25. Tyrosine PhosphorylationLit-fui Lau and Richard L Huganir.
- Tyrosine Phosphorylation in the Nervous System
- Protein Tyrosine Kinases
- Protein Tyrosine Phosphatases
- Role of Tyrosine Phosphorylation in the Nervous System
- Acknowledgments
- References
- Chapter 26. Transcription Factors in the Central Nervous SystemJames Eberwine.
- The Transcriptional Process
- Regulation of Transcription by Transcription Factors
- Glucocorticoid and Mineralocorticoid Receptors as Transcription Factors
- cAMP Regulation of Transcription
- Transcription as a Target for Drug Development
- References
- Chapter 20. G Proteins
- Part Four. Growth, Development and Differentiation
- Chapter 27. DevelopmentJean de Vellis and Ellen Carpenter.
- Fundamental Concepts Unifying Developmental Diversity
- General Development of the Nervous System
- Developmental Processes: Environmental Forces Molding Genetic Potential
- Molecular Mechanisms of Development
- Cell Lineages of the Nervous System
- Conclusions
- Acknowledgments
- References
- Chapter 28. Axonal TransportDavid L Stenoien and Scott T Brady.
- Neuronal Organelles in Motion
- Discovery and Conceptual Development of Fast and Slow Axonal Transport
- Fast Axonal Transport
- Slow Axonal Transport
- Molecular Motors: Kinesin, Dynein and Myosin
- Axonal Transport and Neuropathology
- Conclusions
- Acknowledgments
- References
- Chapter 29. Axon Sprouting and RegenerationCarl W Cotman.
- Introduction
- Axon Sprouting and Reactive Synaptogenesis
- Regeneration
- Brain and Spinal Cord Transplants
- Summary and Conclusions
- References
- Chapter 30. Biochemistry of AgingCaleb E Finch and George S Roth.
- Overview on Aging
- Cell Numbers
- Plasticity and Aging
- Neurotransmitters and Receptors
- Aging Pigments and Membranes
- Energy Metabolism
- Instability in the Nuclear and Mitochondrial Genomes
- Gene Expression
- Proteins
- Experimental Manipulations of Brain Aging
- Neuroendocrinology and Sleep During Aging
- Mammals Are Not the Only Animal Models for Aging
- Prospects
- Acknowledgments
- References
- Chapter 27. Development
- Part Five. Metabolism
- Chapter 31. Circulation and Energy Metabolism of the BrainDonald D Clarke and Louis Sokoloff.
- Intermediary Metabolism
- Differences Between In Vitro and In Vivo Brain Metabolism
- Cerebral Energy Metabolism In Vivo
- Regulation of Cerebral Metabolic Rate
- Substrates of Cerebral Metabolism
- Age and Development Influence Cerebral Energy Metabolism
- Cerebral Metabolic Rate in Various Physiological States
- Cerebral Energy Metabolism in Pathological States
- References
- Chapter 32. Blood—Brain—Cerebrospinal Fluid BarriersJohn Laterra, Richard Keep, Lorris A Betz, and Gary W Goldstein.
- Constancy of the Internal Environment of the Brain
- Membrane Transport Processes
- Blood—Brain Barrier
- Blood—Cerebrospinal Fluid Barrier
- Cerebrospinal Fluid—Brain interface
- Bypassing the Barriers with Drugs
- Acknowledgments
- References
- Chapter 33. Nutrition and Brain FunctionGary E Gibson and John P Blass.
- Nutrition and Functional Neurochemistry
- Nutrition and Structural Aspects of the Brain
- Nutrition and Brain Development
- Nutrition and Aging of the Nervous System
- Nutrition and the Treatment of Neurodegenerative Disease
- Nutrition and Genetics
- Neuronal Control of Food Intake
- Summary
- References
- Chapter 34. Hypoxic-Ischemic Brain Injury and Oxidative StressLaura L Dugan and Dennis W Choi.
- Hypoxia-Ischemia and Brain infarction
- Microvascular injury in Hypoxia-Ischemia
- Excitotoxic injury in Hypoxia-Ischemia
- Zn2+ and Hypoxia-Ischemia
- Ischemic Apoptosis
- Free Radicals in Hypoxia-Ischemia
- References
- Chapter 35. Eicosanoids, Platelet-Activating Factor and InflammationNicolas G Bazan.
- Sources of Bioactive Lipids
- Phospholipases a2
- Eicosanoids
- Platelet-Activating Factor
- Cyclooxygenases
- Lipid Signaling Pathways and Neuroinflammation
- References
- Chapter 36. NeuropathyDavid E Pleasure.
- Regeneration in the Central and Peripheral Nervous Systems
- Examples of Peripheral Nervous System-Specific Diseases
- Diseases Affecting Both the Peripheral and Central Nervous Systems
- Diseases of the Enteric Nervous System
- References
- Chapter 37. Epileptic Seizures and EpilepsyBrian Meldrum and Astrid Chapman.
- Epilepsies Are Disorders Characterized by Spontaneous, Recurrent Seizures
- Epileptogenesis
- Epilepsy Models
- Basic Electrophysiology
- Changes in Neurotransmitter Systems Underlying Epilepsy
- Anticonvulsant Drug Mechanisms
- Metabolic Consequences of Seizures
- Pathological Changes Secondary to Seizures or Related to Epileptogenesis
- References
- Chapter 38. Metabolic EncephalopathiesRoger F Butterworth.
- Brain Energy Metabolism
- Hypoglycemic Encephalopathy
- Hypoxic Encephalopathy
- Hepatic Encephalopathy
- Hypercapnic Encephalopathy
- Uremic and Dialysis Encephalopathies
- References
- Chapter 39. Diseases Involving MyelinRichard H Quarles, Pierre Morell, and Henry F McFarland.
- General Classification
- Acquired Disorders of Myelin
- Genetic Disorders of Myelin
- Toxic and Nutritional Disorders of Myelin
- Disorders Primarily Affecting Neurons with Secondary Involvement of Myelin
- Remyelination
- References
- Chapter 31. Circulation and Energy Metabolism of the Brain
- Part Six. Inherited and Neurodegenerative Diseases
- Chapter 40. Genetics of Inherited DiseasesKunihiko Suzuki.
- Genetic Neurological Disorders
- Nature of Mutations in Genetic Disorders
- Gene Transfer and Expression
- Unique Nature of Genetic Disorders Affecting the Brain
- References
- Chapter 41. Lysosomal and Peroxisomal DiseasesKunihiko Suzuki and Marie T Vanier.
- The Lysosome
- The Peroxisome
- Molecular Genetics
- Diagnosis and Treatment
- Animal Models
- Lysosomal Disease
- Peroxisomal Disease
- Update Added in Proof
- References
- Chapter 42. Diseases of Carbohydrate, Fatty Acid and Mitochondrial MetabolismSalvatore diMauro and Darryl C De Vivo.
- Diseases of Carbohydrate and Fatty Acid Metabolism in Muscle
- Diseases of Carbohydrate and Fatty Acid Metabolism in Brain
- Diseases of Mitochondrial Metabolism
- Acknowledgments
- References
- Chapter 43. Disorders of Muscle ExcitabilityRobert L Barchi.
- Muscle Fibers Are Organized in Repeating Units
- Membrane Systems Couple Nerve Excitation to Muscle Contraction
- Defects in Neuromuscular Transmission Can Interrupt Normal Muscle Function
- Toxins and Diseases Can Also Block Transmission at the Postsynaptic Level
- Abnormal Excitability of the Sarcolemma Can Affect Muscle Function
- Defects at the Triad Can Also Affect Muscle Function
- References
- Chapter 44. Diseases of Amino Acid MetabolismMarc Yudkoff.
- Biochemistry of Amino Acid Disorders
- Pathogenesis of Clinical Features
- Branched-Chain Amino Acid Metabolism
- Disorders of Organic Acid Metabolism
- Organic Acid Metabolism
- Phenylalanine Metabolism: Phenylketonuria
- Glycine Metabolism: Nonketotic Hyperglycinemia
- Sulfur Amino Acid Metabolism: Homocystinuria
- Urea Cycle
- Biotin Metabolism
- Glutathione Metabolism
- GABA Metabolism
- N-Acetylaspartate Metabolism: Canavan's Disease
- References
- Chapter 45. Neurotransmitters and Disorders of the Basal GangliaJ Sian, MBH Youdim, P Riederer, and M Gerlach.
- Biochemical Anatomy of the Basal Ganglia and Associated Neural Systems
- Parkinson's Disease
- MPTP-Induced Parkinsonian Syndrome
- Drug- Or Toxin-Induced Movement Disorders
- Hepatolenticular Degeneration: Wilson's Disease
- Amyotrophic Lateral Sclerosis—Parkinsonism—Dementia of Guam
- Huntington's Disease
- Kernicterus
- Acknowledgments
- References
- Chapter 46. Biochemistry of Alzheimer's and Prion DiseasesDennis J Selkoe and Peter J Lansbury Jr.
- Alzheimer's Disease Is the Most Common Neurodegenerative Disorder
- Prion Diseases
- References
- Chapter 40. Genetics of Inherited Diseases
- Part Seven. Neural Processing and Behavior
- Chapter 47. Molecular Biology of VisionHitoshi Shichi.
- Physiological Background
- Photoreceptor Membranes and Visual Pigments
- Phototransduction
- Color Blindness
- Retinitis Pigmentosa
- Age-Related Macular Degeneration
- References
- Chapter 48. Molecular Biology of Olfaction and TasteStuart J Firestein, Robert F Margolskee, and Sue Kinnamon.
- Olfaction
- Taste
- Acknowledgments
- References
- Chapter 49. Endocrine Effects on the Brain and Their Relationship to BehaviorBruce S McEwen.
- Behavioral Control of Hormonal Secretion
- Classification of Hormonal Effects
- Biochemistry of Steroid and Thyroid Hormone Actions
- Intracellular Steroid Receptors: Properties and Topography
- Identification of Membrane Steroid Receptors
- Biochemistry of Thyroid Hormone Actions on Brain
- Diversity of Steroid Hormone Actions on the Brain
- References
- Chapter 50. Learning and MemoryBernard W Agranoff, Carl W Cotman, and Michael D Uhler.
- Introduction
- Basic Assumptions
- Synaptic Plasticity as a Model for Learning and Memory Research
- Invertebrate Learning and Memory
- Studies of Learning and Memory in Vertebrates
- Studies of Learning and Memory in Humans
- Remaining Questions and Future Directions
- References
- General References
- Chapter 51. Neurochemistry of SchizophreniaHerbert Y Meltzer and Ariel Y Deutch.
- Clinical Aspects of Schizophrenia
- Etiology
- Cellular and Pharmacological Studies
- References
- Chapter 52. Biochemical Hypotheses of Mood and Anxiety DisordersJack D Barchas and Margaret Altemus.
- Depression and Manic-Depressive Illness: Two Major Categories of Mood Disorders
- Biological Concomitants of Mood Disorders
- Monoamine Hypotheses of Mood Disorders
- Acetylcholine Mechanisms Have Been Implicated in Mood Disorders
- Receptor Hypotheses of Mood Disorders
- Li+ and Anticonvulsants are Important in the Treatment of Mood Disorders
- Endocrine, Circadian and Behavioral Processes in Mood Disorders
- Anxiety Disorders
- Biochemical Aspects of Anxiety
- References
- Chapter 53. Neurochemical Bases of Drug AbuseGeorge R Uhl.
- General Principles
- Molecular Targets for Drug Reward
- Brain Circuits Activated by Rewarding Drugs
- Cellular Changes Exerted by Abused Substances
- Individual Differences
- Conclusions
- Acknowledgments
- References
- Chapter 54. Positron Emission TomographyKirk A Frey.
- Methods in Positron Emission Tomography
- Physiological and Biochemical Measurements Using Positron Emission Tomography
- Clinical Applications of Cerebral Positron Emission Tomography
- Acknowledgments
- References
- Chapter 47. Molecular Biology of Vision
- Glossary
- Amino Acids in Proteins
Care has been taken to confirm the accuracy of the information presented and to describe generally accepted practices. However, the authors, editors, and publisher are not responsible for errors or omissions or for any consequences from application of the information in this book and make no warranty, express or implied, with respect to the contents of the publication.
The authors, editors, and publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accordance with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new or infrequently employed drug.
Some drugs and medical devices presented in this publication have Food and Drug Administration (FDA) clearance for limited use in restricted research settings. It is the responsibility of the health careprovider to ascertain the FDA status of each drug or device planned for use in their clinical practice.
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