Basic Neurochemistry,
Edition 7 Molecular, Cellular and Medical AspectsEditors: Edited by Scott Brady, George Siegel, R. Wayne Albers and Donald Price
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Basic Neurochemistry: Molecular, Cellular and Medical Aspects, a comprehensive text on neurochemistry, is now updated and revised in its Seventh Edition. This well-established text has been recognized worldwide as a resource for postgraduate trainees and teachers in neurology, psychiatry, and basic neuroscience, as well as for graduate and postgraduate students and instructors in the neurosciences. It is an excellent source of information on basic biochemical processes in brain function and disease for qualifying examinations and continuing medical education.
Key Features
- Completely updated with 60% new authors and material, and entirely new chapters
- Over 400 fully revised figures in splendid color
About the author
Edited by Scott Brady, University of Illinois, Chicago IL; George Siegel, Loyola University, Chicago, IL, USA; R. Wayne Albers, National Institutes of Health, Bethesda MD, USA and Donald Price, The Johns Hopkins University School of Medicine, Baltimore MD
Section Editors
Contributors
Acknowledgments and History
Preface to the Seventh Edition
Pierre Morell, Ph.D. 1941–2003
PART I: Cellular Neurochemistry and Neural Membranes
Chapter 1: Neurocellular Anatomy
UNDERSTANDING NEUROANATOMY IS NECESSARY TO STUDY NEUROCHEMISTRY
CHARACTERISTICS OF THE NEURON
CHARACTERISTICS OF NEUROGLIA
ACKNOWLEDGMENTS
Chapter 2: Cell Membrane Structures and Functions
PHOSPHOLIPID BILAYERS
MEMBRANE PROTEINS
BIOLOGICAL MEMBRANES
Chapter 3: Lipids
PROPERTIES OF BRAIN LIPIDS
COMPLEX LIPIDS
ANALYSIS OF BRAIN LIPIDS
BRAIN LIPID BIOSYNTHESIS
GENES FOR LIPID-SYNTHESIZING ENZYMES
LIPIDS IN THE CELLULAR MILIEU
Chapter 4: Myelin Formation, Structure and Biochemistry
THE MYELIN SHEATH
CHARACTERISTIC COMPOSITION OF MYELIN
DEVELOPMENTAL AND METABOLIC ASPECTS OF MYELIN
ACKNOWLEDGMENTS
Chapter 5: Membrane Transport
INTRODUCTION
PRIMARY ION TRANSPORTERS
Ca2+ PUMPS
V0V1-PROTON PUMPS
ATP-BINDING CASSETTES
SECONDARY ACTIVE TRANSPORT
PHYSIOLOGICAL ASPECTS OF THE NEUROTRANSMITTER TRANSPORTERS
CATION ANTIPORTERS
FACILITATORS
Chapter 6: Electrical Excitability and Ion Channels
MEMBRANE POTENTIALS AND ELECTRICAL SIGNALS IN EXCITABLE CELLS
ACTION POTENTIALS IN ELECTRICALLY EXCITABLE CELLS
FUNCTIONAL PROPERTIES OF VOLTAGE-GATED ION CHANNELS
THE VOLTAGE-GATED ION CHANNEL SUPERFAMILY
THE MOLECULAR BASIS FOR ION CHANNEL FUNCTION
ION CHANNEL DIVERSITY
ACKNOWLEDGMENTS
Chapter 7: Cell Adhesion Molecules
OVERVIEW
THE IMMUNOGLOBULIN GENE SUPERFAMILY
THE CADHERIN FAMILY
CELL ADHESION MOLECULES AND AXONAL OUTGROWTH
CELL ADHESION MOLECULES IN MYELINATION
SUMMARY
Chapter 8: The Cytoskeleton of Neurons and Glia
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
Chapter 9: Intracellular Trafficking
GENERAL MECHANISMS OF INTRACELLULAR MEMBRANE TRAFFICKING IN MAMMALIAN CELLS INCLUDE BOTH UNIVERSAL AND HIGHLY SPECIALIZED PROCESSES
FUNDAMENTALS OF MEMBRANE TRAFFICKING ARE BASED ON A SET OF COMMON PRINCIPLES
THE BIOSYNTHETIC SECRETORY PATHWAY INCLUDES SYNTHETIC, PROCESSING, TARGETING AND SECRETORY STEPS
THE ENDOCYTIC PATHWAY PLAYS MULTIPLE ROLES IN CELLS OF THE NERVOUS SYSTEM
SYNAPTIC VESICLE TRAFFICKING IS A SPECIALIZED FORM OF REGULATED SECRETION AND RECYCLING OPTIMIZED FOR SPEED AND EFFICIENCY
ACKNOWLEDGMENTS
PART II: Intercellular Signaling
Chapter 10: Synaptic Transmission and Cellular Signaling: An Overview
SYNAPTIC TRANSMISSION
CELLULAR SIGNALING MECHANISMS
ACKNOWLEDGMENTS
Chapter 11: Acetylcholine
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
Chapter 12: Catecholamines
INTRODUCTION
BIOSYNTHESIS OF CATECHOLAMINES
STORAGE AND RELEASE OF CATECHOLAMINES
ANATOMY OF CATECHOLAMINERGIC SYSTEMS
CATECHOLAMINE RECEPTORS
DOPAMINE RECEPTORS
ADRENERGIC RECEPTORS
DYNAMICS OF CATECHOLAMINE RECEPTORS
ACKNOWLEDGMENTS
Chapter 13: Serotonin
SEROTONIN, THE NEUROTRANSMITTER
SEROTONIN RECEPTORS
Chapter 14: Histamine
HISTAMINE: THE MESSENGER AND THE MOLECULE
HISTAMINERGIC CELLS OF THE CENTRAL NERVOUS SYSTEM: ANATOMY AND MORPHOLOGY
DYNAMICS OF HISTAMINE IN THE BRAIN
MOLECULAR SITES OF HISTAMINE ACTION
H1-linked intracellular messengers.
HISTAMINE ACTIONS ON THE NERVOUS SYSTEM
SIGNIFICANCE OF BRAIN HISTAMINE FOR DRUG ACTION
ACKNOWLEDGMENTS
Chapter 15: Glutamate
THE AMINO ACID GLUTAMATE IS THE MAJOR EXCITATORY NEUROTRANSMITTER IN THE BRAIN
BRAIN GLUTAMATE IS DERIVED FROM BLOOD-BORNE GLUCOSE AND AMINO ACIDS THAT CROSS THE BLOOD–BRAIN BARRIER
GLUTAMINE IS AN IMPORTANT IMMEDIATE PRECURSOR FOR GLUTAMATE: THE GLUTAMINE CYCLE
SYNAPTIC VESICLES ACCUMULATE TRANSMITTER GLUTAMATE BY VESICULAR GLUTAMATE TRANSPORTERS
IS ASPARTATE A NEUROTRANSMITTER?
LONG-TERM POTENTIATION OR DEPRESSION OF GLUTAMATERGIC SYNAPSES MAY UNDERLIE LEARNING
THE NEURONAL PATHWAYS OF THE HIPPOCAMPUS ARE ESSENTIAL STRUCTURES FOR MEMORY FORMATION
IONOTROPIC AND METABOTROPIC GLUTAMATE RECEPTORS ARE PRINCIPAL PROTEINS AT THE POSTSYNAPTIC DENSITY
THREE CLASSES OF IONOTROPIC GLUTAMATE RECEPTORS ARE IDENTIFIED
GLUTAMATE PRODUCES EXCITATORY POSTSYNAPTIC POTENTIALS
METABOTROPIC GLUTAMATE RECEPTORS MODULATE SYNAPTIC TRANSMISSION
GLUTAMATE RECEPTORS DIFFER IN THEIR POSTSYNAPTIC DISTRIBUTION
PROTEINS OF THE POSTSYNAPTIC DENSITY MEDIATE INTRACELLULAR EFFECTS OF GLUTAMATE RECEPTOR ACTIVATION
SMALL GTP-BINDING PROTEINS (GTPases) MEDIATE CHANGES IN GENE EXPRESSION UPON NMDA RECEPTOR ACTIVATION
DENDRITIC SPINES ARE MOTILE, CHANGING THEIR SHAPE AND SIZE IN RESPONSE TO SYNAPTIC ACTIVITY WITHIN MINUTES
SODIUM-DEPENDENT SYMPORTERS IN THE PLASMA MEMBRANES CLEAR GLUTAMATE FROM THE EXTRACELLULAR SPACE
SODIUM-DEPENDENT GLUTAMINE TRANSPORTERS IN PLASMA MEMBRANES MEDIATE THE TRANSFER OF GLUTAMINE FROM ASTROCYTES TO NEURONS
EXCESSIVE GLUTAMATE RECEPTOR ACTIVATION MAY MEDIATE CERTAIN NEUROLOGICAL DISORDERS
Chapter 16: GABA and Glycine
GABA SYNTHESIS, UPTAKE AND RELEASE
GABA RECEPTOR PHYSIOLOGY AND PHARMACOLOGY
STRUCTURE AND FUNCTION OF GABA RECEPTORS
GLYCINE AS A CENTRAL NEUROTRANSMITTER: GLYCINE SYNTHESIS, UPTAKE AND DEGRADATION
GLYCINE RECEPTOR PHYSIOLOGY AND PHARMACOLOGY
GLYCINE RECEPTORS: STRUCTURE, PATHOLOGY AND LOCALIZATION
GABA AND GLYCINE ARE THE MAJOR RAPIDLY ACTING INHIBITORY NEUROTRANSMITTERS IN BRAIN
Chapter 17: Purinergic Systems
NOMENCLATURE OF PURINES AND PYRIMIDINES
PURINE RELEASE AND METABOLISM
PURINERGIC RECEPTORS
EFFECTS OF PURINES IN THE NERVOUS SYSTEM: ADENOSINE RECEPTORS
EFFECTS OF PURINES IN THE NERVOUS SYSTEM: ATP RECEPTORS
Chapter 18: Peptides
NEUROPEPTIDES
NEUROPEPTIDE RECEPTORS
NEUROPEPTIDE FUNCTIONS AND REGULATION
PEPTIDERGIC SYSTEMS IN DISEASE
PART III: Intracellular Signaling
Chapter 19: G Proteins
HETEROTRIMERIC G PROTEINS
SMALL G PROTEINS
OTHER FEATURES OF G PROTEINS
Chapter 20: Phosphoinositides
THE INOSITOL LIPIDS
THE INOSITOL PHOSPHATES
DIACYLGLYCEROL
PHOSPHOINOSITIDES AND CELL REGULATION
ACKNOWLEDGMENTS
Chapter 21: Cyclic Nucleotides in the Nervous System
INTRODUCTION: THE SECOND MESSENGER HYPOTHESIS
ADENYLYL CYCLASES
GUANYLYL CYCLASE
PHOSPHODIESTERASES
FUNCTIONAL ROLES FOR CYCLIC cAMP AND CYCLIC cGMP
FUTURE PERSPECTIVES
Chapter 22: Calcium
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
Chapter 23: Serine and Threonine Phosphorylation
PROTEIN PHOSPHORYLATION IS OF FUNDAMENTAL IMPORTANCE IN BIOLOGICAL REGULATION
PROTEIN SERINE–THREONINE KINASES
PROTEIN SERINE–THREONINE PHOSPHATASES
NEURONAL PHOSPHOPROTEINS
PROTEIN PHOSPHORYLATION MECHANISMS IN DISEASE
ACKNOWLEDGMENT
Chapter 24: Tyrosine Phosphorylation
TYROSINE PHOSPHORYLATION IN THE NERVOUS SYSTEM
PROTEIN TYROSINE KINASES
PROTEIN TYROSINE PHOSPHATASES
ROLE OF TYROSINE PHOSPHORYLATION IN THE NERVOUS SYSTEM
PART IV: Growth, Development and Differentiation
Chapter 25: Development
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
Chapter 26: Transcription Factors in the Central Nervous System
THE TRANSCRIPTIONAL PROCESS
REGULATION OF TRANSCRIPTION BY TRANSCRIPTION FACTORS
GLUCOCORTICOID AND MINERALOCORTICOID RECEPTORS AS TRANSCRIPTION FACTORS
CYCLIC AMP REGULATION OF TRANSCRIPTION
TRANSCRIPTION AS A TARGET FOR DRUG DEVELOPMENT
Chapter 27: Growth Factors
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
Chapter 28: Axonal Transport
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
CONCLUSION
ACKNOWLEDGMENTS
Chapter 29: Stem Cells in the Nervous System
STEM CELLS ARE MULTIPOTENT AND SELF-RENEWING
STEM CELLS CONTRIBUTE TO THE DEVELOPING NERVOUS SYSTEM
NEUROGENESIS OCCURS IN THE ADULT BRAIN
STEM CELLS OFFER THE POTENTIAL FOR REPAIR IN THE ADULT NERVOUS SYSTEM
STEM CELL TRANSPLANTS FOR NEURAL REPAIR
EXPANDING ENDOGENOUS NEURAL STEM CELLS FOR REPAIR
COMMON STEM CELL THERAPY CHALLENGES
CONCLUSIONS
Chapter 30: Axonal Growth in the Adult Mammalian Nervous System: Regeneration and Compensatory Plasticity
REGENERATION IN THE PERIPHERAL NERVOUS SYSTEM
REGENERATION IN THE CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM INJURY AND COMPENSATORY PLASTICITY
SUMMARY AND CONCLUSIONS
ACKNOWLEDGMENTS
PART V: Metabolism
Chapter 31: Energy Metabolism of the Brain
INTRODUCTION
SUBSTRATES FOR CEREBRAL ENERGY METABOLISM
AGE AND DEVELOPMENT INFLUENCE CEREBRAL ENERGY METABOLISM
REGULATION OF THE CEREBRAL METABOLIC RATE
METABOLISM IN THE BRAIN IS HIGHLY COMPARTMENTALIZED
GLYCOGEN IS ACTIVELY SYNTHESIZED AND DEGRADED IN BRAIN, PROVIDING A DYNAMIC SOURCE OF CARBOHYDRATE
GLYCOLYSIS: CONVERSION OF GLUCOSE TO PYRUVATE OR LACTATE
THE PENTOSE PHOSPHATE SHUNT IS ACTIVE IN BRAIN
GLYCEROL PHOSPHATE DEHYDROGENASE IS AN NADH OXIDIZING ENZYME RELATED TO GLYCOLYSIS
THE MALATE–ASPARTATE SHUTTLE HAS A KEY ROLE IN BRAIN METABOLISM
THERE IS DYNAMIC METABOLISM OF LACTATE IN BRAIN
THE COMPLETE OXIDATION OF GLUCOSE REQUIRES TRICARBOXYLIC ACID CYCLE ACTIVITY
ENERGY OUTPUT AND OXYGEN CONSUMPTION ARE ASSOCIATED WITH TCA CYCLE ACTIVITY
MANY TCA CYCLE ENZYMES AND COMPONENTS OF OXIDATIVE PHOSPHORYLATION ARE DIFFERENTIALLY DISTRIBUTED IN NEURONAL AND GLIAL MITOCHONDRIA
GLUTAMATE/GLUTAMINE METABOLISM IS LINKED TO ENERGY METABOLISM
HOW COMPARTMENTALIZED BRAIN METABOLISM IS STUDIED
RELATION OF ENERGY METABOLISM TO PATHOLOGICAL CONDITIONS IN THE BRAIN
ACKNOWLEDGMENT
Chapter 32: Hypoxic–Ischemic Brain Injury and Oxidative Stress
HYPOXIA–ISCHEMIA AND BRAIN INFARCTION
MICROVASCULAR INJURY IN HYPOXIA–ISCHEMIA
EXCITOTOXIC INJURY IN HYPOXIA–ISCHEMIA
ISCHEMIC APOPTOSIS
FREE RADICALS IN HYPOXIA–ISCHEMIA
NEUROPROTECTIVE STRATEGIES FOR HYPOXIC–ISCHEMIC INJURY
Chapter 33: Eicosanoids, Docosanoids, Platelet-Activating Factor and Inflammation
STORAGE OF LIPID MESSENGERS IN NEURAL MEMBRANE PHOSPHOLIPIDS
PHOSPHOLIPASE A2
EICOSANOIDS
PLATELET-ACTIVATING FACTOR
CYCLOOXYGENASES
DIACYLGLYCEROL KINASES
LIPID SIGNALING PATHWAYS AND NEUROINFLAMMATION
DOCOSAHEXAENOIC ACID
LIPID PEROXIDATION AND OXIDATIVE STRESS
NEUROPROTECTIN D1: A DOCOSAHEXAENOIC-ACID-DERIVED MEDIATOR
THE FUTURE OF LIPID SIGNALING IN THE NERVOUS SYSTEM
Chapter 34: Metabolic Encephalopathies
BRAIN ENERGY METABOLISM
METABOLIC ENCEPHALOPATHY DUE TO LACK OF ENERGY SUBSTRATE
HYPONATREMIC ENCEPHALOPATHY
HYPERCAPNIC ENCEPHALOPATHY
METABOLIC ENCEPHALOPATHY DUE TO PERIPHERAL ORGAN FAILURE
THIAMINE DEFICIENCY (WERNICKE’S) ENCEPHALOPATHY
PYRIDOXINE (VITAMIN B6) DEFICIENCY
COBALAMIN (VITAMIN B12) DEFICIENCY
Chapter 35: Apoptosis and Necrosis
DISTINGUISHING FEATURES OF APOPTOSIS AND NECROSIS
APOPTOSIS
NECROSIS
TARGETING APOPTOSIS AND NECROSIS IN NEUROLOGICAL DISORDERS
PART VI: Inherited and Neurodegenerative Diseases
Chapter 36: Peripheral Neuropathy
INTRODUCTION: CLINICAL FEATURES OF NEUROPATHIES
FEATURES COMMON TO THE PERIPHERAL AND CENTRAL NERVOUS SYSTEM IMPORTANT IN THE PATHOGENESIS AND PATHOPHYSIOLOGY OF NEUROPATHIES
FEATURES OF PERIPHERAL NERVES THAT INFLUENCE THEIR VULNERABILITY TO DISEASE AND CAPACITY FOR REGENERATION
PATHOGENESIS OF NEUROPATHIES
HEREDITARY AND ACQUIRED DISEASES INVOLVING THE ENTERIC NERVOUS SYSTEM
Chapter 37: The Epilepsies: Phenotype and Mechanisms
EPILEPSY IS A COMMON NEUROLOGICAL DISORDER
MECHANISMS OF ANTISEIZURE DRUGS
GENETICS OF EPILEPSY
Chapter 38: Diseases Involving Myelin
GENERAL CLASSIFICATION
ACQUIRED ALLERGIC AND/OR INFECTIOUS DISEASES OF MYELIN
GENETICALLY DETERMINED DISORDERS OF MYELIN
TOXIC AND NUTRITIONAL DISORDERS OF MYELIN
DISORDERS PRIMARILY AFFECTING NEURONS WITH SECONDARY INVOLVEMENT OF MYELIN
REPAIR IN DEMYELINATING DISEASES
Chapter 39: Genetics of Neurodegenerative Diseases
GENETIC ASPECTS OF COMMON NEURODEGENERATIVE DISEASES
ALZHEIMER’S DISEASE
PARKINSON’S DISEASE
LEWY BODY DEMENTIA
FRONTOTEMPORAL DEMENTIA
AMYOTROPHIC LATERAL SCLEROSIS
NEURODEGENERATIVE TRIPLET REPEAT DISORDERS
CREUTZFELDT–JAKOB DISEASE AND OTHER PRION DISEASES
CONCLUDING REMARKS
Chapter 40: Disorders of Amino Acid Metabolism
INTRODUCTION
DISORDERS OF BRANCHED-CHAIN AMINO ACIDS: MAPLE SYRUP URINE DISEASE
DISORDERS OF PHENYLALANINE METABOLISM: PHENYLKETONURIA
DISORDERS OF GLYCINE METABOLISM: NONKETOTIC HYPERGLYCINEMIA
DISORDERS OF SULFUR AMINO ACID METABOLISM: HOMOCYSTINURIA
THE UREA CYCLE DEFECTS
DISORDERS OF GLUTATHIONE METABOLISM
DISORDERS OF ¿-AMINOBUTYRIC ACID METABOLISM
DISORDERS OF N-ACETYL ASPARTATE METABOLISM
Chapter 41: Lysosomal and Peroxisomal Diseases
LYSOSOMAL DISEASES
PEROXISOMAL DISORDERS
DIAGNOSIS OF LYSOSOMAL AND PEROXISOMAL DISORDERS
PATHOGENESIS OF LYSOSOMAL AND PEROXISOMAL DISORDERS
THERAPY OF LYSOSOMAL AND PEROXISOMAL DISORDERS
Chapter 42: Diseases of Carbohydrate, Fatty Acid and Mitochondrial Metabolism
DISEASES OF CARBOHYDRATE AND FATTY ACID METABOLISM IN MUSCLE
DISEASES OF CARBOHYDRATE AND FATTY ACID METABOLISM IN BRAIN
DISEASES OF MITOCHONDRIAL METABOLISM
ACKNOWLEDGMENTS
Chapter 43: Disorders of Muscle Excitability
ORGANIZATION OF THE NEUROMUSCULAR JUNCTION
EXCITATION AND CONTRACTION OF THE MUSCLE FIBER
GENETIC DISORDERS OF THE NEUROMUSCULAR JUNCTION
HEREDITARY DISEASES OF MUSCLE MEMBRANES
IMMUNE DISEASES OF MUSCLE EXCITABILITY
TOXINS AND METABOLITES THAT ALTER MUSCULAR EXCITATION
Chapter 44: Motor Neuron Diseases
AMYOTROPHIC LATERAL SCLEROSIS IS THE MOST COMMON ADULT ONSET MOTOR NEURON DISEASE
NON-TRANSGENIC, INDUCED MODELS OF MOTOR NEURON DISEASE
SELECTED GENETIC MODELS OF RELEVANCE TO AMYOTROPHIC LATERAL SCLEROSIS
ACKNOWLEDGMENTS
Chapter 45: Neurodegenerative a-Synucleinopathies and Tauopathies
THE SYNUCLEIN FAMILY
PARKINSON’S DISEASE AND OTHER LEWY BODY DISEASES
MULTIPLE SYSTEM ATROPHY
SYNTHETIC a-SYNUCLEIN FILAMENTS
ANIMAL MODELS OF HUMAN a-SYNUCLEINOPATHIES
a-SYNUCLEINOPATHIES—OUTLOOK
TAU ISOFORMS AND THEIR INTERACTIONS WITH MICROTUBULES
TAU AND ALZHEIMER’S DISEASE
SPORADIC TAUOPATHIES
MUTATIONS CAUSING TAUOPATHY—THE FTDP-17 SYNDROMES
RELEVANCE FOR THE SPORADIC TAUOPATHIES
SYNTHETIC TAU FILAMENTS
ANIMAL MODELS OF HUMAN TAUOPATHIES
TAUOPATHIES — OUTLOOK
Chapter 46: Neurotransmitters and Disorders of the Basal Ganglia
ANATOMY AND PHYSIOLOGY OF THE BASAL GANGLIA
DISORDERS THAT INVOLVE BASAL GANGLIA DYSFUNCTION
Chapter 47: Neurobiology of Alzheimer’s Disease
ALZHEIMER’S DISEASE IS THE MOST PREVALENT NEURODEGENERATIVE DISORDER
ACKNOWLEDGMENTS
Chapter 48: Molecular Basis of Prion Diseases
INTRODUCTION
PRION DISEASES ARE BIOLOGICALLY UNIQUE
ANIMAL PRION DISEASES
HUMAN PRION DISEASES
PRION DISEASE PATHOLOGY AND PATHOGENESIS
THE PROTEIN-ONLY HYPOTHESIS OF PRION PROPAGATION
CHARACTERIZATION OF PrPC
CHARACTERIZATION OF PrPSC
THE MOLECULAR BASIS OF PRION STRAIN DIVERSITY
PRION TRANSMISSION BARRIERS
CELL DEATH IN PRION DISEASE
FUTURE PERSPECTIVES
PART VII: Sensory Transduction
Chapter 49: Molecular Biology of Vision
PHYSIOLOGICAL BACKGROUND
PHOTORECEPTOR MEMBRANES AND VISUAL PIGMENTS
PHOTOTRANSDUCTION
COLOR BLINDNESS
RETINITIS PIGMENTOSA
AGE-RELATED MACULAR DEGENERATION
Chapter 50: Molecular Biology of Olfaction and Taste
OLFACTION
TASTE
ACKNOWLEDGMENTS
Chapter 51: Molecular Biology of Hearing and Balance
GENERAL FEATURES OF MECHANORECEPTORS
MODEL SYSTEMS
HAIR CELLS
DEAFNESS
CONCLUSIONS
PART VIII: Neural Processing and Behavior
Chapter 52: Endocrine Effects on the Brain and Their Relationship to Behavior
INTRODUCTION
BEHAVIORAL CONTROL OF HORMONAL SECRETION
CLASSIFICATION OF HORMONAL EFFECTS
BIOCHEMISTRY OF STEROID AND THYROID HORMONE ACTIONS
INTRACELLULAR STEROID RECEPTORS: PROPERTIES AND TOPOGRAPHY
MEMBRANE STEROID RECEPTORS AND SIGNALING PATHWAYS
BIOCHEMISTRY OF THYROID HORMONE ACTIONS ON BRAIN
DIVERSITY OF STEROID-HORMONE ACTIONS ON THE BRAIN
Chapter 53: Learning and Memory
BRIEF HISTORY OF MEMORY RESEARCH IN HUMANS
DIVISIONS OF MEMORY
MOLECULAR MECHANISMS OF LEARNING
MOLECULAR MECHANISMS OF MEMORY CONSOLIDATION AND STORAGE
FUTURE DIRECTIONS AND CHALLENGES
Chapter 54: The Neurochemistry of Schizophrenia
CLINICAL ASPECTS OF SCHIZOPHRENIA
BRAIN IMAGING
CELLULAR AND MOLECULAR STUDIES
CONCLUSION
Chapter 55: Neurobiology of Severe Mood and Anxiety Disorders
MOOD DISORDERS
NEUROTRANSMITTER AND NEUROPEPTIDE SYSTEMS ARE IMPLICATED IN THE PATHOPHYSIOLOGY OF BIPOLAR AND MAJOR DEPRESSIVE DISORDERS
ABNORMALITIES OF SLEEP RHYTHMS IN MOOD DISORDERS
NEUROANATOMICAL AND NEUROPATHOLOGICAL CORRELATES OF MOOD DISORDERS
STRESS, GLUCOCORTICOIDS AND NEUROPLASTICITY IN THE PATHOLOGY OF MOOD DISORDERS
INTRACELLULAR SIGNALING PATHWAYS INTEGRATE ENVIRONMENTAL AND GENETIC CUES INVOLVED IN MOOD
INTRACELLULAR CALCIUM SIGNALING STUDIES IN BIPOLAR DISORDER
ANXIETY DISORDERS
INTRACELLULAR TARGETS FOR ANXIETY DISORDERS
FUTURE DIRECTIONS AND THE DEVELOPMENT OF NOVEL THERAPEUTICS
Chapter 56: Addiction
GENERAL PRINCIPLES
NEURONAL CIRCUITRY OF ADDICTION
OPIATES
PSYCHOMOTOR STIMULANTS
CANNABINOIDS (MARIJUANA)
NICOTINE
ETHANOL, SEDATIVES AND ANXIOLYTICS
HALLUCINOGENS AND DISSOCIATIVE DRUGS
ADDICTION AND NEURONAL PLASTICITY SHARE COMMON CELLULAR MECHANISMS
ACKNOWLEDGMENTS
Chapter 57: Pain
INTRODUCTION: THE PAIN PATHWAY
PRIMARY SENSORY NEURONS
DORSAL HORN
THE BRAIN
CLINICAL PAIN
INFLAMMATORY PAIN
NEUROPATHIC PAIN
CONCLUSION
Chapter 58: Neuroimaging
MAGNETIC RESONANCE IMAGING (MRI)
MAGNETIC RESONANCE SPECTROSCOPY (MRS)
POSITRON EMISSION TOMOGRAPHY (PET) AND SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY (SPECT)
APPLICATIONS OF PET AND SPECT FOR BRAIN FUNCTION
CNS DRUG DESIGN AND PRECLINICAL/CLINICAL DRUG DEVELOPMENT
CLINICAL APPLICATIONS OF PET AND SPECT
APPENDIX
Glossary
Index
Byrne and Roberts: From Molecules to Networks (Dec 2003, ISBN-10/13: 0-12-148660-5/ 978-0-12-148660-0)
Bhagavan: Medical Biochemistry, 4e (Sep 2001, ISBN-10/13: 0-12-095440-0/ 978-0-12-095440-7)
