This comprehensive textbook offers an in-depth exploration of how thyroid hormones influence brain development and function, particularly on cellular and molecular mechanisms. Readers will find current insights into the complex interplay between the thyroid and neurological systems, making it a valuable resource for researchers, advanced learners and clinicians in the fields of endocrinology, neuroscience, and developmental biology.
The book starts with a review of thyroid physiology, setting the stage for subsequent chapters that cover specific topics such as the impact of maternal thyroid hormones on fetal brain development and the effects of iodine deficiency. From here, the book progresses to cover the regulation of brain gene expression, neuronal and glial cell differentiation, and myelination by thyroid hormones, and how thyroid hormones shape the brain. Finally, the book addresses the link between thyroid dysfunction and mood disorders.
Key features
A thorough examination of the historical and the latest research findings through 14 chapters
Clear explanations of molecular pathways
Emphasis on both theoretical knowledge and practical applications
Detailed and research-focused content scientific references for further reading
Readership
Medical students, residents, researchers (neuroscience and developmental biology), and healthcare professionals (neurologists and endocrinologists) who need to understand the regulation of brain development by thyroid hormones and the treatment of thyroid-related neurological conditions.
Table of Contents
CONTENTS
FOREWORD
PREFACE
ACKNOWLEDGEMENTS
CHAPTER 1 AN INTRODUCTION TO THYROID PHYSIOLOGY
INTRODUCTION
THE UNIQUENESS OF THE THYROID GLAND
- Embryology
- The Thyroid Follicles
- Thyroid Hormone Synthesis
CIRCULATING THYROID HORMONES
THYROID HORMONE METABOLISM
- Deiodinases
- Type 1 Deiodinase (DIO1)
- Type 2 Deiodinase (DIO2)
- Type 3 Deiodinase (DIO3)
- Thyronamines
THYROID HORMONE ACTION
- Type 1: Nuclear Receptor-Dependent Signaling with Direct Binding to DNA
- Type 2: Nuclear Receptor-Dependent Signaling with Indirect Binding to DNA
- Type 3: Nuclear Receptor-Dependent Signaling without DNA Binding
- Type 4: Nuclear Receptor-Independent Signaling
- The Endocrine Disruptor Bisphenol A (BPA) and its Interaction with Thyroid
- Hormone Receptors
EVOLUTIONARY ASPECTS OF THYROID HORMONES
CONCLUDING REMARKS
REFERENCES
CHAPTER 2 CONGENITAL HYPOTHYROIDISM
INTRODUCTION
PRIMARY CONGENITAL HYPOTHYROIDISM
- Thyroid Dysgenesis
- Thyroid Dyshormonogenesis
- Iodide Transporters
- Iodide Oxidation and Organification
- Thyroglobulin
- Dehalogenase
- TSH Resistance
CENTRAL CONGENITAL HYPOTHYROIDISM
DEVELOPMENTAL ARREST IN CONGENITAL HYPOTHYROIDISM
- Untreated Congenital Hypothyroidism
- Persistence of Brain Damage Despite Early Treatment
CONCLUDING REMARKS
REFERENCES
CHAPTER 3 DEIODINASES IN THE BRAIN
INTRODUCTION
THYROXINE, A TRIIODOTHYRONINE PRECURSOR
DEIODINASES IN THE RODENT BRAIN
- Type 1 Deiodinase
DEDICATION
- Type 2 Deiodinase
- Developmental Changes in Type-2 Deiodinase Activity
- Dio2 Regional and Cellular Expression in the Brain
- The Paracrine Model of Deiodination and Action
- The Significance of Dio2 Expression in Astrocytes
- How the Lack of DIO2 Impacts the Brain
- Type 3 Deiodinase
- Developmental Changes in Type-3 Deiodinase Activity
- How the Lack of DIO3 Impacts the Brain
REGULATION OF DEIODINASE BRAIN EXPRESSION AND ACTIVITY
DEIODINASES IN THE HUMAN BRAIN
- Thyroid Hormone Concentrations and Deiodinase Activity in the Human Fetal Brain
- DIO2 in Stem Cells of the Developing Human Fetal Cerebral Cortex
- Genetic Deficiencies in Deiodinase Function
- The Thr92Ala-DIO2 Polymorphism
CONCLUDING REMARKS
REFERENCES
CHAPTER 4 UNRAVELING THE ROLE OF MATERNAL THYROID HORMONES ON FETAL DEVELOPMENT
INTRODUCTION
PLACENTAL PERMEABILITY TO THYROID HORMONES IN RODENTS
- The Relevance of T4 as the Source of T3 in the Fetal Brain
THE PERMEABILITY OF THE HUMAN PLACENTA TO THYROID HORMONES
- Maternal Thyroid Hormones in the Fetus During Early Pregnancy
MATERNAL HYPOTHYROIDISM AND HYPOTHYROXINEMIA
- Maternal Hypothyroidism and Infant Brain Development: Experimental Studies
- Maternal Clinical Hypothyroidism
- Maternal Hypothyroxinemia
CONCLUDING REMARKS
REFERENCES
CHAPTER 5 ENDEMIC GOITER AND CRETINISM: PATHOPHYSIOLOGY OF IODINE DEFICIENCY
INTRODUCTION
THE IODINE CYCLE
- Iodine Requirements
ENDEMIC GOITER AND CRETINISM
- Neurological Manifestations of Endemic Cretinism
- Pathogenesis
- Myxedematous Cretinism
PHYSIOLOGICAL MECHANISMS SET IN MOTION BY IODINE DEFICIENCY IN EXPERIMENTAL ANIMALS
- Thyroid Autoregulation
- Thyroidal Iodotyrosine Dehalogenase
- Mechanisms Leading to Preferential Secretion of T3
- Changes in Thyroid Hormone Deiodination in Extrathyroidal Organs
- Iodine Deficiency in Developing Rats
- The Sheep Model
CONCLUDING REMARKS
REFERENCES
CHAPTER 6 CELLULAR TRANSPORTERS FOR THYROID HORMONES
INTRODUCTION
PROTEIN FAMILIES WITH THYROID HORMONE TRANSPORTING ACTIVITY
- Bile Acid Transporters
- Amino Acid Transporters
- Organic Anion Transporter Polypeptides (OATPs)
- A Syndrome of Cerebral Hypometabolism and Juvenile Neurodegeneration Caused by Mutated SLCO1C1
- Monocarboxylate Transporters
- Monocarboxylate Transporter 8 (MCT8)
- Monocarboxylate Transporter 10 (MCT10)
TRANSPORT OF THYROID HORMONES THROUGH THE BRAIN BARRIERS
- The Blood-Brain Barrier (BBB)
- The Blood-Cerebrospinal Fluid Barrier (BCSFB)
- The Meningeal Barrier
- Circumventricular Organs
- Transient Embryonic CSF-Brain Barrier
TRANSPORT OF THYROID HORMONES IN OTHER ORGANISMS
- Thyroid Hormone Transporters in Zebrafish
- Thyroid Hormone Transport in Chicken
CONCLUDING REMARKS
REFERENCES
CHAPTER 7 THE ALLAN-HERNDON-DUDLEY SYNDROME: PATHOPHYSIOLOGY AND MOUSE MODELS OF MCT8 DEFICIENCY
INTRODUCTION
THE ALLAN-HERNDON-DUDLEY SYNDROME
- Clinical Aspects
- Histopathological Changes in the MCT8-Deficient Brain
- Histopathology of MCT8-Deficient Fetus Brain
- Histopathology of an MCT8-Deficient Child Brain
MCT8 DEFICIENCY IN MICE
- Altered Thyroid Gland Secretion and Tissue Deiodinase Activity
- Changes in Thyroid Gland Secretion
- Changes in Deiodinase Activities
- Proposed Sequence of Events in MCT8 Deficiency
- The Phenotype of MCT8-Deficient Mice
- Peripheral Metabolism
- Brain Metabolism
- Brain Architecture and Function
- Perinatal Brain Hyperthyroidism
MOUSE MODELS OF ALLAN-HERNDON-DUDLEY SYNDROME
- Mice Deficient in MCT8 and OATP1C1
- Mice Deficient in MCT8 and DIO2
THERAPEUTIC APPROACHES
- Thyroxine
- Intraamniotic Thyroxine Treatment
- Diiodothyropropionic Acid (DITPA)
- 3,5,3’-Triiodothyroacetic Acid
- Sobetirome
- The MCT8P253L Variant
- Sodium Phenylbutyrate (NaPB)
- Gene Therapy
CONCLUDING REMARKS
REFERENCES
CHAPTER 8 THYROID HORMONE RECEPTORS IN THE BRAIN: DISTRIBUTION AND DELETION EFFECTS ON BRAIN STRUCTURE AND BEHAVIOR
INTRODUCTION
T3 RECEPTOR EXPRESSION IN THE RODENT BRAIN
- Early Expression and Distribution of Receptor mRNAs
- Receptor Protein Distribution
- Receptor Expression in Different Cell Types
UNDERSTANDING RECEPTOR FUNCTION THROUGH MOUSE GENETIC
MODIFICATIONS
- The Phenotypes of Thyroid Hormone Receptor Knockout Mice
- TRα1 in the Control of Emotions, Learning, and Memory
- What the Receptor Gene Deletions Tell About Their in vivo Functions
- Why Receptor Deletion is Not Equivalent to Hormone Deprivation: Aporeceptor
- Function
- Aporeceptor Function in Developmental Timing Control
T3 RECEPTOR EXPRESSION IN THE HUMAN FETAL BRAIN
CONCLUDING REMARKS
REFERENCES
CHAPTER 9 PATHOPHYSIOLOGY AND MOUSE MODELS OF THYROID HORMONE
RESISTANCE SYNDROMES: A FOCUS ON THE BRAIN
INTRODUCTION
GENERAL ASPECTS OF RTH
THE BRAIN PHENOTYPE OF RTH
- Resistance to Thyroid Hormone Due to THRB Mutations (RTHβ)
- Resistance to Thyroid Hormone Due to THRA Mutations (RTHα)
- Compound TRα1 and TRα2 Mutations
MOUSE MODELS OF RTH
- The PV Mutation
- The Family S Mutation
- The R384C Mutation
CONCLUDING REMARKS
REFERENCES
CHAPTER 10 THYROID HORMONE-REGULATED GENES IN THE BRAIN
INTRODUCTION
PATTERNS OF BRAIN GENE REGULATION BY THYROID HORMONE IN VIVO
- Controlling Gene Expression Timing
- Reelin Expression
- Myelin Gene Expression
- Regional Control of Gene Expression
- Regional Control of Neurogranin (Nrgn) Expression
THOUSANDS OF GENES ARE SENSITIVE TO THYROID HORMONE IN VIVO
- The Diversity of Genes Regulated by Thyroid Hormone
- Are There Universal T3 Transcriptionally-Responsive Genes?
THE CAMK4 SIGNALING NETWORK
Author
- Juan Bernal
