The Human Hypothalamus: Anterior Region (Volume 179) (Handbook of Clinical Neurology, Volume 179)

The Hypothalamus is an important area of the brain for understanding a variety of neurological disorders. This volume summarizes for readers the anatomy and physiology of the anterior hypothalamus, to better understand pathology and treatment of hypothalamus related disorders. In addition to anatomy and physiology in humans, cytoarchitecture and chemoarchitecture in rodents is provided. The volume explores the role of the hypothalamus in disorders of eating, sleeping, anxiety, and mood, as well as its role in sexual behavior and gender identity. Coverage includes how Parkinson's, Alzheimer's and other neurological disorders relate to the hypothalamus. Reviews the anatomy and physiology of the anterior hypothalamus Provides cytoarchitecture and chemoarchitecture from rodents Discusses hypothalamic related disorders of eating, sleeping, anxiety, and mood Covers how Parkinson's, Alzheimer's and other neurological disorders relate to the hypothalamus Explores the role of the hypothalamus in sexual behavior and gender identity Front Cover The Human Hypothalamus: Anterior Region Copyright Available Titles Foreword Preface The HCN volumes on the Human Hypothalamus The hypothalamus: Arbitrary borders References Contributors Contents Contents of related volumes Section 1: Introduction Chapter 1: Introduction: The anterior hypothalamus Section 1: Introduction Section 2: The Basal Forebrain Cholinergic System Section 3: The Circadian System Section 4: Bed Nucleus of the Stria Terminalis and the Fear Circuit Section 5: Preoptic Area Reference Chapter 2: History of hypothalamic research: ``The spring of primitive existence ́ ́ Discipline of Neuroendocrinology: Current Definitions Neurosecretion and central effects of neuropeptides Portal system Early Ideas About Pituitary and Pineal Gland Function Neurosecretion and the Neurohypophysis Neuroendocrine neurons Vasopressin, oxytocin, and the neurophysins Blood Supply to the Hypothalamus and Pituitary The portal system Releasing Factors Neuropeptides as Neurotransmitters or Neuromodulators: The Central Pathways Involved Central effect of neuropeptides Control of Autonomic Functions by the Hypothalamus The first evidence: An accident or a logical step in a chain of events in the 1900s in Vienna? The ``peripheral ́ ́ nervous system Claude Bernard: From the periphery back to the brain The diencephalon and vital body functions The emotional diencephalon A conflict in Vienna The hypothalamus and the autonomic nervous system: From the isolated pupil reflexes to complex body functions Between the wars: The rise of endocrinology Lipodystrophy: A neurological disease ``Old-fashioned ́ ́ internist-neurologists and the feeling of being hungry Further exploration of hypothalamic-autonomic interaction: New methods Tracing techniques and the antagonistic model of catabolic and anabolic regions in the hypothalamus Future Directions References Chapter 3: Anatomy and cytoarchitectonics of the human hypothalamus Gross Anatomy Vascular Supply Cytoarchitecture Hypothalamic Pathways References Chapter 4: Morphology and distribution of hypothalamic peptidergic systems Introduction Hypothalamic Peptidergic Systems in Human Corticotropin-releasing hormone system Gonadotropin-releasing hormone system Growth hormone-releasing hormone system Somatostatinergic system Thyrotropin-releasing hormone system β-endorphin-system Enkephalin system Kisspeptin/neorkinin B/dynorphin system Galanin system Galanin-like peptide system Neuropeptide Y system Substance P system Concluding Remarks References Chapter 5: MRI maps, segregation, and white matter connectivity of the human hypothalamus in health Introduction MRI Mapping and Fiber Tracking of the Hypothalamus 3D and 2D Hypothalamic Architecture Macroconnectivity Conclusion References Chapter 6: Magnetic resonance imaging of the hypothalamo-pituitary region Introduction History of Pituitary and Hypothalamic Imaging Technique and Methodology of Magnetic Resonance Imaging Normal MRI of the Pituitary Gland and Hypothalamic Region Indications for Pituitary MRI Imaging of Sellar, Parasellar, and Hypothalamic Lesions Benign Lesions (Macroadenomas, Microadenomas, Craniopharyngiomas, Meningiomas, Pituicytomas, Schwannomas) Cystic Lesions (Rathke's Cleft Cysts, Epidermoid Cysts, Dermoid Cysts, Arachnoid Cysts) Malignant Tumors (Chordomas, Chondrosarcomas, Primary Germ Cell Tumors, Gliomas, Metastases and Lymphomas) Vascular, Inflammatory, and Infectious Lesions (Aneurysms, Hypophysitides, Abscesses) Empty Sella Congenital Abnormalities (Pituitary Stalk Interruption Syndrome, Hamartomas) Surgical Indications Nonfunctioning adenomas Functioning adenomas Intraoperative MRI Summary References Chapter 7: Resting-state functional connectivity of the human hypothalamus Introduction Resting States Functional Connectivity Analyzing Resting-State Functional Connectivity Imaging of the Hypothalamus Using MRI Functional Imaging of the Hypothalamus Hypothalamus RSFC Hypothalamus RSFC in Metabolism and Eating Behavior Hypothalamus RSFC in Persons of Normal and Excessive Weight Effect of Hunger and Satiety on the Hypothalamic Functional Connectivity Network Effect of Nutritional Modulation on Hypothalamus RSFC Hormonal Modulation of the Hypothalamic Resting-State Network Hypothalamus RSFC in Neurological and Psychiatric Diseases Hypothalamus RSFC in Addiction and Depression Hypothalamus RSFC in Neurological Diseases Hypothalamus RSFC in Patients with Migraine Concluding Comments References Chapter 8: Neurogenesis in the adult hypothalamus: A distinct form of structural plasticity involved in metabolic and cir ... Introduction The Hypothalamic Neurogenic Niche: A Brief Overview of the Experimental Models Does the Adult Human Hypothalamus Contain a Neurogenic Niche? Evidence for the presence of neural stem cells in the adult human hypothalamus Organization of the human hypothalamic neural stem cell niche Are new neurons produced in the adult human hypothalamus? Comparative Assessment of the Hypothalamic Niche between Rodents and Humans Current view of the niche organization in rodents The hypothalamic niche in human vs rodents: Similarities and discrepancies Pathophysiologic Implications of Hypothalamic Neurogenesis in Humans How to Move Forward? Acknowledgments References Chapter 9: Matching of the postmortem hypothalamus from patients and controls Introduction Clinical diagnosis and neuropathology Neuropathology of controls Potential Confounding Factors Antemortem factors Genetic background Systemic diseases, prolonged illness, and gravity of illness Medicines and addictive compounds used Development and aging Sex, gender identity, and sexual orientation Circadian variations Seasonal variations Lateralization Factors during dying Agonal state Stress of dying Postmortem factors PMD Storage time of body or tissues Conclusion Acknowledgments References Section 2: The basal forebrain cholinergic system Chapter 10: Spatial topography of the basal forebrain cholinergic projections: Organization and vulnerability to degeneration Introduction Topographic Projections of the BF in Rodents and Nonhuman Primates Topographic Projections of the Basal Forebrain in Humans Ex vivo localization of the human basal forebrain nuclei In vivo MRI of the human basal forebrain nuclei and topographic projections In vivo PET of the human basal forebrain compartments and projections Spatial Topography of Basal Forebrain Vulnerability to Neurodegeneration Topography of basal forebrain vulnerability in Alzheimer's disease Topography of basal forebrain vulnerability in Parkinson's and dementia with Lewy bodies Selective neuronal vulnerability to neurodegeneration: Factors and future directions Acknowledgments References Chapter 11: The diagonal band of Broca in health and disease Introduction Locating the ``Diagonal Band ́ ́ Defining the ``Nucleus ́ ́ and the ``Limbs ́ ́ of the Diagonal Band Rostro-Caudal Mapping of the DBB The Neurochemical Profile of Neurons in the nvlDBB The Often Neglected nhlDBB Delineation of the Boundaries of the nvlDBB Neuropathology of the nvlDBB Alzheimer's Disease (AD) Parkinson's Disease (PD) and Lewy Body Dementias (LBD) Other Neurological Conditions and Aging Functional Correlates of nvlDBB Cell Loss Conclusion References Chapter 12: Nucleus basalis of Meynert degeneration predicts cognitive impairment in Parkinson ́s disease Introduction Cognitive Impairment in Parkinson's Disease The Nucleus Basalis of Meynert Structure and function of the nucleus basalis of Meynert Pathological studies in Parkinson's disease Neuroimaging Techniques to Study Cognitive Impairment and the Role of the Nucleus Basalis of Meynert in Parkinson's Disease Positron emission tomography Glucose metabolic PET molecular imaging Cholinergic PET molecular imaging Magnetic resonance imaging Structural gray matter volumetric MRI Microstructural white matter diffusion MRI Therapeutic Interventions Deep brain stimulation Conclusion and Future Directions References Chapter 13: Enlargement of early endosomes and traffic jam in basal forebrain cholinergic neurons in Alzheimer ́s disease Introduction Basal Forebrain Cholinergic Neurons Degeneration Possible Iatrogenic Mechanisms of Cholinergic Degeneration Intrinsic Mechanism: Failed NGF Signaling Blocking the path Abnormal tracks Loss of motors Destruction of the signal Endosomal enlargement Therapeutic Strategies Targeting the Cholinergic System Improving ACh neurotransmission Improving NGF signaling Conclusions Acknowledgment References Further reading Chapter 14: Gene and cell therapy for the nucleus basalis of Meynert with NGF in Alzheimer ́s disease Introduction The Cholinergic System and the Basal Forebrain Treatment with ChEIs in Alzheimer's Disease Rationale for Nerve Growth Factor in Alzheimer's Disease Intracerebroventricular Infusion of NGF Painless NGF Local Delivery of NGF NGF delivery via genetically modified cells or viral vectors to the nbM Encapsulated cell biodelivery of NGF to the nbM Conclusion References Section 3: The circadian system Chapter 15: The circadian system: From clocks to physiology Introduction The need to synchronize our activities with the light-dark cycle The central clock as a coordinator of physiology Clock Genes: The Driving Force Behind the Rhythm in the SCN and of the Metabolism in Peripheral Cells Circadian Rhythms in Physiology: Continuously Changing Homeostasis Rhythmic Secretion ofHormones: A Reflection of SCN Activity Cortisol secretion: Associated with the onset of activity or with food intake Circumventricular organs: Monitoring the circulation for cortisol and metabolites LH secretion The SCN Controls the Rhythmic Physiology of All the Organs in the Body Disturbances in SCN Activity Trigger Pathologies Desynchrony of Behavior With the Light-Dark Cycle: A Deviation in Modern Life Leads to a Wide Variation Conclusion References Chapter 16: Development of the circadian system and relevance of periodic signals for neonatal development Introduction Development of the circadian system Maternal influence in the development of the circadian system during gestation Biological rhythms in the newborn Factors influencing early circadian development Relevance of a LD in the neonatal intensive care unit Final comments Acknowledgment References Further reading Chapter 17: Disrupted circadian rhythms and mental health Introduction Circadian System Disruption of Circadian Rhythms and Anxiety Disruption of Circadian Rhythms and Major Depressive Disorder Circadian Rhythm Disruption and Bipolar Disorder Circadian Rhythm Disruption and Schizophrenia Conclusions and Future Directions Acknowledgments References Chapter 18: Diurnal and seasonal molecular rhythms in the human brain and their relation to Alzheimer disease Diurnal Rhythms and Dementia in Older Adults Diurnal rhythms and normal human brain function Altered diurnal rhythms, cognitive impairment, and dementia in older adults Seasonal Rhythms and Dementia in Older Adults Diurnal Brain Molecular Rhythms in Model Organisms Organization of the circadian timing system Diurnal rhythms of brain gene expression Diurnal rhythms of brain epigenetic modification Seasonal Brain Molecular Rhythms in Model Organisms Diurnal and Seasonal Molecular Rhythms in the Human Neocortex Diurnal molecular rhythms Seasonal molecular rhythms Limitations and opportunities References Chapter 19: Circadian changes in Alzheimer ́s disease: Neurobiology, clinical problems, and therapeutic opportunities Introduction Pathogenesis of AD: Beaten Tracks and Novel Emerging Concepts Hypothalamus at the Crossroads of Early Circadian and Metabolic Disruptions in AD: Evidence From Animal Models Functional Consequences of an Early Hypothalamic Involvement in AD Pathogenesis Circadian rhythmicity and sleep Metabolic dysregulation Clinical Challenges: From Bench to Bedside Diagnosis Comorbidities Bidirectional vicious cycle Neurodegeneration Therapeutic Opportunities Restoring circadian rhythmicity Reducing inflammation and neuroinflammation Increasing neuronal resilience Optimizing vascular health Increasing insulin sensitivity Conclusion/Summary References Chapter 20: The circadian system in Parkinson ́s disease, multiple system atrophy, and progressive supranuclear palsy Introduction Circadian Alterations in PD, MAS, and PSP Parkinson's disease Multiple system atrophy Progressive supranuclear palsy Neuropathologic and Functional Dissection of the Neuronal Circuitry Governing Circadian Rhythms in PD, MSA, and PSP Pathologic Status of the Afferent Pathways to the Clock Pathologic Status of the Central SCN Clock Pathologic Status of the Efferent Pathways of the Clock Conclusions References Chapter 21: Retina and melanopsin neurons Melanopsin Retinal Ganglion Cells: Anatomy, Physiology, and Functions Melanopsin retinal ganglion cells: Discovery and anatomy Melanopsin retinal ganglion cells: Physiology Melanopsin retinal ganglion cells: Functions Melanopsin Retinal Ganglion Cells: Resistance to Neurodegeneration in Mitochondrial Optic Neuropathies Melanopsin Retinal Ganglion Cells in Age-Related Neurodegenerative Disorders Alzheimer's disease Parkinson's disease Other neurodegenerative disorders Melanopsin Retinal Ganglion Cells in Aging Conclusions Acknowledgments Funding References Chapter 22: Melatonin and the circadian system: Keys for health with a focus on sleep Introduction Melatonin: Identification and Synthesis Melatonin: Role, Mechanisms of Action, and Clinical Perspectives Role of endogenous melatonin in the circadian system Role of exogenous melatonin: From hormone to chronobiotic drug Melatonin and sleep Sites and mechanisms of action mediating the chronobiotic effects of melatonin Melatonin receptors and their localization Melatonin receptor agonists/antagonists and drugs Conclusions Acknowledgments References Chapter 23: Melatonin receptors, brain functions, and therapies Introduction Expression of Melatonin Receptors in the Human Hypothalamus Suprachiasmatic nucleus (SCN) SCN subregions and cell populations Circadian variation Variation with disease Supraoptic nucleus (SON) and paraventricular nucleus (PVN) Function of Melatonin Receptors in Hypothalamus Circadian rhythm and melatonin receptors in the hypothalamus The pituitary-hypothalamic connection Drugs Targeting Melatonin Receptors Prolonged-release melatonin Ramelteon Tasimelteon Agomelatine Future Drug Developments References Chapter 24: Chronotherapy Introduction Biological Rhythms: An Overview Relevant for Chronotherapy The Sleep/Wake Cycle, A Target for Chronotherapy Some Basic Concepts About Chronopharmacology Melatonin, A Chronobiotic Prototype Future of Chronotherapy Concluding Remarks References Chapter 25: The use of melatonin to mitigate the adverse metabolic side effects of antipsychotics Introduction Antipsychotics and Their Side Effects: A Bad Name Melatonin Use in Antipsychotic-Induced Adverse Metabolic Effects: Clinical Studies Why Melatonin? The Circadian System and Metabolic Regulation Mechanisms Implicated in Antipsychotic-Induced AMEs and Their Prevention With Melatonin Clinical Implications Conclusions References Section 4: Bed nucleus of the stria terminalis and the fear circuit Chapter 26: Chemoarchitecture of the bed nucleus of the stria terminalis: Neurophenotypic diversity and function Introduction Neurotransmitters Neuropeptides Corticotropin-releasing factor Urocortin Neurotensin Pituitary adenylate cyclase-activating polypeptide Vasoactive intestinal peptide Opioid peptides Calcitonin gene-related peptide Neuropeptide Y Somatostatin Oxytocin and vasopressin BNST Sexual Dimorphism and Control of Sexual Behaviors Human BNST Overview and Conclusions References Chapter 27: Functional anatomy of the bed nucleus of the stria terminalis-hypothalamus neural circuitry: Implications for ... Introduction Anterior BNST Circuitry Posterior BNST Circuitry BNST-Hypothalamus Circuitry BNST-Hypothalamus Circuitry in Valence Surveillance The BNST in Addiction BNST-Hypothalamus Circuitry in Feeding BNST-Hypothalamus Circuitry in Social Behavior Sex Differences in the BNST Concluding Comments References Chapter 28: Roles of the bed nucleus of the stria terminalis and amygdala in fear reactions Overview Defining Fear The Bed Nucleus of the Stria Terminalis Anatomy Current theories of the BNST in behavioral, subjective, and physiological fear responses Overview Behavioral responses Subjective responses Physiological responses The Amygdala Overview Anatomy Current theories of the amygdala in behavioral, subjective, and physiological fear responses Threat physiology and behavior Subjective experience Differences between the amygdala and BNST in contributions to fear Threat imminence Temporal predictability and response duration Outcome predictability Integrative model of the role of the amygdala and BNST in fear References Section 5: Preoptic area Chapter 29: The median preoptic nucleus: A major regulator of fluid, temperature, sleep, and cardiovascular homeostasis Introduction Neurochemical Properties of MnPO Neurons Neural Connectivity Afferent neural connections Efferent neural connections Collaterals Body Fluid Homeostasis Thirst Inhibition of thirst Antidiuretic hormone secretion Renal sodium excretion Body Temperature Homeostasis Cutaneous thermoreceptors influence MnPO neurons Hot flushes Fever Sleep Homeostasis Cardiovascular Homeostasis Concluding Remarks References Chapter 30: The neuroendocrinology of the preoptic area in menopause: Symptoms and therapeutic strategies Introduction to the Preoptic Area and Thermoregulation Estrogen and Dysfunctional Thermoregulation The Importance of KNDy Neurons in Menopause and Thermoregulation Neurokinin B and Hot Flushes Antagonism of NKB/NK3R Signaling as a Therapy for Hot Flushes Conclusion Acknowledgments References Chapter 31: The intermediate nucleus in humans: Cytoarchitecture, chemoarchitecture, and relation to sleep, sex, and Alzh ... Chemoarchitecture of the Intermediate Nucleus The galaninergic neurons in the intermediate nucleus across aging, gender, sexual orientation, and sexual identity The effects of dementia on the galaninergic neurons in the intermediate nucleus The role of the ventrolateral preoptic nucleus galaninergic neurons in wake-sleep Conclusion References Index Back Cover