The Human Hypothalamus

Anterior Region

1st Edition, Volume 179 - June 15, 2021
Editors: Dick F. Swaab, Felix Kreier, Paul J. Lucassen, Ahmad Salehi, Ruud M. Buijs
Language: English
Hardback ISBN:
9 7 8 - 0 - 1 2 - 8 1 9 9 7 5 - 6
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 1 9 9 7 6 - 3

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 an… Read more

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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.

Cover image
Title page
Table of Contents
Copyright
Handbook of Clinical Neurology 3rd Series
Foreword
Preface
The HCN volumes on the Human Hypothalamus
Contributors
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
Chapter 2: History of hypothalamic research: “The spring of primitive existence”
Abstract
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
Blood Supply to the Hypothalamus and Pituitary
Releasing Factors
Neuropeptides as Neurotransmitters or Neuromodulators: The Central Pathways Involved
Control of Autonomic Functions by the Hypothalamus
Future Directions
Chapter 3: Anatomy and cytoarchitectonics of the human hypothalamus
Abstract
Gross Anatomy
Vascular Supply
Cytoarchitecture
Hypothalamic Pathways
Chapter 4: Morphology and distribution of hypothalamic peptidergic systems
Abstract
Introduction
Hypothalamic Peptidergic Systems in Human
Concluding Remarks
Chapter 5: MRI maps, segregation, and white matter connectivity of the human hypothalamus in health
Abstract
Introduction
MRI Mapping and Fiber Tracking of the Hypothalamus
3D and 2D Hypothalamic Architecture
Macroconnectivity
Conclusion
Chapter 6: Magnetic resonance imaging of the hypothalamo–pituitary region
Abstract
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
Summary
Chapter 7: Resting-state functional connectivity of the human hypothalamus
Abstract
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
Chapter 8: Neurogenesis in the adult hypothalamus: A distinct form of structural plasticity involved in metabolic and circadian regulation, with potential relevance for human pathophysiology
Abstract
Introduction
The Hypothalamic Neurogenic Niche: A Brief Overview of the Experimental Models
Does the Adult Human Hypothalamus Contain a Neurogenic Niche?
Comparative Assessment of the Hypothalamic Niche between Rodents and Humans
Pathophysiologic Implications of Hypothalamic Neurogenesis in Humans
How to Move Forward?
Acknowledgments
Chapter 9: Matching of the postmortem hypothalamus from patients and controls
Abstract
Introduction
Potential Confounding Factors
Conclusion
Acknowledgments
Section 2: The basal forebrain cholinergic system
Chapter 10: Spatial topography of the basal forebrain cholinergic projections: Organization and vulnerability to degeneration
Abstract
Introduction
Topographic Projections of the BF in Rodents and Nonhuman Primates
Topographic Projections of the Basal Forebrain in Humans
Spatial Topography of Basal Forebrain Vulnerability to Neurodegeneration
Acknowledgments
Chapter 11: The diagonal band of Broca in health and disease
Abstract
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
Chapter 12: Nucleus basalis of Meynert degeneration predicts cognitive impairment in Parkinson's disease
Abstract
Introduction
Cognitive Impairment in Parkinson's Disease
The Nucleus Basalis of Meynert
Neuroimaging Techniques to Study Cognitive Impairment and the Role of the Nucleus Basalis of Meynert in Parkinson's Disease
Therapeutic Interventions
Conclusion and Future Directions
Chapter 13: Enlargement of early endosomes and traffic jam in basal forebrain cholinergic neurons in Alzheimer's disease
Abstract
Introduction
Basal Forebrain Cholinergic Neurons Degeneration
Possible Iatrogenic Mechanisms of Cholinergic Degeneration
Intrinsic Mechanism: Failed NGF Signaling
Therapeutic Strategies Targeting the Cholinergic System
Conclusions
Acknowledgment
Chapter 14: Gene and cell therapy for the nucleus basalis of Meynert with NGF in Alzheimer's disease
Abstract
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
Local Delivery of NGF
Conclusion
Section 3: The circadian system
Chapter 15: The circadian system: From clocks to physiology
Abstract
Introduction
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
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 of Pathologies
Conclusion
Chapter 16: Development of the circadian system and relevance of periodic signals for neonatal development
Abstract
Introduction
Final comments
Acknowledgment
Chapter 17: Disrupted circadian rhythms and mental health
Abstract
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
Chapter 18: Diurnal and seasonal molecular rhythms in the human brain and their relation to Alzheimer disease
Abstract
Diurnal Rhythms and Dementia in Older Adults
Seasonal Rhythms and Dementia in Older Adults
Diurnal Brain Molecular Rhythms in Model Organisms
Seasonal Brain Molecular Rhythms in Model Organisms
Diurnal and Seasonal Molecular Rhythms in the Human Neocortex
Chapter 19: Circadian changes in Alzheimer's disease: Neurobiology, clinical problems, and therapeutic opportunities
Abstract
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
Clinical Challenges: From Bench to Bedside
Therapeutic Opportunities
Conclusion/Summary
Chapter 20: The circadian system in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy
Abstract
Introduction
Circadian Alterations in PD, MAS, and PSP
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
Chapter 21: Retina and melanopsin neurons
Abstract
Melanopsin Retinal Ganglion Cells: Anatomy, Physiology, and Functions
Melanopsin Retinal Ganglion Cells: Resistance to Neurodegeneration in Mitochondrial Optic Neuropathies
Melanopsin Retinal Ganglion Cells in Age-Related Neurodegenerative Disorders
Melanopsin Retinal Ganglion Cells in Aging
Conclusions
Chapter 22: Melatonin and the circadian system: Keys for health with a focus on sleep
Abstract
Introduction
Melatonin: Identification and Synthesis
Melatonin: Role, Mechanisms of Action, and Clinical Perspectives
Conclusions
Acknowledgments
Chapter 23: Melatonin receptors, brain functions, and therapies
Abstract
Introduction
Expression of Melatonin Receptors in the Human Hypothalamus
Function of Melatonin Receptors in Hypothalamus
Drugs Targeting Melatonin Receptors
Future Drug Developments
Chapter 24: Chronotherapy
Abstract
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
Chapter 25: The use of melatonin to mitigate the adverse metabolic side effects of antipsychotics
Abstract
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
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
Abstract
Introduction
Neurotransmitters
Neuropeptides
BNST Sexual Dimorphism and Control of Sexual Behaviors
Human BNST
Overview and Conclusions
Chapter 27: Functional anatomy of the bed nucleus of the stria terminalis–hypothalamus neural circuitry: Implications for valence surveillance, addiction, feeding, and social behaviors
Abstract
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
Chapter 28: Roles of the bed nucleus of the stria terminalis and amygdala in fear reactions
Abstract
Overview
Defining Fear
The Bed Nucleus of the Stria Terminalis
The Amygdala
Differences between the amygdala and BNST in contributions to fear
Section 5: Preoptic area
Chapter 29: The median preoptic nucleus: A major regulator of fluid, temperature, sleep, and cardiovascular homeostasis
Abstract
Introduction
Neurochemical Properties of MnPO Neurons
Neural Connectivity
Body Fluid Homeostasis
Body Temperature Homeostasis
Sleep Homeostasis
Cardiovascular Homeostasis
Concluding Remarks
Chapter 30: The neuroendocrinology of the preoptic area in menopause: Symptoms and therapeutic strategies
Abstract
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
Chapter 31: The intermediate nucleus in humans: Cytoarchitecture, chemoarchitecture, and relation to sleep, sex, and Alzheimer disease
Abstract
Chemoarchitecture of the Intermediate Nucleus
Conclusion
Index

Dick F. Swaab

Dick Swaab (1944) earned his medical and doctoral degrees at the University of Amsterdam, where he became involved in brain research during his third year of medical school. He was Director of the Netherlands Institute for Brain Research from 1978 to 2005. Since 1979 he is Professor of Neurobiology at the Medical Faculty, University of Amsterdam.

In 1985, Dr. Swaab founded the Netherlands Brain Bank (NBB) to serve as a source of clinically and neuropathologically well-documented research tissue. Since its founding, the Brain Bank has provided samples from more than 4,000 autopsies to 500 research groups in 25 countries. He was director of the NBB until 2005.

He is Leader Research team Neuropsychiatric Disorders, Neth. Inst for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences (KNAW). Swaab is also appointed for 2011-2017 Chao Kuang Piu Chair of Zhejiang University, Hangzhou, P.R. China.

His major research interests focus on, sexual differentiation of the human brain in relation to gender identity and sexual orientation, aging of the brain, Alzheimer’s disease, the neurobiological basis of depression, suicide and eating disorders. He has published over 540 papers in SCI journals, authored more than 200 chapters in books, and edited more than 60 books. Swaab mentored 84 PhD students from which 16 are now full professor. He is “Companion in the Order of the Dutch Lion”, bestowed by her Royal Majesty Queen Beatrix of the Netherlands. In 2008 Swaab obtained the Academy medal for his role in national and international neuroscience.

Dick Swaab is author of the 2 volume monograph The Human Hypothalamus that appeared in the Handbook of Clinical Neurology series, Elsevier, Amsterdam (1000 pp) and the Dutch best seller We are our Brains (450.000 copies sold), that is translated in 14 languages. A children's version of the book (You are your brains) has also appeared in Dutch in 2013 and Russian (2014). Swaab's H-factor is 76.

Affiliations and expertise

Netherlands Institute for Brain Research, University of Amsterdam, Amsterdam, The Netherlands

Felix Kreier

Felix Kreier is a pediatrician and affiliated with OLVG Hospitals in Amsterdam, The Netherlands.

Affiliations and expertise

OLVG Hospitals, Amsterdam, The Netherlands

Paul J. Lucassen

Paul J. Lucassen did his PhD in 1995 on Alzheimer’s Disease at the Netherlands Institute for Brain Research in Amsterdam. After a.o. a postdoc in Leiden, he became Full Professor of Brain Plasticity in 2011 at the Swammerdam Institute for Life Sciences (SILS) of the University of Amsterdam, The Netherlands. His group studies molecular, nutritional, pharmacological and environmental regulation of brain plasticity. They combine molecular tools, in vitro/vivo model systems, human brain tissue, cohort studies and brain imaging. A major focus is on adult neurogenesis and cognition in relation to; (early life) stress, exercise, enrichment, depression, brain insults and dementia.

Affiliations and expertise

Swammerdam Institute for Life Sciences (SILS) - Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands

Ahmad Salehi

Ahmad Salehi is affiliated with Stanford Medical School, Department of Psychiatry & Behavioral Sciences, in Palo Alto, CA, United States.

Affiliations and expertise

Stanford Medical School, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, United States

Ruud M. Buijs

Dr. Ruud M. Buijs is head of the Physiology department of the I.I.Biomedicas at the UNAM university and leader of the group Hypothalamic Integration Mechanisms. In that group, the scientists study how the brain and body interact with each other, and hereby the attention is focussed on autonomic and hormonal regulation of body functions under the influence of the biological clock of the brain.

Affiliations and expertise

Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Ciudad Universitaria, Mexico D.F.

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The Human Hypothalamus

Anterior Region

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Institutional subscription on ScienceDirect

Dick F. Swaab

Felix Kreier

Paul J. Lucassen

Ahmad Salehi

Ruud M. Buijs