The Human Hypothalamus in Health and Disease

Recent volumes in Progress in Brain Research

List of Contributors

Preface

Acknowledgements

Section I - Structure of the Human Hypothalamus

Chapter 1: Anatomy of the human hypothalamus (chiasmatic and tuberal region)

Introduction

The hypothalamic gray

The magnocellular neurosecretory complex

The sexually dimorphic intermediate nucleus

The suprachiasmatic nucleus

The retrochiasmatic nucleus and the melanin-containing hypothalamic nerve cells

The ventromedial, posteromedial and dorsomedial nuclei

The periventricular and infundibular nuclei

The lateral tuberal nucleus

The tuberomamillary nucleus

Summary and conclusions

Acknowledgements

Discussion

Section II - Clinical Manifestations of Hypothalamic Diseases

Chapter 2: Endocrine functions of the hypothalamus and alterations in neuroendocrine function – focus on thyrotropin and growth hormone

Introduction

Thyroid stimulating hormone (TSH)

Growth hormone (GH)

Perspectives

Discussion

Chapter 3: Neurologic manifestations of hypothalamic disease

Introduction

Case descriptions

Discussion

Summary and conclusions

Discussion

Section III - Technical Potentialities and Pitfalls in the Use of Human Material

Chapter 4: In situ hybridization histochemistry in the human hypothalamus

Introduction

In situ hybridization histochemistry: methodological considerations

Neuropeptide mRNA visualization in human basal ganglia

Neuropeptide mRNA alterations in Parkinson’s disease and Huntington’s chorea basal ganglia

Summary and conclusions

Acknowledgements

Chapter 5: Receptor localization in the human hypothalamus

Introduction: neurotransmitter receptor structure and function

Techniques for the visualization of receptors in human post-mortem materials. Radioligand binding autoradiography

Receptors in human hypothalamus

Other techniques for receptor visualization

Summary and conclusions

Discussion

Chapter 6: Human hypothalamic and pituitary neuroendocrine function during in vitro perifusion

Introduction

Methods

Hypothalamus

Pituitary

Strengths and weaknesses of the perifusion methodology

Acknowledgements

Discussion

Chapter 7: Brain banking and the human hypothalamus – factors to match for, pitfalls and potentials

Introduction

Ante-mortem factors

Post-mortem factors

Summary and conclusions

Acknowledgements

Section IV - Biological Rhythms

The fourth C.U. Ariëns Kappers lecture

Chapter 8: The organization of the human circadian timing system

Introduction

Functional organization of the rodent CTS

Organization of the primate CTS

Summary and conclusions

Acknowledgements

Discussion

Chapter 9: Pre-natal development of a hypothalamic biological clock

Introduction

Tick tock, it’s a fetal clock

Mother communicates circadian information to the fetus

Potential functions of an entrained fetal clock

Development of a biological clock in humans

Summary and conclusions

Discussion

Chapter 10: The human hypothalamus: comparative morphometry and photoperiodic influences

Introduction

Size and scaling of the hypothalamus

The preoptic region of the hypothalamus

Seasonal variations in the human SCN

Photoperiodic influences on the SCN

Summary and conclusions

Acknowledgements

Discussion

Chapter 11: Circadian rhythms and the suprachiasmatic nucleus in perinatal development, aging and Alzheimer’s disease

Introduction

Circadian rhythms in early human development

Human SCN changes during early development

Circadian rhythms change in aging and in AD

Human SCN changes during aging and in AD

Summary and conclusions

Discussion

Section V - Development, Aging and Dementia

Chapter 12: Ontogeny of peptides in human hypothalamus in relation to sudden infant death syndrome (SIDS)

Introduction

Methodological questions raised by studies of peptides and binding sites in the human hypothalamus

Immunohistochemistry

Quantitative autoradiography

SRIF binding sites

TRH binding sites

Distribution of SRIF immunoreactive neurons

Distribution of SRIF binding sites

Comparison of the distribution of SRIF and its binding sites (Fig. 3)

Distribution of TRH binding sites

Immunohistochemical distribution of LHRH neurons

Summary and conclusions

Acknowledgements

Discussion

Chapter 13: LHRH neurons: functions and development

Introduction

Normal controls on adult LHRH neurons, in perspective

LHRH neuronal migration during development

LHRH-expressing cells in Kallmann’s syndrome, a human hypogonadal disease

Summary and conclusions

Discussion

Chapter 14: The human hypothalamus in relation to gender and sexual orientation

History

Sexual differentiation of the human hypothalamus

The human hypothalamus, sexual orientation and gender identity

Conclusions and summary

Acknowledgements

Discussion

Chapter 15: Hormonal influences on morphology and neuropeptide gene expression in the infundibular nucleus of postmenopausal women

Introduction

Neuronal hypertrophy occurs in a subpopulation of neurons in the infundibular nucleus of postmenopausal women

Hypertrophied neurons in the infundibular nucleus of post-menopausal women express estrogen receptor gene transcripts

Hypertrophied neurons in the infundibular nucleus of post-menopausal women contain substance P and neurokinin B messenger RNAs

Menopause is associated with marked increases in tachykinin gene expression

General discussion

Summary and conclusions

Acknowledgements

Discussion

Chapter 16: The human hypothalamo-neurohypophyseal system in relation to development, aging and Alzheimer’s disease

Introduction

Changes in HNS function during aging: early studies

Evidence of increased HNS activity during aging

Alzheimer’s disease

Suprachiasmatic nucleus

Fetal development

Summary and conclusions

Acknowledgements

Discussion

Chapter 17: The hypothalamic lateral tuberal nucleus: normal anatomy and changes in neurological diseases

Introduction

Normal anatomy

NTL changes in normal aging and neurological diseases

Discussion

Summary and conclusions

Acknowledgements

Chapter 18: Galanin tuberomammillary neurons in the hypothalamus in Alzheimer’s and Parkinson’s diseases

Introduction

The Zurich study

Computer-assisted quantitative morphological analyses

Galanin neurons

Conclusions and summary

Section VI - Osmoregulation

Chapter 19: Animal models for osmoregulatory disturbances

Introduction

Primary polydipsic diabetes insipidus

Nephrogenic diabetes insipidus

Familial neurogenic diabetes insipidus

Summary and conclusions

Discussion

Chapter 20: Autoimmune hypothalamic diabetes insipidus (“autoimmune hypothalamitis”)

Introduction

Detection of cytoplasmic vasopressin cell antibodies

Reactivity of the specific vasopressin cell autoantigen

Vasopressin cell antibodies in different forms of diabetes insipidus

Polyendocrine autoimmunity and hypothalamic diabetes insipidus

Conclusions and outlook

Discussion

Chapter 21: The molecular biology of human hereditary central diabetes insipidus

Introduction

Biochemical, histological and genetic investigations

Molecular biology of the AVP gene

Molecular biology of hereditary central DI in the rat

Molecular biology of human AVP gene in central DI

Linkage strategy

Sequence analysis of AVP gene

Summary and conclusions

Discussion

Chapter 22: The use of linkage analysis and the Centre d’Etude Polymorphisme Humain (CEPH) panel of DNA in the study of the arginine vasopressin, oxytocin and prodynorphin gene loci

Introduction

Basics of linkage analysis

Southern blots and restriction enzyme analysis

Discussion

Section VII - Hypothalamus and Reproduction

Chapter 23: Animal models for brain and pituitary gonadal disturbances

Introduction

The hypogonadal mouse

Neural transplantation

Sex differences in neurotransmitters

Future perspectives

Discussion

Chapter 24: Genetic, hypothalamic and endocrine features of clinical and experimental obesity

Introduction

Hypothalamic obesity

Endocrine obesity

Genetic obesity

Summary and conclusions

Acknowledgements

Discussion

Chapter 25: Hypothalamic involvement in sexuality and hostility: comparative psychological aspects

Introduction

Behavior as hypothalamic output

Psychoneuroendocrinology and psychological functions: behavior as hypothalamic input

Hypothalamus, the polycystic ovarian syndrome and psychological concomitants

Summary and conclusions

Section VIII - Hypothalamus and Stress

Chapter 26: Re-examination of the glucocorticoid hypothesis of stress and aging

Introduction

Two lines of evidence for the glucocorticoid cascade hypothesis

Age-related deficits in HPA function

Changes in hippocampal adrenal steroid receptors with aging

Neuronal degenerative changes during aging and the possible role of glucocorticoids

Does the glucocorticoid cascade hypothesis apply to the human hippocampus?

Possible mechanisms of degenerative effects of glucocorticoids on the hippocampus

Can age-related neuronal degeneration be retarded?

Conclusions

Acknowledgements

Discussion

Chapter 27: The role of corticotropin-releasing hormone in the pathogenesis of Cushing’s disease, anorexia nervosa, alcoholism, affective disorders and dementia

Introduction

Functional neuroanatomy and regulation of the CRH neuron

Regulation of the human CRH (hCRH) gene promoter by cAMP and glucocorticoids

Preclinical studies

Clinical studies

Aging, dementia and Alzheimer’s disease

Conclusions

Chapter 28: Endogenous pyrogens in the CNS: role in the febrile response

Introduction

Role of prostaglandins as mediators in the febrile reaction

Cyclooxygenase in the central nervous system

Cytokines as neuromodulators

A new model for endogenous pyrogens in the brain

Summary and conclusions

Acknowledgements

Discussion

Section IX - Psychiatric Diseases

Chapter 29: Endorphins and schizophrenia

Introduction

Formation and biological activities of endorphins

The endorphin excess hypothesis of schizophrenia

The endorphin deficiency hypothesis of schizophrenia

γ-Type endorphins and schizophrenia

Conclusions

Acknowledgements

Discussion

Chapter 30: Neurohypophyseal peptides and psychopathology

Introduction

Influence of exogenous AVP and OT on human behavior

Neurohypophyseal function in psychiatric disorders

Conclusions and perspectives

Discussion

Subject Index