Histamine In The Brain

Brain aminergic pathways are organized in parallel and interacting systems, which support a range of functions, from homoeostatic regulations to cognitive, and motivational processes. Despite overlapping functional influences, dopamine, serotonin, noradrenaline and histamine systems provide different contributions to these processes. The histaminergic system, long ignored as a major regulator of the sleep-wake cycle, has now been fully acknowledged also as a major coordinator of attention, learning and memory, decision making. Although histaminergic neurons project widely to the whole brain, they are functionally heterogeneous, a feature which may provide the substrate for differential regulation, in a region-specific manner, of other neurotransmitter systems. Neurochemical preclinical studies have clearly shown that histamine interacts and modulates the release of neurotransmitters that are recognized as major modulators of cognitive processing and motivated behaviours. As a consequence, the histamine system has been proposed as a therapeutic target to treat sleep-wake disorders and cognitive dysfunctions that accompany neurodegenerative and neuroinflammatory pathologies. Last decades have witnessed an unexpected explosion of interest in brain histamine system, as new receptors have been discovered and selective ligands synthesised. Nevertheless, the complete picture of the histamine systems fine-tuning and its orchestration with other pathways remains rather elusive. This Research Topic is intended to offer an inter-disciplinary forum that will improve our current understanding of the role of brain histamine and provide the fundamentals necessary to drive innovation in clinical practice and to improve the management and treatment of neurological disorders.

Research in the field of histamine receptors over the past 100 years went hand-in-hand with the development of modern pharmacology. Advances in histamine research led by outstanding scientists was so incisive that the clinical approach to treat allergies and gastrointestinal ailments was revolutionized. The pharmacological treatment of peptic ulcer and gastroesophageal reflux was indeed a revolution, as it ended the surgical intervention. Interest in histamine pharmacology was resurrected by the discovery of another histamine receptor, number 4, using genomics-based reverse pharmacological approaches for screening orphan GPCRs. This receptor is preferentially expressed by immune cells and its discovery raised hopes for its translational exploitation as a new therapeutic target for unmet medical needs ranging from asthma to cancer. However, several drawbacks emerged and dramatically slowed down research in the field. A better understanding of receptor intra-and interspecies heterogeneity will certainly improve and accelerate the translation of experimental data into clinical practice. Also, the plethora of data on brain histamine is hinting at a fundamental role of this system as a hub that receives internal and peripheral stimuli to allocate the necessary excitation to specific brain circuits that preside the appropriate behavioral responses. The development of new histaminergic ligands is an ongoing process that constantly provide new preclinical tools. The aim of this book is to cover the most important aspects of histamine receptor function and pharmacology in the central nervous system and to provide a comprehensive overview of the preclinical and clinical advances made in recent decades and the exciting prospects for the future. It highlights the clinical areas where there is a great need for new therapeutic approaches and where novel histaminergic agents may be useful for personalized medicine.

This book provides an overview on the histaminergic neuron system in the brain for neuroscience, anatomy, pharmacology, biochemistry, and medical researchers. Topics discussed include the biochemistry of enzymes; histamine receptors (H1, H2, and H3); morphology, coexistance, and development of the histaminergic neuron system; electrophysiological studies on vertebrate and invertebrate neurons; as well as the functions of the histamine neurons.

The year 2010 marks the centennial for the identification of histamine and the first glimpse of its many physiological functions. From these initial findings a rich tapestry of research has uncovered roles for histamine in almost every physiological process with new findings emerging every year. These diverse roles of histamine have made for fertile ground for the discovery of novel therapeutics, and these drugs have been so successful that the term “antihistamine” has entered the common lexicon. This volume is an attempt to give a snapshot in time as to the current understanding of the role of histamine in just one important therapeutic area—inflammation. The first three chapters provide some background context for the rest of the book starting out with a historical perspective by Figueroa and Shankley. Bongers et al provide an overview of the pharmacology of the four histamine receptors and the chapter by Hiroshi Ohtsu describes how histamine is synthesized as well as the insights derived from mice where this synthesis is disrupted. The next several chapters discuss disease areas where histamine is known to be involved. Chapter 4 by Thomas Taylor-Clark outlines the role of histamine in allergic rhinitis, an area were antihistamines are commonly used. This is also true for ocular allergy as discussed by Ohbayashi et al. Both of these chapters highlight aspects of these conditions that are still not well-controlled and suggest the utility of new antihistamines targeting other histamine receptors.

Reveals an Emerging Avenue of Potential Treatments for a Host of Challenging Diseases and DisordersThe H3 receptor is known to play a major role in a range of CNS disorders, including those affecting cognitive functions such as ADHD and Alzheimer's disease, as well as sleep disorders, obesity, epilepsy, schizophrenia, depression, and neurodege

Advances in itch research have elucidated differences between itch and pain but have also blurred the distinction between them. There is a long debate about how somatic sensations including touch, pain, itch, and temperature sensitivity are encoded by the nervous system. Research suggests that each sensory modality is processed along a fixed, direct-line communication system from the skin to the brain. Itch: Mechanisms and Treatment presents a timely update on all aspects of itch research and the clinical treatment of itch that accompanies many dermatological conditions including psoriasis, neuropathic itch, cutaneous t-cells lymphomas, and systemic diseases such as kidney and liver disease and cancer. Composed of contributions from distinguished researchers around the world, the book explores topics such as: Neuropathic itch Peripheral neuronal mechanism of itch The role of PAR-2 in neuroimmune communication and itch Mrgprs as itch receptors The role of interleukin-31 and oncostatin M in itch and neuroimmune communication Spinal coding of itch and pain Spinal microcircuits and the regulation of itch Examining new findings on cellular and molecular mechanisms, the book is a compendium of the most current research on itch, its prevalence in society, and the problems associated with treatment.

A comprehensive and detailed overview of the current state of preclinical research on histamine and histamine receptors. Part of the book focuses on novel approaches to the study of histamine receptors such as polymorphism, genetic linkage, and computational analysis, and on the use of new histaminergic ligands in diseases such as asthma and dermatitis. Several chapters will be devoted to the role of histamine in the control of homeostatic and behavioral responses such as the sleep-wake cycle, regulation of the blood brain barrier, food intake, alertness, itch, and memory formation and consolidation.