Journal of Neural Transmission. Supplementa – serie

Substance-related disorders pose an increasing challenge not only to the field of psychiatry but also to public health. The rapid development of our society has also changed the face of substance use and abuse, both quantitatively and qualitatively. In this volume international experts present reviews of the latest research covering many areas ranging from neurobiology to psychological management, as well as different drugs, from alcohol to ecstasy.

Substance-related disorders pose an increasing challenge not only to the field of psychiatry but also to public health. The rapid development of our society has also changed the face of substance use and abuse, both quantitatively and qualitatively. In this volume international experts present reviews of the latest research covering many areas ranging from neurobiology to psychological management, as well as different drugs, from alcohol to ecstasy.

Experts in the fields of neurology, neuroscience, neurobiology and psychiatry review and present novel findings of basic and clinical research on extrapyramidal disorders and allied conditions. New insights on the nature of extrapyramidal dysfunction and its therapy in the fields of neurology, psychiatry and neuroscience are presented.

Experts in the fields of neurology, neuroscience, neurobiology and psychiatry review and present novel findings of basic and clinical research on extrapyramidal disorders and allied conditions. New insights on the nature of extrapyramidal dysfunction and its therapy in the fields of neurology, psychiatry and neuroscience are presented.

Traditionally the International Congress of Parkinson’s Disease and Related disorders (ICPD) is reflected in publishing its proceedings. This is to (1) sum up the current knowledge in this particular spectrum disorder and (2) to remind clinicians and basic researchers on the development and progress made overtime with respect to etiology, pathology, genetics, endogenous vulnerability factors, models, drug treatment strategies, e.g. levodopa, neuroprotective drugs, new developments in neurotherapeutics, neurosurgery, plasticity of nerve cell structures and clinical issues (e.g. staging, early diagnosis, differential diagnostic aspects, clinico-pathological correlations, new scales etc.). All these topics that have been brought forward at the 16. ICPD congress 2005, Berlin, are now available in a subsumed version in supplementum 70 of Journal Neural Transmission.This book gives a comprehensive overview on current clinical and basic research issues related to Parkinson’s disease and its related disorders and is suitable for neurologists, psychiatrists, neurosurgeons, basic researchers, geneticists and patients as well as their relatives.

This book deals with basic and clinical aspects of monoamine oxidase (MAO) subtypes A and B highlighting its importance in neurological and psychiatric diseases. Consequently the therapeutic actions of MAO-A and -B inhibitors in Parkinson’s disease (PK) and depression are the focus of several chapters. As MAO is the basis of the development of the "oxidative stress hypothesis" of PD, several chapters are devoted to iron and iron-induced oxidative stress in various experimental studies and clinical conditions. Based on these findings, new compounds have been developed which not only block MAO, but are in addition, either inhibitors of acetylcholine esterase or have iron chelating properties. The aspect of "preclinical" and "clinical" neuro protection as well as MAO neuroprotection are additional topics covered in this book. MAO, iron and neuroprotection are seen in the framework of general anti Parkinson’s therapy with chapters on levodopa, dopaminergic receptor agonists and clinical issues.

"Advances in Down Syndrome Research” represents updated research in several areas of Down Syndrome (DS).A new promising animal model of DS is reported and this opens new opportunities to study pathomechanisms and pharmacological approaches as it is more than difficult to carry out studies in humans and the clinical features are highly variable. In terms of biology, cell cycle and stem cell studies and in terms of biochemistry, relevance of studies on a specific protein kinase, channels, transporters, superoxide dismutase, antioxidant system, chromosome assembly factor and other important biological structures are provided. And again, the gene dosage hypothesis is addressed and although the vast majority of chromosome 21 gene products is unchanged in fetal DS brain, a few specific chromosome 21 encoded structures including transcription factors are indeed overexpressed although findings in fetal DS are different from those in adult DS brain when Alzheimer-like neuropathology supervenes.

Advances in Down Syndrome Research represents updated research in several areas of Down Syndrome (DS).A new promising animal model of DS is reported and this opens new opportunities to study pathomechanisms and pharmacological approaches as it is more than difficult to carry out studies in humans and the clinical features are highly variable. In terms of biology, cell cycle and stem cell studies and in terms of biochemistry, relevance of studies on a specific protein kinase, channels, transporters, superoxide dismutase, antioxidant system, chromosome assembly factor and other important biological structures are provided. And again, the gene dosage hypothesis is addressed and although the vast majority of chromosome 21 gene products is unchanged in fetal DS brain, a few specific chromosome 21 encoded structures including transcription factors are indeed overexpressed although findings in fetal DS are different from those in adult DS brain when Alzheimer-like neuropathology supervenes.

This multidisciplinary book includes current research papers and reviews in the areas of basic neuroscience, neural mechanisms underlying neurodegenerative disorders. It further includes new approaches for neuroprotective treatments, clinical, neurobiological and treatment aspects of psychiatric disorders. The book was conceived as a celebration of the professional life and work of Peter Riederer to mark the occasion of his retirement.

The papers in this volume are the invited lectures at the Second Workshop on Amine Oxidases held at the Biomedical Center, Uppsala University, 2 to 4 August 1986. It was a great pleasure for the organizers to see, in Uppsala, so many old and new friends, all brought together by our common interest in the fascinating field of Amine Oxidases. The Workshop was the successor of a long row of successful predecessors to start with the 1972 meeting in Cagliari, Sardinia, and recently preceded by the first meeting of Workshop design, held in Cambridge 1984. Several of the previous meetings have been dedicated to distinguished senior research workers within the field. To start this Workshop a memorial lecture was given. This lecture, given by Prof. T. P. Singer, was dedicated to the late Prof. K. Kamijo, who was one of the pioneers of what is now worldwide interest in Amine Oxidases and who organized the superb meeting in Hakone 1981. To the great honour of all the participants the family of the late Prof. Kamijo visited the Workshop. Abstracts of all the presentations have been published as a Supplement of Acta Pharmacologica et Toxicologica (Copenhagen).

At this meeting, a number of critical groups confirmed and extended the original findings by J.A. Obeso and his colleagues. These authors found that continuous s.c. infusion of lisuride, a watersoluble dopaminergic 8 aminoergoline with dopaminergic properties which can be injected or infused, can improve - sometimes quite considerably - motor function in severely disabled fluctuating Parkinsonian patients. The concurrent use of the peripheral dopamine antagonist domperidone attenuates or prevents side-effects related to the stimulation of "peripheral" dopamine receptors, including the chemoreceptor trigger zone and some areas of the hypothalamus outside the blood-brain barrier. The clinical results discussed in this volume may not only be a basis for further improvements in the knowledge and therapeutic strategies in Parkinsonism, they point to the so far neglected importance of different ways of stimulating neurological or other systems, for example, discontinous, oscillatory effects caused by frequent oral application vs continuous stimulation as described here with the lisuride s.c. infusion.

Neurotransmitter changes taking place in the brain of patients with dementia disorders, mainly Alzheimer type dementia, are reported. Their role in the pathogenesis of Alzheimer's disease is discussed; and the neurochemical changes are considered as a base for formulating treatment strategies. By studying markers in the cerebrospinal fluid, diagnostic methods may be achieved that will aid in diagnosing subgroups of dememtia.

The Amine Oxidase Workshop was the brain child of Brian Callingham and Keith Tipton. The present book is the proceedings of the fourth in the series and in the past we have dedicated our meeting to individuals who have made significant fundamental contributions to the biochemistry, physiology and pharmacology of this interesting group of enzymes. The present meeting is not an exception because we have gathered here in Wtirzburg to honour an individual whose outstanding work on the autonomic pharmacology has span- ned more than 30 years and whose contribution has made a vast impact in our understanding of the kinetic relationship between amine metabolism (that uptake and enzymatic inactivation) and adrenergic neurotransmission. We speak of course of Professor Ullrich Trendelenburg, or Ulli as he likes to be known. Like the amine oxidases, he has a unique place in Pharmacology. Professor Trendelenburg was born on the eve of the new year of 1922 in the city of Rostock in northern Germany, where his father was Professor of Pharmacology at the Faculty of Medicine of Rostock.His father accepted the offer to take over the corresponding chair in Freiburg im Breisgrau (in Southern Germany). As the youngest of four children, Ulli grew up mainly in the garden of the department, in the animal quarters and in the workshop. Of the various coworkers of his father, one he liked especially was Otto Krayer, the young pharmacologist.

This volume covers selected contributions from the Conference on Age-associated Neurological Diseases held in Vienna, 1989. Fields covered include age-associated memory impairment (AAMI), Alzheimer's and Parkinson's diseases and dementias and movement disorders of other types. Concerning dementia, some papers deal with diagnosis employing neuro-imaging methods - PET, SPECT, MRI and XCT - and others by means of electro-physiological methods. An important aspect covered is the early preclinical diagnosis of dementia using neuropsychological tests to enhance the chance of effective treatment. Finally, drugs now under clinical investigation are discussed and preliminary results for several compounds are presented. The findings in this volume should be of interest to physicians treating elderly persons with age-associated degenerative diseases. This book of proceedings on neurology, psychiatry, internal and geriatric medicine is intended for the use of researchers and specialists, physicians and psychologists.

Presenting the proceedings of a symposium held in honour of Professor Ullrich Trendelenburg, this text is concerned with research on the pharmacology and physiology of such neurotransmitters as noradrenaline, dopmanine, 5-hydroxytrypemine and ATP. The articles have been written by specialists in the field of transmitter pharmacology. It is hoped that the new research activities and results they report on will advance understanding about the autonomic nervous system.

Generalized non convulsive epilepsy (GNCE), also called absence or petit mal epilepsy, is a disease appearing during childhood. EEG, clinical, pharmacological and genetic characteristics differ from those of convulsive or focal epilepsies. No underlying structural or biochemical abnormality has been identified for generalized absence seizures and the etiology of this disorder is unknown. It is unlikely that the precise pathophysiology of GNCE can be resolved in studies that focus on humans. Therefore a number of animal models reproducing the human diseases have been developed. The aim of this supplementum is to characterize such models in rodents. First, recent models are extensively described. These include the genetic model of spontaneous GNCE in Strasbourg's Wistar rats and in tottering mice as well as bilateral spike and wave discharges induced by GHB, PTZ or GABA mimetics. Second, this supplementum provides information on putative mechanisms underlying generalized absence seizures.Third, various experimental approaches aimed at investigating the neural substrate of this particular kind of epilepsy are described with various electrophysiological, pharmacological, biochemical, metabolic, ionic and molecular data.

Positron emission tomography (PET) has been used for a decade in psychiatric research to study regional brain glucose metabolism, and the results seem to be inconsistent. However, the inconsistency may be explained by differences in methods and clinical protocols. This problem has been recognized by the EEC Concerted Action on PET, which is why a special psychiatric group was convened. Researchers with knowledge in different aspects of PET methodology like mathematical models, cameras, brain atlas, stimulation studies and psychiatric research organized a meeting to discuss standardization problems and how to minimize errors in PET investigations. This volume aims to provide the reader knowledge about the state of the art, define problems and discuss possible solutions. It gives suggestions for good clinical PET practice.

Schizophrenia has been the subject of intense research interest in recent years, as investigators have explored the biological bases for the disorder and for various approaches to its diagnosis and treatment. This volume focuses on three aspects of such recent research connecting basic neuroscience to schizophrenia. In one, Professors Budinger, Gur, and Pettegrew provide critical reviews of brain imaging studies as they relate to cognitive monoamine systems and their varied role in prefontal cortical circuitry and function. In the third, Professors Deutsch, Gerfen, and Grace discuss the structure, organization, and function of the basal ganglia, as they relate to schizophrenia and the mechanisms of neuroleptic action. These papers were presented at an interdisciplinary workshop on the subject at the University of Pittsburgh, in May 1991, and the discussion between the authors and other panelists in basic and clinical sciences are included in this volume as well. The presentation of these diverse approaches in an integrated fashion provides the reader with a unique perspective and a wealth of new questions for future collaborative research.

Monoamine oxidase plays a major role in the pathogenesis of neuropsychiatric disorders including depressive illness, Parkinson's disease and Alzheimer's disease. The new generation of selective monoamine oxidase inhibitors, devoid of major side effects, has found a prominent place in the treatment of these diseases. This volume presents a collection of research papers on monoamine oxidase and its inhibitors. The topic is treated from the point of view of chemistry, biochemistry, pharmacology, physiology, neurology and psychiatry. The book serves as a quick and comprehensive reference source for obtaining the most up-to-date information.

This monograph summarizes recent developments in clinical and basic research in progressive supranuclear palsy (PSP). This disorder is the second most common cause of parkinsonism seen in practice. Only recently we have been able to diagnose it regularly in living patients. There is an outporing of new interest in PSP in many research centers around the world and this volume is an expression of this research interest. Different clinical and basic subjects on PSP are covered in this monograph by individual experts in the field, incorporating their latest advances in research. With this book the reader will be able to have on hand the most recent advances on PSP covering areas such as epidemiology, neuropathology and neurophysiological, and neuroimaging aspects, as well as recent advances in neurochemistry, neuropathology and treatment of this disorder.

Although age has been recognized as a risk factor for late-onset dementia of Alzheimer type, its etiology is unknown as yet. Several age-related metabolic abnormalities may thus become important for the pathogenesis of the late-onset form. Studies at the cellular/molecular level in brain tissue are possible post mortem, but lack information on the beginning of the disorder. In this supplement, different approaches are dealt with how to induce structural and/or metabolic abnormalities in relevant cell cultures, in brain slices and in experimental animals, and how behavioral changes parallel the metabolic variations.

Dementia is an acquired disorder of higher cerebral functions and cognition. Because of increasing life expectancy dementia poses a major health and socio- economic problem. Alzheimer's disease accounts for 70-90% of mental decline in the elderly. Degenerative non-Alzheimer's dementi as are responsi- ble for 7-30%. These include a variety of disorders clinically characterised by progressive cognitive dysfunction often combined with focal neurological def- icits, e.g. Parkinson-plus syndromes, Lewy body dementia, lobar and multisys- tem atrophies, other neurodegenerative disorders, and prion diseases. Often it is difficult to distinguish these illnesses from Alzheimer's disease and vascu- lar dementia. In spite of considerable progress in molecular genetics, biochemistry, and neuropathology, the classification and pathogenesis of non-Alzheimer's dementias are still debatable. Diagnosis is frequently made only at postmor- tem. Because disease markers are not available for the majority of non- Alzheimer's dementias, consensus criteria for the identification of such diseas- es are warranted.These criteria could serve at a basis for early diagnosis and distinction from other dementing disorders.

Expert clinicians and basic scientists with a special interest in Parkinson's disease review the current state of science and clinical therapeutics of the disease. Therefore these articles represent an authorative review of the current state of knowledge regarding preclinical course and symptomatology, subtypes with their impact on the pathology, genetic alterations, novel mechanisms of neuronal cell death, diagnostic tools and old and novel therapeutic approaches with respect to neuroprotection and neuroregeneration in Parkinson's disease. Particular emphasis has been placed on a novel antiparkinsonian drug called budipine with various modes of action also influencing altered non dopaminergic systems in Parkinson's disease. It is evident, that many questions on the cause, course and treatment of Parkinson's disease are still unanswered and therefore the ideal way to treat a parkinsonian patient remains to be defined.

Volume 5 of the series "Advances in Research on Neurodegeneration" is concerned with themes which are currently the focus of intensive research, and in which advances in our understanding of the pathological mechanisms un­ derlying neurodegenerative diseases are expected in the near future. The first section contains five reviews devoted to the various neuroimaging technolo­ gies. The discussion is concerned with the question of whether neuroimaging techniques make it possible to follow the process of degeneration as it occurs, and which methods offer the required sensitivity and quantifiability for this purpose. However, the question needs to be examined of whether, given the physical and chemical limitations of these techniques, even under optimal conditions, anatomical resolution can be improved to the extent that neuro­ degenerative diseases can be diagnosed earlier than currently possible and a confident diagnosis made. The possibilities of using neuroimaging techniques to provide information regarding the effects of neuroprotective or neuroregen­ erative therapeutic strategies, and for correlating the results of neuropsycho­ logical research with imaging data are also discussed. The second section is concerned with the significance of endogenous or exogenous neurotoxins as triggers for neurodegenerative processes that may lead to Parkinsonism. Vulnerability factors, which include such factors as nerve ending sensitivity, the synergistic effects of drugs and the various mechanisms underlying different toxins are discussed.

Neurodegeneration is one of the most important subjects of the investigation now and in the coming 21st century. Alzheimer's disease is the leading cause of dementia in the elderly people and Parkinson's disease is one of the major neurologic disorders with the prevalence between 1 and 2/1 000 population in advanced countries. Many others are suffering from intractable neurodegener­ ative disorders such as amyotrophic lateral sclerosis, Huntington's disease, or spinocerebellar degeneration. No truly effective treatment is available for any of these neurodegenerative disorders except for Parkinson's disease; even in Parkinson's disease, still it is impossible to slow down the disease process with the currently available treatment. It is urgently needed to develop new effective technique to halt or slow down the disease process in each of those disorders. Recent advance in the molecular biological and molecular genetic technique has brought us great progress in the understanding of etiology and pathogenesis of these disorders, but still it is not known how neurons are going to die in these disorders. To explore the question, mutual cooperation and exchange of ideas between basic scientists and clinical peoples are of utmost importance.

In his original essay on the shaking palsy (1817) James Parkinson remarked that the "senses and intellect were uninjured". Thus, it was only in later years that the complexity ofparkinsonism and in particular Parkinson's disease with dementia was recognised. Cognitive impairment in Parkinson's disease is common and is estimated to affect more than forty per cent of patients with disease onset after age 65. Recent studies suggest that pathology of Parkin­ son's disease now ranks second to Alzheimer's disease as the commonest sub­ strate of dementia in elderly patients. The condition is heterogeneous and there remain many complicated and unresolved questions concerning cause, diagnosis and classification. In an attempt to clarify these issues, scientists and members of the European Brain Bank Network (EBBN) gathered in London for a meeting entitled "Dementia in Parkinsonism". The resultant monograph is testimony to the wide-ranging clinical, morphological and biochemical aspects of this condition. We are grateful to all contributors for expressing their expert opinions and for being so generous with their time taken in prepa­ ration of the manuscripts. The meeting was funded by the Commission of the European Communities as part of a Biomed-l Programme. We wish to thank Amgen Limited, Lilly Industries Limited and Roche Products Limited for additional sponsorship. The expert secretarial assistance of R. Nani in the pre­ paration of this book has been very much appreciated. London, November 1997 S. E. Daniel F. F. Cruz-Sanchez A. J. Lees Contents Stern, G. : The language of the basal ganglia . . . . . . . . . . . . . . . . . . . . . .

Monoamine oxidase (MAO) is linked to psychiatric and neurological disorders, because inhibitors of the enzyme are used clinically for treatment of affective disorders and Parkinson’s disease. One of the interesting new aspects of MAO is the occurrence in the human population of deletions of genes coding for one or the other enzyme subtype (A or B). This leads to the possibility of a genetic basis for psychiatric disorders based on MAO. Subjects with deletions of type A or B, and combined deletions, have been described. In the first group of 6 papers in this book, the occurrence and characterization of these phenotypes, as well as the structure of MAO genes, is explored. Advances in the biochemistry of MAO subtypes and their physiological function and localization in brain and periphery is included. Other sections of the book deal with the neuroprotective action of MAO inhibitors and their pharmacology, especially the pharmacology of new MAO-B inhibitors.

This volume brings together the reports of basic scientists and clinical investigators on Alzheimers disease. The issue bridges the gap between laboratory work in basic science and the development of urgently needed therapeutic strategies. Areas presented are the molecular and cellular biology of the disease, pathogenetic mechanisms and potential therapeutic targets, genetics, risk factors, strategies of prevention and treatment as well as practical aspects of medical and social care for patients with Alzheimers disease.

Ageing and dementia are closely related conditions. Increasing age of the general population causes increasing incidence of dementing disorders in later life, although cognitive impairment is not necessarily a consequence of advancing age. The book presents the papers of the International Symposium on Ageing and Dementia, October 17–19, 1997 in Graz, where internationally renowned experts in the field of ageing and dementia gave an overview of the current knowledge about the epidemiology, pathomorphology, clinical diagnosis and course of brain ageing processes and related dementing disorders, biochemical markers and imaging procedures for the diagnosis of Alzheimer’s disease and current approaches to a successful treatment of dementia. "... this book will be of interest to clinicians with previous experience of clinical dementia assessements, and to researchers who want a comprehensive update on research areas of dementia with which they are less familiar. It will also be of interest to those following the development of neurotrophe factors for treatment of dementia who need an extensive introduction to the preclinical studies of Cerebrolysin®. The book will be fairly useful as a textbook for clinicians who are learning about clinical dementia assessments for the first time.” Acta Psychiatrica Scandinavica