Current Topics in Neurotoxicity – serie

The specific topic, “Isoquinolines And Beta-Carbolines As Neurotoxins And Neuroprotectants – New Perspectives In Parkinson`S Disease Therapy,” was chosen in light of accumulating neurobiological evidence indicating that, in addition to exogenous neurotoxins (e.g., 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine [MPTP]), endogenous compounds may play an important role in the most common neurodegenerative disorders (e.g., Parkinson`s disease). Two groups of amine related compounds, which appeared chemically like MPTP, were detected in human brain and cerebrospinal fluid (CSF): ß-carbolines (BCs) and tetrahydroisoquinolines  (TIQs). These are heterocyclic compounds formed endogenously from phenylalanine/tyrosine (TIQs) and tryptophan, tryptamine, and 5-hydroxytryptamine (BCs), respectively and exert a wide spectrum of psychopharmacological and behavioral effects. The TIQs and BCs may bind to their own high affinity sites on neuronal membranes associated with or located close to the receptors of neurotransmitters. Research on TIQs and BCs is stimulated also by their possible role in pathological conditions, especially parkinsonism and alcoholism. Recently, clinical interest has been spurred by their role as neuroprotective, and even neurorestorative, anticonvulsant and antiaddictive, substances.             In this book we are going to summarize, for the first time, the results from behavioral, neurochemical and molecular experiments, which demonstrate a wide spectrum of TIQs and BCs effects - from their rather mild neurotoxic actions to the important neuroprotective and antiaddictive properties. Additionally, the recent results of experimental studies in vivo have allowed a much better understanding and simultaneous comparison of the neurochemical and molecular mechanisms underlying the neuroprotective and neurotoxic actions of endogenous TIQs and BCs and have pointed to the possibility oftheir therapeutic applications in neurodegenerative diseases such as Parkinson's disease.

Mercury (Hg) is a global pollutant that knows no environmental boundaries. Even the most stringent control of anthropogenic Hg sources will not eliminate exposure given its ubiquitous presence. Exposure to Hg occurs primarily via the food chain due to MeHg’s accumulation in fish. Latest US statistics indicate that 46 States have fish consumption advisories. In addition, Hg is a common pollutant in hazardous waste sites, with an estimated 3-4 million children living within one mile of at least one of the 1,300+ active hazardous waste sites in the US. The effects on intellectual function in children prenatally exposed to MeHg via maternal fish consumption have been the subject of two on-going major, prospective, longitudinal studies in the Seychelles and the Faroe Islands. It is important to recognize that the risk for MeHg exposure is not limited only to islanders with high fish consumption.  This book will provide state-of-the-art information to the graduate student training in toxicology, risk assessors, researchers and medical providers at large. It is aimed to bring the reader up to date on contemporary issues associated with exposure to methylmercury, from its effects on stem cells and neurons to population studies.

Since the very early stages of life, we all experience some form of stress. Stressors can be mild to severe and can range from unsuccessfully longing for maternal milk in infancy, to recklessly wiggling on a motorbike to be on time to watch the NBA finals on TV, to breaking up a relationship. All those events that we call “stress” have the capability of perturbing a given state of psychological and physiological equilibrium and moving it to a different level. The transition from crawling to walking has to be considered a form of stress as much as losing a job. It is through a continuous cross-talk between environmental stressors and individual adaptations that we build our personalities and our ways to cope with daily hassles. External challenges should not necessarily be regarded as “bad”, but instead seen as constructive forces forming our ability to navigate a changing world.What is stress good for? What is stress bad for? When and why do we need to be “stressed”? Should we worry about stress? When does stress equate to “normality”? When does it turn into pathology? We hope with this book to provide some answers to these fundamental questions.

Currently, there are tremendous advances being made in understanding the basic science of both the structure and function of botulinum neurotoxins. This knowledge is opening up opportunities in regard to both therapeutic uses and treatment and protection options for civil and bio-defense applications. This volume fully evaluates the status of neurotoxin research and exploitation with a focus on clinical application. The book is a multi-authored collection of chapters written by the leading authorities responsible for the current scientific and clinical research that is advancing the understanding and exploitation of the neurotoxins and is both up to date and authoritative.

Since the very early stages of life, we all experience some form of stress. Stressors can be mild to severe and can range from unsuccessfully longing for maternal milk in infancy, to recklessly wiggling on a motorbike to be on time to watch the NBA finals on TV, to breaking up a relationship. All those events that we call “stress” have the capability of perturbing a given state of psychological and physiological equilibrium and moving it to a different level. The transition from crawling to walking has to be considered a form of stress as much as losing a job. It is through a continuous cross-talk between environmental stressors and individual adaptations that we build our personalities and our ways to cope with daily hassles. External challenges should not necessarily be regarded as “bad”, but instead seen as constructive forces forming our ability to navigate a changing world.What is stress good for? What is stress bad for? When and why do we need to be “stressed”? Should we worry about stress? When does stress equate to “normality”? When does it turn into pathology? We hope with this book to provide some answers to these fundamental questions.

The specific topic, “Isoquinolines And Beta-Carbolines As Neurotoxins And Neuroprotectants – New Perspectives In Parkinson`S Disease Therapy,” was chosen in light of accumulating neurobiological evidence indicating that, in addition to exogenous neurotoxins (e.g., 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine [MPTP]), endogenous compounds may play an important role in the most common neurodegenerative disorders (e.g., Parkinson`s disease). Two groups of amine related compounds, which appeared chemically like MPTP, were detected in human brain and cerebrospinal fluid (CSF): ß-carbolines (BCs) and tetrahydroisoquinolines  (TIQs). These are heterocyclic compounds formed endogenously from phenylalanine/tyrosine (TIQs) and tryptophan, tryptamine, and 5-hydroxytryptamine (BCs), respectively and exert a wide spectrum of psychopharmacological and behavioral effects. The TIQs and BCs may bind to their own high affinity sites on neuronal membranes associated with or located close to the receptors of neurotransmitters. Research on TIQs and BCs is stimulated also by their possible role in pathological conditions, especially parkinsonism and alcoholism. Recently, clinical interest has been spurred by their role as neuroprotective, and even neurorestorative, anticonvulsant and antiaddictive, substances.             In this book we are going to summarize, for the first time, the results from behavioral, neurochemical and molecular experiments, which demonstrate a wide spectrum of TIQs and BCs effects - from their rather mild neurotoxic actions to the important neuroprotective and antiaddictive properties. Additionally, the recent results of experimental studies in vivo have allowed a much better understanding and simultaneous comparison of the neurochemical and molecular mechanisms underlying the neuroprotective and neurotoxic actions of endogenous TIQs and BCs and have pointed to the possibility oftheir therapeutic applications in neurodegenerative diseases such as Parkinson's disease.

Mercury (Hg) is a global pollutant that knows no environmental boundaries. Even the most stringent control of anthropogenic Hg sources will not eliminate exposure given its ubiquitous presence. Exposure to Hg occurs primarily via the food chain due to MeHg’s accumulation in fish. Latest US statistics indicate that 46 States have fish consumption advisories. In addition, Hg is a common pollutant in hazardous waste sites, with an estimated 3-4 million children living within one mile of at least one of the 1,300+ active hazardous waste sites in the US. The effects on intellectual function in children prenatally exposed to MeHg via maternal fish consumption have been the subject of two on-going major, prospective, longitudinal studies in the Seychelles and the Faroe Islands. It is important to recognize that the risk for MeHg exposure is not limited only to islanders with high fish consumption.  This book will provide state-of-the-art information to the graduate student training in toxicology, risk assessors, researchers and medical providers at large. It is aimed to bring the reader up to date on contemporary issues associated with exposure to methylmercury, from its effects on stem cells and neurons to population studies.

Currently, there are tremendous advances being made in understanding the basic science of both the structure and function of botulinum neurotoxins. This knowledge is opening up opportunities in regard to both therapeutic uses and treatment and protection options for civil and bio-defense applications. This volume fully evaluates the status of neurotoxin research and exploitation. The book is a multi-authored collection of chapters written by the leading authorities responsible for the current scientific and clinical research that is advancing the understanding and exploitation of the neurotoxins and is both up to date and authoritative.

Currently, there are tremendous advances being made in understanding the basic science of both the structure and function of botulinum neurotoxins. This knowledge is opening up opportunities in regard to both therapeutic uses and treatment and protection options for civil and bio-defense applications. This volume fully evaluates the status of neurotoxin research and exploitation with a focus on clinical application. The book is a multi-authored collection of chapters written by the leading authorities responsible for the current scientific and clinical research that is advancing the understanding and exploitation of the neurotoxins and is both up to date and authoritative.

Currently, there are tremendous advances being made in understanding the basic science of both the structure and function of botulinum neurotoxins. This knowledge is opening up opportunities in regard to both therapeutic uses and treatment and protection options for civil and bio-defense applications. This volume fully evaluates the status of neurotoxin research and exploitation. The book is a multi-authored collection of chapters written by the leading authorities responsible for the current scientific and clinical research that is advancing the understanding and exploitation of the neurotoxins and is both up to date and authoritative.

Over the last decade, and particularly during the recent five years, a rapidly increasing number of novel psychoactive substance (NPSs), often marketed as “designer drugs”, “legal highs”, “herbal highs”, “research or intermediate chemicals” and “laboratory reagents”, has appeared on the drug market in an effort to bypass controlled substance legislation. NPSs encompass a wide range of different compounds and drug classes but had been dominated by synthetic cannabinomimetics and psychostimulatory synthetic cathinones, so-called β-keto amphetamines. Compounds from the later class were first detected in Europe in 2004, and since then 103 new cathinones have been identified and reported to the European Monitoring Centre for Drugs and Drug Addiction, with 57 during the last two years.Synthetic cathinones – novel addictive and stimulatory psychoactive substances is the first publication of this kind that provides readers with background on chemical structures, detection, prevalence and motivation of use of the very popular group of NPSs. This book also presents comprehensive overview of the mechanisms of action, pharmacological activity, and main metabolic pathways of synthetic cathinones, followed by a detailed discussion of the acute and chronic toxicity associated with the use of these substances. Written by international experts in the field, this multi-authored book is a valuable reference not only for scientists, clinicians and academics, but also for readers representing different professional background who are involved in educational-prophylactic activities directed to harm reduction of psychoactive compounds.

Psychiatric disorders are one of the most dramatic burdens for humankind. The role of immune dysfunction in the pathophysiology of these disorders has emerged during the last years, because there has been tremendous progress in psychoneuroimmunological research. Many results are presented here by pioneers in the field. The book addresses various effects of the immune system on the pathophysiology and course of psychiatric disorders and highlights the possible future impact on treatment decisions of various psychiatric disorders, including schizophrenia and depression. The contributions cover the role of in utero immune challenges on the development of schizophrenia, the role of infections, and autoimmune diseases and mild immune activation in the development of depression and schizophrenia, the influence of immune responses in other disorders such as Tourette's, Alzheimer's, and OCD, the connections between mental and physical pain as well as between anti-inflammatory and antipsychotic drugs.​

Comprehensive overview of different aspects of autophagy as it relates to neurodegenerative diseases. The pathogenesis of the main neurodegenerative disorders includes either the accumulation of altered or misfolded proteins or exposure to several toxics. Autophagy constitute one of the two principal cellular pathways implicate in the clearance of these material and can serve as a neuroprotective mechanism. Topics include: the role of autophagy in the brain, the role of autophagy in the principal neurodegenerative disorders, and the mechanism by which different molecules cause neurotoxicity and the role autophagy plays.

Adenosine A2A receptor antagonists have shown great promise in the treatment of Parkinson's Disease and alleviation of symptoms. This book addresses various aspects of this class of drugs from their chemical development to their clinical use. Among the many insightful chapters contained in this book, there are three unique reviews that have not previously been published in any format: (1) a history of istradefylline, the first A2A antagonist approved for treatment of Parkinson's Disease, (2) an overview of neuroimaging studies in human death and disease and (3) a study of urate as a possible biomarker and neuroprotectant.

The first comprehensive book to cover all aspects of the last 25 years of PACAP (pituitary adenylate cyclase activating polypeptide) research, this book contains contributions from virtually all the leading researchers in the field, and addresses some of the following topics: evolutionary aspects of PACAP, distribution and occurrence of PACAP and its receptors, hormonal effects of PACAP, intracellular signaling, effects on cellular proliferation and differentiation, protective effects of PACAP, behavioral effects of PACAP, developmental aspects of PACAP, other physiological effects of PACAP (cardiovascular, thermoregulatory), human studies, drug design, metabolism and transport. This compendium can serve as an important reference for researchers and students in PACAP research and can also be a thorough introduction for those in related fields.

Adenosine A2A receptor antagonists have shown great promise in the treatment of Parkinson's Disease and alleviation of symptoms. This book addresses various aspects of this class of drugs from their chemical development to their clinical use. Among the many insightful chapters contained in this book, there are three unique reviews that have not previously been published in any format: (1) a history of istradefylline, the first A2A antagonist approved for treatment of Parkinson's Disease, (2) an overview of neuroimaging studies in human death and disease and (3) a study of urate as a possible biomarker and neuroprotectant.

Psychiatric disorders are one of the most dramatic burdens for humankind. The role of immune dysfunction in the pathophysiology of these disorders has emerged during the last years, because there has been tremendous progress in psychoneuroimmunological research. Many results are presented here by pioneers in the field. The book addresses various effects of the immune system on the pathophysiology and course of psychiatric disorders and highlights the possible future impact on treatment decisions of various psychiatric disorders, including schizophrenia and depression. The contributions cover the role of in utero immune challenges on the development of schizophrenia, the role of infections, and autoimmune diseases and mild immune activation in the development of depression and schizophrenia, the influence of immune responses in other disorders such as Tourette's, Alzheimer's, and OCD, the connections between mental and physical pain as well as between anti-inflammatory and antipsychotic drugs.​

Comprehensive overview of different aspects of autophagy as it relates to neurodegenerative diseases. The pathogenesis of the main neurodegenerative disorders includes either the accumulation of altered or misfolded proteins or exposure to several toxics. Autophagy constitute one of the two principal cellular pathways implicate in the clearance of these material and can serve as a neuroprotective mechanism. Topics include: the role of autophagy in the brain, the role of autophagy in the principal neurodegenerative disorders, and the mechanism by which different molecules cause neurotoxicity and the role autophagy plays.

Over the last decade, and particularly during the recent five years, a rapidly increasing number of novel psychoactive substance (NPSs), often marketed as “designer drugs”, “legal highs”, “herbal highs”, “research or intermediate chemicals” and “laboratory reagents”, has appeared on the drug market in an effort to bypass controlled substance legislation. NPSs encompass a wide range of different compounds and drug classes but had been dominated by synthetic cannabinomimetics and psychostimulatory synthetic cathinones, so-called β-keto amphetamines. Compounds from the later class were first detected in Europe in 2004, and since then 103 new cathinones have been identified and reported to the European Monitoring Centre for Drugs and Drug Addiction, with 57 during the last two years.Synthetic cathinones – novel addictive and stimulatory psychoactive substances is the first publication of this kind that provides readers with background on chemical structures, detection, prevalence and motivation of use of the very popular group of NPSs. This book also presents comprehensive overview of the mechanisms of action, pharmacological activity, and main metabolic pathways of synthetic cathinones, followed by a detailed discussion of the acute and chronic toxicity associated with the use of these substances. Written by international experts in the field, this multi-authored book is a valuable reference not only for scientists, clinicians and academics, but also for readers representing different professional background who are involved in educational-prophylactic activities directed to harm reduction of psychoactive compounds.