Neuroscience Intelligence Unit – serie

Cell-Cycle Mechanisms and Neuronal Cell Death examines the role of cell cycle activation in the molecular mechanisms leading to neuronal degeneration. Leading Authors discuss this topic in relation to the major neurological disorders, including Alzheimer’s disease, stroke and epilepsy. This book serves to gain new insights into the molecular determinants of neuronal death and to establish new targets for therapeutic intervention.

The decade of the brain has brought us a few steps closer to some of the key questions in neuroscience. The complexity of memory is seen on the systems and cellular level, and different types of memory are implemented in several cellular changes that can interact, or work independently. From Messengers to Molecules: Memories are Made of These, follows the arguments from different research teams for their particular area of expertise. All chapters are written to stand-alone and provide an up-to-date introduction to the topic for both specialists and novices alike. As a result, a comprehensive compendium covering cellular mechanisms contributing to memory formation in an unusual breadth has emerged. This books will be of interest to researchers working on the pharmacology, physiology and genetics of memory formation, clinicians memory disorders, industry and students in advanced courses in Neuroscience or Pharmacology.

The 21 century will witness the unprecedented marketing of therapeutic drugs developed from cannabinoids and the endocannabinoid system. Cannabinoids is a timely volume, which represents a comprehensive review of the most important issues in cannabinoid research as well as those of most likely therapeutic relevance. For the first time, the multi-faceted aspects of cannabinoid chemistry, biology and medicine are presented in one volume. Key topics of discussion: This book is a must for graduate and pre- and post-doctoral students in disciplines ranging from organic and natural product chemistry, pharmacology, biochemistry and medicine.

The book gives an account of results obtained from experiments where grafts of neuronal, glial and other tissues as well as artificial materials were placed into the spinal cord. It attempts to evaluate the contributions made by these studies to our understanding of basic neurobiologies questions. These include factors that regulate neuronal growth during development as well as regenera­ tion following injury to the nervous system. The model of neural transplanta­ tion is also useful for the study of cell-to-cell interactions, and this applies to interactions between glial cells and neurones, between various populations of neuronal cells and finally between axons and skeletal muscle fibres. The mecha­ nisms involved in the establishment of specific synaptic connections between neurones can also be investigated in this experimental paradigm. Important in­ formation regarding this issue was also obtained on systems other than the spinal cord, i. e. the cerebellum, hippocampus and striatum. Although such in­ formation of precise connections between the host and the grafted embryonic tissue is still lacking in the spinal cord, there is much information on the re­ sponse of the host nervous system to the grafted embryonic tissue, and that of the graft to its new host environment. It appears that embryonic grafts are able to induce repair processes follow­ ing injury to the nervous system.

eat shock proteins (HSPs), also called stress proteins, are not only induced in response to elevated temperatures, but also as a result of various stress situations, including environmental strains, viral H infection, ischemia, anoxia and oxidative stress. These stress situations trigger cellular defence mechanisms that act as an emergency system capable of combatting the toxic consequences due to the accumulation of misfolded proteins. Heat shock proteins are involved in many physiological processes, including development and differentiation, organisation of the cytoarchi tecture by binding to cytoskeletal elements and regulation of the balance between cell death and survival. Many heat shock proteins work as molecular chaperones. In this role, they contribute to in vivo protein folding and prevent nonproductive interactions with other proteins and cellular c- ponents. In recent years it has been found that the chaperone system and the proteolytic machinery work closely together, and that proteasomal - hibition causes the upregulation of stress proteins.Impairment of the proteasomal machinery and chaperone functions lead to protein damage, which contributes to neurodegenerative disorders and to the aging process.

eat shock proteins (HSPs), also called stress proteins, are not only induced in response to elevated temperatures, but also as a result of various stress situations, including environmental strains, viral H infection, ischemia, anoxia and oxidative stress. These stress situations trigger cellular defence mechanisms that act as an emergency system capable of combatting the toxic consequences due to the accumulation of misfolded proteins. Heat shock proteins are involved in many physiological processes, including development and differentiation, organisation of the cytoarchi tecture by binding to cytoskeletal elements and regulation of the balance between cell death and survival. Many heat shock proteins work as molecular chaperones. In this role, they contribute to in vivo protein folding and prevent nonproductive interactions with other proteins and cellular c- ponents. In recent years it has been found that the chaperone system and the proteolytic machinery work closely together, and that proteasomal - hibition causes the upregulation of stress proteins.Impairment of the proteasomal machinery and chaperone functions lead to protein damage, which contributes to neurodegenerative disorders and to the aging process.

The 21st century will witness the unprecedented marketing of therapeutic drugs developed from cannabinoids and the endocannabinoid system. Cannabinoids is a timely volume, which represents a comprehensive review of the most important issues in cannabinoid research as well as those of most likely therapeutic relevance. For the first time, the multi-faceted aspects of cannabinoid chemistry, biology and medicine are presented in one volume. Key topics of discussion: -major families of phytocannabinoids; -pharmacological activity of phytocannabinoids; -interactions of phytocannabinoids with their proposed molecular target; -components of the endocannabinoid system; -molecular mechanisms of the endocannabinoid system; -Physiological and pathological role of endocannabinoids; -industrial applications of studies on the cannabinoids; -therapeutic uses of agonists and antagonists of cannabinoids receptors. This book is a must for graduate and pre- and post-doctoral students in disciplines ranging from organic and natural product chemistry, pharmacology, biochemistry and medicine.

N aney J. Rothwell ytokine neurobiology is now a hot topic! Only a few years ago C most neuroscientists were only dimly aware of cytokines and knew little about their function or biological importance. Cytokines, now a huge collection of polypeptides with diverse activities, were until quite recently, studied by those interested in the immune system, inflamma- tion, cancer or infection in peripheral tissues, and did not feature in neuroscience. For example, less than five years ago virtually no refer- ence was made to cytokines in any of the numerous abstracts at the American Society for Neuroscience annual meeting. This situation has now changed dramatically. In an article in early 1995 (Hopkins and Rothwell), we reported an exponential increase in articles on cytokines and the nervous system within the previous year and it seems that this publication frenzy is continuing. There are sev- eral reasons for such interest in cytokines and the nervous system. Firstly, the field of neuroimmunology (or psychoneuroimmunologyl psychoneuroendocrinology) has developed considerably in the past five years.Thus the importance of interactions between the nervous, im- mune and endocrine systems in responses to disease, injury and stress is now recognized. These bidirectional communications have been mirrored by active dialogue (and even collaboration) between neuro- scientists and immunologists. Cytokines form a critical part of neuroimmune interactions.

The book gives an account of results obtained from experiments where grafts of neuronal, glial and other tissues as well as artificial materials were placed into the spinal cord. It attempts to evaluate the contributions made by these studies to our understanding of basic neurobiologies questions. These include factors that regulate neuronal growth during development as well as regenera­ tion following injury to the nervous system. The model of neural transplanta­ tion is also useful for the study of cell-to-cell interactions, and this applies to interactions between glial cells and neurones, between various populations of neuronal cells and finally between axons and skeletal muscle fibres. The mecha­ nisms involved in the establishment of specific synaptic connections between neurones can also be investigated in this experimental paradigm. Important in­ formation regarding this issue was also obtained on systems other than the spinal cord, i. e. the cerebellum, hippocampus and striatum. Although such in­ formation of precise connections between the host and the grafted embryonic tissue is still lacking in the spinal cord, there is much information on the re­ sponse of the host nervous system to the grafted embryonic tissue, and that of the graft to its new host environment. It appears that embryonic grafts are able to induce repair processes follow­ ing injury to the nervous system.

Cell-Cycle Mechanisms and Neuronal Cell Death examines the role of cell cycle activation in the molecular mechanisms leading to neuronal degeneration. Leading Authors discuss this topic in relation to the major neurological disorders, including Alzheimer’s disease, stroke and epilepsy. This book serves to gain new insights into the molecular determinants of neuronal death and to establish new targets for therapeutic intervention.

Claus W. Heizmann and Katharina Braun ore than 10,000 articles were published in 1994 on calcium, M 2 emphasizing the widespread interest and progress in Ca +- 2 related research. This book focuses mainly on Ca + -binding pro- 2 teins in the central nervous system, where Ca + ions have been found to activate fundamental processes such as release of neu- rotransmitters, axonal flow, long term potentiation, cell motility, differentiation, secretion, and apoptosis. It has also been found that a number of neurodegenerative disorders have been attributed 2 1 to aberrations of intracellular Ca + homeostasis. 2 2 Intracellular Ca + levels and Ca + signaling within cells must 2 3 2 be tightly controlled. * Ca + overload as a result of seizures or ischemia is supposed to activate biochemical processes, leading to enzymatic breakdown of proteins and lipids, malfunctioning of 2 mitochondria, energy failure and ultimately cell death.There is 3 experimental evidence that electrically induced irreversible depo- larization of hippocampal neurons, which may be an early indica- 2 tion of neuronal damage, could be prevented by injecting Ca + chelators and thereby increasing intracellular buffering capacity. Thus, it is reasonable to assume that neurons containing certain 2 intracellular Ca +-binding proteins, and therefore having a greater 2 capacity to buffer Ca +, could be more resistant to degeneration.

This book is about the role of cholecystokinin (CCK) in the neurobiology of anxiety and panic attacks. An up-to-date review of the topic is given in a multidisciplinary perspective ranging from neurochemistry to human behavior. This volume is equally informative to basic and clinical scientists.

A Cytoplasm Connexon or Hemichannel Cytoplasm external loop I - P. M. N-Termlnus Fig. 1. 1. Topology of gap junction channels. (A) Cap junction channels, extending from the cytoplasm of one cell to the cytoplasm of another, are formed by two connexons or hemichannels connected across extracellular space. (B) Each connexon is formed from six connexin subunits, each having four membrane-spanning domains and both amino and carboxyl termini within the cytoplasm. External/oops (I and II} are believed to provide the high affinity interactions between the hemichannels. 4 Gap }unctions in the Nervous System P-region of voltage sensitive nonjunctional molecules; these contributed disulfide 9 channels. And Delmar's group has ob- bridges are presumably involved in intra- tained evidence that intracellular acidifi- connexin and inter-EL loop tertiary struc- cation may result in a conformational ture.An old observation that should be change analogous to the ball and chain repeated stoichiometrically with modern techniques is that gap junction channels model of inactivation of voltage gated ionic can be split into connexons or hemi- channels, whereby the carboxyl terminal channels using hyperosmotic disaccharide portion of connexin43 binds to CL, closing 23 solutions again implying that linkage is the channel. Higher order structure of the channel not covalent. is believed to consist of six connexins form- ing the hemichannel or connexon in a 3.

erebellar ataxia is a failure in muscular coordination that re­ C sults from a slow, progressive deterioration of neurons in the cerebellum. An estimated 150,000 people are affected by the he­ reditary ataxias and related disorders in the United States. At present, there is no known cure. In an experimental treatment aimed at reconstructing the damaged pathway through exog­ enous neuronal supplementation, genetically ataxic mice have been used for intracerebral grafting of genetically healthy cerebellar neuroblasts, and evidence has been obtained for graft-induced en­ hancement of behavioral responses after bilateral cerebellar grafts. Such results are encouraging and underscore the potential of the neural grafting technique in restoring cerebellar function. How­ ever, many of the pathological and biochemical mechanisms in the interaction between grafted tissue and the host brain need to be further elucidated in extensive experimental studies, and great cau­ tion must be used in contemplating the theoretical feasibility of a possible application in humans.

Some general aspects of opiate dependence are described in a first section including a brief historical description and an explanation of the different models currently used to investigate opiate dependence. The neurobiological bases of opiate withdrawal are detailed in a second section, which particularly emphasizes the neurophysiological adaptative changes, the processes of homologous and heterologous regulation, and the role played by different brain structures and several endogenous peptides acting as antiopiates. The last part reports several basic aspects more directly related to the clinical perspectives of opiate dependence, such as the new expectations in the treatment of opiate withdrawal or the relationships between sensitization, tolerance and withdrawal.

xidative stress refers to the cytotoxic consequences of reactive oxy- O gen species (ROS) which are generated as by-products of normal or aberrant metabolic processes that utilize molecular oxygen, or changes in protection systems. Thus, generation of ROS is a part of normal life and their interaction with host defense systems appears to exert a sig- nificant influence on the normal and abnormal functioning of the cen- tral nervous system. Oxidative stress could also be a secondary conse- quence of defects in energy metabolism involving mitochondria. A subbtle shift toward the prooxidant status that occurs in brain aging could contribute to the pathogenesis and neuropathology of neurodegenerative disorders exemplified by Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. The attractive fea- ture of the oxidative stress hypothesis is that it can account for cumula- tive damage associated with the delayed onset and the progressive na- ture of these conditions. Oxidative damage may constitute a common pathogenic link between these seemingly diverse neurodegenerative dis- orders.This book examines current knowledge and recent advances of fundamental processes involved in neuronal death, particularly oxida- tive stress as a causal, or at least an ancillary, factor in neuronal death. This book also presents an up-to-date account of the current state of knowledge about of oxidative stress in neuronal apoptosis and its role in the neuropathogenesis of age-related neurodegenerative diseases.