The Role of Glia in Neurotoxicity Second Edition

Presenting the latest research in glial cell function gleaned from new techniques in imaging and molecular biology, The Role of Glia in Neurotoxicity, Second Edition covers multiple aspects of glial cells, including morphology, physiology, ...

The Role of Glia in Neurotoxicity  Second Edition

Presenting the latest research in glial cell function gleaned from new techniques in imaging and molecular biology, The Role of Glia in Neurotoxicity, Second Edition covers multiple aspects of glial cells, including morphology, physiology, pharmacology, biochemistry, pathology, and their involvement in the pathophysiology of neurological diseases. The book is structured to examine the interactions between glial cells and neurons during development, adulthood, and senescence, followed by specific examples of directly mediated glial neurotoxicity. The book also covers miscellaneous topics in glial physiology/biochemistry such as signaling and edema. The book includes coverage of advances in our knowledge and understanding of glial physiology and biochemistry. Discover what's new in the Second Edition: Neuronal-glia metabolic interactions Neuronal-glia interactions (glutamate homeostasis) Zinc transporters in glia Energy deprivation/mitochondrial dysfunction - unique astrocyte susceptibilities Astrocytes and MPTP neurotoxicity Astroglia and food toxins Current understanding of the importance of glia has caused a boom in published information. Yet while many of the published textbooks are multifaceted and multidisciplinary, none includes the role of glia in neurotoxicity. Written by leaders in the field of glial research, this text fills this missing gap in the literature. Broader in scope than the first edition, including contributions from internationally known researchers, this is still the only book dedicated to exploring the role of glial cells in mediating neurotoxicology. Features Summarizes the latest research in glial cell function gleaned from new techniques in imaging and molecular biology Contains tables and figures that give you quick and easy access to precise data Includes a contemporary summary of literature that puts information useful for grant submissions at your fingertips Features new chapters covering metabolic interactions, glutamate homeostasis, transporters, energy deprivation/mitochondrial dysfunction, astrocytes, and food toxins Explores the role of glial cells in mediating neurotoxicity and incorporates information on specific effects of many compounds

The Role of Glia in Neurotoxicity Second Edition

The book also covers miscellaneous topics in glial physiology/biochemistry such as signaling and edema. The book includes coverage of advances in our knowledge and understanding of glial physiology and biochemistry.

The Role of Glia in Neurotoxicity  Second Edition

Presenting the latest research in glial cell function gleaned from new techniques in imaging and molecular biology, The Role of Glia in Neurotoxicity, Second Edition covers multiple aspects of glial cells, including morphology, physiology, pharmacology, biochemistry, pathology, and their involvement in the pathophysiology of neurological diseases. The book is structured to examine the interactions between glial cells and neurons during development, adulthood, and senescence, followed by specific examples of directly mediated glial neurotoxicity. The book also covers miscellaneous topics in glial physiology/biochemistry such as signaling and edema. The book includes coverage of advances in our knowledge and understanding of glial physiology and biochemistry. Discover what's new in the Second Edition: Neuronal-glia metabolic interactions Neuronal-glia interactions (glutamate homeostasis) Zinc transporters in glia Energy deprivation/mitochondrial dysfunction - unique astrocyte susceptibilities Astrocytes and MPTP neurotoxicity Astroglia and food toxins Current understanding of the importance of glia has caused a boom in published information. Yet while many of the published textbooks are multifaceted and multidisciplinary, none includes the role of glia in neurotoxicity. Written by leaders in the field of glial research, this text fills this missing gap in the literature. Broader in scope than the first edition, including contributions from internationally known researchers, this is still the only book dedicated to exploring the role of glial cells in mediating neurotoxicology. Features Summarizes the latest research in glial cell function gleaned from new techniques in imaging and molecular biology Contains tables and figures that give you quick and easy access to precise data Includes a contemporary summary of literature that puts information useful for grant submissions at your fingertips Features new chapters covering metabolic interactions, glutamate homeostasis, transporters, energy deprivation/mitochondrial dysfunction, astrocytes, and food toxins Explores the role of glial cells in mediating neurotoxicity and incorporates information on specific effects of many compounds

Role of Glial CCR5 in Mediating HIV 1 Tat and Opiate Neurotoxicity and Behavioral Phenotype

We hypothesize this is due to converging actions on the CCL5-CCR5 signaling axis by HIV-1 Tat and morphine co-exposure, primarily mediated at the level of the glia, whose consequent activation leads to neuronal damage.

Role of Glial CCR5 in Mediating HIV 1 Tat and Opiate Neurotoxicity and Behavioral Phenotype

Human immunodeficiency virus type 1 (HIV-1) persists in certain CNS cell populations, despite peripheral control of the infection with modern antiretroviral therapy. Infected and/or activated cells release viral proteins, such as trans-activator of transcription (Tat) and various pro-inflammatory factors such as CCL5, creating a positive loop of neuro-inflammation. This serves as the basis for the resulting sublethal and lethal neuropathology that manifests as a spectrum of HIV-mediated CNS impairments, known as HIV-associated neurocognitive disorders (HAND). Opiates, which exist as an interlinked epidemic with HIV-1 infections, exacerbate these neurological effects through direct and indirect mechanisms that disrupt both glial and neuronal function. We hypothesize this is due to converging actions on the CCL5-CCR5 signaling axis by HIV-1 Tat and morphine co-exposure, primarily mediated at the level of the glia, whose consequent activation leads to neuronal damage. We performed repeated measure studies on mixed glia and neuron co-cultures obtained from C57Bl/6J and/or CCR5 knockout mice, treated with Tat and/or morphine for 72 hours. As established in prior studies, morphine worsened Tat-induced neurotoxicity in wild-type co-cultures; substitution of CCR5-null glia eliminated the interactive effects of Tat and morphine, but substitution of CCR5-null neurons did not. Overall, these results suggest that glial CCR5, but not neuronal CCR5, is a convergence point for the interactive effects of Tat and morphine that result in neuron loss. Additional experiments involving treatments with naloxone, a MOR antagonist, or the CCR5 antagonist maraviroc, confirmed each receptor's role in mediating Tat + morphine toxicity. Quite surprisingly, in co-cultures of wild-type neurons and CCR5-null glia, morphine entirely protected neurons from the neurotoxic effects of Tat. We hypothesize that this effect may reflect an imbalance of neurotrophic factors, particularly BDNF and its neurotoxic precursor proBDNF, whose levels are altered in HIV+ and illicit drug-using patients and may contribute to changes in neuronal signaling and survival exhibited in HAND. Related behavioral tests of anxiety, motor and cognitive function - three areas of neurologic decline seen in HAND - were performed in inducible Tat-transgenic mice that were treated with maraviroc via oral gavage. Tat-mediated impairment was observed in the Barnes Maze, a measure of spatial memory, and was ameliorated by maraviroc. Finally, we assessed the role of CCR5 in mediating Tat and/or morphine effects on psychomotor sensitization and dendritic morphology. With both in vitro and in vivo studies, our findings support the hypothesis that CCR5 plays a central role in driving HIV-1 Tat and/or morphine-mediated neuronal damage.

Neurotoxicology

This second edition of Neurotoxicology is valuable for scientists in government and industry who are responsible for public health and for the safe and efficient use of chemicals.

Neurotoxicology

This second edition of Neurotoxicology is valuable for scientists in government and industry who are responsible for public health and for the safe and efficient use of chemicals. This integrated approach to neurotoxicology will aid in the understanding of the sites and mechanisms of neurotoxicity, stimulate the formulation of testable hypotheses about how chemicals affect the nervous system, and help improve the risk assessment process. This edition focuses primarily on the neurobiological basis underlying neurotoxic sites and modes of action. The contents include: *molecular biological and in vitro approaches *potential cellular and molecular sites involving neuron-glia interactions *axonal transport *ion channels *metabolic influences on neurotoxicity *role of free radical formation in neurotoxicity *interaction between chemicals and trophic factors *endocrine disruptors *apoptosis in neurotoxicity *in vivo brain imaging *advances in measuring cognitive function *advances in developing quantitative models for neurotoxicology/risk assessment

The Brain s Best Friend Microglial Neurotoxicity Revisited

This review is aimed to critically reconsider the term microglia neurotoxicity and to discuss experimental problems around microglia biology, that often have led to the conclusion that microglia are neurotoxic cells

The Brain s Best Friend  Microglial Neurotoxicity Revisited

Abstract: One long standing aspect of microglia biology was never questioned; their involvement in brain disease. Based on morphological changes (retracted processes and amoeboid shape) that inevitably occur in these cells in case of damage in the central nervous system, microglia in the diseased brain were called "activated." Because "activated" microglia were always found in direct neighborhood to dead or dying neuron, and since it is known now for more than 20 years that cultured microglia release numerous factors that are able to kill neurons, microglia "activation" was often seen as a neurotoxic process. From an evolutionary point of view, however, it is difficult to understand why an important, mostly post-mitotic and highly vulnerable organ like the brain would host numerous potential killers. This review is aimed to critically reconsider the term microglia neurotoxicity and to discuss experimental problems around microglia biology, that often have led to the conclusion that microglia are neurotoxic cells

The Role of Glia in Alzheimer s Disease

We believe that the role of glia is the next frontier to be explored in Alzheimer’s disease research.

The Role of Glia in Alzheimer s Disease

We believe that the role of glia is the next frontier to be explored in Alzheimer’s disease research. This eBook is an update on both the current knowledge of astrocytes and microglia involvement in Alzheimer’s disease pathophysiology, and some of the techniques available to study them.

Microglia Neurotoxicity

This novel in vitro model of the ischemic penumbra will be very useful for delineating processes more relevant to neuroinflammation following ischemic stroke.

Microglia   Neurotoxicity

Microglia, the resident immune cells of the CNS, are important for orchestrating acute brain inflammation following stroke. Over the past decade, there is growing evidence that microglia K+ channels may play a role in regulating microglia function. In this study, we show that Ca2+ /calmodulin-activated, small-conductance K+ channels (KCNN1/SK1/KCa2.1, KCNN2/SK2/KCa2.2, KCNN3/SK3/KCa2.3 and KCNN4/SK4/KCa3.1) are expressed in rat microglia. In paricular, we found that only KCa3.1 channel mRNA was highly expressed in resting microglia relative to other CNS cells (e.g. astrocytes and neurons), while activated microglia had higher levels KCa2.3 expression. To examine if these channels regulate microglia-induced neurotoxicity, we tested them in co-culture model with LPS-treated microglia and neurons. Interestingly, LPS-activated microglia killed neurons and killing was markedly reduced by specifically blocking either microglia KCa2.3 or KCa3.1 channels. Blocking either KCa3.1 or KCa2.3 channels inhibited LPS-induced iNOS expression and nitric oxide production by microglia. LPS activated p38 mitogen activated protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB) in microglia, and either KCa2.3 or KCa3.1 channel blockade inhibited p38 MAPK phosphorylation, but not NF-kappaB activation. In addition to our in vitro findings, intraocular injections of the KCa3.1 channel blocker TRAM-34 reduced the death of retinal ganglion cells. Together these findings suggest that selective blockade of KCa3.1 or KCa2.3 channels in microglia might provide therapeutic benefits in neurodegenerative disorders. The latter part of this study, we developed an in vitro model of microglia activation that is more relevant to the penumbra region, where microglia can respond to ischemia-stressed neurons. To mimic this in vitro, microglia, grown on porous Transwell(TM) inserts, were activated by oxygen glucose-deprived (OGD) neurons. We found that the OGD-stressed neurons released glutamate, which acted on microglial group II metabotropic glutamate receptors to activate the microglia through NF-kappaB-mediated pathway. Subsequently, we found that these activated microglia killed naive neurons through an apoptotic mechanism, mediated by TNF-alpha. Unlike the earlier LPS model, this killing was not affected by an iNOS inhibitor (SMT) or a peroxynitrite scavenger (FeTmPyP). This novel in vitro model of the ischemic penumbra will be very useful for delineating processes more relevant to neuroinflammation following ischemic stroke.

Neuron Glia Interaction in Neuroinflammation

In this book, we focused on neuron-glia interaction of various aspects for understanding of pathophysiology of neuroinflammation in development of inflammatory as well as degenerative neurological disorders.

Neuron Glia Interaction in Neuroinflammation

Accumulation on glia is an active pathological element in many neurological disorders. Gliosis produces neuroinflammation through both neurotrophic and inflammatory means, but the exact mechanism through which this happens remain unclear. It is suspected that damage to neurons activates the growth of glial cells. The proposed book focuses on the interaction between neurons and glia to help elucidate the pathophysiology of neuroinflammation in neurological disorders.​

Site Selective Neurotoxicity

This unique volume provides interdisciplinary coverage of the mechanistic perspective of neurotoxicity that focuses on the site of action of known neurotoxins.

Site Selective Neurotoxicity

This unique volume provides interdisciplinary coverage of the mechanistic perspective of neurotoxicity that focuses on the site of action of known neurotoxins. It provides the reader with an insight into the common characteristics of neurotoxin action on the nervous system and examines sites of action at three levels of complexity: molecular, cellu

The Role of Line 1 Transposable Element in Methamphetamine Neurotoxicity in the Neurogenic Zones

Methamphetamine (METH) is a widely abused psychostimulant, which can cause neurotoxicity in the striatum and hippocampus.

The Role of Line 1 Transposable Element in Methamphetamine Neurotoxicity in the Neurogenic Zones

Methamphetamine (METH) is a widely abused psychostimulant, which can cause neurotoxicity in the striatum and hippocampus. Several epigenetic changes were identified after binge METH exposure, including histone modification, DNA methylation, and changes in miRNA levels. We have shown that binge METH increases expression and activity of Long INterspersed Element (LINE-1), a transposable element, in doublecortin-positive neurons within rat neurogenic zones [1]. The goal of the present study was to identify which type(s) of cells show increases in LINE-1 following binge METH exposure, and determine whether binge METH-induced increases in LINE-1 are associated with cell death. To achieve this goal, male adult Sprague Dawley rats were treated with binge METH (4x 10mg/kg, i.p. every 2 h) or saline, sacrificed 24 hours later, and examined for LINE-1 expression and either markers of cell types in neurogenic zones or signs of apoptosis within the neurogenic zones. We found that increased LINE-1 expression co-localized with most GFAP-positive cells in both the subgranular zone (SGZ) and subventricular zone (SVZ), as well as most NeuN-positive cells in SGZ. We also found that LINE-1 expression co-localized with some, but not all, apoptotic marker expression within the neurogenic zones. However, LINE-1 expression did co-localize with an oxidative stress marker. Collectively, our data suggest that systemic administration of neurotoxic doses of binge METH increases the activity of LINE-1 mostly in glial cells and post-mitotic cells, and may be associated with responses to oxidative stress and/or gliosis.

Methylmercury and Neurotoxicity

This book will provide state-of-the-art information to the graduate student training in toxicology, risk assessors, researchers and medical providers at large.

Methylmercury and Neurotoxicity

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.

The Role of P2X Receptors in HIV and Opiate related Neurotoxicity

Emerging evidence suggests that opioid drugs can exacerbate neuroAIDS.

The Role of P2X Receptors in HIV and Opiate related Neurotoxicity

Emerging evidence suggests that opioid drugs can exacerbate neuroAIDS. Microglia are the principal neuroimmune effectors thought to be responsible for neuron damage in HIV-infected individuals, and evidence suggests that drugs acting via opioid receptors in microglia aggravate the neuropathophysiological effects of HIV. The P2X family of ATP activated ligand-gated ion channels regulates key aspects of microglial function. In addition, opioid-dependent microglial activation has been reported to be mediated through P2X4 signaling, prompting us to investigate P2X receptors contribution to the neurotoxic effects of HIV and morphine. In vitro experiments showed treatment with TNP-ATP prevented the neurotoxic effects of morphine and/or HIV Tat, or ATP alone in a concentration dependent manner. This evidence suggests P2X receptors mediate the neurotoxic effects of these insults in striatal neurons. P2X1, P2X3, and P2X7 selective receptor antagonists did not prevent Tat- and/or morphine-induced neurotoxicity, implying cellular pathways activated may not involve these subtypes. Cells from P2X4KO mice show that activation of the P2X4 receptor on glia are necessary to cause Tat and/or morphine toxicity. However, data implied that baseline neuronal function may be altered due to lack of P2X4 receptor expression, and also gave evidence for altered Tat and morphine cellular signaling when the two are given in combination versus alone. Surgeries were performed on P2X4 KO and WT mice, which received intrastriatal Tat injections and morphine and/or naltrexone pellets. WT mice showed significant increases in inflammatory markers when treated with Tat and/or morphine. Increases in inflammatory markers were not seen in P2X4 KO mice, implying P2X4 receptors play a role in neuroinflammation resulting from Tat and/or morphine. Finally, human tissue samples from the National NeuroAIDS Tissue Consortium were analyzed. Changes in P2X5 and P2X7 mRNA were found in microarray data, but only changes in P2X7 mRNA levels were confirmed by RT-PCR. No changes in P2X4 mRNA levels were detected. Our experiments indicate the P2X receptor family contributes to Tat- and morphine- related neuronal injury, and reveal that members of the P2X receptor family, especially P2X4, may be novel therapeutic targets for restricting the synaptodendritic injury and neurodegeneration that accompany neuroAIDS and opiate abuse.

The Role of Glia in Plasticity and Behavior

Neuronal NMDARs play a critical role in synaptic plasticity, neuroprotection, and neurotoxicity, but relatively little is known about their regulation by glial cells. Our study identified a novel form of astrocytic NMDAR modulation that ...

The Role of Glia in Plasticity and Behavior

Glial cells are no longer considered passive bystanders in neuronal brain circuits. Not only are they required for housekeeping and brain metabolism, they are active participants in regulating the physiological function and plasticity of brain circuits and the online control of behavior both in invertebrate and vertebrate model systems. In invertebrates, glial cells are essential for normal function of sensory organs (C. elegans) and necessary for the circadian regulation of locomotor activity (D. melanogaster). In the mamallian brain, astrocytes are implicated in the regulation of cortical brain rhythms and sleep homeostasis. Disruption of AMPA receptor function in a subset of glial cell types in mice shows behavioral deficits. Furthermore, genetic disruption of glial cell function can directly control behavioral output. Regulation of ionic gradients by glia can underlie bistability of neurons and can modulate the fidelity of synaptic transmission. Grafting of human glial progenitor cells in mouse forebrain results in human glial chimeric mice with enhanced plasticity and improved behavioral performance, suggesting that astrocytes have evolved to cope with information processing in more complex brains. Taken together, current evidence is strongly suggestive that glial cells are essential contributors to information processing in the brain. This Research Topic compiles recent research that shows how the molecular mechanisms underlying glial cell function can be dissected, reviews their impact on plasticity and behavior across species and presents novel approaches to further probe their function.