Glial Cell Mechanisms Regulate Alcohol Sedation in Drosophila Melanogaster

Glial Cell Mechanisms Regulate Alcohol Sedation in Drosophila Melanogaster PDF Author: Kristen M. Lee
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Approximately 16 million people in America are diagnosed with Alcohol Use Disorder (AUD) but no efficacious medical treatments exist. Alcohol-related behaviors can be studied in model organisms, and changes in these behaviors can be correlated with either (i) a risk for alcohol dependence or (ii) a symptom/feature of AUD itself. Although AUD is a disease of the central nervous system, a majority of research has focused on the neuronal underpinnings, leaving glial contributions largely undescribed. We used Drosophila melanogaster (fruit fly) to identify genes whose expression in glia regulates alcohol sedation. Mammals and Drosophila have conserved behavioral responses to alcohol and functionally similar adult glial cells, especially astrocytes. Since previous research in mammals and flies has demonstrated that glia respond to alcohol administration, we hypothesized that glia are important regulators of alcohol-related behaviors. To pursue this, we characterized a pan-glial steroid-inducible GeneSwitch transgenic fly, which allows gene manipulation within glia during adulthood. We performed a targeted screen and manipulated genes that were known to be expressed within Drosophila glia and measured their alcohol sedation sensitivity using the ethanol sedation assay. We identified the genes Cysteine proteinase 1 (Cp1) and Tyramine decarboxylase 2 (Tdc2). Knocking down Cp1 in cortex glia, as well as all glia during adulthood, increased alcohol sedation sensitivity and may also enhance rapid tolerance development. We could not identify what pathway Cp1 was functioning within to mediate this response, suggesting that Cp1 may have a unique function within glia. Knockdown or overexpression of Tdc2 in glia increased or decreased alcohol sedation sensitivity, respectively. Tdc2 functions upstream of the vesicular monoamine transporter (VMAT) and the SNARE complex to regulate alcohol sedation. These results were specific to astrocytes, as well as all glia during adulthood. These results suggest that tyramine synthesis via Tdc2 and its release via vesicular exocytosis regulates alcohol sedation. Taken together, these results suggest that glia are important regulators of alcohol-related behaviors in flies. Interestingly, fly cortex glia and astrocytes are functionally similar to mammalian astrocytes, indicating that these results may be translatable to mammals.

Glial Cell Mechanisms Regulate Alcohol Sedation in Drosophila Melanogaster

Glial Cell Mechanisms Regulate Alcohol Sedation in Drosophila Melanogaster PDF Author: Kristen M. Lee
Publisher:
ISBN:
Category :
Languages : en
Pages :

Get Book Here

Book Description
Approximately 16 million people in America are diagnosed with Alcohol Use Disorder (AUD) but no efficacious medical treatments exist. Alcohol-related behaviors can be studied in model organisms, and changes in these behaviors can be correlated with either (i) a risk for alcohol dependence or (ii) a symptom/feature of AUD itself. Although AUD is a disease of the central nervous system, a majority of research has focused on the neuronal underpinnings, leaving glial contributions largely undescribed. We used Drosophila melanogaster (fruit fly) to identify genes whose expression in glia regulates alcohol sedation. Mammals and Drosophila have conserved behavioral responses to alcohol and functionally similar adult glial cells, especially astrocytes. Since previous research in mammals and flies has demonstrated that glia respond to alcohol administration, we hypothesized that glia are important regulators of alcohol-related behaviors. To pursue this, we characterized a pan-glial steroid-inducible GeneSwitch transgenic fly, which allows gene manipulation within glia during adulthood. We performed a targeted screen and manipulated genes that were known to be expressed within Drosophila glia and measured their alcohol sedation sensitivity using the ethanol sedation assay. We identified the genes Cysteine proteinase 1 (Cp1) and Tyramine decarboxylase 2 (Tdc2). Knocking down Cp1 in cortex glia, as well as all glia during adulthood, increased alcohol sedation sensitivity and may also enhance rapid tolerance development. We could not identify what pathway Cp1 was functioning within to mediate this response, suggesting that Cp1 may have a unique function within glia. Knockdown or overexpression of Tdc2 in glia increased or decreased alcohol sedation sensitivity, respectively. Tdc2 functions upstream of the vesicular monoamine transporter (VMAT) and the SNARE complex to regulate alcohol sedation. These results were specific to astrocytes, as well as all glia during adulthood. These results suggest that tyramine synthesis via Tdc2 and its release via vesicular exocytosis regulates alcohol sedation. Taken together, these results suggest that glia are important regulators of alcohol-related behaviors in flies. Interestingly, fly cortex glia and astrocytes are functionally similar to mammalian astrocytes, indicating that these results may be translatable to mammals.

Dissertation Abstracts International

Dissertation Abstracts International PDF Author:
Publisher:
ISBN:
Category : Dissertations, Academic
Languages : en
Pages : 652

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Autophagy in Health and Disease

Autophagy in Health and Disease PDF Author:
Publisher: Academic Press
ISBN: 0128220228
Category : Science
Languages : en
Pages : 446

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Book Description
Autophagy in Health and Disease, Volume 175, presents the latest insights from renowned experts in the field who discuss the key role of autophagic responses in the preservation of cellular and organismal homeostasis and how defects in the molecular apparatus for autophagy drive or accompany disease. Specific chapters in this new release include Crosstalk between autophagy and cell death signaling: mechanisms and therapeutic relevance, C. elegans to model autophagy-related human disorders, Autophagy in Kidney Disease: advances and therapeutic potential, Autophagy in Chronic Lung Disease, Autophagy in motoneuronal disorders, Strategies employed by viruses to manipulate autophagy, and much more. - Provides an outstanding panel of recognized experts in the field who discuss the latest in autophagy - Includes critical discussions of autophagy in the context of each major human disorder - Models autophagy-related human pathologies in lower eukaryotes

Behavioral Neurobiology of Alcohol Addiction

Behavioral Neurobiology of Alcohol Addiction PDF Author: Wolfgang Sommer
Publisher: Springer Science & Business Media
ISBN: 3642287204
Category : Medical
Languages : en
Pages : 721

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Book Description
The question how alcohol alters mood states and why this may end up becoming an addiction is puzzling alcohol researchers since decades. In this volume, an assembly of highly distinguished experts and leaders in alcohol addiction research provides lucid presentations of the current knowledge and research challenges as well as interesting viewpoints on future research directions aimed to stimulate communication and convergence between clinical and preclinical researchers, and to renew interest in the vibrant field of alcohol addiction research among a wide scientifically minded audience. Five Current Topics are discussed in this volume: Neurobiological mechanisms of alcoholism, Genetics, Clinical phenotypes and their preclinical models, Brain imaging, and Translational approaches for treatment development, both pharmacological and non-pharmacological. These areas have in our opinion brought alcohol research substantially forward and influenced our thinking about how to reach our common paramount goal, namely to offer effective treatment solutions for an extensive group of patients with largely unmet medical needs.

Foundations of Psychiatric Sleep Medicine

Foundations of Psychiatric Sleep Medicine PDF Author: John W. Winkelman
Publisher: Cambridge University Press
ISBN: 1139494341
Category : Medical
Languages : en
Pages : 435

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Book Description
Sleep-related complaints are extremely common across the spectrum of psychiatric illness. Accurate diagnosis and management of sleep disturbances requires an understanding of the neurobiological mechanisms underlying sleep and wakefulness, the characteristics of sleep disturbance inherent to psychiatric illness and primary sleep disorders, as well as the psychopharmacologic and behavioral treatments available. Foundations of Psychiatric Sleep Medicine provides a uniquely accessible, practical, and expert summary of current clinical concepts at the sleep-psychiatry interface. Topics covered include: basic principles in sleep science, clinical sleep history taking, primary sleep disorders in psychiatric contexts, and sleep disturbance across a range of mood, anxiety, psychotic, substance use, cognitive and developmental disorders. Written by outstanding experts in the field of sleep medicine and psychiatry, this academically rigorous and clinically useful text is an essential resource for psychiatrists, psychologists and other health professionals interested in the relationship between sleep and mental illness.

Brain Transcriptome

Brain Transcriptome PDF Author:
Publisher: Academic Press
ISBN: 9780128011058
Category : Science
Languages : en
Pages : 0

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Book Description
Published since 1959, International Review of Neurobiology is a well-known series appealing to neuroscientists, clinicians, psychologists, physiologists, and pharmacologists. Led by an internationally renowned editorial board, this important serial publishes both eclectic volumes made up of timely reviews and thematic volumes that focus on recent progress in a specific area of neurobiology research. This volume, concentrates on the brain transcriptome.

Histamine in the brain

Histamine in the brain PDF Author: Jian-Sheng Lin
Publisher: Frontiers Media SA
ISBN: 2889194345
Category : Brain
Languages : en
Pages : 100

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Book Description
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.

Addiction

Addiction PDF Author: Gene M. Heyman
Publisher: Harvard University Press
ISBN: 0674057279
Category : Psychology
Languages : en
Pages : 213

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Book Description
In a book sure to inspire controversy, Gene Heyman argues that conventional wisdom about addictionÑthat it is a disease, a compulsion beyond conscious controlÑis wrong. Drawing on psychiatric epidemiology, addictsÕ autobiographies, treatment studies, and advances in behavioral economics, Heyman makes a powerful case that addiction is voluntary. He shows that drug use, like all choices, is influenced by preferences and goals. But just as there are successful dieters, there are successful ex-addicts. In fact, addiction is the psychiatric disorder with the highest rate of recovery. But what ends an addiction? At the heart of HeymanÕs analysis is a startling view of choice and motivation that applies to all choices, not just the choice to use drugs. The conditions that promote quitting a drug addiction include new information, cultural values, and, of course, the costs and benefits of further drug use. Most of us avoid becoming drug dependent, not because we are especially rational, but because we loathe the idea of being an addict. HeymanÕs analysis of well-established but frequently ignored research leads to unexpected insights into how we make choicesÑfrom obesity to McMansionizationÑall rooted in our deep-seated tendency to consume too much of whatever we like best. As wealth increases and technology advances, the dilemma posed by addictive drugs spreads to new products. However, this remarkable and radical book points to a solution. If drug addicts typically beat addiction, then non-addicts can learn to control their natural tendency to take too much.

Invertebrate Learning and Memory

Invertebrate Learning and Memory PDF Author: Martin Giurfa
Publisher: Elsevier Inc. Chapters
ISBN: 0128071516
Category : Medical
Languages : en
Pages : 34

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Book Description
The behavior of insects transcends elementary forms of adaptive responding to environmental changes. We discuss examples of exploration, instrumental and observational learning, expectation, learning in a social context, and planning of future actions. We show that learning about sensory cues allows insects to transfer flexibly their responses to novel stimuli attaining thereby different levels of complexity, from basic generalization to categorization and concept learning consistent with rule extraction. We argue that updating of existing memories requires multiple forms of memory processing. A key element in these processes is working memory, an active form of memory considered to allow evaluation of actions on the basis of expected outcome. We discuss which of these cognitive faculties can be traced to specific neural processes and how they relate to the overall organization of the insect brain.

Cumulated Index Medicus

Cumulated Index Medicus PDF Author:
Publisher:
ISBN:
Category : Medicine
Languages : en
Pages : 1848

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Book Description