Astrocytic Pathological Calcium Homeostasis and Impaired Vesicle Trafficking in Neurodegeneration
Although the central nervous system (CNS) consists of highly heterogeneous populations of neurones and glial cells, clustered into diverse anatomical regions with specific functions, there are some conditions, including alertness, awareness and attention that require simultaneous, coordinated and sp...
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Published in | International journal of molecular sciences Vol. 18; no. 2; p. 358 |
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Abstract | Although the central nervous system (CNS) consists of highly heterogeneous populations of neurones and glial cells, clustered into diverse anatomical regions with specific functions, there are some conditions, including alertness, awareness and attention that require simultaneous, coordinated and spatially homogeneous activity within a large area of the brain. During such events, the brain, representing only about two percent of body mass, but consuming one fifth of body glucose at rest, needs additional energy to be produced. How simultaneous energy procurement in a relatively extended area of the brain takes place is poorly understood. This mechanism is likely to be impaired in neurodegeneration, for example in Alzheimer's disease, the hallmark of which is brain hypometabolism. Astrocytes, the main neural cell type producing and storing glycogen, a form of energy in the brain, also hold the key to metabolic and homeostatic support in the central nervous system and are impaired in neurodegeneration, contributing to the slow decline of excitation-energy coupling in the brain. Many mechanisms are affected, including cell-to-cell signalling. An important question is how changes in cellular signalling, a process taking place in a rather short time domain, contribute to the neurodegeneration that develops over decades. In this review we focus initially on the slow dynamics of Alzheimer's disease, and on the activity of locus coeruleus, a brainstem nucleus involved in arousal. Subsequently, we overview much faster processes of vesicle traffic and cytosolic calcium dynamics, both of which shape the signalling landscape of astrocyte-neurone communication in health and neurodegeneration. |
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AbstractList | Although the central nervous system (CNS) consists of highly heterogeneous populations of neurones and glial cells, clustered into diverse anatomical regions with specific functions, there are some conditions, including alertness, awareness and attention that require simultaneous, coordinated and spatially homogeneous activity within a large area of the brain. During such events, the brain, representing only about two percent of body mass, but consuming one fifth of body glucose at rest, needs additional energy to be produced. How simultaneous energy procurement in a relatively extended area of the brain takes place is poorly understood. This mechanism is likely to be impaired in neurodegeneration, for example in Alzheimer’s disease, the hallmark of which is brain hypometabolism. Astrocytes, the main neural cell type producing and storing glycogen, a form of energy in the brain, also hold the key to metabolic and homeostatic support in the central nervous system and are impaired in neurodegeneration, contributing to the slow decline of excitation-energy coupling in the brain. Many mechanisms are affected, including cell-to-cell signalling. An important question is how changes in cellular signalling, a process taking place in a rather short time domain, contribute to the neurodegeneration that develops over decades. In this review we focus initially on the slow dynamics of Alzheimer’s disease, and on the activity of locus coeruleus, a brainstem nucleus involved in arousal. Subsequently, we overview much faster processes of vesicle traffic and cytosolic calcium dynamics, both of which shape the signalling landscape of astrocyte-neurone communication in health and neurodegeneration. |
Author | Zorec, Robert Vardjan, Nina Verkhratsky, Alexej |
AuthorAffiliation | 1 Laboratory of Cell Engineering, Celica BIOMEDICAL, 1000 Ljubljana, Slovenia 4 Achucarro Center for Neuroscience, IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain 3 Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK 2 Laboratory of Neuroendocrinology & Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia |
AuthorAffiliation_xml | – name: 4 Achucarro Center for Neuroscience, IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain – name: 2 Laboratory of Neuroendocrinology & Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia – name: 1 Laboratory of Cell Engineering, Celica BIOMEDICAL, 1000 Ljubljana, Slovenia – name: 3 Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK |
Author_xml | – sequence: 1 givenname: Nina surname: Vardjan fullname: Vardjan, Nina email: nina.vardjan@mf.uni-lj.si, nina.vardjan@mf.uni-lj.si organization: Laboratory of Neuroendocrinology & Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia. nina.vardjan@mf.uni-lj.si – sequence: 2 givenname: Alexej surname: Verkhratsky fullname: Verkhratsky, Alexej email: alexej.verkhratsky@manchester.ac.uk, alexej.verkhratsky@manchester.ac.uk, alexej.verkhratsky@manchester.ac.uk, alexej.verkhratsky@manchester.ac.uk organization: Achucarro Center for Neuroscience, IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain. alexej.verkhratsky@manchester.ac.uk – sequence: 3 givenname: Robert surname: Zorec fullname: Zorec, Robert email: robert.zorec@mf.uni-lj.si, robert.zorec@mf.uni-lj.si organization: Laboratory of Neuroendocrinology & Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia. robert.zorec@mf.uni-lj.si |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28208745$$D View this record in MEDLINE/PubMed |
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Keywords | Alzheimer’s disease vesicle traffic excitation-energy coupling neurodegeneration calcium homeostasis noradrenaline cAMP astrocyte glia locus coeruleus Parkinson’s disease |
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SubjectTerms | Alzheimer Disease - etiology Alzheimer Disease - metabolism Alzheimer Disease - pathology Alzheimer’s disease Animals astrocyte Astrocytes - metabolism Astrocytes - pathology Atrophy Calcium - metabolism calcium homeostasis cAMP Cell Communication Cell Membrane - metabolism Cyclic AMP - metabolism excitation-energy coupling glia Homeostasis Humans locus coeruleus Locus Coeruleus - metabolism Locus Coeruleus - pathology Neocortex - metabolism Neocortex - pathology Nervous system Neurodegeneration Neurodegenerative Diseases - etiology Neurodegenerative Diseases - metabolism Neurodegenerative Diseases - pathology Neuronal Plasticity Neurons - metabolism noradrenaline Parkinson’s disease Review Signal Transduction Transport Vesicles - metabolism vesicle traffic |
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Title | Astrocytic Pathological Calcium Homeostasis and Impaired Vesicle Trafficking in Neurodegeneration |
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