title: Astrocytic Pathological Calcium Homeostasis and Impaired Vesicle Trafficking in Neurodegeneration.
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.
authors.affiliation: Laboratory of Cell Engineering, Celica BIOMEDICAL, 1000 Ljubljana, Slovenia. nina.vardjan@mf.uni-lj.si.|Laboratory of Neuroendocrinology & Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia. nina.vardjan@mf.uni-lj.si.
authors.forename: Nina
authors.initials: N
authors.lastname: Vardjan
authors.affiliation: Laboratory of Cell Engineering, Celica BIOMEDICAL, 1000 Ljubljana, Slovenia. alexej.verkhratsky@manchester.ac.uk.|Laboratory of Neuroendocrinology & Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia. alexej.verkhratsky@manchester.ac.uk.|Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK. alexej.verkhratsky@manchester.ac.uk.|Achucarro Center for Neuroscience, IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain. alexej.verkhratsky@manchester.ac.uk.
authors.forename: Alexej
authors.initials: A
authors.lastname: Verkhratsky
authors.affiliation: Laboratory of Cell Engineering, Celica BIOMEDICAL, 1000 Ljubljana, Slovenia. robert.zorec@mf.uni-lj.si.|Laboratory of Neuroendocrinology & Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia. robert.zorec@mf.uni-lj.si.
authors.forename: Robert
authors.initials: R
authors.lastname: Zorec
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D001284:Atrophy; D002118:Calcium / Q000378:metabolism*; D002450:Cell Communication; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008125:Locus Coeruleus / Q000378:metabolism / Q000473:pathology; D019579:Neocortex / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D015398:Signal Transduction; D022161:Transport Vesicles / Q000378:metabolism*
chemical_list: D000242:Cyclic AMP; D002118:Calcium
keywords: Alzheimer’s disease; Parkinson’s disease; astrocyte; cAMP; calcium homeostasis; excitation-energy coupling; glia; locus coeruleus; neurodegeneration; noradrenaline; vesicle traffic