title: Astroglial Vesicular Trafficking in Neurodegenerative Diseases.
abstract: The neocortex represents one of the largest estates of the human brain. This structure comprises ~30-40 billions of neurones and even more of non-neuronal cells. Astrocytes, highly heterogeneous homoeostatic glial cells, are fundamental for housekeeping of the brain and contribute to information processing in neuronal networks. Gray matter astrocytes tightly enwrap synapses, contact blood vessels and, naturally, are also in contact with the extracellular space, where convection of fluid takes place. Thus astrocytes receive signals from several distinct extracellular domains and can get excited by numerous mechanisms, which regulate cytosolic concentration of second messengers, such as Ca2+and cAMP. Excited astrocytes often secrete diverse substances (generally referred to as gliosignalling molecules) that include classical neurotransmitters such as glutamate and ATP or neuromodulators such as D-serine or neuropeptides. Astrocytic secretion occurs through several mechanisms: by diffusion through membrane channels, by translocation via plasmalemmal transporters or by vesicular exocytosis. Vesicular release of gliosignalling molecules appears fundamentally similar to that operating in neurones, since it depends on the SNARE proteins-dependent merger of the vesicle membrane with the plasmalemma. However, the coupling between the stimulus and astroglial vesicular secretion is at least one order of magnitude slower than that in neurones. Here we review mechanisms of astrocytic excitability and the molecular, anatomical and physiological properties of vesicular apparatus mediating the release of gliosignalling molecules in health and in the neurodegenerative pathology.
authors.affiliation: Celica Biomedical, 1000, Ljubljana, Slovenia. robert.zorec@mf.uni-lj.si.|Faculty of Medicine, Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, University of Ljubljana, 1000, Ljubljana, Slovenia. robert.zorec@mf.uni-lj.si.
authors.forename: Robert
authors.initials: R
authors.lastname: Zorec
authors.affiliation: Atomic Force Microscopy and Nanotechnology Laboratories, Department of Neurobiology, Civitan International Research Center and Center for Glial Biology in Medicine, Evelyn F. McKnight Brain Institute, University of Alabama, 1719 6th Avenue South, CIRC 429, Birmingham, AL, 35294-0021, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Parpura
authors.affiliation: Faculty of Life Sciences, The 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.|Department of Neurosciences, University of the Basque Country UPV/EHU and CIBERNED, Leioa, Spain. Alexej.Verkhratsky@manchester.ac.uk.|University of Nizhny Novgorod, Nizhny Novgorod, 603022, Russia. Alexej.Verkhratsky@manchester.ac.uk.
authors.forename: Alexei
authors.initials: A
authors.lastname: Verkhratsky
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D005089:Exocytosis; D006801:Humans; D019579:Neocortex / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D050600:SNARE Proteins / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: D050600:SNARE Proteins
keywords: Cytosolic Ca2+; Gliocrine system; Gliosignalling molecules; Regulated exocytosis; Signalling; Vesicle dynamics; cAMP