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Astroglial Vesicular Trafficking in Neurodegenerative Diseases

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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.

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Fig. 1
Fig. 2

Adapted from [158]

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Abbreviations

GPCRs:

G-protein coupled receptors

LC:

Locus coeruleus

NA:

Norepinephrine

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Acknowledgments

This work was supported by Grants P3 310, J3 4051, J3 3632, J3 6790, J3 6789 and J3 4146 from the Slovenian Research Agency (ARRS), CipKeBip, COST Action BM1002, and the EduGlia ITN EU grant (to RZ). We acknowledge the support by the National Institutes of Health (The Eunice Kennedy Shriver National Institute of Child Health and Human Development award HD078678 to VP). AV was supported in part by the Federal Target Program “Research and development in priority areas of the development of the scientific and technological complex of Russia for 2014–2020” of the Ministry of Education and Science of Russia, contract 14.581.21.0016 (Project ID RFMEFI58115X0016).

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Authors and Affiliations

  1. Celica Biomedical, 1000, Ljubljana, Slovenia

    Robert Zorec

  2. Faculty of Medicine, Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, University of Ljubljana, 1000, Ljubljana, Slovenia

    Robert Zorec

  3. 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

    Vladimir Parpura

  4. Faculty of Life Sciences, The University of Manchester, Manchester, M13 9PT, UK

    Alexei Verkhratsky

  5. Achucarro Center for Neuroscience, IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Spain

    Alexei Verkhratsky

  6. Department of Neurosciences, University of the Basque Country UPV/EHU and CIBERNED, Leioa, Spain

    Alexei Verkhratsky

  7. University of Nizhny Novgorod, Nizhny Novgorod, 603022, Russia

    Alexei Verkhratsky

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  1. Robert Zorec
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Correspondence to Robert Zorec or Alexei Verkhratsky.

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Zorec, R., Parpura, V. & Verkhratsky, A. Astroglial Vesicular Trafficking in Neurodegenerative Diseases. Neurochem Res 42, 905–917 (2017). https://doi.org/10.1007/s11064-016-2055-1

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