The dual face of connexin-based astroglial Ca communication: A key player in brain physiology and a prime target in pathology |
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Authors: | Marijke De Bock,Elke Decrock,Nan Wang,Mé lissa Bol,Mathieu Vinken,Geert Bultynck,Luc Leybaert |
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Affiliation: | 1. Department of Basic Medical Sciences, Physiology group, Faculty of Medicine and Health Sciences, Ghent University, B-9000 Ghent, Belgium;2. Department of Toxicology, Center for Pharmaceutical Research, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, B-1090 Brussels, Belgium;3. Department of Cellular and Molecular Medicine, Laboratory of Molecular and Cellular Signalling, KULeuven, Campus Gasthuisberg O/N-I bus 802, B-3000 Leuven, Belgium |
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Abstract: | For decades, studies have been focusing on the neuronal abnormalities that accompany neurodegenerative disorders. Yet, glial cells are emerging as important players in numerous neurological diseases. Astrocytes, the main type of glia in the central nervous system , form extensive networks that physically and functionally connect neuronal synapses with cerebral blood vessels. Normal brain functioning strictly depends on highly specialized cellular cross-talk between these different partners to which Ca2 +, as a signaling ion, largely contributes. Altered intracellular Ca2 + levels are associated with neurodegenerative disorders and play a crucial role in the glial responses to injury. Intracellular Ca2 + increases in single astrocytes can be propagated toward neighboring cells as intercellular Ca2 + waves, thereby recruiting a larger group of cells. Intercellular Ca2+ wave propagation depends on two, parallel, connexin (Cx) channel-based mechanisms: i) the diffusion of inositol 1,4,5-trisphosphate through gap junction channels that directly connect the cytoplasm of neighboring cells, and ii) the release of paracrine messengers such as glutamate and ATP through hemichannels (‘half of a gap junction channel’). This review gives an overview of the current knowledge on Cx-mediated Ca2 + communication among astrocytes as well as between astrocytes and other brain cell types in physiology and pathology, with a focus on the processes of neurodegeneration and reactive gliosis. Research on Cx-mediated astroglial Ca2 + communication may ultimately shed light on the development of targeted therapies for neurodegenerative disorders in which astrocytes participate. This article is part of a Special Issue entitled: Calcium signaling in health and disease. Guest Editors: Geert Bultynck, Jacques Haiech, Claus W. Heizmann, Joachim Krebs, and Marc Moreau. |
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Keywords: | Aβ, amyloid-β AD, Alzheimer's disease ALS, amyotrophic lateral sclerosis AQP4, aquaporin 4 APP, amyloid precursor protein BAPTA, 1,2-bis(2-aminophenoxy)ethane-N,N,N&prime ,N&prime -tetraacetic acid BBB, blood&ndash brain barrier [Ca2 +]e, extracellular Ca2 + concentration [Ca2 +]i, cytoplasmic Ca2 + concentration cADPR, cyclic adenosine diphosphoribose CNS, central nervous system CRACs, Ca2 + release activated channels CSD, cortical spreading depression Cx, connexin EAE, experimental autoimmune encephalomyelitis ER, endoplasmic reticulum GFAP, glial fibrillary acidic protein GJ, gap junction GJIC, gap junction-mediated intercellular coupling GPCR, G-protein-coupled receptor HC, hemichannel IICR, inositol 1,4,5-trisphosphate-induced Ca2 + release ICW, intercellular Ca2 + wave IL-1β, interleukin-1β IP3, inositol 1,4,5-trisphosphate IP3R, inositol 1,4,5-trisphosphate receptor [K+]e, extracellular K+ concentration KO, knock-out l-AAA, l-alpha-aminoadipic acid LPS, lipopolysaccharide MAM, mitochondria-associated endoplasmic reticulum membrane MCU, mitochondrial Ca2 + uniporter GluR, glutamate receptor MW, molecular weight NAD +, nicotinamide adenine dinucleotide NCX, Na+/Ca2 + exchanger NFAT, nuclear factor of activated T-cells NFTs, neurofibrillary tangles NGVU, neuro-glio-vascular unit NMDAR, N-methyl-d-aspartate receptor NO, nitric oxide Panx, Pannexin PLC, phospholipase C PGE2, prostaglandin E2 PS, presenilins PDS, paroxysomal depolarization shift PTP, permeability transition pore ROS, reactive oxygen species RyR, ryanodine receptor SMC, smooth muscle cell SOCE, store-operated Ca2 + entry TNF-α, tumor necrosis factor-α TRP channel, transient receptor potential channel VDAC, voltage-dependent anion channel |
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