title: Astrocyte Sodium Signalling and Panglial Spread of Sodium Signals in Brain White Matter.
abstract: In brain grey matter, excitatory synaptic transmission activates glutamate uptake into astrocytes, inducing sodium signals which propagate into neighboring astrocytes through gap junctions. These sodium signals have been suggested to serve an important role in neuro-metabolic coupling. So far, it is unknown if astrocytes in white matter-that is in brain regions devoid of synapses-are also able to undergo such intra- and intercellular sodium signalling. In the present study, we have addressed this question by performing quantitative sodium imaging in acute tissue slices of mouse corpus callosum. Focal application of glutamate induced sodium transients in SR101-positive astrocytes. These were largely unaltered in the presence of ionotropic glutamate receptors blockers, but strongly dampened upon pharmacological inhibition of glutamate uptake. Sodium signals induced in individual astrocytes readily spread into neighboring SR101-positive cells with peak amplitudes decaying monoexponentially with distance from the stimulated cell. In addition, spread of sodium was largely unaltered during pharmacological inhibition of purinergic and glutamate receptors, indicating gap junction-mediated, passive diffusion of sodium between astrocytes. Using cell-type-specific, transgenic reporter mice, we found that sodium signals also propagated, albeit less effectively, from astrocytes to neighboring oligodendrocytes and NG2 cells. Again, panglial spread was unaltered with purinergic and glutamate receptors blocked. Taken together, our results demonstrate that activation of sodium-dependent glutamate transporters induces sodium signals in white matter astrocytes, which spread within the astrocyte syncytium. In addition, we found a panglial passage of sodium signals from astrocytes to NG2 cells and oligodendrocytes, indicating functional coupling between these macroglial cells in white matter.
authors.affiliation: Institute of Neurobiology, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, Universitätsstrasse 1, 40225, Düsseldorf, Germany.
authors.forename: Behrouz
authors.initials: B
authors.lastname: Moshrefi-Ravasdjani
authors.affiliation: Institute of Neurobiology, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, Universitätsstrasse 1, 40225, Düsseldorf, Germany.
authors.forename: Evelyn L
authors.initials: EL
authors.lastname: Hammel
authors.affiliation: Institute of Neurobiology, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, Universitätsstrasse 1, 40225, Düsseldorf, Germany.
authors.forename: Karl W
authors.initials: KW
authors.lastname: Kafitz
authors.affiliation: Institute of Neurobiology, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, Universitätsstrasse 1, 40225, Düsseldorf, Germany. rose@uni-duesseldorf.de.
authors.forename: Christine R
authors.identifier: http://orcid.org/0000-0002-9684-3592
authors.initials: CR
authors.lastname: Rose
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology*; D066127:White Matter / Q000187:drug effects / Q000502:physiology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D015222:Sodium Channels; D018698:Glutamic Acid; D012964:Sodium
keywords: Astrocyte; Corpus callosum; Glutamate; NG2 cell; Oligodendrocyte; SBFI