P2X7 receptors at adult neural progenitor cells of the mouse subventricular zone

Messemer, Nanette; Kunert, Christin; Grohmann, Marcus; Sobottka, Helga; Nieber, K; Zimmermann, Herbert; Franke, Heike; Nörenberg, Wolfgang; Straub, Isabelle; Schaefer, Michael; Riedel, Thomas; Illéš, Peter; Rubini, Patrizia

doi:10.1016/j.neuropharm.2013.05.017

Cited by 61 publications

(49 citation statements)

References 60 publications

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“…P2X7 receptors may also contribute to niche maintenance by facilitating phagocytic clearance of apoptotic cell bodies. Figure is a schematic representation of the roles subserved by P2X7 based on findings from the present study as well as earlier investigators . The presence of P2X7 receptors within the adult neurogenic niches is of importance given the therapeutic potential of some antagonists following ischemic injury .…”

Section: Discussionsupporting

confidence: 63%

“…Cultured neurons also had increased axonal growth and branching in conditions of P2X7 inhibition, highlighting the negative influence of extracellular ATP, and P2X7 activation, on neurons in the hippocampus . In response to higher concentrations of ATP (≥1 mM, such as those found following inflammatory events), P2X7 receptors form large transmembrane pores permeable to molecules up to 800 Da, leading to osmotic dysregulation and cell death . P2X7 pore formation also plays a significant role in inflammatory processes during ischemic events, such as a stroke, where the large amounts of ATP released from dying cells can activate the P2X7 receptors on neighboring cells and exacerbate the initial infarct .…”

Section: Introductionmentioning

confidence: 99%

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P2X7 Receptors Regulate Phagocytosis and Proliferation in Adult Hippocampal and SVZ Neural Progenitor Cells: Implications for Inflammation in Neurogenesis

et al. 2018

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Identifying the signaling mechanisms that regulate adult neurogenesis is essential to understanding how the brain may respond to neuro-inflammatory events. P2X7 receptors can regulate pro-inflammatory responses, and in addition to their role as cation channels they can trigger cell death and mediate phagocytosis. How P2X7 receptors may regulate adult neurogenesis is currently unclear. Here, neural progenitor cells (NPCs) derived from adult murine hippocampal subgranular (SGZ) and cerebral subventricular (SVZ) zones were utilized to characterize the roles of P2X7 in adult neurogenesis, and assess the effects of high extracellular ATP, characteristic of inflammation, on NPCs. Immunocytochemistry found NPCs in vivo and in vitro expressed P2X7, and the activity of P2X7 in culture was demonstrated using calcium influx and pore formation assays. Live cell and confocal microscopy, in conjunction with flow cytometry, revealed P2X7 NPCs were able to phagocytose fluorescent beads, and this was inhibited by ATP, indicative of P2X7 involvement. Furthermore, P2X7 receptors were activated with ATP or BzATP, and 5-ethynyl-2'-deoxyuridine (EdU) used to observe a dose-dependent decrease in NPC proliferation. A role for P2X7 in decreased NPC proliferation was confirmed using chemical inhibition and NPCs from P2X7 mice. Together, these data present three distinct roles for P2X7 during adult neurogenesis, depending on extracellular ATP concentrations: (a) P2X7 receptors can form transmembrane pores leading to cell death, (b) P2X7 receptors can regulate rates of proliferation, likely via calcium signaling, and (c) P2X7 can function as scavenger receptors in the absence of ATP, allowing NPCs to phagocytose apoptotic NPCs during neurogenesis. Stem Cells 2018;36:1764-1777.

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Section: Discussionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

P2X7 Receptors Regulate Phagocytosis and Proliferation in Adult Hippocampal and SVZ Neural Progenitor Cells: Implications for Inflammation in Neurogenesis

et al. 2018

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“…The inward current is carried by Na + and Ca 2+ ions, the latter of which being responsible for the [Ca 2+ ] i increase (Sperlágh et al 2006;Skaper et al 2010). The (partial) sensitivity of the astroglial Bz-ATP current to blockade by selective P2X7 receptor antagonists in a low X 2+ medium has been documented repeatedly (Nörenberg et al 2010;Oliveira et al 2011;Messemer et al 2013) and was, therefore, not studied in the present experiments.…”

Section: Resultsmentioning

confidence: 95%

Functional P2X7 receptors at cultured hippocampal astrocytes but not neurons

Rubini

Pagel

Mehri

et al. 2014

Naunyn-Schmiedeberg's Arch Pharmacol

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P2X7 receptors have been suggested to be located both on neurons and astrocytes of the central and peripheral nervous systems. In the present Ca(2+)-imaging and patch-clamp study, we reinvestigated these findings on mixed neuronal-astrocytic cell cultures prepared from embryonic or newborn rat hippocampi. We found in a Mg(2+)-free bath medium that the prototypic P2X7 receptor agonist dibenzoyl-adenosine triphosphate (Bz-ATP) increased the intracellular Ca(2+) concentration ([Ca(2+)]i) both in the neuronal cell bodies and in their axo-dendritic processes only to a very minor extent. However, Bz-ATP produced marked [Ca(2+)]i transients in the neuronal processes, when they grew above a glial carpet, which was uniformly sensitive to Bz-ATP. These glial signals might be misinterpreted as neuronal responses because of the poor focal discrimination by a fluorescent microscope. Most astrocytes had a polygonal shape without clearly circumscribable boundaries, but a subgroup of them had neuron-like appearance. The cellular processes of this astrocytic subgroup, just as their cell somata and their polygonal counterparts, appeared to possess a high density of functional P2X7 receptors. In contrast to astrocytes, in a low Ca(2+)/no Mg(2+)-containing bath medium, hippocampal neurons failed to respond to Bz-ATP with membrane currents. In addition, neither the amplitude nor the frequency of spontaneous excitatory postsynaptic currents, representing the quantal release of glutamate, was modified by Bz-ATP. We conclude that cultured hippocampal neurons, in contrast to astrocytes, possess P2X7 receptors, if at all, only at a low density.

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“…Primary neurospheres prepared from the SVZ of mice expressed only P2X4,7R mRNA as well as mRNA for all P2YR subtypes (Stafford et al, ). However, after growth factor deprivation and plating, the resulting proliferating NPCs became endowed with all P2XR mRNA subtypes (Messemer et al, ).…”

Section: P2y and P2xr Messengersmentioning

confidence: 99%

Regulation of adult neural progenitor cell functions by purinergic signaling

Tang

Illéš

2016

Glia

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Extracellular purines are signaling molecules in the neurogenic niches of the brain and spinal cord, where they activate cell surface purinoceptors at embryonic neural stem cells (NSCs) and adult neural progenitor cells (NPCs). Although mRNA and protein are expressed at NSCs/NPCs for almost all subtypes of the nucleotide-sensitive P2X/P2Y, and the nucleoside-sensitive adenosine receptors, only a few of those have acquired functional significance. ATP is sequentially degraded by ecto-nucleotidases to ADP, AMP, and adenosine with agonistic properties for distinct receptor-classes. Nucleotides/nucleosides facilitate or inhibit NSC/NPC proliferation, migration and differentiation. The most ubiquitous effect of all agonists (especially of ATP and ADP) appears to be the facilitation of cell proliferation, usually through P2Y1Rs and sometimes through P2X7Rs. However, usually P2X7R activation causes necrosis/apoptosis of NPCs. Differentiation can be initiated by P2Y2R-activation or P2X7R-blockade. A key element in the transduction mechanism of either receptor is the increase of the intracellular free Ca concentration, which may arise due to its release from intracellular storage sites (G protein-coupling; P2Y) or due to its passage through the receptor-channel itself from the extracellular space (ATP-gated ion channel; P2X). Further research is needed to clarify how purinergic signaling controls NSC/NPC fate and how the balance between the quiescent and activated states is established with fine and dynamic regulation. GLIA 2017;65:213-230.

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P2X7 receptors at adult neural progenitor cells of the mouse subventricular zone

Cited by 61 publications

References 60 publications

P2X7 Receptors Regulate Phagocytosis and Proliferation in Adult Hippocampal and SVZ Neural Progenitor Cells: Implications for Inflammation in Neurogenesis

P2X7 Receptors Regulate Phagocytosis and Proliferation in Adult Hippocampal and SVZ Neural Progenitor Cells: Implications for Inflammation in Neurogenesis

Functional P2X7 receptors at cultured hippocampal astrocytes but not neurons

Regulation of adult neural progenitor cell functions by purinergic signaling

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