Details

Autor(en) / Beteiligte

• Leeson, Hannah C.
• Kasherman, Maria A.
• Chan‐Ling, Tailoi
• Lovelace, Michael D.
• Brownlie, Jeremy C.
• Toppinen, Kelly M.
• Gu, Ben J.
• Weible, Michael W.

Titel

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

Ist Teil von

• Stem cells (Dayton, Ohio), 2018-11, Vol.36 (11), p.1764-1777

Ort / Verlag

Hoboken, USA: John Wiley & Sons, Inc

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 We demonstrate P2X7 could have multiple roles in adult neurogenesis. As a calcium channel, P2X7 signaling may negatively regulate neural progenitor cell proliferation, whereas retaining its canonical role as a death receptor via the formation of transmembrane pores. P2X7 may also contribute to niche maintenance by facilitating phagocytosis of apoptotic cells. This has implications for neurogenesis given the presence of inflammation and extracellular ATP.