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Neuroglia 2018, 1(1), 258-270; https://doi.org/10.3390/neuroglia1010017

Inflammatory Cytokines Facilitate the Sensitivity of P2X7 Receptors Toward Extracellular ATP at Neural Progenitor Cells of the Rodent Hippocampal Subgranular Zone

1
Rudolf-Boehm-Institut für Pharmakologie und Toxikologie, Universität Leipzig, 04107 Leipzig, Germany
2
Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
*
Author to whom correspondence should be addressed.
Received: 26 July 2018 / Revised: 14 August 2018 / Accepted: 16 August 2018 / Published: 22 August 2018
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Abstract

Organotypic hippocampal slice cultures were used to model the effects of neuroinflammatory conditions following an epileptic state on functional P2X7 receptors (Rs) of subgranular zone (SGZ) neural progenitor cells (NPCs). The compound, 4-aminopyridine (4-AP), is known to cause pathological firing of neurons, consequently facilitating the release of various transmitter substances including ATP. Lipopolysaccharide (LPS) and interleukin-1β (IL-1β) both potentiated the dibenzoyl-ATP (Bz-ATP)-induced current amplitudes in NPCs, although via different mechanisms. Whereas LPS acted via promoting ATP release, IL-1β acted via its own receptor to directly influence P2X7Rs. Thus, the effect of LPS was inhibited by the ecto-ATPase inhibitor, apyrase, but not by the IL-1β antagonist, interleukin-1RA (IL-1RA); by contrast, the effect of IL-1β was inhibited by IL-1RA, but not by apyrase. Eventually, incubation with 4-AP upregulated the number of nestin/glial fibrillary acidic protein/P2X7R immunoreactive cells and their appropriate staining intensity, suggesting increased synthesis of P2X7Rs at NPCs. In conclusion, inflammatory cytokines accumulating after epilepsy-like neuronal firing may facilitate the effect of endogenous ATP at P2X7Rs of NPCs, thereby probably promoting necrosis/apoptosis and subsequent cell death. View Full-Text
Keywords: neural progenitor cells; extracellular ATP; P2X7 receptors; neuroinflammation; cytokines neural progenitor cells; extracellular ATP; P2X7 receptors; neuroinflammation; cytokines
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Liu, J.; Khan, M.T.; Tang, Y.; Franke, H.; Illes, P. Inflammatory Cytokines Facilitate the Sensitivity of P2X7 Receptors Toward Extracellular ATP at Neural Progenitor Cells of the Rodent Hippocampal Subgranular Zone. Neuroglia 2018, 1, 258-270.

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