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-1(IL-1) both
potentiated the dibenzoyl-ATP (Bz-ATP)-induced current amplitudes in NPCs, although via different
mechanisms. Whereas LPS acted via promoting ATP release, IL-1 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-1 antagonist, interleukin-1RA (IL-1RA); by contrast, the effect of IL-1
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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84600 |
| Date | 06 April 2023 |
| Creators | Liu, Juan, Tahir Khan, Muhammad, Tang, Yong, Franke, Heike, Illes, Peter |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
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