P2X7 receptor of olfactory bulb microglia plays a pathogenic role in stress-related depression in mice with allergic rhinitis

Neurobiol Dis. 2024 Feb 6;192:106432. doi: 10.1016/j.nbd.2024.106432. Online ahead of print.ABSTRACTThe aim of this study was to explore the role and mechanism of the olfactory bulb (OB) microglial P2X7 receptor (P2X7R) in allergic rhinitis (AR)-related depression, with the objective of identifying a potential clinical target. An AR mouse model was induced using ovalbumin (OVA), while chronic stress was employed to induce depression. The study used P2X7R-specific antagonists and OB microglia-specific P2X7R knockdown mice as crucial tools. The results showed that mice in the OVA + stress group exhibited more pronounced depressive-like phenotypes. Furthermore, there was an observed increase in microglial activation in the OB, followed by a rise in the level of inflammation. The pharmacological inhibition of P2X7R significantly mitigated the depression-like phenotype and the OB inflammatory response in OVA + stress mice. Notably, the specific knockdown of microglial P2X7R in the OB resulted in a similar effect, possibly linked to the regulation of IL-1β via the "ATP-P2X7R-Caspase 1" axis. These findings collectively demonstrate that microglial P2X7R in the OB acts as a direct effector molecule in AR-related depression, and its inhibition may offer a novel strategy for clinical prevention and treatment.PMID:38331352 | DOI:10.1016/j.nbd.2024.106432
Source: Neurobiology of Disease - Category: Neurology Authors: Source Type: research