Exploring the Role of P2X7 Receptor in Regulation of Microglial Function and Behaviour

Bielecka, Hanna (2025) Exploring the Role of P2X7 Receptor in Regulation of Microglial Function and Behaviour. Doctoral thesis, University of East Anglia.

Preview

PDF Download (8MB) | Preview

Abstract

P2X7 is a purinergic receptor and a non-selective ion channel that becomes activated by high levels of extracellular ATP. Predominantly expressed by immune cells, P2X7 plays a vital role in facilitating immune and inflammatory responses, as well as cell death. In microglia, the resident immune cells of the CNS, P2X7 expression has been linked to various functions beyond inflammation, such as survival, metabolic switch, phagocytosis, and cytokine release. Microglia perform vital functions from development to aging. As such, they are highly adaptable and flexible, responding to the demands in their environment. Modifying microglial responses in health and disease is a promising target for the management of neuroinflammation, neurodegenerative, and neurodevelopmental diseases, yet the full understanding of how microglia function is still to be unravelled. The aim of this thesis was to shed light on the role of the P2X7 receptor in microglia.

The project demonstrated that P2X7 expression, in the BV-2 murine microglial cell line, or in the transfected HEK 293 cell line, does not have a trophic effect and does not affect proliferation. An Alamar blue metabolic assay revealed an interesting advantage of P2X7-expressing cells related to cellular metabolism. P2X7 did not affect cell activation or the expression of polarisation markers in BV-2 cells. P2X7 itself was upregulated with pro-inflammatory stimulants LPS and IFN-γ.

P2X7 expression was shown to promote multinucleation and giant cell (GMC) formation in BV-2 microglia. The GMCs were more numerous and reached larger sizes in the 72h incubation time when P2X7 was expressed. GMCs could be induced with pro-inflammatory stimuli such as LPS, but not with IL-4 or IL-13, and would also form spontaneously without any induction. The effect of pharmacological modulation and inhibition of P2X7 was explored in GMC formation. Microglial GMC morphology, protein expression, and function were evaluated in the BV-2 and BV-2P2X7- model system.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Chemistry, Pharmacy and Pharmacology
Depositing User:	Chris White
Date Deposited:	07 Sep 2026 08:16
Last Modified:	07 Sep 2026 08:16
URI:	https://ueaeprints.uea.ac.uk/id/eprint/104435
DOI:

Downloads

Actions (login required)

View Item