Effect of the β-amyloid peptide on microglia activationATP release

Résumé

Previous studies have shown a key role of microglial cells in the neuroinflammatory processes associated with some neurodegenerative diseases, such as Alzheimer’s disease (AD). Microglia sense several types of diffusible molecules that regulate the multiple repertoire of microglial functions. Among them, extracellular nucleotides, acting on microglial P2 receptors, have central roles. In this sense, the ionotropic P2X7 receptor has gained recognition as a key regulator of microglial-mediated inflammatory responses. It is known that microglia releases ATP and other nucleotides to the extracellular medium. Although several mechanisms, such as release trough conexins or panexins, has been proposed, a vesicular origin for this released nucleotides, relying on the activity of the vesicular nucleotide transporter (VNUT), cannot be ruled out. In this work we evaluated whether the expression of VNUT and the P2X7 receptor, as well as the ATP release, could be modified in the reactive microglia. To achieve microglia activation we stimulated the cells with the lipopolysaccharide (LPS). Moreover, we analyzed the effect of the b-amyloid peptide b1-42, which is also able to activate the microglial cells, on the expression of VNUT and the ATP release in the microglia