Health Topics A-Z | Involvement of phosphoinositide 3-kinase gamma in the neuro-inflammatory response and cognitive impairments induced by beta-amyloid 1-40 peptide in mice.

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Involvement of phosphoinositide 3-kinase gamma in the neuro-inflammatory response and cognitive impairments induced by beta-amyloid 1-40 peptide in mice.

In this report we have investigated whether phosphoinositide 3-kinase gamma (PI3K gamma), which is important in inflammatory cell migration, plays a critical role in the neuro-inflammation, synaptic dysfunction, and cognitive deficits induced by intracerebroventricular injection of Abeta(1-40) in mice. We found that the selective inhibitor of PI3Kgamma, AS605240, was able to attenuate the Abeta(1-40)-induced accumulation of activated astrocytes and microglia in the hippocampus, and decrease immuno-staining for p-Akt and cyclooxygenase-2 (COX-2). Interestingly, Abeta(1-40) activated macrophages treated with AS605240 or another PI3Kgamma inhibitor, AS252424, displayed impaired chemotaxis in vitro, but their expression of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1bet...