Changes in phagocytosis and potassium channel activity in microglia of 5xFAD mice indicate alterations in purinergic signalling in a mouse model of Alzheimer's Disease

Publication date: Available online 8 June 2017
Source:Neurobiology of Aging
Author(s): Stefan Wendt, Meron Maricos, Natascha Vana, Niklas Meyer, Dilansu Guneykaya, Marcus Semtner, Helmut Kettenmann
As the immunocompetent cells of the central nervous system, microglia accumulate at Abeta plaques in Alzheimer's disease (AD) and acquire a morphological phenotype of activated microglia. Recent functional studies, however, indicate that in mouse models of amyloidosis and AD, these cells are rather dysfunctional indicated by a reduced phagocytic activity. Here, we report that this reduction in phagocytic activity is associated with perturbed purinergic receptor signalling, since phagocytosis could be stimulated by P2Y6 receptor activation in control, but not in 5xFAD transgenic animals, an animal model of amyloid deposition. Impaired phagocytosis is not innate, and develops only at later stages of amyloidosis. Furthermore, we show that membrane currents induced by UDP, a ligand activating P2Y6 receptors, are altered in response rate and amplitude in microglia in close vicinity to plaques, but not in plaque-free areas of 5xFAD animals. These changes were accompanied by changes in membrane properties and potassium channel activity of plaque-associated microglia in early and late stages of amyloidosis. As a conclusion, the physiological properties of plaque-associated microglia are altered with a strong impact on purinergic signalling.



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