Background Previous results from our group showed that abeta‐stimulated astrocytes release factors that are detrimental to neurons. Our aim is to investigate and validate those factors. One cytokine in particular is shown to be increased after treatment with low concentrations of oligomeric abeta and has been associated with abnormal tau cleavage. We analysed the effect of the cytokine on neuronal health and complexity and on localisation of tau. We also investigated whether the change in phenotype of astrocytes in response to abeta depends on abeta internalisation, and which pathways are involved. Method Primary astrocytic and neuronal cultures were prepared from CD1 mice following standard protocols. Neurons were treated with the cytokine and/or its receptor antagonist and transfected with GFP to allow measurement of dendritic spine density and neurite complexity. Localisation of tau was examined in similarly treated neurons by immunocytochemistry. To investigate abeta internalisation, transgenic conditioned media containing abeta was collected from Tg2576 neurons, with medium from littermate wild type neurons as a control. Astrocytes were treated with conditioned media in the presence or absence of Dynasore, a small molecule inhibitor of dynamin GTPases, and abeta uptake assessed by immunocytochemistry. Result Exposure of neurons to the cytokine results in a reduction of dendritic spine density and neuronal complexity which is rescued when its receptor is blocked by a specific inhibitor. Exposure to the cytokine also seems to affect tau localisation in neurons, causing mislocalisation of tau from the axonal to the somatodendritic compartment. Preliminary data shows that astrocytes internalise abeta quite quickly following addition to the medium, at least in part through endocytosis. Conclusion The phenotype of astrocytes is altered in response to abeta, causing their secretion of molecules, including cytokines. Exposure of neurons to one of these cytokines causes reduced neuronal health and complexity, further confirming that factors released by astrocytes are synaptotoxic.
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