Figure 3

Microglia phagocytic activity is increased in presence of hTau^P301L-expressing, but appears non-sufficient in eliminating all apoptotic neurons. (A) Schematic illustration of 7 dpf embryo in dorsal view. The red square shows the region of the optic tectum where the time-lapse (B,C) was recorded. (B,C) Time-lapse imaging of a microglial cell phagocyting a diseased neuron (yellow arrowhead) in a 7 dpf Tg(ApoE-eGFP; HuC-hTau^P301L:DsRed) embryo; (B, Supplementary Video 3) merge of GFP and DsRed; (C) DsRed only. (D, p = 0.0262) Quantification of the engulfed neuronal volume in Tg(ApoE-eGFP; HuC-RFP) (n = 7) and Tg(ApoE-eGFP; HuC-hTau^P301L:DsRed) (n = 9) embryos, showing a significantly increased phagocytosis level by microglial cells in the presence of hTau^P301L-expressing neurons. (E–H, Supplementary Video 4) Time-lapse image sequences from the optic tectum of a double transgenic Tg(ApoE-eGFP; HuC-hTau^P301L:DsRed) 7 dpf embryo, showing a detail of a microglial cell in the process of phagocyting a neuron labeled with an apoptosis marker, acridine orange (merge: E, GFP and acridine: F, DsRed only: G, acridine only: H). The microglial cell filled with other dead tauopathic neurons extends its process to another dying tauopathic neuron and draws it toward its body cell to complete the phagocytosis process. (I, p = 0.027), Quantification of the number of non-engulfed apoptotic neurons in Tg(ApoE-eGFP; HuC-RFP) (n = 11) and double transgenic Tg(ApoE-eGFP; HuC-hTau^P301L:DsRed) (n = 4) embryos in which there is a significantly higher number of non-engulfed apoptotic neurons. ^***p < 0.001; ^*p < 0.05. Scale bar (B,C,E–H) = 20 μm.