Figure 11.
Aggregated mouse Tau is toxic to hippocampal neurons. A, NFT pathology (Gallyas silver staining) in the hippocampus of proaggregation mutant mice after switching off the TauRD/ΔK280 transgene expression for 1.5 months (10 months ON and 1.5 months OFF). B, NeuN staining of CA1 and CA3 hippocampal area with NFT pathology displays neuronal loss (arrows) after switching off the transgene for 1.5 months (10 months ON and 1.5 months OFF). C, Higher magnification of A showing NFT pathology by Gallyas silver staining. D, Higher magnification of B showing altered neuronal morphology and loss of neurons in the areas affected by NFT pathology after 1.5 months of switching off the transgene. Note that region of higher silver staining in C corresponds to lower neuron count in D (arrows). In contrast, the areas not affected by NFT pathology do not display altered neuronal morphology (stars). E–H, Phosphorylation of endogenous mouse Tau at S46, T231, S202, and S404 in the CA3 region of proaggregation mutant mice after 1.5 months of switching off gene expression (10 months ON and 1.5 months OFF). Note hyperphosphorylation of aggregated mouse Tau. I, J, The astrocytosis identified by GFAP was reduced in the proaggregation mutant after 1.5 months switching off (J) (4.5 months ON and 1.5 months OFF), compared with the proaggregation mutant with continuous transgene expression (I) (6 months ON). Scale bars: A, B, 100 μm; C–J, 50 μm.