Figure 4.

Taxol blocks the somatic accumulation of both mitochondria and tau. A, Time-lapse video microscopy showing the movement of mitotracker-stained mitochondria (green) in neurites of a representative neuron in a control culture, a control culture treated with taxol (5 nm), and a culture treated with 50 nm annonacin (Anno) and taxol. Addition of taxol to the culture medium blocked all movement of mitochondria in both control and annonacin-treated cells. Images were taken at 10 min intervals. The first image (t₁) was taken 10 min after addition of annonacin to the culture medium. Individual mitochondria are indicated in successive images with arrows of the same color. Scale bar, 10 μm. B, Immunofluorescence images showing that 50 nm annonacin, in the absence of taxol, induced the redistribution of AD2⁺ tau (red) from the β-III-tubulin⁺ axons (green) to the neuronal cell body (*). The presence of taxol (5 nm) in the culture medium prevented the annonacin-induced accumulation of AD2⁺ tau in the cell body. Arrows indicate neuritic hypertrophy caused by taxol-induced polymerization of β-III-tubulin. Scale bar, 20 μm. C, D, Quantification of AD2⁺ cell bodies (C) and neuronal survival (D) in cultures exposed for 48 h exposure to 50 nm annonacin in the absence or presence of 5 nm taxol. **p < 0.01 versus control. ^##p < 0.01 annonacin plus taxol versus annonacin alone.