Non-cell-autonomous changes in retrograde signaling lead to cell death

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Non-cell-autonomous changes in retrograde signaling lead to cell death. Non-cell-autonomous changes in retrograde signaling lead to cell death. E14 embryonic rat motor neurons were grown in the presence or absence of glial cells and infected with either HSV-wtSOD or HSV-SOD1G85R. A–F, Staining by P-Trk decreased (A, C, D) and p75 reactivity along neuronal processes expressing mSOD1 increased (B, E, F) in neurons cocultured with glia. Line scans compare relative signal intensities along processes of neurons expressing mutant or wild-type SOD1 in the absence (green) or presence (orange) of glia. NF, neurofilament. Scale bar, 5 μm. G, H, Expression of mSOD1 led to enhanced reactivity with antibodies to caspase-3 compared with neurons expressing wtSOD1. The bar graph represents average ± SEM of percentage cells containing activated caspase-3 from ∼100 cells from three independent experiments. Activation of caspase-3 was more pronounced in neurons cocultured with glia also expressing mSOD1 (*p < 0.01). W, wtSOD1; S, mSOD1; Casp3, caspase-3. Scale bar, 8 μm. Eran Perlson et al. J. Neurosci. 2009;29:9903-9917 ©2009 by Society for Neuroscience