Figure 4

Reduced toxicity by decreasing shRNA expression levels in the red nucleus. GFP expressing neurons in the red nucleus shows normal morphology after injection with AAV1-GFP throughout the red nucleus (A). AAV1-shRNA injection results in profound neuronal degeneration and only occasional GFP-positive profiles of transduced neurons are observed usually at some distance from the injection site (arrow heads) (B). Lowering shRNA expression by reducing the injected AAV1 particles 10 fold (C) or using AAV2 particles (D) nearly completely alleviates toxicity. Scale bar A: 50 μm