Figure 3.

CA150 attenuates the striatal neuropathology induced by mutant htt overexpression in a (Gln-ala)₃₈-dependent manner. Rat striata injected with the indicated lentiviruses were examined for Neu-N and DARPP-32 expression 8 or 12 weeks after infection. A, Quantification of striatal lesions at 8 and 12 weeks. At 8 weeks, CA150 rescued 77.3% of the DARPP-32 downregulation and 70% of the Neu-N downregulation, whereas CA150ΔQA rescued 37.16% of the DARPP-32 downregulation and 34.1% of the Neu-N downregulation. No effect was observed at 12 weeks. Data are mean ± SD from seven to eight animals (∗∗∗p < 0.0001, ∗∗p < 0.001, and ∗p < 0.05 compared with rats injected with htt171-82Q alone). B, Examples of DARPP-32 immunostaining. The arrowheads indicate lesions. C, Examples of Neu-N immunostaining. The black arrowheads indicate lesions at 8 or 12 weeks. Also shown are high-magnification views (bottom panels) of the lesions at 12 weeks. The blue arrowheads indicate Neu-N-positive cells that survived in the lesion of rats coinjected with htt171-82Q and CA150. D, Examples of immunostaining (HA epitope) revealing the expression of extragenous CA150 species. Shown here are the lesioned areas. The most intense staining was observed in the presence of CA150 rescuing activity. E, Examples of human mutant htt expression revealed by 2B4 (8 weeks) and EM48 (12 weeks) immunostaining. The black arrowheads show the lesions produced by mutant htt.