Figure 7. Lipofuscin-Rich Granules Increase with Age in the Striatum of HD Animals and Are Inhibited with XJB-5–131 Treatment.
(A) Age-dependent perinuclear lipid granules (red), are quenched by TrueBlack (TB). The granules increase with age only in the STR of HD mice. Age-dependent perinuclear lipid granules are suppressed by treatment with mitochondrial targeted antioxidant XJB-5–131 (HD + XJB-5–131). Lipofuscin granule size was 2.09 ± 0.08 μm2 (WT) and 2.93 ± 0.08 μm2 (HD) at 100 weeks. WT and HD are HdhQ(wt/wt) and HdhQ(150/150) mice, respectively. Scale bar is 10 μm.
(B) Quantification of lipofuscin signal intensity in the STR from (A). Mice were treated with XJB-5–131 antioxidant (treatment for 50 weeks) (p < 0.05, two-tailed Student’s t test). (n = 3 tissue sections imaged per sample).
(C) Representative Nissl stained images of the STR or CBL as described in (Figure 1).
(D) (Top) Images from STR (left) and CBL (right) (scale bar is 50 μm) and (bottom) magnified images (scale bar is 10 μm) of red insets illustrating the large lipid-rich granules in the STR or CBL of HD animals at 100 weeks; WT and HD are HdhQ(wt/wt) and HdhQ(150/150) mice, respectively. Staining for DAPI, blue, nuclear; lipofuscin, lipid, red; and NeuN, green, neurons are visible in the image. Error bars are SE.
(E) Model for metabolic reprogramming in HdhQ(150/150) animals, as described in the text. Neuron-glia cartoon modified from (Pierre J. Magistretti, Journal of Experimental Biology. 2006. 209: 2304–2311).
See also Figure S6F.