Neuropil aggregates and synaptic UPS activity in HD knock-in mouse brain. (A) Immunostaining of heterozygous HD knock-in mice with the 1C2 antibody showing an increase in neuropil aggregates in the striatum with age. Bars, 10 μm. (B and C) Expression of presynaptic (SNAP25-GFPu/-RFP) (B) and postsynaptic (PSD95-GFP/-RFP) (C) reporters in the striatum of HD knock-in mice at 12 mo of age 7 d after injection of adenoviral UPS reporters. Note the increase in GFPu signals over time. Bars, 10 μm. (D) The ratios of GFPu to RFP in synapses (30–48 each group) of HD knock-in mice at 4, 8, and 12 mo of age were quantified. **, P < 0.01. (E) Chymotrypsin-like proteasomal activity of synaptosomes isolated from the cortex and striatum of wild-type or heterozygous HD knock-in mice at 4, 8, and 12 mo of age. The data were obtained from five experiments and are represented as mean + SEM (n = 48). *, P < 0.05 as compared with wild-type samples. The chymotrypsin-like activity of brain homogenates and post-glutamyl and trypsin-like activity of synaptosomes are presented in Fig. S1 and Fig. 2.