Fig. 7.

Early, widespread up-regulation of TSPO, a neuroinflammation biomarker, in brain of BAC-225Q animals, and late, region-specific up-regulation in YAC128 mice, an established model of adult-onset HD. (A) Binding of [³H]-DPA-713, a ligand of neuroinflammation biomarker, TSPO, was measured in BAC-225Q mice using autoradiography (n=6-8). TSPO is up-regulated in all examined regions except hippocampus. In most of the analyzed regions TSPO pathology starts early – increased ligand binding is observed at 3, 6 and 10 months in periaqueductal gray (^*t-test, p=0.017, p<0.001, p<0.001, respectively), hypothalamus (p=0.013, p=0.021, p=0.015, respectively), motor cortex (p=0.018, p<0.001, p<0.001, respectively) and striatum, (p=0.011, p=0.003, p<0.001, respectively) and at 6 and 9 months in globus pallidus (p<0.001, p=0.017, respectively) and thalamus (p<0.001, p=0.003, respectively). (B) To validate TSPO as a marker of ongoing neurodegeneration in HD models, autoradiography experiments were performed also in the most commonly used transgenic model of adult-onset HD, YAC128 mice (n=7–10). Only three regions with increased binding of [³H]-DPA-713 are found, and TSPO phenotype is observed later than in BAC-225Q animals – at 6 months in hypothalamus (^*t-test, p=0.026), at 6 and 10 months in thalamus (^*t-test, p=0.021, p=0.036, respectively) and at 10 months in striatum (p=0.048). These findings confirm juvenile-like, widespread degeneration in BAC225Q mice and more specific, adult-like degeneration in YAC128 mice.