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. 2016 Feb 25;6:21917. doi: 10.1038/srep21917

Figure 2. BACE inhibition induces hair depigmentation in mice.

Figure 2

(A) Example photos of vehicle and NB-360-treated mice. Fur color scores of chronically treated male C57BL/6J mice for 8 weeks with NB-360. Dose-dependent sustained hair depigmentation on the ventral part was obvious after 15 days of treatment for the high dose (100μmol/kg) and 25 days for the low dose (20μmol/kg). In some animals the depigmentation was widespread and extensive while in others it was patchier. In this experiment only the ventral body was affected while the dorsal part showed no change. Statistics: Kruskal-Wallis with Dunn’s post-hoc (*p < 0.05, **p < 0.01 versus vehicle). Vehicle: n = 8, NB-360: each n = 8. Black arrow: final scoring was performed blinded. (B) Left: Hair depigmentation assessment by trichoscopy. Hair melanin content was markedly reduced in female wildtype C57BL/6 littermates of the APP51 line treated for 6 weeks with 100 μmol/kg NB-360. Right: Hematoxylin/eosin histopathology of anagen hair follicles showing decreased pigment content in NB-360 treated mice (100μmol/kg) (C) Normalized NB-360 black and grey hair skin exposure determination from experiment shown in (A) (normalized to dose at 4 h in pmol/g). Grey symbols: High dose group (100 μmol/kg), Black symbols: low dose group (20μmol/kg). Statistics: two-tailed unpaired t-test (*p < 0.05). (D) Fur color score of chronically treated female wildtype C57BL/6 littermates of the APP51 line for 44 days with subsequent washout of 98 days, fur plucking and observation without treatment for further 100 days. Example photos of NB-360 treated mice before treatment stop, after grey (white bold arrows) and black (grey arrows) fur plucking and after hair regrowth. No fur score change was seen during the washout phase, but regrowth of black hair appeared after hair plucking. In this experiment the dorsal part of the mice was more affected. (E) Fur color scores of 5-day orally treated male C57BL/6J mice with 100μmol/kg NB-360. After treatment stop the animals were further monitored. Hair depigmentation affecting ventral and dorsal part of the body was again obvious after 2 weeks. (F) Animals (APP23 and APPPS1) treated for 6 months with a high dose of NB-360 (food pellet dosing, 0.5 g/kg) were completely grey. For all graphs: Data is shown as mean ± SEM.