Figure 8. MB concentrates in the brain and reduces tau levels in treated mice. Cerebella were collected from MB and vehicle-treated animals and were subjected to LC–MS analysis (A). Animals given 0.02 mg/kg MB per day had an average 0.7 ± 0.1 μg MB per 100 mg of tissue. Mice in the 2 and 20 mg/kg per day groups had an average brain concentration of 1.73 ± 0.3 and 7.99 ± 0.78, respectively. All bars represent average values and error bars SEM. Male JNPL3 mice (n = 10 per group) were given 0.02mg/kg/day MB or water vehicle by daily oral gavage for two weeks. Brains were collected and fractionated to produce total, and sarkosyl insoluble (aggregated) tau. (B) shows immunoblots from these fractions probed for total tau and the following phosphorylated tau epitopes—ser199, ser202, thr231/ser235, ser396/404 and ser422. (C) shows the chemiluminescence signal (CU) quantified and expressed as the average per group ± SE. MB (gray bar) treatment resulted in lower total tau compare with control (black bar) (**p < 0.01). No significant change was observed in the levels of sarkosyl insoluble tau (data not shown). MB treatment led to a significant decrease in the levels of tau phosphorylated at ser199, ser202, thr231/ser235, and ser422 (*p < 0.05, **p < 0.01). Levels were normalized to total tau and expressed as an average ± SE.