Fig. 1: Enhancement of the BBB permeability of PhAc by methyl esterification.
a Schematic representation of drug delivery. PhAcM in the circulating blood is translocated across the BBB and enters the brain, where PhAcM is converted to PhAc by endogenous esterase activity and PhAc activates the IR84a/IR8a complex. b Plot of changes in the normalized firing rate after the tail vein injection of PhAcM (20 mg/kg) or vehicle in the TH-IR84a/IR8a (Tg) mice (n = 6 mice for vehicle/pre, n = 7 mice for vehicle/post, n = 5 mice for PhAcM/pre, and n = 7 mice for PhAcM/post). *p < 0.05 vs. PhAcM/pre. c Plot of changes in NE[ext] in the ACC of Tg and non-transgenic (non-Tg) littermates before and after lateral tail vein injection of PhAcM (10 mg/kg) (n = 4 mice for each group). NE[ext] is expressed as a percentage of the average baseline levels of each mouse. Arrow indicates the timing of drug injection. NE[ext] in PhAcM-administered Tg mice was significantly higher than that of the vehicle-administered Tg mice at the 30- to 120-min fractions (ts(63) = 3.38, 6.12, 6.43, 3.41, p = 0.004, p < 0.001, p < 0.001, p = 0.003, rs = 0.39, 0.61, 0.63, 0.39, respectively) and that of the PhAcM-administered non-Tg at the 60- to 120-min fractions (ts(63) = 5.90, 6.06, 2.89, p < 0.001, p < 0.001, p = 0.016, rs = 0.60, 0.61, 0.34, respectively). *p < 0.05 vs. Tg Vehicle; †p < 0.05 vs. Non-Tg PhAcM. Data are presented as mean with accompanying error bar (standard error of the mean or SEM) and individual data points superimposed (b, c).
