Figure 3.
Effects of ligands for nuclear receptors in vitro and in vivo. (a) Top row: schematic of the experiment using OLP6 cells. During the first 4 days, the cells were cultured in an undifferentiated condition. During the subsequent 4 days, the cells were cultured in a differentiated condition. On day 7, each ligand was added. On day 8, the transcript levels were measured by quantitative RT-PCR. Bottom row: quantitative RT-PCR analysis of oligodendrocyte-related genes in OLP6 cells treated with 0.1, 0.3 or 1 μm bexarotene or 5, 15 or 50 μm bezafibrate. This examination was performed in triplicate. (b) Top row: schematic of the experiment using KATO-III cells. Bottom row: gene expression of CCK and CALB2 in KATO-III cells treated with 0.1, 0.3 or 1 μm bexarotene or 5, 15 or 50 μm bezafibrate and analyzed by quantitative RT-PCR. Values are means±s.e. Gapdh / GAPDH was used as an internal control. P-values were calculated using Dunnett’s test for multiple comparisons (compared with DMSO). This examination was performed in triplicate. (c) Top row: experimental design for the administration of bexarotene. Mice received daily injections from 6 to 9 weeks of age (vehicle or bexarotene, 30 or 100 mg kg−1, once per day). Bottom row: gene expression of Olig2 and Apc in mouse prefrontal cortexes (PFCs) analyzed by quantitative RT-PCR. Values are means±s.e. Gapdh was used as an internal control. P-values were calculated using Dunnett's test for multiple comparisons (compared with vehicle). Note that 30 mg kg−1 bexarotene administration elicited a significant increase in the expression of Olig2 and Apc. (d, e) Locomotor responses to injection of MK-801 (0.3 mg kg−1) in the vehicle- and bexarotene (30 mg kg−1)-pretreated mouse groups. For both groups, the last treatment was administered 180 min before MK-801 injection. Values are means±s.e. P-values were calculated using two-way repeated measures ANOVA followed by post hoc Mann–Whitney U test d. P-values were calculated using unpaired t-tests e. #P<0.1, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.