Article Figures & Data
Figures
- Figure 1.
Characterization of TPH1 and TPH2. A, B, Developmental change in the expression of TPH1 and TPH2 mRNAs in the brainstem. Brains of C57BL/6 mice at P7, P21, and adult stage were studied using semiquantitative RT-PCR with 27 or 40 cycles (TPH1 and TPH2) (A) or in situ hybridization (TPH1) (B). Plots of ratio of TPH1 and TPH2 product densities to those of GAPDH are also shown (n = 4, each) (A). Scale bar, 20 μm. Error bars represent mean ± SEM. *p < 0.05; **p < 0.01. C, Comparison of the kinetics between TPH1 and TPH2. The top panels are the Michaelis–Menten plots of tryptophan hydroxylase activity (TPH1/left vs TPH2/right) versus tryptophan concentrations at three different concentrations of BH4 (4 μm, open circle; 40 μm, gray circle; 400 μm, closed circle). The bottom panels are corresponding double reciprocal plots. Km values estimated at the extrapolated cross points for TPH1 were 16.6, 11.4, and 7.5μm at 400, 40, and 4μm BH4, respectively, and 19.2μm at all BH4 concentrations for TPH2.
- Figure 2.
Functional polymorphisms in the TPH1 gene in NZW and SWR mice. A, B, Sequences of the promoter (A) and 3′UTR (B) of TPH1 from several strains (top) and luciferase activities using sequences from NZB and NZW mice (bottom). The sequence is numbered relative to the transcription initiation site (+1) (A) or the 3′UTR initiation site (B). Identity and a single base pair deletion are indicated by –and *, respectively. Mismatch is indicated by the corresponding nucleotides. Putative transcription factor binding sites are underlined according to the study by Stoll and Goldman (1991). C, Comparison of TPH1 and TPH2 mRNA levels between NZB and NZW mouse brains at P21 using semiquantitative RT-PCR with 27 or 40 cycles. Plots of ratio of TPH1 and TPH2 product densities to those of GAPDH are also shown (n = 4, each). Error bars represent mean ± SEM. **p < 0.01.
- Figure 3.
Decreased 5-HT levels in the developing raphe nucleus of NZW and SWR mice. Lateral parts of dorsal raphe nucleus, indicated by the open square in the Nissl-stained coronal sections of the brainstem (left), were stained with anti-5-HT antibody in NZB, NZW, and SWR mice at P21 and P65. The intensities of signals were quantitatively shown (right). Scale bars: left, 200 μm; middle, 50 μm. Error bars represent mean ± SEM. **p < 0.01.
- Figure 4.
Depression-related behavior. A–C, Forced swim test. Immobility time was measured during 15 min on day 1 and 5 min on day 2 in NZB (n = 6), NZW (n = 12), and SWR (n = 8) mice (A). To assess the effects of antidepressants, immobility time of paroxetine-treated NZB (n = 6) or NZW (n = 7) mice was compared with that of vehicle-treated mice (n = 7, each) during 5 min (B). Imipramine-treated NZB (n = 7) or NZW (n = 7) mice were also compared with vehicle-treated mice during 5 min (n = 7 and 8, respectively) (C). D, Tail suspension test. Immobility time was measured during 5 min in NZB (n = 7), NZW (n = 7), and SWR (n = 8) mice. Error bars represent mean ± SEM. *p < 0.05, **p < 0.01.
