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Rapid CommunicationAccelerated Communication

Thermoregulation-Independent Regulation of Sleep by Serotonin Revealed in Mice Defective in Serotonin Synthesis

Xian Zhang, Hongming Yan, Yanjia Luo, Zili Huang and Yi Rao
Molecular Pharmacology June 2018, 93 (6) 657-664; DOI: https://doi.org/10.1124/mol.117.111229
Xian Zhang
School of Life Sciences, Beijing Normal University, Beijing, China (H.Y.); Peking-Tsinghua Center for Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Beijing Innovation Center for Genomics, Peking University School of Life Sciences, Beijing, China (X.Z., H.Y., Y.R.); Department of Pharmacology, Fudan University School of Medicine, Shanghai, China (Y.L., Z.H.); and Chinese Institute for Brain Research, Zhongguanchun Life Sciences Park, Beijing, China (Y.R.)
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Hongming Yan
School of Life Sciences, Beijing Normal University, Beijing, China (H.Y.); Peking-Tsinghua Center for Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Beijing Innovation Center for Genomics, Peking University School of Life Sciences, Beijing, China (X.Z., H.Y., Y.R.); Department of Pharmacology, Fudan University School of Medicine, Shanghai, China (Y.L., Z.H.); and Chinese Institute for Brain Research, Zhongguanchun Life Sciences Park, Beijing, China (Y.R.)
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Yanjia Luo
School of Life Sciences, Beijing Normal University, Beijing, China (H.Y.); Peking-Tsinghua Center for Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Beijing Innovation Center for Genomics, Peking University School of Life Sciences, Beijing, China (X.Z., H.Y., Y.R.); Department of Pharmacology, Fudan University School of Medicine, Shanghai, China (Y.L., Z.H.); and Chinese Institute for Brain Research, Zhongguanchun Life Sciences Park, Beijing, China (Y.R.)
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Zili Huang
School of Life Sciences, Beijing Normal University, Beijing, China (H.Y.); Peking-Tsinghua Center for Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Beijing Innovation Center for Genomics, Peking University School of Life Sciences, Beijing, China (X.Z., H.Y., Y.R.); Department of Pharmacology, Fudan University School of Medicine, Shanghai, China (Y.L., Z.H.); and Chinese Institute for Brain Research, Zhongguanchun Life Sciences Park, Beijing, China (Y.R.)
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Yi Rao
School of Life Sciences, Beijing Normal University, Beijing, China (H.Y.); Peking-Tsinghua Center for Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Beijing Innovation Center for Genomics, Peking University School of Life Sciences, Beijing, China (X.Z., H.Y., Y.R.); Department of Pharmacology, Fudan University School of Medicine, Shanghai, China (Y.L., Z.H.); and Chinese Institute for Brain Research, Zhongguanchun Life Sciences Park, Beijing, China (Y.R.)
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    Fig. 1.

    Both Lmx1bf/f/p and Tph2−/− mice exhibited elevated locomotion but maintained body temperature. (A) Mean body temperature (Tcore; top) and activity [arbitrary units (A.U.); bottom] of Lmx1bf/f/p (red) vs. Lmx1bf/f (blue) mice over 24 hours at room temperature (RT). (B) Mean Tcore and activity by phase (light and dark) of Lmx1b mice at RT (P = 0.0061 for both dark and light, Mann-Whitney tests; n = 7 for Lmx1bf/f, n = 4 for Lmx1bf/f/p; data are mean ± S.E.M.). **P = 0.0061. (C) Tcore (top) and activity (arbitrary units bottom) of Tph2−/− (red) vs. Tph2+/+ (blue) mice over 24 hours at RT. (D) Mean Tcore and activity by phase (light and dark) of Tph2 mice at RT (P = 0.0082, Mann-Whitney test for the light phase; n = 6 for Tph2+/+; n = 7 for Tph2−/−; Data are mean ± S.E.M.). **P = 0.0082.

  • Fig. 2.
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    Fig. 2.

    Body temperature was maintained by Tph2−/− mice but not by Lmx1bf/f/p mice when the ambient temperature was 4°C. (A) Tcore of Lmx1bf/f/p (red) vs. Lmx1bf/f (blue) mice recorded for 5 hours at 4°C (mean ± S.E.M., S.E.M. indicated in gray). (B) Activity of Lmx1bf/f/p (red) vs. Lmx1bf/f (blue) mice recorded for 5 hours at 4°C (mean ± S.E.M., S.E.M. indicated in gray). (C) Mean Tcore and activity of Lmx1b mice at 4°C (for mean Tcore, P < 0.01, Mann-Whitney test; n = 7 for Lmx1bf/f, n = 5 for Lmx1bf/f/p; data are mean ± S.E.M.). **P < 0.01. (D) Tcore of Tph2−/− (red) vs. Tph2+/+ (blue) mice recorded for 5 hours at 4°C (mean ± S.E.M., S.E.M. indicated in gray). (E) Activity of Tph2−/− (red) vs. Tph2+/+ (blue) mice recorded for 5 hours at 4°C (mean ± S.E.M., S.E.M. indicated in gray). (F) Mean Tcore and activity of Lmx1b mice at 4°C (n = 7 for Tph2+/+, n = 9 for Tph2−/−; data are mean ± S.E.M.).

  • Fig. 3.
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    Fig. 3.

    Both Lmx1bf/f/p and Tph2 mice exhibited elevated activity at room temperature (RT) and 33°C. (A and B) Mean locomotion distance of Lmx1bf/f/p (red) vs. Lmx1bf/f (blue) mice at RT (P < 0.0001 for both dark and light phase in (B), Mann-Whitney tests; data are mean ± S.E.M.). (C and D) Mean active time of Lmx1bf/f/p (red) vs. Lmx1bf/f (blue) mice at RT (P < 0.0001 for dark phase and P = 0.0112 for light phase in (D), Mann-Whitney tests; data are mean ± S.E.M.; n = 16 for Lmx1bf/f, n = 12 for Lmx1bf/f/p). (E and F) Mean locomotion distance of Tph2−/− (red) vs. Tph2+/+ (blue) mice at RT (P = 0.0002 for dark and P = 0.0006 for light phase in (F), Mann-Whitney tests; data are mean ± S.E.M.). (G and H) Mean active time of Tph2−/− (red) vs. Tph2+/+ (blue) mice at RT (P = 0.0005 for dark phase and P < 0.0001 for light phase in (H), Mann-Whitney tests; data are mean ± S.E.M.; n = 36 for Tph2+/+, n = 33 for Tph2−/−). (I and J) Mean locomotion distance of Lmx1bf/f/p (red) vs. Lmx1bf/f (blue) mice at 33°C (P < 0.01 for both dark and light phase in (J), Mann-Whitney tests; data are mean ± S.E.M.). (K and L) Mean active time of Lmx1bf/f/p (red) vs. Lmx1bf/f (blue) mice at 33°C [P < 0.01 for both dark and light phase in (L), Mann-Whitney tests; data are mean ± S.E.M.; n = 15 for Lmx1bf/f, n = 13 for Lmx1bf/f/p]. (M and N) Mean locomotion distance of Tph2−/− (red) vs. Tph2+/+ (blue) mice at 33°C [P < 0.01 for the light phase in (N), Mann-Whitney tests; data are mean ± S.E.M.]. (O and P) Mean active time of Tph2−/− (red) vs. Tph2+/+ (blue) mice at 33°C [P < 0.01 for the light phase in (P), Mann-Whitney tests; data are mean ± S.E.M.; n = 30 for Tph2+/+, n = 29 for Tph2−/−]. For (A, C, E, G, I, K, M, and O), *P < 0.05; **P < 0.01; ***in F, P = 0.0002 for first column, P = 0.0006 for second column, in H, P = 0.0005; ****in D, P < 0.0001; ‡P < 0.01; †P < 0.001; #P < 0.0001; Mann-Whitney tests.

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    Fig. 4.

    Analysis of EEG/EMG patterns reveals that Tph2−/− mice exhibited less sleep at both RT and 33°C. (A and B) Examples of time spent on wake, NREM, and REM by Tph2+/+ (A) and Tph2−/− (B) over 24 hours at RT. (C–E) Mean percentage of wake (C), NREM (D), and REM (E) by phase (light and dark) at RT [P < 0.01 for light phase in (E), Mann-Whitney test; data are mean ± S.E.M.; n = 20 for Tph2+/+, n = 22 for Tph2−/−]. (F and G) Examples of time spent on wake, NREM, and REM by Tph2+/+ (F) and Tph2−/− (G) over 24 hours at 33°C. (H–J) Mean percentage of wake (H), NREM (I), and REM (J) by phase (light and dark) at 33°C [P < 0.01 for dark phase in (H), P < 0.01 for dark phase in (I), P < 0.01 for both dark and light phase in (J); Mann-Whitney test; data are mean ± S.E.M.; n = 20 for Tph2+/+, n = 21 for Tph2−/−]. **P < 0.01.

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      Comparison of locomotion activity of mice with same genotype between room temperature and 33°C

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Molecular Pharmacology: 93 (6)
Molecular Pharmacology
Vol. 93, Issue 6
1 Jun 2018
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Rapid CommunicationAccelerated Communication

5-HT and Sleep

Xian Zhang, Hongming Yan, Yanjia Luo, Zili Huang and Yi Rao
Molecular Pharmacology June 1, 2018, 93 (6) 657-664; DOI: https://doi.org/10.1124/mol.117.111229

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5-HT and Sleep

Xian Zhang, Hongming Yan, Yanjia Luo, Zili Huang and Yi Rao
Molecular Pharmacology June 1, 2018, 93 (6) 657-664; DOI: https://doi.org/10.1124/mol.117.111229
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