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Mol Pharmacol. 2018 Jun;93(6):657-664. doi: 10.1124/mol.117.111229. Epub 2018 Apr 9.

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

Author information

1
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.).
2
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.) yrao@pku.edu.cn.

Abstract

A role for 5-hydroxytryptamine (5-HT) or serotonin in sleep has been known for decades but was challenged by recent papers that concluded that the apparent sleep phenotype was secondary to defective thermoregulation. Those studies used mice lacking serotonergic neurons resulting from the loss of function mutations in the gene encoding the LIM homeobox transcription factor 1 (Lmx1b). Here we show that, while Lmx1b mutants failed to keep the physiologic body temperature, they exhibited more activities at the room and elevated temperatures. More importantly, we used mice deficient in the gene encoding tryptophan hydroxylase 2 (Tph2), which could not synthesize 5-HT in the brain. Tph2 mutants were capable of thermoregulation and keeping physiologic body temperature when the environmental temperature was reduced and exhibited significantly more activities at both the room and elevated temperatures. Electroencephalographic (EEG) recording also showed decreased sleep in Tph2-deficient mice. Our results indicate that 5-HT is important for sleep regulation but not thermoregulation.

PMID:
29632139
DOI:
10.1124/mol.117.111229
[Indexed for MEDLINE]

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