RT Journal Article
SR Electronic
T1 Thermoregulation-Independent Regulation of Sleep by Serotonin Revealed in Mice Defective in Serotonin Synthesis
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP mol.117.111229
DO 10.1124/mol.117.111229
A1 Xian Zhang
A1 Hongming Yan
A1 Yanjia Luo
A1 Zhili Huang
A1 Yi Rao
YR 2018
UL http://molpharm.aspetjournals.org/content/early/2018/04/10/mol.117.111229.abstract
AB A role for 5-hydroxytryptamine (5-HT) or serotonin in sleep has been known for decades but was challenged by recent papers which 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 physiological 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 physiological 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.