title: Postnatal maintenance of the 5-Ht1a-Pet1 autoregulatory loop by serotonin in the raphe nuclei of the brainstem.
abstract: BACKGROUND
  Despite the importance of 5-HT1A as a major target for the action of several anxiolytics/antidepressant drugs, little is known about its regulation in central serotonin (5-hydroxytryptamine, 5-HT) neurons.
  
  
  RESULTS
  We report that expression of 5-HT1A and the transcription factor Pet1 was impaired in the rostral raphe nuclei of mice lacking tryptophan hydroxylase 2 (Tph2) after birth. The downregulation of Pet1 was recapitulated in 5-Ht1a-/- mice. Using an explant culture system, we show that reduction of Pet1 and 5-HT1A was rescued in Tph2-/- brainstem by exogenous 5-HT. In contrast, 5-HT failed to rescue reduced expression of Pet1 in 5-Ht1a-/- brainstem explant culture.
  
  
  CONCLUSIONS
  These results suggest a causal relationship between 5-HT1A and Pet1, and reveal a potential mechanism by which 5-HT1A-Pet1 autoregulatory loop is maintained by 5-HT in a spatiotemporal-specific manner during postnatal development. Our results are relevant to understanding the pathophysiology of certain psychiatric and developmental disorders.
authors: Ji-Young
authors: JY
authors: Kim
authors: Ana
authors: A
authors: Kim
authors: Zhong-Qiu
authors: ZQ
authors: Zhao
authors: Xian-Yu
authors: XY
authors: Liu
authors: Center for the Study of Itch, Washington University School of Medicine, St, Louis 63110, USA. chenz@wustl.edu.
authors: Zhou-Feng
authors: ZF
authors: Chen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D025461:Feedback, Physiological / Q000187:drug effects*; D050990:GATA3 Transcription Factor / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism*; D044282:Receptor, Serotonin, 5-HT1A / Q000172:deficiency / Q000378:metabolism*; D059326:Serotonergic Neurons / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000172:deficiency / Q000378:metabolism
chemical_list: C484684:Fev protein, mouse; D050990:GATA3 Transcription Factor; D014157:Transcription Factors; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase