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Publication : Postnatal maintenance of the 5-Ht1a-Pet1 autoregulatory loop by serotonin in the raphe nuclei of the brainstem.

First Author  Kim JY Year  2014
Journal  Mol Brain Volume  7
Pages  48 PubMed ID  24972638
Mgi Jnum  J:220591 Mgi Id  MGI:5635511
Doi  10.1186/1756-6606-7-48 Citation  Kim JY, et al. (2014) Postnatal maintenance of the 5-Ht1a-Pet1 autoregulatory loop by serotonin in the raphe nuclei of the brainstem. Mol Brain 7:48
abstractText  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.
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