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Mol Brain. 2014 Jun 28;7:48. doi: 10.1186/1756-6606-7-48.

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

Author information

1
Center for the Study of Itch, Washington University School of Medicine, St, Louis 63110, USA. chenz@wustl.edu.

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.

PMID:
24972638
PMCID:
PMC4086287
DOI:
10.1186/1756-6606-7-48
[Indexed for MEDLINE]
Free PMC Article

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