N-acetylserotonin activates TrkB receptor in a circadian rhythm

Sung Wuk Jang, Xia Liu, Sompol Pradoldej, Gianluca Tosini, Qiang Chang, P. Michael Iuvone, Keqiang Ye

Research output: Contribution to journalArticlepeer-review

122 Scopus citations

Abstract

Brain-derived neurotrophic factor (BDNF) is a cognate ligand for the TrkB receptor. BDNF and serotonin often function in a cooperative manner to regulate neuronal plasticity, neurogenesis, and neuronal survival. Here we show that NAS (N-acetylserotonin) swiftly activates TrkB in a circadian manner and exhibits antidepressant effect in a TrkB-dependent manner. NAS, a precursor of melatonin, is acetylated from serotonin by AANAT (arylalkylamine Nacetyltransferase). NAS rapidly activates TrkB, but not TrkA or TrkC, in a neurotrophin- and MT3 receptor-independent manner. Administration ofNASactivates TrkB in BDNFknockout mice. Furthermore, NAS, but not melatonin, displays a robust antidepressant-like behavioral effect in a TrkB-dependent way. Endogenous TrkB is activated in wild-type C3H/f+/+ mice but not in AANAT-mutated C57BL/6J mice, in a circadian rhythm; TrkB activation is high at night in the dark and low during the day. Hence, our findings support that NAS is more than a melatonin precursor, and that it can potently activate TrkB receptor.

Original languageEnglish
Pages (from-to)3876-3881
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number8
DOIs
StatePublished - Feb 23 2010

Keywords

  • Depression
  • Neuroprotection
  • Neurotrophin
  • Serotonin

ASJC Scopus subject areas

  • General

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