한빛사논문
- 조회3,520
Abstract
Sung-Wuk Janga, Xia Liua, Sompol Pradoldeja, Gianluca Tosinib, Qiang Changc, P. Michael Iuvoned, and Keqiang Yea,1
aDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322;
bNeuroscience Institute, Morehouse School of Medicine, Atlanta, GA 30310;
cDepartment of Genetics and Neurology, Waisman Center, University of Wisconsin, Madison, WI 53705-2280; and
dDepartments of Ophthalmology and Pharmacology, Emory University School of Medicine, Atlanta, GA 30322
Edited* by Solomon Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved December 30, 2009 (received for review October 29, 2009)
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 N-acetyltransferase). NAS rapidly activates TrkB, but not TrkA or TrkC, in a neurotrophin- and MT3 receptor-independent manner. Administration of NAS activates TrkB in BDNF knockout 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.
depression, neuroprotection, neurotrophin, serotonin
Footnotes
1To whom correspondence should be addressed.
Author contributions: S.-W.J. and K.Y. designed research; S.-W.J., X.L., S.P., G.T., and P.M.I. performed research; Q.C. contributed new reagents and analytical tools; P.M.I. and K.Y. analyzed data; and S.-W.J., P.M.I., and K.Y. wrote the paper.
The authors declare no conflict of interest.
*This Direct Submission article had a prearranged editor.
This article contains supporting information online at
www.pnas.org/cgi/content/full/0912531107/DCSupplemental.
논문정보
- Research article
- 2010년 02월 (BRIC 등록일 )
- 국외 연구진
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