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PNAS 108 (21): 8844-8849

Copyright © 2011 by the National Academy of Sciences.

BIOLOGICAL SCIENCES / NEUROSCIENCE

N-acetylserotonin promotes hippocampal neuroprogenitor cell proliferation in sleep-deprived mice

Pradoldej Sompola, Xia Liua, Kenkichi Babab, Ketema N. Paulb, Gianluca Tosinib, P. Michael Iuvonec, and Keqiang Yea,1

Departments of aPathology and Laboratory Medicine and cOphthalmology and Pharmacology, Emory University School of Medicine, Atlanta, GA 30322; and bNeuroscience Institute, Morehouse School of Medicine, Atlanta, GA 30310

Edited* by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved April 12, 2011 (received for review March 30, 2011)

Abstract: N-acetylserotonin (NAS), the immediate precursor of melatonin, the pineal gland indole, is regulated in a circadian rhythm. NAS swiftly activates TrkB in a circadian manner and exhibits antidepressant effect in a TrkB-dependent manner. Here we show that NAS regulates an early event of neurogenesis by increasing neuronal progenitor cell (NPC) proliferation. Subchronic and chronic NAS administration induces NPC proliferation in adult mice. Chronic NAS treatment triggers TrkB receptor activation and its downstream signaling in NPCs. Blockade of TrkB abolishes NAS-elicited neurogenesis in TrkBF616A knockin mice, suggesting that TrkB activation is essential for the effect of NAS-induced NPC proliferation. Moreover, NAS induces NPC proliferation in both active and sleeping phases of the mice. Strikingly, NAS significantly enhances NPC proliferation in sleep-deprived mice. Thus, our finding demonstrates a unique function of NAS in promoting robust NPC proliferation, which may contribute to hippocampal plasticity during sleeping period.

Key Words: sleep deprivation • brain-derived neurotrophic factor

Author contributions: P.S., K.B., G.T., P.M.I., and K.Y. designed research; P.S., X.L., and K.B. performed research; K.N.P. contributed new reagents/analytic tools; P.S., K.B., G.T., P.M.I., and K.Y. analyzed data; and P.S., G.T., 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/lookup/suppl/doi:10.1073/pnas.1105114108/-/DCSupplemental.

1To whom correspondence should be addressed. E-mail: kye{at}emory.edu.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
N-Acetylserotonin: Neuroprotection, Neurogenesis, and the Sleepy Brain.
G. Tosini, K. Ye, and P. M. Iuvone (2012)
Neuroscientist 18, 645-653
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N-acetyl serotonin derivatives as potent neuroprotectants for retinas.
J. Shen, K. Ghai, P. Sompol, X. Liu, X. Cao, P. M. Iuvone, and K. Ye (2012)
PNAS 109, 3540-3545
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