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Author Notes:

To whom correspondence should be addressed. E-mail: kye@emory.edu.

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

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.

Subject:

Research Funding:

This work is supported by National Institutes of Health Grants RO1 NS045627 (to K.Y.), R01 NS43459 (to G.T.), and R01 EY004864 and P30 EY006360 (to P.M.I.).

Keywords:

  • sleep deprivation
  • brain-derived neurotrophic factor

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

Tools:

Journal Title:

Proceedings of the National Academy of Sciences

Volume:

Volume 108, Number 21

Publisher:

, Pages 8844-8849

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

Beginning with articles submitted in Volume 106 (2009) the author(s) retains copyright to individual articles, and the National Academy of Sciences of the United States of America retains an exclusive license to publish these articles and holds copyright to the collective work.

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