title: N-acetylserotonin promotes hippocampal neuroprogenitor cell proliferation in sleep-deprived mice.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine and Ophthalmology and Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Pradoldej
authors.initials: P
authors.lastname: Sompol
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.forename: Kenkichi
authors.initials: K
authors.lastname: Baba
authors.forename: Ketema N
authors.initials: KN
authors.lastname: Paul
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tosini
authors.forename: P Michael
authors.initials: PM
authors.lastname: Iuvone
authors.forename: Keqiang
authors.initials: K
authors.lastname: Ye
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D006624:Hippocampus / Q000166:cytology*; D008562:Membrane Glycoproteins; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects; D055495:Neurogenesis; D011505:Protein-Tyrosine Kinases; D012701:Serotonin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D012892:Sleep Deprivation / Q000473:pathology*; D020813:Receptor, trkB
chemical_list: D000928:Antidepressive Agents; D008562:Membrane Glycoproteins; D011505:Protein-Tyrosine Kinases; D012701:Serotonin; C064371:Ntrk2 protein, mouse; D020813:Receptor, trkB; C006389:N-acetylserotonin