TY - JOUR
T1 - N-acetylserotonin activates TrkB receptor in a circadian rhythm
AU - Jang, Sung Wuk
AU - Liu, Xia
AU - Pradoldej, Sompol
AU - Tosini, Gianluca
AU - Chang, Qiang
AU - Iuvone, P. Michael
AU - Ye, Keqiang
PY - 2010/2/23
Y1 - 2010/2/23
N2 - 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.
AB - 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.
KW - Depression
KW - Neuroprotection
KW - Neurotrophin
KW - Serotonin
UR - http://www.scopus.com/inward/record.url?scp=77649258523&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77649258523&partnerID=8YFLogxK
U2 - 10.1073/pnas.0912531107
DO - 10.1073/pnas.0912531107
M3 - Article
C2 - 20133677
AN - SCOPUS:77649258523
SN - 0027-8424
VL - 107
SP - 3876
EP - 3881
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 8
ER -