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N -acetylserotonin activates TrkB receptor in a circadian rhythm
Open accessAbstract
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 ( a ryl a lkylamine N - a cetyl t ransferase). 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.
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Cites
TrkB Regulates Hippocampal Neurogenesis and Governs Sensitivity to Antidepressive Treatment
Li, Y., Luikart, B. W., Birnbaum, S., Chen, J., Kwon, C.-H., Kernie, S. G., Bassel-Duby, R., & Parada, L. F. (2008) · Neuron · doi:10.1016/j.neuron.2008.06.023 · Cited by 634
Dias, B. (2003) · Neuropharmacology · doi:10.1016/s0028-3908(03)00198-9 · Cited by 274
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Epigenetic Regulation of the BDNF Gene: Implications for Psychiatric Disorders
Boulle, F., van den Hove, D. L. A., Jakob, S. B., Rutten, B. P., Hamon, M., van Os, J., Lesch, K.-P., Lanfumey, L., Steinbusch, H. W., & Kenis, G. (2012) · Molecular Psychiatry · doi:10.1038/mp.2011.107 · Cited by 282
The role of the gut microbiota in multiple sclerosis
Correale, J., Hohlfeld, R., & Baranzini, S. E. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00697-8 · Cited by 207
A time to remember: The role of circadian clocks in learning and memory.
Smarr, B. L., Jennings, K. J., Driscoll, J. R., & Kriegsfeld, L. J. (2014) · Behavioral Neuroscience · doi:10.1037/a0035963 · Cited by 166
The serotonin-N-acetylserotonin-melatonin pathway as a biomarker for autism spectrum disorders
Pagan, C., Delorme, R., Callebert, J., Goubran-Botros, H., Amsellem, F., Drouot, X., Boudebesse, C., Le Dudal, K., Ngo-Nguyen, N., Laouamri, H., et al. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.120 · Cited by 165
Metadata
- Authors
- Jang, S.-W., Liu, X., Pradoldej, S., Tosini, G., Chang, Q., Iuvone, P. M., & Ye, K.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2010-02-23
- Volume
- 107
- Issue
- 8
- Pages
- 3876-3881
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2111842512
- Cited by
- 214
- References
- 2
- FWCI
- 4.42
- Type
- journal article
- Language
- en
- Open access
- green
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- Jang, S.-W., Liu, X., Pradoldej, S., Tosini, G., Chang, Q., Iuvone, P. M., & Ye, K. (2010). N -acetylserotonin activates TrkB receptor in a circadian rhythm. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0912531107
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