Please use this identifier to cite or link to this item: https://doi.org/10.1073/pnas.0711496105
Title: Role of GSK3β in behavioral abnormalities induced by serotonin deficiency
Authors: Beaulieu, J.-M.
Zhang, X. 
Rodriguiz, R.M.
Sotnikova, T.D.
Cools, M.J.
Wetsel, W.C.
Gainetdinov, R.R.
Caron, M.G.
Keywords: Functional polymorphism
GSK-3
Mood disorders
Serotonin
Tph2
Issue Date: 29-Jan-2008
Source: Beaulieu, J.-M., Zhang, X., Rodriguiz, R.M., Sotnikova, T.D., Cools, M.J., Wetsel, W.C., Gainetdinov, R.R., Caron, M.G. (2008-01-29). Role of GSK3β in behavioral abnormalities induced by serotonin deficiency. Proceedings of the National Academy of Sciences of the United States of America 105 (4) : 1333-1338. ScholarBank@NUS Repository. https://doi.org/10.1073/pnas.0711496105
Abstract: Dysregulation of brain serotonin (5-HT) neurotransmission is thought to underlie mental conditions as diverse as depression, anxiety disorders, bipolar disorder, autism, and schizophrenia. Despite treatment of these conditions with serotonergic drugs, the molecular mechanisms by which 5-HT is involved in the regulation of aberrant emotional behaviors are poorly understood. Here, we generated knockin mice expressing a mutant form of the brain 5-HT synthesis enzyme, tryptophan hydroxylase 2 (Tph2). This mutant is equivalent to a rare human variant (R441H) identified in few individuals with unipolar major depression. Expression of mutant Tph2 in mice results in markedly reduced (≈80%) brain 5-HT production and leads to behavioral abnormalities in tests assessing 5-HT-mediated emotional states. This reduction in brain 5-HT levels is accompanied by activation of glycogen synthase kinase 3β (GSK3β), a signaling molecule modulated by many psychiatric therapeutic agents. Importantly, inactivation of GSK3β in Tph2 knockin mice, using pharmacological or genetic approaches, alleviates the aberrant behaviors produced by 5-HT deficiency. These findings establish a critical role of Tph2 in the maintenance of brain serotonin homeostasis and identify GSK3β signaling as an important pathway through which brain 5-HT deficiency induces abnormal behaviors. Targeting GSK3β and related signaling events may afford therapeutic advantages for the management of certain 5-HT-related psychiatric conditions. © 2008 by The National Academy of Sciences of the USA.
Source Title: Proceedings of the National Academy of Sciences of the United States of America
URI: http://scholarbank.nus.edu.sg/handle/10635/130472
ISSN: 00278424
DOI: 10.1073/pnas.0711496105
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

236
checked on Jan 17, 2018

WEB OF SCIENCETM
Citations

232
checked on Jan 17, 2018

Page view(s)

11
checked on Jan 23, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.