2006 issue 4

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Volume 15, issue 4

Review article

The CREB transcriptional factor contribution to the mechanism of the antidepressant effect

Tadeusz Pietras1, Piotr Gałecki2, Janusz Szemraj3
1. Kliniki Pneumonologii i Alergologii Katedry Medycyny Wewnętrznej Uniwersytetu Medycznego w Łodzi
2. Klinika Psychiatrii Dorosłych Uniwersytetu Medycznego w Łodzi
3. Zakładu Biochemii Medycznej Uniwersytetu Medycznego w Łodzi
Postępy Psychiatrii i Neurologii 2006; 15 (4): 287-276
Keywords: antidepressants, CREB transcriptional factor
Abstract

Objectives. The aim of the article is to review the current literature on the CREB factor role in the mechanism underlying the action of antidepressants.

Review. The antidepressant effect due to an increased direct receptor serotonin and noradrenergic transmission seems to be doubtful. While catecholamine reuptake inhibition can be seen immediately on drug administration, the antidepressant effect related to serotoninergic transmission occurs sometimes with a few week delay. Nowadays, the mechanism underlying the antidepressant action is often associated with an increased protein expression of some transcriptional factors, including CREB (cyclic AMP-responsive element binding). The CREB factor regulates the expression ofgenes connected with synaptic and neuronal plasticity, trophic factors for neurons (e.g. the BDNF - brain-derived neurotrophic factor), and proteins of membrane receptors. The CREB transcriptional factor phosphorylation responsible for delayed effects of the mediator influence on a receptor (connected with adenylane cyclase), is linked to gene expression regulation. All the examined antidepressants were shown to increase mRNA expression in hippocampal cells for the CREB factor, BDNF proteins, and for the oncogene Trk product. The reported research findings confirm an increased expression and phosphorylation of the CREB protein in animal brains after administration of various antidepressants.

Conclusions. In the authors' opinion the action of antidepressants may be associated with gene expression regulation, since an anti-depressant effect of these drugs can be seen only after a few weeks of treatment.

Address for correspondence:
Dr Tadeusz Pietras, Klinika Pneumonologii i Alergologii Katedry Medycyny Wewnętrznej Uniwersytetu Medycznego,
ul. Kopcińskiego 22, 91-123 Łódź, tel./fax: (42) 6782129