cAMP Response Element-Mediated Gene Transcription Is Upregulated by Chronic Antidepressant Treatment

Thome, Johannes; Sakai, Norio; Shin, Kyung-Ho; Steffen, Cathy; Zhang, Y.-J.; Impey, Soren; Storm, Daniel R.; Duman, R. S.

doi:10.1523/jneurosci.20-11-04030.2000

Cited by 478 publications

(286 citation statements)

References 47 publications

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“…One piece of evidence of particular interest was discovered when we were studying the influence of antidepressants on CREB phosphorylation. We reported that antidepressant treatment increases the phosphorylation of CREB, measured with a phospho-specific antibody ( Figure 5) (Thome et al 2000). The additional point of interest in these studies was that under basal conditions there was prominent expression of phospho-CREB in cells within, or adjacent to, the subgranular zone where the progenitor cells are located (Figure 4).…”

Section: Role Of the Camp-creb Cascade In Adult Neurogenesismentioning

confidence: 94%

“…This has led to the discovery that repeated long-term antidepressant administration up-regulates the cAMP-CREB (cAMP response element binding protein) cascade and expression of brain derived neurotrophic factor (BDNF) in hippocampus ( Figure 2) (Nibuya et al 1995(Nibuya et al , 1996Thome et al 2000). Both CREB and BDNF are known to play a role in synaptic plasticity as well as neuronal survival (see Finkbeiner 2000;Duman et al 2000).…”

Section: Antidepressant Treatment Increases Adult Neurogenesismentioning

confidence: 99%

“…Localization of phospho-CREB (pCREB) in dentate gyrus. Chronic antidepressant treatment increases levels of pCREB, determined by immunohistochemistry with a pCREB specific antibody (see Thome et al 2000). In vehicle treated controls the expression of pCREB was observed in cells located within or adjacent to the subgranular zone (arrowheads).…”

Section: Role Of the Camp-creb Cascade In Adult Neurogenesismentioning

confidence: 99%

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Regulation of Adult Neurogenesis by Antidepressant Treatment

Duman

Nakagawa

Malberg

2001

Neuropsychopharmacology

428

249

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Demonstration of neurogenesis in adult brainOur understanding of how the brain functions and undergoes adaptation and plasticity has changed dramatically over the past several years. A great deal of work has demonstrated that altered levels of neurotransmitters, second messenger pathways, and gene expression profiles underlie cellular and behavioral plasticity. This includes models of learning and memory as well as models of depression, anxiety, and psychosis, and the long-term actions of psychotropic drugs. However, it is now becoming increasing evident that changes in cellular morphology and even more pronounced alterations in brain structure also contribute to neural plasticity or remodeling. At the cellular level these changes can occur in the form of up or down-regulation of synapse formation and spine density or extension and retraction of dendrites. Another very dramatic example is up or down-regulation of neurogenesis in adult brain. Studies in recent years demonstrate that new cell birth occurs in adult brain and that the rate of neurogenesis and the survival of new neurons is regulated by a number of environmental, endocrine, and pharmacological treatments.In this paper we discuss the evidence that structural remodeling may be involved in the pathophysiology and treatment of mood disorders. The potential role of neurogenesis is also discussed as well as the molecular mechanisms which underlie antidepressant regulation of new cell birth and survival. The studies to date suggest an exciting possibility for the role of neurogenesis

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Section: Role Of the Camp-creb Cascade In Adult Neurogenesismentioning

confidence: 94%

Section: Antidepressant Treatment Increases Adult Neurogenesismentioning

confidence: 99%

Section: Role Of the Camp-creb Cascade In Adult Neurogenesismentioning

confidence: 99%

See 1 more Smart Citation

Regulation of Adult Neurogenesis by Antidepressant Treatment

Duman

Nakagawa

Malberg

2001

Neuropsychopharmacology

428

249

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“…While the expression of CREB in the hippocampus of WT mice was enhanced by chronic administration of both desipramine and fluoxetine, CREB mRNA levels in the cortex were not significantly affected by either antidepressant drug. Support for a selective region-specific effect of antidepressants on CREB expression is provided by a study using post-mortem tissue from patients suffering from major depression that showed CREB expression to be enhanced in the temporal, but not occipital, cortex after treatment with antidepressants (Dowlatshahi et al 1998).One explanation for the different expression patterns of CREB displayed by the cortex and hippocampus may be the upregulation of two cAMP specific phosphodiesterase isoforms, PDE4A and PDE4B, that were upregulated in the cortex but not in the hippocampus of rats after chronic antidepressant treatment (Fujimaki et al 2000;Thome et al 2000). Phosphodiesterases play a crucial role in converting cAMP to 5Ј-AMP, and inhibit the transduction pathway leading to the activation of CREB.…”

mentioning

confidence: 99%

Altered Regulation of CREB by Chronic Antidepressant Administration in the Brain of Transgenic Mice with Impaired Glucocorticoid Receptor Function

Blom

Tascedda

Carra

et al. 2002

Neuropsychopharmacology

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Various effects of antidepressant drugs on gene transcription have been described and altered gene expression has been proposed as being a common biological basis underlying depressive illness. One target for the common action of antidepressants is a modifying effect on the regulation of postreceptor pathways and genes related to the cAMP cascade. Recent studies have demonstrated that long-term antidepressant treatment resulted in sustained activation of the cyclic adenosine 3 Ј ,5 Ј -monophosphate system and in increased expression of the transcription factor cAMP response element binding protein (CREB). KEY WORDS : CREB; Antidepressant drugs; Glucocorticoid receptor; Transgenic miceWhile the regulation of monoamine levels and their receptors or the restoration of hypothalamus-pituitaryadrenal (HPA) system feedback may represent initial effects of antidepressant drugs, their therapeutic action could be related to subsequent action on genes involved in postreceptor mechanisms. One such postreceptor target that can be influenced by either 5HT or NE as well as by drugs that affect these systems is the nuclear transcription factor cAMP response element binding protein (CREB) (Montminy, et al. 1990;Meyer and Habener 1993;Nibuya et al. 1996;Duman et al. 1997Duman et al. , 1999Thome et al. 2000). A role for the cAMP cascade in the long-term ac- (Nestler et al. 1989) and that the activity of CREB is enhanced following its phosphorylation by PKA (Meyer and Habener 1993;Ghosh and Greenberg 1995). Furthermore, viral mediated over-expression of CREB in two animal models of depression produced an antidepressant effect and resulted in improved behavioral performance in both models (Chen et al. 2001).Based on the hypothesis that the apparent lack of sensitivity to corticosteroids observed in major depression is causally linked to the pathogenesis of depression (Holsboer and Barden 1996;Holsboer 2000;Pariante and Miller 2001) as well as to the therapeutic effectiveness of antidepressant drugs (Barden 1996), a transgenic animal model of neuroendocrine changes associated with depression was developed (Pepin et al. 1992a). Insertion into the mouse genome of a transgene expressing antisense RNA complementary to a fragment of the glucocorticoid receptor (GR) cDNA produced an animal with a defect in the neuronal glucocorticoid receptors that mediate the effects of high "stress" levels of glucocorticoids on the negative feedback of the HPA system. These transgenic mice displayed impaired endogenous GR function and were characterized by dysfunctional glucocorticoid inhibitory feedback and disturbed ACTH and corticosterone secretory responses Karanth et al. 1997;Dijkstra et al. 1998). Long-term treatment of the transgenic mice with antidepressant drugs caused an increase in GR gene expression and produced significant normalization of the HPA system hyperactivity through restoration of functional glucocorticoid inhibitory feedback (Pepin et al. 1992b;Barden et al. 1995;Barden et al. 1997).Because the second messenger cyclic AMP plays a...

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“…Levels of CREB and of CREB-mediated transcription are increased in the hippocampus and cerebral cortex by chronic antidepressant treatments, including ECS (Nibuya et al, 1996;Thome et al, 2000;Koch et al, 2002;Nakagawa et al, 2002). This upregulation of CREB may help restore normal cAMP signaling in these brain regions, whereas abnormally low levels of CREB in depressed patients have been reported (Dowlatshahi et al, 1998;D'Sa and Duman, 2002).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of the CCAAT-Enhancer Binding Protein β in ΔFosB Transgenic Mice and by Electroconvulsive Seizures

Chen

Newton

Zeng

et al. 2003

Neuropsychopharmacol

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Previous studies demonstrate that chronic, but not acute electroconvulsive seizures (ECS), increases levels of DFosB, a long-lasting transcription factor, in the hippocampus, and this effect correlates with the slow onset and long-lasting clinical effects of antidepressant treatment. To understand how DFosB mediates long-term plasticity in the hippocampus, we analyzed the gene expression profile of inducible transgenic mice expressing DFosB with a highly sensitive microarray assay and a customized computer analysis program. The CCAAT-enhancing binding protein-b (C/EBPb) was identified as one of the genes downregulated by DFosB in the hippocampus. The downregulation of C/EBPb in the inducible DFosB transgenic mice was confirmed by other quantitative assays including real-time RT-PCR and low density dot blotting. Analysis of the C/EBPb expression in the hippocampus of rats treated with ECS revealed that the C/EBPb mRNA was also downregulated by chronic, but not acute ECS administration, the most effective treatment for depression. Given the reported role of C/EBPb in behavioral conditioning models, it is possible that the DFosB-mediated downregulation of C/EBPb in the hippocampus may be a molecular mechanism by which antidepressants alleviate some of the symptoms of depressed patients.

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cAMP Response Element-Mediated Gene Transcription Is Upregulated by Chronic Antidepressant Treatment

Cited by 478 publications

References 47 publications

Regulation of Adult Neurogenesis by Antidepressant Treatment

Regulation of Adult Neurogenesis by Antidepressant Treatment

Altered Regulation of CREB by Chronic Antidepressant Administration in the Brain of Transgenic Mice with Impaired Glucocorticoid Receptor Function

Downregulation of the CCAAT-Enhancer Binding Protein β in ΔFosB Transgenic Mice and by Electroconvulsive Seizures

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