Early induction of CREB activation and CREB-regulating signalling by antidepressants.

@article{Tardito2009EarlyIO,
  title={Early induction of CREB activation and CREB-regulating signalling by antidepressants.},
  author={Daniela Tardito and Laura Musazzi and Ettore Tiraboschi and Alessandra Mallei and Giorgio Racagni and Maurizio Popoli},
  journal={The international journal of neuropsychopharmacology},
  year={2009},
  volume={12 10},
  pages={
          1367-81
        }
}
Converging evidence points to adaptive changes in neuroplasticity and gene expression as mediators of therapeutic action of antidepressants. Activation of cAMP response-element binding protein (CREB) and CREB-regulating signalling are considered main effectors in these mechanisms. We analysed the temporal profile of intracellular changes induced by antidepressants, by measuring activation of major CREB-regulating signalling cascades and activation (Ser133 phosphorylation) of CREB. The main aims… 

Figures from this paper

Time-dependent activation of MAPK/Erk1/2 and Akt/GSK3 cascades: modulation by agomelatine

In naïve rats chronic agomelatine, contrary to traditional antidepressants, did not increase CREB phosphorylation, but modulates the time-dependent regulation of MAPK/Erk1/2 and Akt/glycogen synthase kinase-3 (GSK-3) pathways.

Early raise of BDNF in hippocampus suggests induction of posttranscriptional mechanisms by antidepressants

It is found that mature BDNF protein is induced more rapidly than mRNA, by both drugs in hippocampus (weeks 1–2 and by reboxetine in prefrontal/frontal cortex (week 1).

Pharmacological characterization of BDNF promoters I, II and IV reveals that serotonin and norepinephrine input is sufficient for transcription activation.

A rapidly detectable and highly sensitive reporter gene assay was applied to characterize the selective activation profile of BDNF and CRE promoters, through specific and different pharmacological stimuli.

Molecular and cellular mechanisms of antidepressant action.

  • T. Sharp
  • Biology, Psychology
    Current topics in behavioral neurosciences
  • 2013
Previous and current knowledge of antidepressant drug action on monoamine signalling at molecular and cellular levels are brought together, and current thinking that these changes interact with neuropsychological processes ultimately to elevate mood is introduced.

The Role of Arrestins in the Neuroprotective Effects of Antidepressant Drugs

An overview of recent advances concerning the major role played by beta-arrestins in the regulation of the neuroprotective processes underlying the pathophysiology of mood disorders and the mechanism of action of antidepressant drugs is provided.

Chronic antidepressant treatments induce a time-dependent up-regulation of AMPA receptor subunit protein levels

2 The Role of Monoamines in Antidepressant Drug Action

Previous and current knowledge of antidepressant drug action on monoamine signalling at molecular and cellular levels are brought together, and current thinking that these changes interact with neuropsychological processes ultimately to elevate mood is introduced.

The transcriptional response to chronic stress and glucocorticoid receptor blockade in the hippocampal dentate gyrus

The identified genetic pathways provide insight into the stress‐induced adaptive plasticity of the hippocampal DG that is so central in learning and memory and will direct future studies on the functional outcome and modulation of these stress effects.

Physical exercise and acute restraint stress differentially modulate hippocampal brain‐derived neurotrophic factor transcripts and epigenetic mechanisms in mice

The results suggest that physical exercise and stress are able to differentially modulate the expression of BDNF transcripts by possible different epigenetic mechanisms.

References

SHOWING 1-10 OF 49 REFERENCES

Selective Phosphorylation of Nuclear CREB by Fluoxetine is Linked to Activation of CaM Kinase IV and MAP Kinase Cascades

The results show that FLX exerts a more marked effect on CREB phosphorylation and suggest that CaMKIV and MAP kinase cascades are involved in this effect.

Signaling Pathways Regulating Gene Expression, Neuroplasticity, and Neurotrophic Mechanisms in the Action of Antidepressants: A Critical Overview

The available evidence is reviewed with an attempt to identify the reasons for experimental discrepancies and possible directions for future research into the regulation of brain-derived neurotrophic factor, a CREB-regulated gene, which has been implicated in both the pathophysiology and pharmacology of mood disorders.

Reduced CREB phosphorylation after chronic lithium treatment is associated with down-regulation of CaM kinase IV in rat hippocampus.

Assessment of the effects of prolonged lithium administration on cAMP responsive element-binding protein (CREB) phosphorylation and CaM kinase IV (CaMKIV), one of the main kinases phosphorylating CREB in neurons following synaptic activation, suggests for the first time the involvement of CaMKIV in the mechanism of action of lithium.

Pharmacologically Diverse Antidepressants Rapidly Activate Brain-Derived Neurotrophic Factor Receptor TrkB and Induce Phospholipase-Cγ Signaling Pathways in Mouse Brain

The data suggest that rapid activation of the TrkB neurotrophin receptor and PLCγ1 signaling is a common mechanism for all antidepressant drugs.

Chronic Antidepressants Induce Redistribution and Differential Activation of αCaM Kinase II between Presynaptic Compartments

Overall, antidepressants induce a complex pattern of modifications in distinct subcellular compartments; at presynaptic level, these changes are in line with a dampening of glutamate release.

Activity-Dependent Neuroprotection and cAMP Response Element-Binding Protein (CREB): Kinase Coupling, Stimulus Intensity, and Temporal Regulation of CREB Phosphorylation at Serine 133

Cellular and molecular signaling events that couple excitotoxic and nontoxic levels of NMDA receptor stimulation to activation of the cAMP response element-binding protein (CREB)/cAMPresponse element (CRE) pathway in cultured cortical neurons provide a framework to begin to understand how the neuroprotective and excitOToxic effects ofNMDA receptor activity function in an antagonistic manner at the level of the CREB/CRE transcriptional pathway.

Regulation of Activin mRNA and Smad2 Phosphorylation by Antidepressant Treatment in the Rat Brain: Effects in Behavioral Models

The results suggest that regulation of activin and Smad signaling may contribute to the actions of antidepressant treatment and may represent novel targets for antidepressant drug development.

What turns CREB on?

The many faces of CREB