INT62577

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Context Info
Confidence 0.59
First Reported 1996
Last Reported 2010
Negated 2
Speculated 1
Reported most in Body
Documents 55
Total Number 56
Disease Relevance 19.68
Pain Relevance 18.10

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

mitochondrion (Creb1) nucleus (Creb1) DNA binding (Creb1)
transcription factor binding (Creb1)
Anatomy Link Frequency
hippocampus 7
forebrain 4
nucleus accumbens 4
striatum 3
neurons 3
Creb1 (Mus musculus)
Pain Link Frequency Relevance Heat
Hippocampus 370 100.00 Very High Very High Very High
amygdala 87 100.00 Very High Very High Very High
Nucleus accumbens 252 99.84 Very High Very High Very High
Enkephalin 8 99.78 Very High Very High Very High
antagonist 53 99.76 Very High Very High Very High
Anterior cingulate 6 99.74 Very High Very High Very High
Inflammation 37 99.44 Very High Very High Very High
Morphine 127 99.42 Very High Very High Very High
Spinal cord 3 99.20 Very High Very High Very High
withdrawal 108 99.16 Very High Very High Very High
Disease Link Frequency Relevance Heat
Stress 546 100.00 Very High Very High Very High
Anxiety Disorder 132 100.00 Very High Very High Very High
Nociception 23 99.92 Very High Very High Very High
Targeted Disruption 522 99.50 Very High Very High Very High
INFLAMMATION 40 99.44 Very High Very High Very High
Shock 50 99.16 Very High Very High Very High
Scrapie 8 99.06 Very High Very High Very High
Pain 8 98.84 Very High Very High Very High
Cognitive Disorder 89 98.56 Very High Very High Very High
Apoptosis 406 97.56 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Consequently, the 90% reduction of CREB in CREBalphaDelta mutant mice differentially affects CREB phosphorylation and induction of downstream targets of CREB in the NAc and VTA.
Negative_regulation (reduction) of CREB in NAc associated with ventral tegmentum and nucleus accumbens
1) Confidence 0.59 Published 2003 Journal J. Neurochem. Section Abstract Doc Link 14622103 Disease Relevance 0 Pain Relevance 0.72
Chronic but not acute treatment with imipramine reduced CREB activity which was most pronounced in the hippocampus.
Negative_regulation (reduced) of CREB in hippocampus associated with hippocampus
2) Confidence 0.58 Published 2007 Journal PLoS ONE Section Body Doc Link PMC1855984 Disease Relevance 0.71 Pain Relevance 0.34
Interestingly, as reviewed by Tardito et al.[15] particularly the specific pro-noradrenergic antidepressants such as desimipramine and reboxetine have been shown to inhibit CREB activity[43], whereas selective serotonin reuptake inhibitors (SSRI) induce an activation of CREB.
Negative_regulation (inhibit) of CREB associated with antidepressant and ssri
3) Confidence 0.58 Published 2007 Journal PLoS ONE Section Body Doc Link PMC1855984 Disease Relevance 0.31 Pain Relevance 0.57
Next, we wanted to determine if inhibiting CREB activity, by overexpressing mCREB, might affect the survival of cingulate neurons.
Negative_regulation (inhibiting) of CREB in neurons
4) Confidence 0.57 Published 2006 Journal Mol Pain Section Body Doc Link PMC1459854 Disease Relevance 0.42 Pain Relevance 0.54
To determine if CREB activity contributes to neuronal survival in adult anterior cingulate neurons, we inhibited CREB activity by over-expressing pCMV-CREB133, a dominant negative CREB (mCREB), in the ACC of adult mice using a newly developed method of microelectroporation [16].
Negative_regulation (inhibited) of CREB in anterior associated with anterior cingulate cortex and anterior cingulate
5) Confidence 0.57 Published 2006 Journal Mol Pain Section Body Doc Link PMC1459854 Disease Relevance 0.56 Pain Relevance 0.42
Inhibition of CREB activity impaired behavioral performance in various memory tests across different species, while the overexpression of CREB facilitated long-term memory [2,3].
Negative_regulation (Inhibition) of CREB
6) Confidence 0.57 Published 2006 Journal Mol Pain Section Body Doc Link PMC1459854 Disease Relevance 0.24 Pain Relevance 0.12
Loss of neurons due to inhibition of CREB activity may provide a molecular mechanism for cellular loss in forebrain regions related to various mental illnesses.
Negative_regulation (inhibition) of CREB in forebrain
7) Confidence 0.57 Published 2006 Journal Mol Pain Section Body Doc Link PMC1459854 Disease Relevance 0.35 Pain Relevance 0.03
Downregulation of total CREB protein in the rat spinal cord by antisense-oligonucleotides resulted in antinociceptive effects.
Negative_regulation (Downregulation) of CREB in spinal cord associated with antinociceptive and spinal cord
8) Confidence 0.57 Published 2007 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 17692820 Disease Relevance 0.73 Pain Relevance 0.38
Mice with prenatal central loss of CREB and CREM died at P1, as they did not suckle for milk; brain structures in these mice were unaffected, but cell density was markedly diminished, largely due to apoptosis; expected Mendelian ratios were observed however.
Negative_regulation (loss) of CREB in brain structures associated with apoptosis
9) Confidence 0.57 Published 2007 Journal Current Neuropharmacology Section Body Doc Link PMC2656817 Disease Relevance 0.55 Pain Relevance 0.16
Mice with postnatal central loss of CREB and CREM displayed an abnormal phenotype of retraction of limbs when suspended for 20s, characterising a neurological impairment owing to neurodegeneration, and considerable progressive atrophy of the dorsolateral striatum and CA1 hippocampal neurons; widespread astrogliosis was revealed (glial cell apoptosis) in dorsolateral striatum, CA1, DG and some in amygdala, cortex and thalamus, although a single copy of Crem prevented this (suggesting accomodation for loss of CREB); expected Mendelian ratios were observed.
Negative_regulation (loss) of CREB in limbs associated with frailty, thalamus, apoptosis and amygdala
10) Confidence 0.57 Published 2007 Journal Current Neuropharmacology Section Body Doc Link PMC2656817 Disease Relevance 0.57 Pain Relevance 0.20
Mice with postnatal central loss of CREB and CREM displayed an abnormal phenotype of retraction of limbs when suspended for 20s, characterising a neurological impairment owing to neurodegeneration, and considerable progressive atrophy of the dorsolateral striatum and CA1 hippocampal neurons; widespread astrogliosis was revealed (glial cell apoptosis) in dorsolateral striatum, CA1, DG and some in amygdala, cortex and thalamus, although a single copy of Crem prevented this (suggesting accomodation for loss of CREB); expected Mendelian ratios were observed.
Negative_regulation (loss) of CREB in striatum associated with frailty, thalamus, apoptosis and amygdala
11) Confidence 0.57 Published 2007 Journal Current Neuropharmacology Section Body Doc Link PMC2656817 Disease Relevance 0.62 Pain Relevance 0.16
The nestin promoter/enhancer is associated with widespread central deletion of the Creb gene, as nestin expresses from embryonic stage in all brain regions before separation of neuronal and glial lineages [68], with CREB loss observed in neurons and glial cells.
Negative_regulation (loss) of CREB in neuronal
12) Confidence 0.57 Published 2007 Journal Current Neuropharmacology Section Body Doc Link PMC2656817 Disease Relevance 0.24 Pain Relevance 0.26
is an 8.5kb promoter expressed in forebrain neurons from approximately P7 [5, 68] and this model has shown CREB loss in almost eighty percent of forebrain neurons.
Negative_regulation (loss) of CREB in neurons
13) Confidence 0.57 Published 2007 Journal Current Neuropharmacology Section Body Doc Link PMC2656817 Disease Relevance 0.26 Pain Relevance 0.48
While papaverine treatment reduced CREB protein levels in the hippocampus and striatum, fluoxetine increased CREB in the hippocampus.
Negative_regulation (reduced) of CREB in striatum associated with hippocampus and fluoxetine
14) Confidence 0.54 Published 2008 Journal Eur Neuropsychopharmacol Section Abstract Doc Link 17913473 Disease Relevance 1.00 Pain Relevance 0.59
Excision of exon 10 from Creb1 leads to translation of CREB deficient in DNA binding and dimerization functional domains, such that the protein is unstable and thus, there is loss of CREB [68].
Negative_regulation (loss) of CREB
15) Confidence 0.50 Published 2007 Journal Current Neuropharmacology Section Body Doc Link PMC2656817 Disease Relevance 0.14 Pain Relevance 0
These results further emphasize the role of CREB in stress-induced gene expression and suggest furthermore that inhibition of stress-induced CREB activity may be a common mechanism of action of SSRIs underlying their antidepressive effect.
Negative_regulation (inhibition) of CREB associated with stress and ssri
16) Confidence 0.43 Published 2010 Journal Eur. J. Pharmacol. Section Abstract Doc Link 20122921 Disease Relevance 0.62 Pain Relevance 0.53
The behavioral and biochemical consequences of opiate withdrawal were investigated in mice with a genetic disruption of the alpha and Delta isoforms of the cAMP-responsive element-binding protein (CREB).
Spec (investigated) Negative_regulation (disruption) of cAMP-responsive element-binding protein associated with opiate and withdrawal
17) Confidence 0.43 Published 1996 Journal Science Section Abstract Doc Link 8662559 Disease Relevance 0 Pain Relevance 0.98
The notion that imipramine affects gene transcription through inhibition of CREB is also supported by the observation that various antidepressants down-regulate components of the cAMP signalling pathway, e.g. adenylate cyclase activity in the limbic forebrain[44].
Negative_regulation (inhibition) of CREB in forebrain associated with antidepressant
18) Confidence 0.43 Published 2007 Journal PLoS ONE Section Body Doc Link PMC1855984 Disease Relevance 0.55 Pain Relevance 0.54
Knockdown of CREB in slice cultures from floxed CREB mice similarly decreased LC excitability.
Negative_regulation (Knockdown) of CREB associated with locus ceruleus
19) Confidence 0.43 Published 2010 Journal Proc. Natl. Acad. Sci. U.S.A. Section Abstract Doc Link 20837544 Disease Relevance 0.09 Pain Relevance 1.20
In addition, the immunosuppressant cyclosporine A inhibits CREB transactivational activity despite of its phosphorylation of Ser-133[16].
Negative_regulation (inhibits) of CREB
20) Confidence 0.42 Published 2007 Journal PLoS ONE Section Body Doc Link PMC1855984 Disease Relevance 0.23 Pain Relevance 0

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