Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Occasionally, multiple names are given to the same gene/protein. When this happens, different names can be used in subsequent publications, for example in different research areas, sometimes with little or no awareness that the same entity known under a different name may have a major role in another field of science. Recent reports about the protein p11 presented findings that this protein, commonly known as S100A10, may play a crucial role in depression and antidepressant treatment mechanisms. One set of data showed an increased expression of this protein in the brain of mice treated with antidepressants. P11/S100A10 is only one of several S100 proteins expressed in the brain. Interestingly, it has been previously noted that antidepressant treatment increases the brain content of another S100 protein, S100B. It appears that up-regulating the brain content of various S100 proteins might be a common feature of antidepressants. In cells coexpressing S100A10 and S100B, these proteins may interact and exert opposite regulatory roles. Nevertheless, S100A10 is predominantly expressed in certain types of neurons whereas S100B is more abundant in glia. Thus, an interplay among multiple members of the S100 proteins might be important in determining the region and cell specificity of antidepressant mechanisms. Calling the p11 protein by its other name, S100A10, may prompt more investigators from different fields to participate in this new direction of neurobiological research.
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PMID:Nomen est Omen: do antidepressants increase p11 or S100A10? 1672 32

p11 (S100A10) is a member of the S100 protein family and forms a heterotetrameric complex with annexin 2. p11 has also been found to interact with a diverse set of proteins that includes several ion channels and the serotonin 5-HT1B receptor. Several factors such as dexamethasone, growth factors, nitric oxide and antidepressant therapies regulate the expression of p11. Furthermore, studies using mutant mouse models, RNA interference and antisense constructs have implicated p11 in several biological processes; in particular, there is evidence that p11 is involved in the pathophysiology underlying nociception and depression-like states.
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PMID:p11 (S100A10)--an inducible adaptor protein that modulates neuronal functions. 1708 73

Recent rodent models of antidepressant response implicate a novel set of genes in mechanisms of antidepressant action. The authors examined variants in four such genes (KCNK2 (TREK1), SLC18A2 (VMAT2), S100A10, and HDAC5) for association with remission in a large effectiveness trial of antidepressant treatments. Subjects were drawn from the Sequenced Treatment Alternatives to Relieve Depression (STAR(*)D) study, a multicenter, prospective, effectiveness trial in major depressive disorder (MDD). Outpatients with nonpsychotic MDD were initially treated with citalopram for up to 14 weeks; those who did not remit with citalopram were sequentially randomized to a series of next-step treatments, each for up to 12 weeks. Single-nucleotide polymorphisms in four genes were examined for association with remission, defined as a clinician-rated Quick Inventory of Depressive Symptomatology (QIDS-C(16)) score < or =5. Of 1554 participants for whom DNA was available, 565 (36%) reached remission with citalopram treatment. No association with any of the four genes was identified. However, among the 751 who entered next-step treatment, variants in KCNK2 were associated with treatment response (Bonferroni-corrected, gene-based empirical p<0.001). In follow-up analyses, KCNK2 was also associated with effects of similar magnitude for third-step treatment among those with unsatisfactory benefit to both citalopram and one next-step pharmacotherapy (n=225). These findings indicate that genetic variation in KCNK2 may identify individuals at risk for treatment resistance. More broadly, they indicate the utility of animal models in identifying genes for pharmacogenetic studies of antidepressant response.
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PMID:Pharmacogenetic analysis of genes implicated in rodent models of antidepressant response: association of TREK1 and treatment resistance in the STAR(*)D study. 1828 90

Posttraumatic stress disorder (PTSD) is one of the most common psychiatric disorders. Despite the extensive study of the neurobiological correlates of this disorder, the underlying mechanisms of PTSD are still poorly understood. Recently, a study demonstrated that dexamethasone (Dex), a synthetic glucocorticoid, can up-regulate p11, known as S100A10-protein which is down-regulated in patients with depression, (Yao et al., 1999; Huang et al., 2003) a common comorbid disorder in PTSD. These observations led to our hypothesis that traumatic stress may alter expression of p11 mediated through a glucocorticoid receptor. Here, we demonstrate that inescapable tail shock increased both prefrontal cortical p11 mRNA levels and plasma corticosterone levels in rats. We also found that Dex up-regulated p11 expression in SH-SY5Y cells through glucocorticoid response elements (GREs) within the p11 promoter. This response was attenuated by either RU486, a glucocorticoid receptor (GR) antagonist or mutating two of three glucocorticoid response elements (GRE2 and GRE3) in the p11 promoter. Finally, we showed that p11 mRNA levels were increased in postmortem prefrontal cortical tissue (area 46) of patients with PTSD. The data obtained from our work in a rat model of inescapable tail shock, a p11-transfected cell line and postmortem brain tissue from PTSD patients outline a possible mechanism by which p11 is regulated by glucocorticoids elevated by traumatic stress.
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PMID:p11 is up-regulated in the forebrain of stressed rats by glucocorticoid acting via two specific glucocorticoid response elements in the p11 promoter. 1844 Jan 54

The p11 protein (also called S100A10), which plays a pivotal role in the dynamic modulation of serotonergic 1B receptor function, has been implicated in the pathogenesis of major depressive disorder (MDD) and the therapeutic mechanisms of antidepressant action. Humans and mice with depression have lower central p11 levels, and treatment with antidepressant agents raises p11 levels in animals. Furthermore, brain p11 mRNA expression is lower in post mortem brains from patients who were suffering from depression and had committed suicide compared with control subjects who had died from other causes. From the above findings, the p11 gene may be considered a candidate gene for the investigation of MDD susceptibility, response to antidepressants or the likelihood of attempting suicide. Three p11 polymorphisms were genotyped in 470 patients with MDD and 447 normal controls. No significant association with MDD was discovered in single locus or haplotype analyses. The analysis for genotypic effects showed no significant association between any of the three p11 single nucleotide polymorphisms (SNPs) and MDD therapeutic response. With regard to the risk of suicide attempt, 51 of the 470 MDD patients were found to have attempted suicide in the depressive episode during which they were monitored. No significant association with suicide attempt was shown in both the alleles and genotypes of single loci or of haplotypes constructed from these three p11 polymorphisms. Our findings suggest that p11 genetic variants do not play a major role in the MDD susceptibility, antidepressant therapeutic response or the risk of suicide attempt in MDD.
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PMID:Association study of p11 gene with major depressive disorder, suicidal behaviors and treatment response. 1883 10

p11 (S100A10), a member of a large family of S100 proteins, interacts with serotonin receptor 1B (5-HTR1B), modulates 5-HT1B receptor signal transduction, and is required for antidepressant responses to activation of this receptor. In the current study, we investigated the specificity of the interaction between 5-HTR1B and p11 by screening brain-expressed S100 proteins against serotonin and noradrenergic receptors. The data indicate that p11 is unique among its family members for its interactions with defined serotonin receptors. We identify a novel p11-interacting receptor (5-HTR4) and characterize the interaction between p11 and 5-HTR4, demonstrating that (1) p11 and 5-HTR4 mRNA and protein are coexpressed in brain regions that are relevant for major depression, (2) p11 increases 5-HTR4 surface expression and facilitates 5-HTR4 signaling, and (3) p11 is required for the behavioral antidepressant responses to 5-HTR4 stimulation in vivo. The essential role played by p11 in modulating signaling through 5-HT4 as well as 5-HT1B receptors supports the concept that this protein may be a key determinant of vulnerability to depression.
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PMID:Role of p11 in cellular and behavioral effects of 5-HT4 receptor stimulation. 1921

Bipolar disorder (BPD) is characterized by vulnerability to episodic depression and mania and spontaneous cycling. Because of marked advances in candidate-gene and genome-wide association studies, the list of risk genes for BPD is growing rapidly, creating an unprecedented opportunity to understand the pathophysiology of BPD and to develop novel therapeutics for its treatment. However, genetic findings are associated with major unresolved issues, including whether and how risk variance leads to behavioral abnormalities. Although animal studies are key to resolving these issues, consensus is needed regarding how to define and monitor phenotypes related to mania, depression and mood swing vulnerability in genetically manipulated rodents. In this study we discuss multiple facets of this challenging area, including theoretical considerations, available tests, limitations associated with rodent behavioral modeling and promising molecular-behavioral findings. These include CLOCK, glycogen synthase kinase 3beta (GSK-3beta), glutamate receptor 6 (GluR6), extracellular signal-regulated kinase-1 (ERK1), p11 (or S100A10), vesicular monoamine transporter 2 (VMAT2 or SLC18A2), glucocorticoid receptors (GRs), Bcl-2-associated athanogene-1 (BAG1) and mitochondrial DNA polymerase-gamma (POLG). Some mutant rodent strains show behavioral clusters or activity patterns that cross-species phenocopy objective/observable facets of mood syndromes, and changes in these clustered behaviors can be used as outcome measures in genetic-behavioral research in BPD.
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PMID:Translational research in bipolar disorder: emerging insights from genetically based models. 2014 20

P11 (S100A10) has been associated with the pathophysiology of depression both in human and rodent models. Different types of antidepressants have been shown to increase P11 levels in distinct brain regions and P11 gene therapy was recently proven effective in reversing depressive-like behaviours in mice. However, the molecular mechanisms that govern P11 gene expression in response to antidepressants still remain elusive. In this study we report decreased levels of P11, associated with higher DNA methylation in the promoter region, in the prefrontal cortex of the Flinders Sensitive Line (FSL) genetic rodent model of depression. This hypermethylated pattern was reversed to normal, as indicated by the control line, after chronic administration of escitalopram (a selective serotonin reuptake inhibitor; SSRI). The escitalopram-induced hypomethylation was associated with both an increase in P11 gene expression and a reduction in mRNA levels of two DNA methyltransferases that have been shown to maintain DNA methylation in adult forebrain neurons (Dnmt1 and Dnmt3a). In conclusion, our data further support a role for P11 in depression-like states and suggest that this gene is controlled by epigenetic mechanisms that can be affected by antidepressant treatment.
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PMID:Antidepressant treatment is associated with epigenetic alterations in the promoter of P11 in a genetic model of depression. 2168 46

Studies of the multifunctional protein p11 (also known as S100A10) are shedding light on the molecular and cellular mechanisms underlying depression. Here, we review data implicating p11 in both the amplification of serotonergic signalling and the regulation of gene transcription. We summarize studies demonstrating that levels of p11 are regulated in depression and by antidepressant regimens and, conversely, that p11 regulates depression-like behaviours and/or responses to antidepressants. Current and future studies of p11 may provide a molecular and cellular framework for the development of novel antidepressant therapies.
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PMID:p11 and its role in depression and therapeutic responses to antidepressants. 2400 51

The comorbidity of depression and cocaine addiction suggests shared mechanisms and anatomical pathways. Specifically, the limbic structures, such as the nucleus accumbens (NAc), play a crucial role in both disorders. P11 (S100A10) is a promising target for manipulating depression and addiction in mice. We summarized the recent genetic and viral strategies used to determine how the titration of p11 levels within the NAc affects hedonic behavior and cocaine reward learning in mice. In particular, p11 in the ChAT+ cells or DRD1+ MSN of the NAc, controls depressive-like behavior or cocaine reward, respectively. Treatments to counter maladaptation of p11 levels in the NAc could provide novel therapeutic opportunities for depression and cocaine addiction in humans.
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PMID:[Depression and addiction comorbidity: towards a common molecular target?]. 2605 6


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