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)

The pathophysiology of depression remains enigmatic, although abnormalities in serotonin signaling have been implicated. We have found that the serotonin 1B receptor [5-hydroxytryptamine (5-HT1B) receptor] interacts with p11. p11 increases localization of 5-HT1B receptors at the cell surface. p11 is increased in rodent brains by antidepressants or electroconvulsive therapy, but decreased in an animal model of depression and in brain tissue from depressed patients. Overexpression of p11 increases 5-HT1B receptor function in cells and recapitulates certain behaviors seen after antidepressant treatment in mice. p11 knockout mice exhibit a depression-like phenotype and have reduced responsiveness to 5-HT1B receptor agonists and reduced behavioral reactions to an antidepressant.
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PMID:Alterations in 5-HT1B receptor function by p11 in depression-like states. 1640 Jan 39

The adrenergic system has been implicated in the etiology of depression based on a number of lines of evidence, particularly, the mechanism of some classes of antidepressants which increase the synaptic levels of norepinephrine. Further, several genome scans for mood disorders, both unipolar and bipolar, have indicated linkage to the chromosomal regions of 5q23-q33.3, 8p12-p11.2, 4p16, and 10q24-q26, the location of the adrenergic receptors alpha1B (ADRA1B), beta3 (ADRB3), alpha2C (ADRA2C), alpha2A (ADRA2A), and beta1 (ADRB1). In this manuscript, we report on the relationship of the adrenergic receptors and depression using a family based association approach and 189 families (223 affected children) with childhood-onset mood disorder (COMD) collected in Hungary. We found no significant evidence for an association with any of the 24 markers, in total, tested across these genes using single marker analysis or haplotypes of markers across these genes. The results in the present sample indicate that these nine genes are unlikely to be major susceptibility genes contributing to COMD.
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PMID:Association study of the adrenergic receptors and childhood-onset mood disorders in Hungarian families. 1652 32

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

Major depressive disorder (MDD) is a common disabling psychiatric illness with an unknown etiology. Evidence from animal and human studies suggests that a disturbance in serotonergic (5-HT) activity and/or brain-derived neurotrophic factor (BDNF) signaling may be implicated in the pathogenesis of MDD. Recently, a protein, p11, has been found to increase the number of 5-HT(1B) receptors on the surface of cells and enhance 5-HT(1B) receptor function. Furthermore, mice over-expressing p11 acted as if they were undergoing treatment with antidepressants and p11 knockout mice exhibit a depression-like phenotype and reduced behavioural reactions to an antidepressant. As tissue-type plasminogen activator (tPA)/plasminogen proteolytic cascade is implicated in the cleavage of proBDNF to BDNF, and p11, a component of the Annexin II, which can greatly enhance the activation of plasmin by tPA, it is proposed that p11 may act through the tPA/plasminogen/BDNF pathway to achieve its antidepressant effect. Attempts to confirm this hypothesis may lead to new directions in the study of the pathogenesis of MDD and the development of a novel intervention for this disorder. In addition, BDNF is also implicated in several psychiatric diseases such as schizophrenia, bipolar disorder, attention-deficit hyperactivity disorder and Alzheimer's disease; whether p11 and other components related to the tPA/plasminogen pathway may be related to the pathogenesis of these diseases needs further exploration.
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PMID:The P11, tPA/plasminogen system and brain-derived neurotrophic factor: Implications for the pathogenesis of major depression and the therapeutic mechanism of antidepressants. 1689 Mar 84

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 evidence suggests a potential role for the p11 gene in conferring risk to depressive disorders. p11 has been shown to influence serotonergic transmission, and its expression was found to be reduced in a mouse model of depression, as well as in post-mortem brain tissue from major depressive disorder (MDD) cases. In the present study, we tested for rare variants in p11 by resequencing promoter, exonic and flanking intronic regions in 176 MDD cases and 176 matched controls. We also assessed common variation by genotyping eight single nucleotide polymorphisms (SNPs), seven tag SNPs and one found through resequencing, in 641 cases and 650 controls. Resequencing revealed nine novel rare variants, including a missense mutation (Asp60Glu) observed in one case and one control, and four variants that occurred only in cases and not controls. The number of rare variants in cases did not exceed that expected by chance for the length of sequence analyzed, and also was not significantly greater than that observed in controls. Resequencing also identified two known SNPs, one (rs4845720) of which was significantly more frequent in cases than controls in the resequenced sample (3.1% vs. 0.9%, P = 0.03), though not in the larger sample (3% vs. 2%, P = 0.15). None of the tag SNPs showed any evidence of association. Our results do not support a major role for either common or rare p11 SNPs with MDD. Several limitations of the study are discussed.
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PMID:Investigating the role of p11 (S100A10) sequence variation in susceptibility to major depression. 1751 Sep 52

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

Posttraumatic stress disorder (PTSD) is a severely debilitating anxiety disorder. Over 80% of patients with PTSD also exhibit other psychiatric condition, such as bipolar disorder (BP) or major depression (MDD). Previously, it has been found that p11 mRNA expression was significantly changed in post mortem cortex of patients with PTSD and depression. We hypothesize that p11 mRNA levels in the peripheral blood cells will be a potential biomarker for PTSD with heterogeneity in terms of type of trauma, time since trauma and duration of illness. We examined the peripheral blood mononuclear cell (PBMC) P11 mRNA of patients with PTSD (n=13), major depressive disorder (MDD, n=16), bipolar disorder (BP, n=24), and schizophrenia (SCZ, n=12) or controls (n=14) using quantitative real-time PCR and the circulating levels of cortisol in blood plasma and saliva of PTSD using radioimmunoassay kit CORT-CT2. The Hamilton Rating Scale for Depression (HAMD) and Anxiety (HARS), the Chinese version of the Davidson Trauma Scale-Frequency (CDTS-F) and the Chinese version of the Davidson Trauma Scale-Severity (CDTS-S), and Impact of Event Scale-Revised (IES-R) were administered. We found that patients with PTSD had lower levels of p11 mRNA than control subjects, while those with MDD, BP and SCZ had significantly higher p11 levels than the controls. P11 mRNA levels were positively correlated with the scores of HAMD (r=0.62, p<0.05), CDTS-F (r=0.71, p<0.05) and CDTS-S (r=0.62, p<0.05), while they did not correlate with scores of HARS and IES-R. Basal levels of plasma and salivary cortisol of PTSD patients were not statistically different from those of controls. Our findings suggest that PBMC p11 mRNA expression levels may serve as a potential biomarker to distinguish PTSD from BP, MDD and SCZ.
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PMID:Levels of the potential biomarker p11 in peripheral blood cells distinguish patients with PTSD from those with other major psychiatric disorders. 1938 Jan 52


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