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 aim was to determine serum levels of prolactin (PRL) and dehydroepiandrosterone sulphate (DHEAS), and to demonstrate a link between PRL or DHEAS and soluble immune mediators in patients with systemic sclerosis (SSc) with different degrees of disease-induced organ involvement. Thirty-one patients with SSc were studied to evaluate 18 possible disease manifestations. In the serum, PRL, DHEAS and soluble immune mediators were determined by ELISA. Compared to SSc with <9 disease manifestations, patients with > or =9 disease manifestations had higher PRL (P = 0.044), higher soluble interleukin 2 receptor (sIL-2R, P = 0.004) and vascular cell adhesion molecule (sVCAM, P = 0.044), and lower DHEAS (P = 0.029). PRL (R(Rank) = 0.490, P = 0.003) and DHEAS (R(Rank) = -0.399, P = 0.013) were significantly correlated with the number of disease manifestations. The inverse correlation between PRL and DHEAS showed a trend (P = 0.059). PRL correlated with sIL-2R (R(Rank) = 0.553, P = 0.001) and sVCAM (R(Rank) = 0.520, P = 0.002). The number of disease manifestations and sIL-2R correlated significantly (R(Rank) = 0.463, P = 0.006). Psychometric variables to examine the presence of depression were not measured, but from the general aspect, the patients were not suffering from major depression which may have influenced our results. In conclusion, this study demonstrates the close association between DHEAS and, particularly, PRL and SSc severity and T-lymphocyte mechanisms.
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PMID:High prolactin and low dehydroepiandrosterone sulphate serum levels in patients with severe systemic sclerosis. 915 34

L1 and Thy-1 are members of the immunoglobulin (Ig) superfamily of cell adhesion molecules (CAMs) that are vital for normal neural development. Abnormalities in CAM expression could lead to the histological abnormalities that have previously been described in the frontal cortex of patients with schizophrenia. A postmortem immunohistochemical study of L1 and Thy-1 in the normal human prefrontal cortex revealed positive immunostaining of axons in all layers of the cortex. Quantifying the intensity of immunostaining in the prefrontal cortex of patients with schizophrenia, bipolar disorder and depression failed to reveal any significant differences when compared to that of normal controls.
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PMID:Immunohistochemical localization of the cell adhesion molecules Thy-1 and L1 in the human prefrontal cortex patients with schizophrenia, bipolar disorder, and depression. 1008 8

Recent studies have revealed that endocytosis and exocytosis of postsynaptic receptors play a major role in the regulation of synaptic function, particularly during long-term potentiation and long-term depression. Interestingly, many of the proteins implicated in exocytosis and endocytosis of synaptic vesicles are also involved in postsynaptic protein cycling. In vertebrates, Amphiphysin is postulated to function during endocytosis in nerve terminals; however, several recent reports using a Drosophila amphiphysin (damph) null mutant have failed to substantiate such a role at fly synapses. In addition, Damph is surprisingly enriched at the postsynapse. Here we used the glutamatergic larval neuromuscular junction to study the synaptic role of Damph. By selectively labeling internal and external pools of the cell adhesion molecule Fasciclin II (FasII), and by using a novel in vivo surface FasII immunocapture protocol, we show that the level of external FasII is decreased in damph mutants although the total level of FasII remains constant. In vivo FasII internalization assays indicate that the reincorporation of FasII molecules into the cell surface is severely inhibited in damph mutants. Moreover, we show that blocking soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) function in postsynaptic muscle cells interferes with FasII exocytosis. These experiments suggest that in Drosophila, Damph functions during SNARE-dependent postsynaptic FasII membrane cycling. This study challenges the notion that synaptic Amphiphysin is involved exclusively in endocytosis and suggests a novel role for this protein in postsynaptic exocytosis.
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PMID:Drosophila amphiphysin functions during synaptic Fasciclin II membrane cycling. 1462 56

Interferon-alpha (IFN-alpha) treatment is frequently complicated by symptoms of depression. The mechanism by which peripherally administered IFN-alpha enters and modulates the central nervous system remains unclear. The cell adhesion molecule ICAM-1 is involved in the regulation of blood-brain barrier (BBB) permeability. ICAM-1 expression was shown to increase during IFN-alpha treatment and recently the expression of ICAM-1 on vascular endothelial cells in the brain was found to be correlated with the development of depression. We therefore hypothesized that soluble ICAM-1 may be involved in the development of IFN-alpha associated depression. In a prospective study, serum levels of soluble ICAM-1 (double sandwich ELISA test) and symptoms of depression (SDS) were measured in 48 patients with malignant melanoma before and during adjuvant IFN-alpha treatment. Both, depression scores and the serum levels of sICAM-1 significantly increased after three months of IFN-alpha treatment compared to baseline levels (p < .001). Patients who developed depression (SDS-index scores > or = 50) after three months of treatment had higher sICAM-1 levels compared to non-depressed patients. Furthermore, sICAM-1 levels were positively correlated with SDS values (r = .367, p = .018). Our data provides evidence for an association between the induction of sICAM-1 and the development of symptoms of depression during IFN-alpha treatment, possibly by enhancing BBB-permeability.
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PMID:Correlation between sICAM-1 and depressive symptoms during adjuvant treatment of melanoma with interferon-alpha. 1533 Nov 26

Proinflammatory cytokines have been linked to depression of myocardial contractility in vivo in patients with acute septic shock and in vitro models employing isolated myocytes exposed to serum from such patients. The key pathways involved in mediating this septic organ dysfunction (cell adhesion molecule expression, inducible nitric-oxide synthase induction, and apoptosis) are known to be regulated by transcription factors STAT1, IRF1, and NF-kappaB. Utilizing a model that mimics human disease, we have demonstrated activation of the transcription factors STAT1, IRF1, and NF-kappaB in human fetal myocytes exposed to human septic serum. Both reporter and electrophoretic mobility shift assays demonstrated a 5-19-fold increase in activation of transcription factors STAT1, IRF1, and NF-kappaB in response to incubation with human septic serum. The addition of human septic serum to human fetal myocytes induced apoptosis in human fetal myocytes and activation of the mitogen-activated protein kinase c-Jun NH -terminal kinase and caspase 1 as measured by Western blot. These data suggest that transcription factor activation and early myocyte apoptosis play a mechanistic role in septic myocardial depression and sepsis-induced organ dysfunction.
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PMID:Human serum from patients with septic shock activates transcription factors STAT1, IRF1, and NF-kappaB and induces apoptosis in human cardiac myocytes. 1622 33

The cell adhesion molecule N-cadherin has been proposed to regulate synapse formation in mammalian central neurons. This is based on its synaptic localization enabling alignment of presynaptic and postsynaptic specializations by an adhesion mechanism. However, a potential role of N-cadherin in regulating synaptic transmission has remained elusive. In this paper, a functional analysis of N-cadherin knock-out synapses was enabled by in vitro neuronal differentiation of mouse embryonic stem cells circumventing the early embryonic lethality of mice genetically null for N-cadherin. In our in vitro system, initial synapse formation was not altered in the absence of N-cadherin, which might be attributable to compensatory mechanisms. Here, we demonstrate that N-cadherin is required for regulating presynaptic function at glutamatergic synapses. An impairment in the availability of vesicles for exocytosis became apparent selectively during high activity. Short-term plasticity was strongly altered with synaptic depression enhanced in the absence of N-cadherin. Most intriguingly, facilitation was converted to depression under specific stimulation conditions. This indicates an important role of N-cadherin in the control of short-term plasticity. To analyze, whether N-cadherin regulates presynaptic function by a transsynaptic mechanism, we studied chimeric cultures consisting of wild-type neocortical neurons and ES cell-derived neurons. With N-cadherin absent only postsynaptically, we observed a similar increase in short-term synaptic depression as found in its complete absence. This indicates a retrograde control of short-term plasticity by N-cadherin. In summary, our results revealed an unexpected involvement of a synaptic adhesion molecule in the regulation of short-term plasticity at glutamatergic synapses.
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PMID:N-cadherin transsynaptically regulates short-term plasticity at glutamatergic synapses in embryonic stem cell-derived neurons. 1680 26

Antidepressants protect against hippocampal volume loss in humans and reverse stress-induced atrophic changes in animals thus supporting the hypothesis that the pathophysiology of stress-related disorders such as depression involves reductions in neuronal connectivity and this effect is reversible by antidepressant treatment. However, it is unclear which brain areas demonstrate such alterations in plasticity in response to antidepressant treatment. The aim of the present study was to examine the effect of antidepressant treatment on the expression of three plasticity-associated marker proteins, the polysialylated form of nerve cell adhesion molecule (PSA-NCAM), phosphorylated cyclic-AMP response element binding protein (pCREB) and growth-associated protein 43 (GAP-43), in the rat brain. To this end, rats were treated either acutely (60 min) or chronically (21 days) with imipramine (30 and 15 mg/kg, respectively) and the expression of PSA-NCAM, pCREB, and GAP-43 was assessed using immunohistochemistry. Initial mapping revealed that chronic imipramine treatment increased expression of these plasticity-associated proteins in the hippocampus, medial prefrontal cortex and piriform cortex but not in the other brain regions examined. Since PSA-NCAM and pCREB are expressed in recently-generated neurons in the dentate gyrus, it is likely that chronic imipramine treatment increased their expression in the hippocampus at least partially by increasing neurogenesis. In contrast, since chronic imipramine treatment is not associated with neurogenesis in the medial prefrontal cortex, increased expression of PSA-NCAM and pCREB in the prelimbic cortex implicates changes in synaptic connectivity in this brain region. Acute treatment with imipramine increased the number of pCREB positive nuclei in the hippocampus and the prefrontal cortex but did not alter expression of GAP-43 or PSA-NCAM in any of the brain regions examined. Taken together, the results of the present study suggest that antidepressant treatment increases synaptic plasticity and connectivity in brain regions associated with mood disorders.
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PMID:Chronic antidepressant treatment selectively increases expression of plasticity-related proteins in the hippocampus and medial prefrontal cortex of the rat. 1704 69

Adhesive and repellent molecular cues guide migrating cells and growing neurites during development. They also contribute to synaptic function, learning and memory in adulthood. Here, we review the roles of cell adhesion molecules of the immunoglobulin superfamily (Ig-CAMs) and semaphorins (some of which also contain Ig-like domains) in regulation of synaptic transmission and plasticity. Interestingly, among the seven studied Ig-CAMs, the neuronal cell adhesion molecule proved to be important for all tested forms of hippocampal plasticity, while its associated unusual glycan polysialic acid is necessary and sufficient part for synaptic plasticity only at CA3-CA1 synapses. In contrast, Thy-1 and L1 specifically regulate long-term potentiation (LTP) at synapses formed by entorhinal axons in the dentate gyrus and cornu ammonis, respectively. Contactin-1 is important for long-term depression but not for LTP at CA3-CA1 synapses. Analysis of CHL1-deficient mice illustrates that at intermediate stages of development a deficit in a cell adhesion molecule is compensated but appears as impaired LTP during early and late postnatal development. The emerging mechanisms by which adhesive Ig-CAMs contribute to synaptic plasticity involve regulation of activities of NMDA receptors and L-type Ca2+ channels, signaling via mitogen-activated protein kinase p38, changes in GABAergic inhibition and motility of synaptic elements. Regarding repellent molecules, available data for semaphorins demonstrate their activity-dependent regulation in normal and pathological conditions, synaptic localization of their receptors and their potential to elevate or inhibit synaptic transmission either directly or indirectly.
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PMID:Modulation of synaptic transmission and plasticity by cell adhesion and repulsion molecules. 1967 6

Persistent changes in spine shape are coupled to long-lasting synaptic plasticity in hippocampus. The molecules that coordinate such persistent structural and functional plasticity are unknown. Here, we generated mice in which the cell adhesion molecule N-cadherin was conditionally ablated from postnatal, excitatory synapses in hippocampus. We applied to adult mice of either sex a combination of whole-cell recording, two-photon microscopy, and spine morphometric analysis to show that postnatal ablation of N-cadherin has profound effects on the stability of coordinated spine enlargement and long-term potentiation (LTP) at mature CA1 synapses, with no effects on baseline spine density or morphology, baseline properties of synaptic neurotransmission, or long-term depression. Thus, N-cadherin couples persistent spine structural modifications with long-lasting synaptic functional modifications associated selectively with LTP, revealing unexpectedly distinct roles at mature synapses in comparison with earlier, broader functions in synapse and spine development.
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PMID:Persistence of coordinated long-term potentiation and dendritic spine enlargement at mature hippocampal CA1 synapses requires N-cadherin. 2066 83

Attention-deficit/hyperactivity disorder (ADHD) is a common, early onset and enduring neuropsychiatric disorder characterized by developmentally inappropriate inattention, hyperactivity, increased impulsivity and motivational/emotional dysregulation with similar prevalence rates throughout different cultural settings. Persistence of ADHD into adulthood is associated with considerable risk for co-morbidities such as depression and substance use disorder. Although the substantial heritability of ADHD is well documented the etiology is characterized by a complex coherence of genetic and environmental factors rendering identification of risk genes difficult. Genome-wide linkage as well as single nucleotide polymorphism (SNP) and copy-number variant (CNV) association scans recently allow to reliably define aetiopathogenesis-related genes. A considerable number of novel ADHD risk genes implicate biological processes involved in neurite outgrowth and axon guidance. Here, we focus on the gene encoding Cadherin-13 (CDH13), a cell adhesion molecule which was replicably associated with liability to ADHD and related neuropsychiatric conditions. Based on its unique expression pattern in the brain, we discuss the molecular structure and neuronal mechanisms of Cadherin-13 in relation to other cadherins and the cardiovascular system. An appraisal of various Cadherin-13-modulated signaling pathways impacting proliferation, migration and connectivity of specific neurons is also provided. Finally, we develop an integrative hypothesis of the mechanisms in which Cadherin-13 plays a central role in the regulation of brain network development, plasticity and function. The review concludes with emerging concepts about alterations in Cadherin-13 signaling contributing to the pathophysiology of neurodevelopmental disorders.
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PMID:Impact of the ADHD-susceptibility gene CDH13 on development and function of brain networks. 2279


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