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)

Depression is a debilitating mental disease affecting a large population worldwide, the pathophysiological mechanisms of which remain incompletely understood. Prenatal infection and associated activation of the maternal immune system (MIA) are prominently related to an increased risk for the development of several psychiatric disorders including schizophrenia and autism in the offsprings. However, the role of MIA in the etiology of depression and its neurobiological basis are insufficiently investigated. Here we induced MIA in mice by challenge with polyinosinic:polycytidylic phosphate salt-a synthetic analog of double-stranded RNA, which enhances maternal levels of the cytokine interleukin-6 (IL-6)-and demonstrate a depression-like behavioral phenotype in adult offsprings. Adult offsprings additionally show deficits in cognition and hippocampal long-term potentiation (LTP) accompanied by disturbed proliferation of newborn cells in the dentate gyrus and compromised neuronal maturation and survival. The behavioral, neurogenic and functional deficiencies observed are associated with reduced hippocampal expression of vascular endothelial growth factor (VEGF)A-VEGFR2. IL-6-STAT3-dependent aberrant VEGFA-VEGFR2 signaling is proposed as neurobiological mechanism mediating the effects of MIA on the developing fetal brain and ensuing consequences in adulthood.
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PMID:Long-term effects of maternal immune activation on depression-like behavior in the mouse. 2454 78

Decreased concentrations of plasma brain-derived neurotrophic factor (BDNF) and serum BDNF have been proposed to be a state marker of depression and a biological indicator of loaded psychosocial stress. Stress evaluations of participants in military mission are critically important and appropriate objective biological parameters that evaluate stress are needed. In military circumstances, there are several problems to adopt plasma BDNF concentration as a stress biomarker. First, in addition to psychosocial stress, military missions inevitably involve physical exercise that increases plasma BDNF concentrations. Second, most participants in the mission do not have adequate quality or quantity of sleep, and sleep deprivation has also been reported to increase plasma BDNF concentration. We evaluated plasma BDNF concentrations in 52 participants on a 9-week military mission. The present study revealed that plasma BDNF concentration significantly decreased despite elevated serum enzymes that escaped from muscle and decreased quantity and quality of sleep, as detected by a wearable watch-type sensor. In addition, we observed a significant decrease in plasma vascular endothelial growth factor (VEGF) during the mission. VEGF is also neurotrophic and its expression in the brain has been reported to be up-regulated by antidepressive treatments and down-regulated by stress. This is the first report of decreased plasma VEGF concentrations by stress. We conclude that decreased plasma concentrations of neurotrophins can be candidates for mental stress indicators in actual stressful environments that include physical exercise and limited sleep.
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PMID:Decreased plasma brain-derived neurotrophic factor and vascular endothelial growth factor concentrations during military training. 2458 90

Recent studies suggest that the angiogenic cytokine vascular endothelial growth factor (VEGF) is involved in the pathogenesis of depression. However, only a few studies have investigated serum VEGF levels in individuals with depression, or the possible association between genetic variants within the VEGF gene and depression. The purpose of the present study was to investigate differences between serum VEGF levels in individuals with depression vs. control individuals, and associations between genetic markers located within VEGF and depression. In addition, determinants of the serum VEGF levels were identified. One-hundred and fifty-five depressed subjects and 280 controls were included in the study. All individuals returned a questionnaire and participated in a semi-structured diagnostic interview. Eleven single nucleotide polymorphisms were successfully analysed. VEGF levels were measured in serum by immunoassay and independent determinants of the serum VEGF level were assessed by generalized linear models.The main findings were that depression, severity of depression, previous depressive episodes, age and body mass index (BMI) were associated with higher serum VEGF levels. The genetic marker rs10434 was significantly associated with depression after correction for multiple testing, but not with the serum VEGF level. Our final model included depression and BMI as predictors of serum VEGF levels. Our study suggests a role for circulating serum VEGF in depression. Furthermore, our data also demonstrate that other factors than a diagnosis of depression influence the serum VEGF level. The importance of these factors should be emphasized when studies are compared.
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PMID:Depression and BMI influences the serum vascular endothelial growth factor level. 2463 31

Elevated levels of vascular endothelial growth factor (VEGF) are observed in conditions with vessel and neuron damage or pathological arborization and can therefore be detected in chronic inflammatory process, cardiovascular disease and depression. Hyperlipidemia and cigarette smoking are two factors that have been implicated in endothelial damage. The high comorbidity between cardiovascular disease and major depression disorder (MDD) prompted us to study the effect of cigarette smoking, hyperlipidemia and statin treatment on the VEGFA mRNA and protein expression levels measured in MDD patients. We analyzed 38 MDD patients and 38 healthy control individuals and observed that the MDD group had a significantly higher VEGFA mRNA level and protein serum concentration (P=0.001; P<0.001, respectively). We found no significant association between VEGFA expression at the mRNA or protein level and cigarette smoking, hyperlipidemia or treatment with statins (P>0.05). Interestingly, patients who had attempted suicide had a lower VEGF serum level compared with patients who had not attempted suicide. The translational value of this finding remains unknown. A higher VEGF concentration may play a potentially significant role in the pathogenesis of depression, and the expression level appears to be unaffected by additional factors.
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PMID:Vascular endothelial growth factor A gene expression level is higher in patients with major depressive disorder and not affected by cigarette smoking, hyperlipidemia or treatment with statins. 2471 46

Post-stroke depression (PSD) is a prevalent complex psychiatric disorder that causes delay to functional recovery from rehabilitation and also increases cognitive impairment. The etiology of PSD remains controversial and appears to be physical and psycho-social in origin, alone or in combination. The causes of PSD as well as the mechanisms conferring beneficial antidepressant effects in the context of ischemic brain injury are still unknown. In addition, appropriate treatment strategies for therapy to prevent stroke-induced depression-like behavior remain to be developed. This paper, therefore, proposes two hypotheses for post-stroke depression: The inflammatory hypothesis, which is the increased production of proinflammatory cytokines resulting from brain ischemia in cerebral areas causing the pathogenesis of post-stroke depression and the glutamate hypothesis, where the excess glucocorticoids released from stress-induced over-activation of hypothalamus-pituitary-adrenal (HPA) lead to dysfunction of glutamatergic transmission. Neurotrophins, especially brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) both play various roles in the central nervous system (CNS), attenuate apoptosis in cultured neurons, stimulate neurogenesis and increase survival and protect neuronal tissues from cell death induced by ischemia or depression. We also touch upon recent treatment strategies including inhibition of pro-inflammatory cytokines, SSRI, neurotrophins and cell-based therapies. In the present review, we provide an overview of recent evidence concerning the mechanisms of post-stroke depression and propose four prospective treatment strategies so as to provide references for clinical evidence-based medications.
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PMID:Systematic hypothesis for post-stroke depression caused inflammation and neurotransmission and resultant on possible treatments. 2487 79

Proteinuria is not only a sign of kidney damage but is also involved in the progression of renal disease as an independent pathologic factor. Although patients with mutated type 1 cannabinoid receptors (CB1) polymorphism are associated with renal microvascular damage, the biologic role of CB1 signaling in proteinuria remains uncharacterized till now. Herein, we investigate whether CB1 participates in glomerular proteinuria in CB1 transgenic mice and treatment with CB1 agonist WIN55212-2 rat, neither of which are diabetic models. The CB1 transgenic mice and rats treated with CB1 agonist WIN55212-2 had higher kidney weight and urinary protein concentrations but not blood glucose levels compared with the wild-type group. A combination of laser-capture microsdissection, quantitative reverse transcription-polymerase chain reaction, immunoblotting and immunohistochemical validation revealed that CB1 transgenic mice and rats treated with CB1 agonist WIN55212-2 had higher vascular endothelial growth factor (VEGF) expression in renal glomeruli than that of the wild-type group. Geneticorpharmacological activation of CB1 by transgenic CB1 mice or treatment with WIN55212-2 reduced nephrin expression in the renal glomeruli compared with that of the wild-type group in the glomerular mesanglium. Taken together, CB1 transgenic mice and rats treated with CB1 agonist WIN55212-2 induced proteinuria with upregulation of CB1 resulting in impaired nephrin expression, by inducing excess VEGF reaction in the renal glomeruli. Genetic and pharmacological manipulation of CB1 signaling revealed VEGF-dependent nephrin depression of glomerulopathy. Controlling CB1 activity can be used an alternative strategy for sustaining renal function in the presence of CB1 activation.
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PMID:Induction of proteinuria by cannabinoid receptors 1 signaling activation in CB1 transgenic mice. 2547 24

Prenatal stress and depression affects 10-25% of pregnant women and is associated with disruption of fetal neurodevelopment, higher rates of placental abnormalities, preeclampsia, spontaneous abortion, or preterm birth. Markers of genetic vulnerability are catechol-O-methyltransferase, monoamine oxidase-A, variation of serotonin transporters, low levels of dopamine-beta-hydroxylase, and brain derived neurotrophic factor Val66Met (BDNF), while hyperactivity of HPA (hypothalamic-pituitary-adrenal) axis and massive release of endogenous cortisol, regulated by metalloproteinase-1, -2, -3 and -9, and are involved both in depressive symptoms and neurodevelopmental abnormalities in fetus. In women with prenatal stress and depression which suffered spontaneous abortion were observed placental abnormalities as regular shape and necrotic villi, decidua with large areas of necrosis, acute inflammation and effusion areas correlated with increase in proinflammatory factors, immune deficit and infections, hyaline type fibrosis, intervilos and deciduous intense hemorrhage, associated with increase of vascular endothelial growth factor. Taking into account the important societal and economic costs becomes important for an interdisciplinary approach, in which pregnancy and its risks are a central point for women mental health.
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PMID:Prenatal depression and stress - risk factors for placental pathology and spontaneous abortion. 2560 99

Coronary heart disease (CHD) and depression are very common and often co-existing disorders. In addition to psychological and social morbidity, depression exacerbates adverse cardiac outcomes in CHD patients. Inflammation has been proposed as one of the mechanisms involved in the association between these two debilitating diseases. Therefore, the present study aimed to evaluate inflammatory responses as well as to investigate the pathophysiological mechanisms underlying the putative inflammatory activation in CHD patients with and without depression, by assessing the function of two important biological factors regulating inflammation, the hypothalamus-pituitary-adrenal (HPA) axis and the glucocorticoid receptor (GR). Eighty-three CHD patients with (n=28) and without (n=55) comorbid depression were recruited from primary care services in South London. Depression status was assessed by means of Clinical Interview Schedule Revised for diagnosis of depression, and Beck Depression Inventory for the presence of depressive symptoms. Serum C-reactive protein (CRP), plasma vascular endothelial growth factor (VEGF), and plasma and salivary cortisol were measured using commercially available ELISA kits. Gene expression of GR and interleukin-6 (IL-6) were conducted via qPCR. GR sensitivity was evaluated in vitro in isolated peripheral blood mononuclear cells using the dexamethasone inhibition of lipopolysaccharide-stimulated IL-6 levels. Serum levels of kynurenine pathway metabolites were measured using high performance liquid chromatography. Our results show that CHD patients with depression had higher levels of CRP, IL-6 gene expression, and VEGF compared with CHD non-depressed, as well as lower plasma and saliva cortisol levels. The CHD depressed group also exhibited a reduction in GR expression and sensitivity. Finally, tryptophan levels were significantly lower in patients with depression, who also showed an increased kynurenine/tryptophan ratio. In conclusion, CHD patients with depression had elevated levels of inflammation in the context of HPA axis hypoactivity, GR resistance, and increased activation of the kynurenine pathway. Reduced cortisol bioavailability and attenuated glucocorticoid responsiveness due to decreased expression and sensitivity of GR may lead to insufficient glucocorticoid signaling and thus elevation of inflammation in these patients.
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PMID:Insufficient glucocorticoid signaling and elevated inflammation in coronary heart disease patients with comorbid depression. 2568 98

Bedridden patients develop atrophied muscles, their daily activities greatly reduced, and some display a depressive mood. Patients who are able to receive physical rehabilitation sometimes show surprising clinical improvements, including reduced depression and attenuation of other stress-related behaviors. Regenerative medicine has advanced two major stem cell-based therapies for CNS disorders, namely, transplantation of exogenous stem cells and amplification of endogenous neurogenesis. The latter strategy embraces a natural way of reinnervating the damaged brain and correcting the neurological impairments. In this study, we discussed how immobilization-induced disuse atrophy, using the hindlimb suspension model, affects neurogenesis in rats. The overarching hypothesis is that immobilization suppresses neurogenesis by reducing the circulating growth or trophic factors, such as vascular endothelial growth factor or brain-derived neurotrophic factor. That immobilization alters neurogenesis and stem cell differentiation in the CNS requires characterization of the stem cell microenvironment by examining the trophic and growth factors, as well as stress-related proteins that have been implicated in exercise-induced neurogenesis. Although accumulating evidence has revealed the contribution of "increased" exercise on neurogenesis, the reverse paradigm involving "lack of exercise," which mimics pathological states (e.g., stroke patients are often immobile), remains underexplored. This novel paradigm will enable us to examine the effects on neurogenesis by a nonpermissive stem cell microenvironment likely produced by lack of exercise. BrdU labeling of proliferative cells, biochemical assays of serum, cerebrospinal fluid and brain levels of trophic factors, growth factors, and stress-related proteins are proposed as indices of neurogenesis, while quantitative measurements of spontaneous movements will reveal psychomotor components of immobilization. Studies designed to reveal how in vivo stimulation, or lack thereof, alters the stem cell microenvironment are needed to begin to develop treatment strategies for enhancing neurogenesis in bedridden patients.
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PMID:No pain, no gain: lack of exercise obstructs neurogenesis. 2580 58

Recent evidences indicate that cerebral neurotrophic factors like vascular endothelial growth factor plus signaling pathways of the glutamatergic neuroreceptor system (L-Glu) are determinant modulators of depression-like states. In the present study, the type of interaction(s) exerted by the AMPAergic antagonist, 6-cyano-7-nitroquinoxalin-2,3-dione (CNQX) and the brain derived neurotrophic factor (BDNF) on depression-like behaviors in hamsters (Mesocricetus auratus) were investigated. Sub-chronic administration of BDNF in the hippocampal dentate gyrus (DG) of stressed hamsters was responsible for very evident (p<0.001) sucrose consumption along with notably elevated swimming bouts and reduced immobility states in the forced swim test (FST). Meanwhile, CNQX displayed evident anxiolytic actions in the elevated plus maze (EPM) as shown by marked (p<0.01) increases of movements to and from both arms. Interestingly cerebral neurodegeneration events, which are viewed during depression states, were reduced following treatment with both compounds. Contextually, marked mRNA expression levels of the BDNF receptor (tropomyosin-related kinase B; TrkB) were detected in DG and the oriens-pyramidalis of HIP (Or-Py) while a moderate (p<0.05) up-regulation was registered in the amygdalar central nucleus (CeA) and the hypothalamic ventromedial nucleus (VMH) of hamsters treated with BDNF. Similarly, this treatment caused moderate increases of the major stress protein (Hsp70) in DG and Or-Py. Conversely, while CNQX induced similar TrkB expression levels, it instead accounted for a moderate reduction of Hsp70 mRNAs in the same brain areas. Overall these results support crucial roles played by BDNF and AMPAergic neurosignaling mechanisms during distinct adaptive responses of depression- and anxiety-like states in hamsters.
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PMID:Exposure to sub-chronic unpredictable stress accounts for antidepressant-like effects in hamsters treated with BDNF and CNQX. 2640 18


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