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

Because of a decrease in central brain-derived neurotrophic factor (BDNF) levels in Alzheimer's disease (AD) and the important role of BDNF in neuronal survival, BDNF may represent a candidate gene conferring susceptibility to AD. Recently, a functional BDNF Val66Met polymorphism has been associated with AD in an Italian population. In the present study, we investigated a possible role of this BDNF polymorphism in the susceptibility of AD or AD onset in a Chinese population. Comparing AD patients and controls, the distribution of the BDNF genotypes and alleles did not differ significantly. The onset age was not significantly different comparing the three BDNF genotype groups. Our negative findings suggest that it is unlikely that the BDNF Val66Met polymorphism plays a major role in the pathogenesis of AD in the Chinese population and do not support previous findings that homozygosity for the 66Val allele confers an increased risk for AD. Further studies with genetic variations in BDNF relating either to AD-associated depression or to the AD treatment response are suggested.
 ...
PMID:Association analysis of brain-derived neurotrophic factor Val66Met polymorphisms with Alzheimer's disease and age of onset. 1473 Jan 94

The issue of neurotrophins is recognized as a new lead in the quest for a deeper understanding of mood disorders. This hypothesis has emerged from experimental evidence suggesting that antidepressant drugs might work by a neuroprotective effect through the stimulation of the neurotrophin expression in distinct regions of the CNS. Endogenous levels of BDNF protein were measured in the serum samples of 118 healthy unrelated volunteers (64 male, 54 female, age: 42.1+/-13.0 years), and the NEO-FFI has been performed in all subjects. BDNF serum values amounted to 16.3+/-7.3 ng/ml. BDNF concentration correlated significantly with age (r=0.182, p=0.048), but showed no gender differences (male 16.1+/-7.2, female 16.5+/-7.4 ng/ml). A negative correlation between the BDNF serum concentration and the depression-related factor neuroticism (r=-0.212, p=0.022) has been found. Low BDNF levels in healthy humans with depressive personality traits might constitute a risk marker, reflecting a personality profilethat is linked to vulnerability to mood disorders. These results provide further support for the hypothesis that BDNF may be central to the development of depressive mood states.
 ...
PMID:BDNF serum concentrations in healthy volunteers are associated with depression-related personality traits. 1473 33

Principal mental disorders affecting the geriatric population include dementia and depression. A lack of trophic support is thought to contribute to the pathology of these disorders. Physical activity and antidepressant treatment increase the expression of brain-derived neurotrophic factor (BDNF) in the young rat hippocampus. Herein, we investigated the responsiveness of the aging rat hippocampus to antidepressant treatment and voluntary exercise. In situ hybridization revealed that, in young animals, exercise, antidepressant treatment, or their combination elevated BDNF mRNA levels in several hippocampal regions, most notably in the CA3, CA4, and dentate gyrus (DG). This effect was rapid (detectable at 2 days) and sustainable to 20 days. In aged (22-month-old) rats, hippocampal responsiveness to antidepressant treatment and exercise was also rapid and sustainable, but evident mostly in the CA1 and CA2. Daily swimming also revealed that small amounts of activity led to marked elevations in hippocampal BDNF mRNA. The differences in regional patterns of BDNF mRNA elevations between young and aged animals observed with running were maintained with this different exercise modality. Our results indicate that the aged brain is responsive to exercise and antidepressant treatment, and changes in regional response patterns may reflect shifts in hippocampal physiology during the lifespan.
 ...
PMID:Exercise, antidepressant treatment, and BDNF mRNA expression in the aging brain. 1475 47

Major depressive disorder (MDD) is a common mental disease with unknown etiology. Recent studies have suggested that decreased brain-derived neurotrophic factor (BDNF) may be implicated in the pathogenesis of MDD. Instead of a decrease in central BDNF, however, studies utilizing genetic depression animal models have found elevated levels of the factor. In the brain, BDNF exerts its influence chiefly by signaling through tyrosine receptor kinase B (Trk-B). In this report, it is suggested that Trk-B pathway down-regulation may be the major pathogenesis for MDD, while stress, which may reduce central BDNF, acts as a precipitation factor to further dampen central BDNF activity and contribute to the development of depression. Further, several possible mechanisms of Trk-B pathway down-regulation, and the implications for this down-regulation in MDD are discussed.
 ...
PMID:Down-regulation of the Trk-B signal pathway: the possible pathogenesis of major depression. 1496 29

The "neurotrophin hypothesis" of depression predicts that depressive disorders in humans coincide with a decreased activity and/or expression of brain-derived neurotrophic factor (BDNF) in the brain. Therefore, we investigated whether mice with a reduced BDNF expression due to heterozygous gene disruption demonstrate depression-like neurochemical changes or behavioral symptoms. BNDF protein levels of adult BDNF(+/-) mice were reduced to about 60% in several brain areas investigated, including the hippocampus, frontal cortex, striatum, and hypothalamus. The content of monoamines (serotonin, norepinephrine, and dopamine) as well as of serotonin and dopamine degradation products was unchanged in these brain regions. By contrast, choline acetyltransferase activity was significantly reduced by 19% in the hippocampus of BDNF(+/-) mice, indicating that the cholinergic system of the basal forebrain is critically dependent on sufficient endogenous BDNF levels in adulthood. Moreover, BDNF(+/-) mice exhibited normal corticosterone and adrenocorticotropic hormone (ACTH) serum levels under baseline conditions and following immobilization stress. In a panel of behavioral tests investigating locomotor activity, exploration, anxiety, fear-associated learning, and behavioral despair, BDNF(+/-) mice were indistinguishable from wild-type littermates. Thus, a chronic reduction of BDNF protein content in adult mice is not sufficient to induce neurochemical or behavioral alterations that are reminiscent of depressive symptoms in humans.
 ...
PMID:Mice with reduced brain-derived neurotrophic factor expression show decreased choline acetyltransferase activity, but regular brain monoamine levels and unaltered emotional behavior. 1496 34

Basic research in rodents has demonstrated that exposure to stress decreases levels of brain-derived neurotrophic factor (BDNF) in brain regions associated with depression. In contrast, antidepressant treatment produces the opposite effect and blocks the effects of stress on BDNF. BDNF upregulation and possibly other neurotrophic/growth factors could reverse or block the atrophy and cell loss that has been observed in rodent stress models and in depressed patients. The morphological alterations observed in depressed patients could result from decreased size or number of glia and/or neurons and may include regulation of adult neurogenesis. This article reviews the primary work leading to a neurotrophic hypothesis of depression and antidepressant action and the cellular mechanisms and signal transduction pathways that underlie these effects.
 ...
PMID:Role of neurotrophic factors in the etiology and treatment of mood disorders. 1500 9

Exercise is increasingly recognized as an intervention that can reduce CNS dysfunctions such as cognitive decline, depression and stress. Previously we have demonstrated that brain-derived neurotrophic factor (BDNF) is increased in the hippocampus following exercise. In this study we tested the hypothesis that exercise can counteract a reduction in hippocampal BDNF protein caused by acute immobilization stress. Since BDNF expression is suppressed by corticosterone (CORT), circulating CORT levels were also monitored. In animals subjected to 2 h immobilization stress, CORT was elevated immediately following, and at 1 h after the cessation of stress, but remained unchanged from baseline up to 24 h post-stress. The stress protocol resulted in a reduction in BDNF protein at 5 and 10 h post-stress that returned to baseline at 24 h. To determine if exercise could prevent this stress-induced reduction in BDNF protein, animals were given voluntary access to running wheels for 3 weeks prior to the stress. Stressed animals, in the absence of exercise, again demonstrated an initial elevation in CORT (at 0 h) and a subsequent decrease in hippocampal BDNF at the 10 h time point. Exercising animals, both non-stressed and stressed, demonstrated circulating CORT and hippocampal BDNF protein levels that were significantly elevated above control values at both time points examined (0 and 10 h post-stress). Thus, the persistently high CORT levels in exercised animals did not affect the induction of BDNF with exercise, and the effect of immobilization stress on BDNF protein was overcome. To examine the role of CORT in the stress-related regulation of BDNF protein, experiments were carried out in adrenalectomized (ADX) animals. BDNF protein was not downregulated as a result of immobilization stress in ADX animals, while there continued to be an exercise-induced upregulation of BDNF. This study demonstrates that CORT modulates stress-related alterations in BDNF protein. Further, exercise can override the negative effects of stress and high levels of CORT on BDNF protein. Voluntary physical activity may, therefore, represent a simple non-pharmacological tool for the maintenance of neurotrophin levels in the brain.
 ...
PMID:Voluntary exercise protects against stress-induced decreases in brain-derived neurotrophic factor protein expression. 1502 38

Electroconvulsive therapy (ECT) remains the treatment of choice for drug-resistant patients with depressive disorders, yet the mechanism for its efficacy remains unknown. Gene transcription changes were measured in the frontal cortex and hippocampus of rats subjected to sham seizures or to 1 or 10 electroconvulsive seizures (ECS), a model of ECT. Among the 3500-4400 RNA sequences detected in each sample, ECS increased by 1.5- to 11-fold or decreased by at least 34% the expression of 120 unique genes. The hippocampus produced more than three times the number of gene changes seen in the cortex, and many hippocampal gene changes persisted with chronic ECS, unlike in the cortex. Among the 120 genes, 77 have not been reported in previous studies of ECS or seizure responses, and 39 were confirmed among 59 studied by quantitative real time PCR. Another 19 genes, 10 previously unreported, changed by <1.5-fold but with very high significance. Multiple genes were identified within distinct pathways, including the BDNF-MAP kinase-cAMP-cAMP response element-binding protein pathway (15 genes), the arachidonic acid pathway (5 genes), and more than 10 genes in each of the immediate-early gene, neurogenesis, and exercise response gene groups. Neurogenesis, neurite outgrowth, and neuronal plasticity associated with BDNF, glutamate, and cAMP-protein kinase A signaling pathways may mediate the antidepressant effects of ECT in humans. These genes, and others that increase only with chronic ECS such as neuropeptide Y and thyrotropin-releasing hormone, may provide novel ways to select drugs for the treatment of depression and mimic the rapid effectiveness of ECT.
 ...
PMID:Electroconvulsive seizures regulate gene expression of distinct neurotrophic signaling pathways. 1502 59

The neurotrophin brain-derived neurotrophic factor (BDNF) is considered to be a key factor for neuronal survival, differentiation and plasticity. According to a proposed hypothetical model BDNF expression might play a central role in the pathogenesis of depression. The BDNF gene is rather complex in its structure and it can express four different mRNA isoforms by alternative splicing, each producing the same protein. This might reflect fine tuning of gene regulation by different signalling networks. Since the BDNF gene has been reported to be upregulated by antidepressants, the expression of the four BDNF mRNA isoforms was measured by real-time quantitative RT-PCR in rat hippocampi after chronic and acute treatment with the antidepressant drug fluoxetine and GR205171, a selective NK-1 receptor antagonist with anxiolytic-like properties. The aim of this study was to test the hypothesis of differential regulation of the mRNA isoforms by those compounds. Our results indicate that the expression of BDNF mRNA isoforms is not affected by chronic or acute treatment with fluoxetine or GR205171.
 ...
PMID:Expression analysis of brain-derived neurotrophic factor (BDNF) mRNA isoforms after chronic and acute antidepressant treatment. 1505 62

The purpose of this review is to integrate what is currently known about the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of mood disorders including major depressive disorder (MDD) and bipolar disorder (BD). We reviewed the pre-clinical and clinical papers demonstrating that BDNF plays a role in the pathophysiology of mood disorders and in the mechanism of action of therapeutic agents. Pre-clinical studies suggest that the expression of BDNF might be a downstream target of antidepressant treatments and mood stabilizers such as lithium and valproate, and that BDNF exerts antidepressant activity in animal models of depression. Furthermore, BDNF protects against stress-induced neuronal damage, and it might affect neurogenesis in the hippocampus, which is thought to be involved in the pathogenesis of mood disorders. Clinical studies have demonstrated that serum levels of BDNF in drug-naive patients with MDD are significantly decreased as compared with normal controls, and that BDNF might be an important agent for therapeutic recovery from MDD. Moreover, recent findings from family-based association studies have suggested that the BDNF gene is a potential risk locus for the development of BD. These findings suggest that BDNF plays a critical role in the pathophysiology of mood disorders and in the activity of therapeutic agents in patients with mood disorders. New agents capable of enhancing BDNF levels may lead aid the development of novel therapeutic drugs for patients with mood disorders.
 ...
PMID:Critical role of brain-derived neurotrophic factor in mood disorders. 1514 21


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>