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)

Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor family, and is widely expressed in the adult mammalian brain. Besides its well known neuroprotective activity after traumatic brain injury the evidences regarding its activity dependent release by the pathophysiology of major depression are rapidly replicating. Considering the data that stress plays an important role by the development of depression which is characterized with prominent hippocampal cell death, as well as the well known neuroprotective effects of BDNF, we aimed to investigate the link between the BDNF, stress and depression. Thus we prepared a minireview in order to evaluate the neuroprotective role of BDNF by psychiatric disorders which are characterized with prominent neuronal cell death.
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PMID:Brain-derived neurotrophic factor, stress and depression: a minireview. 1911 10

An increased inflammatory response and deficient synthesis of neurotrophic factors (NTFs) may contribute to the etiology of depression. However, the interrelationship between inflammation and NTFs is unknown. Recently, ethyl-eicosapentaenoate (EPA) has been used to treat depression. The mechanism by which EPA benefits depression is also unclear. Using the olfactory bulbectomized (OB) rat model of depression, this study evaluated two pathways from bulbectomy to the induction of depression-like changes (the inflammation-hypothalamic-pituitary-adrenal axis-stress response pathway and inflammation-nerve growth factor-memory pathway) and the effect of EPA on these pathways. When compared with sham-operated rats fed a control diet, significantly increased locomotor and rearing activities in an "open field," impaired memory in the Morris water maze, increased expression of corticotrophin-releasing factor (CRF), and increased secretion of corticosterone were found in OB rats. mRNA expression of nerve growth factor (NGF) was significantly lower in the hippocampus, and phospholipase A2 (PLA2) was higher in the hypothalamus; this change was associated with increased interleukin-1beta (IL-1beta) and prostaglandin E2 (PGE2) in the serum and brain. EPA treatments normalized these behavioral impairments and reduced CRF expression and corticosterone secretion. EPA also reduced serum concentrations of IL-1beta and PGE2, but reversed NGF reduction. Similar to the effects of EPA, the anti-inflammatory drug celecoxib significantly reduced blood PGE2, IL-1beta, and corticosterone concentrations and increased NGF expression in OB rats. Furthermore, anti-NGF treatment blocked EPA effects on behavior. These results suggest that an interaction exists between inflammation and NGF in the depression model. EPA may improve depression via its anti-inflammation properties and the upregulation of NGF.
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PMID:Increased phospholipase A2 activity and inflammatory response but decreased nerve growth factor expression in the olfactory bulbectomized rat model of depression: effects of chronic ethyl-eicosapentaenoate treatment. 1912 80

Escitalopram (ES-CIT) is a widely used, highly specific antidepressant. Until now there has been very little evidence on how this drug under pathological conditions affects an important feature within the pathophysiology of stress-related disorders such as depression: the endogenous neurotrophins. By using a well-characterized rat model in which chronic stress induces depressive-like behavior, the levels of neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were determined in representative brain regions and serum using a highly sensitive improved fluorometric two-site ELISA system. There was a significant increase of BDNF in the left and right cortices after stress treatment (twofold increase) that was reversed by application of ES-CIT. An ES-CIT-dependent NGF reduction in stressed rats was detectable in the right cortex only (P = 0.027). The left hippocampus revealed significantly higher amounts of BDNF (2.5-fold increase) protein than the right hippocampus. These interhemispheric differences were unrelated to stress or ES-CIT treatment in all animals. BDNF and NGF of the frontal cortex, cerebellum, and serum did not change between the study groups. There was a negative correlation between body weight and serum BDNF, independent of stress or ES-CIT treatment. In conclusion, BDNF and NGF show substantial changes in this rodent model of chronic social stress, which is susceptible to antidepressant treatment with ES-CIT and therefore may constitute a neurobiological correlate for the disease.
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PMID:Effects of escitalopram on the regulation of brain-derived neurotrophic factor and nerve growth factor protein levels in a rat model of chronic stress. 1936 Sep 2

Invasive procedures, such as the lumbar puncture, can cause anxiety and pain in children undergoing treatment for acute lymphoblastic leukaemia (ALL). We investigated the safety and efficacy of two different protocols for analgo-sedation in 20 children with ALL undergoing lumbar puncture. We have conducted a prospective, cross-over study. Protocol A was composed of an association between propofol and alfentanil. Protocol B consisted in the combination of propofol and ketamine. We also evaluated the levels of nerve growth factor, substance P and enkephalins in the cerebrospinal fluid of these patients. All patients showed a satisfactory sedation and analgesia. We found a statistically significant difference of vital parameters between protocol A and protocol B, while there were no significant differences between sedation scores and the other parameters evaluated. Patients in protocol A showed a higher incidence of major side effects, such as respiratory depression. Pain neuromediator levels did not show any statistical difference between the two groups. This study shows that both protocols are effective to obtain a good sedation and analgesia in children with ALL undergoing lumbar puncture, but the association between propofol and ketamine appears to be safer due to the lower incidence of side effects.
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PMID:Propofol/alfentanil and propofol/ketamine procedural sedation in children with acute lymphoblastic leukaemia: safety, efficacy and their correlation with pain neuromediator expression. 1949 10

Clinicians have long used lithium to treat manic depression. They have also observed that lithium causes granulocytosis and lymphopenia while it enhances immunological activities of monocytes and lymphocytes. In fact, clinicians have long used lithium to treat granulocytopenia resulting from radiation and chemotherapy, to boost immunoglobulins after vaccination, and to enhance natural killer activity. Recent studies revealed a mechanism that ties together these disparate effects of lithium. Lithium acts through multiple pathways to inhibit glycogen synthetase kinase-3beta (GSK3 beta). This enzyme phosphorylates and inhibits nuclear factors that turn on cell growth and protection programs, including the nuclear factor of activated T cells (NFAT) and WNT/beta-catenin. In animals, lithium upregulates neurotrophins, including brain-derived neurotrophic factor (BDNF), nerve growth factor, neurotrophin-3 (NT3), as well as receptors to these growth factors in brain. Lithium also stimulates proliferation of stem cells, including bone marrow and neural stem cells in the subventricular zone, striatum, and forebrain. The stimulation of endogenous neural stem cells may explain why lithium increases brain cell density and volume in patients with bipolar disorders. Lithium also increases brain concentrations of the neuronal markers n-acetyl-aspartate and myoinositol. Lithium also remarkably protects neurons against glutamate, seizures, and apoptosis due to a wide variety of neurotoxins. The effective dose range for lithium is 0.6-1.0 mM in serum and >1.5 mM may be toxic. Serum lithium levels of 1.5-2.0 mM may have mild and reversible toxic effects on kidney, liver, heart, and glands. Serum levels of >2 mM may be associated with neurological symptoms, including cerebellar dysfunction. Prolonged lithium intoxication >2 mM can cause permanent brain damage. Lithium has low mutagenic and carcinogenic risk. Lithium is still the most effective therapy for depression. It "cures" a third of the patients with manic depression, improves the lives of about a third, and is ineffective in about a third. Recent studies suggest that some anticonvulsants (i.e., valproate, carbamapazine, and lamotrigene) may be useful in patients that do not respond to lithium. Lithium has been reported to be beneficial in animal models of brain injury, stroke, Alzheimer's, Huntington's, and Parkinson's diseases, amyotrophic lateral sclerosis (ALS), spinal cord injury, and other conditions. Clinical trials assessing the effects of lithium are under way. A recent clinical trial suggests that lithium stops the progression of ALS.
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PMID:Review of lithium effects on brain and blood. 1952 43

This chapter reviews the expression and regulation of opioid receptors in sensory neurons and the interactions of these receptors with endogenous and exogenous opioid ligands. Inflammation of peripheral tissues leads to increased synthesis and axonal transport of opioid receptors in dorsal root ganglion neurons. This results in opioid receptor upregulation and enhanced G protein coupling at peripheral sensory nerve terminals. These events are dependent on neuronal electrical activity, and on production of proinflammatory cytokines and nerve growth factor within the inflamed tissue. Together with the disruption of the perineurial barrier, these factors lead to an enhanced analgesic efficacy of peripherally active opioids. The major local source of endogenous opioid ligands (e.g. beta-endorphin) is leukocytes. These cells contain and upregulate signal-sequence-encoding messenger RNA of the beta-endorphin precursor proopiomelanocortin and the entire enzymatic machinery necessary for its processing into the functionally active peptide. Opioid-containing immune cells extravasate using adhesion molecules and chemokines to accumulate in inflamed tissues. Upon stressful stimuli or in response to releasing agents such as corticotropin-releasing factor, cytokines, chemokines, and catecholamines, leukocytes secrete opioids. Depending on the cell type, this release is contingent on extracellular Ca(2+) or on inositol triphosphate receptor triggered release of Ca(2+) from endoplasmic reticulum. Once secreted, opioid peptides activate peripheral opioid receptors and produce analgesia by inhibiting the excitability of sensory nerves and/or the release of proinflammatory neuropeptides. These effects occur without central untoward side effects such as depression of breathing, clouding of consciousness, or addiction. Future aims include the development of peripherally restricted opioid agonists, selective targeting of opioid-containing leukocytes to sites of painful injury, and the augmentation of peripheral opioid peptide and receptor synthesis.
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PMID:Opioids and sensory nerves. 1965 16

Diverse factors such as changes in neurotrophins and brain plasticity have been proposed to be involved in the actions of antidepressant drugs (ADs). However, in mouse models of depression based on chronic stress, it is still unclear whether simultaneous changes in behavior and neurotrophin expression occur and whether these changes can be corrected or prevented comparably by chronic administration of ADs or genetic manipulations that produce antidepressant-like effects such as the knockout of the norepinephrine transporter (NET) gene. Here we show that chronic restraint or social defeat stress induce comparable effects on behavior and changes in the expression of neurotrophins in depression-related brain regions. Chronic stress caused down-regulation of BDNF, nerve growth factor, and neurotrophin-3 in hippocampus and cerebral cortex and up-regulation of these targets in striatal regions. In wild-type mice, these effects could be prevented by concomitant chronic administration of five pharmacologically diverse ADs. In contrast, NET knock out (NETKO) mice were resistant to stress-induced depressive-like changes in behavior and brain neurotrophin expression. Thus, the resistance of the NETKO mice to the stress-induced depression-associated behaviors and biochemical changes highlight the importance of noradrenergic pathways in the maintenance of mood. In addition, these mice represent a useful model to study depression-resistant behaviors, and they might help to provide deeper insights into the identification of downstream targets involved in the mechanisms of antidepressants.
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PMID:Knockout of the norepinephrine transporter and pharmacologically diverse antidepressants prevent behavioral and brain neurotrophin alterations in two chronic stress models of depression. 1969 5

Separating rat pups from their mothers during the early stages of life is an animal model commonly used to study the development of psychiatric disorders such as anxiety and depression. The present study investigated how soon after the termination of the maternal separation period behavioural and neuroendocrine abnormalities relevant to above-mentioned illnesses would manifest. Sprague Dawley rat pups were subjected to maternal separation (3 h per day from postnatal day 2 through 14) and their behaviour and HPA axis activity determined 7 d later. We also measured nerve growth factor levels in their hippocampi and assessed the DNA methylation status of the promoter region of exon 1(7) of the glucocorticoid receptor in this brain region. As early as 7 d after the termination of the adverse event, a change in behaviour was observed that was associated with increased plasma corticosterone release and elevated nerve growth factor levels in the hippocampus. No alteration in the methylation status of the exon 1(7) glucocorticoid receptor promoter region was observed. Our data indicate that early life adversity may lead to the rapid development of abnormal behaviours and HPA axis dysregulation though no epigenetic changes to the exon 1(7) glucocorticoid receptor promoter region occurred. We further propose that the observed increased neurotrophin levels reflect compensatory mechanisms that attempt to combat the long-term deleterious effects of maternal separation.
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PMID:Maternal separation alters nerve growth factor and corticosterone levels but not the DNA methylation status of the exon 1(7) glucocorticoid receptor promoter region. 1981 61

Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are members of the neurotrophin family that normally play a role in the development and maintenance of the nervous system. However, neurotrophin dysregulation has been implicated in several neurodegenerative diseases and psychiatric disorders including Alzheimer's disease, Parkinson's disease, neuropathic pain, depression, and substance abuse. Despite their central role in the nervous system, neurotrophins have proved to be an elusive pharmacological target. Here, we describe a novel multipotent neurotrophin antagonist, 3-[(5E)-4-oxo-5-[[5-(4-sulfamoylphenyl)-2-furyl]methylene]-2-thioxo-thiazolidin-3-yl]propanoic acid (Y1036). Y1036 binds BDNF (K(D) = 3.5 +/- 0.3 microM) and NGF (K(D) = 3.0 +/- 0.4 microM) preventing either BDNF or NGF from interacting with their obligate receptor(s). Y1036 prevents both BDNF- and NGF-mediated trk activation, downstream activation of the p44/42 mitogen-activated protein kinase pathway, and neurotrophin-mediated differentiation of dorsal-root ganglion sensory neurons. Identification of a BDNF- and NGF-specific antagonist is of considerable interest in the study and treatment of diseases where dysregulation of multiple neurotrophins has been implicated.
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PMID:Multipotent neurotrophin antagonist targets brain-derived neurotrophic factor and nerve growth factor. 1992 40

The root part of Paeonia lactiflora Pall., commonly known as peony, is a commonly used Chinese herb for the treatment of depression-like disorders. Previous studies in our laboratory have showed that total glycosides of peony (TGP) produced antidepressant-like action in various mouse models of behavioral despair. The present study aimed to investigate the mechanism(s) underlying the antidepressant-like action of TGP by measuring neurotrophins including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in non-stressed and chronic unpredictable mild stress (CUMS)-treated rats. TGP (80 or 160 mg/kg/day) was administered by oral gavage to the animals for 5 weeks. The results showed that CUMS caused depression-like behavior in rats, as indicated by the significant decreases in sucrose consumption and locomotor activity (assessed by open-field test). In addition, it was found that BDNF contents in the hippocampus and frontal cortex were significantly decreased in CUMS-treated rats. CUMS treatment also significantly decreased the level of NGF in the frontal cortex of the animals. Daily intragastric administration of TGP (80 or 160 mg/kg/day) during the five weeks of CUMS significantly suppressed behavioral and biochemical changes induced by CUMS. Treating non-stressed animals with TGP (160 mg/kg) for 5 weeks also significantly increased BDNF contents in the hippocampus and frontal cortex, and NGF contents in the frontal cortex. The results suggest that the antidepressant-like action of TGP is mediated, at least in part, by increasing the expression of BDNF and NGF in selective brain tissues.
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PMID:Long-term treatment with peony glycosides reverses chronic unpredictable mild stress-induced depressive-like behavior via increasing expression of neurotrophins in rat brain. 2017 57


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