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 pancreatic polypeptide (PP-fold) family of peptides consists of the endocrine peptides, pancreatic polypeptide (PP) and peptide YY (PYY), and the neuroneally derived peptide, neuropeptide Y (NPY). All three peptides are found in the circulation, with PP found primarily in the pancreas and PYY found principally in the gut. NPY is released into the circulation from neuroneal stores in response to stress. These peptides have broad peripheral actions on a number of organs. Not surprisingly, PYY and PP are believed to play an important role in the function of the gastrointestinal tract while NPY is a potent vasconstrictor and may have effects on the gut through the enteric nervous system. In the brain, NPY has been implicated in anxiety and depression, feeding and obesity, memory retention, neuroneal excitability, endocrine function, and metabolism. Recent advances in the molecular biology of the receptors for these peptides have resulted in the identification of at least six receptor subtypes with varying peptide pharmacology. Compared to other G-protein coupled receptor families, the PP-fold peptide receptors exhibit a relatively low level of sequence identity. Further advances in the development of selective agonists and antagonists for individual receptor subtypes will be needed to understand further their role in physiological function.
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PMID:Multiple receptors for the pancreatic polypeptide (PP-fold) family: physiological implications. 957 48

1. Concentrations of neuropeptide Y (NPY)-, neurokinin A (NKA)- and neurotensin (NT)-like immunoreactivity (-LI) were measured in brain tissues of Fawn Hooded (FH) (a model of depression), Wistar (W) (control for depression) and Sprague Dawley (SD) rats (control for strain) with the aim to explore possible associations between neuropeptides and models of depression. 2. In addition, peptides were determined after six electroconvulsive stimuli (ECS) or six sham ECS ("baseline") in order to investigate ECS mechanisms of action. 3. Baseline NPY-LI concentrations were markedly lower in the hippocampus of the "depressed" FH compared to the W and SD animals. 4. Baseline NKA-LI concentrations were higher in the occipital cortex and NT-LI concentrations in the occipital cortex, frontal cortex, and hypothalamus of the FH and W compared to the SD rats. 5. ECS increased NPY-LI in the hippocampus, frontal cortex and occipital cortex of all three strains. In the hippocampus, the increase was significantly larger in the FH compared to the W and SD rats. ECS also increased NKA-LI in the hippocampus. 6. In contrast, ECS decreased NT-LI in the occipital cortex of the FH and W animals. 7. The results indicate that NPY may play a role in depression and that changes in NPY and NKA probably constitute one of the mechanisms of ECT action. More speculatively, NT may also be involved in depression.
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PMID:Neuropeptide Y, neurokinin A and neurotensin in brain regions of Fawn Hooded "depressed", Wistar, and Sprague Dawley rats. Effects of electroconvulsive stimuli. 961 49

To investigate the possible link between neuropeptide Y (NPY) and depression, we analyzed NPY and its receptors in different limbic-related regions in the Flinder sensitive line (FSL), a genetic animal model of depression. In situ hybridization histochemistry was used to measure mRNA expression levels of NPY and NPY receptors, Y1 and Y2, in the FSL as compared to the control Flinder resistant Line rats (FRL). In the FSL rats, NPY mRNA expression levels were significantly decreased in the nucleus accumbens and CA regions, but increased in the arcuate nucleus and anterior cingulate cortex. Y1 receptor mRNA expression was decreased in different cortical regions (retrosplenial, anterior cingulate, and occipital) and in the hippocampal dentate gyrus. Y2 mRNA expression levels did not differ between FSL and FRL animals. The effect of the antidepressant drug fluoxetine (a serotonin reuptake inhibitor) in the two rat strains was also studied. There was an increase of the NPY mRNA hybridization signal in the arcuate nucleus of both strains following the antidepressant treatment (10 micromol/kg; daily for 14 days). However, in other brain regions, fluoxetine administration caused a differential effect on the induction of NPY-related genes in the two rat strains: in the CA region and dentate gyrus NPY mRNA expression was increased in the FSL, but decreased in the FRL. In contrast, Y1 mRNA levels tended to be decreased by fluoxetine in the nucleus accumbens of the FSL rats, but increased in the FRL. These findings suggest an involvement of the Y1, but not the Y2, receptor subtype in depressive disorder. Overall, the results appear to sustain the importance of the FSL rats as an animal model of depression in view of the impairment of NPY genes and the ability of fluoxetine treatment to normalize NPY-related gene expression selectively in this strain.
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PMID:Alterations in neuropeptide Y and Y1 receptor mRNA expression in brains from an animal model of depression: region specific adaptation after fluoxetine treatment. 972 78

We examined the effects of intrathecal (i.t.) administration of neuropeptide Y (NPY) on the excitability of the flexor reflex in normal rats and 24 h after inflammation induced by subcutaneous carrageenan. In normal rats, i.t. NPY at low doses (10 and 100 ng) caused a brief facilitation of the flexor reflex with no subsequent depression. At higher doses (1 and 10 microg), the effect of NPY was mainly inhibitory, causing substantial and usually prolonged depression of the flexor reflex. At 24 h after the injection of carrageenan, when inflammation was at its peak, the magnitude of the reflex was increased and discharge duration became prolonged. I.t. NPY produced similar pattern of dose-dependent facilitatory and depressive effects on the flexor reflex. The facilitatory effect of i.t. NPY, particularly for the higher doses, was significantly enhanced in inflamed rats compared to normals. In contrast, the depressive effect of high doses of i.t. NPY was unchanged. These data suggest that the changes in levels of NPY and NPY receptors in the spinal cord known to occur after inflammation, are associated with an increased excitatory effect of this peptide.
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PMID:The effect of intrathecal neuropeptide Y on the flexor reflex in rats after carrageenan-induced inflammation. 984 6

Depressive disorder rates in stimulant-dependent individuals are substantially higher than community rates. Further, depressive symptoms are considered a major component of stimulant withdrawal. The comorbidity of these disorders may reflect shared neurochemical alterations in the function of serotonin, dopamine, and peptide systems, such as corticotropin releasing factor (CRF) and neuropeptide Y (NPY). These alterations are observed in patients, and in animal models of depression and stimulant dependence, particularly in limbic brain structures. This shared neurobiology does not seem to result from significant shared heritability or genetic linkage; stimulants may induce changes in neurobiology that are similar to those found in depression, and these changes might provide a therapeutic target. Stimulant-dependent patients with a depressive disorder may be a specific subpopulation for antidepressant trials, and they might reduce their stimulant abuse when treated with antidepressants. Nevertheless, concomitant dependence on alcohol or opioids may influence this response, and antidepressants appear to be more effective for depression in combined stimulant and opioid dependence than in combined stimulant and alcohol dependence.
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PMID:Depression and stimulant dependence: neurobiology and pharmacotherapy. 986 11

Bilateral olfactory bulbectomy in the rat produces a well-characterized syndrome that is independent of anosmia. This syndrome is reversed by chronic antidepressant administration, which provides the basis for the olfactory bulbectomy model of depression. The present experiments focused on neuropeptide plasticity in central olfactory/limbic structures following olfactory bulbectomy in rats. Male Sprague-Dawley rats received bilateral surgical ablation of the olfactory bulbs, sham surgery, or no surgery and were killed either three, seven, 14 or 28 days later. Relative levels of messenger RNA encoding neuropeptide Y, somatostatin, thyrotropin-releasing hormone, and corticotropin-releasing factor precursors in the forebrain were measured by quantitative in situ hybridization histochemistry using oligonucleotide probes. Prepro-neuropeptide Y messenger RNA levels in the piriform cortex and dentate gyrus were significantly elevated in bulbectomized rats 14 and 28 days after surgery compared to sham-operated and surgically naive rats. Prepro-somatostatin messenger RNA levels in the piriform cortex were marginally increased in bulbectomized rats at these time-points. Thyrotropin-releasing hormone and corticotropin-releasing factor precursor messenger RNA levels were not altered in the brain regions studied. The results indicate that olfactory bulbectomy causes long-term increases in the expression of the neuropeptide Y gene. These findings suggest that neuropeptide Y plasticity in the olfactory/limbic system may contribute to the olfactory bulbectomy syndrome in rats, and they provide further evidence of a role for neuropeptide Y in the pathophysiology of depression.
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PMID:Effects of olfactory bulbectomy on neuropeptide gene expression in the rat olfactory/limbic system. 988 71

Neuropeptides: corticotropin releasing factor (CRF), neuropeptide Y (NPY) and somatostatin (STS) have been associated with depression and anxiety, while neurotensin (NT), calcitonin gene-related peptide (CGRP) and tachykinins [neurokinin A (NKA) and substance P (SP)] are presumed to also play a role in the function of the dopaminergic system. Moreover, investigations in the past decade have shown that psychotomimetics and antipsychotic drugs as well as lithium affect brain synthesis, tissue concentrations, and release of some neuropeptides. In view of the above, experiments were carried out to explore whether changes in neuropeptides constitute one of the mechanisms of action of electroconvulsive treatment (ECT). Human cerebrospinal fluid (CSF) was studied before and after ECT, and brains from healthy and models of depression rats were investigated in electroconvulsive stimuli (ECS)-treated and sham-treated animals. The major findings were that a series of ECTs, in parallel to clinical recovery, increased CSF concentrations of NPY-like immunoreactivity (-LI), STS-LI, and CRF-LI, and in one study endothelin-LI. A series of ECS, but not a single treatment, reproducibly elevated concentrations of NPY-LI, NKA-LI, and STS-LI--but not NT-LI, SP-LI, galanin-LI, or CGRP-LI--in hippocampus, frontal cortex, and occipital cortex. No changes were measured in other regions, e.g., striatum. NPY and STS mRNAs were also increased indicating that ECS affects peptide synthesis. Generalized seizures induced by, e.g., kainic acid or pentylenetetrazole, had similar effects on neuropeptides. The changes persisted for at least 1 week after the last treatment. Pretreatment with compounds reducing seizures, such as benzodiazepines and MK-801; had no effect on magnitude of neuropeptide changes although the seizure duration was decreased by > 50%. On the basis of these findings, it is suggested that neuropeptides are involved in ECT's mechanisms of action. Since ECT is therapeutically efficient in both schizophrenia and depression and, taking into account that antipsychotic drugs and psychotomimetics as well as lithium selectively affect some neuropeptides, it is hypothesized that distinct combinations of neuropeptide and monoamine changes in selected neuronal populations constitute the underpinnings of ECT's effects on specific disease symptoms, conceivably independent of diagnosis.
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PMID:Neuropeptides and electroconvulsive treatment. 1018 19

In order to receive a further understanding of stress-regulation in depressed suicide attempters, peptides that are supposed to be related to the stress system (the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system) were studied in plasma. When compared with healthy controls, cortisol was high (p<0.001) and corticotropin releasing hormone (CRH) and neuropeptide Y (NPY) appeared to be low (p<0.001) in patients who had recently attempted suicide. Patients who had repeatedly attempted suicide had the lowest NPY. A correlation between NPY and cortisol (p<0.05) was found in suicidal patients with depression NOS, whereas beta-endorphins correlated with cortisol (p<0.01) in suicidal patients with major depressive disorder. A postdexamethasone decrease of NPY was noted in the controls but not in the patients. These results suggest stress system alterations in suicidal patients with mood disorders.
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PMID:Alterations of corticotropin releasing hormone (CRH) and neuropeptide Y (NPY) plasma levels in mood disorder patients with a recent suicide attempt. 1020 89

The inhibitory control of growth hormone (GH) release by somatostatin (SRIH) has been conserved throughout vertebrate evolution. In contrast, the neuropeptides involved in the stimulatory control of GH vary according to species and/or physiological situations. We investigated the direct pituitary regulation of GH release in a primitive teleost, the European eel (Anguilla anguilla L.) at the juvenile stage. Short-term serum-free primary cultures of dispersed pituitary cells were used, and GH release was measured by an homologous radioimmunoassay. Whereas growth hormone-releasing hormone (GHRH), gonadotropin-releasing hormone (GnRH), thyrotropin-releasing hormone (TRH), neuropeptide Y (NPY) and cholecystokinin (CCK) failed to induce any change in GH release, corticotropin-releasing hormone (CRH) dose-dependently stimulated GH release with a significant effect at 1 nM and a maximal effect (> or =400% of controls at 24 h) at 100 nM. In agreement with our previous studies, PACAP also stimulated GH release but its maximal effect was lower than that of CRH. Proopiomelanocortin (POMC)-peptides, corticotropin (ACTH), melanotropin (alpha-MSH), beta-endorphin) had no effect on GH release, at any dose tested (0.1-1000 nM), indicating that the stimulatory effect of CRH on GH release by somatotrophs was not mediated by CRH-induced release of POMC-peptides from corticotrophs and melanotrophs. The CRH antagonist, alpha-helical CRH(9-41), significantly inhibited the stimulatory effect of CRH on GH release, suggesting the implication of specific CRH receptors related to mammalian ones. The stimulatory effect of CRH on GH release was reduced after 24 h of incubation, indicating a desensitization. In contrast, no desensitization to the inhibitory effect of SRIH was observed. SRIH inhibited CRH action in a dose-dependent manner. The effect of SRIH was overriding, 1 nM SRIH being able to abolish the effect of 1000 nM CRH. In conclusion, in the eel, CRH stimulates GH release directly at the pituitary cell level. GH and cortisol secretions could interact in controlling several physiological functions such as metabolism and ion exchange. This study suggests that CRH may have played an important early role in vertebrates co-ordinating the activation of various endocrine axes involved in metamorphosis, osmoregulation, stress and fasting. The stimulatory role of CRH on GH release may have been partially conserved during evolution, as it is found in some human physio-pathological situations such as stress, fasting and depression.
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PMID:Evidence that corticotropin-releasing hormone acts as a growth hormone-releasing factor in a primitive teleost, the European eel (Anguilla anguilla). 1032 May 66

Previously, we observed specific alterations of neuropeptide Y (NPY) and Y1 receptor mRNA expression in discrete regions of the Flinders Sensitive Line rats (FSL), an animal model of depression. In order to clarify the correlation between mRNA expression and protein content, radioimmunoassay and receptor autoradiography were currently performed. In the FSL rats, NPY-like immunoreactivity (NPY-LI) was decreased in the hippocampal CA region, while Y1 binding sites were increased; NPY-LI was increased in the arcuate nucleus. Fluoxetine treatment elevated NPY-LI in the arcuate and anterior cingulate cortex and increased Y1 binding sites in the medial amygdala and occipital cortex in both strains. No differences were found regarding the Y2 binding sites. The results demonstrate a good correlation between NPY peptide and mRNA expression, and sustain the possible involvement of NPY and Y1 receptors in depression.
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PMID:Alterations in neuropeptide Y levels and Y1 binding sites in the Flinders Sensitive Line rats, a genetic animal model of depression. 1032 63


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