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)

Neuropeptide Y (NPY) has been proposed to play a role in the pathophysiology of depression and also to act as an endogenous anticonvulsant. Repeated administration of electroconvulsive stimulations (ECS) has been shown to induce a long-term increase in hippocampal NPY neurotransmission, while the effects of single ECS are largely unexplored. In this study, we assessed extracellular levels of NPY in the dorsal hippocampus of freely moving rats following a single ECS. We also studied the effect of locally administered BIBP3226, a selective NPY Y1 receptor antagonist with reported anticonvulsant properties, on the duration of the ECS-induced seizure and NPY release in freely moving animals. Our data demonstrate that a single ECS increases extracellular NPY-like immunoreactivity (LI) levels in the dorsal hippocampus, reaching statistical significance 2h following the treatment. KCl transiently and calcium-dependently increased extracellular levels of NPY, suggesting that the measured NPY-LI is derived from functional neurons. Local BIBP3226 perfusion essentially abolished the ECS-induced seizure but had no effect on the basal NPY-LI outflow or on the ECS-induced rise in extracellular NPY levels. Our data are in line with the hypothesis that one mechanism of action of ECS is to release NPY in the hippocampus and suggest that the increase is in itself not associated with anticonvulsant activity but may represent other properties of NPY.
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PMID:Extracellular levels of NPY in the dorsal hippocampus of freely moving rats are markedly elevated following a single electroconvulsive stimulation, irrespective of anticonvulsive Y1 receptor blockade. 1245 Jul 42

A bidirectional interaction between sleep electroencephalogram and endocrine activity is well established in various species including humans. Various hormones (peptides and steroids) participate in sleep regulation. A key role was shown for the reciprocal interaction between sleep-promoting growth hormone-releasing hormone (GHRH) and sleep-impairing corticotropin-releasing hormone (CRH). Changes in the GHRH : CRH ratio result in changes of sleep-endocrine activity. It is thought that the change of this ratio in favour of CRH contributes to aberrations of sleep during ageing and depression (shallow sleep, blunted GH and elevated cortisol). Besides GHRH, ghrelin and galanin enhance slow wave sleep. Somatostatin is another sleep-impairing factor. Neuropeptide Y acts as a CRH antagonist and induces sleep onset. There are hints that CRH promotes rapid eye movement sleep (REMS). In animals prolactin enhances REMS. In humans vasoactive intestinal polypeptide (VIP) appears to play a role in the temporal organization of sleep as, after VIP, the non-REMS-REMS cycle decelerated. Cortisol appears to enhance REMS. Finally, gonadal hormones participate in sleep regulation. Oestrogen replacement therapy and CRH-1 receptor antagonism in depression are beneficial clinical applications of sleep-endocrine research.
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PMID:Sleep and endocrinology. 1282 39

Neuropeptide Y (NPY) has been implicated in the pathophysiology of certain mood disorders, including depression and anxiety. It is, however, not known which of the five cloned NPY receptors mediate these functions. We investigated the effect of Y2 receptor deletion on anxiety and stress-related behaviours. In the elevated plus maze, Y2 knock out (Y2(-/-)) mice showed a 2.7-fold higher frequency of entering into, and spent 3.8 times more time within, the open arms compared to controls, while entries into the closed arms did not differ. Similarly Y2(-/-) mice entered the central area of the open field 1.7 times more frequently and also spent 1.8 times more time there. In the light/dark test Y2(-/-) mice had a 4.8-fold lower latency to enter the lit area but stayed there 2.6 times longer than control mice. Y2(-/-) mice displayed 3.2-fold less immobility in the forced swim test, indicating improved stress coping ability. Y2 receptors are predominantly located presynaptically where they mediate feedback inhibition of neurotransmitter release. Deletion of these receptors may result in enhanced release of NPY, GABA and/or glutamate in brain areas linked to the manifestation of anxiety, and stress-related behaviour such as the amygdala. Taken together, deletion of the Y2 receptor has revealed an important role of Y2 receptors in the generation of anxiety-related and stress-related behaviours in mice.
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PMID:Reduced anxiety and improved stress coping ability in mice lacking NPY-Y2 receptors. 1285 47

Neuropeptide Y (NPY) and cholecystokinin (CCK) are known to play important roles in the response to stress and the control of anxiety. In order to investigate the role of NPY and CCK in chronic mild stress (CMS), an animal model of depression, we examined the effects of CMS on sucrose intake as a measure of anhedonia, and expression of NPY and CCK in the rat brain utilizing immunohistochemistry. Sprague-Dawley rats were exposed to a variety of chronic unpredictable mild stressors for 8 weeks. CMS rats significantly reduced the consumption of sucrose intake and gained body weight more slowly, compared to control rats. CMS dramatically produced a decrease in NPY expression in several diencephalic regions including the parvocellular subregion of the paraventricular hypothalamic nucleus (PVN), the periventricular hypothalamic nucleus (PE), the paraventricular thalamic nucleus (PV) and the arcuate nucleus (ACN). In contrast, CCK-like immunoreactivity throughout these areas was substantially increased in chronic mild stressed rats. These results clearly demonstrated that exposure of chronic mild stress upregulated CCK synthesis and downregulated NPY synthesis within the hypothalamus. The present results demonstrated that there was an inverse relationship between NPY and CCK in mediating stress response in an animal model of depression. These findings suggest that CCK and NPY systems may play important roles in expressing the symptopathology of the chronic stress responses such as depression, abnormality of food intake or anxiety-related disorders.
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PMID:Expression of neuropeptide Y and cholecystokinin in the rat brain by chronic mild stress. 1291 81

Neuropeptide Y (NPY) is one of the most abundant peptides in the central nervous system and currently there are four known receptor subtypes Y1, Y2, Y4 and Y5. Central NPY and its receptors have been implicated in a variety of physiological processes such as epilepsy, sleep, obesity, learning and memory, gastrointestinal regulation, alcoholism, depression and anxiety. The localization of these receptors within the brain is consistent with the roles mentioned, as they are found in varying density within the limbic structures, such as the hippocampal formation, amygdala, hypothalamus and septum. It is well understood that NPY produces anxiolytic responses following central administration under stressful or anxiety-provoking situations. In contrast, central administration of the neuropeptide corticotropin-releasing factor (CRF) produces anxiogenic behaviors. It has been proposed that NPY counteracts the effects of CRF to maintain no net change in emotional state, e.g., emotional homeostasis. In this article, we review the scientific literature describing the NPY-CRF relationship, specifically as it relates to the modulation of the CRF-mediated stress responses via the amygdala, a key forebrain structure involved in the regulation of emotional states.
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PMID:Interactions between NPY and CRF in the amygdala to regulate emotionality. 1533 74

Neuropeptide Y (NPY) and alpha-melanocyte stimulating hormone (alpha-MSH) have been implicated in pathophysiology of feeding and certain mood disorders, including anxiety and depression. Both the peptides are abundantly present in CNS, especially in the hypothalamus and amygdala. Although they are known to exert opposite effects, particularly with reference to anxiety, the underlying mechanisms are not known. We were interested in studying the interaction between these two peptides in the regulation of anxiety, within the framework of amygdala. We administered agents like NPY, alpha-MSH, selective melanocortin-4 receptor (MC4-R) antagonist HS014 and NPY Y1 receptor agonist [Leu(31), Pro(34)]-NPY, alone and in combinations, unilaterally in right amygdala of rats and measured the response using elevated plus maze test. While NPY and [Leu(31), Pro(34)]-NPY increased the time spent and number of entries in the open arms suggesting anxiolytic-like effects, alpha-MSH resulted in opposite responses. Anxiolytic-like effect of NPY (10 nM) or [Leu(31), Pro(34)]-NPY (5 nM) was significantly reduced following prior alpha-MSH (250 ng) administration. Co-administration of HS014 (1 nM) and NPY (5 nM) or [Leu(31), Pro(34)]-NPY (1 nM) at subeffective doses evoked synergistic anxiolysis. Since the closed arm entries displayed by animals of all the groups were in a similar range, the effects might not be ascribed to the changes in general locomotor activity. These results suggest that endogenous alpha-MSH and NPY containing systems may interact in the amygdala and regulate exploratory behavior in an animal model of anxiety.
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PMID:Interaction between neuropeptide Y and alpha-melanocyte stimulating hormone in amygdala regulates anxiety in rats. 1586 23

Neuropeptide Y (NPY) is considered to be an important neuromodulator in the regulation of emotional behavior. For example, NPY is consistently involved in anxiety-related behaviors and there is increasing support for a role of this peptide in mood disorders such as depression. Furthermore, recent evidence suggests that NPY has a significant role in the neurobiological response to alcohol, including alcohol consumption, dependence, and withdrawal. In addition, NPY is beginning to emerge as an important modulator in the etiology of alcoholism that is independent from the addictive and reinforcing properties of the traditional system commonly associated with dopamine and instead, is strongly associated with innate emotionality. The recent developments elucidating the role of NPY in emotion and alcohol dependence are reviewed and the potential of the NPY system as a novel therapeutic strategy in the treatment of anxiety, depression and alcohol-related disorders is examined.
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PMID:Neuropeptide y: role in emotion and alcohol dependence. 1661 Oct 91

Neuropeptide Y (NPY) was shown to modulate anxiety- and depression-related behaviors in various animal models. Previous studies demonstrated that NPY Y2 receptor knockout (KO) mice display an anxiolytic- and antidepressant-like phenotype compared with control animals. However, the long-term effect of the deletion of this receptor in aged animals is unknown. Thus, anxiety- and depression-related behaviors were investigated in 2-yr-old NPY Y2 KO mice. Aged NPY Y2 KO mice display an anxiolytic-like profile as assessed in the elevated plus-maze and open field, providing further support for a role for Y2 receptors in anxiety-related behaviors. Furthermore, aged NPY Y2 KO mice have significantly lower immobility scores in the forced swim test; supporting the role for this receptor in antidepressant-like behaviors. These data provide further evidence that modulators of the NPY Y2 receptor subtype are drug targets for the treatment of anxiety and mood disorders in human subjects.
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PMID:Emotional behavior in aged neuropeptide Y (NPY) Y2 knockout mice. 1669 Oct 11

Serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) have been the putative markers of MDD. Neuropeptide Y (NPY) may have an important role in the pathophysiology of major depressive disorder (MDD). However, direct measures of cerebrospinal fluid (CSF) 5-HT and NPY in severe MDD have been lacking. In the present study, we examined CSF 5-HT, 5-HIAA and NPY levels and correlate them with gender and suicidal behavior of severe major depressive disorder. Forty drug-free subjects with a severe major depressive disorder and forty control subjects underwent lumber puncture and psychiatric evaluation. Cerebrospinal fluid levels of 5-HT, 5-HIAA and NPY were assayed by enzyme-linked immunosorbent assay (ELISA) test. The relationships among 5-HT, 5-HIAA, NPY and clinical variables were statistically evaluated. There were no differences between severe major depressive disorder and controls in all parameters measured. In severe MDD group, significantly lower CSF 5-HT and higher 5-HT turnover (5-HIAA/5-HT) were found in female patients compared with male patients. The patients with intense suicidal intents and suicidal attempts had significantly lower CSF 5-HT compared to patients with nonsuicidal intents. Additionally, significantly lower CSF NPY was found in first episode depressed patients compared with recurrent depressed patients. Gender-related difference in CSF 5-HT implied a female preponderance in major depression to some extent. Cerebrospinal fluid 5-HT levels and 5-HT turnover (5-HIAA/5-HT) could be valuable tools for prediction of suicidality and potential markers for evaluating major depressive disorder. NPY was perhaps a marker for first episode depression.
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PMID:CSF serotonin, 5-hydroxyindolacetic acid and neuropeptide Y levels in severe major depressive disorder. 1671 89

Neuropeptide Y (NPY) is contained in at least four types of GABAergic interneurons in the dentate gyrus, many of which also contain somatostatin and give rise to the dense NPY innervation of the dentate outer molecular layer. In humans but not rats, minute amounts of NPY are also normally expressed in dentate granule cells, while seizure activity in rats induces robust NPY expression in granule cells. Y1 and Y2 receptors are the most abundant NPY receptors expressed in the dentate gyrus. Y1 receptors are postsynaptic receptors, primarily located on granule cell dendrites in the molecular layer and some interneurons, while Y2 receptors are presynaptic receptors mediating inhibition of glutamate release, and potentially that of NPY and GABA depending on their presynaptic localization, and may also be expressed on some hilar interneurons. In humans, monkeys and mice, Y2 receptors are also present on mossy fibers, but not in most rat species, though functional evidence suggests their presence. Hilar interneurons containing NPY degenerate in temporal lobe epilepsy and in Alzheimer's disease and reduced levels of NPY in dentate hilus are associated with depression. By activating Y1 receptors, NPY also exerts powerful neuroproliferative effects on subgranular zone progenitor cells, increasing the number of newly born granule cells in the adult dentate gyrus. Functionally, NPY exerts anticonvulsive actions mediated by Y2 receptors at mossy fiber terminals, but there are no presynaptic responses to NPY at perforant path inputs to dentate granule cells in rats or mice. NPY also has potentially complicated actions on NPY-containing interneurons. Elevated expression of NPY in mossy fibers of the rat, sprouting of NPY interneurons in the human dentate, and over-expression of Y2 receptors in mossy fibers indicate an anticonvulsive role of endogenous NPY in epilepsy. However, the physiological role of NPY in the healthy dentate gyrus remains unclear.
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PMID:Neuropeptide Y in the dentate gyrus. 1776 25


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