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)

Human and animal studies support the involvement of neuropeptide Y (NPY) in the pathophysiology of depression. Thus, hippocampal NPY-LI is decreased in genetic models of depression, the Flinders Sensitive Line and Fawn Hooded rats. Maternal "deprivation" has been identified as one risk factor in the development of psychopathology, including depression in adulthood. In view of these findings we hypothesized that brain NPY may also be decreased in an animal model of early life maternal deprivation. To test this hypothesis, male and female Sprague-Dawley rats were maternally separated (MS) 6 h/day or briefly handled from postnatal day 2 (PN2) to PN6 and from PN9 to PN13. At 12 weeks of age the rats were sacrificed, the brains dissected and NPY-LI measured by radioimmunoassay. MS rats had lower NPY-LI in the hippocampus. NPY-LI was also lower in female compared to male rats in hippocampus. Lastly, NPY-LI was increased in the hypothalamus of both male and female MS rats. These findings support the hypothesis that altered NPY in the limbic region is a common denominator of several models of depression and might be a trait marker of vulnerability to affective disorders.
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PMID:Early maternal separation alters neuropeptide Y concentrations in selected brain regions in adult rats. 1171 45

A model for the pathophysiology of depression is discussed in the context of other existing theories. The classic monoamine theory of depression suggests that a deficit in monoamine neurotransmitters in the synaptic cleft is the primary cause of depression. More recent elaborations of the classic theory also implicitly include this postulate, other theories of depression frequently prefer to depart from the monoamine-based model altogether. We suggest that the primary defect emerges in the regulation of firing rates in brainstem monoaminergic neurons, which brings about a decrease in the tonic release of neurotransmitters in their projection areas, an increase in postsynaptic sensitivity, and concomitantly, exaggerated responses to acute increases in the presynaptic firing rate and transmitter release. It is proposed that the initial defect involves, in particular, the noradrenergic innervation from the locus coeruleus (LC). Dysregulation of the LC projection activities may lead in turn to dysregulation of serotonergic and dopaminergic neurotransmission. Failure of the LC function could explain the basic impairments in the processing of novel information, intensive processing of irrational beliefs, and anxiety. Concomitant impairments in the serotonergic neurotransmission may contribute to the mood changes and reduction in the mesotelencephalic dopaminergic activity to loss of motivation, and anhedonia. Dysregulation of CRF and other neuropeptides such as neuropeptide Y, galanin and substance P may reinforce the LC dysfunction and thus further weaken the adaptivity to stressful stimuli.
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PMID:Depression as a spreading adjustment disorder of monoaminergic neurons: a case for primary implication of the locus coeruleus. 1175 Sep 28

Cortical spreading depression (CSD) may be the underlying mechanism of migraine aura. The role of CSD in initiating a migraine headache remains to be determined, but it might involve specific changes in gene expression in the brain. To examine these changes, four episodes of CSD at 5-minute intervals were induced in the mouse brain by application of 300mM KCl, and gene expression was examined 2 hours later using cDNA array and reverse transcriptase-polymerase chain reaction. Controls consisted of groups that received anesthesia only, attachment of recording electrodes only, and application of 0.9% NaCl. Of the over 1,180 genes examined in our experiments, those consistently regulated by CSD included vasoactive peptides; the vasodilator atrial natriuretic peptide was induced by CSD, while the vasoconstrictor neuropeptide Y was downregulated. Other genes specifically regulated by CSD were involved in oxidative stress responses (major prion protein, glutathione-S-transferase-5, and apolipoprotein E). L-type calcium channel mRNA was upregulated. In summary, CSD regulates genes that are intrinsic to its propagation, that identify accompanying vascular responses as a potential source of pain, and that protect against its potential pathological consequences. We believe these observations have strong relevance to the mechanisms of migraine and its outcomes.
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PMID:Cortical spreading depression and gene regulation: relevance to migraine. 1192 Oct 56

'Stress' embraces the reaction to a multitude of poorly defined factors that disturb homeostasis or allostasis. In this overview, the activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system have been utilized as objective measurements of stress reactions. Although long-term activation of the sympathetic nervous system is followed by primary hypertension, consequences of similar activation of the HPA axis have not been clearly defined. The focus of this overview is to examine whether or not repeated activation of these two stress centres may be involved in the pathogenesis of abdominal obesity and its comorbidities. In population studies adrenal hormones show strong statistical associations to centralization of body fat as well as to obesity. There is considerable evidence from clinical to cellular and molecular studies that elevated cortisol, particularly when combined with secondary inhibition of sex steroids and growth hormone secretions, is causing accumulation of fat in visceral adipose tissues as well as metabolic abnormalities (The Metabolic Syndrome). Hypertension is probably due to a parallel activation of the central sympathetic nervous system. Depression and 'the small baby syndrome' as well as stress exposure in men and non-human primates are followed with time by similar central and peripheral abnormalities. Glucocorticoid exposure is also followed by increased food intake and 'leptin resistant' obesity, perhaps disrupting the balance between leptin and neuropeptide Y to the advantage of the latter. The consequence might be 'stress-eating', which, however, is a poorly defined entity. Factors activating the stress centres in humans include psychosocial and socioeconomic handicaps, depressive and anxiety traits, alcohol and smoking, with some differences in profile between personalities and genders. Polymorphisms have been defined in several genes associated with the cascade of events along the stress axes. Based on this evidence it is suggested that environmental, perinatal and genetic factors induce neuroendocrine perturbations followed by abdominal obesity with its associated comorbidities.
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PMID:Do stress reactions cause abdominal obesity and comorbidities? 1211 65

While the mechanisms are not fully understood, olfactory bulbectomy (OBX) is a well-known rat model of depression and depression-related disorders such as anxiety and aggression. Alterations in neuropeptide Y (NPY) levels in the brain have been linked to depression and have been shown to be involved in the response to stress. This study explored the possible regulation of NPY immunoreactivity in specific regions of the amygdala 14 days after OBX in adult male Sprague-Dawley rats (n=6). Unilateral OBX and immunohistochemistry permitted comparisons of NPY in the ipsilateral amygdala with NPY in the contralateral (sham) amygdala. OBX resulted in significant increases (P<0.05) in NPY immunoreactivity in the anterior medial amygdala (threefold) and the posterior medial amygdala (2.5-fold). These regions receive projections from the accessory olfactory bulb (AOB). In contrast, the anterior and posterolateral cortical nuclei of the amygdala receive projections from the main olfactory bulb (MOB). NPY was not increased in these nuclei. These data show that not only does OBX increase NPY immunoreactivity in the amygdala, but also suggest that the AOB plays a prominent role in this regulation.
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PMID:Regulation of neuropeptide Y in the rat amygdala following unilateral olfactory bulbectomy. 1223 58

New agents offering novel mechanisms of action are required in the treatment of depressive disorder. Established agents targeting monoamine systems are unsatisfactory because of full and partial treatment resistance, delay in the onset of their effect and the occurrence of side effects. The monoamine hypothesis of depression is now recognised to provide an incomplete explanation of the pathophysiology of depression. New theories have recently developed and new targets for treatment have emerged. We briefly review some important candidate systems and therapeutic targets in depression: the hypothalamic-pituitary-adrenal axis (HPA) and the glucocorticoid and corticotrophin-releasing factor receptors, synaptic plasticity and neurotrophins and the N-methyl-D-aspartate (NMDA) receptor. The putative role of the neuropeptides substance P and neuropeptide Y, the nicotinic system and the potential therapeutic benefits of cannabinoids are also reviewed. Vagal nerve stimulation (VNS) and transcranial magnetic stimulation, serendipitous advances in treatment, are discussed briefly.
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PMID:Emerging targets for the treatment of depressive disorder. 1254 Feb 86

THE FIRST ROUTES OF RESEARCH: The first antidepressants were developed after the discovery of the existence during depression of a perturbation in the synaptic transmission of the principle monoamines: noradrenalin, serotonin and dopamine. The pharmacological effect of the various molecules developed is mainly on the metabolisation routes of neurotransmitters, but may also concern the different receptors present on synaptic level. THE AWARENESS OF NEW MEDIATORS: The progress in research on antidepressants has widened the scope of the development of such medicinal products to the domain of endocrinology (hypothalamo-pituitary-adrenal axis, progestogen hormones, thyreotropic axis) and studies on neuropeptides (substance P, neuropeptide Y). The complexity of the physiopathological mechanisms of depression hence appears enhanced.
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PMID:[Development of antidepressant drugs. Experience and prospects]. 1273 93

Maternal separation (MS) is a risk factor in the development of mood-related disorders such as depression. Human and animal studies support the involvement of neuropeptide Y (NPY) in the pathology of depression. To investigate the effect of acupuncture on depression-like behavior and examine changes in NPY expression associated with MS, we observed body weight and locomotor activity, and performed NPY immunohistochemistry in the hippocampus. MS for 7 days beginning on postnatal day 14 induced a significant decrease in body weight and locomotion, while acupuncture treatment at acupoint Shenmen (HT7) resulted in a significant increase in both. NPY-immunoreactive cells in area CA1 and the dentate gyrus were decreased in the MS group, but significantly increased in the acupuncture group. These findings suggest that acupuncture has an effect on the depression-like disorder caused by MS, possibly by modulating NPY expression in the hippocampus.
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PMID:Acupuncture increases neuropeptide Y expression in hippocampus of maternally-separated rats. 1274 95

Anorexia nervosa (AN) and bulimia nervosa (BN) are eating disorders characterized by an aberrant pattern of eating behavior, relentless pursuit of thinness, an intense fear about weight gain and an altered perception of body shape. The pathobiology of eating disorders is complex. Several social, psychological and developmental phenomena are proposed to contribute to the etiology of eating disorders. The role of neuropeptide Y, corticotropin releasing hormone and leptin has also been investigated to understand the pathogenesis of eating disorders. However, most of the neuropeptide alterations noted in eating disorders are secondary to starvation. Several nonpharmacological approaches such as cognitive and behavior-based therapy and interpersonal therapy have been developed to assist weight gain and to modify the behavioral impairment associated with eating disorders. Pharmacotherapy serves as an adjunct in AN, whereas it plays a more significant role in the management of BN. Antidepressants are effective in a limited number of AN patients with comorbid depression. On the other hand, the efficacy of fluoxetine in BN patients in reducing the frequency of binge eating and in the severity of behavioral abnormalities is quite impressive. Several adjunct therapies such as prokinetics and anxiolytics have also been used in AN and BN to assist eating behavior. An insight into genetic and neurochemical abnormalities occurring in eating disorders will help to find better therapeutic agents for these disorders. (c) 2001 Prous Science. All rights reserved.
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PMID:Anorexia nervosa and bulimia nervosa: An appraisal. 1276 23

Although a high prevalence of overweight is present in elderly people, the main concern in the elderly is the reported decline in food intake and the loss of the motivation to eat. This suggests the presence of problems associated with the regulation of energy balance and the control of food intake. A reduced energy intake causing body weight loss may be caused by social or physiological factors, or a combination of both. Poverty, loneliness, and social isolation are the predominant social factors that contribute to decreased food intake in the elderly. Depression, often associated with loss or deterioration of social networks, is a common psychological problem in the elderly and a significant cause of loss of appetite. The reduction in food intake may be due to the reduced drive to eat (hunger) resulting from a lower need state, or it arises because of more rapidly acting or more potent inhibitory (satiety) signals. The early satiation appears to be predominantly due to a decrease in adaptive relaxation of the stomach fundus resulting in early antral filling, while increased levels and effectiveness of cholecystokinin play a role in the anorexia of aging. The central feeding drive (both the opioid and the neuropeptide Y effects) appears to decline with age. Physical factors such as poor dentition and ill-fitting dentures or age-associated changes in taste and smell may influence food choice and limit the type and quantity of food eaten in older people. Common medical conditions in the elderly such as gastrointestinal disease, malabsorption syndromes, acute and chronic infections, and hypermetabolism often cause anorexia, micronutrient deficiencies, and increased energy and protein requirements. Furthermore, the elderly are major users of prescription medications, a number of which can cause malabsorption of nutrients, gastrointestinal symptoms, and loss of appetite. There is now good evidence that, although age-related reduction in energy intake is largely a physiologic effect of healthy aging, it may predispose to the harmful anorectic effects of psychological, social, and physical problems that become increasingly frequent with aging. Poor nutritional status has been implicated in the development and progression of chronic diseases commonly affecting the elderly. Protein-energy malnutrition is associated with impaired muscle function, decreased bone mass, immune dysfunction, anemia, reduced cognitive function, poor wound healing, delayed recovery from surgery, and ultimately increased morbidity and mortality. An increasing understanding of the factors that contribute to poor nutrition in the elderly should enable the development of appropriate preventive and treatment strategies and improve the health of older people.
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PMID:Eating habits and appetite control in the elderly: the anorexia of aging. 1283 2


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