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 depression of physiological processes characteristic of mammalian hibernation is precisely regulated by the central nervous system, especially by the neuropeptidergic apparatus of the hypothalamus. Because of inhibitory influences on neuronal circuits within the brain and suppressive effects on the metabolism via the endocrine axis, somatostatin has been implicated in the regulation of hibernation. The somatostatin system of the brain was investigated with immunocytochemistry, in situ hybridization, and radioimmunoassays in euthermic summer, euthermic winter, and hibernating European hamsters (Cricetus cricetus). Numerous somatostatin-immunoreactive perikarya were observed in the periventricular hypothalamic nucleus. The striatum, amygdala, and cortex contained only scattered immunoreactive perikarya. These entities also contained immunoreactive fiber profiles, although the highest density of immunoreactive fibers was found in the median eminence. Immunocytochemistry and radioimmunoassays showed that the number of somatostatin-immunoreactive perikarya and fibers and the content of somatostatin in the hypothalamus and the median eminence was conspicuously lower in euthermic winter animals than in euthermic summer animals. This decrease was more pronounced in hibernating specimens. In situ hybridization also demonstrated a decrease in the expression and synthesis rate of somatostatin in euthermic winter animals; again, this was even more dramatic in hibernating hamsters. These changes were less pronounced or non-significant in the extrahypothalamic somatostatin-immunoreactive perikarya and fiber systems, as shown by immunocytochemistry and radioimmunoassay, respectively.
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PMID:The somatostatin system of the brain and hibernation in the European hamster (Cricetus cricetus). 913 58

The ontogeny of somatostatin binding sites was studied in 16 respiratory nuclei of the human brainstem, from 19 postconceptional weeks to 6 months postnatal, by quantitative autoradiography using [(125)I-Tyr0,DTrp8]S14 as a radioligand. In the early gestational stages (19-21 postconceptional weeks), moderate to high concentrations of [(125)I-Tyr0,DTrp8]S14 binding sites were found in all nuclei, the highest density being measured in the locus coeruleus. From 19 weeks of fetal life to 6 months postnatal, a decrease in the density of labeling was observed in all nuclei. The most dramatic reduction in site density (80-90%) was found in the ventral part of the nucleus medullae oblongata lateralis and in the nucleus paragigantocellularis lateralis. A 70-80% decrease was detected in the dorsal part of the nucleus tractus solitarius, the nucleus nervi hypoglossi, the ventral part of the nucleus medullae oblongatae centralis, the nucleus ambiguus, the nucleus paragigantocellularis dorsalis, and the nucleus gigantocellularis, and a 60-70% decrease in the nucleus parabrachialis medialis, the ventrolateral and ventromedial parts of the nucleus tractus solitarius, and the nucleus praepositus hypoglossi. A 50-60% decrease was observed in the caudal part of the nucleus tractus solitarius, the nucleus dorsalis motorius nervi vagi, and the nucleus parabrachialis lateralis, whereas in the nucleus locus coeruleus, the concentration of recognition sites decreased by only 30%. The profiles of the decrease in site density differed in the various structures. In the majority of the nuclei, a gradual diminution of binding density was observed either throughout the developmental period studied or mainly during fetal life. Conversely, in two nuclei, i.e., the nucleus parabrachialis lateralis and the locus coeruleus, an abrupt decrease occurred around birth. The differential decrease in the density of somatostatin binding sites observed in respiratory nuclei during development, together with the observation that microinjection of somatostatin in some of these nuclei causes ventilatory depression and apnea, strongly suggests that the somatostatinergic systems of the human brainstem are involved in the maturation of the respiratory control.
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PMID:Ontogeny of somatostatin binding sites in respiratory nuclei of the human brainstem. 913 3

The pathogenesis of trigeminal neuralgia remains largely unknown. "Peripheral" as well as "central" causes have been suggested. To investigate the role of serotonergic, noradrenergic, dopaminergic, and peptidergic systems, we determined the concentrations of epinephrine, norepinephrine, and their breakdown product, vanillylmandelic acid, in the cerebrospinal fluid of 16 patients (55.3 +/- 8.3 years) with trigeminal neuralgia. As a marker for the dopaminergic system, we determined cerebrospinal fluid concentrations of dopamine and its metabolite, homovanillic acid. As a marker for the serotonergic system, we measured cerebrospinal fluid levels of the serotonin metabolite, 5-hydroxyindoleacetic acid. In addition, levels of the neuropeptides, substance P and somatostatin, were determined. The concentration of norepinephrine (P < 0.01) and its metabolite, vanillylmandelic acid, (P < 0.05) were significantly decreased in our patients. The level of the dopamine metabolite, homovanillic acid, was also significantly reduced (P < 0.01). Also significantly decreased was 5-hydroxyindoleacetic acid (P < 0.01). Substance P was significantly elevated (P < 0.05). Somatostatin was significantly decreased (P < 0.05). We hypothesize that the sum of complex neurochemical changes plays a role in the pathogenesis of trigeminal neuralgia. The elevated substance P could support the concept of a neurogenic inflammation in the trigeminovascular system, whereas changes in the monoaminergic transmitters and their metabolites seem to reflect a more central dysfunction possibly due to a longer duration of the disease and an accompanying depression.
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PMID:Cerebrospinal fluid neuropeptides and monoaminergic transmitters in patients with trigeminal neuralgia. 915 Jun 15

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the most common types of progressive neurodegenerative disorder in our catchment area. The distribution of cortical degeneration in FTD is mainly the reverse of that in AD, while there are both differences and similarities in the clinical characteristics. Somatostatin and neuropeptide Y (NPY) are neuropeptides with a widespread distribution in the human cerebral cortex. Somatostatin is involved in the regulation of hormone release from the anterior pituitary and may act as a neurotransmitter-modulator. NPY is a potent anxiolytic neuropeptide. Somatostatin and NPY coexist in the cerebral cortex, basal ganglia and in amygdaloid complexes. The present study of AD (n = 34) and FTD (n = 22) analyses the cerebrospinal-fluid (CSF) levels of somatostatin-like immunoreactivity and NPY-like immunoreactivity and correlates their levels to 54 different clinical items, such as restlessness, anxiety, irritability and depression. The CSF levels of the two neuropeptides somatostatin and NPY were significantly correlated in FTD (p < 0.02), but not in AD. Several significant correlations to the clinical signs were found: in AD disorientation and dyspraxia, and in FTD agitation, irritability and restlessness. Somatostatin showed a significant negative correlation with severity of dementia in AD (p < 0.013).
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PMID:Somatostatin and neuropeptide Y in cerebrospinal fluid: correlations with severity of disease and clinical signs in Alzheimer's disease and frontotemporal dementia. 921 68

The effect of bolus infusion of increasing somatostatin (SMS) concentrations (1, 10, 100, 200 micrograms/100 g body wt) on pancreatic microcirculation and pancreatic tissue PO2 were investigated by using in vivo epifluorescence microscopy and a polarographic PO2 measurement technique. Additionally, the microperfusion of the pancreas, liver, spleen, stomach, and duodenum was measured by a laser Doppler device. Bolus infusion of SMS caused a significant, transient, and dose-dependent decrease in pancreatic capillary RBC velocities (to 50% of baseline) and acinar capillary overall perfusion (to 20% of baseline), which was not caused by a macrocirculatory depression. This pronounced decrease in microperfusion was not paralleled by a decline in tissue PO2. Laser Doppler measurements revealed that pancreatic and gastric microperfusion were reduced only at maximal SMS concentrations, considering that microperfusion of the liver, spleen, and duodenum was not altered. Therefore, we found further evidence that circulatory adjustment might occur during SMS inhibited secretory activity of the exocrine pancreas.
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PMID:Effects of somatostatin (SMS) on pancreatic microcirculation. 939 3

In rat CA1 hippocampal pyramidal neurons (HPNs), somatostatin (SST) has inhibitory postsynaptic actions, including hyperpolarization of the membrane at rest and augmentation of the K+ M-current. However, the effects of SST on synaptic transmission in this brain region have not been well-characterized. Therefore we used intracellular voltage-clamp recordings in rat hippocampal slices to assess the effects of SST on pharmacologically isolated synaptic currents in HPNs. SST depressed both (R, S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate and N-methyl--aspartate (NMDA) receptor-mediated excitatory postsynaptic currents (EPSCs) in a reversible manner, with an apparent IC50 of 22 nM and a maximal effect at 100 nM. In contrast, SST at concentrations up to 5 microM had no direct effects on either gamma-aminobutyric acid-A (GABAA) or GABAB receptor-mediated inhibitory postsynaptic currents (IPSCs). The depression of EPSCs by SST was especially robust during hyperexcited states when polysynaptic EPSCs were present, suggesting that this peptide could play a compensatory role during seizurelike activity. SST effects were greatly attenuated by the alkylating agent N-ethylmaleimide, thus implicating a transduction mechanism involving the Gi/Go family of G-proteins. Use of 2 M Cs+ in the recording electrode blocked the postsynaptic modulation of K+ currents by SST, but did not alter the effects of SST on EPSCs, indicating that postsynaptic K+ currents are not involved in this action of SST. However, 2 mM external Ba2+ blocked the effect of SST on EPSCs, suggesting that presynaptic K+ channels or other presynaptic mechanisms may be involved. These findings and previous results from our laboratory show that SST has multiple inhibitory effects in hippocampus.
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PMID:Somatostatin depresses excitatory but not inhibitory neurotransmission in rat CA1 hippocampus. 940 20

Results from preclinical studies have validated the participation of neuropeptides in sleep regulation. In recent human and clinical studies it has been shown that peripheral administration of various peptides results in specific changes in the sleep electroencephalogram in humans. Furthermore, it has been demonstrated that certain peptides are common regulators of the electrophysiological and neuroendocrine components of sleep. It is now well established that the balance between the neuropeptides growth hormone-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) plays a key role in normal and pathological sleep regulation. In young normal subjects, GHRH stimulates slow-wave sleep and growth hormone secretion but inhibits cortisol release, whereas CRH has the opposite effect. During normal aging and during acute depression, the GHRH:CRH ratio is changed in favor of CRH, resulting in disturbances in sleep endocrine activity. In addition to GHRH, galanin, growth hormone-releasing peptide, and neuropeptide Y also promote sleep, unlike ACTH(4-9), which disturbs sleep. In elderly subjects, sleep deteriorates after acute administration of somatostatin but improves after chronic treatment with vasopressin. Vasoactive intestinal polypeptide decelerates the non-rapid eye movement-rapid eye movement cycle and advances the occurrence of the cortisol nadir. The impact of delta sleep-inducing peptide, cholecystokinin, and thyrotropin-releasing hormone on human sleep regulation is not yet clear. This paper reviews recent work investigating the influence of these various neuropeptides on sleep.
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PMID:Neuropeptides and human sleep. 945 70

Epidemiological and clinical data indicate high comorbidity between depression and drug dependence that may reflect an attempt to self-medicate with drugs of abuse. The present review examines whether these two psychiatric disorders are related by attempting to identify similarities in the neurobiology of depression and drug dependence. Emphasis is put on the neuromechanisms that may mediate specific core symptoms of both disorders that reflect alterations in reward and motivational processes. First, the epidemiological and clinical data on the comorbidity of the two disorders are reviewed briefly. Then, the neuroadaptations associated with psychomotor stimulant, opiate, ethanol, nicotine, and benzodiazepine dependence in animals are reviewed. Finally, the neurotransmitter systems whose function appears to be altered in depression (i.e., serotonin, norepinephrine, acetylcholine, dopamine, gamma-aminobutyric acid, corticotropin releasing factor, neuropeptide Y, and somatostatin), as revealed primarily by animal studies, are discussed. It is concluded that drug dependence and depression may be associated with alterations in some of the same neurotransmitter systems and, in particular, with alterations of neurotransmitter function in limbic-related brain structures. Thus, these two psychiatric disorders may be linked by some shared neurobiology. Nevertheless, it remains unclear whether drug abuse and depression are different symptomatic expressions of the same preexisting neurobiological abnormalities, or whether repeated drug abuse leads to the abnormalities mediating depression (i.e., drug-induced depressions). The hypothesis of self-medication of non-drug- and drug-induced depressions with drugs of abuse is also discussed as a potentially important explanatory concept in understanding the observed clinical comorbidity of these two psychiatric disorders.
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PMID:Neurobiological similarities in depression and drug dependence: a self-medication hypothesis. 947 Nov 14

We have found that phosphorylation of a G-protein-coupled receptor by protein kinase C (PKC) disrupts modulation of ion channels by the receptor. In AtT-20 cells transfected with rat cannabinoid receptor (CB1), the activation of an inwardly rectifying potassium current (Kir current) and depression of P/Q-type calcium channels by cannabinoids were prevented by stimulation of protein kinase C by 100 nM phorbol 12-myristate 13-acetate (PMA). In contrast, activation of Kir current by somatostatin was unaffected, and inhibition of calcium channels was only modestly attenuated. The possibility that PKC acted by phosphorylating CB1 receptors was confirmed by demonstrating that PKC phosphorylated a single serine (S317) of a fusion protein incorporating the third intracellular loop of CB1. Mutating this serine to alanine did not affect the ability of CB1 to modulate currents, but it eliminated disruption by PMA, demonstrating that PKC can disrupt ion channel modulation by receptor phosphorylation.
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PMID:Protein kinase C disrupts cannabinoid actions by phosphorylation of the CB1 cannabinoid receptor. 952

Administration of hormones to humans and animals results in specific effects on the sleep electroencephalogram (EEG) and nocturnal hormone secretion. Studies with pulsatile administration of various neuropeptides in young and old normal controls and in patients with depression suggest they play a key role in sleep-endocrine regulation. Growth hormone (GH)-releasing hormone (GHRH) stimulates GH and slow wave sleep (SWS) and inhibits cortisol, whereas corticotropin-releasing hormone (CRH) exerts opposite effects. Changes in the GHRH:CRH ratio contribute to sleep-endocrine aberrations during normal ageing and acute depression. In addition, galanin and neuropeptide Y promote sleep, whereas, in the elderly, somatostatin impairs sleep. The rapid eye movement (REM)-nonREM cycle is modulated by vasoactive intestinal polypeptide. Cortisol stimulates SWS and GH, probably by feedback inhibition of CRH. Neuroactive steroids exert specific effects on the sleep EEG, which can be explained by gamma-aminobutyric acid(A) receptor modulation.
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PMID:Effects of hormones on sleep. 955 Jan 12


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