Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied beta-adrenergic and muscarinic cholinergic receptor (MR) expression and proliferative response in lymphocytes from animals under chronic mild stress (CMS) model of depression (CMS animals). Animals were subjected to CMS (periods of food or water deprivation, changes in lighting conditions, tilted cage, etc.) for 12 weeks. CMS lymphocytes showed an altered mitogen-induced proliferation. CMS-B and -T lymphocytes showed an increment on beta-adrenoceptor number and on intracellular responses to a beta-agonist. CMS-T cells showed higher MR expression and lower cGMP responses than normal lymphocytes. MR were not detectable in normal B cells while CMS-B cells showed both MR expression and cGMP response. Beta and muscarinic stimulation influenced lymphocyte proliferative responses, in accordance with cAMP and cGMP responses. After 12 weeks of the CMS procedure, animals were treated with fluoxetine while the CMS procedure continued. Fluoxetine treatment reverted the alterations induced by CMS. These findings suggest a possible mechanism for the immune alterations found in depressive disorders and for the effect of fluoxetine treatment on immune response.
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PMID:Altered expression of autonomic neurotransmitter receptors and proliferative responses in lymphocytes from a chronic mild stress model of depression: effects of fluoxetine. 1209 82

Fluoxetine (Prozac) produces sexual dysfunction in a substantial number of patients. In the few animal studies designed to address this sexual dysfunction in females, data have been inconsistent. Some investigators report that the drug disrupts sexual behavior without affecting the estrous cycle while we have reported robust effects of fluoxetine on the estrous cycle. The current studies were designed to initiate examination of procedural differences that may account for these contradictory outcomes. In the first experiment, intact, regularly cycling female rats were injected daily for 10 days with 10 mg/kg fluoxetine (intraperitoneally) or vehicle. Male-exposed, fluoxetine- or vehicle-treated rats were housed in a room with males and placed for 5 min/day into a male's cage. Other fluoxetine-treated females were housed in a room separate from males. In the second experiment, this protocol was repeated for 20 days and an additional group of females were exposed to male bedding for 5 min/day. Without male exposure, fluoxetine rapidly disrupted vaginal estrus and sexual receptivity so that approximately 50% of the rats failed to show vaginal estrus during the first 5 days; and the majority of the rats had a blocked cycle by 10 days of treatment. With male exposure, these reproductive effects were attenuated. The majority of rats cycled normally during the first 5 days of treatment and more than half cycled throughout the experiment. Loss of behavioral receptivity occurred even when normal estrous cyclicity was present. Although exposure to the male's bedding may have delayed the onset of estrous cycle disruption, five min daily exposure to a male's bedding did not prevent the disruptive effects of fluoxetine. These findings are consistent with evidence that fluoxetine's effect on female sexual dysfunction may result, in part, from the drugs' disruption of the hypothalamic-pituitary-gonadal axis. However, the data also evidence dissociation between the effects of fluoxetine on vaginal and behavioral estrus. These findings may also explain why different laboratories have reported the presence or absence of estrous cycle disturbances following daily treatment with fluoxetine.
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PMID:Daily male exposure attenuates estrous cycle disruption by fluoxetine. 1824 51

Selective serotonin reuptake inhibitors (SSRIs) have been used to treat various psychiatric disorders. Although the cellular mechanisms underlying amelioration of particular symptoms are mostly unknown, recent studies have shown critical importance of the dentate gyrus of the hippocampus in behavioral effects of SSRIs in rodents. Here, we show that serotonin potentiates synaptic transmission between mossy fibers, the sole output of the dentate granule cells, and CA3 pyramidal cells in mouse hippocampal slices. This potentiation is mediated by activation of 5-HT(4) receptors and intracellular cAMP elevation. A chronic treatment of mice with fluoxetine, a widely used SSRI, bidirectionally modulates the 5-HT-induced potentiation: Fluoxetine enhances the potentiation induced by lower concentrations of serotonin, while attenuates that by the higher concentration, which represents stabilization of synaptic 5-HT action. In contrast to the chronic treatment, an acute application of fluoxetine in slices induces a leftward shift in the dose-response curve of the 5-HT-induced potentiation. Thus, acute and chronic fluoxetine treatments have distinct effects on the serotonergic modulation of the mossy fiber synaptic transmission. Exposure of mice to novel environments induces increases in locomotor activity and hippocampal extracellular 5-HT levels. In mice chronically treated with fluoxetine, the novelty-induced hyperactivity is reduced without significant alterations in home cage activity and motor skills. Our results suggest that the chronic fluoxetine treatment can stabilize the serotonergic modulation of the central synaptic transmission, which may contribute to attenuation of hyperactive behaviors.
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PMID:Chronic fluoxetine bidirectionally modulates potentiating effects of serotonin on the hippocampal mossy fiber synaptic transmission. 1855 Jul 70

We have previously reported that inhibition of the serotonin transporter (SERT) by selective serotonin reuptake inhibitor (SSRI) fluoxetine significantly reduces the number of tryptophan hydroxylase (TPH)-positive cells in the dorsal raphe nucleus (DRN). We have been interested in exploring whether this SSRI-induced change in TPH might be modified by housing in an enriched environment. Like SSRI antidepressants, environmental enrichment (EE) and physical exercise have been found to have efficacy in the prevention and alleviation of depression. We postulated that EE with exercise and SERT inhibition would similarly affect TPH regulation and that EE with exercise might modify the effect of fluoxetine on TPH. Three week old male Sprague-Dawley rats were housed in either a standard cage (SE) or an enriched environment (EE). SE animals were singly housed with no access to enrichment objects. EE animals were group housed and were provided with various enrichment objects (e.g. running wheel) that were changed and rearranged regularly. Nine weeks after the experiment began, the rats were randomly assigned to one of four treatment groups: (1) SE control; (2) SE fluoxetine; (3) EE control; or (4) EE fluoxetine. Fluoxetine (5 mg/kg/day) was placed in the drinking water. Sections of DRN were processed for TPH immunohistochemistry. The number of TPH-positive cells was determined by blinded, manual counting. Results were analyzed by analysis of variance (ANOVA) followed by post-hoc Tukey tests. Significance was set at P < 0.05. For animals housed in a standard environment, fluoxetine induced a significant 29% reduction in the number of TPH-immunoreactive cells in the DRN. A similar reduction in TPH immunoreactivity was observed in animals that were housed in an enriched environment but not exposed to fluoxetine (39%). The number of TPH-positive cells in the DRN for animals housed in an enriched environment and exposed to fluoxetine was not significantly different than animals housed in an enriched environment and not exposed to fluoxetine. The reduction of TPH immunoreactivity in the DRN by EE with exercise suggests that a modified housing environment and voluntary exercise affects regulation of TPH, possibly via a mechanism similar to that of SERT inhibitors. This downregulation of serotonin biosynthesis by fluoxetine and EE with exercise may ultimately play a role in the therapeutic action of both interventions.
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PMID:The comparative effects of environmental enrichment with exercise and serotonin transporter blockade on serotonergic neurons in the dorsal raphe nucleus. 2212 Oct 41

The olfactory bulbectomy (OB) is an animal model of depression that results in behavioral, neurochemical and neuroendocrinological changes, features comparable to those seen in depressive patients. This study investigated OB-induced alterations in locomotor activity and exploratory behavior in the open-field test, self-care and motivational behavior in the splash test, hyperactivity in the novel object test and novel cage test, and the influence of chronic treatment with fluoxetine (10mg/kg, p.o., once daily for 14days) on these parameters. Fluoxetine reversed OB-induced hyperactivity in the open-field test, locomotor hyperactivity and the increase in exploratory behavior induced by novelty in the novel object and novel cage tests, and the loss of self-care and motivational behavior in the splash test. Moreover, OB decreased the number of grooming and fecal boli in the open-field and novel cage tests, alterations that were not reversed by fluoxetine. OB caused an increase in hippocampal, but not in prefrontal acetylcholinesterase (AChE) activity. Fluoxetine was able to reverse the increase in hippocampal AChE activity induced by OB. Serum corticosterone was increased in SHAM and bulbectomized mice treated with fluoxetine. In conclusion, OB mice exhibited depressive-like behaviors associated with an increase in hippocampal AChE activity, effects that were reversed by chronic treatment with fluoxetine.
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PMID:Fluoxetine reverses depressive-like behaviors and increases hippocampal acetylcholinesterase activity induced by olfactory bulbectomy. 2296 Jan 27

Fluoxetine is the only selective serotonin reuptake inhibitor registered for the treatment of major depressive disorder in pediatric populations, despite reports that it is disproportionately associated with an array of adverse side effects that include agitation, hostility, and overt acts of pathological aggression and violence in youth. This study examined the effects of repeated adolescent fluoxetine administration on offensive aggression and the development of the serotonin (5HT) and vasopressin (AVP) neural systems modulating this behavior using pubertal Syrian hamsters (Mesocricetus auratus) as an adolescent-animal model. Adolescent hamsters administered fluoxetine were tested for offensive aggression using the resident/intruder test, sacrificed the following day, and, using immunohistochemistry, examined for 5HT and AVP afferent innervation/development to areas of the brain implicated in aggression control. Repeated exposure to a low dose (0.3 mg/kg/day) of fluoxetine during adolescence increased nearly all measures of offensive aggression (i.e., upright offensive attacks, lateral attacks, flank/rump bites, pursuits, flank marks), whereas measures of social interest (i.e., olfactory investigation, contact time), comfort (i.e., grooming), and locomotion (i.e., contact time, cage climbing) remained constant. Fluoxetine exposure also increased 5HT and AVP afferent development to brain areas implicated in aggressive behavior, most notably the latero-anterior hypothalamus (LAH)-an area of convergence for developmental and neuroplastic changes correlated with offensive aggression in hamsters. These data indicate that repeated administration of clinically relevant doses of fluoxetine during adolescent development directly stimulates aggressive behavior and alters LAH 5HT and AVP development, yet only alterations in AVP afferent development within the LAH correlate with the fluoxetine-induced aggressive behavioral phenotype.
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PMID:Repeated fluoxetine administration during adolescence stimulates aggressive behavior and alters serotonin and vasopressin neural development in hamsters. 2302 36

The abuse of methamphetamine causes abnormal behaviors which are indistinguishable from schizophrenia in humans. Recent reports have shown that selective serotonin reuptake inhibitors (SSRIs) have beneficial effects on methamphetamine-related behaviors, including behavioral sensitization and rewarding effects in animals. However, the exact mechanisms by which SSRIs affect methamphetamine-related behaviors are not yet clear. The present study was designed to investigate the effects of SSRIs on the development of methamphetamine-induced behavioral sensitization and rewarding effects in mice. Behavioral sensitization was measured by examining the locomotor activity of mice in a tilting cage after repeated injections of methamphetamine. Repeated administration of methamphetamine significantly induced a behavioral sensitization. Some SSRIs (fluoxetine and fluvoxamine), which have sigma-1 receptor agonistic activity, inhibited the development of methamphetamine-induced behavioral sensitization. Fluoxetine also dose-dependently attenuated the rewarding effects of methamphetamine as measured by the conditioned place preference paradigm. Furthermore, the sigma-1 receptor antagonist NE-100 significantly reversed the inhibitory effects of fluoxetine on methamphetamine-induced behavioral sensitization and rewarding effects. These results suggest that sigma-1 receptor agonistic activity might be involved in the attenuating effects of fluoxetine and fluvoxamine on methamphetamine-induced behavioral sensitization and rewarding effects.
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PMID:Involvement of sigma 1 receptor in the SSRI-induced suppression of the methamphetamine-induced behavioral sensitization and rewarding effects in mice. 2506 39

Somatically acquired genomic alterations that drive oncogenic cellular processes are of great scientific and clinical interest. Since the initiation of large-scale cancer genomic projects (e.g., the Cancer Genome Project, The Cancer Genome Atlas, and the International Cancer Genome Consortium cancer genome projects), a number of web-based portals have been created to facilitate access to multidimensional oncogenomic data and assist with the interpretation of the data. The portals provide the visualization of small-size mutations, copy number variations, methylation, and gene/protein expression data that can be correlated with the available clinical, epidemiological, and molecular features. Additionally, the portals enable to analyze the gathered data with the use of various user-friendly statistical tools. Herein, we present a highly illustrated review of seven portals, i.e., Tumorscape, UCSC Cancer Genomics Browser, ICGC Data Portal, COSMIC, cBioPortal, IntOGen, and BioProfiling.de. All of the selected portals are user-friendly and can be exploited by scientists from different cancer-associated fields, including those without bioinformatics background. It is expected that the use of the portals will contribute to a better understanding of cancer molecular etiology and will ultimately accelerate the translation of genomic knowledge into clinical practice.
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PMID:Oncogenomic portals for the visualization and analysis of genome-wide cancer data. 2648 15

Protein-protein interactions (PPIs) control all functions and physiological states of the cell. Identification and understanding of novel PPIs would facilitate the discovery of new biological models and therapeutic targets for clinical intervention. Numerous resources and PPI databases have been developed to define a global interactome through the PPI data mining, curation, and integration of different types of experimental evidence obtained with various methods in different model systems. On the other hand, the recent advances in cancer genomics and proteomics have revealed a critical role of genomic alterations in acquisition of cancer hallmarks through a dysregulated network of oncogenic PPIs. Deciphering of cancer-specific interactome would uncover new mechanisms of oncogenic signaling for therapeutic interrogation. Toward this goal our team has developed a high-throughput screening platform to detect PPIs between cancer-associated proteins in the context of cancer cells. The established network of oncogenic PPIs, termed the OncoPPi network, is available through the OncoPPi Portal, an interactive web resource that allows to access and interpret a high-quality cancer-focused network of PPIs experimentally detected in cancer cell lines integrated with the analysis of mutual exclusivity of genomic alterations, cellular co-localization of interacting proteins, domain-domain interactions, and therapeutic connectivity. This chapter presents a guide to explore the OncoPPi network using the OncoPPi Portal to facilitate cancer biology.
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PMID:Explore Protein-Protein Interactions for Cancer Target Discovery Using the OncoPPi Portal. 3158 37