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C-fos Expression (c-fo + expression)
Selected AbstractsDifferential c-fos expression in the rhinencephalon and striatum after enhanced sleep,wake states in the catEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2000J. P. Sastre Abstract In order to delimit the supra-brainstem structures that are activated during the sleep,waking cycle, we have examined c-fos immunoreactivity in four groups of polygraphically recorded cats killed after 3 h of prolonged waking (W), slow-wave sleep (SWS), or paradoxical sleep (PS), following microinjection of muscimol (a ,-aminobutyric acid, GABA agonist) into the periaqueductal grey matter and adjacent areas [Sastre et al. (1996) , Neuroscience, 74, 415,426]. Our results demonstrate that there was a direct relationship between a significant increase in c-fos labelling and the amount of PS in the laterodorsalis tegmenti in the pons, supramamillary nucleus, septum, hippocampus, gyrus cingulate, amygdala, stria terminalis and the accumbens nuclei. Moreover, in all these structures, the number of Fos-like immunoreactive neurons in the PS group was significantly higher (three to 30-fold) than in the SWS and W groups. We suggest that the dense expression of the immediate-early gene c-fos in the rhinencephalon and striatum may be considered as a tonic component of PS at the molecular level and that, during PS, the rhinencephalon and striatum are the main targets of an excitatory system originating in the pons. [source] Previous experience of withdrawal from chronic diazepam ameliorates the aversiveness of precipitated withdrawal and reduces withdrawal-induced c-fos expression in nucleus accumbensEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2000Sarah J. Dunworth Abstract Flumazenil (20 mg/kg, i.p.)-precipitated withdrawal from chronic treatment with diazepam (DZP, 15 mg/kg, s.c. in sesame oil for 21 days) resulted in a decreased seizure threshold to the convulsant, pentylenetetrazole (PTZ), infused into the tail vein; withdrawal from 21-day chronic diazepam treatment, interspersed with two periods of drug withdrawal, resulted in a greater decrease in convulsant threshold. A separate experiment showed that consumption of a sucrose solution immediately prior to precipitated withdrawal resulted in a decreased subsequent consumption of the sucrose solution; no such evidence of a conditioned taste aversion (CTA) was seen in mice given prior experience of withdrawal. Thus, prior experience of withdrawal enhanced the effects of a subsequent precipitated withdrawal in increasing seizure sensitivity, but weakened the ability of this withdrawal to serve as an aversive unconditioned stimulus (US). The weakening of the aversive properties of precipitated withdrawal may reflect habituation to the withdrawal stimulus, and was accompanied by a loss of the ability of withdrawal to induce c-fos expression in the shell of the nucleus accumbens, an area sensitive to both novel, and stressful, as well as rewarding stimuli. [source] Galanin knockout mice reveal nociceptive deficits following peripheral nerve injuryEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2000Bradley J. Kerr Abstract The neuropeptide galanin has been identified as a potential neurotransmitter/neuromodulator within the central nervous system. In the present study, the role of endogenous galanin in nociceptive processing in the nervous system has been analysed by using mice carrying a targeted mutation in the galanin gene. Supporting this, the effect of chronic administration of exogenous galanin on nociceptive sensory inputs has been assayed in adult rats. In the absence of peripheral nerve injury, the sensitivity to threshold noxious stimuli is significantly higher in galanin mutant mice than wild-type controls. Following peripheral nerve injury, in conditions under which endogenous galanin levels are elevated, spontaneous and evoked neuropathic pain behaviours are compromised in mutant mice. Conversely, chronic intrathecal delivery of exogenous galanin to nerve-intact adult rats is associated with persistent behavioural hypersensitivity, a significant increase in c-fos expression and an increase in PKC, immunoreactivity within the spinal cord dorsal horn. The present results demonstrate that a relationship exists between the degree of nerve injury-induced galanin expression and the degree of behavioural hypersensitivity, and show that galanin may play a role in nociceptive processing in the spinal cord, with interrelated inhibitory and excitatory effects. [source] RANKing Intracellular Signaling in OsteoclastsIUBMB LIFE, Issue 6 2005Xu Feng Abstract RANKL plays a pivotal role in the differentiation, function and survival of osteoclasts, the principal bone-resorbing cells. RANKL exerts the effects by binding RANK, the receptor activator of NF-,B, in osteoclasts and its precursors. Upon binding RANKL, RANK activates six major signaling pathways: NFATc1, NF-,B, Akt/PKB, JNK, ERK and p38, which play distinct roles in osteoclast differentiation, function and survival. Recent studies have not only provided more insights into RANK signaling but have also revealed that several factors, including INF-,, IFN-,, and ITAM-activated costimulatory signals, regulate osteoclastogenesis via direct crosstalk with RANK signaling. It was recently shown that RANK contains three functional motifs capable of mediating osteoclastogenesis. Moreover, although both IFN-, and IFN-, inhibit osteoclastogenesis, they exert the inhibitory effects by distinct mechanisms. Whereas IFN-, has been shown to block osteoclastogenesis by promoting degradation of TRAF6, IFN-, inhibits osteoclastogenesis by down-regulating c-fos expression. In contrast, the ITAM-activated costimulatory signals positively regulate osteoclastogenesis by mediating the activation of NFATc1 through two ITAM-harboring adaptors: FcR, and DAP12. This review is focused on discussing the current understanding of RANK signaling and signaling crosstalk between RANK and the various factors in osteoclasts. IUBMB Life, 57: 389-395, 2005 [source] The MAPK pathway is required for depolarization-induced "promiscuous" immediate-early gene expression but not for depolarization-restricted immediate-early gene expression in neuronsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2008Hidevaldo B. Machado Abstract Depolarization, growth factors, neurotrophins, and other stimuli induce expression of immediate early genes (IEGs) in neurons. We identified a subset of IEGs, IPD-IEGs, which are induced preferentially by depolarization, but not by neurotrophins or growth factors, in PC12 cells. The "promiscuous" IEGs Egr1 and c-fos, induced by growth factors and neurotrophins, in addition to depolarization, require activation of the MAP kinase signaling pathway for induction in response to KCl depolarization in PC12 cells; MEK1/2 inhibitors block KCl-induced Egr1 and c-fos expression. In contrast, MEK1/2 inhibition has no effect on KCl-induced expression of the known IPD-IEGs in PC12 cells. Additional "candidate" IDP-IEGs were identified by a microarray comparison of genes induced by KCl in the presence vs. the absence of an MEK1/2 inhibitor in PC12 cells. Northern blot analyses demonstrated that representative newly identified candidate IPD-IEGs, as with the known IPD-IEGs, are also induced by a MAP kinase- independent pathway in response to depolarization, both in PC12 cells and in rat primary cortical neurons. Nerve growth factor and epidermal growth factor are unable to induce the expression of the Crem/Icer, Nur77, Nor1, Rgs2, Dusp1 (Mkp1), and Dscr1 genes in PC12 cells, validating their identification as IPD-IEGs. Inhibiting calcium/calmodulin-dependent kinase II (CaMKII), calcineurin, or protein kinase A (PKA) activity prevents KCl-induced IPD-IEG mRNA accumulation, suggesting that the IPD-IEG genes are induced by depolarization in neurons via a combination of calcineurin/PKA- and CaMKII-dependent pathways. © 2007 Wiley-Liss, Inc. [source] New component of the limbic system: Marginal division of the neostriatum that links the limbic system to the basal nucleus of MeynertJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2003Si Yun Shu Abstract The limbic system refers to a group of connected neural regions that are associated with motivation, learning, and memory. The marginal division (MrD) is a zone located at the caudal border of the neostriatum in mammalian brains that has been shown to be involved in learning and memory. In a previous study, c-fos expression showed functional connections between the MrD, basal nucleus of Meynert (NBM) and limbic system (Shu et al., 1988a, 1999). In the present study, to explore the relationship between these regions, the expression of limbic system-associated membrane protein (LAMP) was investigated using molecular and immunohistochemical methods. Synaptic and functional connections between the MrD and the NBM were studied also using tract tracing, electron microscopic and behavioral methods. LAMP is thought to be a marker of the limbic system and expression of LAMP protein and mRNA was observed in both the MrD and the limbic system. From such results, it is concluded that the MrD is a new component of the limbic system. Fibers from the MrD were observed projecting and synapsing on cholinergic neurons of the NBM. As reduction of learning and memory was induced by lesioning the projection from the MrD to the NBM, it would seem that the MrD modulates the learning and memory function of the NBM. In conclusion, the results of these studies suggest that the MrD is a new component of the limbic system, and there are functional and structural connections between the MrD, NBM and limbic system. The MrD seems to act as a link between the limbic system and the NBM, and plays a role in learning and memory. © 2002 Wiley-Liss, Inc. [source] Detection of c-fos expression in benign and malignant musculoskeletal lesionsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2001Jason S. Weisstein The proto-oncogene c-fos has been implicated in the development of both benign and malignant lesions of bone. Although c-fos expression in such lesions has been well studied in transgenic mouse models, less is known about its role in human musculoskeletal pathology. To clarify this relationship, we used in situ hybridization to localize c-fos m-RNA transcripts in 26 fibrous lesions (eight cases of extra-abdominal fibromatosis and six cases each of fibrous dysplasia, fibrosarcoma, and malignant fibrous histiocytoma of bone) as well as six chondrosarcomas and eight conventional high grade osteosarcomas. We found detectable levels of c-fos expression in tissues from each type of lesion tested. Moreover, all fibrous lesions consistently demonstrated high levels of expression in a majority of cells in each lesion. Chondrosarcomas and osteosarcomas exhibited more heterogeneity in c-fos expression than fibrous tissues. Three of six chondrosarcomas showed moderate expression of c-fos while only one of six was considered high. Similarly, only three of eight osteosarcomas had high expression of c-fos. These findings indicate that the expression of c-fos may be important in the development of a broad range of fibrous lesions as well as in bone and cartilaginous tumors. Additionally, this is the first report, to our knowledge, of detectable c-fos m-RNA in human chondrosarcoma. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Cellular Adaptation to Chronic Ethanol Results in Altered Compartmentalization and Function of the Scaffolding Protein RACK1ALCOHOLISM, Issue 10 2003Alicia J. Vagts Background: Previously, we found that acute ethanol induces the translocation of the scaffolding protein RACK1 to the nucleus. Recently, we found that nuclear RACK1 mediates acute ethanol induction of immediate early gene c-fos expression. Alterations in gene expression are thought to lead to long-term changes that ultimately contribute to the development of alcohol addiction and toxicity. Therefore, we sought to determine the effects of chronic exposure of cells to ethanol on the cellular compartmentalization of RACK1 and on c-fos messenger RNA (mRNA) and protein expression. Methods: Rat C6 glioma cells were used as the cell culture model. Immunohistochemistry was implemented to visualize the localization of RACK1 and to monitor the protein level of c-fos. Reverse-transcription polymerase chain reaction was used to measure c- fos mRNA levels. The Tat-protein transduction method was used to transduce recombinant Tat-RACK1 into cells as previously described. Results: Chronic exposure of cells to 200 mM ethanol for 24 and 48 hr resulted in the gradual re-distribution of RACK1 out of the nucleus. It is interesting to note that acute ethanol re-challenge immediately after chronic treatment did not result in RACK1 translocation to the nucleus, and nuclear compartmentalization of RACK1 in response to acute ethanol was detected only after 24 hr of withdrawal. Similar patterns were obtained for c-fos expression. Chronic exposure to ethanol did not result in an increase in mRNA or protein levels of c-fos. Furthermore, acute ethanol exposure did not increase c-fos protein levels in cells that were first treated chronically with ethanol. However, transduction of exogenous RACK1 expressed as a Tat-fusion protein was able to rescue c- fos mRNA expression after chronic ethanol exposure. Conclusions: Our data suggest that RACK1 nuclear compartmentalization and ethanol-induced c-fos expression are transient and are desensitized to ethanol during prolonged exposure to high concentrations. The desensitization is temporary, and RACK1 can respond to acute ethanol treatment after a 24-hr withdrawal period. Our data further suggest that the altered compartmentalization of RACK1 leads to differences in c-fos expression upon acute or chronic exposure to ethanol. In summary, RACK1 is an important molecular mediator of the acute and chronic actions of ethanol on the expression of c-fos. These findings could have implications for the molecular signaling pathways leading to pathologic states associated with alcoholism, including toxicity. [source] Chinese medicine Banxia-houpu decoction regulates c-fos expression in the brain regions in chronic mild stress model in ratsPHYTOTHERAPY RESEARCH, Issue 3 2004Weiyun Zhang Abstract Banxia-houpu decoction is a safe and effective traditional Chinese medicinal formula used in the treatment of mild and manic-depressive disorders for centuries. There has been increasing interest in its therapeutic application in depression. However, the mechanisms behind behavioural changes are still poorly understood. Chronic mild stress (CMS)-induced preference behaviour change has been used as a model to predict the clinical ef,cacy of many types of antidepressant treatment. Both EtOH and water extracts (AE and WE) of Banxia-houpu decoction exhibited a signi,cantly increased sucrose intake in the CMS model in rats, but there was no effect in unstressed animals. In the present study, it was found that the c-fos expression in cerebral cortex, hippocampus and striatum corpora were very high in the CMS model in rats. WE and AE at a dose of 130 mg/kg exhibited a signi,cantly decreased c-fos expression in the cerebral regions in CMS model in rats, respectively. The former was more potent than the latter. However, no signi,cant changes in the c-fos expression were observed in unstressed rats treated with the decoction. Fluoxetine not only signi,cantly reduced c-fos expression in all regions in the CMS model in rats, but only showed a marked decrease in c-fos expression in the hippocampus in unstressed animals. A different molecular mechanism of Banxia-houpu decoction and ,uoxetine may be implied. The cerebral cortex, hippocampus and striatum conpora might be important structural substrates in the central nervous system mediating the section of the Banxia-houpu decoction on preference behaviour in CMS-induced rats, and fos protein might be the common substrate of the signal transduction process of the decoction. Copyright © 2004 John Wiley & Sons, Ltd. [source] Retrograde adenoviral vector targeting of nociresponsive pontospinal noradrenergic neurons in the rat in vivoTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 2 2009Patrick W. Howorth Abstract The spinal dorsal horn receives a dense innervation of noradrenaline-containing fibers that originate from pontine neurons in the A5, locus coeruleus (LC), and A7 cell groups. These pontospinal neurons are believed to constitute a component of the endogenous analgesic system. We used an adenoviral vector with a catecholaminergic-selective promoter (AVV-PRS) to retrogradely label the noradrenergic neurons projecting to the lumbar (L4,L5) dorsal horn with enhanced green fluorescent protein (EGFP) or monomeric red fluorescent protein (mRFP). Retrogradely labeled neurons (145 ± 12, n = 14) were found in A5-12%, LC-80% and A7-8% after injection of AVV-PRS-EGFP to the dorsal horn of L4,L5. These neurons were immunopositive for dopamine ,-hydroxylase, indicating that they were catecholaminergic. Retrograde labeling was optimal 7 days after injection, persisted for over 4 weeks, and was dependent on viral vector titer. The spinal topography of the noradrenergic projection was examined using EGFP- and mRFP-expressing adenoviral vectors. Pontospinal neurons provide bilateral innervation of the cord and there was little overlap in the distribution of neurons projecting to the cervical and lumbar regions. The axonal arbor of the pontospinal neurons was visualized with GFP immunocytochemistry to show projections to the inferior olive, cerebellum, thalamus, and cortex but not to the hippocampus or caudate putamen. Formalin testing evoked c-fos expression in these pontospinal neurons, suggesting that they were nociresponsive (A5-21%, LC-16%, and A7-26%, n = 8). Thus, we have developed a viral vector-based strategy to selectively, retrogradely target the pontospinal noradrenergic neurons that are likely to be involved in the descending control of nociception. J. Comp. Neurol. 512:141,157, 2009. © 2008 Wiley-Liss, Inc. [source] Hypoxia-sensing properties of the newborn rat ventral medullary surface in vitroTHE JOURNAL OF PHYSIOLOGY, Issue 1 2006N. Voituron The ventral medullary surface (VMS) is a region known to exert a respiratory stimulant effect during hypercapnia. Several studies have suggested its involvement in the central inhibition of respiratory rhythm caused by hypoxia. We studied brainstem,spinal cord preparations isolated from newborn rats transiently superfused with a very low O2 medium, causing reversible respiratory depression, to characterize the participation of the VMS in hypoxic respiratory adaptation. In the presence of 0.8 mm Ca2+, very low O2 medium induced an increase in c-fos expression throughout the VMS. The reduction of synaptic transmission and blockade of the respiratory drive by 0.2 mm Ca2+,1.6 mm Mg2+ abolished c-fos expression in the medial VMS (at the lateral edge of the pyramidal tract) but not in the perifacial retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) VMS, suggesting the existence of perifacial RTN/pFRG hypoxia-sensing neurons. In the presence of Ca2+ (0.8 mm), lesioning experiments suggested a physiological difference in perifacial RTN/pFRG VMS between the lateral VMS (beneath the ventrolateral part of the facial nucleus) and the middle VMS (beneath the ventromedial part of the facial nucleus), at least in newborn rats. The lateral VMS lesion, corresponding principally to the most rostral part of the pFRG, produced hypoxia-induced stimulation, whereas the middle VMS lesion, corresponding to the main part of the RTN, abolished hypoxic excitation. This may involve relay via the medial VMS, which is thought to be the parapyramidal group. [source] Effects of Intrathecal Injection of Nicotine on the Analgesic Effects of Isoflurane in a Model of Inflammatory PainBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2009Wei Cheng After having established the mice model of analgesia by intraperitoneally injecting (i.p.) appropriate doses of isoflurane, nicotine, a neuronal nicotinic acetylcholine receptor agonist was intrathecally injected. The effects of isoflurane and nicotine on paw licking times and formalin-induced c-fos expression in the spinal cord dorsal horn were examined. Our correlative studies have shown that isoflurane can decrease the paw licking times and simultaneously suppress c-fos expression after injection of formalin in the mice. Nicotine can partially antagonize the effects induced by isoflurane above. Spinal neuronal nicotinic acetylcholine receptors may be important targets for the analgesic effects of isoflurane in formalin pain. [source] Type 4 phosphodiesterase inhibitor suppresses experimental bladder inflammationBJU INTERNATIONAL, Issue 10 2008Takeya Kitta OBJECTIVE To evaluate the effects of orally administered YM976, a specific inhibitor of type 4 phosphodiesterase (PDE4), on bladder activity in a rat model with hydrochloric acid (HCl)-induced cystitis (IC), hypothesizing that a PDE4 inhibitor might suppress bladder overactivity and bladder pain responses in bladder-hypersensitive disorders such as IC. MATERIALS AND METHODS Wistar rats with HCl-induced IC were treated with YM976 or vehicle and their voiding observed and assessed by cystometry. The severity of bladder inflammation (BI) was quantified using the BI index (BII), which comprises three factors (oedema, leukocyte infiltration and haemorrhage). Nociceptive neural activity was also examined using an immunohistochemical study of spinal c-fos expression. RESULTS YM976 significantly reduced the number of voids, and the volume per void was significantly higher than in control (vehicle) group. Cystometry showed a significant increase in bladder capacity, voided volume and voiding efficiency, and a decrease in the amplitude of voiding pressure in rats treated with YM976. All BII scores were significantly lower in the YM976 than in the control group. c-fos expression in the spine was less in the YM976 than in the control group. CONCLUSIONS Oral administration of YM976 significantly improved the voiding behaviour and histological damage in rats with IC induced by HCl. These results indicate that PDE4 inhibitor might be effective in relieving bladder symptoms with IC. [source] TLR4 monoclonal antibody blockade suppresses dextran-sulfate-sodium-induced colitis in miceJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 1 2010Yi Liu Abstract Background and Aim:, Ulcerative colitis (UC) refers to a kind of inflammatory bowel disease, of which the accurate pathogenesis is not yet well understood. Recently, the toll-like receptor 4 (TLR4) and the TLR4 signaling pathway have been proved as playing an important role in the pathogenesis of UC. The objective of this study was to evaluate the effect of TLR4 monoclonal antibody on dextran-sulfate-sodium-induced colitis in a mouse model. Methods:, We evaluated the effects of the TLR4 monoclonal antibody (TLR4mAb) on the development of dextran-sulfate-sodium-(DSS)-induced colitis. Tissue samples were evaluated by the disease activity index and histopathological score. Meanwhile, the mucosal mRNA expression of cytokines, tumor necrosis factor-,, interferon-, and interleukin-1, were analyzed by semiquantitative reverse transcription polymerase chain reaction. The mucosal protein P38-MAPK, c-jun and c-fos expressions of the TLR4-P38MAPK pathway were analyzed using Western blot. Results:, After the treatment with TLR4mAb against DSS-induced colitis, the bodyweight was significantly increased and both disease activity index and histopathological score were decreased significantly. Furthermore, the mucosal expression of messenger RNA of tumor necrosis factor-,, interferon-, and interleukin-1, were observed to be 8,15-fold more than the baseline, whereas the mucosal expressions of P38MAPK and c-jun were found to be decreased. Conclusion:, Blocking TLR4 by TLR4mAb can prevent the development of DSS-induced colitis through the TLR4-P38MAPK-c-jun pathway. [source] | |||||||||||||