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Differential Modulation (differential + modulation)
Selected AbstractsDifferential modulation by monoamine membrane receptor agonists of reticulospinal input to lamina VIII feline spinal commissural interneuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2007Ingela Hammar Abstract Noradrenaline and serotonin have previously been demonstrated to facilitate the transmission between descending reticulospinal tracts fibres and commissural interneurons coordinating left,right hindlimb muscle activity. The aim of the present study was to investigate the contribution of subclasses of monoaminergic membrane receptors to this facilitation. The neurons were located in Rexed lamina VIII in midlumbar segments and identified by their projections to the contralateral gastrocnemius,soleus motor nuclei and by lack of projections rostral to the lumbosacral enlargement. The effects of ionophoretically applied membrane receptor agonists [phenylephrine (noradrenergic ,1), clonidine (noradrenergic ,2), 8-OH-DPAT (5-HT1A, 5-HT7), 2-me-5-HT (5-HT3), 5-me-5-HT (5-HT2) and ,-me-5-HT (5-HT2)] were examined on extracellularly recorded spikes evoked monosynaptically by electric stimulation of descending reticulospinal fibres in the medial longitudinal fascicle. Application of ,1 and 5-HT2 agonists resulted in a facilitation of responses in all investigated neurons while application of ,2, 5-HT1A/7 and 5-HT3 agonists resulted in a depression. These opposite modulatory effects of different agonists suggest that the facilitatory actions of noradrenaline and serotonin on responses of commissural interneurons reported previously following ionophoretic application are the net outcome of the activation of different subclasses of monoaminergic membrane receptors. As these receptors may be distributed predominantly, or even selectively, at either pre- or postsynaptic sites their differential modulatory actions could be compatible with a presynaptically induced depression and a postsynaptically evoked enhancement of synaptic transmission between reticulospinal neurons and commissural interneurons. [source] Differential modulation of AMPA receptors by cyclothiazide in two types of striatal neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2000Vladimir S. Vorobjev Abstract The modulation of ,-amino-3-hydroxy-5-methyl-4-isoxazol-propionate (AMPA) receptor-mediated currents by cyclothiazide was investigated in acutely isolated cells from rat striatum with whole-cell patch-clamp recording. Single-cell reverse transcriptase-polymerase chain reaction (RT-PCR) was used to identify medium spiny and giant aspiny neurons and to determine their AMPA receptor subunit composition mostly in separate experiments. After pretreatment with cyclothiazide, kainate-induced AMPA responses were more strongly potentiated in medium spiny than in giant aspiny neurons; cyclothiazide induced a ninefold leftward shift in the kainate concentration,response curve for medium spiny neurons (not giant aspiny neurons). The EC50s for the cyclothiazide potentiation did not differ substantially between medium spiny neurons and giant aspiny neurons. The recovery of kainate-activated currents from modulation by cyclothiazide was slower for medium spiny neurons than for giant aspiny neurons. Medium spiny neurons expressed GluR-A, GluR-B and GluR-C, but not GluR-D subunits in both flip and flop splice variants. All giant aspiny neurons expressed GluR-A and GluR-D, exclusively in the flop form, half of them also expressed GluR-B and GluR-C. This is in keeping with slow and fast desensitization kinetics in medium spiny neurons and giant aspiny neurons, respectively, and differences in cyclothiazide modulation. The rate of cyclothiazide dissociation from the AMPA receptor, activated by glutamate, was ,,90 times slower in medium spiny neurons than in giant aspiny neurons. In giant aspiny neurons (not medium spiny neurons) this rate was strongly dependent on the presence of an agonist; 1 m m glutamate increased it 30-fold. Thus, two major cell groups in the striatum display distinct AMPA receptor compositions carrying specific properties of glutamate responses. Excitatory transmission will thus be differentially affected by cyclothiazide-type compounds. [source] Differential modulation of rat hepatic stellate phenotype by natural and synthetic retinoidsHEPATOLOGY, Issue 1 2004Karine Hellemans Activation of hepatic stellate cells (HSC) is a central event in the pathogenesis of liver fibrosis during chronic liver injury. We examined the expression of retinoic acid (RAR) and retinoid X receptors (RXR) during HSC activation and evaluated the influence of natural and synthetic retinoic acids (RA) on the phenotype of culture-activated HSC. The expression of the major RAR/RXR subtypes and isoforms was analyzed by Northern hybridization. Presence of functional receptor proteins was established by gel shift analysis. Retinoic acids, RAR, and RXR selective agonists and an RAR antagonist were used to evaluate the effects of retinoid signalling on matrix synthesis by Northern blotting and immunoprecipitation, and on cell proliferation by BrdU incorporation. The 9- cisRA and synthetic RXR agonists reduced HSC proliferation and synthesis of collagen I and fibronectin. All- trans RA and RAR agonists both reduced the synthesis of collagen I, collagen III, and fibronectin, but showed a different effect on cell proliferation. Synthetic RAR agonists did not affect HSC proliferation, indicating that ATRA inhibits cell growth independent of its interaction with RARs. In contrast, RAR specific antagonists enhance HSC proliferation and demonstrate that RARs control proliferation in a negative way. In conclusion, natural RAs and synthetic RAR or RXR specific ligands exert differential effects on activated HSC. Our observations may explain prior divergent results obtained following retinoid administration to cultured stellate cells or to animals subjected to fibrogenic stimuli. (HEPATOLOGY 2004;39:97,108.) [source] Differential modulation of CD8, by rat ,, and ,, T cells after activationIMMUNOLOGY, Issue 3 2001Frank Straube Summary Major histocompatibility complex (MHC) class I-restricted ,, T cells express the CD8,, heterodimer, which acts as a MHC class I-specific co-receptor. Rats are so far the only species with frequent expression of the CD8,, by MHC-unrestricted ,, T cells. This study compares CD8,, expression by splenic rat ,, and ,, T cells and reveals a lineage-specific difference in the control of CD8, expression. After activation in vitro, many ,, T cells, but not ,, T cells, persistently down-modulate the expression of CD8,, but not CD8,, at the RNA level. Down-regulation occurred after stimulation with T-cell receptor (TCR)-specific monoclonal antibody (mAb) and interleukin-2 (IL-2) or CD28-mediated costimulation, and after activation with phorbol 12-myristate 13-acetate (PMA) and ionomycin. Functional differences between modulating and non-modulating cells were not found with respect to interferon-, (IFN-,) production and cytolytic activity. The modulation could be indicative for a fundamental difference between ,, and ,, T cells and also limits the use of CD8, as a stable marker of ,, T-cell subsets. Possibly, CD8, modulation provides a mechanism to escape over-stimulation by (auto-)antigens by increasing the threshold of TCR-mediated activation in ,, T cells. [source] Differential modulation of innate immune cell functions by the Burkholderia cepacia complex: Burkholderia cenocepacia but not Burkholderia multivorans disrupts maturation and induces necrosis in human dendritic cellsCELLULAR MICROBIOLOGY, Issue 10 2008Kelly L. MacDonald Summary Burkholderia cepacia complex (BCC) bacteria cause pulmonary infections that can evolve into fatal overwhelming septicemia in chronic granulomatous disease or cystic fibrosis patients. Burkholderia cenocepacia and Burkholderia multivorans are responsible for the majority of BCC infections in cystic fibrosis patients, but B. cenocepacia is generally associated with a poorer prognosis than B. multivorans. The present study investigated whether these pathogens could modulate the normal functions of primary human monocyte-derived dendritic cells (DCs), important phagocytic cells that act as critical orchestrators of the immune response. Effects of the bacteria on maturation of DCs were determined using flow cytometry. DCs co-incubated for 24 h with B. cenocepacia, but not B. multivorans, had reduced expression of costimulatory molecules when compared with standard BCC lipopolysaccharide-matured DCs. B. cenocepacia, but not B. multivorans, also induced necrosis in DCs after 24 h, as determined by annexin V and propidium iodide staining. DC necrosis only occurred after phagocytosis of live B. cenocepacia; DCs exposed to heat-killed bacteria, bacterial supernatant or those pre-treated with cytochalasin D then exposed to live bacteria remained viable. The ability of B. cenocepacia to interfere with normal DC maturation and induce necrosis may contribute to its pathogenicity in susceptible hosts. [source] The proportion of CD40+ mucosal macrophages is increased in inflammatory bowel disease whereas CD40 ligand (CD154)+ T cells are relatively decreased, suggesting differential modulation of these costimulatory molecules in human gut lamina propriaINFLAMMATORY BOWEL DISEASES, Issue 11 2006Dr. Hege S. Carlsen MD Abstract Background: Signal transduction through binding of CD40 on antigen-presenting cells and CD40 ligand (CD154) on T cells appears to be crucial for mutual cellular activation. Antibodies aimed at blocking the CD40,CD154 costimulatory pathway dampen the severity of experimental colitis. To elucidate the microanatomical basis for signaling through this costimulatory pathway in human inflammatory bowel disease, we studied in situ the cellular distribution of these 2 molecules on lamina propria macrophages and T cells, respectively. Methods: Colonic specimens from 8 patients with ulcerative colitis and 8 with Crohn's disease, 8 small bowel specimens of Crohn's disease, and histologically normal control samples (6 from colon and 6 from small bowel) were included. Multicolor immunofluorescence in situ staining was performed to determine the percentage of subepithelial macrophages expressing CD40 and that of lamina propria T cells expressing CD154 while avoiding cells in lymphoid aggregates. Results: The proportion of subepithelial CD40highCD68+ macrophages was significantly increased in normal colon compared with normal small bowel and showed further elevation in both colon and small bowel afflicted with inflammatory bowel disease. In addition, on a per-CD68+ -cell basis, CD40 expression was significantly increased in severely inflamed compared with moderately inflamed colonic specimens. Conversely, the proportion of CD154+ T cells was similar in colon and small bowel, and interestingly, it was significantly reduced in colonic inflammatory bowel disease. Conclusions: Our findings suggested that modulation of CD40 expression by subepithelial macrophages and CD154 by lamina propria T cells is inversely modulated in the human gut. [source] Evidence for two conductive pathways in P2X7 receptor: differences in modulation and selectivityJOURNAL OF NEUROCHEMISTRY, Issue 3 2010Susanna Alloisio J. Neurochem. (2010) 113, 796,806. Abstract The P2X7 receptor (P2X7R) is an ATP-gated cation channel whose biophysical properties remain to be unravelled unequivocally. Its activity is modulated by divalent cations and organic messengers such as arachidonic acid (AA). In this study, we analysed the differential modulation of magnesium (Mg2+) and AA on P2X7R by measuring whole-cell currents and intracellular Ca2+ ([Ca2+]i) and Na+ ([Na+]i) dynamics in HEK293 cells stably expressing full-length P2X7R and in cells endowed with the P2X7R variant lacking the entire C-terminus tail (trP2X7R), which is thought to control the pore activation. AA induced a robust potentiation of the P2X7R- and trP2X7R-mediated [Ca2+]i rise but did not affect the ionic currents in both conditions. Extracellular Mg2+ reduced the P2X7R- and trP2X7R-mediated [Ca2+]i rise in a dose-dependent manner through a competitive mechanism. The modulation of the magnitude of the P2X7R-mediated ionic current and [Na+]i rise were strongly dependent on Mg2+ concentration but occurred in a non-competitive manner. In contrast, in cells expressing the trP2X7R, the small ionic currents and [Na+]i signals were totally insensitive to Mg2+. Collectively, these results support the tenet of a functional structure of P2X7R possessing at least two distinct conductive pathways one for Ca2+ and another for monovalent ions, with the latter which depends on the presence of the receptor C-terminus. [source] MAPKs are differentially modulated in arctic ground squirrels during hibernationJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2005Xiongwei Zhu Abstract Hibernating animals are very tolerant of trauma to the central nervous system such that dramatic fluctuations in cerebral blood flow occur during hibernation and arousal without apparent damage. Indeed, it was demonstrated that Arctic ground squirrels (AGS) experience acute and severe systemic hypoxia along with the dramatic fluctuation in cerebral blood flow when the animals are aroused from hibernation. While initial hypotheses concerned protective mechanisms in the hibernating state, recent evidence of sustained elevation of HIF1, in euthermic AGS from our laboratory suggests that a preparatory program of protective gene expression is chronically expressed in euthermic AGS. In this study we evaluated potential neuroprotective adaptations by examining the alteration of intracellular MAPK pathways that may be modulated by hypoperfusion/reperfusion in AGS during hibernation and arousal. We found that ERK and JNK are activated in both euthermic and aroused AGS compared to the hibernating group which positively correlated with HIF1, levels. The activation of ERK and JNK associated with HIF1, may play an important role in mediating neuroprotective adaptations that is essential for successful hibernation. Interestingly, p38 is activated in euthermic AGS but not in aroused AGS, which shows strong correlation with iNOS induction. Therefore, the attenuation of p38 activation and iNOS induction in hibernating and aroused animals may contribute to the attenuation of inflammation that plays important neuroprotective roles during hibernation. Taken together, the differential modulation of the MAPK pathways may be critical for neuroprotection of AGS necessary for fluctuations in oxygen and nutrient delivery during hibernation. © 2005 Wiley-Liss, Inc. [source] Glutathione cycle in stable chronic obstructive pulmonary diseaseCELL BIOCHEMISTRY AND FUNCTION, Issue 6 2010Biljak, Vanja Radi Abstract Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and oxidant/antioxidant imbalance. Glutathione is the most abundant cellular low-molecular weight thiol and the glutathione redox cycle is the fundamental component of the cellular antioxidant defence system. Concentration of total glutathione and catalytic activities of glutathione peroxidase and glutathione reductase were determined in peripheral blood of patients (n,=,109) and healthy subjects (n,=,51). Concentration of total glutathione in patients was not changed in comparison to healthy controls. However, we found statistically significant difference between patients with moderate and severe disease stages. Glutathione reductase activity was increased, while glutathione proxidase activity was decreased in the patients with COPD, when compared to healthy controls. We found no significant difference in glutathione peroxidase and glutathione reductase activities between stages. Patients who smoked had lower concentration of total glutathione compared with former smokers and never-smoking patients. Lung function parameters were inversely associated with glutathione level. Evidence is presented for differential modulation of glutathione peroxidase and glutathione reductase activities in peripheral blood of patients with stable COPD. We suppose that in addition to glutathione biosynthesis, glutathione reductase-dependent regulation of the glutathione redox state is vital for protection against oxidative stress. Copyright © 2010 John Wiley & Sons, Ltd. [source] | |||||||||||||