Effect of water restrictions on the physiological parameters,psychological behavior and brain c-Fos expression in rat

1 Introduction Exposure to hostile stressors causes a series of coor- dinated responses in the body, such as alterations of neu- roendocrine secretion, immune reaction and behavioral manifestation to maintain homeostasis stability and sur-vival of the organisms. Stressors are divided into two main categories: physical, or systemic, and psychological, or emotional / processive. Each stressor might activate a spe- cific central pathway to induce a special neuroendocrine response, even cause stre…     

Expression of c-fos, fos B, and egr-1 in the medial preoptic area and bed nucleus of the stria terminalis during maternal behavior in rats

The spatial and temporal pattern of expression of the protein products of immediate early genes (IEGs) c-fos, fos B, and egr-1 were mapped in medial preoptic area (MPOA) and ventral bed nucleus of stria terminalis (VBST) during maternal behavior in rats. Immunocytochemical analysis indicated significant increases in the number of cells expressing c-Fos after 2 h of pup exposure, while Fos B levels showed a delayed response, reaching maximal levels after 6 h.     

N(omega)-nitro-L-arginine methyl ester attenuates lithium-induced c-Fos, but not conditioned taste aversion, in rats

Lithium chloride (LiCl) at doses sufficient to induce conditioned taste aversion (CTA) causes c-Fos expression in the relevant brain regions and activates the hypothalamic-pituitary-adrenal (HPA) axis. It has been suggested that nitric oxide (NO) in the central nervous system may play a role not only in the activation of HPA axis but also in CTA learning, and that LiCl may activate the brain NO system. To determine the role of NO in lithium-induced CTA, we examined the lithium-induced CTA, brain c-Fos expression, and plasma corticosterone level with Nomega-nitro-L-arginine methyl ester (L-NAME) pretreatment. Intraperitoneal L-NAME (30 mg/kg) given 30 min prior to LiCl significantly decreased lithium-induced c-Fos expression in the brain regions implicated in CTA learning, such as the hypothalamic paraventricular nucleus (PVN), central nucleus of amygdala (CeA), and nucleus tractus of solitarius. However, either the lithium-induced CTA acquisition or the increase in plasma corticosterone was not attenuated by l-NAME pretreatment. These results suggest that NO may be involved in lithium-induced neuronal activation of the brain regions, but not in the CTA acquisition or the HPA axis activation.     

Increased c-Fos/activator protein-1 confers resistance against anergy induction on antigen-specific T cell

We have studied the contribution of c-Fos/activator protein-1 (AP-1) to antigen-specific T cell response with reference to T cell anergy by increasing c-Fos/AP-1 in vivo and in vitro. First, after injection of a high dose of staphylococcus enterotoxin B (SEB), clonal deletion of SEB-reactive V(beta)8(+) CD4 T cells occurred both in control B6 and H2-c-fos transgenic (fos) mice, whereas proliferation of T cells against SEB was profoundly depressed in B6 but not in fos mice. Second, the keyhole limpet hemocyanin-specific CD4 T(h)1 cell clone produced decreasing amounts of IL-2 in response to increasing amounts of concanavalin A (Con A) in vitro, whereas the decrease was less significant in the T(h)1 clones stably transfected with c-fos gene. Electrophoretic mobility shift assay with nuclear protein from the transformants showed that overexpression of the c-fos gene compensated the amounts of AP-1 in the nuclei of Con A-treated T(h)1 clones. Thus, increased c-Fos/AP-1 confers resistance against anergy induction on antigen-specific T cells.     

Potent anti-inflammatory/analgesic effects of lornoxicam in comparison to other nsaids: A c-fos study in the rat

This study evaluates the anti-inflammatory/analgesic effects of lornoxicam, a new non-steroidal anti-inflammatory drug, using the method of c-Fos protein immunoreactivity in the carrageenan model of inflammatory nociception in the rat. The immunohistochemical revelation of inflammatory/nociceptive stimulation evoked c-Fos expression in spinal neurons was used as an indirect marker of neurons involved in spinal nociceptive transmission. Lornoxicam (0.1, 0.3, 1, 3 and 9 mg/kg; n=10 rats for each group) was preadministered intravenously 25 min before an intraplantar injection of carrageenan (6 mg/150 ml of saline). Three hours after carrageenan, the peripheral oedema (paw and ankle diameters) and the number of c-Fos-protein-like immunoreactive (c-Fos-LI) neurons in the lumbar spinal cord, were assessed. Preadministered lornoxicam dose relatedly reduced the total number of c-Fos-LI neurons (regression coefficient r=0.79; p<0.001) with the strongest effect corresponding to the 75±2% reduction (p<0.001) for the highest dose of 9 mg/kg, and the 45±3% reduction (p<0.001) for the low dose of 0.3 mg/kg. Lornoxicam (0.1, 0.3, 1, 3 and 9 mg/kg iv) significantly reduced the number of c-Fos-LI neurons in both superficial (24±6, 33±5, 53±4, 54±4, and 63±4% reduction, respectively, p<0.001 for all doses) and deep (28±4, 48±4, 62±2, 69±3 and 79±2% reduction, respectively, p<0.001 for all doses) laminae of the dorsal horn of the spinal cord. These reducing effects were dose related in both superficial and deep laminae (regression coefficient r=0.66 and r=0.08, respectively; p<0.001 for both). The lowes dose of lornoxicam (0.1 mg/kg iv) had a similar effect in both superficial and deep laminae, whereas the four higher doses (0.3, 1, 3 and 9 mg/kg iv) had a significantly stronger effect on the number of c-Fos-LI neurons in deep laminae as compared to that in superficial laminae. Lornoxicam (0.1, 0.3, 1, 3 and 9 mg/kg iv) dose relatedly reduced the carrageenan induced oedema at both the paw and ankle levels (regression coefficient r=0.63 and r=0.53, respectively, p<0.001 for both), with a stronger effect on the ankle diameter (34±8, 61±9, 66±8, 80±6 and 83±5% reduction, respectively p<0.001 for all doses). Furthermore reductions of the carrageenan evoked peripheral oedema and spinal c-Fos expression were positively correlated (correlation coefficient r=0.74 and r=0.57 for the paw and ankle diameter respectively, p<0.001 for both). These correlations suggest a predominant peripheral site, without excluding central site of action of lornoxicam in the carrageenan-induced inflammation. Our results provide clear evidence for a potent anti-inflammatory/analgesic effects of low doses of lornoxicam which have a reduced risk of sideeffects. Taken together, the results of the present study revealed the effects of lornoxicam in the same range as those of other previously studied NSAIDs, more precisely, closely comparable to the effects of ketoprofen.     

Effects of opioid receptor antagonists on the effects of i.v. morphine on carrageenin evoked c-Fos expression in the superficial dorsal horn of the rat spinal cord

This study performed in freely moving rats evaluated the ability of specific opioid receptor antagonists to reverse the inhibitory effects of morphine on carrageenin-induced c-Fos expression in the spinal cord. Our study focused on the superficial dorsal horn (laminae I-II), which is the main termination site of nociceptive primary afferent fibers and is rich in opioid receptors. In order to replicate clinical routes of administration, all agents were administered intravenously (i.v.). As previously demonstrated, pre-administered i.v. morphine (3 mg/kg) produced a marked decrease (58+/-5%) in the number of Fos-LI neurones measured at 2 h after intraplantar (i.pl.) carrageenin (6 mg/150 microl) and yet was without influence on peripheral oedema. This decrease in c-Fos expression was completely blocked by combined administration of morphine with the mu-opioid receptor antagonist, [D-Phe-Cys-Tyr-D-Orn-Thr-Pen-Thr-NH2] (CTOP-1+1 mg/kg). Naltrindole (NTI-1+1 mg/kg), a delta-opioid receptor antagonist partially blocked the effects of systemic morphine, so that the inhibitory effects of morphine after NTI injection are now 40+/-4%. However, this effect of NTI was weak since the depressive effects of morphine were still highly significant (p<0.001). In contrast, nor-binaltorphimine (nor-BNI-1+1 mg/kg), a kappa-opioid receptor antagonist, had no significant effect on the effects of morphine. These results indicate the major contribution of mu-opioid receptors to the antinociceptive effects of systemic morphine at the level of the superficial dorsal horn. The observed effect of NTI is not necessarily related to a direct action of morphine on delta-opioid receptors and some possible actions of this antagonist are discussed.     

Expression of c-fos-like immunoreactivity in the feline brainstem in response to isometric muscle contraction and baroreceptor reflex changes in arterial pressure

This study compared whether activation of muscle ergoreceptor afferents caused by isometric muscle contraction, activation of baroreceptor afferents induced by i.v. infusion of phenylephrine, or baroreceptor afferent inactivation, caused by carotid artery occlusion, elicit similar patterns of c-Fos induction in brainstem areas. Adult cats were anesthetized with alpha-chloralose, and in each case, the experimental intervention caused an increase in the arterial blood pressure. There were two sets of control experiments: in both, animals underwent the same surgical procedures but then either remained at rest for the entire study, or the tibial nerve was stimulated, as in the contraction group, following muscle paralysis with tubocurarine. Following the procedures, animals rested for 90 min to allow neuronal expression of c-Fos. Control cats showed very little c-Fos immunoreactivity (c-Fos-ir) in the brainstem. Muscle contraction induced c-Fos-ir expression mainly in the nucleus tractus solitarius, lateral reticular nucleus, lateral tegmental field, vestibular nucleus, subretrofacial nucleus, spinal trigeminal tract and in a lateral region of the periaqueductal grey (P 0.5-1.0). The majority of the c-Fos-ir was found in brainstem areas contralateral to the contracted muscle. In addition, muscle contraction induced c-Fos-ir in the dorsal horns of spinal segments L6-S1 on the ipsilateral side of the spinal cord. Phenylephrine infusion caused c-Fos-ir expression in the nucleus tractus solitarius, spinal trigeminal tract, solitary tract, and dorsal motor nucleus of the vagus. No c-Fos-ir was apparent in the periaqueductal grey. Carotid occlusions induced c-Fos-ir expression in the area postrema, nucleus tractus solitarius, solitary tract, and spinal trigeminal tract. Expression was bilateral. Areas that exhibited c-Fos-ir correspond to sites previously reported to release various neuropeptides in response to muscle contraction or carotid occlusions. These results indicate that the exercise pressor reflex and baroreflex activate similar, but not completely identical, sites in the brainstem.     

肾癌组织 DGFR及c-Fos的表达研究

目的探讨PDGFR及蛋白c-Fos的表达与肾细胞癌(CC)发生的关系.方法应用免疫组化SP法检测12例正常肾组织、14例癌旁肾组织、46例肾细胞癌组织中PDGFR和c-Fos蛋白的表达,并结合肾癌的分级、分期和随访结果进行分析.结果 PDGFR及c-Fos在RCC组织中的表达阳性率分别为73.91%及52.17%,明显高于正常组织及癌旁组织,有显著性差异.PDGFR在透明细胞癌中的表达阳性率明显高于颗粒细胞癌,有显著性差异.PDGFR及c-Fos在RCC组织血管中的表达明显增强.PDGFR的表达与RCC的分级相关.结论 PDGFR及c-Fos的过度表达与RCC的发生密切相关,并与肿瘤血管形成相关.PDGFR的表达与RCC的恶性程度相关.