Morphine or U-50,488 suppresses Fos protein-like immunoreactivity in the spinal cord and nucleus tractus solitarii evoked by a noxious visceral stimulus in the rat.

Immunohistochemical visualization of Fos protein, the nuclear phosphoprotein product of the early-immediate gene c-fos, permits identification of populations of neurons that are activated in response to a variety of stimuli. This study examined the distribution of Fos-like immunoreactive (FLI) neurons in the spinal cord and the nucleus tractus solitarii (NTS) of the caudal medulla evoked by a noxious visceral stimulus in the unanesthetized rat. It also compared the inhibition of pain behavior and Fos expression by a mu-selective opioid agonist, morphine, and a kappa-selective opioid agonist, U-50,488. Intraperitoneal injection of 3.5% acetic acid in the unanesthetized rat evoked the expression of FLI in a discrete population of spinal cord neurons, the distribution of which closely mirrored the spinal terminations of visceral primary afferents. Specifically, FLI neurons were concentrated in laminae I, IIo, V, VII, and X. Large numbers of Fos-immunoreactive neurons were also present in the NTS of the caudal medulla, most likely as a result of spinosolitary tract and vaginal afferent input. The number of labeled neurons in both the spinal cord and the NTS was significantly correlated with the number of abdominal stretches, a pain behavior measure. Both morphine (1-10 mg/kg s.c.) and U-50,488 (3-30 mg/kg s.c.) produced a dose-dependent inhibition of the pain behavior in these animals and a dose-dependent suppression of the number of FLI neurons in both the spinal cord and in the NTS; complete suppression of FLI neurons was, however, not necessary for the production of antinociception. Furthermore, although equianalgesic doses of morphine and U-50,488 reduced the number of labelled neurons in the spinal cord to a comparable extent, morphine reduced the number of immunoreactive neurons in the NTS to a greater extent than did U-50,488. These results suggest that morphine and U-50,488 have comparable effects on the transmission of visceral nociceptive messages by spinal neurons, but differentially affect the autonomic response to noxious visceral stimuli.     

侧脑室注射STZ造模致大鼠阿尔茨海默病的实验研究

目的以行为学和免疫组化为指标,探讨STZ在AD大鼠造模中的作用。方法 36只健康Wistar大鼠随机分为正常组、模型对照组、模型组。用水迷宫检测学习记忆,免疫组化法检测NGF及c-fos的表达。结果模型组大鼠逃避潜伏期和游泳路程明显延长,c-fos表达高于正常组而NGF表达低于正常组,差异均有统计学意义(P<0.01)。结论侧脑室注射STZ可以引起大鼠学习记忆障碍、c-fos表达增强及NGF表达降低。此造模方法可以作为研究AD的一种有用的动物模型。     

EGFR、HER2、c-jun、c-fos、p21、p16、p53在非小细胞肺癌中的表达及临床病理特征

目的探讨EGFR、HER2、c-jun、c-fos、p21、p16、p53在非小细胞肺癌(NSCLC)中的表达及临床病理特征。方法采用荧光原位杂交技术(FISH)和免疫组织化学法(SP)检测64例非小细胞肺癌组织中EGFR、HER2、c-jun、c-fos、p21、p16、p53的表达。结果 (1)64例NSCLC中EGFR和HER2阳性扩增率分别为39.0%和29.7%,在不同病理分级、不同临床TNM分期及有无淋巴结转移间无显著差异(P>0.05)。HER2基因在腺癌的扩增率明显高于鳞癌(P<0.05)。(2)c-jun、c-fos、p21、p16、p53蛋白在不同临床TNM分期有明显差异(P<0.05),在不同病理类型及分级间无明显差异(P>0.05),p53的表达水平在淋巴结转移组明显高于无淋巴结转移组(P<0.05)。(3)EGFR与HER2、c-jun、c-fos、p21的表达水平在NSCLC中呈正相关。结论联合检测EGFR、HER2、c-jun、c-fos、p21、p16、p53,有助于为NSCLC的早期诊断及个体化治疗提供新思路和新方法。NSCLC中HER2、c-jun、c-fos、p21在EGFR介导的信号传导通路中发挥了正性调节的作用。     

脱氧胆酸溶液灌肠对大鼠内脏敏感性及脊髓c-fos mRNA表达的影响

目的:研究脱氧胆酸溶液灌肠对大鼠结肠敏感性和脊髓背根神经节上c-los mRNA表达的影响.方法:以脱氧胆酸溶液连续灌肠3d建立大鼠炎症后慢性内脏痛觉过敏模型,在灌肠前及灌肠后第1,2,3,4周采用结直肠扩张法(CRD)测定腹壁回撤反射(AWR)评分和内脏感觉压力阈值,然后处死大鼠,取出远端结肠组织,行髓过氧化物酶(M...     

Physiological mechanisms regulating photic induction of Fos-like protein in hamster suprachiasmatic nucleus

Immediate early genes including c-fos are selectively induced in cells of the hamster suprachiasmatic nucleus (SCN) by nocturnal light stimulation, suggesting that the Fos protein may play a role in the photic entrainment of circadian rhythms. To examine the physiological regulation of the induction of c-fos in the SCN, we studied the effects of antagonists of excitatory amino acids (EAA) receptors on photic induction of Fos-like immunoreactivity (Fos-lir) in the hamster SCN. We also examined the effects of electrical stimulation of the intergeniculate leaflet (IGL) to see whether neural input from IGL to SCN is involved in the induction of Fos protein in SCN cells. The results indicate that for most SCN cells EAA receptors mediate photic input involved in Fos induction but that another mechanism affects cells in restricted area of the caudal SCN. The neurochemical mechanisms and pathways by which these cells are activated by light remain undetermined.     

川芎嗪对青霉素致痫大鼠神经元内c-fos表达的影响

目的:用免疫组织化学方法观察川芎嗪（TM）对青霉素致痫大鼠大脑皮层神经元内c-fos表达的影响。方法:使用青霉素癫痫模型,采用BL-410生物机能实验系统记录双侧大脑皮层癫痫放电,观察腹腔注射TMP对大鼠癫痫放电大脑皮层神经元内c-fos表达的影响。结果:腹腔注射TMP（20-40mg/kg）后,大脑皮层神经元内c-fos表达较对照组明显降低。结论:TMP能明显抑制c-fos的表达,具有抗癫痫放电作用。     

Adenosinergic modulation of caffeine-induced c-fos mRNA expression in mouse brain

The adenosine receptor antagonist, caffeine, transiently induced proto-oncogene c-fos mRNA in mouse brain in a dose-dependent fashion. In situ hybridization revealed that caffeine-induced c-fos expression was high in caudate-putamen and olfactory tubercle at both subconvulsive and convulsive doses. The pattern of c-fos mRNA distribution following caffeine administration differs from that reported after seizures induced by electroconvulsive shock (ECS) or other chemical convulsants, and closely parallels the distribution of adenosine A₂ receptors. Furthermore, the potent adenosine A₂ receptor agonist,5′-N-ethylcarboxamide adenosine (NECA) blocked caffeine-induced c-fos expression whereas the adenosine A₁ receptor ligand, N⁶-cyclohexyladenosine (CHA), had no effect. This study suggests that the caffeine-induced expression of c-fos mRNA may be mediated by the adenosine A₂ receptor in mouse brain.     

Effect of Touch-stimulus on the Expression of C-fos and TrkA in Spinal Cord Following Chronic Constriction Injury of the Sciatic Nerve in Rats

Central sensitization is a key mechanism in thedevelopment and maintenance of the chronic pain.Previous studies show that NGF triggers long last ing plasticity of central nociception, and the specif ic receptor of NGF TrkA is up regulated in thechronic inflammatory pain in the primary sensoryneurons[1], but their mechanisms are not fully un derstood so far. In order to examine the effect ofTrkA on the chronic pain, in this study, the C fosgene was used as a marker of neur…     

Opioid circuits originating from the nucleus paragigantocellularis and their potential role in opiate withdrawal

Neurons in the rat nucleus paragigantocellularis (PGi), located in the ventrolateral medulla, send collateral projections to the locus coeruleus (LC) and to the nucleus of the solitary tract (NTS). The present study examined whether neurons in the PGi that project to both the LC and NTS contain leucine(5)-enkephalin (ENK), and also whether opioid-containing neurons in the PGi are activated following withdrawal from opiates. Retrograde transport of Fluoro-Gold (FG) from the LC and transport of a protein-gold tracer from the NTS was combined with detection of an antibody directed against ENK in the PGi. Using fluorescence and brightfield microscopy, it was established that more than half of the neurons containing both FG and the protein-gold tracer, also exhibited immunolabeling for ENK. The most frequent location of triply labeled neurons was the retrofacial portion of the PGi. In a separate series, rats were chronically implanted with morphine or placebo pellets and, on the fifth day, were subjected to an intraperitoneal injection of naltrexone. Two hours following initiation of withdrawal, rat brains were obtained and processed for detection of c-fos and in situ hybridization labeling of preproenkephalin (PPE) mRNA. Naltrexone injections into morphine-dependent rats caused a dramatic increase in c-fos as compared to control rats. Approximately 66% of the c-fos-labeled neurons exhibited labeling for PPE mRNA. These were also enriched in the retrofacial portion of the PGi. Taken together, the present data indicate that withdrawal from opiates engages opioid neurons in the PGi, some of which may coordinate activity of neurons in both the NTS and the LC.     

精神分裂症动物模型大鼠脑内c-fos表达和行为的变化

目的探讨精神分裂症动物模型大鼠的行为表现对中枢神经元c-fos表达的变化。方法选用Sprague-Dawley大鼠32只。将大鼠随机分为4组,每组8只,其中,实验组腹腔注射地卓西平马来酸盐(MK801)建立精神分裂症的动物模型,对照组注射等量生理盐水;分别用Norton氏行为观察量表和c-fos蛋白免疫组化的方法测量动物模型的行为变化和脑中c-fos蛋白的表达。结果用MK801建立精神分裂症的动物模型,c-fos蛋白能在模型动物大脑的额叶皮层、海马和垂体3区表达最明显,这种表达随着动物模型保持时间的延长,并有表达增加的趋势;而在边缘叶、丘脑、视前区和中脑4区表达亦明显。在c-fos蛋白表达增强的同时,模型动物的行为表现紊乱和不协调程度亦随着动物模型保持时间的延长加重。在第3,5天行为紊乱表现更为明显(9.06±0.73)分,与对照组[(5.63±0.87)分]比较差异有显著性(P<0.01)。这种行为紊乱有一定的节律性,中午、下午两时间点行为分值较低[(8.47±1.70)分;(8.33±2.18)分],而在早、晚两时间点行为分值较高[(9.56±2.72)分;(10.45±1.66)分],其中晚上的行为分值[(10.45±1.66)分]在一天中最高。结论精神分裂症动物模型大鼠脑内存在c-fos蛋白表达的增强,这种表达增强有一定的区域性。Norton氏行为观察量表分值随着动物模型保持时间的延长有明显的增加。