Neurochemistry of nerve fibers apposing sympathetic preganglionic neurons activated by sustained hypotension

Sympathetic preganglionic neurons (SPN) in rat spinal cord were activated by the reflex stimulation of bulbospinal sympathetic neuronal pathways after a nitroprusside-induced hypotension. Hypotension-sensitive SPN, identified by immunoreactivity (IR) to the product of the immediate early gene c-fos and to choline acetyltransferase, were localized in the intermediolateral cell column of thoracic and upper lumbar cord, particularly middle to lower thoracic cord. Putative neurotransmitters, or their markers, in varicose fiber networks around SPN were identified. Nearly all hypotension-sensitive (Fos-IR) SPN were apposed by varicose fibers immunoreactive for tyrosine hydroxylase, serotonin, substance P, or enkephalin. Neuropeptide Y (NPY)- or phenylethanolamine-N-methyl transferase (PNMT)-IR varicose fibers apposed Fos-IR SPN in the upper and middle thoracic spinal cord, but in lower thoracic segments some Fos-IR SPN lacked these appositions. In thoracic segment 12, 51% +/- 5% of Fos-IR SPN (n = 9 rats) lacked PNMT contacts and 25% +/- 3% of Fos-IR SPN (n = 8 rats) lacked NPY contacts. In contrast to other chemically defined afferents, galanin-IR varicose fibers apposed fewer than half of the Fos-IR SPN in the middle to lower thoracic cord. Neurotransmitters/neuromodulators that might influence the activity of SPN acting in the baroreflex-mediated control of blood pressure have been identified. Uniformity in the neurochemistry of some fibers making connections with Fos-IR SPN, regardless of their segmental origin, suggests that common sets of neurons provide convergent inputs to all hypotension-sensitive SPN. Other fibers show topographic differences in their contacts with Fos-IR SPN, suggesting that subgroups of hypotension-sensitive SPN are targeted by particular neuron groups.     

2,3,7,8-Tetrachlorodibenzo-p-dioxin treatment induces c-Fos expression in the forebrain of the Long-Evans rat

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most toxic environmental pollutants. In the present study, we examined c-Fos expression in the central nervous system (CNS) after administration of a lethal dose of TCDD to the adult Long-Evans rat to clarify if the CNS participates in TCDD-induced intoxication. A single dose of TCDD (dissolved in olive oil, 50 microg/kg) or olive oil alone was administered to the rats by gavage. Animals were allowed to survive for 1 day to 5 weeks. Three days after the administration, a significantly large number of Fos-immunopositive cells were found in the hypothalamus (i.e. dorsomedial hypothalamic nucleus, paraventricular hypothalamic nucleus, medial preoptic nucleus), central amygdaloid nucleus and bed nucleus of the stria terminalis. These results suggest that some TCDD toxicity may be induced by its direct action on the CNS.     

Effects of extrinsic autonomic inputs on expression of c-Fos immunoreactivity in myenteric neurons of the guinea pig distal colon

c-Fos protein is a nuclear protein coded by c-fos proto-oncogene subsequent to synaptic activation of the neurons. We used immunohistochemical methods to visualize the expression of c-Fos protein in myenteric neurons of the guinea pig distal colon and examined the effects of the extrinsic autonomic inputs on the enteric circuits. No c-Fos immunoreactivity was observed in the colonic segments fixed immediately after removal from the animal body. A number of c-Fos-immunoreactive nuclei of myenteric neurons, however, appeared in all preparations that were incubated in Krebs solution in vitro (n=10). Application of tetrodotoxin (0.2 microM) abolished the expression of c-Fos-immunoreactivity (n=6), but hexamethonium (100 microM) failed to decrease the number of c-Fos-positive neurons despite a complete suppression of spontaneous peristaltic movements (n=5). Neither the electrical stimulation (n=8) nor the severing of the pelvic nerves (n=5) changed the number of c-Fos-positive neurons. Application of clonidine, an alpha(2)-agonist, (0.1 microM) abolished the expression of c-Fos protein in all preparations (n=5), while denervation of the sympathetic fibers in the lumbar colonic and hypogastric nerves in vivo increased the number of c-Fos-positive neurons (n=5). The results indicate that the enteric circuit in the distal part of the gastrointestinal tract is under tonic inhibition by the sympathetic nervous system from the lumbar spinal cord. c-Fos immunoreactivity expressed in the colonic preparations in vivo might be the results of enhanced activation of non-nicotinic receptors after removal of the sympathetic inhibition.     

The effects of sympathectomy on capsaicin-evoked fos expression of spinal dorsal horn GABAergic neurons

In various hypothalamic and adjacent brain regions we have previously found a remarkable increase in nuclear estrogen receptor staining in Alzheimer's disease (AD). In order to see whether this was a general phenomenon or rather specific for those areas that are affected by the AD process we investigated ERalpha and ERbeta expression in the arginine-vasopressin (AVP) neurons of the human dorsolateral suparoptic nucleus (dl-SON), that is the major source of plasma AVP. These neurons remain exceptionally intact in AD. Changes in ER expression were studied in relation to early Alzheimer changes (i.e. hyperphosphorylated tau) and neuronal metabolism in AD as determined by the size of the Golgi apparatus (GA) or cell size. No difference in neuronal metabolism (i.e. GA size or cell size) of AVP neurons was observed between AD and control patients and no early cytoskeletal AD alterations were found confirming the resistance of the dl-SON to AD. While no differences between AD and control patients were present for ERalpha and ERbeta staining except for a lower proportion of nuclear ERbeta AVP-positive neurons in AD subjects, complex sex differences not directly related to AD were observed within each group. The main finding of the present study is that in the dl-SON, that remains active and spared of AD changes, the increase in nuclear ERs seen in adjacent affected areas in AD patients does not occur. This indicates that a rise of nuclear ERs is not a generally occurring phenomenon but rather related to the pathogenetic alterations of the AD process.     

乙醇诱导大鼠急性胃炎后Fos在中枢神经系统的表达

目的：探讨乙醇诱导大鼠急性胃炎后Fos在中枢神经系统的表达及其意义。方法：取30只成年雄性Wistar大鼠，随机分为5组，每组6只。A组：单纯生理盐水灌胃组；B组：单纯乙醇灌胃组；C组：膈下迷走神经切断乙醇灌胃组；D组：内脏大、小神经切断乙醇灌胃组；E组：膈下迷走神经和内脏大、小神经均切断乙醇灌胃组。运用免疫组化技术显示Fos阳性神经元在大鼠中枢神经系统(CNS)中的分布。结果：B、C组动物的Fos阳性神经元在丘脑腹后外侧核、第9胸髓后角胶状质内大量存在，疑核和迷走神经背核内有少量聚集；B、D组Fos阳性神经元在疑核和迷走神经背核内有较多聚集，但远低于B、C组在丘脑腹后外侧核、第9胸髓后角胶状质内的Fos阳性神经元数。而A、E组在上述4个核团内Fos阳性神经元则较少。结论：胃的痛觉冲动以交感神经传入为主。     

复方高原春颗粒对缺氧脑损伤CAI区Fos蛋白表达的影响

目的研究中藏药高原春颗粒对缺氧脑损伤CAI区Fos蛋白表达的影响。方法利用缺氧脑损伤模型,通过免疫组织化学方法,观察24 h缺氧结束时及复氧后24 h两个时段大脑海马CAI区Fos蛋白表达的变化,同时观察预防性应用高原春颗粒后对上述指标的影响。结果缺氧后大脑海马CAI区Fos蛋白表达减少,而服用高原春颗粒后,缺氧大脑海马CAI区Fos蛋白表达有一定程度的增加。结论中藏药复方高原春颗粒的抗缺氧作用可能与影响大脑海马CAI区Fos蛋白表达有关。     

实验性运动病大鼠脑细胞c-fos基因表达

取SD大鼠16只分为两组，其中一组按Crampton的方法进行旋转刺激诱导运动病；而另一非旋转组作为对照。用原位杂交和免疫组化方法、图像分析技术对旋转刺激组大鼠及对照组大鼠大脑皮质、脑干和小脑皮质中c-fosmRNA、Fos蛋白含显变化进行定位、定量研究。结果表明，旋转刺激后三种组织中c-fosmRNA、Fos蛋白的含量均有增加．推测应激反应基因c－fos的表达参与运动病的发生和发展。     

Cell death in the normal developing brain, and following ionizing radiation, methyl-azoxymethanol acetate, and hypoxia-ischaemia in the rat

Naturally occurring (programmed) cell death in the developing brain has morphological characteristics of apoptosis and is associated with internucleosomal DNA fragmentation. Apoptosis also plays a role in cell death following hypoxia-ischaemia in the developing rat brain. Ionizing radiation-induced cell death in the brain of the young rat has morphological characteristics of apoptosis. is mediated by protein synthesis and is associated with internucleosomal UNA fragmentation. Methylazoxymethanol (MAM) acetate injection in the young rat produces apoptotic cell death in the external granule cell layer of the cerebellum. In addition, strong c-Jun immunore-activity is observed in apoptotic cells during normal development and following experimentally induced cell death. Moreover, c-Jun mRNA induction and de novo c-Jun protein synthesis, together with activation of c-Jun/AP-1, as revealed with gel mobility shift assay, occurs in irradiated animals. Western blotting of total brain homogenates shows a c-Jun-immunoreactive band at p39, which corresponds to the molecular weight of c-Jun. in control rats. However, a thick c-Jun-immunoreactive band at about p62, accompanied by a decrease of the p39 band, occurs in irradiated and MAM-treated rats. A thin band immediately above the thick p62 band, suggestive of c-Jun phosphorylation, is also observed in treated rats. Taken together, these observations indicate that c-Jun expression is associated with apoptotic cell death in the developing central nervous system.     

Forebrain patterns of c-Fos and FosB induction during cancer-associated anorexia-cachexia in rat

Forebrain structures are necessary for the initiation of food intake and its coupling to energy expenditure. The cancer-related anorexia-cachexia syndrome is typified by a prolonged increase in metabolic rate resulting in body weight loss which, paradoxically, is accompanied by reduced food intake. The aim of the present work was to study the forebrain expression of Fos proteins as activation markers and thus to identify potential neurobiological mechanisms favouring catabolic processes or modulating food intake in rats suffering from cancer-related anorexia-cachexia. Neurons in forebrain structures showing most pronounced induction of Fos proteins were further identified neurochemically. To provoke anorexia-cachexia, cultured Morris hepatoma 7777 cells were injected subcutaneously in Buffalo rats. This resulted in a slowly growing tumour inducing approximately 7% body weight loss and a 20% reduction in food intake when the tumour represented 1-2% of body mass. Anorexia-cachexia in these animals was found to be accompanied by Fos induction in several hypothalamic nuclei including the paraventricular and ventromedial hypothalamus, in the parastrial nucleus, the amygdala, the bed nucleus of the stria terminalis, ventral striatal structures and the piriform and somatosensory cortices. Neurochemical identification revealed that the vast majority of FosB-positive neurons in the nucleus accumbens, ventral caudate-putamen and other ventral striatal structures contained prodynorphin or proenkephalin mRNA. These findings indicate that forebrain structures that are part of neuronal networks modulating catabolic pathways and food ingestion are activated during tumour-associated anorexia-cachexia and may contribute to the lack of compensatory eating in response to weight loss characterizing this syndrome.     

Activation and circuitry of uterine-cervix-related neurons in the lumbosacral dorsal root ganglia and spinal cord at parturition

Stimulation of the uterine cervix at parturition activates neural circuits involving primary sensory nerves and supraspinally projecting neurons of the lumbosacral spinal cord, resulting in output of hypothalamic neurohormones. Dorsal root ganglia (DRG) and spinal neurons of these circuits are not well-characterized. The objectives of this study were to detail the activation of DRG and spinal neurons of the L6/S1 levels that are stimulated at late pregnancy, verify hypothalamic projections of activated spinal neurons, and determine whether activated neurons express estrogen receptor-alpha (ERalpha). Expression of phosphorylated cyclic-AMP response element-binding protein (PCREB) and Fos immunohistochemistry were used to "mark" activated DRG and spinal neurons, respectively. Retrograde tracing identified uterine-cervix-related and spinohypothalamic neurons. Baseline PCREB expression in the DRG increased during pregnancy and peaked during the last trimester. Some PCREB-expressing neurons contained retrograde tracer identifying them as cervix-related neurons. Fos-expressing neurons were few in spinal cords of nonpregnant and day 22 pregnant rats but were numerous in parturient animals. Some Fos-expressing neurons located in the dorsal half of the spinal cord contained retrograde tracer identifying them as spinohypothalamic neurons. Some DRG neurons expressing PCREB also expressed ERalpha, and some spinal neurons activated at parturition projected axons to the hypothalamus and expressed ERalpha. These results indicate that DRG and spinal cord neurons are activated at parturition; that those in the spinal cord are present in areas involved in autonomic and sensory processing; that some spinal neurons project axons to the hypothalamus, ostensibly part of a neuroendocrine reflex; and that sensory and spinal neurons can respond to estrogens. Moreover, some activated sensory neurons may be involved in the animal's perception of labor pain.