Extra-hypothalamic afferent inputs to the supraoptic nucleus area of the rat as determined by retrograde and anterograde tracing techniques

To detect neuronal cell bodies whose axon projects to the hypothalamic supraoptic nucleus, small volumes (10-50 nl) of 30% horseradish peroxidase or 2% fast blue solutions were pressure-injected into the area of one supraoptic nucleus of rats. Both dorsal and ventral approaches to the nucleus were used. In animals where the injection site extended beyond the limits of the supraoptic nucleus, retrogradely labelled cell bodies were found in many areas of the brain, mainly in the septum, the nucleus of the diagonal band of Broca and ventral subiculum in the limbic system; the dorsal raphe nucleus, the locus coeruleus, the nucleus of the dorsal tegmentum, the dorsal parabrachial nucleus, the nucleus of the solitary tract and the catecholaminergic A1 region in the brain stem; in the subfornical organ and the organum vasculosum of the lamina terminalis, as well as in the median preoptic nucleus. In contrast, when the site of injection was apparently restricted to the supraoptic nucleus, labelling was only clearcut in the two circumventricular organs, the median preoptic nucleus, the nucleus of the solitary tract and the A1 region. Injections of wheat germ agglutinin coupled with horseradish peroxidase (60-80 nl of a 2.5% solution) made in the septum and in the ventral subiculum anterogradely labelled fibers coursing in an area immediately adjacent to the supraoptic nucleus but not within it. In contrast, labelling within the nucleus was found following anterograde transport of tracer deposited in the A1 region and in an area that includes the nucleus of the solitary tract. Neurones located in the perinuclear area were densely labelled by small injections into the supraoptic nucleus; they may represent a relay station for some afferent inputs to the supraoptic nucleus. These results suggest that the supraoptic nucleus is influenced by the same brain areas which project to its companion within the magnocellular system, the paraventricular nucleus.     

TNFRp55 modulates IL-6 and nitric oxide responses following Yersinia lipopolysaccharide stimulation in peritoneal macrophages

While cytokines are major regulators of macrophage activation following host-pathogen interactions, they also act to limit inflammation to avoid tissue damage. In previous studies we reported the development of progressive Yersinia enterocolitica-induced reactive arthritis (ReA) in mice lacking the tumor necrosis factor receptor p55 (TNFRp55). In this work, we analyzed the response of TNFRp55^−/− macrophages to Y. enterocolitica antigens. We found higher concentration of nitric oxide (NO) in TNFRp55^−/− compared to wild-type macrophages in response to heat-killed Yersinia (HKY) and Yersinia outer membranes (OM). Moreover, Toll-like receptor (TLR)4 expression was increased in OM-stimulated TNFRp55^−/− versus wild-type (WT) macrophages. Accordingly, NO production was inhibited in TLR4-deficient macrophages following stimulation with OM, suggesting that LPS may function as a major OM component implicated in these responses. Thus, augmented NO production together with enhanced expression of inducible nitric oxide synthase (iNOS) and higher IL-6 production, may provide a pro-inflammatory setting in Yersinia LPS-stimulated TNFRp55^−/− macrophages. Augmented synthesis of NO and IL-6 was prevented by treatment with Polymyxin B, or by exposure to a specific NF-κB p65 oligonucleotide antisense, indicating the involvement of TLR4-mediated NF-κB activation in the unleashed pro-inflammatory response triggered by TNFRp55 deficiency. Thus, TNFRp55 modulates macrophage functions in response to Yersinia LPS stimulation through mechanisms involving NO, IL-6 and NF-κB pathways, suggesting an essential regulatory role of TNF via TNFRp55 signaling.     

Electrophysiological correlates of visually processing subject's own name

We investigated the electrophysiological correlates of the processing of subject's own name (SON) in comparison to familiar and unfamiliar names in the Chinese language. The three types of names were the deviants in an oddball paradigm among lexical and non-lexical phrases. All items consisted of three characters, and the non-lexical items were the targets. All names caused a clear N170 component of identical size which we take as a correlate of structural encoding. Only SON elicited a large N250 component, reflecting attentional capturing of SON. Additionally, SON caused a larger but later peaking P300 than the other two name stimuli which we interpret as a correlate of access to self-reference information.     

The role of the brain renin–angiotensin system in hypertension: Implications for new treatment

Hypertension affects 26% of adults and is in constant progress related to increased incidence of obesity and diabetes. One-third of hypertensive patients may be successfully treated with one antihypertensive agent, one-third may require two agents and in the remaining patients will need three agents for effective blood pressure (BP) control. The development of new classes of antihypertensive agents with different mechanisms of action therefore remains an important goal. Brain renin–angiotensin system (RAS) hyperactivity has been implicated in hypertension development and maintenance in several types of experimental and genetic hypertension animal models. Among the main bioactive peptides of the brain RAS, angiotensin (Ang) II and Ang III have similar affinities for type 1 (AT1) and type 2 (AT2) Ang II receptors. Following intracerebroventricular (i.c.v.) injection, Ang II and Ang III similarly increase arginine–vasopressin (AVP) release and BP. Blocking the brain RAS may be advantageous as it simultaneously (1) decreases sympathetic tone and consequently vascular resistance, (2) decreases AVP release, reducing blood volume and vascular resistance and (3) blocks angiotensin-induced baroreflex inhibition, decreasing both vascular resistance and cardiac output. However, as Ang II is converted to Ang III in vivo, the exact nature of the active peptide is not precisely determined. We summarize here the main findings identifying AngIII as one of the major effector peptides of the brain RAS in the control of AVP release and BP. Brain AngIII exerts a tonic stimulatory effect on BP in hypertensive rats, identifying brain aminopeptidase A (APA), the enzyme generating brain Ang III, as a potentially candidate target for hypertension treatment. This has led to the development of potent orally active APA inhibitors, such as RB150 — the prototype of a new class of centrally acting antihypertensive agents.     

高渗刺激后大鼠视上核星形胶质细胞和神经元的反应及其相互关系的光、电镜研究

目的探讨大鼠尾静脉注射高渗盐水(9％NaCl，5．5mL／kg)后，视上核(SON)内星形胶质细胞和神经元的可塑性反应及相互间的关系。方法用免疫组织化学和免疫电镜技术，观察刺激后15，45，90，180和360minSON内缝隙连接蛋白43(Cx43)和蛋白32(Cx32)的变化及超微结构。结果光镜下观察到Cx43阳性星形胶质细胞在15min出现，45min达到高峰；Cx32阳性神经元90min达到高峰。电镜下在SON内，观察到下列四种超微结构：(1)突触样结构(synapse like structure)，位于神经元的轴突末梢与Cx43阳性的星形胶质细胞突起之间；(2)三成分的突触复合体(tripartite synaptic structure)，由突触前膜、突触后膜和靠近此突触的星形胶质细胞突起共同组成；(3)同源性缝隙连接(gap junction，GJ)，位于星形胶质细胞突起之间，两侧均为Cx43；(4)“异源性缝隙连接样结构”(heterotypic gap junctions，HGJ)，是由Cx32阳性神经元和Cx43阳性星形胶质细胞突起组成的一种超微结构。结论高渗刺激后，SON内Cx43阳性星形胶质细胞和Cx32阳性神经元明显增加，前者出现和高峰的时间早于神经元；两者之间的HGJ数量明显增加，其他结构的数量变化不明显，因此两者可能是通过HGJ进行快速的信息交流。     

Developmental programing of thirst and sodium appetite

Thirst and sodium appetite are the sensations responsible for the motivated behaviors of water and salt intake, respectively, and both are essential responses for the maintenance of hydromineral homeostasis in animals. These sensations and their related behaviors develop very early in the postnatal period in animals. Many studies have demonstrated several pre- and postnatal stimuli that are responsible for the developmental programing of thirst and sodium appetite and, consequently, the pattern of water and salt intake in adulthood in need-free or need-induced conditions. The literature systematically reports the involvement of dietary changes, hydromineral and cardiovascular challenges, renin–angiotensin system and steroid hormone disturbances, and lifestyle in these developmental factors. Therefore, this review will address how pre- and postnatal challenges can program lifelong thirst and sodium appetite in animals and humans, as well as which neuroendocrine substrates are involved. In addition, the possible epigenetic molecular mechanisms responsible for the developmental programing of drinking behavior, the clinical implications of hydromineral disturbances during pre- and postnatal periods, and the developmental origins of adult hydromineral behavior will be discussed.     

Neuronal/glial plasticity in the supraoptic dendritic zone: Dendritic bundling and double synapse formation at parturition

The magnocellular neurosecretory cells of the supraoptic nucleus increase production and release of oxytocin and/or vasopressin under such conditions as parturition, lactation and dehydration. These stimuli have been shown to result in increased direct apposition of neuronal membranes and the formation of double synapses (one presynaptic terminal contacting two postsynaptic elements) within the supraoptic nucleus at the level of the cell bodies. These morphological changes are due to the retraction of the thin glial processes which are normally interposed between adjacent neurons. The present study was undertaken to ascertain whether, and to what extent, neuronal/glial plasticity occurs in the dendritic zone (i.e. the ventral glial laminar area) of the supraoptic nucleus. The instances of two or more dendrites with membrane in direct apposition (dendritic bundles), the number of dendrites per bundle, the amount of dendritic membrane in direct apposition and the percentage of dendrites contacted by double synapses were quantified at the ultrastructural level in virgin female, prepartum (21 days of gestation), postpartum (day of parturition) and lactating rats. All parameters measured varied significantly with the hormone demand states created by pregnancy and lactation, apparently due to glial retraction. Moreover, in the 2–24 h period between pre- and postpartum there was a significant increase in the number of dendrites per bundle, dendritic membrane in direct apposition and the percentage of dendrites contacted by double synapses. This time course corresponds to the known increased release of oxytocin and vasopressin at parturition.These findings constitute the first demonstration that dendritic bundles and double synapses occur in the ventral glial lamina/dendritic zone of the supraoptic nucleus and vary under the physiological conditions of pregnancy, parturition and lactation.