Initiation and propagation of neuronal coactivation in the developing hippocampus

Correlated neuronal activity is ubiquitous in developing nervous systems, where it may introduce spatiotemporal coherence and contribute to the organization of functional circuits. In this report, we used voltage-sensitive dyes and optical imaging to examine the spatiotemporal pattern of a spontaneous network activity, giant depolarizing potentials (GDPs), in rat hippocampal slices during the first postnatal week. The propagation pattern of the GDP is closely correlated to the anatomical organization of the network. In the hilus, where mossy cells and interneurons are not organized in layers, GDPs propagate at the same velocity in all directions. In CA3 and CA1, the activation is synchronous along the axis of the pyramidal cells' dendritic tree. The velocity of wave propagation is significantly different in three hippocampal subfields: it is slowest in the hilus, faster in CA3, and fastest in CA1. The velocity of horizontal propagation (along the axis of the pyramidal layer) has a large variation from trial to trial, suggesting that the horizontal velocity is determined to some extent by dynamic network factors. Imaging revealed that each GDP event is initiated from a small focus. The location of the initiation focus differs from event to event. All together, our data suggest that GDP is a propagating excitation wave, initiated from a small site, and propagating to the whole hippocampus. The spatiotemporal patterns of the wave in CA3 and CA1 areas show better synchrony along the pyramidal cell dendritic trees and progressive activation along the axis of the pyramidal cell layer.     

Possible roles of microfibrils in elastogenesis

On examination in the electron microscope elastic tissue is seen to consist of an amorphous component surrounded by microfibrillar components. The exact relationship between these components is unknown, although during development the microfibrils appear before the amorphous material. In this report we summarize our recent observations on the microfibrillar material. At high magnification the microfibrils are seen to have a poorly staining central core around the periphery of which are arranged more densely staining filaments which appear to wind around the microfibrils in a spiral fashion. Careful measurements of microfibrillar diameters from the aorta of four large species show that there are significant differences in the mean diameter and population distributions with species. The mean diameter of the microfibrils changes with age during fetal and postnatal development. The results of immunoelectronmicroscopic localization of an antibody to a microfibrillar component are reported and the possible roles of microfibrils in elastic tissue formation are examined.     

Origin and characteristics of glycogen cells in the developing murine placenta.

The junctional zone (Jz) of the mouse placenta consists of two main trophoblast populations, spongiotrophoblasts and glycogen cells (GCs), but the development and function of both cell types are unknown. We conducted a quantitative analysis of GC size, number, and invasion of cells into the decidua across gestation. Furthermore, we identified markers of GC function to investigate their possible roles in the placenta. While the spongiotrophoblast cell volume doubles, and cell number increases steadily from E12.5 to E16.5, there is a remarkable 80-fold increase in GC numbers. This finding is followed by a notable decrease by E18.5. Surprisingly, the accumulation of GCs in the decidua did not fully account for the decrease in GC number in the Jz, suggesting loss of GCs from the placenta. Glucagons were detected on GCs, suggesting a steady glucose release throughout gestation. Connexin31 staining was shown to be specific for GCs. GC migration and invasion may be facilitated by temporally regulated expression of matrix metalloproteinase 9 and the imprinted gene product, Decorin. Expression of the clearance receptor for type II insulin-like growth factor (IGF-II), IGF2R, in a short developmental window before E16.5 may be associated with regulating the growth effects of IGF-II from glycogen cells and/or labyrinthine trophoblast on the expansion of the Jz. Thus stereology and immunohistochemistry have provided useful insights into Jz development and function of the glycogen cells.     

Long-lasting adverse effects of prenatal hypoxia on developing autonomic nervous system and cardiovascular parameters in rats

To determine whether prenatal hypoxia increases the risk of developing cardiovascular disorders as an adult and, if so, the identity of the cell mechanisms involved in such dysfunction, we evaluated the sympathoadrenal system and central areas related to cardiovascular events during development and the cardiovascular parameters in adults. Pregnant rats were exposed to hypoxia (10% oxygen) from embryonic day (E) 5 to E20 and the offspring studied at 1, 3, 9 and 12 weeks of age for neurochemistry and at 12 weeks of age for cardiovascular analysis. In the 1-, 3- and 9-week-old offspring, the levels and utilization of catecholamines were reduced in sympathetic ganglia, in target organs, in adrenals and in the rostral part of the A2 cell group in the nucleus tractus solitarius, but were increased in the locus coeruleus. In the 12-week-old adult offspring, the lowered autonomic nervous activity was restricted to cardiac-related structures, i.e. the stellate ganglion, heart and adrenals. In adult rats, prenatal hypoxia did not affect the cardiac parameters under resting conditions but increased blood pressure and the variability of blood pressure and heart rate under stress conditions. The altered metabolic activity of the sympathoadrenal system and related central areas during development and at adulthood for most structures might be part of the potential mechanisms contributing to cardiovascular disorders in adults.     

Origin and fate of fetuin-containing neurons in the developing neocortex of the fetal sheep

Summary The development of the neocortex has previously been extensively studied in carnivores (cat and ferret), rodents (rat and mouse) and primates (monkey and human). In these species, it has been shown that the initial population of cells migrating from the ventricular zone forms the primordial plexiform layer. This is subsequently split into marginal zone and subplate zone by the insertion of later-migrating cells into the primordial plexiform layer, to form the cortical plate proper. Many of the cells derived from the split primordial plexiform layer are transient. The neurons of the subplate zone are found in the deeper part of layer VI, and white matter deep to layer VI in the more mature cortex; most of these neurons disappear by adulthood. [³H]-thymidine labelling in the present study has shown a similar pattern of neocortical development in Artiodactyla (sheep). In addition it has been shown that the previously described staining of subplate and cortical plate cells for the fetal protein fetuin indicates that fetuin is a useful marker for a proportion of this transient population of neurons and defines its extent in neocortical development more clearly. Dividing cells were labelled by a single intra-amniotic injection of [³H]-thymidine at E26 to E35 (birth is at E150). The brains were subsequently examined at E40 or E80 for [³H]-thymidine labelling and fetuin staining by a combination of autoradiography and immunocytochemistry. The earliest generated neocortical cells detected in this study (E26) were found in two layers by E40, the outer marginal zone and inner subplate zone. Neurons of the marginal zone were generated up to E28; those of the early subplate zone were generated up to E31. The cortical plate proper was generated by cells born on E32 and later. This sequence is similar to that described in other species, especially the cat. A proportion of the early-generated neurons in the marginal zone, subplate zone and early cortical plate stained for fetuin. By E80 these earliest-generated, fetuin-positive cells were found in the white matter deep to the forming neocortical layers and in layer VI. In adult brains no fetuin-positive neurons could be identified in the neocortex, and neurons had almost entirely disappeared from the white matter. The fetal glycoprotein fetuin seems to be specifically associated with a population of cells that has the same developmental history as the transient marginal zone and subplate neurons described in other species. However, the distribution of fetuin-containing neurons is more extensive and includes some of the neurons within the cortical plate itself. Thus in addition to being a marker for a proportion of the transient marginal zone and subplate cells, the presence of fetuin in subplate and cortical plate neurons, given the trophic properties attributed to fetuin, may indicate its involvement in early stages of synaptogenesis and connectivity in the developing neocortex.     

Allergy and the cardiovascular system

The most dangerous and life-threatening manifestation of allergic diseases is anaphylaxis, a condition in which the cardiovascular system is responsible for the majority of clinical symptoms and for potentially fatal outcome. The heart is both a source and a target of chemical mediators released during allergic reactions. Mast cells are abundant in the human heart, where they are located predominantly around the adventitia of large coronary arteries and in close contact with the small intramural vessels. Cardiac mast cells can be activated by a variety of stimuli including allergens, complement factors, general anesthetics and muscle relaxants. Mediators released from immunologically activated human heart mast cells strongly influence ventricular function, cardiac rhythm and coronary artery tone. Histamine, cysteinyl leukotrienes and platelet-activating factor (PAF) exert negative inotropic effects and induce myocardial depression that contribute significantly to the pathogenesis of anaphylactic shock. Moreover, cardiac mast cells release chymase and renin that activates the angiotensin system locally, which further induces arteriolar vasoconstriction. The number and density of cardiac mast cells is increased in patients with ischaemic heart disease and dilated cardiomyopathies. This observation may help explain why these conditions are major risk factors for fatal anaphylaxis. A better understanding of the mechanisms involved in cardiac mast cell activation may lead to an improvement in prevention and treatment of systemic anaphylaxis.     

Origin and propagation of individual slow waves along the intact feline small intestine

The pattern of propagation of slow waves in the small intestine is not clear. Specifically, it is not known whether propagation is determined by a single dominant ICC-MP (Interstitial cells of Cajal located in the Myenteric Plexus) pacemaker unit or whether there are multiple active pacemakers. To determine this pattern of propagation, waveforms were recorded simultaneously from 240 electrodes distributed along the whole length of the intact isolated feline small intestine. After the experiments, the propagation patterns of successive individual slow waves were analysed. In the intact small intestine, there was only a single slow wave pacemaker unit active, and this was located at or 6-10 cm from the pyloric junction. From this site, slow waves propagated in the aboral direction at gradually decreasing velocities. The majority of slow waves (73%) reached the ileocaecal junction while the remaining waves were blocked. Ligation of the intestine at one to four locations led to: (a) decrease in the distal frequencies; (b) disappearance of distal propagation blocks; (c) increase in velocities; (d) emergence of multiple and unstable pacemaker sites; and (e) propagation from these sites in the aboral and oral directions. In conclusion, in the quiescent feline small intestine a single pacemaker unit dominates the organ, with occasional propagation blocks of the slow waves, thereby producing the well-known frequency gradient.     

Histamine in the developing sympathoadrenal system

The ontogenetic distribution of histamine in correlation with catecholamines in the developing rat sympathoadrenal system was analyzed by using an indirect immunohistochemical method and a specific rabbit anti-histamine antiserum. Tyrosine hydroxylase (TH) immunoreactivity was used as a marker of catecholamine synthesis. TH immunoreactivity appeared in retroperitoneal sympathetic tissues on embryonic day 12.5 (E 12.5) when it was found in cells of lumbar chain ganglia. In preaortic sympathetic tissue, TH immunoreactivity was observed on day E 13.5 and in adrenal medullae on day E 14.5. Histamine immunoreactivity was expressed in all of these tissues beginning from day E 14.5. First it was found mainly in nerve fibers, but also in some cells. During the embryonic development the number of histamine-immunoreactive cells increased in all sympathetic tissues studied. In newborn rats, histamine immunoreactivity was restricted to a subpopulation of sympathetic cells, i.e. small intensely fluorescent (SIF) cells of sympathetic ganglia, paraganglion-type cells and some adrenaline-synthesizing cells of the adrenal medulla.     

心血管系统的雌激素受体

雌激素对心血管系统的保护作用除了对血脂代谢的改善以外 ,主要来自于雌激素对心血管系统的直接作用。雌激素对靶细胞的特异性作用主要通过基因组效应和非基因组效应完成。具有功能活性的雌激素受体广泛存在于心血管系统     

The myth of ventrally emigrating neural tube (VENT) cells and their contribution to the developing cardiovascular system

The cardiac neural crest cells are a group of cells that emigrate from the dorsal side of the neural tube during a specific time window and contribute to the pharyngeal arch arteries and the aorticopulmonary septum of the heart. Recent publications have suggested that another group of cells emigrating from the ventral side of the neural tube also contributes to the developing cardiovascular system. The first aim of our study was to define the specific time window of cardiac neural crest cell migration by injecting a retrovirus containing a lacZ reporter gene into a chick embryo at different stages during development. The second aim was to study the contribution of the supposed ventrally emigrating neural tube cells to the cardiovascular system using three approaches. One approach was to inject a lacZ retrovirus into the lumen of the chick hindbrain. Secondly, we injected the retrovirus into the neural tube at the position of the 10-12 somite pair. Finally, we used the chimera technique in which we transplanted a quail neural tube segment into a chick embryo. Cardiac neural crest cells were shown to emigrate from the dorsal side of the neural tube between HH9 and HH13(-). The HH13(+) neural tube has ceased to produce cardiac neural crest cells between the level of the otic placode and the fourth pair of somites. Retroviral injection directly into the chick hindbrain at HH14 resulted in 50% of the embryos with minimal labeling of the hindbrain and intense labeling of the adjacent mesenchyme, suggesting that virus was spilled. This implies that this technique is not useful for confirming the existence of ventrally emigrating cells. Both retroviral injections into the neural tube lumen at HH14 at the position of the 10-12 somite pair and the chimeras showed no signs of ventrally emigrating neural tube cells. We conclude that there is no contribution of ventral neural tube cells to the developing cardiovascular system.     

Lead and the developing nervous system

Subtle signs of neural impairment are appearing in children exposed to "low levels" of lead. How does this metal exert its effect on the developing nervous system? The salient features of five mechanisms likely involved are discussed in this review.     

Hormone therapy and the cardiovascular system

The cardiovascular effects of female sex steroids have many faces and are very complex. To make this situation even more complicated different disease situations, different target organs and different therapeutic regimens may exhibit different effects of estrogens and progestines. Furthermore, the interpretation of population studies may be problematic by itself, in view of so many confounders and biases involved and methodological flaws that sometimes are discovered only post-hoc. It seems, therefore, that in such a complicated situation making definite conclusions and guidelines is almost an impossible task. My suggestion to clinicians is to try and follow the main stream of clinical data, looking at the general picture rather than the small details, and try to individualize therapy in order to maximize the benefits and minimize the adverse reactions and risks. This article discusses the current knowledge on hormone replacement therapy (HRT) and the cardiovascular system. It is not an overview, because my intention was not to pump in as much data as possible. Rather, the article presents current ideas and trends in this field to be used by people who practice menopause medicine for their own clinical decisions.