Eugenia Díaz

Effects of preweaning environmental enrichment on basilar dendrites of pyramidal neurons in occipital cortex: a Golgi study

The effects of postnatal environmental stimulation on the branching patterns of cortical dendrites were measured in rats. Pups were exposed to 4 daily multisensory enrichment sessions from days 10-24, while littermates were maintained in standard conditions. At 25 days of age, the brains were stained using the Golgi-Cox-Sholl method. Camera lucida drawings were made of the basilar dendritic trees from a total of 528 layer-III occipital cortex pyramidal neurons. A highly significant increase was found in number and length of segments from order 1-5 in the neurons from the enriched subjects.

Ganglionar nervous cells and telocytes in the pancreas of Octodon degus: Extra and intrapancreatic ganglionar cells and telocytes in the degus

This study shows for the first time the presence of intra and extrapancreatic ganglionar neurons and telocytes in Octodon degus such as those described in human and guinea pig pancreas. Pancreatic ganglionar neurons were identified by their histological characteristics as well as their positive immunostaining with mouse anti-human neuron specific enolase (NSE) antibody. Somatostatin secreting delta cells (D cells) in the islets of Langerhans were identified by positive immunostaining with rabbit antihuman polyclonal somatostatin antibody. Electron microscopy evidenced the presence of some unmyelinated axons in the interlobular spaces or septa, usually located adjacent to blood vessels and the exocrine epithelial ducts. The presence of telocytes with at least 2 telopodes was observed in the interlobular space, frequently in close spatial relationship with blood vessels and nerve endings. Telocytes were often observed in the vicinity or even in close proximity with both secretory acini and exocrine epithelial ducts and regulatory nerves and blood vessel apparatuses. A possible framework has been put forward within which such structures might contribute to elicit physiological responses in the pancreas. Further studies of synaptic interactions within and between pancreatic neuron cells are needed to help clarify the morphological results reported here. A broad overview of the field of neurogastroenterology with focus on the pancreas of O. degus related to the enteric nervous system (ENS) is provided in order to help design future studies on the connections of specific neurons forming pancreatic pathways, their neurotransmission processes and how disruption of these pathways may contribute to pancreatic disease.

Placental Hypoxia and Foetal Development Versus Alcohol Exposure in Pregnancy

AIMS To examine the causes of variability in the effect of maternal drinking on the foetus, with particular reference to the pattern, frequency and duration of the period of drinking, differences in maternal, foetal and placental metabolism of ethanol/acetaldehyde, and genetic factors. METHODS Narrative review of published studies of the pathogenesis of foetal alcohol syndrome (FAS) with emphasis in the development of the central nervous system. RESULTS Animal models suggest that acetaldehyde, the primary hepatic oxidative metabolite of ethanol, reaches the foetus either by placental production or by placental transference, which in turn could affect foetal growth and development. The most likely hypothesis regarding the decrease of foetal growth is via hypoxia and increased oxidative/nitrative stress, which interfere with cellular processes that require oxygen in order to function adequately, such as placental transport. CONCLUSION There seems to be an association between the teratogenic effect, hypoxia and oxidative stress, the molecular mechanism involved (e.g. apoptosis) and the range of effects. The review sums ups the evidence that could explain some of the abnormalities in the brain development that could be related to behavioural problems observed in individuals with FAS/foetal alcohol spectrum disorder. This suggests that alcohol consumption produces failures in the normal migration of radial cells, from which the rest of the brain cells would eventually develop.

Interhemispheric Structural Asymmetry Induced by a Lateralized Reaching Task in the Rat Motor Cortex

The effects of a lateralized reaching task on the morphological structure of the rat motor cortex were studied during the early postweaning period. Our results show that the consistent use of one forelimb accounts for a significant decrease in the numerical density of cells and an increase in cortical thickness of the contralateral‘forelimb’motor cortex. As a consequence of the early motor training the cell distribution, which is lower rostrally than caudally in nontrained hemispheres, is reversed in the trained hemispheres. This may be interpreted as the specific motor training triggering a higher neuronal branching in the corresponding cortical region. The present findings may further the understanding of the mechanisms involved in the generation of morphological brain asymmetries.

Visuospatial discrimination deficit in rats after ibotenate lesions in anteromedial visual cortex

To assess the role of the rat anteromedial extrastriate cortex (AM) in a visuospatial discrimination task, restricted bilateral ibotenic acid lesions were placed stereotaxically in this region. Gray rats with lesions in AM were trained in a task requiring them to discriminate the location of a light stimulus placed vertically at different elevations. Correct responses required pressing right or left levers to obtain rewards. In contrast to unoperated controls, lesioned rats failed in learning the visuospatial discrimination task. A correlation was found between the bilateral extent of the lesion in area AM and the behavioral deficit. Another group of lesioned rats was trained to discriminate brightness differences of the light stimulus but requiring the same egocentric right/left motor response. The performance of these rats was similar to that of controls. From these results we conclude that extrastriate area AM in the rat is necessary for visuospatial discrimination, but not for correct egocentric motor responses. The visuospatial functions of area AM in the rat are reminiscent of visuospatial functions ascribed to the parietal streams of extrastriate visual areas in the monkey.

Morphologic and immunohistochemical organization of the human habenular complex

The habenular complex (HbCpx) is a phylogenetically conserved brain structure located in the epithalamus of vertebrates. Despite its fundamental role in decision‐making processes and the proposed link between habenular dysfunction and neuropsychiatric conditions, little is known about the structural and functional organization of the HbCpx in humans. The goal of this study was thus to provide a first systematic morphologic and immunohistochemical analysis of the human HbCpx to begin dissecting its nuclear and subnuclear organization. Our results confirmed that the human HbCpx is subdivided into medial (MHb) and lateral (LHb) nuclei, each showing a large degree of intranuclear morphologic heterogeneity. Analysis of serially stained sections using a combination of morphologic and immunohistochemical criteria allowed the distinction of five subnuclei in both the MHb and LHb. Overall, the observed subnuclear organization of the MHb in humans resembles the organization of subnuclei in the MHb of rats. The shape, relative size, and intranuclear organization of the LHb, however, show significant differences. The contribution of the LHb to the entire HbCpx is about five times larger in humans than in rats. Noteworthy, a dorsal domain of the LHb that contains afferent myelinated fibers from the stria medullaris and shows GABA‐B‐R1 immunoreactive cells, appears substantially enlarged in humans when compared to rats. This feature seems to account for a large part of the relative growth in size of the LHb in humans and opens the intriguing possibility of an increased influence of limbic and striatal afferents into the LHb of humans. J. Comp. Neurol. 519:3727‐3747, 2011.

Directional asymmetry in the volume of the human habenula

Brain asymmetry is a conserved feature in vertebrates. The dorsal diencephalic habenular complex shows conspicuous structural and functional asymmetries in a wide range of species, yet it is unclear if this condition is also present in humans. Addressing this possibility becomes relevant in light of recent findings presenting the habenula as a novel target for therapeutic intervention of affective disorders through deep brain stimulation. Here we performed volumetric analyses in postmortem diencephalic samples of male and female individuals, and report for the first time, the presence of directional asymmetries in the volume of the human habenula. The habenular volume is larger on the left side in both genders, a feature that can be explained by an enlargement of the left lateral habenula compared to the right counterpart. In contrast, the volume of the medial habenula shows no left–right directional bias in either gender. It is remarkable that asymmetries involve the lateral habenula, which in humans is particularly enlarged compared to other vertebrates and plays relevant roles in aversive processing and aversively motivated learning. Our findings of structural asymmetries in the human habenula are consistent with recent observations of lateral bias in activation, metabolism and damage of the human habenula, highlighting a potential role of habenular laterality in contexts of health and illness.

Effects of Steroidal and Non Steroidal Drugs on the Neovascularization Response Induced by Tumoral TA3 Supernatant on CAM from Chick Embryo

Angiogenesis, the development of new blood vessels from the existing vascular network, may result as a consequence of the increase or decrease of proangiogenic or antiangiogenic factors, respectively. The tumor itself could up-regulate the production of angiogenic factors. Recently, we established that the steroidal drug betamethasone in low concentration inhibit the neovascularization promoted by TA3 Ts on CAM of chick embryos. We describe here the effects of the non-steroidal drug ketoprofen, alone or in association with betamethasone, on the angiogenesis promoted by TA3 Ts on CAM. The main finding reported here is that the formation of new blood vessels is strongly inhibited by low concentrations of ketoprofen. The association of both drugs produced a synergistic effect, significantly decreasing tumoral supernatant angiogenesis. It is known that steroidal anti-inflammatory drugs inhibit the enzymes required for the production of prostaglandins through a nuclear GR mediated mechanism. This may operate as a general mechanism in endothelial cells as well. Considering that the induction of COX 1 and COX2 are inhibited by ketoprofen, and that these enzymes are located in the stromal compartment of the CAM, we propose that its antiangiogenic effect may occur via inhibition of the two COX isoforms. In fact, we found that ketoprofen induced apoptosis in both the stromal fibroblast and endothelial cells. The potentiated effect of the combination of betamethasone and ketoprofen may have some therapeutic projections in the control of pathological angiogenesis.

Effect of sulfated β-cyclodextrin, a water soluble cycloamylose, on the promotion and/or inhibition of angiogenesis

Previous studies have reported that sulfated β-cyclodextrin, a naturally occurring cycloamylose built up from six to eight glucopyranose units, when administered alone promotes angiogenesis, but administered with an angiostatic steroid inhibits angiogenesis in the cick embryo bioassay. In our experiments sulfated β-cyclodextrin has been shown to posses many properties unrelated to its classical functions in the promotion and inhibition of angiogenesis that were not previously described. We studied the angiogenic and angiostatic properties of β-cyclodextrin in a subcutaneosus plastic sponge model in mice. We realized two set of experiments. In each set mice were randomized into five groups (n= 5 mice). The first group was treated with sulfated β-cyclodextrin (200 ng), the second group was treated with sulfated β-cyclodextrin (2000 ng), the third group received unsubstituted β-cyclodextrin (2000 ng), the fourth group was treated with sulfated β-cyclodextrin (20 000 ng) and the last group was used as a control group. In all groups compounds were administered intraperitonally 4 days after subcutaneous implantation of a sterile polyvinyl sponge on day 0, controls were not treated. Cyclodextrin administered alone at low drug concentration (200 ng) promoted angiogenesis and increased the development of venules in the sponge matrix. However, cyclodextrin administered at high drug concentration (2000 and 20 000 ng) reduced the vessel index in the sponge and areas of microhemorraghes were observed. From our results we propose that β-cyclodextrin contains both a promoter and an inhibitor of angiogenesis and that the activation of both is drug concentration dependent.

Effects of Maternal Alcoholism on Placental Function and Lung Fetal Development

Epidemiological and clinical data indicate that alcohol consumption during pregnancy remains a substantial public-health problem as many pregnant women continue to drink alcohol despite clinical recommendations and public health campaigns warning about the risks associated. It is well known that maternal ethanol consumption during pregnancy results in deleterious effects on the developing fetus. Among these effects is the so called Fetal Alcohol Spectrum Disorder (FASD). Fetal Alcohol Syndrome (FAS) is a severe form of FASD and also an irreversible condition. Although all children born to alcoholic mothers show abnormalities, in some cases these may not be clearly observable. There is a wide spectrum of abnormalities regardless of the amount and pattern of alcohol exposure, differences in maternal, foetal and placental metabolism of ethanol/acetaldehyde, as well as genetic factors. In this article we present some of the effects of maternal alcoholism on placental functions and how it affects lung development