Search

Introduccion. El sistema nervioso es una diana de las hormonas esteroides y tambien un tejido esteroidogenico, y produce esteroides que actuan de una forma paracrina o autocrina sobre neuronas y glia. Los esteroides formados en el tejido nervioso se denominan neuroesteroides, para diferenciarlos, por su origen, de los esteroides perifericos, aunque tienen la misma estructura molecular que estos. Desarrollo. Se analiza la capacidad de las neuronas y las celulas de glia de sintetizar esteroides, y se describe el papel de algunas moleculas clave en la esteroidogenesis, como la proteina de regulacion aguda de esteroidogenesis, el receptor periferico de benzodiacepinas y la enzima aromatasa, que cataliza la conversion de testosterona en estradiol. Tambien se describen los diversos mecanismos de accion de los esteroides hormonales y los neuroesteroides en el sistema nervioso. Estos incluyen, tanto la regulacion de la sintesis de proteinas por neuronas y glia, mediante acciones sobre receptores nucleares, como efectos rapidos mediados por receptores de membrana o la modulacion alosterica de receptores para neurotransmisores. Se revisan las evidencias clinicas y experimentales de los efectos neuroprotectores de los esteroides sexuales y neuroesteroides y las limitaciones de la terapia hormonal sustitutiva, tras la menopausia. Conclusiones. Dada la limitacion que plantea el uso sistemico de hormonas como terapia neuroprotectora, se necesitan encontrar estrategias alternativas que aprovechen las propiedades neuroprotectoras de los esteroides, tales como aumentar localmente su sintesis en el cerebro o desarrollar moleculas que activen a los receptores de esteroides en el sistema nervioso y no en los organos perifericos.

The meningeal arrangement of the lumbosacral cord of Gallus is comparable to that of mammals. The meninges are formed by three lamellae: inner, intermediate, and outer. The arachnoid space, between the outer and intermediate lamellae, is wide and filled with a trabecular network, except in the region of the glycogen body and lobes of Lachi. This region is invaded by the glycogen body cells which also disrupt the inner and intermediate lamellae. A similarity between this region and the cerebellomedullary cistern of mammals is postulated, and the meaning of the presence of glycogen in the outer cerebrospinal fluid compartment is also discussed.

The hypothalamic Supraoptic Nucleus (SON) supposes an evolutionary achievement in the reptiles, zoological group in which this nucleus is first differentiated. Its scarce development in the chelonian, subject of the present study, is related to their primitive brain pattern. The peculiar location and the topographical configuration of the SON in the hypothalamus of the turtle Mauremys caspica allows to evidence morphologically the successive steps in the evolutionary process from lower to higher vertebrates. The marked neurosecretory character of the chelonian SON is the unequivocal proof of its philogenetic origin derived from the magnocellular preoptic nucleus of lower vertebrates.

In the apical cytoplasm of some ependymal cells of the Hypothalamic Periventricular Nucleus of the turtle Mauremys caspica large amount of cell structures of difficult diagnose are found. Their morphology is variable seeming to correspond to cell organelles in a process of degeneration, characteristic feature of the high metabolic activity in the ventricular barrier. Their possible physiological significance is discussed in the present work.

Labyrinthic recesses projecting to the subependymal tissue have been observed in the ependyma of the III ventricle in close relation to the neurons of the hypothalamic paraventricular nucleus in the turtle Mauremys caspica. There seems to be evidence of a direct contact between the paraventricular nucleus neurons and the cerebrospinal fluid whose physiological significance is discussed in the present work.

// Emilia Mira 1 , Lorena Carmona-Rodriguez 1 , Manuel Tardaguila 1 , Inigo Azcoitia 2 , Alicia Gonzalez-Martin 1,4 , Luis Almonacid 1 , Josefina Casas 3 , Gemma Fabrias 3 , Santos Manes 1 1 Department of Immunology and Oncology, Centro Nacional de Biotecnologia/CSIC, Madrid, Spain, 2 Department of Cell Biology, School of Biology, Universidad Complutense de Madrid, Madrid, Spain, 3 Department of Biomedicinal Chemistry, Catalan Institute of Advanced Chemistry/CSIC, Barcelona, Spain 4 Present address: The Scripps Research Institute, Department of Immunology and Microbial Science, La Jolla, CA Correspondence: Santos Manes, email: // Emilia Mira, email: // Keywords : inflammation, tumor immunity, macrophage polarization, angiogenesis, vascular normalization, myeloid infiltration, lymphoid infiltration, statins Received : September 05, 2013 Accepted : October 24, 2013 Published : October 26, 2013 Abstract Beyond their ability to inhibit cholesterol biosynthesis, the statins have pleiotropic effects that include anti-inflammatory and immunomodulatory activities. Statins could have clinical utility, alone or in combination with other chemotherapeutics, in the treatment of cancer. The mechanisms that underlie the anti-tumor activity of the statins are nonetheless poorly defined. No studies have analyzed how they alter the tumor-associated leukocyte infiltrate, a central factor that influences tumor stroma and cancer evolution. Here we used HER2/neu transgenic (Tg-neu) mice to analyze the effect of lovastatin (Lov) on the inflammatory reaction of spontaneous mammary tumors. Lov treatment of tumor-bearing Tg-neu mice did not alter growth of established tumors, but significantly reduced the number of new oncogenic lesions in these mice. Moreover, Lov inhibited the growth of newly implanted Tg-neu tumors in immunocompetent but not in immunodeficient mice. We found that Lov enhanced tumor infiltration by effector T cells, and reduced the number of immunosuppressive and pro-angiogenic M2-like tumor-associated macrophages (TAM). Concomitantly, the drug improved the structure and function of the tumor vasculature, measured as enhanced tumor oxygenation and penetration of cytotoxic drugs. Microarray analysis identified a Lov-elicited genetic program in Tg-neu tumors that might explain these effects; we observed Lov-induced downregulation of placental growth factor, which triggers aberrant angiogenesis and M2-like TAM polarization. Our results identify a role for lovastatin in the shaping and re-education of the inflammatory infiltrate in tumors, with functional consequences in angiogenesis and antitumor immunity.

The apical surface and apical cytoplasm of the ependymal cells of the subcommissural organ (SCO) of the chicken, Gallus gallus were investigated by scanning and transmission electron microscopy. The presence of "secretory elements" formed by dilated and irregularly shaped RER cisternae in the proximity of the apical plasma membrane and located into ventricular protusions of apical cytoplasm, evidence an ependymal secretion towards the cerebrospinal fluid (CSF), which is responsible of the Reissner's fibre (RF) by means of an apocrine mechanism. The observed ependymal lysosomal population has been related with an endocytotic mechanism from the ventricular CSF which could also suggest an absorptive role for the SCO.

The basal region of the subcommissural organ (SCO) was studied in the chicken Gallus gallus. The presence of concentric rough endoplasmic reticulum associated with lipid droplets in the basal processes of the ependymal cells, along with the increase of the lysosomal population, can be interpreted as evident signs of degeneration of the basal processes. The nearly absence of secretory processes ending on the meningeal blood vessels, suggests that the leptomeningeal route is missing. On the contrary, the presence of basal ependymal processes in contact with the hypendymal vessels could indicate that the ependymo-vascular pathway is well developed. In this sense, several structural features suggest a basal secretory mechanism from the SCO-cells: 1) Positive staining with paraldehyde-fuchsin of secretory material in the pericapillar region of hypendymal vessels and in the basal processes which reach the capillary wall; 2) presence of secretory material within the process endfeet in contact with hypendymal capillaries, and 3) existence of labyrinthis of the basal lamina of the capillaries.

The nervous system is a target for steroid hormones as well as a steroidogenic tissue, and it produces steroids that have a paracrine or autocrine effect on neurons and glial cells. Steroids formed in nervous tissue are called neurosteroids in order to differentiate them, in terms of their origin, from the peripheral steroids, although they both share the same molecular structure.We analyse the capacity of neurons and glial cells to synthesise steroids and describe the role played in steroidogenesis by certain key molecules, such as steroidogenic acute regulatory protein, peripheral benzodiazepine receptor and aromatase enzyme, which acts as a catalyst in the conversion of testosterone into estradiol. We also provide a description of the different mechanisms of action of the hormonal steroids and neurosteroids in the nervous system. These include both the regulation of protein synthesis by neurons and glial cells, by acting on nuclear receptors, and rapid effects mediated by membrane receptors or the allosteric modulation of neurotransmitter receptors. We review the clinical and experimental evidence for the neuroprotective effects of sex steroids and neurosteroids, and the limitations of hormone replacement therapy following menopause.Given the restraints involved in the systemic use of hormones as neuroprotective therapy, alternative strategies that take advantage of the neuroprotective properties of steroids must be sought. These could involve locally increasing their synthesis inside the brain or developing molecules that activate the steroid receptors in the nervous system and not in the peripheral organs.

The ciliated neurons of the paraventricular nuclei in old hamsters have been studied by electron microscope. These neurons exhibit cilia of 9 + 0 pattern. The single cilia, emerging from typical basal bodies, project into the intercellular space in parallel to the plasmalemma. The basal bodies are connected to ciliary rootlets and close to the Golgi complex. Double or single centrioles in different locations, frequently related to rootlets, can be observed. From a morphological point of view we suggest that these cilia, in the aging process, may represent a sensory structure which could perceive stimuli from the intercellular space.

In the present study we have observed with the electron microscope the glycogen body of the chick, Gallus domesticus, which constitutes a spinal cord circumventricular organ specific of birds. We have detected in young chickens and embryos the presence of considerable amounts of glycogen particles in the cerebrospinal and vascular compartments, coming from the glycogen body cells, which are able to discharge part of their glycogen into either the central canal or the capillary lumen, via ependymal and endothelial cells respectively. If this secretion is a physiological condition, we propose that the glycogen body would play a role in the maintenance of the hydric and glucose haemostasia in the central nervous system, as well as in the osmoregulation.