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Sample records for chordate glial secretion

  1. The central nervous system of sea cucumbers (Echinodermata: Holothuroidea shows positive immunostaining for a chordate glial secretion

    Directory of Open Access Journals (Sweden)

    Grondona Jesus M

    2009-06-01

    Full Text Available Abstract Background Echinoderms and chordates belong to the same monophyletic taxon, the Deuterostomia. In spite of significant differences in body plan organization, the two phyla may share more common traits than was thought previously. Of particular interest are the common features in the organization of the central nervous system. The present study employs two polyclonal antisera raised against bovine Reissner's substance (RS, a secretory product produced by glial cells of the subcomissural organ, to study RS-like immunoreactivity in the central nervous system of sea cucumbers. Results In the ectoneural division of the nervous system, both antisera recognize the content of secretory vacuoles in the apical cytoplasm of the radial glia-like cells of the neuroepithelium and in the flattened glial cells of the non-neural epineural roof epithelium. The secreted immunopositive material seems to form a thin layer covering the cell apices. There is no accumulation of the immunoreactive material on the apical surface of the hyponeural neuroepithelium or the hyponeural roof epithelium. Besides labelling the supporting cells and flattened glial cells of the epineural roof epithelium, both anti-RS antisera reveal a previously unknown putative glial cell type within the neural parenchyma of the holothurian nervous system. Conclusion Our results show that: a the glial cells of the holothurian tubular nervous system produce a material similar to Reissner's substance known to be synthesized by secretory glial cells in all chordates studied so far; b the nervous system of sea cucumbers shows a previously unrealized complexity of glial organization. Our findings also provide significant clues for interpretation of the evolution of the nervous system in the Deuterostomia. It is suggested that echinoderms and chordates might have inherited the RS-producing radial glial cell type from the central nervous system of their common ancestor, i.e., the last common

  2. Developmental genetics in primitive chordates.

    OpenAIRE

    P. SORDINO; L. Belluzzi; De Santis, R; Smith, W.C.

    2001-01-01

    Recent advances in the study of the genetics and genomics of urochordates testify to a renewed interest in this chordate subphylum, believed to be the most primitive extant chordate relatives of the vertebrates. In addition to their primitive nature, many features of their reproduction and early development make the urochordates ideal model chordates for developmental genetics. Many urochordates spawn large numbers of transparent and externally developing embryos on a daily basis. Additionall...

  3. The Chordate Proteome History Database

    OpenAIRE

    Anthony Levasseur; Julien Paganini; Jacques Dainat; Thompson, Julie D; Olivier Poch; Pierre Pontarotti; Philippe Gouret

    2012-01-01

    The chordate proteome history database (http://ioda.univ-provence.fr) comprises some 20,000 evolutionary analyses of proteins from chordate species. Our main objective was to characterize and study the evolutionary histories of the chordate proteome, and in particular to detect genomic events and automatic functional searches. Firstly, phylogenetic analyses based on high quality multiple sequence alignments and a robust phylogenetic pipeline were performed for the whole protein and for each i...

  4. HIV-1B gp120 genes from one patient with AIDS dementia complex can affect the secretion of tumor necrosis factor and interleukin in glial cells

    Institute of Scientific and Technical Information of China (English)

    YAN Yu-fen; WANG Zhi-yu; PU Shuang-shuang; WEN Hong-ling; HUANG Tao; SONG Yan-yan; XU Hong-zhi; ZHAO Li

    2011-01-01

    Background HIV-1 infected and immune-activated macrophages and microglia secrete neurotoxins,such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β),which play major role in the neuronal death.It has been shown that different HIV-1 variants have varying abilities to elicit secretion of TNF-α by peripheral blood mononuclear cell (PBMC); however,whether the difference of gp120 gene could affect the secretion of TNF-α and IL-1β by glial cells is unknown.The aim of this study was to explore the association between gene diversity and induction of neurotoxic cytokines.Methods In this study,we constructed retroviral vectors MSCV-IRES-GFP/gp120 using HIV-1 gp120 genes isolated from four different tissues of one patient who died of AIDS dementia complex (ADC).Recombinant retroviruses produced by cotransfection of MSCV-IRES-GFP/gp120,pCMV-VSV-G and pUMVC into 293T cells were collected and added into U87 glial cells.Concentrations of TNF-α and IL-1β secreted by transduced U87 cells were assayed with ELISA separately.Results The four HIV-1 gp120 were in the different branch of the neighbor-joining tree.Compared to the pMIG retrovirus (gp120-negative) or U87 cells,all the gp120-positive recombinant retroviruses induced more TNF-α (P <0.01) and IL-1β (P <0.01).In addition,compared with the L/MIG retrovirus,all the three brain gp120-positive recombinant retroviruses induced less TNF-α (P <0.01) and IL-1β (P <0.01).Conclusions HIV-1 gp120 could induce U87 cells secret more TNF-α and IL-1β again.The more important is that difference of HIV-1 gp120,especially cell-tropism may account for the different ability in eliciting secretion of TNF-α and IL-1β,which might supply a novel idea helping understand the pathogenesis of ADC.

  5. Secretion of nerve growth factor, brain-derived neurotrophic factor, and glial cell-line derived neurotrophic factor in co-culture of four cell types in cerebrospinal fluid-containing medium

    Institute of Scientific and Technical Information of China (English)

    Sanjiang Feng; Minghua Zhuang; Rui Wu

    2012-01-01

    The present study co-cultured human embryonic olfactory ensheathing cells, human Schwann cells, human amniotic epithelial cells and human vascular endothelial cells in complete culture medium- containing cerebrospinal fluid. Enzyme linked immunosorbent assay was used to detect nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor secretion in the supernatant of co-cultured cells. Results showed that the number of all cell types reached a peak at 7–10 days, and the expression of nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor peaked at 9 days. Levels of secreted nerve growth factor were four-fold higher than brain-derived neurotrophic factor, which was three-fold higher than glial cell line-derived neurotrophic factor. Increasing concentrations of cerebrospinal fluid (10%, 20% and 30%) in the growth medium caused a decrease of neurotrophic factor secretion. Results indicated co-culture of human embryonic olfactory ensheathing cells, human Schwann cells, human amniotic epithelial cells and human vascular endothelial cells improved the expression of nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor. The reduction of cerebrospinal fluid extravasation at the transplant site after spinal cord injury is beneficial for the survival and secretion of neurotrophic factors from transplanted cells.

  6. Seeing chordate evolution through the Ciona genome sequence

    OpenAIRE

    Cañestro, Cristian; Bassham, Susan; Postlethwait, John H.

    2003-01-01

    A draft sequence of the compact genome of the sea squirt Ciona intestinalis, a non-vertebrate chordate that diverged very early from other chordates, including vertebrates, illuminates how chordates originated and how vertebrate developmental innovations evolved.

  7. Hemichordates and the origin of chordates

    Science.gov (United States)

    Gerhart, John; Lowe, Christopher; Kirschner, Marc

    2005-01-01

    Hemichordates, the phylum of bilateral animals most closely related to chordates, could reveal the evolutionary origins of chordate traits such as the nerve cord, notochord, gill slits and tail. The anteroposterior maps of gene expression domains for 38 genes of chordate neural patterning are highly similar for hemichordates and chordates, even though hemichordates have a diffuse nerve-net. About 40% of the domains are not present in protostome maps. We propose that this map, the gill slits and the tail date to the deuterostome ancestor. The map of dorsoventral expression domains, centered on a Bmp-Chordin axis, differs between the two groups; hemichordates resemble protostomes more than they do chordates. The dorsoventral axis might have undergone extensive modification in the chordate line, including centralization of the nervous system, segregation of epidermis, derivation of the notochord, and an inversion of organization.

  8. The Evolution of Dopamine Systems in Chordates

    OpenAIRE

    Philippe Vernier

    2011-01-01

    Dopamine (DA) neurotransmission in the central nervous system (CNS) is found throughout chordates, and its emergence predates the divergence of chordates. Many of the molecular components of DA systems, such as biosynthetic enzymes, transporters, and receptors, are shared with those of other monoamine systems, suggesting the common origin of these systems. In the mammalian CNS, the DA neurotransmitter systems are diversified and serve for visual and olfactory perception, sensory–motor program...

  9. Hemichordates and the Origin of Chordates

    Science.gov (United States)

    Gerhart, John; Kirschner, Marc; Lowe, Chris

    2002-01-01

    At the start of the period of the NASA grant three years ago, we had no information on the organization and development of the body axis of the hemichordate, Saccoglossus kowalevskii. Now we have substantial findings about the anteroposterior axis and dorsoventral axis, and based on this information, we have new insights about the origin of chordates from ancestral deuterostomes. We found ways to obtain and preserve large numbers of embryos and hatched juveniles. We can now collect about 40,000 embryos in the month of September, the time of S. kowalevskii spawning at Woods Hole. Excellent cDNA libraries were prepared from three developmental stages. From these libraries, we directly isolated about 30 gene ortholog sequences by screening and pcr techniques, all of these sequences of interest in the inquiry about the animal's organization and development. We also performed a mid-sized EST project (60,000 randomly picked clones, many of these arrayed). About half of these have been analyzed so far by blastx and are suitable for direct use of clones. We have obtained about 50 interesting sequences from this set. The rest still await analysis. Thus, at this time we have isolated orthologs of 80 genes that are known to be expressed in chordates in conserved domains and known to have interesting roles in chordate organization and development. The orthology of the S. kowalevskii sequences has been verified by neighbor joining and parsimony methods, with bootstrap estimates of validity. The S. kowalevskii sequences cluster with other deuterostome sequences, namely, other hemichordates, echinoderms, ascidians, amphioxus, or vertebrates, depending on what sequences are available in the database for comparison. We have used these sequences to do high quality in situ hybridization on S. kowalevskii embryos, and the results can be divided into three sections-those concerning the anteroposterior axis of S. kowalevskii in comparison to the same axis of chordates, those concerning

  10. New Early Cambrian Chordates from Haikou, Kunming

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Two new chordates, Cathaymyrus haikouensis Luo et Hu sp. nov. andZhongxiniscus intermedius Luo et Hu gen. et sp. nov. are studied in this paper. Both display numerous S-shaped myomeres on their trunk. C. haikouensis shows a long and slim body similar to that of Cathaymyrus diadexus Shu et al., Zhongxiniscus approaches to Myllokunmingia and Haikouichthvs in the dorsal fin, but differs in the myomeres. Zhongxiniscus may be the intermediate form between Ca thaymyrus and Myllokunmingia and Haikouichthys.

  11. The evolution of dopamine systems in chordates

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    Kei eYamamoto

    2011-03-01

    Full Text Available Dopamine (DA neurotransmission in the central nervous system (CNS is found throughout chordates, and its emergence predates the divergence of chordates. Many of the molecular components of DA systems, such as biosynthetic enzymes, transporters and receptors, are shared with those of other monoamine systems, suggesting the common origin of these systems. In the mammalian CNS, the DA neurotransmitter systems are diversified and serve for visual and olfactory perception, sensory-motor programming, motivation, memory, emotion, and endocrine regulations. Some of the functions are conserved among different vertebrate groups, while others are not, and this is reflected in the anatomical aspects of DA systems in the forebrain and midbrain. Recent findings concerning a second tyrosine hydroxylase gene (TH2 revealed new populations of DA synthesizing cells, as evidenced in the periventricular hypothalamic zones of teleost fish. It is likely that the ancestor of vertebrates possessed TH2 DA-synthesizing cells, and the TH2 gene has been lost secondarily in placental mammals. All the vertebrates possess DA cells in the olfactory bulb, retina and in the diencephalon. Midbrain DA cells are abundant in amniotes while absent in some groups, e.g. teleosts. Studies of protochordate DA cells suggest that the diencephalic DA cells were present before the divergence of the chordate lineage. In contrast, the midbrain cell populations have probably emerged in the vertebrate lineage following the development of the midbrain-hindbrain boundary. The functional flexibility of the DA systems, and the evolvability provided by duplication of the corresponding genes permitted a large diversification of these systems. These features were instrumental in the adaptation of brain functions to the very variable way of life of vertebrates.

  12. The evolution of dopamine systems in chordates.

    Science.gov (United States)

    Yamamoto, Kei; Vernier, Philippe

    2011-01-01

    Dopamine (DA) neurotransmission in the central nervous system (CNS) is found throughout chordates, and its emergence predates the divergence of chordates. Many of the molecular components of DA systems, such as biosynthetic enzymes, transporters, and receptors, are shared with those of other monoamine systems, suggesting the common origin of these systems. In the mammalian CNS, the DA neurotransmitter systems are diversified and serve for visual and olfactory perception, sensory-motor programming, motivation, memory, emotion, and endocrine regulations. Some of the functions are conserved among different vertebrate groups, while others are not, and this is reflected in the anatomical aspects of DA systems in the forebrain and midbrain. Recent findings concerning a second tyrosine hydroxylase gene (TH2) revealed new populations of DA-synthesizing cells, as evidenced in the periventricular hypothalamic zones of teleost fish. It is likely that the ancestor of vertebrates possessed TH2 DA-synthesizing cells, and the TH2 gene has been lost secondarily in placental mammals. All the vertebrates possess DA cells in the olfactory bulb, retina, and in the diencephalon. Midbrain DA cells are abundant in amniotes while absent in some groups, e.g., teleosts. Studies of protochordate DA cells suggest that the diencephalic DA cells were present before the divergence of the chordate lineage. In contrast, the midbrain cell populations have probably emerged in the vertebrate lineage following the development of the midbrain-hindbrain boundary. The functional flexibility of the DA systems, and the evolvability provided by duplication of the corresponding genes permitted a large diversification of these systems. These features were instrumental in the adaptation of brain functions to the very variable way of life of vertebrates. PMID:21483723

  13. The amphioxus genome and the evolution of the chordate karyotype

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    Putnam, Nicholas H.; Butts, Thomas; Ferrier, David E.K.; Furlong, Rebecca F.; Hellsten, Uffe; Kawashima, Takeshi; Robinson-Rechavi, Marc; Shoguchi, Eiichi; Terry, Astrid; Yu, Jr-Kai; Benito-Gutierrez, Elia; Dubchak, Inna; Garcia-Fernandez, Jordi; Gibson-Brown, Jeremy J.; Grigoriev, Igor V.; Horton, Amy C.; de Jong, Pieter J.; Jurka, Jerzy; Kapitonov, Vladimir; Kohara, Yuji; Kuroki, Yoko; Lindquist, Erika; Lucas, Susan; Osoegawa, Kazutoyo; Pennacchio, Len A.; Salamov, Asaf A.; Satou, Yutaka; Sauka-Spengler, Tatjana; Schmutz[, Jeremy; Shin-I, Tadasu; Toyoda, Atsushi; Bronner-Fraser, Marianne; Fujiyama, Asao; Holland, Linda Z.; Holland, Peter W. H.; Satoh, Nori; Rokhsar, Daniel S.

    2008-04-01

    Lancelets ('amphioxus') are the modern survivors of an ancient chordate lineage with a fossil record dating back to the Cambrian. We describe the structure and gene content of the highly polymorphic {approx}520 million base pair genome of the Florida lancelet Branchiostoma floridae, and analyze it in the context of chordate evolution. Whole genome comparisons illuminate the murky relationships among the three chordate groups (tunicates, lancelets, and vertebrates), and allow reconstruction of not only the gene complement of the last common chordate ancestor, but also a partial reconstruction of its genomic organization, as well as a description of two genome-wide duplications and subsequent reorganizations in the vertebrate lineage. These genome-scale events shaped the vertebrate genome and provided additional genetic variation for exploitation during vertebrate evolution.

  14. Retinoic acid signaling and the evolution of chordates

    OpenAIRE

    Marlétaz, Ferdinand; Holland, Linda Z; Laudet, Vincent; Schubert, Michael

    2006-01-01

    In chordates, which comprise urochordates, cephalochordates and vertebrates, the vitamin A-derived morphogen retinoic acid (RA) has a pivotal role during development. Altering levels of endogenous RA signaling during early embryology leads to severe malformations, mainly due to incorrect positional codes specifying the embryonic anteroposterior body axis. In this review, we present our current understanding of the RA signaling pathway and its roles during chordate development. In particular, ...

  15. Inversion of the chordate body axis: are there alternatives?

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    Gerhart, J.

    2000-01-01

    One major morphological difference between chordates and annelids or arthropods is the opposite orientation of the nerve cord and heart. A long-standing proposal is that the chordate axis evolved by inverting the body of an ancestor with the annelid/arthropod orientation. However, the data can also be explained by a common ancestor with diffuse dorsoventral organization, followed by oppositely directed condensation of the nerve cord and relocation of the heart in the two lines.

  16. Ascidians and the plasticity of the chordate developmental program

    OpenAIRE

    Lemaire, Patrick; Smith, William C.; Nishida, Hiroki

    2008-01-01

    Little is known about the ancient chordates that gave rise to the first vertebrates, but the descendants of other invertebrate chordates extant at the time still flourish in the ocean. These invertebrates include the cephalochordates and tunicates, whose larvae share with vertebrate embryos a common body plan with a central notochord and a dorsal nerve cord. Tunicates are now thought to be the sister group of vertebrates. However, research based on several species of ascidians, a diverse and ...

  17. Inversion of the chordate body axis: Are there alternatives?

    OpenAIRE

    Gerhart, J.

    2000-01-01

    One major morphological difference between chordates and annelids or arthropods is the opposite orientation of the nerve cord and heart. A long-standing proposal is that the chordate axis evolved by inverting the body of an ancestor with the annelid/arthropod orientation. However, the data can also be explained by a common ancestor with diffuse dorsoventral organization, followed by oppositely directed condensation of the nerve cord and relocation of the heart in the t...

  18. Unique Development in Hemichordates Suggest Some Unique Features of Chordates

    OpenAIRE

    Lowe, Christopher J.; Mark Terasaki; Michael Wu; Freeman, Robert M.; Linda Runft; Kristen Kwan; Saori Haigo; Jochanan Aronowicz; Eric Lander; Chris Gruber; Mark Smith; Marc Kirschner; John Gerhart

    2006-01-01

    We have compared the dorsoventral development of hemichordates and chordates to deduce the organization of their common ancestor, and hence to identify the evolutionary modifications of the chordate body axis after the lineages split. In the hemichordate embryo, genes encoding bone morphogenetic proteins (Bmp) 2/4 and 5/8, as well as several genes for modulators of Bmp activity, are expressed in a thin stripe of ectoderm on one midline, historically called "dorsal." On the opposite midline, t...

  19. Chordate evolution and the three-phylum system

    OpenAIRE

    Satoh, Noriyuki; Rokhsar, Daniel; Nishikawa, Teruaki

    2014-01-01

    Traditional metazoan phylogeny classifies the Vertebrata as a subphylum of the phylum Chordata, together with two other subphyla, the Urochordata (Tunicata) and the Cephalochordata. The Chordata, together with the phyla Echinodermata and Hemichordata, comprise a major group, the Deuterostomia. Chordates invariably possess a notochord and a dorsal neural tube. Although the origin and evolution of chordates has been studied for more than a century, few authors have intimately discussed taxonomi...

  20. Dorsoventral patterning in hemichordates: insights into early chordate evolution.

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    Christopher J Lowe

    2006-09-01

    Full Text Available We have compared the dorsoventral development of hemichordates and chordates to deduce the organization of their common ancestor, and hence to identify the evolutionary modifications of the chordate body axis after the lineages split. In the hemichordate embryo, genes encoding bone morphogenetic proteins (Bmp 2/4 and 5/8, as well as several genes for modulators of Bmp activity, are expressed in a thin stripe of ectoderm on one midline, historically called "dorsal." On the opposite midline, the genes encoding Chordin and Anti-dorsalizing morphogenetic protein (Admp are expressed. Thus, we find a Bmp-Chordin developmental axis preceding and underlying the anatomical dorsoventral axis of hemichordates, adding to the evidence from Drosophila and chordates that this axis may be at least as ancient as the first bilateral animals. Numerous genes encoding transcription factors and signaling ligands are expressed in the three germ layers of hemichordate embryos in distinct dorsoventral domains, such as pox neuro, pituitary homeobox, distalless, and tbx2/3 on the Bmp side and netrin, mnx, mox, and single-minded on the Chordin-Admp side. When we expose the embryo to excess Bmp protein, or when we deplete endogenous Bmp by small interfering RNA injections, these expression domains expand or contract, reflecting their activation or repression by Bmp, and the embryos develop as dorsalized or ventralized limit forms. Dorsoventral patterning is independent of anterior/posterior patterning, as in Drosophila but not chordates. Unlike both chordates and Drosophila, neural gene expression in hemichordates is not repressed by high Bmp levels, consistent with their development of a diffuse rather than centralized nervous system. We suggest that the common ancestor of hemichordates and chordates did not use its Bmp-Chordin axis to segregate epidermal and neural ectoderm but to pattern many other dorsoventral aspects of the germ layers, including neural cell fates

  1. Retinoic acid signaling and the evolution of chordates

    Directory of Open Access Journals (Sweden)

    2006-04-01

    Full Text Available In chordates, which comprise urochordates, cephalochordates and vertebrates, the vitamin A-derived morphogen retinoic acid (RA has a pivotal role during development. Altering levels of endogenous RA signaling during early embryology leads to severe malformations, mainly due to incorrect positional codes specifying the embryonic anteroposterior body axis. In this review, we present our current understanding of the RA signaling pathway and its roles during chordate development. In particular, we focus on the conserved roles of RA and its downstream mediators, the Hox genes, in conveying positional patterning information to different embryonic tissues, such as the endoderm and the central nervous system. We find that some of the control mechanisms governing RA-mediated patterning are well conserved between vertebrates and invertebrate chordates, such as the cephalochordate amphioxus. In contrast, outside the chordates, evidence for roles of RA signaling is scarce and the evolutionary origin of the RA pathway itself thus remains elusive. In sum, to fully understand the evolutionary history of the RA pathway, future research should focus on identification and study of components of the RA signaling cascade in non-chordate deuterostomes (such as hemichordates and echinoderms and other invertebrates, such as insects, mollusks and cnidarians.

  2. Evolution of the organizer and the chordate body plan

    Science.gov (United States)

    Gerhart, J.

    2001-01-01

    The discovery of the organizer by Spemann and Mangold in 1924 raised two kinds of questions: those about the means of patterning the chordate body axis and those about the mechanisms of cell determination by induction. Some researchers, stressing the second, have suggested over the years that the organizer is poorly named and doesn't really organize because inducers act permissively, because they are not unique to the organizer, and because multipotent responsive cells develop complex local differentiations under artificial conditions. Furthermore, with the discovery of meso-endoderm induction in 1969, the possibility arose that this earlier induction generates as much organization as, or more than, does the organizer itself. Evidence is summarized in this article that the organizer does fulfill its title with regard to pattern formation: it adds greatly to embryonic organization by providing information about time, place, scale, and orientation for development by nearby members of the large multipotent competence groups surrounding the organizer. Embryos having smaller or larger organizers due to experimental intervention develop defective axial organization. Without an organizer the embryo develops no body axis and none of the four chordate characters: the notochord, gill slits, dorsal hollow nerve chord, and post-anal tail. For normal axis formation, the organizer's tripartite organization is needed. Each part differs in inducers, morphogenesis, and self-differentiation. The organizer is a trait of development of all members of the chordate phylum. In comparison to hemichordates, which constitute a phylum with some similarities to chordates, the chordamesoderm part is unique to the chordate organizer (the trunk-tail organizer). Its convergent extension displaces the gastrula posterior pole from alignment with the animal-vegetal axis and generates a new anteroposterior axis orthogonal to this old one. Once it has extended to full length, its signaling modifies

  3. Cis-regulatory architecture of a brain signaling center predates the origin of chordates.

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    Yao, Yao; Minor, Paul J; Zhao, Ying-Tao; Jeong, Yongsu; Pani, Ariel M; King, Anna N; Symmons, Orsolya; Gan, Lin; Cardoso, Wellington V; Spitz, François; Lowe, Christopher J; Epstein, Douglas J

    2016-05-01

    Genomic approaches have predicted hundreds of thousands of tissue-specific cis-regulatory sequences, but the determinants critical to their function and evolutionary history are mostly unknown. Here we systematically decode a set of brain enhancers active in the zona limitans intrathalamica (zli), a signaling center essential for vertebrate forebrain development via the secreted morphogen Sonic hedgehog (Shh). We apply a de novo motif analysis tool to identify six position-independent sequence motifs together with their cognate transcription factors that are essential for zli enhancer activity and Shh expression in the mouse embryo. Using knowledge of this regulatory lexicon, we discover new Shh zli enhancers in mice and a functionally equivalent element in hemichordates, indicating an ancient origin of the Shh zli regulatory network that predates the chordate phylum. These findings support a strategy for delineating functionally conserved enhancers in the absence of overt sequence homologies and over extensive evolutionary distances. PMID:27064252

  4. Review: evolution of GnIH and related peptides structure and function in the chordates.

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    Osugi, Tomohiro; Ubuka, Takayoshi; Tsutsui, Kazuyoshi

    2014-01-01

    Discovery of gonadotropin-inhibitory hormone (GnIH) in the Japanese quail in 2000 was the first to demonstrate the existence of a hypothalamic neuropeptide inhibiting gonadotropin release. We now know that GnIH regulates reproduction by inhibiting gonadotropin synthesis and release via action on the gonadotropin-releasing hormone (GnRH) system and the gonadotrope in various vertebrates. GnIH peptides identified in birds and mammals have a common LPXRF-amide (X = L or Q) motif at the C-terminus and inhibit pituitary gonadotropin secretion. However, the function and structure of GnIH peptides are diverse in fish. Goldfish GnIHs possessing a C-terminal LPXRF-amide motif have both stimulatory and inhibitory effects on gonadotropin synthesis or release. The C-terminal sequence of grass puffer and medaka GnIHs are MPQRF-amide. To investigate the evolutionary origin of GnIH and its ancestral structure and function, we searched for GnIH in agnathans, the most ancient lineage of vertebrates. We identified GnIH precursor gene and mature GnIH peptides with C-terminal QPQRF-amide or RPQRF-amide from the brain of sea lamprey. Lamprey GnIH fibers were in close proximity to GnRH-III neurons. Further, one of lamprey GnIHs stimulated the expression of lamprey GnRH-III peptide in the hypothalamus and gonadotropic hormone β mRNA expression in the pituitary. We further identified the ancestral form of GnIH, which had a C-terminal RPQRF-amide, and its receptors in amphioxus, the most basal chordate species. The amphioxus GnIH inhibited cAMP signaling in vitro. In sum, the original forms of GnIH may date back to the time of the emergence of early chordates. GnIH peptides may have had various C-terminal structures slightly different from LPXRF-amide in basal chordates, which had stimulatory and/or inhibitory functions on reproduction. The C-terminal LPXRF-amide structure and its inhibitory function on reproduction may be selected in later-evolved vertebrates, such as birds and mammals

  5. Anteroposterior patterning in hemichordates and the origins of the chordate nervous system

    Science.gov (United States)

    Lowe, Christopher J.; Wu, Mike; Salic, Adrian; Evans, Louise; Lander, Eric; Stange-Thomann, Nicole; Gruber, Christian E.; Gerhart, John; Kirschner, Marc

    2003-01-01

    The chordate central nervous system has been hypothesized to originate from either a dorsal centralized, or a ventral centralized, or a noncentralized nervous system of a deuterostome ancestor. In an effort to resolve these issues, we examined the hemichordate Saccoglossus kowalevskii and studied the expression of orthologs of genes that are involved in patterning the chordate central nervous system. All 22 orthologs studied are expressed in the ectoderm in an anteroposterior arrangement nearly identical to that found in chordates. Domain topography is conserved between hemichordates and chordates despite the fact that hemichordates have a diffuse nerve net, whereas chordates have a centralized system. We propose that the deuterostome ancestor may have had a diffuse nervous system, which was later centralized during the evolution of the chordate lineage.

  6. Amphioxus: a peaceful anchovy fillet to illuminate Chordate Evolution (II

    Directory of Open Access Journals (Sweden)

    Jordi Garcia-Fernàndez

    2006-01-01

    Full Text Available The genome of the amphioxus is on the horizon. With Linda Holland and Jeremy Gibson-Brown at the forefront, with all the amphioxus community behind, and with the Joint Genome Institute, the amphioxus genome will see the light this year, 2006. Hope that it will reflect the “prototypical” preduplicative genome of vertebrates. It may answer definitively what the human genome did not: Are we vertebrates octaploid? Will it shed light on the novelties that helped non-chordates to be chordates? And more, will amphioxus, with a simpler genome, be developed to a senior “experimental model system”, allowing the testing of molecular functions in a non-duplicated genome background and allowing genetic modification to “recapitulate” evolution? Thanks to an outstanding collaboration between labs, the laboratory culture of amphioxus is underway after years of hard work in the field. 2007 looks promising for amphioxus research.

  7. Conservation of Notochord Gene Expression Across Chordates: Insights From the Leprecan Gene Family

    OpenAIRE

    Capellini, Terence D.; Dunn, Matthew P.; Yale J Passamaneck; Selleri, Licia; Di Gregorio, Anna

    2008-01-01

    The notochord is a defining character of the chordates, and the T-box transcription factor Brachyury has been shown to be required for notochord development in all chordates examined. In the ascidian Ciona intestinalis, at least 44 notochord genes have been identified as bona fide transcriptional targets of Brachyury. We examined the embryonic expression of a subset of murine orthologs of Ciona Brachyury target genes in the notochord to assess its conservation throughout chordate evolution. W...

  8. rRNA genes from the lower chordate Herdmania momus: structural similarity with higher eukaryotes.

    OpenAIRE

    Degnan, B M; Yan, J.; Hawkins, C J; Lavin, M F

    1990-01-01

    Ascidians, primitive chordates that have retained features of the likely progenitors to all vertebrates, are a useful model to study the evolutionary relationship of chordates to other animals. We have selected the well characterized ribosomal RNA (rRNA) genes to investigate this relationship, and we describe here the cloning and characterization of an entire ribosomal DNA (rDNA) tandem repeat unit from a lower chordate, the ascidian Herdmania momus. rDNA copy number and considerable sequence...

  9. The Middle Cambrian fossil Pikaia and the evolution of chordate swimming

    OpenAIRE

    Lacalli Thurston

    2012-01-01

    Abstract Conway Morris and Caron (2012) have recently published an account of virtually all the available information on Pikaia gracilens, a well-known Cambrian fossil and supposed basal chordate, and propose on this basis some new ideas about Pikaia’s anatomy and evolutionary significance. Chief among its chordate-like features are the putative myomeres, a regular series of vertical bands that extends the length of the body. These differ from the myomeres of living chordates in that boundari...

  10. Parallel Evolution of Chordate Cis-Regulatory Code for Development

    OpenAIRE

    Doglio, Laura; Goode, Debbie K.; Maria C. Pelleri; Pauls, Stefan; Frabetti, Flavia; Shimeld, Sebastian M; Vavouri, Tanya; Elgar, Greg

    2013-01-01

    Urochordates are the closest relatives of vertebrates and at the larval stage, possess a characteristic bilateral chordate body plan. In vertebrates, the genes that orchestrate embryonic patterning are in part regulated by highly conserved non-coding elements (CNEs), yet these elements have not been identified in urochordate genomes. Consequently the evolution of the cis-regulatory code for urochordate development remains largely uncharacterised. Here, we use genome-wide comparisons between C...

  11. Vertebrate-like regeneration in the invertebrate chordate amphioxus

    OpenAIRE

    Somorjai, Ildikó M. L.; Rajmund L. Somorjai; Garcia-Fernàndez, Jordi; Escrivà, Hector

    2011-01-01

    An important question in biology is why some animals are able to regenerate, whereas others are not. The basal chordate amphioxus is uniquely positioned to address the evolution of regeneration. We report here the high regeneration potential of the European amphioxus Branchiostoma lanceolatum. Adults regenerate both anterior and posterior structures, including neural tube, notochord, fin, and muscle. Development of a classifier based on tail regeneration profiles predicts the assignment of yo...

  12. Genetic and Genomic Toolbox of the Chordate Ciona intestinalis

    OpenAIRE

    Stolfi, Alberto; Christiaen, Lionel

    2012-01-01

    The experimental malleability and unique phylogenetic position of the sea squirt Ciona intestinalis as part of the sister group to the vertebrates have helped establish these marine chordates as model organisms for the study of developmental genetics and evolution. Here we summarize the tools, techniques, and resources available to the Ciona geneticist, citing examples of studies that employed such strategies in the elucidation of gene function in Ciona. Genetic screens, germline transgenesis...

  13. Acquisition of the dorsal structures in chordate amphioxus

    Science.gov (United States)

    Morov, Arseniy R.; Ukizintambara, Tharcisse; Sabirov, Rushan M.

    2016-01-01

    Acquisition of dorsal structures, such as notochord and hollow nerve cord, is likely to have had a profound influence upon vertebrate evolution. Dorsal formation in chordate development thus has been intensively studied in vertebrates and ascidians. However, the present understanding does not explain how chordates acquired dorsal structures. Here we show that amphioxus retains a key clue to answer this question. In amphioxus embryos, maternal nodal mRNA distributes asymmetrically in accordance with the remodelling of the cortical cytoskeleton in the fertilized egg, and subsequently lefty is first expressed in a patch of blastomeres across the equator where wnt8 is expressed circularly and which will become the margin of the blastopore. The lefty domain co-expresses zygotic nodal by the initial gastrula stage on the one side of the blastopore margin and induces the expression of goosecoid, not-like, chordin and brachyury1 genes in this region, as in the oral ectoderm of sea urchin embryos, which provides a basis for the formation of the dorsal structures. The striking similarity in the gene regulations and their respective expression domains when comparing dorsal formation in amphioxus and the determination of the oral ectoderm in sea urchin embryos suggests that chordates derived from an ambulacrarian-type blastula with dorsoventral inversion. PMID:27307516

  14. Acquisition of the dorsal structures in chordate amphioxus.

    Science.gov (United States)

    Morov, Arseniy R; Ukizintambara, Tharcisse; Sabirov, Rushan M; Yasui, Kinya

    2016-06-01

    Acquisition of dorsal structures, such as notochord and hollow nerve cord, is likely to have had a profound influence upon vertebrate evolution. Dorsal formation in chordate development thus has been intensively studied in vertebrates and ascidians. However, the present understanding does not explain how chordates acquired dorsal structures. Here we show that amphioxus retains a key clue to answer this question. In amphioxus embryos, maternal nodal mRNA distributes asymmetrically in accordance with the remodelling of the cortical cytoskeleton in the fertilized egg, and subsequently lefty is first expressed in a patch of blastomeres across the equator where wnt8 is expressed circularly and which will become the margin of the blastopore. The lefty domain co-expresses zygotic nodal by the initial gastrula stage on the one side of the blastopore margin and induces the expression of goosecoid, not-like, chordin and brachyury1 genes in this region, as in the oral ectoderm of sea urchin embryos, which provides a basis for the formation of the dorsal structures. The striking similarity in the gene regulations and their respective expression domains when comparing dorsal formation in amphioxus and the determination of the oral ectoderm in sea urchin embryos suggests that chordates derived from an ambulacrarian-type blastula with dorsoventral inversion. PMID:27307516

  15. Upregulation of mesencephalic astrocyte-derived neurotrophic factor in glial cells is associated with ischemia-induced glial activation

    Directory of Open Access Journals (Sweden)

    Shen Yujun

    2012-11-01

    Full Text Available Abstract Background Mesencephalic astrocyte-derived neurotrophic factor (MANF, a 20 kDa secreted protein, was originally derived from a rat mesencephalic type-1 astrocyte cell line. MANF belongs to a novel evolutionally conserved family of neurotrophic factors along with conserved dopamine neurotrophic factor. In recent years, ever-increasing evidence has shown that both of them play a remarkable protective role against various injuries to neurons in vivo or in vitro. However, the characteristics of MANF expression in the different types of glial cells, especially in astrocytes, remain unclear. Methods The model of focal cerebral ischemia was induced by rat middle cerebral artery occlusion. Double-labeled immunofluorescent staining was used to identify the types of neural cells expressing MANF. Primarily cultured glial cells were used to detect the response of glial cells to endoplasmic reticulum stress stimulation. Propidium iodide staining was used to determine dead cells. Reverse transcription PCR and western blotting were used to detect the levels of mRNA and proteins. Results We found that MANF was predominantly expressed in neurons in both normal and ischemic cortex. Despite its name, MANF was poorly expressed in glial cells, including astrocytes, in normal brain tissue. However, the expression of MANF was upregulated in the glial cells under focal cerebral ischemia, including the astrocytes. This expression was also induced by several endoplasmic reticulum stress inducers and nutrient deprivation in cultured primary glial cells. The most interesting phenomenon observed in this study was the pattern of MANF expression in the microglia. The expression of MANF was closely associated with the morphology and state of microglia, accompanied by the upregulation of BIP/Grp78. Conclusions These results indicate that MANF expression was upregulated in the activated glial cells, which may contribute to the mechanism of ischemia-induced neural injury.

  16. Roles of retinoic acid and Tbx1/10 in pharyngeal segmentation: amphioxus and the ancestral chordate condition

    OpenAIRE

    Koop, Demian; Chen, Jie; Theodosiou, Maria; Carvalho, João E; Alvarez, Susana; de Lera, Angel R.; Holland, Linda Z.; Schubert, Michael

    2014-01-01

    Background Although chordates descend from a segmented ancestor, the evolution of head segmentation has been very controversial for over 150 years. Chordates generally possess a segmented pharynx, but even though anatomical evidence and gene expression analyses suggest homologies between the pharyngeal apparatus of invertebrate chordates, such as the cephalochordate amphioxus, and vertebrates, these homologies remain contested. We, therefore, decided to study the evolution of the chordate hea...

  17. Evolution of anterior Hox regulatory elements among chordates

    Directory of Open Access Journals (Sweden)

    Natale Alfonso

    2011-11-01

    Full Text Available Abstract Background The Hox family of transcription factors has a fundamental role in segmentation pathways and axial patterning of embryonic development and their clustered organization is linked with the regulatory mechanisms governing their coordinated expression along embryonic axes. Among chordates, of particular interest are the Hox paralogous genes in groups 1-4 since their expression is coupled to the control of regional identity in the anterior nervous system, where the highest structural diversity is observed. Results To investigate the degree of conservation in cis-regulatory components that form the basis of Hox expression in the anterior nervous system, we have used assays for transcriptional activity in ascidians and vertebrates to compare and contrast regulatory potential. We identified four regulatory sequences located near the CiHox1, CiHox2 and CiHox4 genes of the ascidian Ciona intestinalis which direct neural specific domains of expression. Using functional assays in Ciona and vertebrate embryos in combination with sequence analyses of enhancer fragments located in similar positions adjacent to Hox paralogy group genes, we compared the activity of these four Ciona cis-elements with a series of neural specific enhancers from the amphioxus Hox1-3 genes and from mouse Hox paralogous groups 1-4. Conclusions This analysis revealed that Kreisler and Krox20 dependent enhancers critical in segmental regulation of the hindbrain appear to be specific for the vertebrate lineage. In contrast, neural enhancers that function as Hox response elements through the action of Hox/Pbx binding motifs have been conserved during chordate evolution. The functional assays reveal that these Hox response cis-elements are recognized by the regulatory components of different and extant species. Together, our results indicate that during chordate evolution, cis-elements dependent upon Hox/Pbx regulatory complexes, are responsible for key aspects of

  18. The candidate histocompatibility locus of a Basal chordate encodes two highly polymorphic proteins.

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    Marie L Nydam

    Full Text Available The basal chordate Botryllus schlosseri undergoes a natural transplantation reaction governed by a single, highly polymorphic locus called the fuhc. Our initial characterization of this locus suggested it encoded a single gene alternatively spliced into two transcripts: a 555 amino acid-secreted form containing the first half of the gene, and a full-length, 1008 amino acid transmembrane form, with polymorphisms throughout the ectodomain determining outcome. We have now found that the locus encodes two highly polymorphic genes which are separated by a 227 bp intergenic region: first, the secreted form as previously described, and a second gene encoding a 531 amino acid membrane-bound gene containing three extracellular immunoglobulin domains. While northern blotting revealed only these two mRNAs, both PCR and mRNA-seq detect a single capped and polyadenylated transcript that encodes processed forms of both genes linked by the intergenic region, as well as other transcripts in which exons of the two genes are spliced together. These results might suggest that the two genes are expressed as an operon, during which both genes are co-transcribed and then trans-spliced into two separate messages. This type of transcriptional regulation has been described in tunicates previously; however, the membrane-bound gene does not encode a typical Splice Leader (SL sequence at the 5' terminus that usually accompanies trans-splicing. Thus, the presence of stable transcripts encoding both genes may suggest a novel mechanism of regulation, or conversely may be rare but stable transcripts in which the two mRNAs are linked due to a small amount of read-through by RNA polymerase. Both genes are highly polymorphic and co-expressed on tissues involved in histocompatibility. In addition, polymorphisms on both genes correlate with outcome, although we have found a case in which it appears that the secreted form may be major allorecognition determinant.

  19. Amphioxus: a peaceful anchovy fillet to illuminate Chordate Evolution (II)

    OpenAIRE

    Jordi Garcia-Fernàndez

    2006-01-01

    The genome of the amphioxus is on the horizon. With Linda Holland and Jeremy Gibson-Brown at the forefront, with all the amphioxus community behind, and with the Joint Genome Institute, the amphioxus genome will see the light this year, 2006. Hope that it will reflect the “prototypical” preduplicative genome of vertebrates. It may answer definitively what the human genome did not: Are we vertebrates octaploid? Will it shed light on the novelties that helped non-chordates to be cho...

  20. Functional modeling of neural-glial interaction

    DEFF Research Database (Denmark)

    Postnov, D.E.; Ryazanova, L.S.; Sosnovtseva, Olga

    2007-01-01

    We propose a generalized mathematical model for a small neural-glial ensemble. The model incorporates subunits of the tripartite synapse that includes a presynaptic neuron, the synaptic terminal itself, a postsynaptic neuron, and a glial cell. The glial cell is assumed to be activated via two dif...

  1. Histone variant innovation in a rapidly evolving chordate lineage

    Directory of Open Access Journals (Sweden)

    Jansen Pascal WTC

    2011-07-01

    Full Text Available Abstract Background Histone variants alter the composition of nucleosomes and play crucial roles in transcription, chromosome segregation, DNA repair, and sperm compaction. Modification of metazoan histone variant lineages occurs on a background of genome architecture that shows global similarities from sponges to vertebrates, but the urochordate, Oikopleura dioica, a member of the sister group to vertebrates, exhibits profound modification of this ancestral architecture. Results We show that a histone complement of 47 gene loci encodes 31 histone variants, grouped in distinct sets of developmental expression profiles throughout the life cycle. A particularly diverse array of 15 male-specific histone variants was uncovered, including a testes-specific H4t, the first metazoan H4 sequence variant reported. Universal histone variants H3.3, CenH3, and H2A.Z are present but O. dioica lacks homologs of macroH2A and H2AX. The genome encodes many H2A and H2B variants and the repertoire of H2A.Z isoforms is expanded through alternative splicing, incrementally regulating the number of acetylatable lysine residues in the functionally important N-terminal "charge patch". Mass spectrometry identified 40 acetylation, methylation and ubiquitylation posttranslational modifications (PTMs and showed that hallmark PTMs of "active" and "repressive" chromatin were present in O. dioica. No obvious reduction in silent heterochromatic marks was observed despite high gene density in this extraordinarily compacted chordate genome. Conclusions These results show that histone gene complements and their organization differ considerably even over modest phylogenetic distances. Substantial innovation among all core and linker histone variants has evolved in concert with adaptation of specific life history traits in this rapidly evolving chordate lineage.

  2. Origins of anteroposterior patterning and Hox gene regulation during chordate evolution.

    OpenAIRE

    Schilling, T. F.; Knight, R D

    2001-01-01

    All chordates share a basic body plan and many common features of early development. Anteroposterior (AP) regions of the vertebrate neural tube are specified by a combinatorial pattern of Hox gene expression that is conserved in urochordates and cephalochordates. Another primitive feature of Hox gene regulation in all chordates is a sensitivity to retinoic acid during embryogenesis, and recent developmental genetic studies have demonstrated the essential role for retinoid signalling in verteb...

  3. How much does the amphioxus genome represent the ancestor of chordates?

    OpenAIRE

    Louis A.; Roest Crollius H.; Robinson-Rechavi M.

    2012-01-01

    One of the main motivations to study amphioxus is its potential for understanding the last common ancestor of chordates, which notably gave rise to the vertebrates. An important feature in this respect is the slow evolutionary rate that seems to have characterized the cephalochordate lineage, making amphioxus an interesting proxy for the chordate ancestor, as well as a key lineage to include in comparative studies. Whereas slow evolution was first noticed at the phenotypic level, it has also ...

  4. Evolutionary Patterns of RNA-Based Duplication in Non-Mammalian Chordates

    OpenAIRE

    Ming Chen; Ming Zou; Beide Fu; Xin Li; Vibranovski, Maria D.; Xiaoni Gan; Dengqiang Wang; Wen Wang; Manyuan Long; Shunping He

    2011-01-01

    The role of RNA-based duplication, or retroposition, in the evolution of new gene functions in mammals, plants, and Drosophila has been widely reported. However, little is known about RNA-based duplication in non-mammalian chordates. In this study, we screened ten non-mammalian chordate genomes for retrocopies and investigated their evolutionary patterns. We identified numerous retrocopies in these species. Examination of the age distribution of these retrocopies revealed no burst of young re...

  5. Characterization of an individual neural crest-like cell lineage in the invertebrate chordate Ciona intestinalis

    OpenAIRE

    Cone, Angela C.

    2008-01-01

    During embryogenesis, all chordate embryos undergo neurulation to form a dorsal, hollow nerve cord. Neural crest cells (NCC), considered a vertebrate innovation, arise during neurulation and later differentiate into a multitude of tissues that account for much of the structural complexity that distinguishes craniates from invertebrate chordates [1, 2]. NCCs are induced and specified at the border of the neural and non-neural ectoderm by a complex network of inductive signals and transcription...

  6. Tunicate mitogenomics and phylogenetics: peculiarities of the Herdmania momus mitochondrial genome and support for the new chordate phylogeny.

    OpenAIRE

    Loya Yossi; Shenkar Noa; Blanquart Samuel; Delsuc Frédéric; Tsagkogeorga Georgia; Singh Tiratha; Douzery Emmanuel JP; Huchon Dorothée

    2009-01-01

    Abstract Background Tunicates represent a key metazoan group as the sister-group of vertebrates within chordates. The six complete mitochondrial genomes available so far for tunicates have revealed distinctive features. Extensive gene rearrangements and particularly high evolutionary rates have been evidenced with regard to other chordates. This peculiar evolutionary dynamics has hampered the reconstruction of tunicate phylogenetic relationships within chordates based on mitogenomic data. Res...

  7. Do glial cells control pain?

    OpenAIRE

    Suter, Marc R; Wen, Yeong-Ray; Decosterd, Isabelle; Ji, Ru-Rong

    2007-01-01

    Management of chronic pain is a real challenge, and current treatments focusing on blocking neurotransmission in the pain pathway have only resulted in limited success. Activation of glia cells has been widely implicated in neuroinflammation in the central nervous system, leading to neruodegeneration in many disease conditions such as Alzheimer’s and multiple sclerosis. The inflammatory mediators released by activated glial cells, such as tumor necrosis factor-α and interleukin-1β can not onl...

  8. Evolutionary origin of GnIH and NPFF in chordates: insights from novel amphioxus RFamide peptides.

    Directory of Open Access Journals (Sweden)

    Tomohiro Osugi

    Full Text Available Gonadotropin-inhibitory hormone (GnIH is a newly identified hypothalamic neuropeptide that inhibits pituitary hormone secretion in vertebrates. GnIH has an LPXRFamide (X = L or Q motif at the C-terminal in representative species of gnathostomes. On the other hand, neuropeptide FF (NPFF, a neuropeptide characterized as a pain-modulatory neuropeptide, in vertebrates has a PQRFamide motif similar to the C-terminal of GnIH, suggesting that GnIH and NPFF have diverged from a common ancestor. Because GnIH and NPFF belong to the RFamide peptide family in vertebrates, protochordate RFamide peptides may provide important insights into the evolutionary origin of GnIH and NPFF. In this study, we identified a novel gene encoding RFamide peptides and two genes of their putative receptors in the amphioxus Branchiostoma japonicum. Molecular phylogenetic analysis and synteny analysis indicated that these genes are closely related to the genes of GnIH and NPFF and their receptors of vertebrates. We further identified mature RFamide peptides and their receptors in protochordates. The identified amphioxus RFamide peptides inhibited forskolin induced cAMP signaling in the COS-7 cells with one of the identified amphioxus RFamide peptide receptors expressed. These results indicate that the identified protochordate RFamide peptide gene is a common ancestral form of GnIH and NPFF genes, suggesting that the origin of GnIH and NPFF may date back to the time of the emergence of early chordates. GnIH gene and NPFF gene may have diverged by whole-genome duplication in the course of vertebrate evolution.

  9. Glial calcium signaling in physiology and pathophysioilogy

    Institute of Scientific and Technical Information of China (English)

    Alexei VERKHRASKY

    2006-01-01

    Neuronal-glial circuits underlie integrative processes in the nervous system.Function of glial syncytium is,to a very large extent,regulated by the intracellular calcium signaling system.Glial calcium signals are triggered by activation of multiple receptors,expressed in glial membrane,which regulate both Ca2+ entry and Ca2+ release from the endoplasmic reticulum.The endoplasmic reticulum also endows glial cells with intracellular excitable media,which is able to produce and maintain long-ranging signaling in a form of propagating Ca2+ waves.In pathological conditions,calcium signals regulate glial response to injury,which might have both protective and detrimental effects on the nervous tissue.

  10. Molecular evolution of a chordate specific family of G protein-coupled receptors

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    Leese Florian

    2011-08-01

    Full Text Available Abstract Background Chordate evolution is a history of innovations that is marked by physical and behavioral specializations, which led to the development of a variety of forms from a single ancestral group. Among other important characteristics, vertebrates obtained a well developed brain, anterior sensory structures, a closed circulatory system and gills or lungs as blood oxygenation systems. The duplication of pre-existing genes had profound evolutionary implications for the developmental complexity in vertebrates, since mutations modifying the function of a duplicated protein can lead to novel functions, improving the evolutionary success. Results We analyzed here the evolution of the GPRC5 family of G protein-coupled receptors by comprehensive similarity searches and found that the receptors are only present in chordates and that the size of the receptor family expanded, likely due to genome duplication events in the early history of vertebrate evolution. We propose that a single GPRC5 receptor coding gene originated in a stem chordate ancestor and gave rise by duplication events to a gene family comprising three receptor types (GPRC5A-C in vertebrates, and a fourth homologue present only in mammals (GPRC5D. Additional duplications of GPRC5B and GPRC5C sequences occurred in teleost fishes. The finding that the expression patterns of the receptors are evolutionarily conserved indicates an important biological function of these receptors. Moreover, we found that expression of GPRC5B is regulated by vitamin A in vivo, confirming previous findings that linked receptor expression to retinoic acid levels in tumor cell lines and strengthening the link between the receptor expression and the development of a complex nervous system in chordates, known to be dependent on retinoic acid signaling. Conclusions GPRC5 receptors, a class of G protein-coupled receptors with unique sequence characteristics, may represent a molecular novelty that helped non-chordates

  11. Evolution of a core gene network for skeletogenesis in chordates.

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    Jochen Hecht

    2008-03-01

    Full Text Available The skeleton is one of the most important features for the reconstruction of vertebrate phylogeny but few data are available to understand its molecular origin. In mammals the Runt genes are central regulators of skeletogenesis. Runx2 was shown to be essential for osteoblast differentiation, tooth development, and bone formation. Both Runx2 and Runx3 are essential for chondrocyte maturation. Furthermore, Runx2 directly regulates Indian hedgehog expression, a master coordinator of skeletal development. To clarify the correlation of Runt gene evolution and the emergence of cartilage and bone in vertebrates, we cloned the Runt genes from hagfish as representative of jawless fish (MgRunxA, MgRunxB and from dogfish as representative of jawed cartilaginous fish (ScRunx1-3. According to our phylogenetic reconstruction the stem species of chordates harboured a single Runt gene and thereafter Runt locus duplications occurred during early vertebrate evolution. All newly isolated Runt genes were expressed in cartilage according to quantitative PCR. In situ hybridisation confirmed high MgRunxA expression in hard cartilage of hagfish. In dogfish ScRunx2 and ScRunx3 were expressed in embryonal cartilage whereas all three Runt genes were detected in teeth and placoid scales. In cephalochordates (lancelets Runt, Hedgehog and SoxE were strongly expressed in the gill bars and expression of Runt and Hedgehog was found in endo- as well as ectodermal cells. Furthermore we demonstrate that the lancelet Runt protein binds to Runt binding sites in the lancelet Hedgehog promoter and regulates its activity. Together, these results suggest that Runt and Hedgehog were part of a core gene network for cartilage formation, which was already active in the gill bars of the common ancestor of cephalochordates and vertebrates and diversified after Runt duplications had occurred during vertebrate evolution. The similarities in expression patterns of Runt genes support the view

  12. Functional specialization of chordate CDK1 paralogs during oogenic meiosis.

    Science.gov (United States)

    Øvrebø, Jan Inge; Campsteijn, Coen; Kourtesis, Ioannis; Hausen, Harald; Raasholm, Martina; Thompson, Eric M

    2015-01-01

    Cyclin-dependent kinases (CDKs) are central regulators of eukaryotic cell cycle progression. In contrast to interphase CDKs, the mitotic phase CDK1 is the only CDK capable of driving the entire cell cycle and it can do so from yeast to mammals. Interestingly, plants and the marine chordate, Oikopleura dioica, possess paralogs of the highly conserved CDK1 regulator. However, whereas in plants the 2 CDK1 paralogs replace interphase CDK functions, O. dioica has a full complement of interphase CDKs in addition to its 5 odCDK1 paralogs. Here we show specific sub-functionalization of odCDK1 paralogs during oogenesis. Differential spatiotemporal dynamics of the odCDK1a, d and e paralogs and the meiotic polo-like kinase 1 (Plk1) and aurora kinase determine the subset of meiotic nuclei in prophase I arrest that will seed growing oocytes and complete meiosis. Whereas we find odCDK1e to be non-essential, knockdown of the odCDK1a paralog resulted in the spawning of non-viable oocytes of reduced size. Knockdown of odCDK1d also resulted in the spawning of non-viable oocytes. In this case, the oocytes were of normal size, but were unable to extrude polar bodies upon exposure to sperm, because they were unable to resume meiosis from prophase I arrest, a classical function of the sole CDK1 during meiosis in other organisms. Thus, we reveal specific sub-functionalization of CDK1 paralogs, during the meiotic oogenic program. PMID:25714331

  13. Regulation of interleukin-6 secretion in murine pituicytes

    DEFF Research Database (Denmark)

    Thorn, Anders; Tuxen, Mikkel; Moesby, Lise;

    2005-01-01

    Pituicytes, the astrocytic glial cells of the neural lobe, are known to secrete interleukin-6 and nitric oxide upon stimulation with various inflammatory mediators, i.e. interleukin-1beta. Nitric oxide is described to modulate the secretion of interleukin-6 in various cell types. The aim of the p...

  14. Glial K(+) Clearance and Cell Swelling

    DEFF Research Database (Denmark)

    Macaulay, Nanna; Zeuthen, Thomas

    2012-01-01

    space into the glial cell are debated. Although spatial buffer currents may occur, their quantitative contribution to K(+) clearance is uncertain. The concept of spatial buffering of K(+) precludes intracellular K(+) accumulation and is therefore (i) difficult to reconcile with the K(+) accumulation...... repeatedly observed in glial cells during K(+) clearance and (ii) incompatible with K(+)-dependent glial cell swelling. K(+) uptake into non-voltage clamped cultured glial cells is carried out by the Na(+)/K(+)-ATPase and the Na(+)/K(+)/Cl(-) cotransporter in combination. In brain slices and intact optic...... nerve, however, only the Na(+)/K(+)-ATPase has been demonstrated to be involved in stimulus-evoked K(+) clearance. The glial cell swelling associated with K(+) clearance is prevented under conditions that block the activity of the Na(+)/K(+)/Cl(-) cotransporter. The Na(+)/K(+)/Cl(-) cotransporter is...

  15. Glial heterotopia of the oral cavity

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    Radhames E. Lizardo

    2015-07-01

    Full Text Available We report an unusual case of a glial heterotopia arising from the oral cavity of an African neonate. The patient presented with an external pedunculated oral mass which was connected to the anterior hard palate by a firm, rubbery stalk of mucosal tissue. While the mass appeared painless, it interfered with the infant's feeding and was disturbing to the parents. After a computed tomography scan excluded an intracranial connection, the mass was excised at its base and sent for biopsy. Histopathology examination confirmed glial heterotopia. Glial heterotopias should be included in the differential diagnosis of congenital masses in the oral region.

  16. Phylostratigraphic profiles in zebrafish uncover chordate origins of the vertebrate brain.

    Science.gov (United States)

    Šestak, Martin Sebastijan; Domazet-Lošo, Tomislav

    2015-02-01

    An elaborated tripartite brain is considered one of the important innovations of vertebrates. Other extant chordate groups have a more basic brain organization. For instance, cephalochordates possess a relatively simple brain possibly homologous to the vertebrate forebrain and hindbrain, whereas tunicates display the tripartite organization, but without the specialized brain centers. The difference in anatomical complexity is even more pronounced if one compares chordates with other deuterostomes that have only a diffuse nerve net or alternatively a rather simple central nervous system. To gain a new perspective on the evolutionary roots of the complex vertebrate brain, we made here a phylostratigraphic analysis of gene expression patterns in the developing zebrafish (Danio rerio). The recovered adaptive landscape revealed three important periods in the evolutionary history of the zebrafish brain. The oldest period corresponds to preadaptive events in the first metazoans and the emergence of the nervous system at the metazoan-eumetazoan transition. The origin of chordates marks the next phase, where we found the overall strongest adaptive imprint in almost all analyzed brain regions. This finding supports the idea that the vertebrate brain evolved independently of the brains within the protostome lineage. Finally, at the origin of vertebrates we detected a pronounced signal coming from the dorsal telencephalon, in agreement with classical theories that consider this part of the cerebrum a genuine vertebrate innovation. Taken together, these results reveal a stepwise adaptive history of the vertebrate brain where most of its extant organization was already present in the chordate ancestor. PMID:25415965

  17. Evolutionary patterns of RNA-based duplication in non-mammalian chordates.

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    Ming Chen

    Full Text Available The role of RNA-based duplication, or retroposition, in the evolution of new gene functions in mammals, plants, and Drosophila has been widely reported. However, little is known about RNA-based duplication in non-mammalian chordates. In this study, we screened ten non-mammalian chordate genomes for retrocopies and investigated their evolutionary patterns. We identified numerous retrocopies in these species. Examination of the age distribution of these retrocopies revealed no burst of young retrocopies in ancient chordate species. Upon comparing these non-mammalian chordate species to the mammalian species, we observed that a larger fraction of the non-mammalian retrocopies was under strong evolutionary constraints than mammalian retrocopies are, as evidenced by signals of purifying selection and expression profiles. For the Western clawed frog, Medaka, and Sea squirt, many retrogenes have evolved gonad and brain expression patterns, similar to what was observed in human. Testing of retrogene movement in the Medaka genome, where the nascent sex chrosomes have been well assembled, did not reveal any significant gene movement. Taken together, our analyses demonstrate that RNA-based duplication generates many functional genes and can make a significant contribution to the evolution of non-mammalian genomes.

  18. Glial Contributions to Neural Function and Disease.

    Science.gov (United States)

    Rasband, Matthew N

    2016-02-01

    The nervous system consists of neurons and glial cells. Neurons generate and propagate electrical and chemical signals, whereas glia function mainly to modulate neuron function and signaling. Just as there are many different kinds of neurons with different roles, there are also many types of glia that perform diverse functions. For example, glia make myelin; modulate synapse formation, function, and elimination; regulate blood flow and metabolism; and maintain ionic and water homeostasis to name only a few. Although proteomic approaches have been used extensively to understand neurons, the same cannot be said for glia. Importantly, like neurons, glial cells have unique protein compositions that reflect their diverse functions, and these compositions can change depending on activity or disease. Here, I discuss the major classes and functions of glial cells in the central and peripheral nervous systems. I describe proteomic approaches that have been used to investigate glial cell function and composition and the experimental limitations faced by investigators working with glia. PMID:26342039

  19. Hypothalamic Glial-to-Neuronal Signaling during Puberty: Influence of Alcohol

    OpenAIRE

    W. Les Dees; Hiney, Jill K.; Srivastava, Vinod K

    2011-01-01

    Mammalian puberty requires complex interactions between glial and neuronal regulatory systems within the hypothalamus that results in the timely increase in the secretion of luteinizing hormone releasing hormone (LHRH). Assessing the molecules required for the development of coordinated communication networks between glia and LHRH neuron terminals in the basal hypothalamus, as well as identifying substances capable of affecting cell-cell communication are important. One such pathway involves ...

  20. Modeling RNA polymerase interaction in mitochondria of chordates

    Directory of Open Access Journals (Sweden)

    Lyubetsky Vassily A

    2012-08-01

    selected genes only relative RNA concentrations have been experimentally determined. Conversely, these characteristics and absolute transcription levels can be obtained using relative RNA concentrations and RNA half-lives known from various experimental studies. In this case, the “inverse problem” is solved with multi-objective optimization. Conclusions In this study, we demonstrate that our model accurately reproduces all relevant experimental data available for plant plastids, as well as the mitochondria of chordates. Using experimental data, the model is applied to estimate binding intensities of phage-type RNA polymerases to their promoters as well as predicting terminator characteristics, including polarization. In addition, one can predict characteristics of phage-type RNA polymerases and the transcription process that are difficult to measure directly, e.g., the association between the promoter’s nucleotide composition and the intensity of polymerase binding. To illustrate the application of our model in functional predictions, we propose a possible mechanism for MELAS syndrome development in human involving a decrease of Phe-tRNA, Val-tRNA and rRNA concentrations in the cell. In addition, we describe how changes in methylation patterns of the mTERF binding site and three promoters in hypothyroid rat correlate with changes in intensities of the mTERF binding and transcription initiations. Finally, we introduce an auxiliary model to describe the interaction between polysomal mRNA and ribonucleases.

  1. Essential role of Bmp signaling and its positive feedback loop in the early cell fate evolution of chordates

    OpenAIRE

    Kozmiková, I. (Iryna); S Candiani; P. Fabian; Gurská, D. (Daniela); Kozmik, Z

    2013-01-01

    In chordates, early separation of cell fate domains occurs prior to the final specification of ectoderm to neural and non-neural as well as mesoderm to dorsal and ventral during development. Maintaining such division with the establishment of an exact border between the domains is required for the formation of highly differentiated structures such as neural tube and notochord. We hypothesized that the key condition for efficient cell fate separation in a chordate embryo is the presence of a p...

  2. Evolution of retinoic acid receptors in chordates: insights from three lamprey species, Lampetra fluviatilis, Petromyzon marinus, and Lethenteron japonicum

    OpenAIRE

    Campo-Paysaa, Florent; Jandzik, David; Takio-Ogawa, Yoko; Cattell, Maria V; Neef, Haley C; Langeland, James A.; Kuratani, Shigeru; Medeiros, Daniel M.; Mazan, Sylvie; Kuraku, Shigehiro; Laudet, Vincent; Schubert, Michael

    2015-01-01

    Background Retinoic acid (RA) signaling controls many developmental processes in chordates, from early axis specification to late organogenesis. The functions of RA are chiefly mediated by a subfamily of nuclear hormone receptors, the retinoic acid receptors (RARs), that act as ligand-activated transcription factors. While RARs have been extensively studied in jawed vertebrates (that is, gnathostomes) and invertebrate chordates, very little is known about the repertoire and developmental role...

  3. Ancient homeobox gene loss and the evolution of chordate brain and pharynx development : deductions from amphioxus gene expression

    OpenAIRE

    Butts, Thomas; Holland, Peter W. H.; Ferrier, David Ellard Keith

    2010-01-01

    Homeobox genes encode a large superclass of transcription factors with widespread roles in animal development. Within chordates there are over 100 homeobox genes in the invertebrate cephalochordate amphioxus and over 200 in humans. Set against this general trend of increasing gene number in vertebrate evolution, some ancient homeobox genes that were present in the last common ancestor of chordates have been lost from vertebrates. Here, we describe the embryonic expression of four amphioxus de...

  4. Retinoic acid influences anteroposterior positioning of epidermal sensory neurons and their gene expression in a developing chordate (amphioxus)

    OpenAIRE

    Schubert, Michael; Holland, Nicholas D; Escriva, Hector; Holland, Linda Z; Laudet, Vincent

    2004-01-01

    In developing chordates, retinoic acid (RA) signaling patterns the rostrocaudal body axis globally and affects gene expression locally in some differentiating cell populations. Here we focus on development of epidermal sensory neurons in an invertebrate chordate (amphioxus) to determine how RA signaling influences their rostrocaudal distribution and gene expression (for AmphiCoe, a neural precursor gene; for amphioxus islet and AmphiERR, two neural differentiation genes; and for AmphiHox1, -3...

  5. Secrets Law

    OpenAIRE

    Luz Helena Guamanzara Torres

    2013-01-01

    This paper provides a review of the book The Law of Secrets, of the author Juan Carlos Martínez-Villalba Riofrío studying the secrets and how law does protect. To this end, the author has analyzed the general theory of secrecy, secrets and methodology, its overall rating, essential elements and their different legal dimensions, the secret as a subjective right. It also establishes that professional secrecy is protected by constitutional principles such as the right to privacy.

  6. Evolution of the role of RA and FGF signals in the control of somitogenesis in chordates

    OpenAIRE

    Stéphanie Bertrand; Daniel Aldea; Silvan Oulion; Lucie Subirana; de Lera, Angel R.; Ildiko Somorjai; Hector Escriva

    2015-01-01

    During vertebrate development, the paraxial mesoderm becomes segmented, forming somites that will give rise to dermis, axial skeleton and skeletal muscles. Although recently challenged, the "clock and wavefront" model for somitogenesis explains how interactions between several cell-cell communication pathways, including the FGF, RA, Wnt and Notch signals, control the formation of these bilateral symmetric blocks. In the cephalochordate amphioxus, which belongs to the chordate phylum together ...

  7. Evolution of anterior Hox regulatory elements among chordates

    OpenAIRE

    Natale Alfonso; Sims Carrie; Chiusano Maria L; Amoroso Alessandro; D'Aniello Enrico; Fucci Laura; Krumlauf Robb; Branno Margherita; Locascio Annamaria

    2011-01-01

    Abstract Background The Hox family of transcription factors has a fundamental role in segmentation pathways and axial patterning of embryonic development and their clustered organization is linked with the regulatory mechanisms governing their coordinated expression along embryonic axes. Among chordates, of particular interest are the Hox paralogous genes in groups 1-4 since their expression is coupled to the control of regional identity in the anterior nervous system, where the highest struc...

  8. The synapsin gene family in basal chordates: evolutionary perspectives in metazoans

    OpenAIRE

    De Bernardi Fiorenza; Pennati Roberta; Moronti Luca; Candiani Simona; Benfenati Fabio; Pestarino Mario

    2010-01-01

    Abstract Background Synapsins are neuronal phosphoproteins involved in several functions correlated with both neurotransmitter release and synaptogenesis. The comprehension of the basal role of the synapsin family is hampered in vertebrates by the existence of multiple synapsin genes. Therefore, studying homologous genes in basal chordates, devoid of genome duplication, could help to achieve a better understanding of the complex functions of these proteins. Results In this study we report the...

  9. The Middle Cambrian fossil Pikaia and the evolution of chordate swimming

    Directory of Open Access Journals (Sweden)

    Lacalli Thurston

    2012-07-01

    Full Text Available Abstract Conway Morris and Caron (2012 have recently published an account of virtually all the available information on Pikaia gracilens, a well-known Cambrian fossil and supposed basal chordate, and propose on this basis some new ideas about Pikaia’s anatomy and evolutionary significance. Chief among its chordate-like features are the putative myomeres, a regular series of vertical bands that extends the length of the body. These differ from the myomeres of living chordates in that boundaries between them (the myosepta are gently curved, with minimal overlap, whereas amphioxus and vertebrates have strongly overlapping V- and W-shaped myomeres. The implication, on biomechanical grounds, is that myomeres in Pikaia exerted much less tension on the myosepta, so the animal would have been incapable of swimming as rapidly as living chordates operating in the fast-twitch mode used for escape and attack. Pikaia either lacked the fast-twitch fibers necessary for such speeds, having instead only slow-twitch fibers, or it had an ancestral fiber type with functional capabilities more like modern slow fibers than fast ones. The first option is supported by the sequence of development in zebrafish, where both myoseptum formation and fast fiber deployment show a dependence on slow fibers, which develop first. For Pikaia, the absence of fast fibers has both behavioral and anatomical implications, which are discussed. Among the latter is the possibility that a notochord may not have been needed as a primary stiffening device if other structures (for example, the dorsal organ could perform that role.

  10. Diversification of the expression patterns and developmental functions of the Dishevelled gene family during chordate evolution

    OpenAIRE

    Gray, Ryan S.; Bayly, Robbie D.; Green, Stephen A.; Agarwala, Seema; Lowe, Christopher J.; Wallingford, John B.

    2009-01-01

    Dishevelled (Dvl) proteins are key transducers of Wnt signaling encoded by members of a multi-gene family in vertebrates. We report here the divergent, tissue-specific expression patterns for all three Dvl genes in Xenopus embryos, which contrast dramatically with their expression patterns in mice. Moreover, we find that the expression patterns of Dvl genes in the chick diverge significantly from those of Xenopus. In addition, in hemichordates, an outgroup to chordates, we find that the one D...

  11. Molecular evolution of a chordate specific family of G protein-coupled receptors

    OpenAIRE

    Leese Florian; Hatt Hanns; Pelz Thomas; Mayer Christoph; Kurtenbach Stefan; Neuhaus Eva M

    2011-01-01

    Abstract Background Chordate evolution is a history of innovations that is marked by physical and behavioral specializations, which led to the development of a variety of forms from a single ancestral group. Among other important characteristics, vertebrates obtained a well developed brain, anterior sensory structures, a closed circulatory system and gills or lungs as blood oxygenation systems. The duplication of pre-existing genes had profound evolutionary implications for the developmental ...

  12. The Transcriptome of an Amphioxus, Asymmetron lucayanum, from the Bahamas: A Window into Chordate Evolution

    OpenAIRE

    Yue, Jia-Xing; Yu, Jr-Kai; Putnam, Nicholas H.; Holland, Linda Z

    2014-01-01

    Cephalochordates, the sister group of tunicates plus vertebrates, have been called “living fossils” due to their resemblance to fossil chordates from Cambrian strata. The genome of the cephalochordate Branchiostoma floridae shares remarkable synteny with vertebrates and is free from whole-genome duplication. We performed RNA sequencing from larvae and adults of Asymmetron lucayanum, a cephalochordate distantly related to B. floridae. Comparisons of about 430 orthologous gene groups among both...

  13. Evolution of the chordate body plan: New insights from phylogenetic analyses of deuterostome phyla

    OpenAIRE

    Cameron, Chris B.; Garey, James R.; Swalla, Billie J.

    2000-01-01

    The deuterostome phyla include Echinodermata, Hemichordata, and Chordata. Chordata is composed of three subphyla, Vertebrata, Cephalochordata (Branchiostoma), and Urochordata (Tunicata). Careful analysis of a new 18S rDNA data set indicates that deuterostomes are composed of two major clades: chordates and echinoderms + hemichordates. This analysis strongly supports the monophyly of each of the four major deuterostome taxa: Vertebrata + Cephalochordata, Urochordata, Hemichordata, and Echinode...

  14. Evolution of the Role of RA and FGF Signals in the Control of Somitogenesis in Chordates.

    Directory of Open Access Journals (Sweden)

    Stéphanie Bertrand

    Full Text Available During vertebrate development, the paraxial mesoderm becomes segmented, forming somites that will give rise to dermis, axial skeleton and skeletal muscles. Although recently challenged, the "clock and wavefront" model for somitogenesis explains how interactions between several cell-cell communication pathways, including the FGF, RA, Wnt and Notch signals, control the formation of these bilateral symmetric blocks. In the cephalochordate amphioxus, which belongs to the chordate phylum together with tunicates and vertebrates, the dorsal paraxial mesendoderm also periodically forms somites, although this process is asymmetric and extends along the whole body. It has been previously shown that the formation of the most anterior somites in amphioxus is dependent upon FGF signalling. However, the signals controlling somitogenesis during posterior elongation in amphioxus are still unknown. Here we show that, contrary to vertebrates, RA and FGF signals act independently during posterior elongation and that they are not mandatory for posterior somites to form. Moreover, we show that RA is not able to buffer the left/right asymmetry machinery that is controlled through the asymmetric expression of Nodal pathway actors. Our results give new insights into the evolution of the somitogenesis process in chordates. They suggest that RA and FGF pathways have acquired specific functions in the control of somitogenesis in vertebrates. We propose that the "clock and wavefront" system was selected specifically in vertebrates in parallel to the development of more complex somite-derived structures but that it was not required for somitogenesis in the ancestor of chordates.

  15. Glial cells are involved in itch processing

    DEFF Research Database (Denmark)

    Andersen, Hjalte H.; Arendt-Nielsen, Lars; Gazerani, Parisa

    2016-01-01

    development of chronic itch akin to their more investigated role in chronic pain. Improvements are needed in the management of chronic itch, and future basic and interventional studies on glial activity modulation would both enhance our understanding of mechanisms underlying the chronification of itch and...... provide novel opportunities for the future prevention or treatment of this debilitating and common condition....

  16. Negative regulation of glial engulfment activity by Draper terminates glial responses to axon injury

    OpenAIRE

    Logan, Mary A.; Hackett, Rachel; Doherty, Johnna; Sheehan, Amy; Speese, Sean D.; Freeman, Marc R

    2012-01-01

    Neuronal injury elicits potent cellular responses from glia, but molecular pathways modulating glial activation, phagocytic function, and termination of reactive responses remain poorly defined. Here we show that positive or negative regulation of glial reponses to axon injury are molecularly encoded by unique isoforms of the Drosophila engulfment receptor Draper. Draper-I promotes engulfment of axonal debris through an immunoreceptor tyrosine-based activation motif (ITAM). In contrast, Drape...

  17. Secrets Law

    Directory of Open Access Journals (Sweden)

    Luz Helena Guamanzara Torres

    2013-01-01

    Full Text Available This paper provides a review of the book The Law of Secrets, of the author Juan Carlos Martínez-Villalba Riofrío studying the secrets and how law does protect. To this end, the author has analyzed the general theory of secrecy, secrets and methodology, its overall rating, essential elements and their different legal dimensions, the secret as a subjective right. It also establishes that professional secrecy is protected by constitutional principles such as the right to privacy.

  18. Progress in glial cell studies in some laboratories in China

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Glial cells in the central nervous system(CNS) consist of a heterogeneous population of cell types,each characterized by distinct morphological features,physiological properties,and specific markers.In contrast to the previous view that glial cells were passive elements in the brain,accumulating evidence suggests that glial cells are active participants in various brain functions and brain disorders.This review summarizes recent progress of glial cell studies from several groups in China,ranging from studies about the mechanisms of neuron-glia crosstalking to investigations on the roles of glial cells in various CNS disorders.

  19. Glial-glial and glial-neuronal interfaces in radiation-induced, glia-depleted spinal cord

    Energy Technology Data Exchange (ETDEWEB)

    Gilmore, S.A.; Sims, T.J. [Arkansas Univ., Little Rock, AR (United States). Medical Center

    1997-01-01

    This review summarises some of the major findings derived from studies using the model of a glia-depleted environment developed and characterised in this laboratory. Glial depletion is achieved by exposure of the immature rodent spinal cord to x-radiation which markedly reduces both astrocyte and oligodendrocyte populations and severely impairs myelination. This glia-depleted, hypomylinated state presents a unique opportunity to examine aspects of spinal cord maturation in the absence of a normal glial population. An associated sequela within 2-3 wk following irradiation is the appearance of Schwann cells in the dorsal portion of the spinal cord. Characteristics of these intraspinal Schwann cells, their patterns of myelination or ensheathment, and their interrelations with the few remaining central glia have been examined. A later sequela is the development of Schwann cells in the ventral aspect of the spinal cord where they occur predominantly in the grey matter. (author).

  20. Glial-glial and glial-neuronal interfaces in radiation-induced, glia-depleted spinal cord

    International Nuclear Information System (INIS)

    This review summarises some of the major findings derived from studies using the model of a glia-depleted environment developed and characterised in this laboratory. Glial depletion is achieved by exposure of the immature rodent spinal cord to x-radiation which markedly reduces both astrocyte and oligodendrocyte populations and severely impairs myelination. This glia-depleted, hypomylinated state presents a unique opportunity to examine aspects of spinal cord maturation in the absence of a normal glial population. An associated sequela within 2-3 wk following irradiation is the appearance of Schwann cells in the dorsal portion of the spinal cord. Characteristics of these intraspinal Schwann cells, their patterns of myelination or ensheathment, and their interrelations with the few remaining central glia have been examined. A later sequela is the development of Schwann cells in the ventral aspect of the spinal cord where they occur predominantly in the grey matter. (author)

  1. mRNA 5′-leader trans-splicing in the chordates

    OpenAIRE

    Vandenberghe, Amanda E.; Meedel, Thomas H.; Hastings, Kenneth E.M.

    2001-01-01

    We report the discovery of mRNA 5′-leader trans-splicing (SL trans-splicing) in the chordates. In the ascidian protochordate Ciona intestinalis, the mRNAs of at least seven genes undergo trans-splicing of a 16-nucleotide 5′-leader apparently derived from a 46-nucleotide RNA that shares features with previously characterized splice donor SL RNAs. SL trans-splicing was known previously to occur in several protist and metazoan phyla, however, this is the first report of SL trans-splicing within ...

  2. Glial heterotopia of the oral cavity

    OpenAIRE

    Lizardo, Radhames E.; Simone Langness; Hassan Mumun; James Murphy; Robert Newbury; Patricia Bromberger; Bickler, Stephen W.

    2015-01-01

    We report an unusual case of a glial heterotopia arising from the oral cavity of an African neonate. The patient presented with an external pedunculated oral mass which was connected to the anterior hard palate by a firm, rubbery stalk of mucosal tissue. While the mass appeared painless, it interfered with the infant's feeding and was disturbing to the parents. After a computed tomography scan excluded an intracranial connection, the mass was excised at its base and sent for biopsy. Histopath...

  3. Bone marrow-derived fibroblast growth factor-2 induces glial cell proliferation in the regenerating peripheral nervous system

    OpenAIRE

    Ribeiro-Resende Victor; Carrier-Ruiz Alvaro; R Lemes Robertha M; Reis Ricardo A M; Mendez-Otero Rosalia

    2012-01-01

    Abstract Background Among the essential biological roles of bone marrow-derived cells, secretion of many soluble factors is included and these small molecules can act upon specific receptors present in many tissues including the nervous system. Some of the released molecules can induce proliferation of Schwann cells (SC), satellite cells and lumbar spinal cord astrocytes during early steps of regeneration in a rat model of sciatic nerve transection. These are the major glial cell types that s...

  4. Evolutionary history of chordate PAX genes: dynamics of change in a complex gene family.

    Directory of Open Access Journals (Sweden)

    Vanessa Rodrigues Paixão-Côrtes

    Full Text Available Paired box (PAX genes are transcription factors that play important roles in embryonic development. Although the PAX gene family occurs in animals only, it is widely distributed. Among the vertebrates, its 9 genes appear to be the product of complete duplication of an original set of 4 genes, followed by an additional partial duplication. Although some studies of PAX genes have been conducted, no comprehensive survey of these genes across the entire taxonomic unit has yet been attempted. In this study, we conducted a detailed comparison of PAX sequences from 188 chordates, which revealed restricted variation. The absence of PAX4 and PAX8 among some species of reptiles and birds was notable; however, all 9 genes were present in all 74 mammalian genomes investigated. A search for signatures of selection indicated that all genes are subject to purifying selection, with a possible constraint relaxation in PAX4, PAX7, and PAX8. This result indicates asymmetric evolution of PAX family genes, which can be associated with the emergence of adaptive novelties in the chordate evolutionary trajectory.

  5. A conserved non-reproductive GnRH system in chordates.

    Directory of Open Access Journals (Sweden)

    Takehiro G Kusakabe

    Full Text Available Gonadotropin-releasing hormone (GnRH is a neuroendocrine peptide that plays a central role in the vertebrate hypothalamo-pituitary axis. The roles of GnRH in the control of vertebrate reproductive functions have been established, while its non-reproductive function has been suggested but less well understood. Here we show that the tunicate Ciona intestinalis has in its non-reproductive larval stage a prominent GnRH system spanning the entire length of the nervous system. Tunicate GnRH receptors are phylogenetically closest to vertebrate GnRH receptors, yet functional analysis of the receptors revealed that these simple chordates have evolved a unique GnRH system with multiple ligands and receptor heterodimerization enabling complex regulation. One of the gnrh genes is conspicuously expressed in the motor ganglion and nerve cord, which are homologous structures to the hindbrain and spinal cord of vertebrates. Correspondingly, GnRH receptor genes were found to be expressed in the tail muscle and notochord of embryos, both of which are phylotypic axial structures along the nerve cord. Our findings suggest a novel non-reproductive role of GnRH in tunicates. Furthermore, we present evidence that GnRH-producing cells are present in the hindbrain and spinal cord of the medaka, Oryzias latipes, thereby suggesting the deep evolutionary origin of a non-reproductive GnRH system in chordates.

  6. Ontology for the asexual development and anatomy of the colonial chordate Botryllus schlosseri.

    Directory of Open Access Journals (Sweden)

    Lucia Manni

    Full Text Available Ontologies provide an important resource to integrate information. For developmental biology and comparative anatomy studies, ontologies of a species are used to formalize and annotate data that are related to anatomical structures, their lineage and timing of development. Here, we have constructed the first ontology for anatomy and asexual development (blastogenesis of a bilaterian, the colonial tunicate Botryllus schlosseri. Tunicates, like Botryllus schlosseri, are non-vertebrates and the only chordate taxon species that reproduce both sexually and asexually. Their tadpole larval stage possesses structures characteristic of all chordates, i.e. a notochord, a dorsal neural tube, and gill slits. Larvae settle and metamorphose into individuals that are either solitary or colonial. The latter reproduce both sexually and asexually and these two reproductive modes lead to essentially the same adult body plan. The Botryllus schlosseri Ontology of Development and Anatomy (BODA will facilitate the comparison between both types of development. BODA uses the rules defined by the Open Biomedical Ontologies Foundry. It is based on studies that investigate the anatomy, blastogenesis and regeneration of this organism. BODA features allow the users to easily search and identify anatomical structures in the colony, to define the developmental stage, and to follow the morphogenetic events of a tissue and/or organ of interest throughout asexual development. We invite the scientific community to use this resource as a reference for the anatomy and developmental ontology of B. schlosseri and encourage recommendations for updates and improvements.

  7. The transcriptome of an amphioxus, Asymmetron lucayanum, from the Bahamas: a window into chordate evolution.

    Science.gov (United States)

    Yue, Jia-Xing; Yu, Jr-Kai; Putnam, Nicholas H; Holland, Linda Z

    2014-10-01

    Cephalochordates, the sister group of tunicates plus vertebrates, have been called "living fossils" due to their resemblance to fossil chordates from Cambrian strata. The genome of the cephalochordate Branchiostoma floridae shares remarkable synteny with vertebrates and is free from whole-genome duplication. We performed RNA sequencing from larvae and adults of Asymmetron lucayanum, a cephalochordate distantly related to B. floridae. Comparisons of about 430 orthologous gene groups among both cephalochordates and 10 vertebrates using an echinoderm, a hemichordate, and a mollusk as outgroups showed that cephalochordates are evolving more slowly than the slowest evolving vertebrate known (the elephant shark), with A. lucayanum evolving even more slowly than B. floridae. Against this background of slow evolution, some genes, notably several involved in innate immunity, stand out as evolving relatively quickly. This may be due to the lack of an adaptive immune system and the relatively high levels of bacteria in the inshore waters cephalochordates inhabit. Molecular dating analysis including several time constraints revealed a divergence time of ∼120 Ma for A. lucayanum and B. floridae. The divisions between cephalochordates and vertebrates, and that between chordates and the hemichordate plus echinoderm clade likely occurred before the Cambrian. PMID:25240057

  8. Genomic analyses reveal a conserved glutathione homeostasis pathway in the invertebrate chordate Ciona intestinalis

    Science.gov (United States)

    Nava, Gerardo M.; Lee, David Y.; Ospina, Javier H.; Cai, Shi-Ying

    2009-01-01

    The major thiol redox buffer glutathione (l-γ-glutamyl-l-cysteinylglycine, GSH) is central to cell fate determination, and thus, associated metabolic and regulatory pathways are exquisitely sensitive to a wide range of environmental cues. An imbalance of cellular redox homeostasis has emerged as a pathologic hallmark of a diverse range of human gene-environment disorders. Despite the central importance of GSH in cellular homeostasis, underlying genetic regulatory pathways remain poorly defined. This report describes the annotation and expression analysis of genes contributing to GSH homeostasis in the invertebrate chordate Ciona intestinalis. A core pathway comprising 19 genes contributing to the biosynthesis of GSH and its use as both a redox buffer and a conjugate in phase II detoxification as well as known transcriptional regulators were analyzed. These genes exhibit a high level of sequence conservation with corresponding human, rat, and mouse homologs and were expressed constitutively in tissues of adult animals. The GSH biosynthetic genes Gclc and Gclm were also responsive to the prototypical antioxidant tert-butylhydroquinone. The present evidence of a conserved GSH homeostasis pathway in C. intestinalis together with its phylogenetic position as a basal chordate and lifestyle as a filter feeder constantly exposed to natural marine toxins introduces this species as an important animal model for defining molecular mechanisms that potentially underlie genetic susceptibility to environmentally associated stress. PMID:19470804

  9. Glial origin of rapidly adhering amniotic fluid cells.

    OpenAIRE

    Aula, P; von Koskull, H; Teramo, K; Karjalainen, O; Virtanen, I.; Lehto, V P; Dahl, D

    1980-01-01

    Rapidly adhering cells (RA cells) from the amniotic fluid of a pregnancy with fetal anencephaly were investigated by immunofluorescence assay with an antiserum against glial cells. After 24 hours' cultivation a high proportion of the cells showed positive glial-specific fluorescence, whereas no staining was seen in cells from samples of normal amniotic fluid. At the 24th week the mother was delivered of a stillborn infant with anencephaly. Immunofluorescence staining of RA cells with glial-sp...

  10. Electrical Coupling Between Glial Cells in the Rat Retina

    OpenAIRE

    Ceelen, Paul W.; Lockridge, Amber; Newman, Eric A.

    2001-01-01

    The strength of electrical coupling between retinal glial cells was quantified with simultaneous whole-cell current-clamp recordings from astrocyte–astrocyte, astrocyte–Müller cell, and Müller cell–Müller cell pairs in the acutely isolated rat retina. Experimental results were fit and space constants determined using a resistive model of the glial cell network that assumed a homogeneous two-dimensional glial syncytium. The effective space constant (the distance from the point of stimulation t...

  11. Enteric glial cells have specific immunosuppressive properties.

    Science.gov (United States)

    Kermarrec, Laetitia; Durand, Tony; Neunlist, Michel; Naveilhan, Philippe; Neveu, Isabelle

    2016-06-15

    Enteric glial cells (EGC) have trophic and neuroregulatory functions in the enteric nervous system, but whether they exert a direct effect on immune cells is unknown. Here, we used co-cultures to show that human EGC can inhibit the proliferation of activated T lymphocytes. Interestingly, EGC from Crohn's patients were effective at one EGC for two T cells whereas EGC from control patients required a ratio of 1:1. These data suggest that EGC contribute to local immune homeostasis in the gastrointestinal wall. They also raise the possibility that EGC have particular immunosuppressive properties in inflammatory bowel diseases such as Crohn's disease. PMID:27235353

  12. Tumores intraventriculares supratentoriales de origen glial

    OpenAIRE

    Miguel A Esquivel M; Jose A Quesada G; Desireé Gutierrez G

    2015-01-01

    Los tumores gliales intraventriculares representan un gran reto de acceso neuroquirúrgico debido a su localización profunda, asociación intima con numerosas estructuras vasculares de áreas críticas cerebrales y su relación circunferencial a múltiples tractos subcorticales. Debido a todo esto, el acceso quirúrgico a estas regiones, debe incluir una serie de consideraciones minuciosas anatómicas para minimizar el riesgo de lesión a estructuras de considerable importancia y funcionabilidad y log...

  13. Glial cells as drug targets: What does it take?

    Science.gov (United States)

    Möller, Thomas; Boddeke, Hendrikus W G M

    2016-10-01

    The last two decades have brought a significant increase in our understanding of glial biology and glial contribution to CNS disease. Yet, despite the fact that glial cells make up the majority of CNS cells, no drug specifically targeting glial cells is on the market. Given the long development times of CNS drugs, on average over 12 years, this is not completely surprising. However, there is increasing interest from academia and industry to exploit glial targets to develop drugs for the benefit of patients with currently limited or no therapeutic options. CNS drug development has a high attrition rate and has encountered many challenges. It seems unlikely that developing drugs against glial targets would be any less demanding. However, the knowledge generated in traditional CNS drug discovery teaches valuable lessons, which could enable the glial community to accelerate the cycle time from basic discovery to drug development. In this review we will discuss steps necessary to bring a "glial target idea" to a clinical development program. GLIA 2016;64:1742-1754. PMID:27121701

  14. Conservation and diversification of an ancestral chordate gene regulatory network for dorsoventral patterning.

    Directory of Open Access Journals (Sweden)

    Iryna Kozmikova

    Full Text Available Formation of a dorsoventral axis is a key event in the early development of most animal embryos. It is well established that bone morphogenetic proteins (Bmps and Wnts are key mediators of dorsoventral patterning in vertebrates. In the cephalochordate amphioxus, genes encoding Bmps and transcription factors downstream of Bmp signaling such as Vent are expressed in patterns reminiscent of those of their vertebrate orthologues. However, the key question is whether the conservation of expression patterns of network constituents implies conservation of functional network interactions, and if so, how an increased functional complexity can evolve. Using heterologous systems, namely by reporter gene assays in mammalian cell lines and by transgenesis in medaka fish, we have compared the gene regulatory network implicated in dorsoventral patterning of the basal chordate amphioxus and vertebrates. We found that Bmp but not canonical Wnt signaling regulates promoters of genes encoding homeodomain proteins AmphiVent1 and AmphiVent2. Furthermore, AmphiVent1 and AmphiVent2 promoters appear to be correctly regulated in the context of a vertebrate embryo. Finally, we show that AmphiVent1 is able to directly repress promoters of AmphiGoosecoid and AmphiChordin genes. Repression of genes encoding dorsal-specific signaling molecule Chordin and transcription factor Goosecoid by Xenopus and zebrafish Vent genes represents a key regulatory interaction during vertebrate axis formation. Our data indicate high evolutionary conservation of a core Bmp-triggered gene regulatory network for dorsoventral patterning in chordates and suggest that co-option of the canonical Wnt signaling pathway for dorsoventral patterning in vertebrates represents one of the innovations through which an increased morphological complexity of vertebrate embryo is achieved.

  15. Cell signaling and transcription factor genes expressed during whole body regeneration in a colonial chordate

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    Rinkevich Baruch

    2008-10-01

    Full Text Available Abstract Background The restoration of adults from fragments of blood vessels in botryllid ascidians (termed whole body regeneration [WBR] represents an inimitable event in the chordates, which is poorly understood on the mechanistic level. Results To elucidate mechanisms underlying this phenomenon, a subtracted EST library for early WBR stages was previously assembled, revealing 76 putative genes belonging to major signaling pathways, including Notch/Delta, JAK/STAT, protein kinases, nuclear receptors, Ras oncogene family members, G-Protein coupled receptor (GPCR and transforming growth factor beta (TGF-β signaling. RT-PCR on selected transcripts documented specific up-regulation in only regenerating fragments, pointing to a broad activation of these signaling pathways at onset of WBR. The followed-up expression pattern of seven representative transcripts from JAK/STAT signaling (Bl-STAT, the Ras oncogene family (Bl-Rap1A, Bl-Rab-33, the protein kinase family (Bl-Mnk, Bl-Cnot, Bl-Slit and Bl-Bax inhibitor, revealed systemic and site specific activations during WBR in a sub-population of circulatory cells. Conclusion WBR in the non-vertebrate chordate Botrylloides leachi is a multifaceted phenomenon, presided by a complex array of cell signaling and transcription factors. Above results, provide a first insight into the whole genome molecular machinery of this unique regeneration process, and reveal the broad participation of cell signaling and transcription factors in the process. While regeneration involves the participation of specific cell populations, WBR signals are systemically expressed at the organism level.

  16. The synapsin gene family in basal chordates: evolutionary perspectives in metazoans

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    De Bernardi Fiorenza

    2010-01-01

    Full Text Available Abstract Background Synapsins are neuronal phosphoproteins involved in several functions correlated with both neurotransmitter release and synaptogenesis. The comprehension of the basal role of the synapsin family is hampered in vertebrates by the existence of multiple synapsin genes. Therefore, studying homologous genes in basal chordates, devoid of genome duplication, could help to achieve a better understanding of the complex functions of these proteins. Results In this study we report the cloning and characterization of the Ciona intestinalis and amphioxus Branchiostoma floridae synapsin transcripts and the definition of their gene structure using available C. intestinalis and B. floridae genomic sequences. We demonstrate the occurrence, in both model organisms, of a single member of the synapsin gene family. Full-length synapsin genes were identified in the recently sequenced genomes of phylogenetically diverse metazoans. Comparative genome analysis reveals extensive conservation of the SYN locus in several metazoans. Moreover, developmental expression studies underline that synapsin is a neuronal-specific marker in basal chordates and is expressed in several cell types of PNS and in many, if not all, CNS neurons. Conclusion Our study demonstrates that synapsin genes are metazoan genes present in a single copy per genome, except for vertebrates. Moreover, we hypothesize that, during the evolution of synapsin proteins, new domains are added at different stages probably to cope up with the increased complexity in the nervous system organization. Finally, we demonstrate that protochordate synapsin is restricted to the post-mitotic phase of CNS development and thereby is a good marker of postmitotic neurons.

  17. A glycine receptor is involved in the organization of swimming movements in an invertebrate chordate

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    Okamura Yasushi

    2010-01-01

    Full Text Available Abstract Background Rhythmic motor patterns for locomotion in vertebrates are generated in spinal cord neural networks known as spinal Central Pattern Generators (CPGs. A key element in pattern generation is the role of glycinergic synaptic transmission by interneurons that cross the cord midline and inhibit contralaterally-located excitatory neurons. The glycinergic inhibitory drive permits alternating and precisely timed motor output during locomotion such as walking or swimming. To understand better the evolution of this system we examined the physiology of the neural network controlling swimming in an invertebrate chordate relative of vertebrates, the ascidian larva Ciona intestinalis. Results A reduced preparation of the larva consisting of nerve cord and motor ganglion generates alternating swimming movements. Pharmacological and genetic manipulation of glycine receptors shows that they are implicated in the control of these locomotory movements. Morphological molecular techniques and heterologous expression experiments revealed that glycine receptors are inhibitory and are present on both motoneurones and locomotory muscle while putative glycinergic interneurons were identified in the nerve cord by labeling with an anti-glycine antibody. Conclusions In Ciona intestinalis, glycine receptors, glycinergic transmission and putative glycinergic interneurons, have a key role in coordinating swimming movements through a simple CPG that is present in the motor ganglion and nerve cord. Thus, the strong association between glycine receptors and vertebrate locomotory networks may now be extended to include the phylum chordata. The results suggest that the basic network for 'spinal-like' locomotion is likely to have existed in the common ancestor of extant chordates some 650 M years ago.

  18. Glial heterotopia of the lip: A rare presentation

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    Mehmet Dadaci

    2016-01-01

    Full Text Available Glial heterotopia represents collections of normal glial tissue in an abnormal location distant to the central nervous system or spinal canal with no intracranial connectivity. Nasal gliomas are non-neoplastic midline tumours, with limited growth potential and no similarity to the central nervous system gliomas. The nose and the nasopharynx are the most common sites of location. Existence of glial heterotopia in the lip region is a rare developmental disorder. We report a case of large glial heterotopia in the upper lip region in a full-term female newborn which had intracranial extension with a fibrotic band. After the surgery, there was no recurrence in the follow-up period of 3 years. When glial heterotopia, which is a rare midline anomaly, is suspected, possible intracranial connection and properties of the mass should be evaluated by magnetic resonance imaging. By this way, lower complication rate and better aesthetic results can be achieved with early diagnosis and proper surgery.

  19. Tumores intraventriculares supratentoriales de origen glial

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    Miguel A Esquivel M

    2015-12-01

    Full Text Available Los tumores gliales intraventriculares representan un gran reto de acceso neuroquirúrgico debido a su localización profunda, asociación intima con numerosas estructuras vasculares de áreas críticas cerebrales y su relación circunferencial a múltiples tractos subcorticales. Debido a todo esto, el acceso quirúrgico a estas regiones, debe incluir una serie de consideraciones minuciosas anatómicas para minimizar el riesgo de lesión a estructuras de considerable importancia y funcionabilidad y lograr una resección máxima posible. Presentamos una reseña de 4 casos los cuales fueron ingresados y atendidos por el servicio de neurocirugía del Hospital México, los cuales ingresaron en un intervalo de 8 meses entre agosto del 2012 y febrero del 2013.

  20. Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for glial and neural-related molecules in central nervous system mixed glial cell cultures: neurotrophins, growth factors and structural proteins

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    Nedelkoska Liljana

    2007-12-01

    Full Text Available Abstract Background In multiple sclerosis, inflammatory cells are found in both active and chronic lesions, and it is increasingly clear that cytokines are involved directly and indirectly in both formation and inhibition of lesions. We propose that cytokine mixtures typical of Th1 or Th2 lymphocytes, or monocyte/macrophages each induce unique molecular changes in glial cells. Methods To examine changes in gene expression that might occur in glial cells exposed to the secreted products of immune cells, we have used gene array analysis to assess the early effects of different cytokine mixtures on mixed CNS glia in culture. We compared the effects of cytokines typical of Th1 and Th2 lymphocytes and monocyte/macrophages (M/M on CNS glia after 6 hours of treatment. Results In this paper we focus on changes with potential relevance for neuroprotection and axon/glial interactions. Each mixture of cytokines induced a unique pattern of changes in genes for neurotrophins, growth and maturation factors and related receptors; most notably an alternatively spliced form of trkC was markedly downregulated by Th1 and M/M cytokines, while Th2 cytokines upregulated BDNF. Genes for molecules of potential importance in axon/glial interactions, including cell adhesion molecules, connexins, and some molecules traditionally associated with neurons showed significant changes, while no genes for myelin-associated genes were regulated at this early time point. Unexpectedly, changes occurred in several genes for proteins initially associated with retina, cancer or bone development, and not previously reported in glial cells. Conclusion Each of the three cytokine mixtures induced specific changes in gene expression that could be altered by pharmacologic strategies to promote protection of the central nervous system.

  1. Essential role of Bmp signaling and its positive feedback loop in the early cell fate evolution of chordates

    Czech Academy of Sciences Publication Activity Database

    Kozmiková, Iryna; Candiani, S.; Fabian, Peter; Gurská, Daniela; Kozmik, Zbyněk

    2013-01-01

    Roč. 382, č. 2 (2013), s. 538-554. ISSN 0012-1606 R&D Projects: GA ČR GCP305/10/J064; GA MŠk EE2.3.30.0027 Institutional support: RVO:68378050 Keywords : Bmp signaling * axial patterning * cell fate * chordates * evolution Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.637, year: 2013

  2. A new vetulicolian from Australia and its bearing on the chordate affinities of an enigmatic Cambrian group

    OpenAIRE

    García-Bellido, Diego C.; Lee, Michael S. Y.; Gregory D. Edgecombe; Jago, James B; Gehling, James G; Paterson, John R

    2014-01-01

    Background Vetulicolians are one of the most problematic and controversial Cambrian fossil groups, having been considered as arthropods, chordates, kinorhynchs, or their own phylum. Mounting evidence suggests that vetulicolians are deuterostomes, but affinities to crown-group phyla are unresolved. Results A new vetulicolian from the Emu Bay Shale Konservat-Lagerstätte, South Australia, Nesonektris aldridgei gen. et sp. nov., preserves an axial, rod-like structure in the posterior body region ...

  3. DoOP: Databases of Orthologous Promoters, collections of clusters of orthologous upstream sequences from chordates and plants

    OpenAIRE

    Barta, Endre; Sebestyén, Endre; Pálfy, Tamás B.; Tóth, Gábor; Ortutay, Csaba P.; Patthy, László

    2004-01-01

    DoOP (http://doop.abc.hu/) is a database of eukaryotic promoter sequences (upstream regions) aiming to facilitate the recognition of regulatory sites conserved between species. The annotated first exons of human and Arabidopsis thaliana genes were used as queries in BLAST searches to collect the most closely related orthologous first exon sequences from Chordata and Viridiplantae species. Up to 3000 bp DNA segments upstream from these first exons constitute the clusters in the chordate and pl...

  4. Trehalose rescues glial cell dysfunction in striatal cultures from HD R6/1 mice at early postnatal development.

    Science.gov (United States)

    Perucho, Juan; Gómez, Ana; Muñoz, María Paz; de Yébenes, Justo García; Mena, María Ángeles; Casarejos, María José

    2016-07-01

    The pathological hallmark of Huntington disease (HD) is the intracellular aggregation of mutant huntingtin (mHTT) in striatal neurons and glia associated with the selective loss of striatal medium-sized spiny neurons. Up to the present, the role of glia in HD is poorly understood and has been classically considered secondary to neuronal disorder. Trehalose is a disaccharide known to possess many pharmacological properties, acting as an antioxidant, a chemical chaperone, and an inducer of autophagy. In this study, we analyzed at an early postnatal development stage the abnormalities observed in striatal glial cell cultures of postnatal R6/1 mice (HD glia), under baseline and stressing conditions and the protective effects of trehalose. Our data demonstrate that glial HD alterations already occur at early stages of postnatal development. After 20 postnatal days in vitro, striatal HD glia cultures showed more reactive astrocytes with increased expression of glial fibrillary acidic protein (GFAP) but with less replication capacity, less A2B5(+) glial progenitors and more microglia than wild-type (WT) cultures. HD glia had lower levels of intracellular glutathione (GSH) and was more susceptible to H2O2 and epoxomicin insults. The amount of expressed GDNF and secreted mature-BDNF by HD astrocytes were much lower than by WT astrocytes. In addition, HD glial cultures showed a deregulation of the major proteolytic systems, the ubiquitin-proteasomal system (UPS), and the autophagic pathway. This produces a defective protein quality control, indicated by the elevated levels of ubiquitination and p62 protein. Interestingly, we show that trehalose, through its capacity to induce autophagy, inhibited p62/SQSTM1 accumulation and facilitated the degradation of cytoplasmic aggregates from mHTT and α-synuclein proteins. Trehalose also reduced microglia activation and reversed the disrupted cytoskeleton of astrocytes accompanied with an increase in the replication capacity. In

  5. Ion channel clustering at the axon initial segment and node of Ranvier evolved sequentially in early chordates.

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    Alexis S Hill

    2008-12-01

    Full Text Available In many mammalian neurons, dense clusters of ion channels at the axonal initial segment and nodes of Ranvier underlie action potential generation and rapid conduction. Axonal clustering of mammalian voltage-gated sodium and KCNQ (Kv7 potassium channels is based on linkage to the actin-spectrin cytoskeleton, which is mediated by the adaptor protein ankyrin-G. We identified key steps in the evolution of this axonal channel clustering. The anchor motif for sodium channel clustering evolved early in the chordate lineage before the divergence of the wormlike cephalochordate, amphioxus. Axons of the lamprey, a very primitive vertebrate, exhibited some invertebrate features (lack of myelin, use of giant diameter to hasten conduction, but possessed narrow initial segments bearing sodium channel clusters like in more recently evolved vertebrates. The KCNQ potassium channel anchor motif evolved after the divergence of lampreys from other vertebrates, in a common ancestor of shark and humans. Thus, clustering of voltage-gated sodium channels was a pivotal early innovation of the chordates. Sodium channel clusters at the axon initial segment serving the generation of action potentials evolved long before the node of Ranvier. KCNQ channels acquired anchors allowing their integration into pre-existing sodium channel complexes at about the same time that ancient vertebrates acquired myelin, saltatory conduction, and hinged jaws. The early chordate refinements in action potential mechanisms we have elucidated appear essential to the complex neural signaling, active behavior, and evolutionary success of vertebrates.

  6. Google Secrets

    CERN Document Server

    Davis, Yvette

    2011-01-01

    Become a Google guru with these effective tips, tricks, and techniques Sure, you use Google. But do you really use Google-and everything it has to offer-in the most effective way possible? Wish you could just sit down with a Google expert who would show you how to take your Google savviness to the next level? With Google Secrets, you can! Tech expert Jerri Ledford reveals the ins, outs, and little-known facts about Google to show you how to sharpen your skills so you can get more done, more efficiently. You may already be familiar with Google's most popular applications, but this indispensable

  7. Modeling cognition and disease using human glial chimeric mice

    DEFF Research Database (Denmark)

    Goldman, Steven A.; Nedergaard, Maiken; Windrem, Martha S.

    2015-01-01

    cognition and information processing. In addition, the cellular humanization of these brains permits their use in studying glial infectious and inflammatory disorders unique to humans, and the effects of those disorders on the glial contributions to cognition. Perhaps most intriguingly, by pairing our...... ability to construct human glial chimeras with the production of patient-specific hGPCs derived from pluripotential stem cells, we may now establish mice in which a substantial proportion of resident glia are both human and disease-derived. These mice in particular may provide us new opportunities for...... studying the human-specific contributions of glia to psychopathology, as well as to higher cognition. As such, the assessment of human glial chimeric mice may provide us new insight into the species-specific contributions of glia to human cognitive evolution, as well as to the pathogenesis of human...

  8. Mood Disorders Are Glial Disorders: Evidence from In Vivo Studies

    OpenAIRE

    Karsten Mueller; Blasig, Ingolf E.; Johann Steiner; Hashim Abdul-Khaliq; Julia Sacher; Matthias L. Schroeter

    2010-01-01

    It has recently been suggested that mood disorders can be characterized by glial pathology as indicated by histopathological postmortem findings. Here, we review studies investigating the glial marker S100B in serum of patients with mood disorders. This protein might act as a growth and differentiation factor. It is located in, and may actively be released by, astro- and oligodendrocytes. Studies consistently show that S100B is elevated in mood disorders; more strongly in major depressive tha...

  9. Quantitation of glial fibrillary acidic protein in human brain tumours

    DEFF Research Database (Denmark)

    Rasmussen, S; Bock, E; Warecka, K;

    1980-01-01

    The glial fibrillary acidic protein (GFA) content of 58 human brain tumours was determined by quantitative immunoelectrophoresis, using monospecific antibody against GFA. Astrocytomas, glioblastomas, oligodendrogliomas, spongioblastomas, ependymomas and medulloblastomas contained relatively high...... amounts of GFA, up to 85 times the concentration in parietal grey substance of normal human brain. GFA was not found in neurinomas, meningiomas, adenomas of the hypophysis, or in a single case of metastasis of adenocarcinoma. Non-glial tumours of craniopharyngioma and haemangioblastoma were infiltrated by...

  10. Neuroimaging Biomarkers for Epilepsy: Advances and Relevance to Glial Cells

    OpenAIRE

    Obenaus, Andre

    2013-01-01

    Glial cells play an important role in normal brain function and emerging evidence would suggest that their dysfunction may be responsible for some epileptic disease states. Neuroimaging of glial cells is desirable, but there are no clear methods to assess neither their function nor localization. Magnetic resonance imaging (MRI) is now part of a standardized epilepsy imaging protocol to assess patients. Structural volumetric and T2-weighted imaging changes can assist in making a positive diagn...

  11. Exosomes secreted by cortical neurons upon glutamatergic synapse activation specifically interact with neurons

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    Mathilde Chivet

    2014-11-01

    Full Text Available Exosomes are nano-sized vesicles of endocytic origin released into the extracellular space upon fusion of multivesicular bodies with the plasma membrane. Exosomes represent a novel mechanism of cell–cell communication allowing direct transfer of proteins, lipids and RNAs. In the nervous system, both glial and neuronal cells secrete exosomes in a way regulated by glutamate. It has been hypothesized that exosomes can be used for interneuronal communication implying that neuronal exosomes should bind to other neurons with some kind of specificity. Here, dissociated hippocampal cells were used to compare the specificity of binding of exosomes secreted by neuroblastoma cells to that of exosomes secreted by cortical neurons. We found that exosomes from neuroblastoma cells bind indiscriminately to neurons and glial cells and could be endocytosed preferentially by glial cells. In contrast, exosomes secreted from stimulated cortical neurons bound to and were endocytosed only by neurons. Thus, our results demonstrate for the first time that exosomes released upon synaptic activation do not bind to glial cells but selectively to other neurons suggesting that they can underlie a novel aspect of interneuronal communication.

  12. Specialized Cortex Glial Cells Accumulate Lipid Droplets in Drosophila melanogaster.

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    Viktor Kis

    Full Text Available Lipid droplets (LDs are common organelles of the majority of eukaryotic cell types. Their biological significance has been extensively studied in mammalian liver cells and white adipose tissue. Although the central nervous system contains the highest relative amount and the largest number of different lipid species, neither the spatial nor the temporal distribution of LDs has been described. In this study, we used the brain of the fruitfly, Drosophila melanogaster, to investigate the neuroanatomy of LDs. We demonstrated that LDs are exclusively localised in glial cells but not in neurons in the larval nervous system. We showed that the brain's LD pool, rather than being constant, changes dynamically during development and reaches its highest value at the beginning of metamorphosis. LDs are particularly enriched in cortex glial cells located close to the brain surface. These specialized superficial cortex glial cells contain the highest amount of LDs among glial cell types and encapsulate neuroblasts and their daughter cells. Superficial cortex glial cells, combined with subperineurial glial cells, express the Drosophila fatty acid binding protein (Dfabp, as we have demonstrated through light- and electron microscopic immunocytochemistry. To the best of our best knowledge this is the first study that describes LD neuroanatomy in the Drosophila larval brain.

  13. Evolutionary functional elaboration of the Elovl2/5 gene family in chordates.

    Science.gov (United States)

    Monroig, Óscar; Lopes-Marques, Mónica; Navarro, Juan C; Hontoria, Francisco; Ruivo, Raquel; Santos, Miguel M; Venkatesh, Byrappa; Tocher, Douglas R; Castro, L Filipe C

    2016-01-01

    The biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFA) provides an intriguing example on how multi-enzymatic cascades evolve. Essential LC-PUFA, such as arachidonic, eicosapentaenoic, and docosahexaenoic acids (DHA), can be acquired from the diet but are also endogenously retailored from C18 precursors through consecutive elongations and desaturations catalyzed, respectively, by fatty acyl elongase and desaturase enzymes. The molecular wiring of this enzymatic pathway defines the ability of a species to biosynthesize LC-PUFA. Exactly when and how in animal evolution a functional LC-PUFA pathway emerged is still elusive. Here we examine key components of the LC-PUFA cascade, the Elovl2/Elovl5 elongases, from amphioxus, an invertebrate chordate, the sea lamprey, a representative of agnathans, and the elephant shark, a basal jawed vertebrate. We show that Elovl2 and Elovl5 emerged from genome duplications in vertebrate ancestry. The single Elovl2/5 from amphioxus efficiently elongates C18 and C20 and, to a marked lesser extent, C22 LC-PUFA. Lamprey is incapable of elongating C22 substrates. The elephant shark Elovl2 showed that the ability to efficiently elongate C22 PUFA and thus to synthesize DHA through the Sprecher pathway, emerged in the jawed vertebrate ancestor. Our findings illustrate how non-integrated "metabolic islands" evolve into fully wired pathways upon duplication and neofunctionalization. PMID:26856376

  14. Evolutionary dynamics of olfactory receptor genes in chordates: interaction between environments and genomic contents

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    Niimura Yoshihito

    2009-12-01

    Full Text Available Abstract Olfaction is essential for the survival of animals. Versatile odour molecules in the environment are received by olfactory receptors (ORs, which form the largest multigene family in vertebrates. Identification of the entire repertories of OR genes using bioinformatics methods from the whole-genome sequences of diverse organisms revealed that the numbers of OR genes vary enormously, ranging from ~1,200 in rats and ~400 in humans to ~150 in zebrafish and ~15 in pufferfish. Most species have a considerable fraction of pseudogenes. Extensive phylogenetic analyses have suggested that the numbers of gene gains and losses are extremely large in the OR gene family, which is a striking example of the birth-and-death evolution. It appears that OR gene repertoires change dynamically, depending on each organism's living environment. For example, higher primates equipped with a well-developed vision system have lost a large number of OR genes. Moreover, two groups of OR genes for detecting airborne odorants greatly expanded after the time of terrestrial adaption in the tetrapod lineage, whereas fishes retain diverse repertoires of genes that were present in aquatic ancestral species. The origin of vertebrate OR genes can be traced back to the common ancestor of all chordate species, but insects, nematodes and echinoderms utilise distinctive families of chemoreceptors, suggesting that chemoreceptor genes have evolved many times independently in animal evolution.

  15. Revaluation of deuterostome phylogeny and evolutionary relationships among chordate subphyla using mitogenome data.

    Science.gov (United States)

    Zhong, Jing; Zhang, Juyong; Mukwaya, Emmanuel; Wang, Yiquan

    2009-03-01

    The traditional knowledge in textbooks indicated that cephalochordates were the closest relatives to vertebrates among all extant organisms. However, this opinion was challenged by several recent phylogenetic studies using hundreds of nuclear genes. The researchers suggested that urochordates, but not cephalochordates, should be the closest living relatives to vertebrates. In the present study, by using data generated from hundreds of mtDNA sequences, we revalue the deuterostome phylogeny in terms of whole mitochondrial genomes (mitogenomes). Our results firmly demonstrate that each of extant deuterostome phyla and chordate subphyla is monophyletic. But the results present several alternative phylogenetic trees depending on different sequence datasets used in the analysis. Although no clear phylogenetic relationships are obtained, those trees indicate that the ancient common ancestor diversified rapidly soon after their appearance in the early Cambrian and generated all major deuterostome lineages during a short historical period, which is consistent with "Cambrian explosion" revealed by paleontologists. It was the 520-million-year's evolution that obscured the phylogenetic relationships of extant deuterostomes. Thus, we conclude that an integrative analysis approach rather than simply using more DNA sequences should be employed to address the distant evolutionary relationship. PMID:19302971

  16. Metaphylogeny of 82 gene families sheds a new light on chordate evolution

    Directory of Open Access Journals (Sweden)

    2006-04-01

    Full Text Available Achieving a better comprehension of the evolution of species has always been an important matter for evolutionary biologists. The deuterostome phylogeny has been described for many years, and three phyla are distinguishable: Echinodermata (including sea stars, sea urchins, etc…, Hemichordata (including acorn worms and pterobranchs, and Chordata (including urochordates, cephalochordates and extant vertebrates. Inside the Chordata phylum, the position of vertebrate species is quite unanimously accepted. Nonetheless, the position of urochordates in regard with vertebrates is still the subject of debate, and has even been suggested by some authors to be a separate phylum from cephalochordates and vertebrates. It was also the case for agnathans species –myxines and hagfish– for which phylogenetic evidence was recently given for a controversial monophyly. This raises the following question: which one of the cephalochordata or urochordata is the sister group of vertebrates and what are their relationships? In the present work, we analyzed 82 protein families presenting homologs between urochordata and other deuterostomes and focused on two points: 1 testing accurately the position of urochordata and cephalochordata phyla in regard with vertebrates as well as chordates monophyly, 2 performing an estimation of the rate of gene loss in the Ciona intestinalis genome. We showed that the urochordate phyla is the vertebrate sister group and that gene loss played a major role in structuring the urochordate genome.

  17. LncRNA analysis of mouse spermatogonial stem cells following glial cell-derived neurotrophic factor treatment

    OpenAIRE

    Lufan Li; Min Wang; Mei Wang; Xiaoxi Wu; Lei Geng; Yuanyuan Xue; Xiang Wei; Yuanyuan Jia; Xin Wu

    2015-01-01

    Spermatonial stem cells (SSCs) are the foundation of spermatogenesis. Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs with at least 200 bp in length, which play important roles in various biological processes. Growth factor glial cell line-derived neurotrophic factor (GDNF), secreted from testis niches, is critical for self-renewal of SSCs in vitro and in vivo. Using Illumina HiSeq™ 2000 high throughput sequencing, we found 55924 lncRNAs which were regulated by GDNF in SSCs in v...

  18. Lipid-mediated glial cell line-derived neurotrophic factor gene transfer to cultured porcine ventral mesencephalic tissue

    DEFF Research Database (Denmark)

    Bauer, Matthias; Meyer, Morten; Brevig, Thomas;

    2002-01-01

    -mediated transfer of the gene for human glial cell line-derived neurotrophic factor (GDNF) to embryonic (E27/28) porcine VM tissue kept as organotypic explant cultures. Treatment of the developing VM with two mitogens, basic fibroblast growth factor and epidermal growth factor, prior to transfection significantly...... increased transfection yields. Expression of human GDNF via an episomal vector could be detected by in situ hybridization and by the measuring of GDNF protein secreted into the culture medium. When compared to mock-transfected controls, VM tissue expressing recombinant GDNF contained significantly higher...

  19. Pax258 and Pax6 alternative splicing events in basal chordates and vertebrates: a focus on paired box domain

    Directory of Open Access Journals (Sweden)

    Peter eFabian

    2015-07-01

    Full Text Available Paired box transcription factors play important role in development and tissue morphogenesis. The number of Pax homologs varies among species studied so far, due to genome and gene duplications that have affected PAX family to a great extent. Based on sequence similarity and functional domains, four Pax classes have been identified in chordates, namely Pax1/9, Pax2/5/8, Pax3/7 and Pax4/6. Numerous splicing events have been reported mainly for Pax2/5/8 and Pax6 genes. Of significant interest are those events that lead to Pax proteins with presumed novel properties, such as altered DNA-binding or transcriptional activity. In the current study, a thorough analysis of Pax2/5/8 splicing events from cephalochordate and vertebrates was performed. We focused more on Pax2/5/8 and Pax6 splicing events in which the paired domain is involved. Three new splicing events were identified in Oryzias latipes, one of which seems to be conserved in Acanthomorphata. Using representatives from deuterostome and protostome phyla, a comparative analysis of the Pax6 exon-intron structure of the paired domain was performed, during an attempt to estimate the time of appearance of the Pax6(5a mRNA isoform. As shown in our analysis, this splicing event is absent in basal chordates and is characteristic of Gnathostomata. Moreover, expression pattern of alternative spliced variants was compared between basal chordates and fish species. In summary, our data indicate expansion of alternative mRNA variants in paired box region of Pax2/5/8 and Pax6 genes during the course of vertebrate evolution.

  20. Testing putative hemichordate homologues of the chordate dorsal nervous system and endostyle: expression of NK2.1 (TTF-1) in the acorn worm Ptychodera flava (Hemichordata, Ptychoderidae)

    Science.gov (United States)

    Takacs, Carter M.; Moy, Vanessa N.; Peterson, Kevin J.

    2002-01-01

    Recent phylogenetic investigations have confirmed that hemichordates and echinoderms are sister taxa. However, hemichordates share several cardinal characterstics with chordates and are thus an important taxon for testing hypotheses of homology between key chordate characters and their putative hemichordate antecedents. The chordate dorsal nervous system (DNS) and endostyle are intriguing characters because both hemichordate larval and adult structures have been hypothesized as homologues. This study attempts to test these purported homologies through examination of the expression pattem of a Ptychodera flava NK2 gene, PfNK2.1, because this gene is expressed both in the DNS and endostyle/thyroid in a wide range of chordate taxa. We found that PfNK2.1 is expressed in both neuronal and pharyngeal structures, but its expression pattem is broken up into distinct embryonic and juvenile phases. During embryogenesis, PfNK2.1 is expressed in the apical ectoderm, with transcripts later detected in presumable neuronal structures, including the apical organ and ciliated feeding band. In the developing juvenile we detected PfNK2.1 signal throughout the pharynx, including the stomochord, and later in the hindgut. We conclude that the similar utilization of NK2.1 in apical organ development and chordate DNS is probably due to a more general role for NK2.1 in neurogenesis and that hemichordates do not possess a homologue of the chordate DNS. In addition, we conclude that P. flava most likely does not possess a true endostyle; rather during the evolution of the endostyle NK2.1 was recruited from its more general role in pharynx development.

  1. The Simple Chordate Ciona intestinalis Has a Reduced Complement of Genes Associated with Fanconi Anemia

    Science.gov (United States)

    Stanley, Edward C.; Azzinaro, Paul A.; Vierra, David A.; Howlett, Niall G.; Irvine, Steven Q.

    2016-01-01

    Fanconi anemia (FA) is a human genetic disease characterized by congenital defects, bone marrow failure, and increased cancer risk. FA is associated with mutation in one of 24 genes. The protein products of these genes function cooperatively in the FA pathway to orchestrate the repair of DNA interstrand cross-links. Few model organisms exist for the study of FA. Seeking a model organism with a simpler version of the FA pathway, we searched the genome of the simple chordate Ciona intestinalis for homologs of the human FA-associated proteins. BLAST searches, sequence alignments, hydropathy comparisons, maximum likelihood phylogenetic analysis, and structural modeling were used to infer the likelihood of homology between C. intestinalis and human FA proteins. Our analysis indicates that C. intestinalis indeed has a simpler and potentially functional FA pathway. The C. intestinalis genome was searched for candidates for homology to 24 human FA and FA-associated proteins. Support was found for the existence of homologs for 13 of these 24 human genes in C. intestinalis. Members of each of the three commonly recognized FA gene functional groups were found. In group I, we identified homologs of FANCE, FANCL, FANCM, and UBE2T/FANCT. Both members of group II, FANCD2 and FANCI, have homologs in C. intestinalis. In group III, we found evidence for homologs of FANCJ, FANCO, FANCQ/ERCC4, FANCR/RAD51, and FANCS/BRCA1, as well as the FA-associated proteins ERCC1 and FAN1. Evidence was very weak for the existence of homologs in C. intestinalis for any other recognized FA genes. This work supports the notion that C. intestinalis, as a close relative of vertebrates, but having a much reduced complement of FA genes, offers a means of studying the function of certain FA proteins in a simpler pathway than that of vertebrate cells. PMID:27279728

  2. Distinctive glial and neuronal interfacing on nanocrystalline diamond.

    Directory of Open Access Journals (Sweden)

    Amel Bendali

    Full Text Available Direct electrode/neuron interfacing is a key challenge to achieve high resolution of neuronal stimulation required for visual prostheses. Neuronal interfacing on biomaterials commonly requires the presence of glial cells and/or protein coating. Nanocrystalline diamond is a highly mechanically stable biomaterial with a remarkably large potential window for the electrical stimulation of tissues. Using adult retinal cell cultures from rats, we found that glial cells and retinal neurons grew equally well on glass and nanocrystalline diamond. The use of a protein coating increased cell survival, particularly for glial cells. However, bipolar neurons appeared to grow even in direct contact with bare diamond. We investigated whether the presence of glial cells contributed to this direct neuron/diamond interface, by using purified adult retinal ganglion cells to seed diamond and glass surfaces with and without protein coatings. Surprisingly, these fully differentiated spiking neurons survived better on nanocrystalline diamond without any protein coating. This greater survival was indicated by larger cell numbers and the presence of longer neurites. When a protein pattern was drawn on diamond, neurons did not grow preferentially on the coated area, by contrast to their behavior on a patterned glass. This study highlights the interesting biocompatibility properties of nanocrystalline diamond, allowing direct neuronal interfacing, whereas a protein coating was required for glial cell growth.

  3. Retinoic acid signaling acts via Hox1 to establish the posterior limit of the pharynx in the chordate amphioxus

    OpenAIRE

    Schubert, Michael; Yu, Jr-Kai; Holland, Nicholas D; Escriva, Hector; Laudet, Vincent; Holland, Linda Z

    2004-01-01

    In the invertebrate chordate amphioxus, as in vertebrates, retinoic acid (RA) specifies position along the anterior/posterior axis with elevated RA signaling in the middle third of the endoderm setting the posterior limit of the pharynx. Here we show that AmphiHox1 is also expressed in the middle third of the developing amphioxus endoderm and is activated by RA signaling. Knockdown of AmphiHox1 function with an antisense morpholino oligonucleotide shows that AmphiHox1 mediates the role of RA ...

  4. Activation of EP2 Prostanoid Receptors in Human Glial Cell Lines Stimulates the Secretion of BDNF

    OpenAIRE

    Hutchinson, Anthony J.; Chou, Chih-Ling; Israel, Davelene D.; Xu, Wei; Regan, John W

    2009-01-01

    Prostaglandin E2 (PGE2) is produced at high levels in the injured central nervous system, where it is generally considered a cytotoxic mediator of inflammation. The cellular actions of PGE2 are mediated by G-protein signaling activated by prostanoid receptors termed EP1, EP2, EP3 and EP4. Recent studies have implicated the EP2 prostanoid receptor in apparently conflicting roles promoting neuronal death in some model systems and the survival of neurons in others. Here we show that treatment of...

  5. Axon-glial interactions in the central nervous system

    OpenAIRE

    Butt, Arthur; Bay, Virginia

    2011-01-01

    Axon-glial interactions are critical for brain information transmission and processing. In the CNS, this is a function of the major types of glia – astrocytes, oligodendrocytes and novel NG2-glia. This special issue of the Journal of Anatomy comprises contributions arising from a symposium entitled ‘Axon-glial interactions in the CNS’, held at the University of Portsmouth, UK in July 2010. The aim of the special issue is to bring together an international group of experts to demonstrate the c...

  6. C/EBPs en la activación glial

    OpenAIRE

    Ejarque-Ortiz, Aroa

    2008-01-01

    [spa] La activación glial es un proceso que se ha implicado en diversas patologías entre las que se incluyen diferentes enfermedades neurodegenerativas, como la enfermedad de Alzheimer o la Esclerosis Lateral Amiotrófica. Esto se debe a que durante la activación glial se producen mediadores proinflamatorios, como la ciclooxigenasa (COX-2), el óxido nítrico (NO), factor de necrosis tumoral (TNF-alfa), la interleuquina-1 (IL-1) o la interleuquina-6 (IL-6), que presentan un potencial neurotóxico...

  7. Long-chain polyunsaturated fatty acid biosynthesis in chordates: Insights into the evolution of Fads and Elovl gene repertoire.

    Science.gov (United States)

    Castro, L Filipe C; Tocher, Douglas R; Monroig, Oscar

    2016-04-01

    Long-chain polyunsaturated fatty acids (LC-PUFA) are major components of complex lipid molecules and are also involved in numerous critical biological processes. Studies conducted mainly in vertebrates have demonstrated that LC-PUFA can be biosynthesized through the concerted action of two sets of enzymes, namely fatty acyl desaturases (Fads) and elongation of very long-chain fatty acid (Elovl) proteins. While LC-PUFA research is a thriving field, mainly focused on human health, an integrated view regarding the evolution of LC-PUFA biosynthetic genetic machinery in chordates is yet to be produced. Particularly important is to understand whether lineage specific life history trajectories, as well as major biological transitions, or particular genomic processes such as genome duplications have impacted the evolution of LC-PUFA biosynthetic pathways. Here we review the gene repertoire of Fads and Elovl in chordate genomes and the diversity of substrate specificities acquired during evolution. We take advantage of the magnitude of genomic and functional data to show that combination duplication processes and functional plasticity have generated a wide diversity of physiological capacities in extant lineages. A clear evolutionary framework is provided, which will be instrumental for the full clarification of functional capacities between the various vertebrate groups. PMID:26769304

  8. Phylogenetic analysis of the tenascin gene family: evidence of origin early in the chordate lineage

    Directory of Open Access Journals (Sweden)

    Tucker RP

    2006-08-01

    suggests that tenascins may be specific to chordates. Later genomic duplication events led to the appearance of four family members in vertebrates: tenascin-C, tenascin-R, tenascin-W and tenascin-X.

  9. Rapid method for culturing embryonic neuron-glial cell cocultures

    DEFF Research Database (Denmark)

    Svenningsen, Åsa Fex; Shan, Wei-Song; Colman, David R;

    2003-01-01

    enteric neurons is seen after 3 weeks (2 weeks in ascorbic acid), suggesting that basal lamina production is important even for glial ensheathment in the enteric nervous system. No overgrowth of fibroblasts or other nonneuronal cells was noted in any cultures, and myelination of the peripheral nervous...

  10. Depression as a Glial-Based Synaptic Dysfunction

    OpenAIRE

    Rial, Daniel; Lemos, Cristina; Pinheiro, Helena; Duarte, Joana M.; Gonçalves, Francisco Q.; Real, Joana I.; Prediger, Rui D.; Gonçalves, Nélio; Gomes, Catarina A.; Canas, Paula M.; Agostinho, Paula; Cunha, Rodrigo A.

    2016-01-01

    Recent studies combining pharmacological, behavioral, electrophysiological and molecular approaches indicate that depression results from maladaptive neuroplastic processes occurring in defined frontolimbic circuits responsible for emotional processing such as the prefrontal cortex, hippocampus, amygdala and ventral striatum. However, the exact mechanisms controlling synaptic plasticity that are disrupted to trigger depressive conditions have not been elucidated. Since glial cells (astrocytes...

  11. Methylphenidate Increases Glutamate Uptake in Bergmann Glial Cells.

    Science.gov (United States)

    Guillem, Alain M; Martínez-Lozada, Zila; Hernández-Kelly, Luisa C; López-Bayghen, Esther; López-Bayghen, Bruno; Calleros, Oscar A; Campuzano, Marco R; Ortega, Arturo

    2015-11-01

    Glutamate, the main excitatory transmitter in the vertebrate brain, exerts its actions through the activation of specific membrane receptors present in neurons and glial cells. Over-stimulation of glutamate receptors results in neuronal death, phenomena known as excitotoxicity. A family of glutamate uptake systems, mainly expressed in glial cells, removes the amino acid from the synaptic cleft preventing an excessive glutamatergic stimulation and thus neuronal damage. Autism spectrum disorders comprise a group of syndromes characterized by impaired social interactions and anxiety. One or the most common drugs prescribed to treat these disorders is Methylphenidate, known to increase dopamine extracellular levels, although it is not clear if its sedative effects are related to a plausible regulation of the glutamatergic tone via the regulation of the glial glutamate uptake systems. To gain insight into this possibility, we used the well-established model system of cultured chick cerebellum Bergmann glia cells. A time and dose-dependent increase in the activity and protein levels of glutamate transporters was detected upon Methylphenidate exposure. Interestingly, this increase is the result of an augmentation of both the synthesis as well as the insertion of these protein complexes in the plasma membrane. These results favour the notion that glial cells are Methylphenidate targets, and that by these means could regulate dopamine turnover. PMID:26384974

  12. Telmisartan Modulates Glial Activation: In Vitro and In Vivo Studies

    Science.gov (United States)

    Torika, Nofar; Asraf, Keren; Danon, Abraham; Apte, Ron N.; Fleisher-Berkovich, Sigal

    2016-01-01

    The circulating renin-angiotensin system (RAS), including the biologically active angiotensin II, is a fundamental regulatory mechanism of blood pressure conserved through evolution. Angiotensin II components of the RAS have also been identified in the brain. In addition to pro-inflammatory cytokines, neuromodulators, such as angiotensin II can induce (through angiotensin type 1 receptor (AT1R)) some of the inflammatory actions of brain glial cells and influence brain inflammation. Moreover, in Alzheimer’s disease (AD) models, where neuroinflammation occurs, increased levels of cortical AT1Rs have been shown. Still, the precise role of RAS in neuroinflammation is not completely clear. The overall aim of the present study was to elucidate the role of RAS in the modulation of glial functions and AD pathology. To reach this goal, the specific aims of the present study were a. to investigate the long term effect of telmisartan (AT1R blocker) on tumor necrosis factor-α (TNF-α), interleukin 1-β (IL1-β) and nitric oxide (NO) release from glial cells. b. to examine the effect of intranasally administered telmisartan on amyloid burden and microglial activation in 5X familial AD (5XFAD) mice. Telmisartan effects in vivo were compared to those of perindopril (angiotensin converting enzyme inhibitor). Long-term-exposure of BV2 microglia to telmisartan significantly decreased lipopolysaccharide (LPS) -induced NO, inducible NO synthase, TNF-α and IL1-β synthesis. The effect of Telmisartan on NO production in BV2 cells was confirmed also in primary neonatal rat glial cells. Intranasal administration of telmisartan (1 mg/kg/day) for up to two months significantly reduced amyloid burden and CD11b expression (a marker for microglia) both in the cortex and hipoccampus of 5XFAD. Based on the current view of RAS and our data, showing reduced amyloid burden and glial activation in the brains of 5XFAD transgenic mice, one may envision potential intervention with the progression

  13. Telmisartan Modulates Glial Activation: In Vitro and In Vivo Studies.

    Directory of Open Access Journals (Sweden)

    Nofar Torika

    Full Text Available The circulating renin-angiotensin system (RAS, including the biologically active angiotensin II, is a fundamental regulatory mechanism of blood pressure conserved through evolution. Angiotensin II components of the RAS have also been identified in the brain. In addition to pro-inflammatory cytokines, neuromodulators, such as angiotensin II can induce (through angiotensin type 1 receptor (AT1R some of the inflammatory actions of brain glial cells and influence brain inflammation. Moreover, in Alzheimer's disease (AD models, where neuroinflammation occurs, increased levels of cortical AT1Rs have been shown. Still, the precise role of RAS in neuroinflammation is not completely clear. The overall aim of the present study was to elucidate the role of RAS in the modulation of glial functions and AD pathology. To reach this goal, the specific aims of the present study were a. to investigate the long term effect of telmisartan (AT1R blocker on tumor necrosis factor-α (TNF-α, interleukin 1-β (IL1-β and nitric oxide (NO release from glial cells. b. to examine the effect of intranasally administered telmisartan on amyloid burden and microglial activation in 5X familial AD (5XFAD mice. Telmisartan effects in vivo were compared to those of perindopril (angiotensin converting enzyme inhibitor. Long-term-exposure of BV2 microglia to telmisartan significantly decreased lipopolysaccharide (LPS -induced NO, inducible NO synthase, TNF-α and IL1-β synthesis. The effect of Telmisartan on NO production in BV2 cells was confirmed also in primary neonatal rat glial cells. Intranasal administration of telmisartan (1 mg/kg/day for up to two months significantly reduced amyloid burden and CD11b expression (a marker for microglia both in the cortex and hipoccampus of 5XFAD. Based on the current view of RAS and our data, showing reduced amyloid burden and glial activation in the brains of 5XFAD transgenic mice, one may envision potential intervention with the

  14. Telmisartan Modulates Glial Activation: In Vitro and In Vivo Studies.

    Science.gov (United States)

    Torika, Nofar; Asraf, Keren; Danon, Abraham; Apte, Ron N; Fleisher-Berkovich, Sigal

    2016-01-01

    The circulating renin-angiotensin system (RAS), including the biologically active angiotensin II, is a fundamental regulatory mechanism of blood pressure conserved through evolution. Angiotensin II components of the RAS have also been identified in the brain. In addition to pro-inflammatory cytokines, neuromodulators, such as angiotensin II can induce (through angiotensin type 1 receptor (AT1R)) some of the inflammatory actions of brain glial cells and influence brain inflammation. Moreover, in Alzheimer's disease (AD) models, where neuroinflammation occurs, increased levels of cortical AT1Rs have been shown. Still, the precise role of RAS in neuroinflammation is not completely clear. The overall aim of the present study was to elucidate the role of RAS in the modulation of glial functions and AD pathology. To reach this goal, the specific aims of the present study were a. to investigate the long term effect of telmisartan (AT1R blocker) on tumor necrosis factor-α (TNF-α), interleukin 1-β (IL1-β) and nitric oxide (NO) release from glial cells. b. to examine the effect of intranasally administered telmisartan on amyloid burden and microglial activation in 5X familial AD (5XFAD) mice. Telmisartan effects in vivo were compared to those of perindopril (angiotensin converting enzyme inhibitor). Long-term-exposure of BV2 microglia to telmisartan significantly decreased lipopolysaccharide (LPS) -induced NO, inducible NO synthase, TNF-α and IL1-β synthesis. The effect of Telmisartan on NO production in BV2 cells was confirmed also in primary neonatal rat glial cells. Intranasal administration of telmisartan (1 mg/kg/day) for up to two months significantly reduced amyloid burden and CD11b expression (a marker for microglia) both in the cortex and hipoccampus of 5XFAD. Based on the current view of RAS and our data, showing reduced amyloid burden and glial activation in the brains of 5XFAD transgenic mice, one may envision potential intervention with the progression of

  15. Immunoglobins in mammary secretions

    DEFF Research Database (Denmark)

    Hurley, W L; Theil, Peter Kappel

    2013-01-01

    Immunoglobulins secreted in colostrum and milk by the lactating mammal are major factors providing immune protection to the newborn. Immunoglobulins in mammary secretions represent the cumulative immune response of the lactating animal to exposure to antigenic stimulation that occurs through...... immunoglobulins found in mammary secretions in the context of their diversity of structure, origin, mechanisms of transfer, and function....

  16. Activated Scavenger Receptor A Promotes Glial Internalization of Aβ

    OpenAIRE

    He Zhang; Ya-jing Su; Wei-wei Zhou; Shao-wei Wang; Peng-xin Xu; Xiao-lin Yu; Rui-tian Liu

    2014-01-01

    Beta-amyloid (Aβ) aggregates have a pivotal role in pathological processing of Alzheimer's disease (AD). The clearance of Aβ monomer or aggregates is a causal strategy for AD treatment. Microglia and astrocytes are the main macrophages that exert critical neuroprotective roles in the brain. They may effectively clear the toxic accumulation of Aβ at the initial stage of AD, however, their functions are attenuated because of glial overactivation. In this study, we first showed that heptapeptide...

  17. Glial cell development and function in the Drosophila visual system

    OpenAIRE

    CHOTARD, CAROLE; Salecker, Iris

    2007-01-01

    In the developing nervous system, building a functional neuronal network relies on coordinating the formation, specification and survival to diverse neuronal and glial cell subtypes. The establishment of neuronal connections further depends on sequential neuron–neuron and neuron–glia interactions that regulate cell-migration patterns and axon guidance. The visual system of Drosophila has a highly regular, retinotopic organization into reiterated interconnected synaptic circuits. It is therefo...

  18. Brain Connexins in Demyelinating Diseases: Therapeutic Potential of Glial Targets

    OpenAIRE

    Cotrina, Maria Luisa; Nedergaard, Maiken

    2012-01-01

    Several demyelinating syndromes have been linked to mutations in glial gap junction proteins, the connexins. Although mutations in connexins of the myelinating cells, Schwann cells and oligodendrocytes, were initially described, recent data have shown that astrocytes also play a major role in the demyelination process. Alterations in astrocytic proteins directly affect the oligodendrocytes’ ability to maintain myelin structure, and associated astrocytic proteins that regulate water and ionic ...

  19. JC polyomavirus in the aetiology and pathophysiology of glial tumours.

    Science.gov (United States)

    Eftimov, Tihomir; Enchev, Yavor; Tsekov, Iliya; Simeonov, Plamen; Kalvatchev, Zlatko; Encheva, Elitsa

    2016-01-01

    Glial brain tumours with their poor prognosis, limited treatment modalities and unclear detailed pathophysiology represent a significant health concern. The purpose of the current study was to investigate and describe the possible role of the human polyomavirus JC as an underlying cancerogenic or co-cancerogenic factor in the complex processes of glial tumour induction and development. Samples from 101 patients with glial tumours were obtained during neurosurgical tumour resection. Small tissue pieces were taken from several areas of the histologically verified solid tumour core. Biopsies were used for DNA extraction and subsequent amplification reactions of sequences from the JC viral genome. Real-time polymerase chain reaction was used for detection and quantification of its non-coding control region (NCCR) and gene encoding the regulatory protein Large T antigen (LT). An average of 37.6% of all patients was found to be LT positive, whereas only 6.9% tested positive for NCCR. The analysis of the results demonstrated significant variance between the determined LT prevalence and the rate for NCCR, with a low starting copy number in all positive samples and threshold cycles in the range of 36 to 42 representing viral load in the range from 10 to 1000 copies/μl. The results most probably indicate incomplete JC viral replication. Under such conditions, mutations in the host cell genome may be accumulated due to interference of the virus with the host cell machinery, and eventually malignant transformation may occur. PMID:26560882

  20. Glial biomarkers in human central nervous system disease.

    Science.gov (United States)

    Garden, Gwenn A; Campbell, Brian M

    2016-10-01

    There is a growing understanding that aberrant GLIA function is an underlying factor in psychiatric and neurological disorders. As drug discovery efforts begin to focus on glia-related targets, a key gap in knowledge includes the availability of validated biomarkers to help determine which patients suffer from dysfunction of glial cells or who may best respond by targeting glia-related drug mechanisms. Biomarkers are biological variables with a significant relationship to parameters of disease states and can be used as surrogate markers of disease pathology, progression, and/or responses to drug treatment. For example, imaging studies of the CNS enable localization and characterization of anatomical lesions without the need to isolate tissue for biopsy. Many biomarkers of disease pathology in the CNS involve assays of glial cell function and/or response to injury. Each major glia subtype (oligodendroglia, astroglia and microglia) are connected to a number of important and useful biomarkers. Here, we describe current and emerging glial based biomarker approaches for acute CNS injury and the major categories of chronic nervous system dysfunction including neurodegenerative, neuropsychiatric, neoplastic, and autoimmune disorders of the CNS. These descriptions are highlighted in the context of how biomarkers are employed to better understand the role of glia in human CNS disease and in the development of novel therapeutic treatments. GLIA 2016;64:1755-1771. PMID:27228454

  1. Dynamical mean field model of a neural-glial mass.

    Science.gov (United States)

    Sotero, Roberto C; Martínez-Cancino, Ramón

    2010-04-01

    Our goal is to model the behavior of an ensemble of interacting neurons and astrocytes (the neural-glial mass). For this, a model describing N tripartite synapses is proposed. Each tripartite synapse consists of presynaptic and postsynaptic nerve terminals, as well as the synaptically associated astrocytic microdomain, and is described by a system of 13 stochastic differential equations. Then, by applying the dynamical mean field approximation (DMA) (Hasegawa, 2003a , 2003b ) the system of 13N equations is reduced to 13(13 + 2) = 195 deterministic differential equations for the means and the second-order moments of local and global variables. Simulations are carried out for studying the response of the neural-glial mass to external inputs applied to either the presynaptic terminals or the astrocytes. Three cases were considered: the astrocytes influence only the presynaptic terminal, only the postsynaptic terminal, or both the presynaptic and postsynaptic terminals. As a result, a wide range of responses varying from singles spikes to train of spikes was evoked on presynaptic and postsynaptic terminals. The experimentally observed phenomenon of spontaneous activity in astrocytes was replicated on the neural-glial mass. The model predicts that astrocytes can have a strong and activity-dependent influence on synaptic transmission. Finally, simulations show that the dynamics of astrocytes influences the synchronization ratio between neurons, predicting a peak in the synchronization for specific values of the astrocytes' parameters. PMID:20028223

  2. Glial Cell-Elicited Activation of Brain Microvasculature in Response to Brucella abortus Infection Requires ASC Inflammasome-Dependent IL-1β Production.

    Science.gov (United States)

    Miraglia, M Cruz; Costa Franco, Miriam M; Rodriguez, Ana M; Bellozi, Paula M Q; Ferrari, Carina C; Farias, Maria I; Dennis, Vida A; Barrionuevo, Paula; de Oliveira, Antonio C P; Pitossi, Fernando; Kim, Kwang Sik; Delpino, M Victoria; Oliveira, Sergio Costa; Giambartolomei, Guillermo H

    2016-05-01

    Blood-brain barrier activation and/or dysfunction are a common feature of human neurobrucellosis, but the underlying pathogenic mechanisms are largely unknown. In this article, we describe an immune mechanism for inflammatory activation of human brain microvascular endothelial cells (HBMEC) in response to infection with Brucella abortus Infection of HBMEC with B. abortus induced the secretion of IL-6, IL-8, and MCP-1, and the upregulation of CD54 (ICAM-1), consistent with a state of activation. Culture supernatants (CS) from glial cells (astrocytes and microglia) infected with B. abortus also induced activation of HBMEC, but to a greater extent. Although B. abortus-infected glial cells secreted IL-1β and TNF-α, activation of HBMEC was dependent on IL-1β because CS from B. abortus-infected astrocytes and microglia deficient in caspase-1 and apoptosis-associated speck-like protein containing a CARD failed to induce HBMEC activation. Consistently, treatment of CS with neutralizing anti-IL-1β inhibited HBMEC activation. Both absent in melanoma 2 and Nod-like receptor containing a pyrin domain 3 are partially required for caspase-1 activation and IL-1β secretion, suggesting that multiple apoptosis-associated speck-like protein containing CARD-dependent inflammasomes contribute to IL-1β-induced activation of the brain microvasculature. Inflammasome-mediated IL-1β secretion in glial cells depends on TLR2 and MyD88 adapter-like/TIRAP. Finally, neutrophil and monocyte migration across HBMEC monolayers was increased by CS from Brucella-infected glial cells in an IL-1β-dependent fashion, and the infiltration of neutrophils into the brain parenchyma upon intracranial injection of B. abortus was diminished in the absence of Nod-like receptor containing a pyrin domain 3 and absent in melanoma 2. Our results indicate that innate immunity of the CNS set in motion by B. abortus contributes to the activation of the blood-brain barrier in neurobrucellosis and IL-1β mediates

  3. Exosomes secreted by cortical neurons upon glutamatergic synapse activation specifically interact with neurons

    OpenAIRE

    Chivet, Mathilde,; Javalet, Charlotte; Laulagnier, Karine; Blot, Béatrice; Fiona J. Hemming; Sadoul, Rémy

    2014-01-01

    Exosomes are nano-sized vesicles of endocytic origin released into the extracellular space upon fusion of multivesicular bodies with the plasma membrane. Exosomes represent a novel mechanism of cell–cell communication allowing direct transfer of proteins, lipids and RNAs. In the nervous system, both glial and neuronal cells secrete exosomes in a way regulated by glutamate. It has been hypothesized that exosomes can be used for interneuronal communication implying that neuronal exosomes should...

  4. LncRNA analysis of mouse spermatogonial stem cells following glial cell-derived neurotrophic factor treatment

    Directory of Open Access Journals (Sweden)

    Lufan Li

    2015-09-01

    Full Text Available Spermatonial stem cells (SSCs are the foundation of spermatogenesis. Long non-coding RNAs (lncRNAs are a class of non-coding RNAs with at least 200 bp in length, which play important roles in various biological processes. Growth factor glial cell line-derived neurotrophic factor (GDNF, secreted from testis niches, is critical for self-renewal of SSCs in vitro and in vivo. Using Illumina HiSeq™ 2000 high throughput sequencing, we found 55924 lncRNAs which were regulated by GDNF in SSCs in vitro; these included 21,929 known lncRNAs from NONCODE library (version 3.0 and 33,975 predicted lncRNAs which were identified using Coding Potential Calculator. Analyses of these data should provide new insights into regulated mechanism in SSC self-renewal and proliferation. The data have been deposited in the Gene Expression Omnibus (series GSE66998.

  5. LncRNA analysis of mouse spermatogonial stem cells following glial cell-derived neurotrophic factor treatment

    Science.gov (United States)

    Li, Lufan; Wang, Min; Wang, Mei; Wu, Xiaoxi; Geng, Lei; Xue, Yuanyuan; Wei, Xiang; Jia, Yuanyuan; Wu, Xin

    2015-01-01

    Spermatonial stem cells (SSCs) are the foundation of spermatogenesis. Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs with at least 200 bp in length, which play important roles in various biological processes. Growth factor glial cell line-derived neurotrophic factor (GDNF), secreted from testis niches, is critical for self-renewal of SSCs in vitro and in vivo. Using Illumina HiSeq™ 2000 high throughput sequencing, we found 55924 lncRNAs which were regulated by GDNF in SSCs in vitro; these included 21,929 known lncRNAs from NONCODE library (version 3.0) and 33,975 predicted lncRNAs which were identified using Coding Potential Calculator. Analyses of these data should provide new insights into regulated mechanism in SSC self-renewal and proliferation. The data have been deposited in the Gene Expression Omnibus (series GSE66998). PMID:26484267

  6. Evolutionary Origin of GnIH and NPFF in Chordates: Insights from Novel Amphioxus RFamide Peptides

    OpenAIRE

    Tomohiro Osugi; Tomoki Okamura; You Lee Son; Makoto Ohkubo; Takayoshi Ubuka; Yasuhisa Henmi; Kazuyoshi Tsutsui

    2014-01-01

    Gonadotropin-inhibitory hormone (GnIH) is a newly identified hypothalamic neuropeptide that inhibits pituitary hormone secretion in vertebrates. GnIH has an LPXRFamide (X = L or Q) motif at the C-terminal in representative species of gnathostomes. On the other hand, neuropeptide FF (NPFF), a neuropeptide characterized as a pain-modulatory neuropeptide, in vertebrates has a PQRFamide motif similar to the C-terminal of GnIH, suggesting that GnIH and NPFF have diverged from a common ancestor. Be...

  7. Bone marrow-derived fibroblast growth factor-2 induces glial cell proliferation in the regenerating peripheral nervous system

    Directory of Open Access Journals (Sweden)

    Ribeiro-Resende Victor

    2012-07-01

    Full Text Available Abstract Background Among the essential biological roles of bone marrow-derived cells, secretion of many soluble factors is included and these small molecules can act upon specific receptors present in many tissues including the nervous system. Some of the released molecules can induce proliferation of Schwann cells (SC, satellite cells and lumbar spinal cord astrocytes during early steps of regeneration in a rat model of sciatic nerve transection. These are the major glial cell types that support neuronal survival and axonal growth following peripheral nerve injury. Fibroblast growth factor-2 (FGF-2 is the main mitogenic factor for SCs and is released in large amounts by bone marrow-derived cells, as well as by growing axons and endoneurial fibroblasts during development and regeneration of the peripheral nervous system (PNS. Results Here we show that bone marrow-derived cell treatment induce an increase in the expression of FGF-2 in the sciatic nerve, dorsal root ganglia and the dorsolateral (DL region of the lumbar spinal cord (LSC in a model of sciatic nerve transection and connection into a hollow tube. SCs in culture in the presence of bone marrow derived conditioned media (CM resulted in increased proliferation and migration. This effect was reduced when FGF-2 was neutralized by pretreating BMMC or CM with a specific antibody. The increased expression of FGF-2 was validated by RT-PCR and immunocytochemistry in co-cultures of bone marrow derived cells with sciatic nerve explants and regenerating nerve tissue respectivelly. Conclusion We conclude that FGF-2 secreted by BMMC strongly increases early glial proliferation, which can potentially improve PNS regeneration.

  8. Authentication Without Secrets

    Energy Technology Data Exchange (ETDEWEB)

    Pierson, Lyndon G. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Robertson, Perry J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-11-01

    This work examines a new approach to authentication, which is the most fundamental security primitive that underpins all cyber security protections. Current Internet authentication techniques require the protection of one or more secret keys along with the integrity protection of the algorithms/computations designed to prove possession of the secret without actually revealing it. Protecting a secret requires physical barriers or encryption with yet another secret key. The reason to strive for "Authentication without Secret Keys" is that protecting secrets (even small ones only kept in a small corner of a component or device) is much harder than protecting the integrity of information that is not secret. Promising methods are examined for authentication of components, data, programs, network transactions, and/or individuals. The successful development of authentication without secret keys will enable far more tractable system security engineering for high exposure, high consequence systems by eliminating the need for brittle protection mechanisms to protect secret keys (such as are now protected in smart cards, etc.). This paper is a re-release of SAND2009-7032 with new figures numerous edits.

  9. Radial glial cell transformation to astrocytes is bidirectional: regulation by a diffusible factor in embryonic forebrain.

    OpenAIRE

    Hunter, K E; Hatten, M E

    1995-01-01

    During development of mammalian cerebral cortex, two classes of glial cells are thought to underlie the establishment of cell patterning. In the embryonic period, migration of young neurons is supported by a system of radial glial cells spanning the thickness of the cortical wall. In the neonatal period, neuronal function is assisted by the physiological support of a second class of astroglial cell, the astrocyte. Here, we show that expression of embryonic radial glial identity requires extri...

  10. Neuroinflammation induces glial aromatase expression in the uninjured songbird brain

    Directory of Open Access Journals (Sweden)

    Saldanha Colin J

    2011-07-01

    Full Text Available Abstract Background Estrogens from peripheral sources as well as central aromatization are neuroprotective in the vertebrate brain. Under normal conditions, aromatase is only expressed in neurons, however following anoxic/ischemic or mechanical brain injury; aromatase is also found in astroglia. This increased glial aromatization and the consequent estrogen synthesis is neuroprotective and may promote neuronal survival and repair. While the effects of estradiol on neuroprotection are well studied, what induces glial aromatase expression remains unknown. Methods Adult male zebra finches (Taeniopygia guttata were given a penetrating injury to the entopallium. At several timepoints later, expression of aromatase, IL-1β-like, and IL-6-like were examined using immunohisotchemistry. A second set of zebra birds were exposed to phytohemagglutinin (PHA, an inflammatory agent, directly on the dorsal surface of the telencephalon without creating a penetrating injury. Expression of aromatase, IL-1β-like, and IL-6-like were examined using both quantitative real-time polymerase chain reaction to examine mRNA expression and immunohistochemistry to determine cellular expression. Statistical significance was determined using t-test or one-way analysis of variance followed by the Tukey Kramers post hoc test. Results Following injury in the zebra finch brain, cytokine expression occurs prior to aromatase expression. This temporal pattern suggests that cytokines may induce aromatase expression in the damaged zebra finch brain. Furthermore, evoking a neuroinflammatory response characterized by an increase in cytokine expression in the uninjured brain is sufficient to induce glial aromatase expression. Conclusions These studies are among the first to examine a neuroinflammatory response in the songbird brain following mechanical brain injury and to describe a novel neuroimmune signal to initiate aromatase expression in glia.

  11. Guanosine protects glial cells against 6-hydroxydopamine toxicity.

    Science.gov (United States)

    Giuliani, Patricia; Ballerini, Patrizia; Buccella, Silvana; Ciccarelli, Renata; Rathbone, Michel P; Romano, Silvia; D'Alimonte, Iolanda; Caciagli, Francesco; Di Iorio, Patrizia; Pokorski, Mieczyslaw

    2015-01-01

    Increasing body of evidence indicates that neuron-neuroglia interaction may play a key role in determining the progression of neurodegenerative diseases including Parkinson's disease (PD), a chronic pathological condition characterized by selective loss of dopaminergic (DA) neurons in the substantia nigra. We have previously reported that guanosine (GUO) antagonizes MPP(+)-induced cytotoxicity in neuroblastoma cells and exerts neuroprotective effects against 6-hydroxydopamine (6-OHDA) and beta-amyloid-induced apoptosis of SH-SY5Y cells. In the present study we demonstrate that GUO protected C6 glioma cells, taken as a model system for astrocytes, from 6-OHDA-induced neurotoxicity. We show that GUO, either alone or in combination with 6-OHDA activated the cell survival pathways ERK and PI3K/Akt. The involvement of these signaling systems in the mechanism of the nucleoside action was strengthened by a reduction of the protective effect when glial cells were pretreated with U0126 or LY294002, the specific inhibitors of MEK1/2 and PI3K, respectively. Since the protective effect on glial cell death of GUO was not affected by pretreatment with a cocktail of nucleoside transporter blockers, GUO transport and its intracellular accumulation were not at play in our in vitro model of PD. This fits well with our data which pointed to the presence of specific binding sites for GUO on rat brain membranes. On the whole, the results described in the present study, along with our recent evidence showing that GUO when administered to rats via intraperitoneal injection is able to reach the brain and with previous data indicating that it stimulates the release of neurotrophic factors, suggest that GUO, a natural compound, by acting at the glial level could be a promising agent to be tested against neurodegeneration. PMID:25310956

  12. Tubular Secretion in CKD.

    Science.gov (United States)

    Suchy-Dicey, Astrid M; Laha, Thomas; Hoofnagle, Andrew; Newitt, Rick; Sirich, Tammy L; Meyer, Timothy W; Thummel, Ken E; Yanez, N David; Himmelfarb, Jonathan; Weiss, Noel S; Kestenbaum, Bryan R

    2016-07-01

    Renal function generally is assessed by measurement of GFR and urinary albumin excretion. Other intrinsic kidney functions, such as proximal tubular secretion, typically are not quantified. Tubular secretion of solutes is more efficient than glomerular filtration and a major mechanism for renal drug elimination, suggesting important clinical consequences of secretion dysfunction. Measuring tubular secretion as an independent marker of kidney function may provide insight into kidney disease etiology and improve prediction of adverse outcomes. We estimated secretion function by measuring secreted solute (hippurate, cinnamoylglycine, p-cresol sulfate, and indoxyl sulfate) clearance using liquid chromatography-tandem mass spectrometric assays of serum and timed urine samples in a prospective cohort study of 298 patients with kidney disease. We estimated GFR by mean clearance of creatinine and urea from the same samples and evaluated associations of renal secretion with participant characteristics, mortality, and CKD progression to dialysis. Tubular secretion rate modestly correlated with eGFR and associated with some participant characteristics, notably fractional excretion of electrolytes. Low clearance of hippurate or p-cresol sulfate associated with greater risk of death independent of eGFR (hazard ratio, 2.3; 95% confidence interval, 1.1 to 4.7; hazard ratio, 2.5; 95% confidence interval, 1.0 to 6.1, respectively). Hazards models also suggested an association between low cinnamoylglycine clearance and risk of dialysis, but statistical analyses did not exclude the null hypothesis. Therefore, estimates of proximal tubular secretion function correlate with glomerular filtration, but substantial variability in net secretion remains. The observed associations of net secretion with mortality and progression of CKD require confirmation. PMID:26614381

  13. Giant Glial Cell: New Insight Through Mechanism-Based Modeling

    DEFF Research Database (Denmark)

    Postnov, D. E.; Ryazanova, L. S.; Brazhe, Nadezda;

    2008-01-01

    The paper describes a detailed mechanism-based model of a tripartite synapse consisting of P- and R-neurons together with a giant glial cell in the ganglia of the medical leech (Hirudo medicinalis), which is a useful object for experimental studies in situ. We describe the two main pathways of the...... establishing the positive feedback in glutamate release that is critical for the self-sustained activity of the postsynaptic neuron. This mechanism differs from the mechanisms of the astrocyte-neuron signaling previously reported....

  14. Diffusion tensor magnetic resonance imaging of glial brain tumors

    International Nuclear Information System (INIS)

    Aim: To evaluate the author's experience with the use of diffusion tensor magnetic resonance imaging (DTI) on patients with glial tumors. Methods: A retrospective evaluation of a group of 24 patients with glial tumors was performed. There were eight patients with Grade II, eight patients with Grade III and eight patients with Grade IV tumors with a histologically proven diagnosis. All the patients underwent routine imaging including T2 weighted images, multidirectional diffusion weighted imaging (measured in 60 non-collinear directions) and T1 weighted non-enhanced and contrast enhanced images. The imaging sequence and evaluation software were produced by Massachusetts General Hospital Corporation (Boston, MA, USA). Fractional anisotropy (FA) maps were calculated in all patients. The white matter FA changes were assessed within the tumorous tissue, on the tumorous borderline and in the normally appearing white matter adjacent to the tumor. A three-dimensional model of the white matter tract was created to demonstrate the space relationship of the tumor and the capsula interna or corpus callosum in each case using the following fiber tracing parameters: FA step 0.25 and a tensor declination angle of 45 gr. An additional assessment of the tumorous tissue enhancement was performed. Results: A uniform homogenous structure with sharp demargination of the Grade II tumors and the wide rim of the intermedial FA in all Grade III tumors respectively, were found during the evaluation of the FA maps. In Grade IV tumors a variable demargination was noted on the FA maps. The sensitivity and specificity for the discrimination of low- and high-grade glial tumors using FA maps was revealed to be 81% and 87% respectively. If the evaluation of the contrast enhancement was combined with the evaluation of the FA maps, both sensitivity and specificity were 100%. Conclusion: Although the evaluation of the fractional anisotropy maps is not sufficient for glioma grading, the combination of

  15. Diffusion tensor magnetic resonance imaging of glial brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Ferda, Jiri, E-mail: ferda@fnplzen. [Department of Radiology, Charles University Hospital Plzen, Medical Faculty Plzen, Alej Svobody 80, 304 60 Plzen (Czech Republic); Kastner, Jan [Department of Radiology, Charles University Hospital Plzen, Medical Faculty Plzen, Alej Svobody 80, 304 60 Plzen (Czech Republic); Mukensnabl, Petr [Sikl' s Institute of Pathological Anatomy, Charles University Hospital Plzen, Medical Faculty Plzen, Alej Svobody 80, 304 60 Plzen (Czech Republic); Choc, Milan [Department of Neurosurgery, Charles University Hospital Plzen, Medical Faculty Plzen, Alej Svobody 80, 304 60 Plzen (Czech Republic); Horemuzova, Jana; Ferdova, Eva; Kreuzberg, Boris [Department of Radiology, Charles University Hospital Plzen, Medical Faculty Plzen, Alej Svobody 80, 304 60 Plzen (Czech Republic)

    2010-06-15

    Aim: To evaluate the author's experience with the use of diffusion tensor magnetic resonance imaging (DTI) on patients with glial tumors. Methods: A retrospective evaluation of a group of 24 patients with glial tumors was performed. There were eight patients with Grade II, eight patients with Grade III and eight patients with Grade IV tumors with a histologically proven diagnosis. All the patients underwent routine imaging including T2 weighted images, multidirectional diffusion weighted imaging (measured in 60 non-collinear directions) and T1 weighted non-enhanced and contrast enhanced images. The imaging sequence and evaluation software were produced by Massachusetts General Hospital Corporation (Boston, MA, USA). Fractional anisotropy (FA) maps were calculated in all patients. The white matter FA changes were assessed within the tumorous tissue, on the tumorous borderline and in the normally appearing white matter adjacent to the tumor. A three-dimensional model of the white matter tract was created to demonstrate the space relationship of the tumor and the capsula interna or corpus callosum in each case using the following fiber tracing parameters: FA step 0.25 and a tensor declination angle of 45 gr. An additional assessment of the tumorous tissue enhancement was performed. Results: A uniform homogenous structure with sharp demargination of the Grade II tumors and the wide rim of the intermedial FA in all Grade III tumors respectively, were found during the evaluation of the FA maps. In Grade IV tumors a variable demargination was noted on the FA maps. The sensitivity and specificity for the discrimination of low- and high-grade glial tumors using FA maps was revealed to be 81% and 87% respectively. If the evaluation of the contrast enhancement was combined with the evaluation of the FA maps, both sensitivity and specificity were 100%. Conclusion: Although the evaluation of the fractional anisotropy maps is not sufficient for glioma grading, the

  16. Dynamic quantum secret sharing

    International Nuclear Information System (INIS)

    In this Letter we consider quantum secret sharing (QSS) between a sender and a dynamic agent group, called dynamic quantum secret sharing (DQSS). In the DQSS, the change of the agent group is allowable during the procedure of sharing classical and quantum information. Two DQSS schemes are proposed based on a special kind of entangled state, starlike cluster states. Without redistributing all the shares, the changed agent group can reconstruct the sender's secret by their cooperation. Compared with the previous quantum secret sharing scheme, our schemes are more flexible and suitable for practical applications. -- Highlights: ► We consider quantum secret sharing between a sender and a dynamic agent group, called dynamic quantum secret sharing (DQSS). ► In the DQSS, the change of the agent group is allowable during the procedure of sharing classical and quantum information. ► Two DQSS schemes are proposed based on a special kind of entangled state, starlike cluster states. ► Without redistributing all the shares, the changed agent group can reconstruct the sender's secret by their cooperation. ► Compared with the previous quantum secret sharing scheme, our schemes are more flexible and suitable for practical applications.

  17. CiMT-1, an unusual chordate metallothionein gene in Ciona intestinalis genome: structure and expression studies.

    Science.gov (United States)

    Franchi, Nicola; Boldrin, Francesco; Ballarin, Loriano; Piccinni, Ester

    2011-02-01

    The present article reports on the characterization of the urochordate metallothionein (MT) gene, CiMT-1, from the solitary ascidian Ciona intestinalis. The predicted protein is shorter than other known deuterostome MTs, having only 39 amino acids. The gene has the same tripartite structure as vertebrate MTs, with some features resembling those of echinoderm MTs. The promoter region shows the canonical cis-acting elements recognized by transcription factors that respond to metal, ROS, and cytokines. Unusual sequences, described in fish and echinoderms, are also present. In situ hybridization suggests that only a population of hemocytes involved in immune responses, i.e. granular amebocytes, express CiMT-1 mRNA. These observations support the idea that urochordates perform detoxification through hemocytes, and that MTs may play important roles in inflammatory humoral responses in tunicates. The reported data offer new clues for better understanding the evolution of these multivalent proteins from non-vertebrate to vertebrate chordates and reinforce their functions in detoxification and immunity. PMID:21328559

  18. A Mathematical Model of Regenerative Axon Growing along Glial Scar after Spinal Cord Injury

    Science.gov (United States)

    Chen, Xuning; Zhu, Weiping

    2016-01-01

    A major factor in the failure of central nervous system (CNS) axon regeneration is the formation of glial scar after the injury of CNS. Glial scar generates a dense barrier which the regenerative axons cannot easily pass through or by. In this paper, a mathematical model was established to explore how the regenerative axons grow along the surface of glial scar or bypass the glial scar. This mathematical model was constructed based on the spinal cord injury (SCI) repair experiments by transplanting Schwann cells as bridge over the glial scar. The Lattice Boltzmann Method (LBM) was used in this model for three-dimensional numerical simulation. The advantage of this model is that it provides a parallel and easily implemented algorithm and has the capability of handling complicated boundaries. Using the simulated data, two significant conclusions were made in this study: (1) the levels of inhibitory factors on the surface of the glial scar are the main factors affecting axon elongation and (2) when the inhibitory factor levels on the surface of the glial scar remain constant, the longitudinal size of the glial scar has greater influence on the average rate of axon growth than the transverse size. These results will provide theoretical guidance and reference for researchers to design efficient experiments.

  19. Glial heterotopia in head and neck, single center experience of 5 cases

    Directory of Open Access Journals (Sweden)

    Ramyapriyadarshini Arikeri

    2016-07-01

    Conclusions: Glial Heterotopias of head and neck are more common in the nasal cavity. Middle ear Glial heterotopias are very rare. Clinical and radiological findings along with histopathology and immuno-histochemistry are essential in diagnosing these lesions. [Int J Res Med Sci 2016; 4(7.000: 3009-3012

  20. Incretin secretion: direct mechanisms

    DEFF Research Database (Denmark)

    Balk-Møller, Emilie; Holst, Jens Juul; Kuhre, Rune Ehrenreich

    2014-01-01

    The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are secreted from gastro-intestinal K- and L-cells, respectively, and play an important role in post-prandial blood glucose regulation. They do this by direct stimulation of the pancreatic β...... enzyme responsible for incretin degradation (dipeptidyl peptidase-4) is inhibited (drugs are already on the market) while the secretion of endogenous GLP-1 secretion is stimulated at the same time may prove particularly rewarding. In this section we review current knowledge on the mechanisms for direct...

  1. Morphological alterations in radial glial cells following brain injury in fetal mice

    Energy Technology Data Exchange (ETDEWEB)

    Sun Xuezhi; Inouye, Minoru; Hayasaka, Shizu; Takagishi, Yoshiko; Yamamura, Hideki [Nagoya Univ. (Japan). Research Inst. of Environmental Medicine

    1995-10-01

    A glia cell population extracted from the developing brain of mice exposed to {gamma}-irradiation at a dose of 1.0 Gy on embryonic day 13 (E13) was evaluated. An immunohistochemical detection method for the anti-GFAP (glial fibrillary acidic protein) anti-body showed that the GFAP-immunoreactive fibers first appeared on E18. These radial glial fibers ran straight to the pial surface in the control, but were crumpled in the irradiated brain samples. Although some radial glial cells transformed into astrocytes over time in both the control and irradiated brains, astrocytes appeared in the irradiated brain earlier than in the control. These findings indicate that 1.0 Gy {gamma}-irradiation causes radial glial fibers to crumple and could affect the transformation process whereby radial glial cells develop into astrocytes. (author).

  2. Honeybee retinal glial cells transform glucose and supply the neurons with metabolic substrate

    International Nuclear Information System (INIS)

    The retina of the honeybee drone is a nervous tissue in which glial cells and photoreceptor cells (sensory neurons) constitute two distinct metabolic compartments. Retinal slices incubated with 2-deoxy[3H]glucose convert this glucose analogue to 2-deoxy[3H]glucose 6-phosphate, but this conversion is made only in the glial cells. Hence, glycolysis occurs only in glial cells. In contrast, the neurons consume O2 and this consumption is sustained by the hydrolysis of glycogen, which is contained in large amounts in the glia. During photostimulation the increased oxidative metabolism of the neurons is sustained by a higher supply of carbohydrates from the glia. This clear case of metabolic interaction between neurons and glial cells supports Golgi's original hypothesis, proposed nearly 100 years ago, about the nutritive function of glial cells in the nervous system

  3. Morphological alterations in radial glial cells following brain injury in fetal mice

    International Nuclear Information System (INIS)

    A glia cell population extracted from the developing brain of mice exposed to γ-irradiation at a dose of 1.0 Gy on embryonic day 13 (E13) was evaluated. An immunohistochemical detection method for the anti-GFAP (glial fibrillary acidic protein) anti-body showed that the GFAP-immunoreactive fibers first appeared on E18. These radial glial fibers ran straight to the pial surface in the control, but were crumpled in the irradiated brain samples. Although some radial glial cells transformed into astrocytes over time in both the control and irradiated brains, astrocytes appeared in the irradiated brain earlier than in the control. These findings indicate that 1.0 Gy γ-irradiation causes radial glial fibers to crumple and could affect the transformation process whereby radial glial cells develop into astrocytes. (author)

  4. Peripheral nerve injury induces glial activation in primary motor cortex

    Directory of Open Access Journals (Sweden)

    Julieta Troncoso

    2015-02-01

    Full Text Available Preliminary evidence suggests that peripheral facial nerve injuries are associated with sensorimotor cortex reorganization. We have characterized facial nerve lesion-induced structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with glial cell density using a rodent facial paralysis model. First, we used adult transgenic mice expressing green fluorescent protein in microglia and yellow fluorescent protein in pyramidal neurons which were subjected to either unilateral lesion of the facial nerve or sham surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1. It was found that facial nerve lesion induced long-lasting changes in dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Pyramidal cells’ dendritic arborization underwent overall shrinkage and transient spine pruning. Moreover, microglial cell density surrounding vM1 layer 5 pyramidal neurons was significantly increased with morphological bias towards the activated phenotype. Additionally, we induced facial nerve lesion in Wistar rats to evaluate the degree and extension of facial nerve lesion-induced reorganization processes in central nervous system using neuronal and glial markers. Immunoreactivity to NeuN (neuronal nuclei antigen, GAP-43 (growth-associated protein 43, GFAP (glial fibrillary acidic protein, and Iba 1 (Ionized calcium binding adaptor molecule 1 were evaluated 1, 3, 7, 14, 28 and 35 days after either unilateral facial nerve lesion or sham surgery. Patches of decreased NeuN immunoreactivity were found bilaterally in vM1 as well as in primary somatosensory cortex (CxS1. Significantly increased GAP-43 immunoreactivity was found bilaterally after the lesion in hippocampus, striatum, and sensorimotor cortex. One day after lesion GFAP immunoreactivity increased bilaterally in hippocampus, subcortical white

  5. Les mots du secret

    OpenAIRE

    Delage, Agnès

    2016-01-01

    Cet article analyse les reconfigurations sémantiques du lexique et des mots du secret en usage dans l’Europe du Sud entre le Moyen Âge et l’époque moderne. En partant des approches récentes du secret et de la dissimulation dans un contexte contemporain de revendication d’un « droit au secret », nous analysons comment l’historiographie actuelle des XVIe et XVIIe siècles aborde une histoire longue des régimes de positivité du secret en Europe. En partant de l’époque pré-moderne, nous étudions l...

  6. Pratiques du secret

    OpenAIRE

    BORELLO, Céline; Domont, Stéphanie; Estier, Delphine; Kaiser, Wolfgang; Le Person, Xavier; Montenach, Anne

    2006-01-01

    Le secret et la dissimulation sont, à l’époque moderne (et bien au-delà), au cœur d’une vaste réflexion savante sur l’art de gouverner et sur la conduite adaptée à la vie en société. Les études rassemblées ici ne considèrent le secret ni comme une vérité cachée – les arcana imperii – ni comme une qualité transcendante – les mystères de l’État. Elles mettent l’accent sur les pratiques et les usages du secret, sur le secret social comme mode d’agir. Elles montrent par là que le discours sur le ...

  7. Sox2 promotes survival of satellite glial cells in vitro

    International Nuclear Information System (INIS)

    Sox2 is a transcriptional factor expressed in neural stem cells. It is known that Sox2 regulates cell differentiation, proliferation and survival of the neural stem cells. Our previous study showed that Sox2 is expressed in all satellite glial cells of the adult rat dorsal root ganglion. In this study, to examine the role of Sox2 in satellite glial cells, we establish a satellite glial cell-enriched culture system. Our culture method succeeded in harvesting satellite glial cells with the somata of neurons in the dorsal root ganglion. Using this culture system, Sox2 was downregulated by siRNA against Sox2. The knockdown of Sox2 downregulated ErbB2 and ErbB3 mRNA at 2 and 4 days after siRNA treatment. MAPK phosphorylation, downstream of ErbB, was also inhibited by Sox2 knockdown. Because ErbB2 and ErbB3 are receptors that support the survival of glial cells in the peripheral nervous system, apoptotic cells were also counted. TUNEL-positive cells increased at 5 days after siRNA treatment. These results suggest that Sox2 promotes satellite glial cell survival through the MAPK pathway via ErbB receptors. - Highlights: • We established satellite glial cell culture system. • Function of Sox2 in satellite glial cell was examined using siRNA. • Sox2 knockdown downregulated expression level of ErbB2 and ErbB3 mRNA. • Sox2 knockdown increased apoptotic satellite glial cell. • Sox2 promotes satellite glial cell survival through ErbB signaling

  8. Sox2 promotes survival of satellite glial cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Koike, Taro, E-mail: koiket@hirakata.kmu.ac.jp; Wakabayashi, Taketoshi; Mori, Tetsuji; Hirahara, Yukie; Yamada, Hisao

    2015-08-14

    Sox2 is a transcriptional factor expressed in neural stem cells. It is known that Sox2 regulates cell differentiation, proliferation and survival of the neural stem cells. Our previous study showed that Sox2 is expressed in all satellite glial cells of the adult rat dorsal root ganglion. In this study, to examine the role of Sox2 in satellite glial cells, we establish a satellite glial cell-enriched culture system. Our culture method succeeded in harvesting satellite glial cells with the somata of neurons in the dorsal root ganglion. Using this culture system, Sox2 was downregulated by siRNA against Sox2. The knockdown of Sox2 downregulated ErbB2 and ErbB3 mRNA at 2 and 4 days after siRNA treatment. MAPK phosphorylation, downstream of ErbB, was also inhibited by Sox2 knockdown. Because ErbB2 and ErbB3 are receptors that support the survival of glial cells in the peripheral nervous system, apoptotic cells were also counted. TUNEL-positive cells increased at 5 days after siRNA treatment. These results suggest that Sox2 promotes satellite glial cell survival through the MAPK pathway via ErbB receptors. - Highlights: • We established satellite glial cell culture system. • Function of Sox2 in satellite glial cell was examined using siRNA. • Sox2 knockdown downregulated expression level of ErbB2 and ErbB3 mRNA. • Sox2 knockdown increased apoptotic satellite glial cell. • Sox2 promotes satellite glial cell survival through ErbB signaling.

  9. Efficient quantum secret sharing

    Science.gov (United States)

    Qin, Huawang; Dai, Yuewei

    2016-05-01

    An efficient quantum secret sharing scheme is proposed, in which the dealer generates some single particles and then uses the operations of quantum-controlled-not and Hadamard gate to encode a determinate secret into these particles. The participants get their shadows by performing the single-particle measurements on their particles, and even the dealer cannot know their shadows. Compared to the existing schemes, our scheme is more practical within the present technologies.

  10. Secrets of Pawnless Endings

    OpenAIRE

    Haworth, Guy McCrossan

    2002-01-01

    It is now 32 years since Ströhlein’s pioneering computation of KRKN and ten years since the publication of Nunn’s Secrets of Rook Endings. This book defined a new genre under his authorship and editorship (Nunn, 1992, 1994, 1995; Müller and Lamprecht, 1999, 2001) and has merited a second edition. Now comes the second edition of Secrets of Pawnless Endings.

  11. How do glial cells contribute to motor control?

    DEFF Research Database (Denmark)

    Christensen, Rasmus Kordt; Petersen, Anders Victor; Perrier, Jean-Francois Marie

    2013-01-01

    activated by neurotransmitters during synaptic transmission. In turn they release other transmitters - called gliotransmitters - that bind to neuronal receptors and modulate synaptic transmission. This feedback, which led to the concept of the tripartite synapse, has been reported with various transmitters...... glia play an active role in several physiological functions. The discovery that a bidirectional communication takes place between astrocytes (the star shaped glial cell of the brain) and neurons, was a major breakthrough in the field of synaptic physiology. Astrocytes express receptors that get...... including glutamate, ATP, GABA or serine. In the present review we will focus on astrocytes and review the evidence suggesting and demonstrating their role in motor control. Rhythmic motor behaviors such as locomotion, swimming or chewing are generated by networks of neurons termed central pattern...

  12. Cytotoxic effects of catechols to glial and neuronal cells

    Directory of Open Access Journals (Sweden)

    Ramon Santos El-Bachá

    2015-04-01

    Full Text Available Catechols are compounds that autoxidises under physiological conditions leading to the formation of reactive oxygen species (ROS, semiquinones, and quinones. These molecules can be formed in organisms because of the metabolism of exogenous aromatic substances, such as benzene. However, there are several important endogenous catechols, which have physiological functions, such as catecholamines. Furthermore, several pharmacological agents are catechols, such as apomorphine, or can be metabolised to generate these compounds. In this presentation we will show that apomorphine can unspecifically bind to proteins during its autoxidation, a phenomenon that is inhibited by thiols. Brain endothelial cells and glial cells express xenobiotic-metabolising enzymes as components of the metabolic blood-brain barrier in an attempt to protect the central nervous system against drugs. Since UDP-glucuronosyltransferases (EC 2.4.1.17 are among these enzymes, we investigated the ability of brain microsomes to conjugate catechols with glucuronate. Despite the fact that 1-naphtol could be glucuronidated in the presence of brain cortex microsomes, the same was not observed for most of catechols that were tested. Therefore, this is not the main mechanism used to protect the brain against them. Indeed, catechols may inhibit other xenobiotic-metabolising enzymes. We showed that apomorphine inhibited the cytochrome P450-dependent dealkylation activity. The production of ROS and reactive quinones, as well as their effects on protein functions, seems to be involved in the cytotoxicity of catechols. Glial cells are more resistant than neuronal cells. Apomorphine was more toxic to rat neurons than to rat C6 glioma cells. 1,2-Dihydroxybenzene (catechol killed human GL-15 cells with an EC50 of 230 uM after 72 h, a effect that was significantly inhibited by superoxide dismutase (EC 1.15.1.1. Another mechanism that we found to be involved in catechol cytotoxicity is the inhibition

  13. DMPD: Multifunctional effects of bradykinin on glial cells in relation to potentialanti-inflammatory effects. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17669557 Multifunctional effects of bradykinin on glial cells in relation to potent... Epub 2007 Jun 27. (.png) (.svg) (.html) (.csml) Show Multifunctional effects of bradykinin on glial cells in relation to poten...nctional effects of bradykinin on glial cells in relation to potentialanti-inflammatory effects. Authors Nod

  14. Depression as a Glial-Based Synaptic Dysfunction.

    Science.gov (United States)

    Rial, Daniel; Lemos, Cristina; Pinheiro, Helena; Duarte, Joana M; Gonçalves, Francisco Q; Real, Joana I; Prediger, Rui D; Gonçalves, Nélio; Gomes, Catarina A; Canas, Paula M; Agostinho, Paula; Cunha, Rodrigo A

    2015-01-01

    Recent studies combining pharmacological, behavioral, electrophysiological and molecular approaches indicate that depression results from maladaptive neuroplastic processes occurring in defined frontolimbic circuits responsible for emotional processing such as the prefrontal cortex, hippocampus, amygdala and ventral striatum. However, the exact mechanisms controlling synaptic plasticity that are disrupted to trigger depressive conditions have not been elucidated. Since glial cells (astrocytes and microglia) tightly and dynamically interact with synapses, engaging a bi-directional communication critical for the processing of synaptic information, we now revisit the role of glial cells in the etiology of depression focusing on a dysfunction of the "quad-partite" synapse. This interest is supported by the observations that depressive-like conditions are associated with a decreased density and hypofunction of astrocytes and with an increased microglia "activation" in frontolimbic regions, which is expected to contribute for the synaptic dysfunction present in depression. Furthermore, the traditional culprits of depression (glucocorticoids, biogenic amines, brain-derived neurotrophic factor, BDNF) affect glia functioning, whereas antidepressant treatments (serotonin-selective reuptake inhibitors, SSRIs, electroshocks, deep brain stimulation) recover glia functioning. In this context of a quad-partite synapse, systems modulating glia-synapse bidirectional communication-such as the purinergic neuromodulation system operated by adenosine 5'-triphosphate (ATP) and adenosine-emerge as promising candidates to "re-normalize" synaptic function by combining direct synaptic effects with an ability to also control astrocyte and microglia function. This proposed triple action of purines to control aberrant synaptic function illustrates the rationale to consider the interference with glia dysfunction as a mechanism of action driving the design of future pharmacological tools to

  15. Depression as a Glial-Based Synaptic Dysfunction

    Directory of Open Access Journals (Sweden)

    Daniel eRial

    2016-01-01

    Full Text Available Recent studies combining pharmacological, behavioral, electrophysiological and molecular approaches indicate that depression results from maladaptive neuroplastic processing occurring in defined frontolimbic circuits responsible for emotional processing such as the prefrontal cortex, hippocampus, amygdala and ventral striatum. However, the exact mechanisms controlling synaptic plasticity that are disrupted to trigger depressive conditions have not been elucidated. Since glial cells (astrocytes and microglia tightly and dynamically interact with synapses, engaging a bi-directional communication critical for the processing of synaptic information, we now revisit the role of glial cells in the etiology of depression focusing on a dysfunction of the ‘quad-partite’ synapse. This interest is supported by the observations that depressive-like conditions are associated with a decreased density and hypofunction of astrocytes and with an increase microglia ‘activation’ in frontolimbic regions, which is expected to contribute for the synaptic dysfunction present in depression. Furthermore, the traditional culprits of depression (glucocorticoids, biogenic amines, BDNF affect glia functioning, whereas antidepressant treatments (SSRIs, electroshock, deep brain stimulation recover glia functioning. In this context of a quad-partite synapse, systems modulating glia-synapse bidirectional communication - such as the purinergic neuromodulation system operated by ATP and adenosine - emerge as promising candidates to re-normalize synaptic function by combining direct synaptic effects with an ability to also control astrocyte and microglia function. This proposed triple action of purines to control aberrant synaptic function illustrates the rationale to consider the interference with glia dysfunction as a mechanism of action driving the design of future pharmacological tools to manage depression.

  16. The significance of Ciona intestinalis as a stem organism in integrative studies of functional evolution of the chordate endocrine, neuroendocrine, and nervous systems.

    Science.gov (United States)

    Matsubara, Shin; Kawada, Tsuyoshi; Sakai, Tsubasa; Aoyama, Masato; Osugi, Tomohiro; Shiraishi, Akira; Satake, Honoo

    2016-02-01

    Ascidians are the closest phylogenetic neighbors to vertebrates and are believed to conserve the evolutionary origin in chordates of the endocrine, neuroendocrine, and nervous systems involving neuropeptides and peptide hormones. Ciona intestinalis harbors various homologs or prototypes of vertebrate neuropeptides and peptide hormones including gonadotropin-releasing hormones (GnRHs), tachykinins (TKs), and calcitonin, as well as Ciona-specific neuropeptides such as Ciona vasopressin, LF, and YFV/L peptides. Moreover, molecular and functional studies on Ciona tachykinin (Ci-TK) have revealed the novel molecular mechanism of inducing oocyte growth via up-regulation of vitellogenesis-associated protease activity, which is expected to be conserved in vertebrates. Furthermore, a series of studies on Ciona GnRH receptor paralogs have verified the species-specific regulation of GnRHergic signaling including unique signaling control via heterodimerization among multiple GnRH receptors. These findings confirm the remarkable significance of ascidians in investigations of the evolutionary processes of the peptidergic systems in chordates, leading to the promising advance in the research on Ciona peptides in the next stage based on the recent development of emerging technologies including genome-editing techniques, peptidomics-based multi-color staining, machine-learning prediction, and next-generation sequencing. These technologies and bioinformatic integration of the resultant "multi-omics" data will provide unprecedented insights into the comprehensive understanding of molecular and functional regulatory mechanisms of the Ciona peptides, and will eventually enable the exploration of both conserved and diversified endocrine, neuroendocrine, and nervous systems in the evolutionary lineage of chordates. PMID:26031189

  17. Photoresponse and Learning Behavior of Ascidian Larvae, a Primitive Chordate, to Repeated Stimuli of Step-Up and Step-Down of Light

    OpenAIRE

    Kawakami, I.; Shiraishi, S; Tsuda, M

    2002-01-01

    Ascidians are lower chordates and their simple tadpole-like larvae share a basic body plan with vertebrates. Newly hatched larvae show no response to a stimulus of light. 4 h after hatching, the larvae were induced to swim upon a step-down of light and stop swimming upon a step-up of light. At weaker intensity of light, the larvae show the same response to a stimulus after presentation of repeated stimuli. When intensity of actinic light was increased, the larvae show sensitization and habitu...

  18. Pax2/5/8 and Pax6 alternative splicing events in basal chordates and vertebrates: a focus on paired box domain

    OpenAIRE

    Fabian, Peter; Kozmikova, Iryna; Kozmik, Zbynek; Pantzartzi, Chrysoula N.

    2015-01-01

    Paired box transcription factors play important role in development and tissue morphogenesis. The number of Pax homologs varies among species studied so far, due to genome and gene duplications that have affected PAX family to a great extent. Based on sequence similarity and functional domains, four Pax classes have been identified in chordates, namely Pax1/9, Pax2/5/8, Pax3/7, and Pax4/6. Numerous splicing events have been reported mainly for Pax2/5/8 and Pax6 genes. Of significant interest ...

  19. Bronchial secretion concentrations of tobramycin.

    Science.gov (United States)

    Alexander, M R; Schoell, J; Hicklin, G; Kasik, J E; Coleman, D

    1982-02-01

    The mean concentrations of tobramycin in bronchial secretions from patients with pneumonia were almost two times greater than secretions from patients free of lung infection. Mean tobramycin bronchial secretion to serum concentration ratios also were higher when obtained from infected lungs (0.66 versus 0.17) These data suggest that lung infection enhances the concentrations of tobramycin in bronchial secretions. PMID:7065524

  20. Reflecting the secret

    Directory of Open Access Journals (Sweden)

    Krstić Predrag

    2007-01-01

    Full Text Available Parallel analysis of children's literature on one hand, and the crime genre on the other, positing children's and serious construction of the world and ego, outlining homology of their narrative and reconstructing social construct that follows, assumes that light could be thrown at certain particularity that is a parasite on a host whom it would like to legitimate. Juxtaposition of the two worlds, or, often, the world whiten the world visualizes the image, an inward tension and perversion of the world for which the attraction of secret service with an aspiration to public action makes it particular. The established analogy directs the attention at two points that mark particularity of the world of secrets: the protocol of the concealment and secret action and to the motives for shifting, compounding and acquiring the identity that follows.

  1. Ovarian tumors secreting insulin.

    Science.gov (United States)

    Battocchio, Marialberta; Zatelli, Maria Chiara; Chiarelli, Silvia; Trento, Mariangela; Ambrosio, Maria Rosaria; Pasquali, Claudio; De Carlo, Eugenio; Dassie, Francesca; Mioni, Roberto; Rebellato, Andrea; Fallo, Francesco; Degli Uberti, Ettore; Martini, Chiara; Vettor, Roberto; Maffei, Pietro

    2015-08-01

    Combined ovarian germ cell and neuroendocrine tumors are rare. Only few cases of hyperinsulinism due to ovarian ectopic secretion have been hypothesized in the literature. An ovarian tumor was diagnosed in a 76-year-old woman, referred to our department for recurrent hypoglycemia with hyperinsulinism. In vivo tests, in particular fasting test, rapid calcium infusion test, and Octreotide test were performed. Ectopic hyperinsulinemic hypoglycemia was demonstrated in vivo and hypoglycemia disappeared after hysteroadnexectomy. Histological exam revealed an ovarian germ cell tumor with neuroendocrine and Yolk sac differentiation, while immunostaining showed insulin positivity in neuroendocrine cells. A cell culture was obtained by tumoral cells, testing Everolimus, and Pasireotide. Insulin was detected in cell culture medium and Everolimus and Pasireotide demonstrated their potentiality in reducing insulin secretion, more than controlling cell viability. Nine cases of hyperinsulinism due to ovarian ectopic secretion reported in literature have been reviewed. These data confirm the ovarian tissue potentiality to induce hyperinsulinemic hypoglycemic syndrome after neoplastic transformation. PMID:25896552

  2. Characterization of bbtTICAM from amphioxus suggests the emergence of a MyD88-independent pathway in basal chordates

    Institute of Scientific and Technical Information of China (English)

    ManyiYang; ShaochunYuan; Shengfeng Huang; Jun Li; Liqun Xu; Huiqing Huang; Xin Tao; Jian peng; Anlong Xu

    2011-01-01

    The MyD88-independent pathway,one of the two crucial TLR signaling routes,Is thought to be a vertebrate innovation.However,a novel Toll/interleukin-1 receptor (TIR) adaptor,designated bbtTICAM,which was identified in the basal chordate amphioxus,links this pathway to invertebrates.The protein architecture of bbtTICAM is similar to that of vertebrate TICAM1 (TIR-containing adaptor molecule-1,also known as TRIF),while phylogenetic analysis based on the TIR domain indicated that bbtTICAM is the oldest ortholog of vertebrate TICAMI and TICAM2(TIR-containing adaptor molecule-2,also known as TRAM).Similar to human TICAM1,bbtTICAM activates NF-κB in a MyD88-independent manner by interacting with receptor interacting protein (RIP) via its RHIM motif.Such activation requires bbtTICAM to form homodimers in endosomes,and it may be negatively regulated by amphioxus SARM (sterile a and armadillo motif-containing protein) and TRAF2.However,bbtTICAM did not induce the production of type I interferon.Thus,our study not only presents the ancestral features of vertebrate TICAM I and TICAM2,but also reveals the evolutionary origin of the MyD88-independent pathway from basal chordates,which will aid in understanding the development of the vertebrate TLR network.

  3. Retinoic acid signaling targets Hox genes during the amphioxus gastrula stage: insights into early anterior-posterior patterning of the chordate body plan.

    Science.gov (United States)

    Koop, Demian; Holland, Nicholas D; Sémon, Marie; Alvarez, Susana; de Lera, Angel Rodriguez; Laudet, Vincent; Holland, Linda Z; Schubert, Michael

    2010-02-01

    Previous studies of vertebrate development have shown that retinoic acid (RA) signaling at the gastrula stage strongly influences anterior-posterior (A-P) patterning of the neurula and later stages. However, much less is known about the more immediate effects of RA signaling on gene transcription and developmental patterning at the gastrula stage. To investigate the targets of RA signaling during the gastrula stage, we used the basal chordate amphioxus, in which gastrulation involves very minimal tissue movements. First, we determined the effect of altered RA signaling on expression of 42 genes (encoding transcription factors and components of major signaling cascades) known to be expressed in restricted domains along the A-P axis during the gastrula and early neurula stage. Of these 42 genes, the expression domains during gastrulation of only four (Hox1, Hox3, HNF3-1 and Wnt3) were spatially altered by exposure of the embryos to excess RA or to the RA antagonist BMS009. Moreover, blocking protein synthesis with puromycin before adding RA or BMS009 showed that only three of these genes (Hox1, Hox3 and HNF3-1) are direct RA targets at the gastrula stage. From these results we conclude that in the amphioxus gastrula RA signaling primarily acts via regulation of Hox transcription to establish positional identities along the A-P axis and that Hox1, Hox3, HNF3-1 and Wnt3 constitute a basal module of RA action during chordate gastrulation. PMID:19914237

  4. Glutathione-Induced Calcium Shifts in Chick Retinal Glial Cells.

    Science.gov (United States)

    Freitas, Hercules R; Ferraz, Gabriel; Ferreira, Gustavo C; Ribeiro-Resende, Victor T; Chiarini, Luciana B; do Nascimento, José Luiz M; Matos Oliveira, Karen Renata H; Pereira, Tiago de Lima; Ferreira, Leonardo G B; Kubrusly, Regina C; Faria, Robson X; Herculano, Anderson Manoel; Reis, Ricardo A de Melo

    2016-01-01

    Neuroglia interactions are essential for the nervous system and in the retina Müller cells interact with most of the neurons in a symbiotic manner. Glutathione (GSH) is a low-molecular weight compound that undertakes major antioxidant roles in neurons and glia, however, whether this compound could act as a signaling molecule in neurons and/or glia is currently unknown. Here we used embryonic avian retina to obtain mixed retinal cells or purified Müller glia cells in culture to evaluate calcium shifts induced by GSH. A dose response curve (0.1-10 mM) showed that 5-10 mM GSH, induced calcium shifts exclusively in glial cells (later labeled and identified as 2M6 positive cells), while neurons responded to 50 mM KCl (labeled as βIII tubulin positive cells). BBG 100 nM, a P2X7 blocker, inhibited the effects of GSH on Müller glia. However, addition of DNQX 70 μM and MK-801 20 μM, non-NMDA and NMDA blockers, had no effect on GSH calcium induced shift. Oxidized glutathione (GSSG) at 5 mM failed to induce calcium mobilization in glia cells, indicating that the antioxidant and/or structural features of GSH are essential to promote elevations in cytoplasmic calcium levels. Indeed, a short GSH pulse (60s) protects Müller glia from oxidative damage after 30 min of incubation with 0.1% H2O2. Finally, GSH induced GABA release from chick embryonic retina, mixed neuron-glia or from Müller cell cultures, which were inhibited by BBG or in the absence of sodium. GSH also induced propidium iodide uptake in Müller cells in culture in a P2X7 receptor dependent manner. Our data suggest that GSH, in addition to antioxidant effects, could act signaling calcium shifts at the millimolar range particularly in Müller glia, and could regulate the release of GABA, with additional protective effects on retinal neuron-glial circuit. PMID:27078878

  5. [Glial cells are involved in iron accumulation and degeneration of dopamine neurons in Parkinson's disease].

    Science.gov (United States)

    Xu, Hua-Min; Wang, Jun; Song, Ning; Jiang, Hong; Xie, Jun-Xia

    2016-08-25

    A growing body of evidence suggests that glial cells play an important role in neural development, neural survival, nerve repair and regeneration, synaptic transmission and immune inflammation. As the highest number of cells in the central nervous system, the role of glial cells in Parkinson's disease (PD) has attracted more and more attention. It has been confirmed that nigral iron accumulation contributes to the death of dopamine (DA) neurons in PD. Until now, most researches on nigral iron deposition in PD are focusing on DA neurons, but in fact glial cells in the central nervous system also play an important role in the regulation of iron homeostasis. Therefore, this review describes the role of iron metabolism of glial cells in death of DA neurons in PD, which could provide evidence to reveal the mechanisms underlying nigral iron accumulation of DA neurons in PD and provide the basis for discovering new potential therapeutic targets for PD. PMID:27546505

  6. A New Outlook on Mental Illnesses: Glial Involvement Beyond the Glue

    KAUST Repository

    Elsayed, Maha

    2015-12-16

    Mental illnesses have long been perceived as the exclusive consequence of abnormalities in neuronal functioning. Until recently, the role of glial cells in the pathophysiology of mental diseases has largely been overlooked. However recently, multiple lines of evidence suggest more diverse and significant functions of glia with behavior-altering effects. The newly ascribed roles of astrocytes, oligodendrocytes and microglia have led to their examination in brain pathology and mental illnesses. Indeed, abnormalities in glial function, structure and density have been observed in postmortem brain studies of subjects diagnosed with mental illnesses. In this review, we discuss the newly identified functions of glia and highlight the findings of glial abnormalities in psychiatric disorders. We discuss these preclinical and clinical findings implicating the involvement of glial cells in mental illnesses with the perspective that these cells may represent a new target for treatment.

  7. Secrets of Successful Homeschooling

    Science.gov (United States)

    Rivero, Lisa

    2011-01-01

    Parents who homeschool gifted children often find the daily practice of home education very different from what they had imagined. Gifted children are complex in both personality and learning styles. Parents who say that homeschooling works well for their gifted children have learned from others or discovered on their own several secrets that make…

  8. In vivo quantification of neuro-glial metabolism and glial glutamate concentration using 1H-[13C] MRS at 14.1T.

    Science.gov (United States)

    Lanz, Bernard; Xin, Lijing; Millet, Philippe; Gruetter, Rolf

    2014-01-01

    Astrocytes have recently become a major center of interest in neurochemistry with the discoveries on their major role in brain energy metabolism. An interesting way to probe this glial contribution is given by in vivo (13) C NMR spectroscopy coupled with the infusion labeled glial-specific substrate, such as acetate. In this study, we infused alpha-chloralose anesthetized rats with [2-(13) C]acetate and followed the dynamics of the fractional enrichment (FE) in the positions C4 and C3 of glutamate and glutamine with high sensitivity, using (1) H-[(13) C] magnetic resonance spectroscopy (MRS) at 14.1T. Applying a two-compartment mathematical model to the measured time courses yielded a glial tricarboxylic acid (TCA) cycle rate (Vg ) of 0.27 ± 0.02 μmol/g/min and a glutamatergic neurotransmission rate (VNT ) of 0.15 ± 0.01 μmol/g/min. Glial oxidative ATP metabolism thus accounts for 38% of total oxidative metabolism measured by NMR. Pyruvate carboxylase (VPC ) was 0.09 ± 0.01 μmol/g/min, corresponding to 37% of the glial glutamine synthesis rate. The glial and neuronal transmitochondrial fluxes (Vx (g) and Vx (n) ) were of the same order of magnitude as the respective TCA cycle fluxes. In addition, we estimated a glial glutamate pool size of 0.6 ± 0.1 μmol/g. The effect of spectral data quality on the fluxes estimates was analyzed by Monte Carlo simulations. In this (13) C-acetate labeling study, we propose a refined two-compartment analysis of brain energy metabolism based on (13) C turnover curves of acetate, glutamate and glutamine measured with state of the art in vivo dynamic MRS at high magnetic field in rats, enabling a deeper understanding of the specific role of glial cells in brain oxidative metabolism. In addition, the robustness of the metabolic fluxes determination relative to MRS data quality was carefully studied. PMID:24117599

  9. Defective Glial Maturation in Vanishing White Matter Disease

    Science.gov (United States)

    Bugiani, Marianna; Boor, Ilja; van Kollenburg, Barbara; Postma, Nienke; Polder, Emiel; van Berkel, Carola; van Kesteren, Ronald E.; Windrem, Martha S.; Hol, Elly M.; Scheper, Gert C.; Goldman, Steven A.; van der Knaap, Marjo S.

    2014-01-01

    Vanishing white matter disease (VWM) is a genetic leukoencephalopathy linked to mutations in the eukaryotic translation initiation factor 2B (eIF2B). It is a disease of infants, children and adults, who experience a slowly progressive neurological deterioration with episodes of rapid clinical worsening triggered by stress and eventually leading to death. Characteristic neuropathological findings include cystic degeneration of the white matter with scarce reactive gliosis, dysmorphic astrocytes, and paucity of myelin despite an increase in oligodendrocytic density. To assess whether a defective maturation of macroglia may be responsible for the feeble gliosis and lack of myelin, we investigated the maturation status of astrocytes and oligodendrocytes in the brains of 8 VWM patients, 4 patients with other white matter disorders and 6 age-matched controls with a combination of immunocytochemistry, histochemistry, scratch-wound assays, Western blot and quantitative PCR. We observed increased proliferation and a defect in the maturation of VWM astrocytes. They show an anomalous composition of their intermediate filament network with predominance of the δ-isoform of the glial fibrillary acidic protein and an increase in the heat shock protein αB-crystallin, supporting the possibility that a deficiency in astrocyte function may contribute to the loss of white matter in VWM. We also demonstrated a significant increase in numbers of pre-myelinating oligodendrocyte progenitors in VWM, which may explain the co-existence of oligodendrocytosis and myelin paucity in the patients’ white matter. PMID:21157376

  10. Endothelium in brain: Receptors, mitogenesis, and biosynthesis in glial cells

    Energy Technology Data Exchange (ETDEWEB)

    MacCumber, M.W.; Ross, C.A.; Snyder, S.H. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA))

    1990-03-01

    The authors have explored the cellular loci of endothelin (ET) actions and formation in the brain, using cerebellar mutant mice was well as primary and continuous cell cultures. A glial role is favored by several observations: (1) mutant mice lacking neuronal Purkinje cells display normal ET receptor binding and enhanced stimulation by ET of inositolphospholipid turnover; (ii) in weaver mice lacking neuronal granule cells, ET stimulation of inositolphospholipid turnover is not significantly diminished; (iii) C{sub 6} glioma cells and primary cultures of cerebellar astroglia exhibit substantial ET receptor binding and ET-induced stimulation of inositolphospholipid turnover; (iv) ET promotes mitogenesis of C{sub 6} glioma cells and primary cerebellar astroglia; and (v) primary cultures of cerebellar astroglia contain ET mRNA. ET also appears to have a neuronal role, since it stimulates inositolphospholipid turnover in primary cultures of cerebellar granule cells, and ET binding declines in granule cell-deficient mice. Thus, ET can be produced by glia and act upon both glia and neurons in a paracrine fashion.

  11. A Digital Realization of Astrocyte and Neural Glial Interactions.

    Science.gov (United States)

    Hayati, Mohsen; Nouri, Moslem; Haghiri, Saeed; Abbott, Derek

    2016-04-01

    The implementation of biological neural networks is a key objective of the neuromorphic research field. Astrocytes are the largest cell population in the brain. With the discovery of calcium wave propagation through astrocyte networks, now it is more evident that neuronal networks alone may not explain functionality of the strongest natural computer, the brain. Models of cortical function must now account for astrocyte activities as well as their relationships with neurons in encoding and manipulation of sensory information. From an engineering viewpoint, astrocytes provide feedback to both presynaptic and postsynaptic neurons to regulate their signaling behaviors. This paper presents a modified neural glial interaction model that allows a convenient digital implementation. This model can reproduce relevant biological astrocyte behaviors, which provide appropriate feedback control in regulating neuronal activities in the central nervous system (CNS). Accordingly, we investigate the feasibility of a digital implementation for a single astrocyte constructed by connecting a two coupled FitzHugh Nagumo (FHN) neuron model to an implementation of the proposed astrocyte model using neuron-astrocyte interactions. Hardware synthesis, physical implementation on FPGA, and theoretical analysis confirm that the proposed neuron astrocyte model, with significantly low hardware cost, can mimic biological behavior such as the regulation of postsynaptic neuron activity and the synaptic transmission mechanisms. PMID:26390499

  12. High Resolution Dissection of Reactive Glial Nets in Alzheimer's Disease.

    Science.gov (United States)

    Bouvier, David S; Jones, Emma V; Quesseveur, Gaël; Davoli, Maria Antonietta; A Ferreira, Tiago; Quirion, Rémi; Mechawar, Naguib; Murai, Keith K

    2016-01-01

    Fixed human brain samples in tissue repositories hold great potential for unlocking complexities of the brain and its alteration with disease. However, current methodology for simultaneously resolving complex three-dimensional (3D) cellular anatomy and organization, as well as, intricate details of human brain cells in tissue has been limited due to weak labeling characteristics of the tissue and high background levels. To expose the potential of these samples, we developed a method to overcome these major limitations. This approach offers an unprecedented view of cytoarchitecture and subcellular detail of human brain cells, from cellular networks to individual synapses. Applying the method to AD samples, we expose complex features of microglial cells and astrocytes in the disease. Through this methodology, we show that these cells form specialized 3D structures in AD that we refer to as reactive glial nets (RGNs). RGNs are areas of concentrated neuronal injury, inflammation, and tauopathy and display unique features around β-amyloid plaque types. RGNs have conserved properties in an AD mouse model and display a developmental pattern coinciding with the progressive accumulation of neuropathology. The method provided here will help reveal novel features of the healthy and diseased human brain, and aid experimental design in translational brain research. PMID:27090093

  13. Proliferation of differentiated glial cells in the brain stem.

    Science.gov (United States)

    Barradas, P C; Cavalcante, L A

    1998-02-01

    Classical studies of macroglial proliferation in muride rodents have provided conflicting evidence concerning the proliferating capabilities of oligodendrocytes and microglia. Furthermore, little information has been obtained in other mammalian orders and very little is known about glial cell proliferation and differentiation in the subclass Metatheria although valuable knowledge may be obtained from the protracted period of central nervous system maturation in these forms. Thus, we have studied the proliferative capacity of phenotypically identified brain stem oligodendrocytes by tritiated thymidine radioautography and have compared it with known features of oligodendroglial differentiation as well as with proliferation of microglia in the opossum Didelphis marsupialis. We have detected a previously undescribed ephemeral, regionally heterogeneous proliferation of oligodendrocytes expressing the actin-binding, ensheathment-related protein 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), that is not necessarily related to the known regional and temporal heterogeneity of expression of CNPase in cell bodies. On the other hand, proliferation of microglia tagged by the binding of Griffonia simplicifolia B4 isolectin, which recognizes an alpha-D-galactosyl-bearing glycoprotein of the plasma membrane of macrophages/microglia, is known to be long lasting, showing no regional heterogeneity and being found amongst both ameboid and differentiated ramified cells, although at different rates. The functional significance of the proliferative behavior of these differentiated cells is unknown but may provide a low-grade cell renewal in the normal brain and may be augmented under pathological conditions. PMID:9686148

  14. Proliferation of differentiated glial cells in the brain stem

    Directory of Open Access Journals (Sweden)

    Barradas P.C.

    1998-01-01

    Full Text Available Classical studies of macroglial proliferation in muride rodents have provided conflicting evidence concerning the proliferating capabilities of oligodendrocytes and microglia. Furthermore, little information has been obtained in other mammalian orders and very little is known about glial cell proliferation and differentiation in the subclass Metatheria although valuable knowledge may be obtained from the protracted period of central nervous system maturation in these forms. Thus, we have studied the proliferative capacity of phenotypically identified brain stem oligodendrocytes by tritiated thymidine radioautography and have compared it with known features of oligodendroglial differentiation as well as with proliferation of microglia in the opossum Didelphis marsupialis. We have detected a previously undescribed ephemeral, regionally heterogeneous proliferation of oligodendrocytes expressing the actin-binding, ensheathment-related protein 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNPase, that is not necessarily related to the known regional and temporal heterogeneity of expression of CNPase in cell bodies. On the other hand, proliferation of microglia tagged by the binding of Griffonia simplicifolia B4 isolectin, which recognizes an alpha-D-galactosyl-bearing glycoprotein of the plasma membrane of macrophages/microglia, is known to be long lasting, showing no regional heterogeneity and being found amongst both ameboid and differentiated ramified cells, although at different rates. The functional significance of the proliferative behavior of these differentiated cells is unknown but may provide a low-grade cell renewal in the normal brain and may be augmented under pathological conditions.

  15. Visualizing the Live Drosophila Glial-neuromuscular Junction with Fluorescent Dyes

    OpenAIRE

    Brink, Dee; Gilbert, Mary; Auld, Vanessa

    2009-01-01

    Our project identified GFP labeled glial structures at the developing larval fly neuromuscular synapse. To look at development of live glial-nerve-muscle synapses, we developed a larval tissue preparation that had features of live intact larvae, but also had good optical properties. This new preparation also allowed for access of perfusates to the synapse. We used fly larvae, immersed them in artificial hemolymph, and relaxed their normal rhythmic body contractions by chilling them. Next we d...

  16. Two forms of cerebellar glial cells interact differently with neurons in vitro

    OpenAIRE

    1984-01-01

    Specific interactions between neurons and glia dissociated from early postnatal mouse cerebellar tissue were studied in vitro by indirect immunocytochemical staining with antisera raised against purified glial filament protein, galactocerebroside, and the NILE glycoprotein. Two forms of cells were stained with antisera raised against purified glial filament protein. The first, characterized by a cell body 9 microns diam and processes 130-150 microns long, usually had two to three neurons asso...

  17. Glial cell modulators attenuate methamphetamine self-administration in the rat

    OpenAIRE

    SNIDER, Sarah E.; Hendrick, Elizabeth S; BEARDSLEY, PATRICK M.

    2013-01-01

    Neuroinflammation induced by activated microglia and astrocytes can be elicited by drugs of abuse. Methamphetamine administration activates glial cells and increases proinflammatory cytokine production, and there is recent evidence of a linkage between glial cell activation and drug abuse-related behavior. We have previously reported that ibudilast (AV411; 3-isobutyryl-2-isopropylpyrazolo-[1,5-a]pyridine), which inhibits phosphodiesterase (PDE) and pro-inflammatory activity, blocks reinstatem...

  18. Transfection of the glial cell line-derived neurotrophic factor gene promotes neuronal differentiation

    OpenAIRE

    Du, Jie; Gao, Xiaoqing; Deng, Li; Chang, Nengbin; Xiong, Huailin; Zheng, Yu

    2014-01-01

    Glial cell line-derived neurotrophic factor recombinant adenovirus vector-transfected bone marrow mesenchymal stem cells were induced to differentiate into neuron-like cells using inductive medium containing retinoic acid and epidermal growth factor. Cell viability, microtubule-associated protein 2-positive cell ratio, and the expression levels of glial cell line-derived neurotrophic factor, nerve growth factor and growth-associated protein-43 protein in the supernatant were significantly hig...

  19. On the morphogenesis of glial compartments in the sensory organs of Caenorhabditis elegans

    OpenAIRE

    Oikonomou, Grigorios; Shaham, Shai

    2012-01-01

    Glial cells surround neuronal endings and isolate them within specialized compartments. This architecture is found at synapses in the central nervous system, as well as at receptive endings of sensory neurons. Recent studies are beginning to uncover the contributions of glial compartments to the functions of the ensheathed neurons. However, the cellular and molecular processes that guide compartment morphogenesis remain unknown. The main sensory organ of Caenorhabditis elegans, the amphid, pr...

  20. Glial protein S100B modulates long-term neuronal synaptic plasticity

    OpenAIRE

    NISHIYAMA, HIROSHI; Knöpfel, Thomas; Endo, Shogo; Itohara, Shigeyoshi

    2002-01-01

    Glial cells are traditionally regarded as elements for structural support and ionic homeostasis, but have recently attracted attention as putative integral elements of the machinery involved in synaptic transmission and plasticity. Here, we demonstrate that calcium-binding protein S100B, which is synthesized in considerable amounts in astrocytes (a major glial cell subtype), modulates long-term synaptic plasticity. Mutant mice devoid of S100B developed normally and had no detectable abnormali...

  1. Neuron- or glial-specific ablation of secreted renin does not affect renal renin, baseline arterial pressure, or metabolism

    OpenAIRE

    Xu, Di; Borges, Giulianna R.; Deborah R Davis; Agassandian, Khristofor; Sequeira Lopez, Maria Luisa S.; Gomez, R. Ariel; Cassell, Martin D.; Grobe, Justin L.; Sigmund, Curt D.

    2010-01-01

    The renin-angiotensin system (RAS), known for its roles in cardiovascular, metabolic, and developmental regulation, is present in both the circulation and in many individual tissues throughout the body. Substantial evidence supports the existence of a brain RAS, though quantification and localization of brain renin have been hampered by its low expression levels. We and others have previously determined that there are two isoforms of renin expressed in the brain. The classical isoform encodin...

  2. Neural and glial progenitor transplantation as a neuroprotective strategy for Amyotrophic Lateral Sclerosis (ALS).

    Science.gov (United States)

    Haidet-Phillips, Amanda M; Maragakis, Nicholas J

    2015-12-01

    ALS is a neurodegenerative disease with a prevalence rate of up to 7.4/100,000 and the overall risk of developing ALS over a lifetime is 1:400. Most patients die from respiratory failure following a course of progressive weakness. To date, only one traditional pharmaceutical agent-riluzole, has been shown to afford a benefit on survival but numerous pharmaceutical interventions have been studied in preclinical models of ALS without subsequent translation to patient efficacy. Despite the relative selectivity of motor neuron cell death, animal and tissue culture models of familial ALS suggest that non-neuronal cells significantly contribute to neuronal dysfunction and death. Early efforts to transplant stem cells had focused on motor neuron replacement. More practically for this aggressive neurodegenerative disease, recent studies, preclinical efforts, and early clinical trials have focused on the transplantation of neural stem cells, mesenchymal stem cells, or glial progenitors. Using transgenic mouse or rat models of ALS, a number of studies have shown neuroprotection through a variety of different mechanisms that have included neurotrophic factor secretion, glutamate transporter regulation, and modulation of neuroinflammation, among others. However, given that cell replacement could involve a number of biologically relevant factors, identifying the key pathway(s) that may contribute to neuroprotection remains a challenge. Nevertheless, given the abundant data supporting the interplay between non-neuronal cell types and motor neuron disease propagation, the replacement of disease-carrying host cells by normal cells may be sufficient to confer neuroprotection. Key preclinical issues that currently are being addressed include the most appropriate methods and routes for delivery of cells to disease-relevant regions of the neuraxis, cell survival and migration, and tracking the cells following transplantation. Central to the initial development of stem cell

  3. Soluble guanylyl cyclase is involved in PDT-induced injury of crayfish glial cells

    Science.gov (United States)

    Kovaleva, V. D.; Uzdensky, A. B.

    2016-04-01

    Photodynamic therapy (PDT) is a potential tool for selective destruction of malignant brain tumors. However, not only malignant but also healthy neurons and glial cells may be damaged during PDT. Nitric oxide is an important modulator of cell viability and intercellular neuroglial communications. NO have been already shown to participate in PDT-induced injury of neurons and glial cells. As soluble guanylyl cyclase is the only known receptor for NO, we have studied the possible role of soluble guanylyl cyclase in the regulation of survival and death of neurons and surrounding glial cells under photo-oxidative stress induced by photodynamic treatment (PDT). The crayfish stretch receptor consisting of a single identified sensory neuron enveloped by glial cells is a simple but informative model object. It was photosensitized with alumophthalocyanine photosens (10 nM) and irradiated with a laser diode (670 nm, 0.4 W/cm2). Using inhibitory analysis we have shown that during PDT soluble guanylyl cyclase, probably, has proapoptotic and antinecrotic effect on the glial cells of the isolated crayfish stretch receptor. Proapoptotic effect of soluble guanylyl cyclase could be mediated by protein kinase G (PKG). Thus, the involvement of NO/sGC/cGMP/PKG signaling pathway in PDT-induced apoptosis of glial cells was indirectly demonstrated.

  4. Distinct angiotensin II receptor in primary cultures of glial cells from rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Raizada, M.K.; Phillips, M.I.; Crews, F.T.; Sumners, C.

    1987-07-01

    Angiotensin II (Ang-II) has profound effects on the brain. Receptors for Ang-II have been demonstrated on neurons, but no relationship between glial cells and Agn-II has been established. Glial cells (from the hypothalamus and brain stem of 1-day-old rat brains) in primary culture have been used to demonstrate the presence of specific Ang-II receptors. Binding of /sup 125/I-Ang-II to glial cultures was rapid, reversible, saturable, and specific for Ang-II. The rank order of potency of /sup 125/I-Ang-II binding was determined. Scatchard analysis revealed a homogeneous population of high-affinity binding sites with a B/sub max/ of 110 fmol/mg of protein. Light-microscopic autoradiography of /sup 125/I-Ang-II binding supported the kinetic data, documenting specific Ang-II receptors on the glial cells. Ang-II stimulated a dose-dependent hydrolysis of phosphatidylinositols in glial cells, an effect mediated by Ang-II receptors. However, Ang-II failed to influence (/sup 3/H) norepinephrine uptake, and catecholamines failed to regulate Ang-II receptors, effects that occur in neurons. These observations demonstrate the presence of specific Ang-II receptors on the glial cells in primary cultures derived from normotensive rat brain. The receptors are kinetically similar to, but functionally distinct from, the neuronal Ang-II receptors.

  5. Therapeutic effects of NogoA vaccine and olfactory ensheathing glial cell implantation on acute spinal cord injury

    Directory of Open Access Journals (Sweden)

    Zhang Z

    2013-10-01

    Full Text Available Zhicheng Zhang, Fang Li, Tiansheng Sun, Dajiang Ren, Xiumei Liu PLA Institute of Orthopedics, Beijing Army General Hospital, Beijing, People's Republic of China Background: Many previous studies have focused on the effects of IN-1, a monoclonal antibody that neutralizes Nogo (a neurite growth inhibitory protein, on neurologic regeneration in spinal cord injury (SCI. However, safety problems and the short half-life of the exogenous antibody are still problematic. In the present study, the NogoA polypeptide was used as an antigen to make a therapeutic NogoA vaccine. Rats were immunized with this vaccine and were able to secrete the polyclonal antibody before SCI. The antibody can block NogoA within the injured spinal cord when the antibody gains access to the spinal cord due to a compromised blood–spinal cord barrier. Olfactory ensheathing glial cell transplantation has been used in a spinal cord contusion model to promote the recovery of SCI. The present study was designed to verify the efficacy and safety of NogoA polypeptide vaccine, the effects of immunotherapy with this vaccine, and the synergistic effects of the vaccine and olfactory ensheathing glial cells in repair of SCI. Methods: A 13-polypeptide fragment of NogoA was synthesized. This fragment was then coupled with keyhole limpet hemocyanin to improve the immunogenicity of the polypeptide vaccine. Immunization via injection into the abdominal cavity was performed in rats before SCI. The serum antibody level and ability of the vaccine to bind with Nogo were detected by enzyme-linked immunosorbent assay. The safety of the vaccine was evaluated according to the incidence and severity of experimental autoimmune encephalomyelitis. Olfactory ensheathing glia cells were obtained, purified, and subsequently implanted into a Wistar rat model of thoracic spinal cord contusion injury. The rats were divided into four groups, ie, an SCI model group, an olfactory ensheathing glia group, a vaccine

  6. The involvement of NF-κB in PDT-induced death of crayfish glial and nerve cells

    Science.gov (United States)

    Berezhnaya, E. V.; Neginskaya, M. A.; Kovaleva, V. D.; Rudkovskii, M. V.; Uzdensky, A. B.

    2015-03-01

    Photodynamic therapy (PDT) is used for selective destruction of cells, in particular, for treatment of brain tumors. However, photodynamic treatment damages not only tumor cells, but also healthy neurons and glial cells. To study the possible role of NF-κB in photodynamic injury of neurons and glial cells, we investigated the combined effect of photodynamic treatment and NF-κB modulators: activator betulinic acid, or inhibitors parthenolide and CAPE on an isolated crayfish stretch receptor consisting of a single neuron surrounded by glial cells. A laser diode (670 nm, 0.4 W/cm2) was used as a light source. The inhibition of NF-κB during PDT increased the duration of neuron firing and glial necrosis and decreased neuron necrosis and glial apoptosis. The activation of NF-κB during PDT increased neuron necrosis and glial apoptosis and decreased glial necrosis. The difference between the effects of NF-κB modulators on photosensitized neurons and glial cells indicates the difference in NF-κB-mediated signaling pathways in these cell types. Thus, NF-κB is involved in PDT-induced shortening of neuron firing, neuronal and glial necrosis, and apoptosis of glial cells.

  7. Detecting ''secret'' quantum numbers

    International Nuclear Information System (INIS)

    For a general quantum mechanical system undergoing a process, it is shown that one can tell from measurements on this system whether or not the system is characterized by quantum numbers the existence of which is unknown to the observer, even though the detection equipment used by the observer is unable to distinguish among the various possible values of the ''secret'' quantum number and hence always averages over them

  8. Adipocytes Secrete Leukotrienes

    OpenAIRE

    Mothe-Satney, Isabelle; Filloux, Chantal; Amghar, Hind; Pons, Catherine; Bourlier, Virginie; Galitzky, Jean; Paul A. Grimaldi; Féral, Chloé C.; Bouloumié, Anne; Obberghen, Emmanuel Van; Neels, Jaap G.

    2012-01-01

    Leukotrienes (LTs) are potent proinflammatory mediators, and many important aspects of innate and adaptive immune responses are regulated by LTs. Key members of the LT synthesis pathway are overexpressed in adipose tissue (AT) during obesity, resulting in increased LT levels in this tissue. We observed that several mouse adipocyte cell lines and primary adipocytes from mice and humans both can secrete large amounts of LTs. Furthermore, this production increases with a high-fat diet (HFD) and ...

  9. Portillo's State Secrets: Mysteries

    OpenAIRE

    Clarke, David

    2015-01-01

    Blog/article commissioned by The National Archives to accompany Episode 4 of the BBC 2 series 'Portillo's State Secrets' (BBC 2, 26 March 2015). The article discusses and places in historical context the contents of Metropolitan Police files on the Jack the Ripper murders; the investigation of the 'Kitchener Coffin Hoax' of WW1 and the Ministry of Defence file on the so-called Rendlesham Forest UFO incident at RAF Woodbridge in 1980.

  10. Secret Key Crypto Implementations

    Science.gov (United States)

    Bertoni, Guido Marco; Melzani, Filippo

    This chapter presents the algorithm selected in 2001 as the Advanced Encryption Standard. This algorithm is the base for implementing security and privacy based on symmetric key solutions in almost all new applications. Secret key algorithms are used in combination with modes of operation to provide different security properties. The most used modes of operation are presented in this chapter. Finally an overview of the different techniques of software and hardware implementations is given.

  11. This secret nuclear industry

    International Nuclear Information System (INIS)

    Some secret affairs (radioactive wastes in the department of Essonne, an organism, the Cea that begins by lies then makes the proofs disappear, a storage center in the Manche, a society Cogema that minimizes the dangers provoked by the spent fuel coming from nuclear power plants) revealed and discussed by Misses Michele Rivasi, aggregate in biology, founder of the Crii-Rad, an independent laboratory specialized in nuclear matters and deputy since June 1997. (N.C.)

  12. Lipids in airway secretions

    International Nuclear Information System (INIS)

    Lipids form a significant portion of airway mucus yet they have not received the same attention that epithelial glycoproteins have. We have analysed, by thin layer chromatography, lipids present in airway mucus under 'normal' and hypersecretory (pathological) conditions.The 'normals' included (1) bronchial lavage obtained from healthy human volunteers and from dogs and (2) secretions produced ''in vitro'' by human (bronchial) and canine (tracheal) explants. Hypersecretory mucus samples included (1) lavage from dogs made bronchitic by exposure to SO2, (2) bronchial aspirates from acute and chronic tracheostomy patients, (3) sputum from patients with cystic fibrosis and chronic bronchitis and (4) postmortem secretions from patients who died from sudden infant death syndrome (SIDS) or from status asthmaticus. Cholesterol was found to be the predominant lipid in 'normal' mucus with lesser amounts of phospholipids. No glycolipids were detected. In the hypersecretory mucus, in addition to neutral and phospholipids, glycolipids were present in appreciable amounts, often the predominant species, suggesting that these may be useful as markers of disease. Radioactive precursors 14C acetate and 14C palmitate were incorporated into lipids secreted ''in vitro'' by canine tracheal explants indicating that they are synthesised by the airway. (author)

  13. Lipids in airway secretions

    Energy Technology Data Exchange (ETDEWEB)

    Bhaskar, K.R.; DeFeudis O' Sullivan, D.; Opaskar-Hincman, H.; Reid, L.M.

    1987-01-01

    Lipids form a significant portion of airway mucus yet they have not received the same attention that epithelial glycoproteins have. We have analysed, by thin layer chromatography, lipids present in airway mucus under 'normal' and hypersecretory (pathological) conditions.The 'normals' included (1) bronchial lavage obtained from healthy human volunteers and from dogs and (2) secretions produced ''in vitro'' by human (bronchial) and canine (tracheal) explants. Hypersecretory mucus samples included (1) lavage from dogs made bronchitic by exposure to SO/sub 2/, (2) bronchial aspirates from acute and chronic tracheostomy patients, (3) sputum from patients with cystic fibrosis and chronic bronchitis and (4) postmortem secretions from patients who died from sudden infant death syndrome (SIDS) or from status asthmaticus. Cholesterol was found to be the predominant lipid in 'normal' mucus with lesser amounts of phospholipids. No glycolipids were detected. In the hypersecretory mucus, in addition to neutral and phospholipids, glycolipids were present in appreciable amounts, often the predominant species, suggesting that these may be useful as markers of disease. Radioactive precursors /sup 14/C acetate and /sup 14/C palmitate were incorporated into lipids secreted ''in vitro'' by canine tracheal explants indicating that they are synthesised by the airway.

  14. Dynamic secrets in communication security

    CERN Document Server

    Xiao, Sheng; Towsley, Donald

    2013-01-01

    Dynamic secrets are constantly generated and updated from messages exchanged between two communication users. When dynamic secrets are used as a complement to existing secure communication systems, a stolen key or password can be quickly and automatically reverted to its secret status without disrupting communication. 'Dynamic Secrets in Communication Security' presents unique security properties and application studies for this technology. Password theft and key theft no longer pose serious security threats when parties frequently use dynamic secrets. This book also illustrates that a dynamic

  15. On Cheating Immune Secret Sharing

    Directory of Open Access Journals (Sweden)

    Josef Pieprzyk

    2004-12-01

    Full Text Available The paper addresses the cheating prevention in secret sharing. We consider secret sharing with binary shares. The secret also is binary. This model allows us to use results and constructions from the well developed theory of cryptographically strong boolean functions. In particular, we prove that for given secret sharing, the average cheating probability over all cheating vectors and all original vectors, i.e., 1/n 2 n ∑ c=1...n ∑ α∈V n ρ c,α, denoted by ρ, satisfies ρ ≥ ½, and the equality holds if and only if ρ c,α satisfies ρ c,α = ½ for every cheating vector δ c and every original vector α. In this case the secret sharing is said to be cheating immune. We further establish a relationship between cheating-immune secret sharing and cryptographic criteria of boolean functions.This enables us to construct cheating-immune secret sharing.

  16. Evolutionary conservation of the presumptive neural plate markers AmphiSox1/2/3 and AmphiNeurogenin in the invertebrate chordate amphioxus

    Science.gov (United States)

    Holland, L. Z.; Schubert, M.; Holland, N. D.; Neuman, T.

    2000-01-01

    Amphioxus, as the closest living invertebrate relative of the vertebrates, can give insights into the evolutionary origin of the vertebrate body plan. Therefore, to investigate the evolution of genetic mechanisms for establishing and patterning the neuroectoderm, we cloned and determined the embryonic expression of two amphioxus transcription factors, AmphiSox1/2/3 and AmphiNeurogenin. These genes are the earliest known markers for presumptive neuroectoderm in amphioxus. By the early neurula stage, AmphiNeurogenin expression becomes restricted to two bilateral columns of segmentally arranged neural plate cells, which probably include precursors of motor neurons. This is the earliest indication of segmentation in the amphioxus nerve cord. Later, expression extends to dorsal cells in the nerve cord, which may include precursors of sensory neurons. By the midneurula, AmphiSox1/2/3 expression becomes limited to the dorsal part of the forming neural tube. These patterns resemble those of their vertebrate and Drosophila homologs. Taken together with the evolutionarily conserved expression of the dorsoventral patterning genes, BMP2/4 and chordin, in nonneural and neural ectoderm, respectively, of chordates and Drosophila, our results are consistent with the evolution of the chordate dorsal nerve cord and the insect ventral nerve cord from a longitudinal nerve cord in a common bilaterian ancestor. However, AmphiSox1/2/3 differs from its vertebrate homologs in not being expressed outside the CNS, suggesting that additional roles for this gene have evolved in connection with gene duplication in the vertebrate lineage. In contrast, expression in the midgut of AmphiNeurogenin together with the gene encoding the insulin-like peptide suggests that amphioxus may have homologs of vertebrate pancreatic islet cells, which express neurogenin3. In addition, AmphiNeurogenin, like its vertebrate and Drosophila homologs, is expressed in apparent precursors of epidermal chemosensory and

  17. The effects of centrally administered fluorocitrate via inhibiting glial cells on working memory in rats

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Although prefrontal and hippocampal neurons are critical for spatial working memory,the function of glial cells in spatial working memory remains uncertain.In this study we investigated the function of glial cells in rats’ working memory.The glial cells of rat brain were inhibited by intracerebroventricular(icv) injection of fluorocitrate(FC).The effects of FC on the glial cells were examined by using electroencephalogram(EEG) recordings and delayed spatial alternation tasks.After icv injection of 10 μL of 0.5 nmol/L or 5 nmol/L FC,the EEG power spectrum recorded from the hippocampus increased,but the power spectrum for the prefrontal cortex did not change,and working memory was unaffected.Following an icv injection of 10 μL of 20 nmol/L FC,the EEG power spectra in both the prefrontal cortex and the hippocampus increased,and working memory improved.The icv injection of 10 μL of 50 nmol/L FC,the EEG power spectra in both the prefrontal cortex and in the hippocampus decreased,and working memory was impaired.These results suggest that spatial working memory is affected by centrally administered FC,but only if there are changes in the EEG power spectrum in the prefrontal cortex.Presumably,the prefrontal glial cells relate to the working memory.

  18. Viscoelastic properties of individual glial cells and neurons in the CNS.

    Science.gov (United States)

    Lu, Yun-Bi; Franze, Kristian; Seifert, Gerald; Steinhäuser, Christian; Kirchhoff, Frank; Wolburg, Hartwig; Guck, Jochen; Janmey, Paul; Wei, Er-Qing; Käs, Josef; Reichenbach, Andreas

    2006-11-21

    One hundred fifty years ago glial cells were discovered as a second, non-neuronal, cell type in the central nervous system. To ascribe a function to these new, enigmatic cells, it was suggested that they either glue the neurons together (the Greek word "gammalambdaiotaalpha" means "glue") or provide a robust scaffold for them ("support cells"). Although both speculations are still widely accepted, they would actually require quite different mechanical cell properties, and neither one has ever been confirmed experimentally. We investigated the biomechanics of CNS tissue and acutely isolated individual neurons and glial cells from mammalian brain (hippocampus) and retina. Scanning force microscopy, bulk rheology, and optically induced deformation were used to determine their viscoelastic characteristics. We found that (i) in all CNS cells the elastic behavior dominates over the viscous behavior, (ii) in distinct cell compartments, such as soma and cell processes, the mechanical properties differ, most likely because of the unequal local distribution of cell organelles, (iii) in comparison to most other eukaryotic cells, both neurons and glial cells are very soft ("rubber elastic"), and (iv) intriguingly, glial cells are even softer than their neighboring neurons. Our results indicate that glial cells can neither serve as structural support cells (as they are too soft) nor as glue (because restoring forces are dominant) for neurons. Nevertheless, from a structural perspective they might act as soft, compliant embedding for neurons, protecting them in case of mechanical trauma, and also as a soft substrate required for neurite growth and facilitating neuronal plasticity. PMID:17093050

  19. MONA Implementation Secrets

    DEFF Research Database (Denmark)

    Klarlund, Nils; Møller, Anders; Schwartzbach, Michael Ignatieff

    2002-01-01

    period of six years. Compared to the first naive version, the present tool is faster by several orders of magnitude. This speedup is obtained from many different contributions working on all levels of the compilation and execution of formulas. We present a selection of implementation "secrets" that have...... been discovered and tested over the years, including formula reductions, DAGification, guided tree automata, three-valued logic, eager minimization, BDD-based automata representations, and cache-conscious data structures. We describe these techniques and quantify their respective effects by...

  20. Windows 8 secrets

    CERN Document Server

    Thurrott, Paul

    2012-01-01

    Tips, tricks, treats, and secrets revealed on Windows 8 Microsoft is introducing a major new release of its Windows operating system, Windows 8, and what better way to learn all its ins and outs than from two internationally recognized Windows experts and Microsoft insiders, authors Paul Thurrott and Rafael Rivera? They cut through the hype to get at useful information you'll not find anywhere else, including what role this new OS plays in a mobile and tablet world. Regardless of your level of knowledge, you'll discover little-known facts about how things work, what's new and different, and h

  1. Ghrelin and gastric acid secretion

    Institute of Scientific and Technical Information of China (English)

    Koji Yakabi; Junichi Kawashima; Shingo Kato

    2008-01-01

    Ghrelin, a novel growth hormone-releasing peptide, was originally isolated from rat and human stomach. Ghrelin has been known to increase the secretion of growth hormone (GH), food intake, and body weight gain when administered peripherally or centrally. Ghrelin is also known to stimulate the gastric motility and the secretion of gastric acid. In the previous studies, the action of ghrelin on acid secretion was shown to be as strong as that of histamine and gastrin in-vivo experiment. In the studies, the mechanism for the action of ghrelin was also investigated. It was shown that vagotomy completely inhibited the action of ghrelin on the secretion of gastric acid suggesting that vagal nerve is involved in the mechanism for the action of ghrelin on acid secretion. As famotidine did not inhibit ghrelin-in-duced acid secretion in the study by Masuda et al, they concluded that histamine was not involved in the action of ghrelin on acid secretion. However, we have shown that famotidine completely inhibited ghrelin-induced acid secretion and histidine decarboxylase (HDC) mRNA was increased in gastric mucosa by ghrelin injection which is inhibited by vagotomy Our results indicate that histamine is involved in the action of ghrelin on acid secretion. Furthermore synergistic action of gastrin and ghrelin on gastric add secretion was shown. Although gastrin has important roles in postprandial secretion of gastric acid, ghrelin may be related to acid secretion during fasting period or at night. However, further studies are needed to elucidate the physiological role of ghrelin in acid secretion.

  2. Partially secret broadcasting, partially secret splitting with quantum entanglement

    International Nuclear Information System (INIS)

    In this paper, we propose a classical secret broadcasting and splitting joint protocol in a quantum scenario. With those genuinely entangled states, the boss can always broadcast some of his secrets and split some others to multi-receivers at the same time. The efficiency of the joint protocol is also compared with that of two separate ones which realise classical secret broadcasting and classical secret splitting respectively, and based on the comparison we can see the promising advantage of our joint protocol is that it can realise the two tasks more efficiently and more conveniently. (general)

  3. On Converting Secret Sharing Scheme to Visual Secret Sharing Scheme

    Directory of Open Access Journals (Sweden)

    Wang Daoshun

    2010-01-01

    Full Text Available Abstract Traditional Secret Sharing (SS schemes reconstruct secret exactly the same as the original one but involve complex computation. Visual Secret Sharing (VSS schemes decode the secret without computation, but each share is m times as big as the original and the quality of the reconstructed secret image is reduced. Probabilistic visual secret sharing (Prob.VSS schemes for a binary image use only one subpixel to share the secret image; however the probability of white pixels in a white area is higher than that in a black area in the reconstructed secret image. SS schemes, VSS schemes, and Prob. VSS schemes have various construction methods and advantages. This paper first presents an approach to convert (transform a -SS scheme to a -VSS scheme for greyscale images. The generation of the shadow images (shares is based on Boolean XOR operation. The secret image can be reconstructed directly by performing Boolean OR operation, as in most conventional VSS schemes. Its pixel expansion is significantly smaller than that of VSS schemes. The quality of the reconstructed images, measured by average contrast, is the same as VSS schemes. Then a novel matrix-concatenation approach is used to extend the greyscale -SS scheme to a more general case of greyscale -VSS scheme.

  4. The neurosteroid allopregnanolone modulates specific functions in central and peripheral glial cells

    Directory of Open Access Journals (Sweden)

    ValerioMagnaghi

    2011-12-01

    Full Text Available Since the first observations on the existence of “neurosteroids” in the 1980’s, our understanding of the importance of these endogenous steroids in the control of the central and peripheral nervous system has increased progressively. Although most of the observations were made in neuronal cells, equally important are the effects that neurosteroids exert on glial cells. Among the different classes of neurosteroids acting on glial cells, the progesterone 5α-3α metabolite, allopregnanolone, displays a particular mechanism of action involving primarily the modulation of classic GABA receptors. In this review, we focus our attention on allopregnanolone because its effects on the physiology of glial cells of the central and peripheral nervous system are intriguing and could potentially lead to the development of new strategies for neuroprotection and/or regeneration of injured nervous tissues.

  5. Opioid-dependent growth of glial cultures: Suppression of astrocyte DNA synthesis by met-enkephalin

    Energy Technology Data Exchange (ETDEWEB)

    Stiene-Martin, A.; Hauser, K.F. (Univ. of Kentucky, Lexington (USA))

    1990-01-01

    The action of met-enkephalin on the growth of astrocytes in mixed-glial cultures was examined. Primary, mixed-glial cultures were isolated from 1 day-old mouse cerebral hemispheres and continuously treated with either basal growth media, 1 {mu}M met-enkephalin, 1 {mu}M met-enkephalin plus the opioid antagonist naloxone, or naloxone alone. Absolute numbers of neural cells were counted in unstained preparations, while combined ({sup 3}H)-thymidine autoradiography and glial fibrillary acid protein (GFAP) immunocytochemistry was performed to identify specific changes in astrocytes. When compared to control and naloxone treated cultures, met-enkephalin caused a significant decrease in both total cell numbers, and in ({sup 3}H)-thymidine incorporation by GFAP-positive cells with flat morphology. These results indicate that met-enkephalin suppresses astrocyte growth in culture.

  6. Opioid-dependent growth of glial cultures: Suppression of astrocyte DNA synthesis by met-enkephalin

    International Nuclear Information System (INIS)

    The action of met-enkephalin on the growth of astrocytes in mixed-glial cultures was examined. Primary, mixed-glial cultures were isolated from 1 day-old mouse cerebral hemispheres and continuously treated with either basal growth media, 1 μM met-enkephalin, 1 μM met-enkephalin plus the opioid antagonist naloxone, or naloxone alone. Absolute numbers of neural cells were counted in unstained preparations, while combined [3H]-thymidine autoradiography and glial fibrillary acid protein (GFAP) immunocytochemistry was performed to identify specific changes in astrocytes. When compared to control and naloxone treated cultures, met-enkephalin caused a significant decrease in both total cell numbers, and in [3H]-thymidine incorporation by GFAP-positive cells with flat morphology. These results indicate that met-enkephalin suppresses astrocyte growth in culture

  7. Nonlinear Secret Image Sharing Scheme

    OpenAIRE

    2014-01-01

    Over the past decade, most of secret image sharing schemes have been proposed by using Shamir's technique. It is based on a linear combination polynomial arithmetic. Although Shamir's technique based secret image sharing schemes are efficient and scalable for various environments, there exists a security threat such as Tompa-Woll attack. Renvall and Ding proposed a new secret sharing technique based on nonlinear combination polynomial arithmetic in order to solve this threat. It is hard to ap...

  8. Long-distance mechanism of neurotransmitter recycling mediated by glial network facilitates visual function in Drosophila.

    Science.gov (United States)

    Chaturvedi, Ratna; Reddig, Keith; Li, Hong-Sheng

    2014-02-18

    Neurons rely on glia to recycle neurotransmitters such as glutamate and histamine for sustained signaling. Both mammalian and insect glia form intercellular gap-junction networks, but their functional significance underlying neurotransmitter recycling is unknown. Using the Drosophila visual system as a genetic model, here we show that a multicellular glial network transports neurotransmitter metabolites between perisynaptic glia and neuronal cell bodies to mediate long-distance recycling of neurotransmitter. In the first visual neuropil (lamina), which contains a multilayer glial network, photoreceptor axons release histamine to hyperpolarize secondary sensory neurons. Subsequently, the released histamine is taken up by perisynaptic epithelial glia and converted into inactive carcinine through conjugation with β-alanine for transport. In contrast to a previous assumption that epithelial glia deliver carcinine directly back to photoreceptor axons for histamine regeneration within the lamina, we detected both carcinine and β-alanine in the fly retina, where they are found in photoreceptor cell bodies and surrounding pigment glial cells. Downregulating Inx2 gap junctions within the laminar glial network causes β-alanine accumulation in retinal pigment cells and impairs carcinine synthesis, leading to reduced histamine levels and photoreceptor synaptic vesicles. Consequently, visual transmission is impaired and the fly is less responsive in a visual alert analysis compared with wild type. Our results suggest that a gap junction-dependent laminar and retinal glial network transports histamine metabolites between perisynaptic glia and photoreceptor cell bodies to mediate a novel, long-distance mechanism of neurotransmitter recycling, highlighting the importance of glial networks in the regulation of neuronal functions. PMID:24550312

  9. Glial modulation by N-acylethanolamides in brain injury and neurodegeneration

    Directory of Open Access Journals (Sweden)

    María Inés Herrera

    2016-04-01

    Full Text Available Neuroinflammation involves the activation of glial cells and represents a key element in normal aging and pathophysiology of brain damage. N-acylethanolamides (NAEs, naturally occurring amides, are known for their pro-homeostatic effects. An increase of NAEs has been reported in vivo and in vitro in the aging brain and in brain injury. Treatment with NAEs may promote neuroprotection and exert anti-inflammatory actions via PPARα activation and/or by counteracting gliosis. This review aims to provide an overview of endogenous and exogenous properties of NAEs in neuroinflammation and to discuss their interaction with glial cells.

  10. Glial Modulation by N-acylethanolamides in Brain Injury and Neurodegeneration

    Science.gov (United States)

    Herrera, María I.; Kölliker-Frers, Rodolfo; Barreto, George; Blanco, Eduardo; Capani, Francisco

    2016-01-01

    Neuroinflammation involves the activation of glial cells and represents a key element in normal aging and pathophysiology of brain damage. N-acylethanolamides (NAEs), naturally occurring amides, are known for their pro-homeostatic effects. An increase in NAEs has been reported in vivo and in vitro in the aging brain and in brain injury. Treatment with NAEs may promote neuroprotection and exert anti-inflammatory actions via PPARα activation and/or by counteracting gliosis. This review aims to provide an overview of endogenous and exogenous properties of NAEs in neuroinflammation and to discuss their interaction with glial cells. PMID:27199733

  11. Hippocampal kindling alters the concentration of glial fibrillary acidic protein and other marker proteins in rat brain

    DEFF Research Database (Denmark)

    Hansen, A; Jørgensen, Ole Steen; Bolwig, T G;

    1990-01-01

    The effect of hippocampal kindling on neuronal and glial marker proteins was studied in the rat by immunochemical methods. In hippocampus, pyriform cortex and amygdala there was an increase in glial fibrillary acidic protein (GFAP), indicating reactive gliosis, and an increase in the glycolytic e...

  12. Secret and research

    Directory of Open Access Journals (Sweden)

    André PETITAT

    2013-12-01

    Full Text Available The postures of secrecy and revelation maintain our common relational dynamics between sharing and not sharing. Science, which has become the dominant form of knowledge, is a rational and empirical knowledge sharing. For this purpose, the knowledge articulates languages, if possible unambiguous, spaces of rational deliberation, technical devices and resources of the imagination. This activity meets other logics called power, prestige, status, profit, customer, blind adherence and revealed truth, in which the postures of secret invite themselves massively. The codes of ethics attempt to regulate this mix of contradictory logics by setting standards of scientific exchanges, recalling the person rights and particularly the subjects observed rights, protecting the working conditions of the researcher, preserving its autonomy from funders and policy makers, and ensuring the dissemination of its results.

  13. Secretion of phosphomannosyl-deficient arylsulphatase A and cathepsin D from isolated human macrophages.

    Science.gov (United States)

    Muschol, Nicole; Matzner, Ulrich; Tiede, Stephan; Gieselmann, Volkmar; Ullrich, Kurt; Braulke, Thomas

    2002-12-15

    The transfer of macrophage-secreted arylsulphatase A (ASA) to enzyme-deficient brain cells is part of the therapeutic concept of bone marrow transplantation in lysosomal storage diseases. Here we have investigated this transfer in vitro. The uptake of (125)I-labelled recombinant human ASA purified from ASA-overexpressing mouse embryonic fibroblasts deficient for mannose 6-phosphate (M6P) receptors in a mouse ASA-deficient astroglial cell line was completely inhibited by M6P. In contrast, when ASA-deficient astroglial cells were incubated with secretions of [(35)S]methionine-labelled human macrophages or mouse microglia, containing various lysosomal enzymes, neither ASA nor cathepsin D (CTSD) were detected in acceptor cells. Co-culturing of metabolically labelled macrophages with ASA-deficient glial cells did not result in an M6P-dependent transfer of ASA or CTSD between these two cell types. In secretions of [(33)P]phosphate-labelled macrophages no or weakly phosphorylated ASA and CTSD precursor polypeptides were found, whereas both intracellular and secreted ASA from ASA-overexpressing baby hamster kidney cells displayed (33)P-labelled M6P residues. Finally, the uptake of CTSD from secretions of [(35)S]methionine-labelled macrophages in rat hepatocytes was M6P-independent. These data indicated that lysosomal enzymes secreted by human macrophages or a mouse microglial cell line cannot be endocytosed by brain cells due to the failure to equip newly synthesized lysosomal enzymes with the M6P recognition marker efficiently. The data suggest that other mechanisms than the proposed M6P-dependent secretion/recapture of lysosomal enzymes might be responsible for therapeutic effects of bone marrow transplantation in the brain. PMID:12296771

  14. Postnatal development of the myenteric glial network and its modulation by butyrate.

    Science.gov (United States)

    Cossais, François; Durand, Tony; Chevalier, Julien; Boudaud, Marie; Kermarrec, Laetitia; Aubert, Philippe; Neveu, Isabelle; Naveilhan, Philippe; Neunlist, Michel

    2016-06-01

    The postnatal period is crucial for the development of gastrointestinal (GI) functions. The enteric nervous system is a key regulator of GI functions, and increasing evidences indicate that 1) postnatal maturation of enteric neurons affect the development of GI functions, and 2) microbiota-derived short-chain fatty acids can be involved in this maturation. Although enteric glial cells (EGC) are central regulators of GI functions, the postnatal evolution of their phenotype remains poorly defined. We thus characterized the postnatal evolution of EGC phenotype in the colon of rat pups and studied the effect of short-chain fatty acids on their maturation. We showed an increased expression of the glial markers GFAP and S100β during the first postnatal week. As demonstrated by immunohistochemistry, a structured myenteric glial network was observed at 36 days in the rat colons. Butyrate inhibited EGC proliferation in vivo and in vitro but had no effect on glial marker expression. These results indicate that the EGC myenteric network continues to develop after birth, and luminal factors such as butyrate endogenously produced in the colon may affect this development. PMID:27056724

  15. Cinnamon Polyphenols Attenuate Neuronal Death and Glial Swelling in Ischemic Injury

    Science.gov (United States)

    Brain edema is a major complication associated with ischemic stroke and is characterized by a volumetric enlargement of the brain. Astrocyte swelling is a major component of brain edema. We investigated the protective effects of polyphenols isolated from green tea and cinnamon in C6 glial cultures s...

  16. CONCENTRATION OF GLIAL FIBRILLARY ACIDIC PROTEIN INCREASES WITH AGE IN THE MOUSE AND RAT BRAIN

    Science.gov (United States)

    The role of aging in the expression of the astrocyte protein, glial fibrillary acidic protein (GFAP), was examined. n both mice and rats the concentration of GFAP increased throughout the brain as a function of aging. he largest increase (2-fold) was observed in striatum for both...

  17. INCREASE IN GLIAL FIBRILLARY ACIDIC PROTEIN FOLLOWS BRAIN HYPERTHERMIA IN RATS

    Science.gov (United States)

    Previously, the authors have demonstrated that an increase in the astrocyte-associated protein, glial fibrillary acidic protein (GFAP), accompanies brain injury induced by a variety of chemical insults. In the present study the authors examined the effects of microwave-induced hy...

  18. Involvement of glial cells in the neurotoxicity of parathion and chlorpyrifos

    International Nuclear Information System (INIS)

    An in vitro model, the aggregating brain cell culture of fetal rat telencephalon, has been used to investigate the influence of glial cells on the neurotoxicity of two organophosphorus pesticides (OPs), chlorpyrifos and parathion. Mixed-cell aggregate cultures were treated continuously for 10 days between DIV 5 and 15. Parathion induced astrogliosis at concentration at which MAP-2 immunostaining, found here to be more sensitive than neuron-specific enzyme activities, was not affected. In contrast, chlorpyrifos induced a comparatively weak gliotic reaction, and only at concentrations at which neurons were already affected. After similar treatments, increased neurotoxicity of parathion and chlorpyrifos was found in aggregate cultures deprived of glial cells. These results suggest that glial cells provide neuroprotection against OPs toxicity. To address the question of the difference in toxicity between parathion and chlorpyrifos, the toxic effects of their leaving groups, p-nitrophenol and trichloropyridinol, were studied in mixed-cell aggregates. General cytotoxicity was more pronounced for trichloropyridinol and both compounds had similar toxic effects on neuron-specific enzyme activities. In contrast, trichloropyridinol induced a much stronger decrease in glutamine synthetase activity, the enzymatic marker of astrocytes. Trichloropyridinol may exert a toxic effect on astrocytes, compromising their neuroprotective function, thus exacerbating the neurotoxicity of chlorpyrifos. This is in line with the suggestion that glial cells may contribute to OPs neurotoxicity, and with the view that OPs may exert their neurotoxic effects through different mechanisms

  19. Potential primary roles of glial cells in the mechanisms of psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Kazuhiko eYamamuro

    2015-05-01

    Full Text Available While neurons have long been considered the major player in multiple brain functions such as perception, emotion and memory, glial cells have been relegated to a far lesser position, acting as merely a glue to support neurons. Multiple lines of recent evidence however, have revealed that glial cells such as oligodendrocytes, astrocytes and microglia, substantially impact on neuronal function and activities and are significantly involved in the underlying pathobiology of psychiatric disorders. Indeed, a growing body of evidence indicates that glial cells interact extensively with neurons both chemically (e.g. through neurotransmitters, neurotrophic factors and cytokines and physically (e.g. through gap junctions, supporting a role for these cells as likely significant modifiers not only of neural function in brain development but also disease pathobiology. Since questions have lingered as to whether glial dysfunction plays a primary role in the biology of neuropsychiatric disorders or a role related solely to their support of neuronal physiology in these diseases, informative and predictive animal models have been developed over the last decade. In this article, we review recent findings uncovered using glia-specific genetically modified mice with which we can evaluate both the causation of glia dysfunction and its potential role in neuropsychiatric disorders such as autism and schizophrenia.

  20. Potential primary roles of glial cells in the mechanisms of psychiatric disorders.

    Science.gov (United States)

    Yamamuro, Kazuhiko; Kimoto, Sohei; Rosen, Kenneth M; Kishimoto, Toshifumi; Makinodan, Manabu

    2015-01-01

    While neurons have long been considered the major player in multiple brain functions such as perception, emotion, and memory, glial cells have been relegated to a far lesser position, acting as merely a "glue" to support neurons. Multiple lines of recent evidence, however, have revealed that glial cells such as oligodendrocytes, astrocytes, and microglia, substantially impact on neuronal function and activities and are significantly involved in the underlying pathobiology of psychiatric disorders. Indeed, a growing body of evidence indicates that glial cells interact extensively with neurons both chemically (e.g., through neurotransmitters, neurotrophic factors, and cytokines) and physically (e.g., through gap junctions), supporting a role for these cells as likely significant modifiers not only of neural function in brain development but also disease pathobiology. Since questions have lingered as to whether glial dysfunction plays a primary role in the biology of neuropsychiatric disorders or a role related solely to their support of neuronal physiology in these diseases, informative and predictive animal models have been developed over the last decade. In this article, we review recent findings uncovered using glia-specific genetically modified mice with which we can evaluate both the causation of glia dysfunction and its potential role in neuropsychiatric disorders such as autism and schizophrenia. PMID:26029044

  1. Controlled adhesion and growth of long term glial and neuronal cultures on Parylene-C.

    Directory of Open Access Journals (Sweden)

    Evangelos Delivopoulos

    Full Text Available This paper explores the long term development of networks of glia and neurons on patterns of Parylene-C on a SiO(2 substrate. We harvested glia and neurons from the Sprague-Dawley (P1-P7 rat hippocampus and utilized an established cell patterning technique in order to investigate cellular migration, over the course of 3 weeks. This work demonstrates that uncontrolled glial mitosis gradually disrupts cellular patterns that are established early during culture. This effect is not attributed to a loss of protein from the Parylene-C surface, as nitrogen levels on the substrate remain stable over 3 weeks. The inclusion of the anti-mitotic cytarabine (Ara-C in the culture medium moderates glial division and thus, adequately preserves initial glial and neuronal conformity to underlying patterns. Neuronal apoptosis, often associated with the use of Ara-C, is mitigated by the addition of brain derived neurotrophic factor (BDNF. We believe that with the right combination of glial inhibitors and neuronal promoters, the Parylene-C based cell patterning method can generate structured, active neural networks that can be sustained and investigated over extended periods of time. To our knowledge this is the first report on the concurrent application of Ara-C and BDNF on patterned cell cultures.

  2. Glial-cell-derived neuroregulators control type 3 innate lymphoid cells and gut defence.

    Science.gov (United States)

    Ibiza, Sales; García-Cassani, Bethania; Ribeiro, Hélder; Carvalho, Tânia; Almeida, Luís; Marques, Rute; Misic, Ana M; Bartow-McKenney, Casey; Larson, Denise M; Pavan, William J; Eberl, Gérard; Grice, Elizabeth A; Veiga-Fernandes, Henrique

    2016-07-21

    Group 3 innate lymphoid cells (ILC3) are major regulators of inflammation and infection at mucosal barriers. ILC3 development is thought to be programmed, but how ILC3 perceive, integrate and respond to local environmental signals remains unclear. Here we show that ILC3 in mice sense their environment and control gut defence as part of a glial–ILC3–epithelial cell unit orchestrated by neurotrophic factors. We found that enteric ILC3 express the neuroregulatory receptor RET. ILC3-autonomous Ret ablation led to decreased innate interleukin-22 (IL-22), impaired epithelial reactivity, dysbiosis and increased susceptibility to bowel inflammation and infection. Neurotrophic factors directly controlled innate Il22 downstream of the p38 MAPK/ERK-AKT cascade and STAT3 activation. Notably, ILC3 were adjacent to neurotrophic-factor-expressing glial cells that exhibited stellate-shaped projections into ILC3 aggregates. Glial cells sensed microenvironmental cues in a MYD88-dependent manner to control neurotrophic factors and innate IL-22. Accordingly, glial-intrinsic Myd88 deletion led to impaired production of ILC3-derived IL-22 and a pronounced propensity towards gut inflammation and infection. Our work sheds light on a novel multi-tissue defence unit, revealing that glial cells are central hubs of neuron and innate immune regulation by neurotrophic factor signals. PMID:27409807

  3. Involvement of interleukin-1 in glial responses to lipopolysaccharide: endogenous versus exogenous interleukin-1 actions.

    Science.gov (United States)

    Molina-Holgado, F; Toulmond, S; Rothwell, N J

    2000-11-01

    Interleukin-1beta (IL-1beta) participates in neuroinflammation and neurodegeneration. Its mechanisms of action are not fully understood, but appear to involve complex interactions between neurons and glia. The objective of this study was to determine the involvement of endogenous IL-1beta in inflammatory responses to LPS in cultured mouse glial cells, and compare this to the effects of exogenous IL-1beta. Activation of primary mixed glial cultures by incubation with LPS (1 microgram/ml, 24 h), caused marked (approximately ten-fold) increases in release of NO, twenty-fold increases in PGE(2) and ninety-fold increases of IL-6 release. Incubation with human recombinant IL-1beta (100 ng/ml) also stimulated NO and IL-6 release to a similar extent to LPS, but IL-1beta (1 or 100 ng/ml) caused only modest increases (approximately seven-fold) in PGE(2) release. Co-incubation with IL-1ra inhibited the effects of LPS on NO release (-65%) and IL-6 production (-30%), but failed to reduce PGE(2) release. These results indicate that exogenous IL-1beta induces release of NO, PGE(2) and IL-6 in mixed glial cultures, and that endogenous IL-1beta mediates inflammatory actions of LPS on NO and to a lesser extent IL-6, but not on PGE(2) release in mixed glial cultures. Indeed endogenous IL-1beta appears to inhibit LPS-induced PGE(2) release. PMID:11063815

  4. Effects of estrogen on collagen gel contraction by human retinal glial cells

    Institute of Scientific and Technical Information of China (English)

    QIU Qing-hua; CHEN Zhi-Yi; YIN Li-li; ZHENG Zhi; WU Xing-wei

    2012-01-01

    Background There are definite gender differences in patients with macular holes.Menopausal women over 50 years are most affected.We aimed to observe the effect of estrogen on collagen gel contraction by cultured human retinal glial cells.It is speculated that estrogen could strengthen the tensile stress of the macula by maintaining the correct morphology and contraction.Methods Estrogen was used to determine its effects on collagen gel contraction,and its function was measured using morphological changes in cells.Human retinal glial cells were cultured in collagen solution.The cells were then exposed to collagen gels and the degree of contraction of the gel was determined.Results Estrogen at differing concentrations had no effect on the growth of human retinal glial cells.However,after exposed to collagen gel block,less contraction was noted in the estrogen-treated group than in the control group.Conclusions Estrogen can inhibit collagen gel contraction by glial cells.These results suggest a mechanism for macular hole formation,which is observed in menopausal females.

  5. Long-distance mechanism of neurotransmitter recycling mediated by glial network facilitates visual function in Drosophila

    OpenAIRE

    Chaturvedi, Ratna; Reddig, Keith; Li, Hong-Sheng

    2014-01-01

    Neurons communicate at synapses through neurotransmitters. For sustained neuronal signaling, neurotransmitters are recycled after release from neuronal terminals. During this process, perisynaptic glial cells take in and convert neurotransmitters such as glutamate, GABA, and histamine into inactive metabolites for transport. It has been assumed that inactive metabolites are delivered directly into neighboring neuronal terminals for neurotransmitter regeneration. Our work in the fruit fly, how...

  6. Fascin expression [corrected] in glial tumors and its prognostic significance in glioblastomas.

    Science.gov (United States)

    Gunal, Armagan; Onguru, Onder; Safali, Mukerrem; Beyzadeoglu, Murat

    2008-08-01

    Fascin is a -55 kDa-actin binding protein. Actin bundles rearranged by fascin proteins are concentrated in cell membrane protrusions and these protrusions provide motility of the cell. In this study, we evaluated fascin expression in glial tumors and its relation with histologic grade. Its prognostic value in glioblastomas (GBs) was also investigated. Seventy-six glial tumors including 44 glioblastomas with known survival time, 18 anaplastic astrocytomas (AAs), six diffuse astrocytomas (DAs), and eight pilocytic astrocytomas (PAs) were examined immunohistochemically for fascin expression. Fascin was observed in the neurons of normal brain tissue and endothelium of vascular spaces in the glial tumors. Fascin expression was correlated with histologic grade in DAs. PAs expressed low levels of fascin. Half of the GBs showed high levels of fascin expression. In the GB group, overall survival was poor for cases with percentage of stained cells >50% having moderate or strong staining intensity. In GBs, overall survival was also poor for >50-year-old cases and cases that refused radiotherapy. Multivariate Cox regression analysis revealed that age (>50 years, P=0.021) and higher level of fascin expression (immunohistochemical score >8, P=0.040) were independent poor prognostic factors. In conclusion, fascin expression levels are correlated with histologic grade and fascin overexpression may play an important role in the biologic behavior of glial astrocytic tumors and in the prognosis of GBs. PMID:18298442

  7. A New CRB1 Rat Mutation Links Müller Glial Cells to Retinal Telangiectasia

    NARCIS (Netherlands)

    Zhao, Min; Andrieu-Soler, Charlotte; Kowalczuk, Laura; Paz Cortés, María; Berdugo, Marianne; Dernigoghossian, Marilyn; Halili, Francisco; Jeanny, Jean-Claude; Goldenberg, Brigitte; Savoldelli, Michèle; El Sanharawi, Mohamed; Naud, Marie-Christine; van Ijcken, Wilfred; Pescini-Gobert, Rosanna; Martinet, Danielle; Maass, Alejandro; Wijnholds, J.; Crisanti, Patricia; Rivolta, Carlo; Behar-Cohen, Francine

    2015-01-01

    We have identified and characterized a spontaneous Brown Norway from Janvier rat strain (BN-J) presenting a progressive retinal degeneration associated with early retinal telangiectasia, neuronal alterations, and loss of retinal Müller glial cells resembling human macular telangiectasia type 2 (MacT

  8. A new CRB1 rat mutation links Müller glial cells to retinal telangiectasia

    NARCIS (Netherlands)

    M. Zhao (Min); C. Andrieu-Soler (Charlotte); L. Kowalczuk (Laura); M.P. Cortés (María Paz); M. Berdugo (Marianne); M. Dernigoghossian (Marilyn); F. Halili (Francisco); J.-C. Jeanny (Jean-Claude); B. Goldenberg (Brigitte); M. Savoldelli (Michèle); M. El Sanharawi (Mohamed); M.-C. Naud (Marie-Christine); W.F.J. van IJcken (Wilfred); R. Pescini-Gobert (Rosanna); D. Martinet (Danielle); A. Maass (Alejandro); J. Wijnholds (Jan); P. Crisanti (Patricia); C. Rivolta (Carlo); F. Behar-Cohen (Francine)

    2015-01-01

    textabstractWe have identified and characterized a spontaneous Brown Norway from Janvier rat strain (BN-J) presenting a progressive retinal degeneration associated with early retinal telangiectasia, neuronal alterations, and loss of retinal Müller glial cells resembling human macular telangiectasia

  9. Multiscale Vision Model Highlights Spontaneous Glial Calcium Waves Recorded by 2-Photon Imaging in Brain Tissue

    DEFF Research Database (Denmark)

    Brazhe, Alexey; Mathiesen, Claus; Lauritzen, Martin

    2013-01-01

    Intercellular glial calcium waves constitute a signaling pathway which can be visualized by fluorescence imaging of cytosolic Ca2+ changes. However, there is a lack of procedures for sensitive and reliable detection of calcium waves in noisy multiphoton imaging data. Here we extend multiscale vis...

  10. Microbiota controls the homeostasis of glial cells in the gut lamina propria

    NARCIS (Netherlands)

    Kabouridis, Panagiotis S; Lasrado, Reena; McCallum, Sarah; Chng, Song Hui; Snippert, HJG; Clevers, Hans; Pettersson, Sven; Pachnis, Vassilis

    2015-01-01

    The intrinsic neural networks of the gastrointestinal tract are derived from dedicated neural crest progenitors that colonize the gut during embryogenesis and give rise to enteric neurons and glia. Here, we study how an essential subpopulation of enteric glial cells (EGCs) residing within the intest

  11. Chemokine expression by glial cells directs leukocytes to sites of axonal injury in the CNS

    DEFF Research Database (Denmark)

    Babcock, Alicia A; Kuziel, William A; Rivest, Serge;

    2003-01-01

    Innate responses in the CNS are critical to first line defense against infection and injury. Leukocytes migrate to inflammatory sites in response to chemokines. We studied leukocyte migration and glial chemokine expression within the denervated hippocampus in response to axonal injury caused by e...

  12. Extracellular matrix of cultured glial cells: Selective expression of chondroitin 4-sulfate by type-2 astrocytes and their progenitors

    International Nuclear Information System (INIS)

    We have studied the extracellular matrix composition of cultured glial cells by immunocytochemistry with different monoclonal and polyclonal antibodies. Double immunofluorescence experiments and metabolic labeling with [3H]glucosamine performed in different types of cerebellar and cortical cultures showed that bipotential progenitors for type-2 astrocytes and for oligodendrocytes synthesize chondroitin sulfate (CS) and deposit this proteoglycan in their extracellular matrix. The distribution of the various [3H]glucosamine-labeled glycosaminoglycans between the intracellular and the extracellular space was different. CS was present both within the cells and in the culture medium, although in different amounts. Bi-potential progenitors became also O4-positive during their development in vitro. At the stage of O4-positivity they were still stained with antibodies against CS. However, when the progenitor cells were maintained in serum-free medium and differentiated into Gal-C-positive oligodendrocytes, they became CS-negative. In the presence of fetal calf serum in the culture medium, the bipotential progenitors differentiated into GFAP-positive type-2 astrocytes. These cells still expressed CS: their Golgi area and their surface were stained with anti-CS antibodies. Staining with monoclonal antibodies specific for different types of CS (4-sulfate, 6-sulfate, and unsulfated) revealed that both bipotential progenitors and type-2 astrocytes synthesized only chondroitin 4-sulfate. Type-1 astrocytes were negative for both the polyclonal and the monoclonal anti-CS antibodies. Finally, type-2 astrocytes and their progenitors were weakly stained with anti-laminin antibodies and unstained with anti-fibronectin. Type-1 astrocytes were positive for both anti-laminin and anti-fibronectin antibodies and appeared to secrete fibronectin in the extracellular space

  13. Glial glutamate transporter and glutamine synthetase regulate GABAergic synaptic strength in the spinal dorsal horn.

    Science.gov (United States)

    Jiang, Enshe; Yan, Xisheng; Weng, Han-Rong

    2012-05-01

    Decreased GABAergic synaptic strength ('disinhibition') in the spinal dorsal horn is a crucial mechanism contributing to the development and maintenance of pathological pain. However, mechanisms leading to disinhibition in the spinal dorsal horn remain elusive. We investigated the role of glial glutamate transporters (GLT-1 and GLAST) and glutamine synthetase in maintaining GABAergic synaptic activity in the spinal dorsal horn. Electrically evoked GABAergic inhibitory post-synaptic currents (eIPSCs), spontaneous IPSCs (sIPSCs) and miniature IPSCs were recorded in superficial spinal dorsal horn neurons of spinal slices from young adult rats. We used (2S,3S)-3-[3-[4-(trifluoromethyl)benzoylamino]benzyloxy]aspartate (TFB-TBOA), to block both GLT-1 and GLAST and dihydrokainic acid to block only GLT-1. We found that blockade of both GLAST and GLT-1 and blockade of only GLT-1 in the spinal dorsal horn decreased the amplitude of GABAergic eIPSCs, as well as both the amplitude and frequency of GABAergic sIPSCs or miniature IPSCs. Pharmacological inhibition of glial glutamine synthetase had similar effects on both GABAergic eIPSCs and sIPSCs. We provided evidence demonstrating that the reduction in GABAergic strength induced by the inhibition of glial glutamate transporters is due to insufficient GABA synthesis through the glutamate-glutamine cycle between astrocytes and neurons. Thus, our results indicate that deficient glial glutamate transporters and glutamine synthetase significantly attenuate GABAergic synaptic strength in the spinal dorsal horn, which may be a crucial synaptic mechanism underlying glial-neuronal interactions caused by dysfunctional astrocytes in pathological pain conditions. PMID:22339645

  14. Valproic acid stimulates proliferation of glial precursors during cortical gliogenesis in developing rat.

    Science.gov (United States)

    Lee, Hee Jae; Dreyfus, Cheryl; DiCicco-Bloom, Emanuel

    2016-07-01

    Valproic acid (VPA) is a neurotherapeutic drug prescribed for seizures, bipolar disorder, and migraine, including women of reproductive age. VPA is a well-known teratogen that produces congenital malformations in many organs including the nervous system, as well as later neurodevelopmental disorders, including mental retardation and autism. In developing brain, few studies have examined VPA effects on glial cells, particularly astrocytes. To investigate effects on primary glial precursors, we developed new cell culture and in vivo models using frontal cerebral cortex of postnatal day (P2) rat. In vitro, VPA exposure elicited dose-dependent, biphasic effects on DNA synthesis and proliferation. In vivo VPA (300 mg/kg) exposure from P2 to P4 increased both DNA synthesis and cell proliferation, affecting primarily astrocyte precursors, as >75% of mitotic cells expressed brain lipid-binding protein. Significantly, the consequence of early VPA exposure was increased astrocytes, as both S100-β+ cells and glial fibrillary acidic protein were increased in adolescent brain. Molecularly, VPA served as an HDAC inhibitor in vitro and in vivo as enhanced proliferation was accompanied by increased histone acetylation, whereas it elicited changes in culture in cell-cycle regulators, including cyclin D1 and E, and cyclin-dependent kinase (CDK) inhibitors, p21 and p27. Collectively, these data suggest clinically relevant VPA exposures stimulate glial precursor proliferation, though at higher doses can elicit inhibition through differential regulation of CDK inhibitors. Because changes in glial cell functions are proposed as mechanisms contributing to neuropsychiatric disorders, these observations suggest that VPA teratogenic actions may be mediated through changes in astrocyte generation during development. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 780-798, 2016. PMID:26505176

  15. Glial cell-expressed mechanosensitive channel TRPV4 mediates infrasound-induced neuronal impairment.

    Science.gov (United States)

    Shi, Ming; Du, Fang; Liu, Yang; Li, Li; Cai, Jing; Zhang, Guo-Feng; Xu, Xiao-Fei; Lin, Tian; Cheng, Hao-Ran; Liu, Xue-Dong; Xiong, Li-Ze; Zhao, Gang

    2013-11-01

    Vibroacoustic disease, a progressive and systemic disease, mainly involving the central nervous system, is caused by excessive exposure to low-frequency but high-intensity noise generated by various heavy transportations and machineries. Infrasound is a type of low-frequency noise. Our previous studies demonstrated that infrasound at a certain intensity caused neuronal injury in rats but the underlying mechanism(s) is still largely unknown. Here, we showed that glial cell-expressed TRPV4, a Ca(2+)-permeable mechanosensitive channel, mediated infrasound-induced neuronal injury. Among different frequencies and intensities, infrasound at 16 Hz and 130 dB impaired rat learning and memory abilities most severely after 7-14 days exposure, a time during which a prominent loss of hippocampal CA1 neurons was evident. Infrasound also induced significant astrocytic and microglial activation in hippocampal regions following 1- to 7-day exposure, prior to neuronal apoptosis. Moreover, pharmacological inhibition of glial activation in vivo protected against neuronal apoptosis. In vitro, activated glial cell-released proinflammatory cytokines IL-1β and TNF-α were found to be key factors for this neuronal apoptosis. Importantly, infrasound induced an increase in the expression level of TRPV4 both in vivo and in vitro. Knockdown of TRPV4 expression by siRNA or pharmacological inhibition of TRPV4 in cultured glial cells decreased the levels of IL-1β and TNF-α, attenuated neuronal apoptosis, and reduced TRPV4-mediated Ca(2+) influx and NF-κB nuclear translocation. Finally, using various antagonists we revealed that calmodulin and protein kinase C signaling pathways were involved in TRPV4-triggered NF-κB activation. Thus, our results provide the first evidence that glial cell-expressed TRPV4 is a potential key factor responsible for infrasound-induced neuronal impairment. PMID:24002225

  16. Pheochromocytomas and secreting paragangliomas

    Directory of Open Access Journals (Sweden)

    Gimenez-Roqueplo Anne-Paule

    2006-12-01

    Full Text Available Abstract Catecholamine-producing tumors may arise in the adrenal medulla (pheochromocytomas or in extraadrenal chromaffin cells (secreting paragangliomas. Their prevalence is about 0.1% in patients with hypertension and 4% in patients with a fortuitously discovered adrenal mass. An increase in the production of catecholamines causes symptoms (mainly headaches, palpitations and excess sweating and signs (mainly hypertension, weight loss and diabetes reflecting the effects of epinephrine and norepinephrine on α- and β-adrenergic receptors. Catecholamine-producing tumors mimic paroxysmal conditions with hypertension and/or cardiac rhythm disorders, including panic attacks, in which sympathetic activation linked to anxiety reproduces the same signs and symptoms. These tumors may be sporadic or part of any of several genetic diseases: familial pheochromocytoma-paraganglioma syndromes, multiple endocrine neoplasia type 2, neurofibromatosis 1 and von Hippel-Lindau disease. Familial cases are diagnosed earlier and are more frequently bilateral and recurring than sporadic cases. The most specific and sensitive diagnostic test for the tumor is the determination of plasma or urinary metanephrines. The tumor can be located by computed tomography, magnetic resonance imaging and metaiodobenzylguanidine scintigraphy. Treatment requires resection of the tumor, generally by laparoscopic surgery. About 10% of tumors are malignant either at first operation or during follow-up, malignancy being diagnosed by the presence of lymph node, visceral or bone metastases. Recurrences and malignancy are more frequent in cases with large or extraadrenal tumors. Patients, especially those with familial or extraadrenal tumors, should be followed-up indefinitely.

  17. Ergodic Secret Alignment

    CERN Document Server

    Bassily, Raef

    2010-01-01

    In this paper, we introduce two new achievable schemes for the fading multiple access wiretap channel (MAC-WT). In the model that we consider, we assume that perfect knowledge of the state of all channels is available at all the nodes in a causal fashion. Our schemes use this knowledge together with the time varying nature of the channel model to align the interference from different users at the eavesdropper perfectly in a one-dimensional space while creating a higher dimensionality space for the interfering signals at the legitimate receiver hence allowing for better chance of recovery. While we achieve this alignment through signal scaling at the transmitters in our first scheme (scaling based alignment (SBA)), we let nature provide this alignment through the ergodicity of the channel coefficients in the second scheme (ergodic secret alignment (ESA)). For each scheme, we obtain the resulting achievable secrecy rate region. We show that the secrecy rates achieved by both schemes scale with SNR as 1/2log(SNR...

  18. Secret Key Generation via a Modified Quantum Secret Sharing Protocol

    Energy Technology Data Exchange (ETDEWEB)

    Smith IV, Amos M [ORNL; Evans, Philip G [ORNL; Lawrie, Benjamin J [ORNL; Legre, Matthieu [ID Quantique, Inc.; Lougovski, Pavel [ORNL; Ray, William R [ORNL; Williams, Brian P [ORNL; Qi, Bing [ORNL; Grice, Warren P [ORNL

    2015-01-01

    We present and experimentally show a novel protocol for distributing secret information between two and only two parties in a N-party single-qubit Quantum Secret Sharing (QSS) system. We demonstrate this new algorithm with N = 3 active parties over 6km of telecom. ber. Our experimental device is based on the Clavis2 Quantum Key Distribution (QKD) system built by ID Quantique but is generalizable to any implementation. We show that any two out of the N parties can build secret keys based on partial information from each other and with collaboration from the remaining N > 2 parties. This algorithm allows for the creation of two-party secret keys were standard QSS does not and signicantly reduces the number of resources needed to implement QKD on a highly connected network such as the electrical grid.

  19. Secret key generation via a modified quantum secret sharing protocol

    Science.gov (United States)

    Smith, A. M.; Evans, P. G.; Lawrie, B.; Legré, M.; Lougovski, P.; Ray, W.; Williams, B. P.; Qi, B.; Grice, W. P.

    2015-05-01

    We present and experimentally show a novel protocol for distributing secret information between two and only two parties in a N-party single-qubit Quantum Secret Sharing (QSS) system. We demonstrate this new algorithm with N = 3 active parties over ~6km of telecom. fiber. Our experimental device is based on the Clavis2 Quantum Key Distribution (QKD) system built by ID Quantique but is generalizable to any implementation. We show that any two out of the N parties can build secret keys based on partial information from each other and with collaboration from the remaining N - 2 parties. This algorithm allows for the creation of two-party secret keys were standard QSS does not and significantly reduces the number of resources needed to implement QKD on a highly connected network such as the electrical grid.

  20. Radiation-induced reduction of the glial population during development disrupts the formation of olfactory glomeruli in an insect

    International Nuclear Information System (INIS)

    Interactions between neurons and between neurons and glial cells have been shown by a number of investigators to be critical for normal development of the nervous system. In the olfactory system of Manduca sexta, sensory axons have been shown to induce the formation of synaptic glomeruli in the antennal lobe of the brain. Oland and Tolbert (1987) found that the growth of sensory axons into the developing antennal lobe causes changes in glial shape and disposition that presage the establishment of glomeruli, each surrounded by a glial envelope. Several lines of evidence lead us to hypothesize that the glial cells of the lobe may be acting as intermediaries in developmental interactions between sensory axons and neurons of the antennal lobe. In the present study, we have tested this hypothesis by using gamma-radiation to reduce the number of glial cells at a time when neurons of the antennal system are postmitotic but glomeruli have not yet developed. When glial numbers are severely reduced, the neuropil of the resulting lobe lacks glomeruli. Despite the presence of afferent axons, the irradiated lobe has many of the features of a lobe that developed in the absence of afferent axons. Our findings indicate that the glial cells must play a necessary role in the inductive influence of the afferent axons

  1. Structural and functional insights into the ligand-binding domain of a nonduplicated retinoid X nuclear receptor from the invertebrate chordate amphioxus.

    Science.gov (United States)

    Tocchini-Valentini, Giuseppe D; Rochel, Natacha; Escriva, Hector; Germain, Pierre; Peluso-Iltis, Carole; Paris, Mathilde; Sanglier-Cianferani, Sarah; Van Dorsselaer, Alain; Moras, Dino; Laudet, Vincent

    2009-01-16

    Retinoid X nuclear receptors (RXRs), as well as their insect orthologue, ultraspiracle protein (USP), play an important role in the transcription regulation mediated by the nuclear receptors as the common partner of many other nuclear receptors. Phylogenetic and structural studies have shown that the several evolutionary shifts have modified the ligand binding ability of RXRs. To understand the vertebrate-specific character of RXRs, we have studied the RXR ligand-binding domain of the cephalochordate amphioxus (Branchiostoma floridae), an invertebrate chordate that predates the genome duplication that produced the three vertebrates RXRs (alpha, beta, and gamma). Here we report the crystal structure of a novel apotetramer conformation of the AmphiRXR ligand-binding domain, which shows some similarity with the structures of the arthropods RXR/USPs. AmphiRXR adopts an apo antagonist conformation with a peculiar conformation of helix H11 filling the binding pocket. In contrast to the arthropods RXR/USPs, which cannot be activated by any RXR ligands, our functional data show that AmphiRXR, like the vertebrates/mollusk RXRs, is able to bind and be activated by RXR ligands but less efficiently than vertebrate RXRs. Our data suggest that amphioxus RXR is, functionally, an intermediate between arthropods RXR/USPs and vertebrate RXRs. PMID:18986992

  2. Secret Key Generation From Mobility

    CERN Document Server

    Gungor, Onur; Koksal, C Emre

    2011-01-01

    We consider secret key generation from relative localization information of a pair of nodes in a mobile wireless network in the presence of a mobile eavesdropper. Our scheme consists of two phases: in the first phase, legitimate node pair exchanges beacon signals to establish localization information based on noisy observations of these beacons; in the second phase, nodes generate secret key bits via a public discussion. Our problem can be categorized under the source models of information theoretic secrecy, where the distance between the legitimate nodes acts as the observed common randomness. We characterize the achievable secret key bit rate in terms of the observation noise variance at the legitimate nodes and the eavesdropper. This work provides a framework that combines information theoretic secrecy and wireless localization, and proves that the localization information provides a significant additional resource for secret key generation in mobile wireless networks.

  3. Stimulation of incretin secreting cells

    OpenAIRE

    Pais, Ramona; Gribble, Fiona M.; Reimann, Frank

    2016-01-01

    The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide-1 (GLP-1) are secreted from enteroendocrine cells in the gut and regulate physiological and homeostatic functions related to glucose control, metabolism and food intake. This review provides a systematic summary of the molecular mechanisms underlying secretion from incretin cells, and an understanding of how they sense and interact with lumen and vascular factors and the enteric nervous system t...

  4. Nonlinear secret image sharing scheme.

    Science.gov (United States)

    Shin, Sang-Ho; Lee, Gil-Je; Yoo, Kee-Young

    2014-01-01

    Over the past decade, most of secret image sharing schemes have been proposed by using Shamir's technique. It is based on a linear combination polynomial arithmetic. Although Shamir's technique based secret image sharing schemes are efficient and scalable for various environments, there exists a security threat such as Tompa-Woll attack. Renvall and Ding proposed a new secret sharing technique based on nonlinear combination polynomial arithmetic in order to solve this threat. It is hard to apply to the secret image sharing. In this paper, we propose a (t, n)-threshold nonlinear secret image sharing scheme with steganography concept. In order to achieve a suitable and secure secret image sharing scheme, we adapt a modified LSB embedding technique with XOR Boolean algebra operation, define a new variable m, and change a range of prime p in sharing procedure. In order to evaluate efficiency and security of proposed scheme, we use the embedding capacity and PSNR. As a result of it, average value of PSNR and embedding capacity are 44.78 (dB) and 1.74t⌈log2 m⌉ bit-per-pixel (bpp), respectively. PMID:25140334

  5. Security of audio secret sharing scheme encrypting audio secrets with bounded shares

    OpenAIRE

    鷲尾, 槙也; 渡邊, 曜大

    2014-01-01

    Secret sharing is a method of encrypting a secret into multiple pieces called shares so that only qualified sets of shares can be employed to reconstruct the secret. Audio secret sharing (ASS) is an example of secret sharing whose decryption can be performed by human ears. This paper examines the security of an audio secret sharing scheme encrypting audio secrets with bounded shares, and optimizes the security with respect to the probability distribution used in its encryption.

  6. Emerging role of glial cells in the control of body weight

    Science.gov (United States)

    García-Cáceres, Cristina; Fuente-Martín, Esther; Argente, Jesús; Chowen, Julie A.

    2012-01-01

    Glia are the most abundant cell type in the brain and are indispensible for the normal execution of neuronal actions. They protect neurons from noxious insults and modulate synaptic transmission through affectation of synaptic inputs, release of glial transmitters and uptake of neurotransmitters from the synaptic cleft. They also transport nutrients and other circulating factors into the brain thus controlling the energy sources and signals reaching neurons. Moreover, glia express receptors for metabolic hormones, such as leptin and insulin, and can be activated in response to increased weight gain and dietary challenges. However, chronic glial activation can be detrimental to neurons, with hypothalamic astrocyte activation or gliosis suggested to be involved in the perpetuation of obesity and the onset of secondary complications. It is now accepted that glia may be a very important participant in metabolic control and a possible therapeutical target. Here we briefly review this rapidly advancing field. PMID:24024117

  7. Induction of the major heat-stress protein in purified rat glial cells

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, R.N.; Dwyer, B.E.; Welch, W.; Cole, R.; de Vellis, J.; Liotta, K.

    1988-05-01

    Cultured purified oligodendroglia and astroglia exposed to heat stress (45 degrees C, 10 or 20 min) synthesized a 68-kDa heat-stress protein, which migrates on two-dimensional gel electrophoresis and reacts with a specific monoclonal antibody suggesting it is similar to a major 72-kDa heat-shock protein previously reported in other cell types. This protein was not detected in control glial cultures. Actinomycin D prevented synthesis of this protein demonstrating an absolute requirement for newly synthesized mRNA. The response was prolonged by increasing the period of heat stress from 10 to 20 min. In addition to the 68-kDa HSP protein, the incorporation of radioactivity into 70-, 89-, and 97-kDa proteins was also increased after heating, but in contrast to the 68 kDa protein these proteins appeared to be made in control glial cultures.

  8. Reappraisal of Bergmann glial cells as modulators of cerebellar circuit function

    Directory of Open Access Journals (Sweden)

    Chris I De Zeeuw

    2015-07-01

    Full Text Available Just as there is a huge morphological and functional diversity of neuron types specialized for specific aspects of information processing in the brain, astrocytes have equally distinct morphologies and functions that aid optimal functioning of the circuits in which they are embedded. One type of astrocyte, the Bergmann glial cell of the cerebellum, is a prime example of a highly diversified astrocyte type, the architecture of which is adapted to the cerebellar circuit and facilitates an impressive range of functions that optimize information processing in the adult brain. In this review we expand on the function of the Bergmann glial cell in the cerebellum to highlight the importance of astrocytes not only in housekeeping functions, but also in contributing to plasticity and information processing in the cerebellum.

  9. [State of the blood coagulation in glial tumors of the brain].

    Science.gov (United States)

    Burgman, G P; Kachkov, I A; Vial'tseva, I N; Shcherbakova, G G

    1979-01-01

    The data presented may be of definite value in the prevention of hemorrhage and thrombosis in patients with malignant glial tumors. A malignant glioma may lead to increased activity of the blood coagulation system (BCS). Preoperative staining of the tumor was not attended by marked changes in the BCS and blood viscocity, though a tendency towards an increase in BCS activity according to some of the indices may sometimes be noted. Chemotherapy with nitrosourea and methotrexate was attended by thrombocytopenia but there was practically no changes in the other BCS indices. The postoperative period is usually marked by increased BCS activity according to most of the indices. Increased blood viscocity is often encountered in patients with glial cerebral tumors in the preoperative and postoperative periods, which is evidently due to the intensive dehydration therapy to which they are subjected in marked increase of intracranial pressure. PMID:223352

  10. Enteric glial cells and their role in gastrointestinal motor abnormalities: Introducing the neuro-gliopathies

    Institute of Scientific and Technical Information of China (English)

    Gabrio Bassotti; Vincenzo Villanacci; Simona Fisogni; Elisa Rossi; Paola Baronio; Carlo Clerici; Christoph A Maurer; Gieri Cathomas; Elisabetta Antonelli

    2007-01-01

    The role of enteric glial cells has somewhat changed from that of mere mechanical support elements, gluing together the various components of the enteric nervous system, to that of active participants in the complex interrelationships of the gut motor and inflammatory events. Due to their multiple functions, spanning from supporting elements in the myenteric plexuses to neurotransmitters, to neuronal homeostasis, to antigen presenting cells, this cell population has probably more intriguing abilities than previously thought. Recently,some evidence has been accumulating that shows how these cells may be involved in the pathophysiological aspects of some diseases. This review will deal with the properties of the enteric glial cells more strictly related to gastrointestinal motor function and the human pathological conditions in which these cells may play a role, suggesting the possibility of enteric neurogliopathies.

  11. Crosslinked gelatin nanofibres: Preparation, characterisation and in vitro studies using glial-like cells

    International Nuclear Information System (INIS)

    Gelatin (GL) nanofibrous matrices mimicking the complex biological structure of the natural extracellular matrix (ECM) were prepared from aqueous solutions by electrospinning technique. GL nanofibres with a diameter size of around 300 nm were obtained optimising the process and solution parameters. To increase the GL stability in aqueous environment γ-glycidoxypropyltrimethoxysilane (GPTMS) was used as GL crosslinker. GPTMS crosslinking did not modify the nanofibrous matrix morphology: fibre diameter and membrane pores size were 327 ± 45 nm and 1.64 ± 0.37 μm, respectively. The produced GPTMS crosslinked GL nanofibres (GL/GPTMSNF) were found to support the in vitro adhesion, proliferation and survival of neonatal olfactory bulb ensheating cells (NOBECs). - Highlights: • Gelatin nanofibres were prepared from aqueous solution. • A silane-coupling agent was used as gelatin crosslinker. • Glial-like cells adhered and proliferated on the developed nanofibres. • Elongated morphology of glial-like cells was observed

  12. Neural stem cell activation and glial proliferation in the hippocampal CA3 region of posttraumatic epileptic rats

    Institute of Scientific and Technical Information of China (English)

    Yuanxiang Lin; Kun Lin; Dezhi Kang; Feng Wang

    2011-01-01

    The present study observed the dynamic expression of CD133, nuclear factor-κB and glial fibrillary acidic protein in the hippocampal CA3 area of the experimental posttraumatic epilepsy rats to investigate whether gliosis occurs after posttraumatic epilepsy. CD133 and nuclear factor-κB expression was increased at 1 day after posttraumatic epilepsy, peaked at 7 days, and gradually decreased up to 14 days, as seen by double-immunohistochemical staining. Glial fibrillary acidic protein/nuclear factor-κB double-labeled cells increased with time and peaked at 14 days after posttraumatic epilepsy. Results show that activation of hippocampal neural stem cells and glial proliferation after posttraumatic epilepsy-induced oxidative stress increases hippocampal glial cell density.

  13. The physiology of salivary secretion.

    Science.gov (United States)

    Proctor, Gordon B

    2016-02-01

    Saliva in the mouth is a biofluid produced mainly by three pairs of major salivary glands--the submandibular, parotid and sublingual glands--along with secretions from many minor submucosal salivary glands. Salivary gland secretion is a nerve-mediated reflex and the volume of saliva secreted is dependent on the intensity and type of taste and on chemosensory, masticatory or tactile stimulation. Long periods of low (resting or unstimulated) flow are broken by short periods of high flow, which is stimulated by taste and mastication. The nerve-mediated salivary reflex is modulated by nerve signals from other centers in the central nervous system, which is most obvious as hyposalivation at times of anxiety. An example of other neurohormonal influences on the salivary reflex is the circadian rhythm, which affects salivary flow and ionic composition. Cholinergic parasympathetic and adrenergic sympathetic autonomic nerves evoke salivary secretion, signaling through muscarinic M3 and adrenoceptors on salivary acinar cells and leading to secretion of fluid and salivary proteins. Saliva gland acinar cells are chloride and sodium secreting, and the isotonic fluid produced is rendered hypotonic by salivary gland duct cells as it flows to the mouth. The major proteins present in saliva are secreted by salivary glands, creating viscoelasticity and enabling the coating of oral surfaces with saliva. Salivary films are essential for maintaining oral health and regulating the oral microbiome. Saliva in the mouth contains a range of validated and potential disease biomarkers derived from epithelial cells, neutrophils, the microbiome, gingival crevicular fluid and serum. For example, cortisol levels are used in the assessment of stress, matrix metalloproteinases-8 and -9 appear to be promising markers of caries and periodontal disease, and a panel of mRNA and proteins has been proposed as a marker of oral squamous cell carcinoma. Understanding the mechanisms by which components enter

  14. The impact of the glial spatial buffering on the K+ Nernst potential

    OpenAIRE

    Noori, H. R.

    2011-01-01

    Astrocytes play a critical role in CNS metabolism, regulation of volume and ion homeostasis of the interstitial space. Of special relevance is their clearance of K+ that is released by active neurons into the extracellular space. Mathematical analysis of a modified Nernst equation for the electrochemical equilibrium of neuronal plasma membranes, suggests that K+ uptake by glial cells is not only relevant during neuronal activity but also has a non-neglectable impact on the basic electrical me...

  15. White Matter Tauopathy with Globular Glial Inclusions: A Distinct Sporadic Frontotemporal Lobar Degeneration

    OpenAIRE

    Kovacs, Gabor G.; Majtenyi, Katalin; Spina, Salvatore; Murrell, Jill R; Gelpi, Ellen; Hoftberger, Romana; Fraser, Graham; Crowther, R. Anthony; Goedert, Michel; Budka, Herbert; Ghetti, Bernardino

    2008-01-01

    Frontotemporal lobar degenerations are a group of disorders characterized by circumscribed degeneration of the frontal and temporal lobes and diverse histopathological features. We report clinical, neuropathological, ultrastructural, biochemical and genetic data on seven individuals with a four-repeat (4R) tauopathy characterized by the presence of globular glial inclusions (GGIs) in brain white matter. Clinical manifestations were compatible with the behavioral variant of frontotemporal deme...

  16. Curcumin alters expression of glial fibrillary acidic protein and nestin following chronic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Peng Zhang; Tianping Yu; Xiong Zhang; Yu Li

    2011-01-01

    Astrocytes can alter their appearance and become reactive following chronic cerebral ischemia. In the present study, a rat model of chronic cerebral ischemia was treated with 50 and 100 mg/kg curcumin. Results showed that pathological changes of neuronal injury in hippocampal CA1 area of rats induced by chronic cerebral ischemia were attenuated, as well as upregulated expression of glial fibrillary acidic protein and nestin, in a dose-dependent manner.

  17. DIAGNOSTIC VALUE OF THE DEJA VU PHENOMENON IN THE CLINICAL PICTURE OF GLIAL BRAIN TUMORS

    OpenAIRE

    Pavel Nikolaevich Vlasov; PavelNikolayevich Vlasov; A. V. Chervyakov; S V Urakov; A A Solokha

    2009-01-01

    In growing glial tumors, epileptic seizures are the first and only symptom of the disease in more than a third of cases. The seizure is commonly characterized by only psychopathological disorders that are frequently ignored by both patients and physicians. The deja vu (DV) phenomenon may be one of such symptoms. Its specific feature is that it occurs in both healthy individuals and patients with various brain pathologies. This investigation was undertaken to study the implication of the DV...

  18. Ciliary Neurotrophic Factor Protects Striatal Neurons against Excitotoxicity by Enhancing Glial Glutamate Uptake

    OpenAIRE

    Beurrier, Corinne; Faideau, Mathilde; Bennouar, Khaled-Ezaheir; Escartin, Carole; Kerkerian-Le Goff, Lydia; Bonvento, Gilles; Gubellini, Paolo

    2010-01-01

    Ciliary neurotrophic factor (CNTF) is a potent neuroprotective cytokine in different animal models of glutamate-induced excitotoxicity, although its action mechanisms are still poorly characterized. We tested the hypothesis that an increased function of glial glutamate transporters (GTs) could underlie CNTF-mediated neuroprotection. We show that neuronal loss induced by in vivo striatal injection of the excitotoxin quinolinic acid (QA) was significantly reduced (by ∼75%) in CNTF-treated anima...

  19. Dissociated neurons and glial cells derived from rat inferior colliculi after digestion with papain.

    Science.gov (United States)

    Kaiser, Odett; Aliuos, Pooyan; Wissel, Kirsten; Lenarz, Thomas; Werner, Darja; Reuter, Günter; Kral, Andrej; Warnecke, Athanasia

    2013-01-01

    The formation of gliosis around implant electrodes for deep brain stimulation impairs electrode-tissue interaction. Unspecific growth of glial tissue around the electrodes can be hindered by altering physicochemical material properties. However, in vitro screening of neural tissue-material interaction requires an adequate cell culture system. No adequate model for cells dissociated from the inferior colliculus (IC) has been described and was thus the aim of this study. Therefore, IC were isolated from neonatal rats (P3_5) and a dissociated cell culture was established. In screening experiments using four dissociation methods (Neural Tissue Dissociation Kit [NTDK] T, NTDK P; NTDK PN, and a validated protocol for the dissociation of spiral ganglion neurons [SGN]), the optimal media, and seeding densities were identified. Thereafter, a dissociation protocol containing only the proteolytic enzymes of interest (trypsin or papain) was tested. For analysis, cells were fixed and immunolabeled using glial- and neuron-specific antibodies. Adhesion and survival of dissociated neurons and glial cells isolated from the IC were demonstrated in all experimental settings. Hence, preservation of type-specific cytoarchitecture with sufficient neuronal networks only occurred in cultures dissociated with NTDK P, NTDK PN, and fresh prepared papain solution. However, cultures obtained after dissociation with papain, seeded at a density of 2×10(4) cells/well and cultivated with Neuro Medium for 6 days reliably revealed the highest neuronal yield with excellent cytoarchitecture of neurons and glial cells. The herein described dissociated culture can be utilized as in vitro model to screen interactions between cells of the IC and surface modifications of the electrode. PMID:24349001

  20. Glial Regulation of the Neuronal Connectome through Local and Long-Distant Communication

    OpenAIRE

    Fields, R. Douglas; Woo, Dong ho; Basser, Peter J.

    2015-01-01

    If “the connectome” represents a complete map of anatomical and functional connectivity in the brain, it should also include glia. Glia define and regulate both the brain’s anatomical and functional connectivity over a broad range of length scales, spanning the whole brain to subcellular domains of synaptic interactions. This Perspective article examines glial interactions with the neuronal connectome, including long-range networks, local circuits, and individual synaptic connections; and hig...

  1. Environmental enrichment alters glial antigen expression and neuroimmune function in the adult rat hippocampus

    OpenAIRE

    Williamson, Lauren L.; Chao, Agnes; Bilbo, Staci D.

    2012-01-01

    Neurogenesis is a well-characterized phenomenon within the dentate gyrus (DG) of the adult hippocampus. Environmental enrichment (EE) in rodents increases neurogenesis, enhances cognition, and promotes recovery from injury. However, little is known about the effects of EE on glia (astrocytes and microglia). Given their importance in neural repair, we predicted that EE would modulate glial phenotype and/or function within the hippocampus. Adult male rats were housed either 12 h/day in an enric...

  2. Neuronal–glial alterations in non-primary motor areas in chronic subcortical stroke

    OpenAIRE

    Carmen M. Cirstea; Nudo, Randolph J.; Craciunas, Sorin C.; Popescu, Elena A.; Choi, In-Young; Lee, Phil; Yeh, Hung-Wen; Savage, Cary R.; Brooks, William M.

    2012-01-01

    Whether functional changes of the non-primary motor areas, e.g., dorsal premotor (PMd) and supplementary motor (SMA) areas, after stroke, reflect reorganization phenomena or recruitment of a pre-existing motor network remains to be clarified. We hypothesized that cellular changes in these areas would be consistent with their involvement in post-stroke reorganization. Specifically, we expected that neuronal and glial compartments would be altered in radiologically normal-appearing, i.e., spare...

  3. Roscovitine reduces neuronal loss, glial activation and neurological deficits after brain trauma

    OpenAIRE

    Hilton, Genell D.; Stoica, Bogdan A.; Byrnes, Kimberly R.; Faden, Alan I.

    2008-01-01

    TBI causes both direct and delayed tissue damage. The latter is associated with secondary biochemical changes such as cell cycle activation that lead to neuronal death, inflammation and glial scarring. Flavopiridol — a CDK inhibitor that is neither specific nor selective — is neuroprotective. To examine the role of more specific CDK inhibitors as potential neuroprotective agents, we studied the effects of roscovitine in TBI. Central administration of roscovitine 30 minutes after injury result...

  4. Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats

    OpenAIRE

    Morel, Gustavo R.; Sosa, Yolanda E.; Bellini, Maria J.; Carri, Nestor G.; Rodriguez, Silvia S.; Bohn, Martha C.; Goya, Rodolfo G.

    2010-01-01

    Progressive dysfunction of hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons during normal aging is associated in the female rat with chronic hyperprolactinemia. We assessed the effectiveness of glial cell line-derived neurotrophic factor (GDNF) gene therapy to restore TIDA neuron function in senile female rats and reverse their chronic hyperprolactinemia. Young (2.5 months) and senile (29 months) rats received a bilateral intrahypothalamic injection (1010 pfu) of either an adenovir...

  5. Sudden death due to a glial cyst of the pineal gland.

    OpenAIRE

    Milroy, C M; Smith, C.L.

    1996-01-01

    Asymptomatic cysts of the pineal gland are found frequently by radiological examination of the brain or at postmortem examination. Symptomatic cysts are rare, and may require surgical intervention. Sudden death due to a cystic lesion of the pineal gland is very rare. A case of a 22 year old man who collapsed and died unexpectedly is reported. Postmortem examination revealed a glial cyst of the pineal gland and evidence of chronic obstructive hydrocephalus. Deaths from colloid cysts and pineal...

  6. Time-lapse imaging reveals stereotypical patterns of Drosophila midline glial migration.

    Science.gov (United States)

    Wheeler, Scott R; Pearson, Joseph C; Crews, Stephen T

    2012-01-15

    The Drosophila CNS midline glia (MG) are multifunctional cells that ensheath and provide trophic support to commissural axons, and direct embryonic development by employing a variety of signaling molecules. These glia consist of two functionally distinct populations: the anterior MG (AMG) and posterior MG (PMG). Only the AMG ensheath axon commissures, whereas the function of the non-ensheathing PMG is unknown. The Drosophila MG have proven to be an excellent system for studying glial proliferation, cell fate, apoptosis, and axon-glial interactions. However, insight into how AMG migrate and acquire their specific positions within the axon-glial scaffold has been lacking. In this paper, we use time-lapse imaging, single-cell analysis, and embryo staining to comprehensively describe the proliferation, migration, and apoptosis of the Drosophila MG. We identified 3 groups of MG that differed in the trajectories of their initial inward migration: AMG that migrate inward and to the anterior before undergoing apoptosis, AMG that migrate inward and to the posterior to ensheath commissural axons, and PMG that migrate inward and to the anterior to contact the commissural axons before undergoing apoptosis. In a second phase of their migration, the surviving AMG stereotypically migrated posteriorly to specific positions surrounding the commissures, and their final position was correlated with their location prior to migration. Most noteworthy are AMG that migrated between the commissures from a ventral to a dorsal position. Single-cell analysis indicated that individual AMG possessed wide-ranging and elaborate membrane extensions that partially ensheathed both commissures. These results provide a strong foundation for future genetic experiments to identify mutants affecting MG development, particularly in guidance cues that may direct migration. Drosophila MG are homologous in structure and function to the glial-like cells that populate the vertebrate CNS floorplate, and study

  7. Characterization of Olfactory Ensheathing Glial Cells Cultured on Polyurethane/Polylactide Electrospun Nonwovens

    OpenAIRE

    Jakub Grzesiak; Ryszard Fryczkowski; Anna Lis; Dariusz Szarek; Jadwiga Laska; Krzysztof Marycz

    2015-01-01

    The aim of this research was to evaluate novel biomaterials for neural regeneration. The investigated materials were composed of polyurethane (PU) and polylactide (PLDL) blended at three different w/w ratios, that is, 5/5, 6/4, and 8/2 of PU/PLDL. Ultrathin fibrous scaffolds were prepared using electrospinning. The scaffolds were investigated for their applicability for nerve regeneration by culturing rat olfactory ensheathing glial cells. Cells were cultured on the materials for seven days, ...

  8. Regulation of Nerve Growth Factor Release by Nitric Oxide through Cyclic GMP Pathway in Cortical Glial Cells

    OpenAIRE

    Xiong, Huabao; YAMADA, Kiyofumi; Jourdi, Hussam; KAWAMURA, MEIKO; TAKEI, NOBUYUKI; HAN, DAIKEN; Nabeshima, Toshitaka; Nawa, Hiroyuki

    1999-01-01

    In the present study, we found that S-nitroso-N-acetyl-dl-penicillamine, a spontaneous nitric oxide (NO) generator, dose-dependently inhibited basal nerve growth factor (NGF) release from mixed glial cells. To elucidate the function of endogenous NO in the regulation of NGF release, the mixed glial cells were stimulated with lipopolysaccharide (LPS) or LPS plus interfer-on-γ (IFNγ). The results showed that LPS alone induced NGF release and moderate NO production. However, costimulation with L...

  9. Anthocyanin Extracts from Black Soybean (Glycine max L.) Protect Human Glial Cells Against Oxygen-Glucose Deprivation by Promoting Autophagy

    OpenAIRE

    KIM, Yong Kwan; Yoon, Hye Hyeon; Lee, Young Dae; Youn, Dong-Ye; Ha, Tae Joung; Kim, Ho-Shik; Lee, Jeong-Hwa

    2012-01-01

    Anthocyanins have received growing attention as dietary antioxidants for the prevention of oxidative damage. Astrocytes, which are specialized glial cells, exert numerous essential, complex functions in both healthy and diseased central nervous system (CNS) through a process known as reactive astrogilosis. Therefore, the maintenance of glial cell viability may be important because of its role as a key modulator of neuropathological events. The aim of this study was to investigate the effect o...

  10. Intrathecal Lamotrigine Attenuates Antinociceptive Morphine Tolerance and Suppresses Spinal Glial Cell Activation in Morphine-Tolerant Rats

    OpenAIRE

    Jun, In-Gu; Kim, Sung-Hoon; Yoon, Yang-In; Park, Jong-Yeon

    2013-01-01

    Glial cells play a critical role in morphine tolerance, resulting from repeated administration of morphine. Both the development and the expression of tolerance are suppressed by the analgesic lamotrigine. This study investigated the relationship between the ability of lamotrigine to maintain the antinociceptive effect of morphine during tolerance development and glial cell activation in the spinal cord. In a rat model, morphine (15 µg) was intrathecally injected once daily for 7 days to indu...

  11. Hydrocortisone stimulates the development of oligodendrocytes in primary glial cultures and affects glucose metabolism and lipid synthesis in these cultures

    OpenAIRE

    Warringa, R.A.J.; Hoeben, R C; Koper, W.J.; Sykes, J.E.C.; Golde, L.M.G. van; Lopes-Cardozo, M.

    1987-01-01

    Cultures of glial cells were prepared from the brains of one-week-old rat pups. After one day in culture, serum was omitted from the medium and replaced by a combination of growth-stimulating hormones and other factors that enhanced the percentage of oligodendrocytes in the cultures. We investigated the effects of hydrocortisone on the development of oligodendrocytes, on the activities of oligodendrocyte-specific enzymes and on glucose- and lipid-metabolism of the glial cells. (1) Hydrocortis...

  12. Persistent productive infection of human glial cells by human immunodeficiency virus (HIV) and by infectious molecular clones of HIV.

    OpenAIRE

    Dewhurst, S; Sakai, K.; de Bresser, J.; Stevenson, M.; Evinger-Hodges, M J; Volsky, D J

    1987-01-01

    The nature of the interaction between human immunodeficiency virus (HIV) and human cells of astrocytic origin was studied in vitro with cultured glial cells and intact HIV or infectious molecular clones of the virus. Infection of glial cells with intact HIV was characterized by low-level expression of viral transcripts as detected by Northern blotting and in situ hybridization (less than 10 copies of HIV RNA per cell), transient virus replication, absence of viral antigens detectable by immun...

  13. Design and screening of a glial cell-specific, cell penetrating peptide for therapeutic applications in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Corey Heffernan

    Full Text Available Multiple Sclerosis (MS is an autoimmune, neurodegenerative disease of the central nervous system (CNS characterized by demyelination through glial cell loss. Current and proposed therapeutic strategies to arrest demyelination and/or promote further remyelination include: (i modulation of the host immune system; and/or (ii transplantation of myelinating/stem or progenitor cells to the circulation or sites of injury. However, significant drawbacks are inherent with both approaches. Cell penetrating peptides (CPP are short amino acid sequences with an intrinsic ability to translocate across plasma membranes, and theoretically represent an attractive vector for delivery of therapeutic peptides or nanoparticles to glia to promote cell survival or remyelination. The CPPs described to date are commonly non-selective in the cell types they transduce, limiting their therapeutic application in vivo. Here, we describe a theoretical framework for design of a novel CPP sequence that selectively transduces human glial cells (excluding non-glial cell types, and conduct preliminary screens of purified, recombinant CPPs with immature and matured human oligodendrocytes and astrocytes, and two non-glial cell types. A candidate peptide, termed TD2.2, consistently transduced glial cells, was significantly more effective at transducing immature oligodendrocytes than matured progeny, and was virtually incapable of transducing two non-glial cell types: (i human neural cells and (ii human dermal fibroblasts. Time-lapse confocal microscopy confirms trafficking of TD2.2 (fused to EGFP to mature oligodendrocytes 3-6 hours after protein application in vitro. We propose selectivity of TD2.2 for glial cells represents a new therapeutic strategy for the treatment of glial-related disease, such as MS.

  14. Effect of glial cell line-derived neurotrophic factor on retinal function after experimental branch retinal vein occlusion

    DEFF Research Database (Denmark)

    Ejstrup, Rasmus; Dornonville de la Cour, Morten; Kyhn, Maria Voss;

    2012-01-01

    The objective of the study was to investigate the effect of glial cell line-derived neurotrophic factor (GDNF) on the multifocal electroretinogram (mfERG) following an induced branch retinal vein occlusion (BRVO) in pigs.......The objective of the study was to investigate the effect of glial cell line-derived neurotrophic factor (GDNF) on the multifocal electroretinogram (mfERG) following an induced branch retinal vein occlusion (BRVO) in pigs....

  15. Enduring Consequences of Early-Life Infection on Glial and Neural Cell Genesis Within Cognitive Regions of the Brain

    OpenAIRE

    Bland, Sondra T.; Beckley, Jacob T; Young, Sarah; Tsang, Verne; Watkins, Linda R; Steven F. Maier; Staci D. Bilbo

    2009-01-01

    Systemic infection with Escherichia coli on postnatal day (P) 4 in rats results in significantly altered brain cytokine responses and behavioral changes in adulthood, but only in response to a subsequent immune challenge with lipopolysaccharide [LPS]. The basis for these changes may be long-term changes in glial cell function. We assessed glial and neural cell genesis in the hippocampus, parietal cortex (PAR), and pre-frontal cortex (PFC), in neonates just after the infection, as well as in a...

  16. Reductions in hypothalamic Gfap expression, glial cells and α-tanycytes in lean and hypermetabolic Gnasxl-deficient mice

    OpenAIRE

    Holmes, Andrew P.; Wong, Shi Quan; Pulix, Michela; Johnson, Kirsty; Horton, Niamh S.; Thomas, Patricia; de Magalhães, João Pedro; Plagge, Antonius

    2016-01-01

    Background Neuronal and glial differentiation in the murine hypothalamus is not complete at birth, but continues over the first two weeks postnatally. Nutritional status and Leptin deficiency can influence the maturation of neuronal projections and glial patterns, and hypothalamic gliosis occurs in mouse models of obesity. Gnasxl constitutes an alternative transcript of the genomically imprinted Gnas locus and encodes a variant of the signalling protein Gαs, termed XLαs, which is expressed in...

  17. A Novel and Efficient Gene Transfer Strategy Reduces Glial Reactivity and Improves Neuronal Survival and Axonal Growth In Vitro

    OpenAIRE

    Mathieu Desclaux; Marisa Teigell; Lahouari Amar; Roland Vogel; Minerva Gimenez Y Ribotta; Alain Privat; Jacques Mallet

    2009-01-01

    Background: The lack of axonal regeneration in the central nervous system is attributed among other factors to the formation of a glial scar. This cellular structure is mainly composed of reactive astrocytes that overexpress two intermediate filament proteins, the glial fibrillary acidic protein (GFAP) and vimentin. Indeed, in vitro, astrocytes lacking GFAP or both GFAP and vimentin were shown to be the substrate for increased neuronal plasticity. Moreover, double knockout mice lacking both G...

  18. Tracheal development in the Drosophila brain is constrained by glial cells

    Science.gov (United States)

    Pereanu, Wayne; Spindler, Shana; Cruz, Luis; Hartenstein, Volker

    2007-01-01

    The Drosophila brain is tracheated by the cerebral trachea, a branch of the first segmental trachea of the embryo. During larval stages the cerebral trachea splits into several main (primary) branches that grow around the neuropile, forming a perineuropilar tracheal plexus (PNP) at the neuropile surface. Five primary tracheal branches whose spatial relationship to brain compartments is relatively invariant can be distinguished, although the exact trajectories and branching pattern of the brain tracheae is surprisingly variable. Immuno-histochemical and electron microscopic demonstrate that all brain tracheae grow in direct contact with the glial cell processes that surround the neuropile. To investigate the effect of glia on tracheal development, embryos and larvae lacking glial cells as a result of a genetic mutation or a directed ablation were analyzed. In these animals, the tracheal branching pattern was highly abnormal. In particular, the number of secondary branches entering the central neuropile was increased. Wild type larvae possess only two central tracheae, typically associated with the mushroom body and the antenno-cerebral tract. In larvae lacking glial cells, six to ten tracheal branches penetrate the neuropile in a variable pattern. This finding indicates that glia-derived signals constrained tracheal growth in the Drosophila brain and restrict the number of branches entering the neuropile. PMID:17046740

  19. Enteric Glial Cells: A New Frontier in Neurogastroenterology and Clinical Target for Inflammatory Bowel Diseases.

    Science.gov (United States)

    Ochoa-Cortes, Fernando; Turco, Fabio; Linan-Rico, Andromeda; Soghomonyan, Suren; Whitaker, Emmett; Wehner, Sven; Cuomo, Rosario; Christofi, Fievos L

    2016-02-01

    The word "glia" is derived from the Greek word "γλoια," glue of the enteric nervous system, and for many years, enteric glial cells (EGCs) were believed to provide mainly structural support. However, EGCs as astrocytes in the central nervous system may serve a much more vital and active role in the enteric nervous system, and in homeostatic regulation of gastrointestinal functions. The emphasis of this review will be on emerging concepts supported by basic, translational, and/or clinical studies, implicating EGCs in neuron-to-glial (neuroglial) communication, motility, interactions with other cells in the gut microenvironment, infection, and inflammatory bowel diseases. The concept of the "reactive glial phenotype" is explored as it relates to inflammatory bowel diseases, bacterial and viral infections, postoperative ileus, functional gastrointestinal disorders, and motility disorders. The main theme of this review is that EGCs are emerging as a new frontier in neurogastroenterology and a potential therapeutic target. New technological innovations in neuroimaging techniques are facilitating progress in the field, and an update is provided on exciting new translational studies. Gaps in our knowledge are discussed for further research. Restoring normal EGC function may prove to be an efficient strategy to dampen inflammation. Probiotics, palmitoylethanolamide (peroxisome proliferator-activated receptor-α), interleukin-1 antagonists (anakinra), and interventions acting on nitric oxide, receptor for advanced glycation end products, S100B, or purinergic signaling pathways are relevant clinical targets on EGCs with therapeutic potential. PMID:26689598

  20. Numerical modelling and in vivo analysis of fluorescent and laser light backscattered from glial brain tumors

    Science.gov (United States)

    Savelieva, Tatiana A.; Kalyagina, Nina A.; Kholodtsova, Maria N.; Loschenov, Victor B.; Goryainov, Sergey A.; Potapov, Aleksander A.

    2012-03-01

    Brain glial tumors have peculiar features of the perifocal region extension, characterized by its indistinct area, which complicates determination of the borders for tissue resection. In the present study filter-reduced back-scattered laser light signals, compared to the data from mathematical modeling, were used for description of the brain white matter. The simulations of the scattered light distributions were performed in a Monte Carlo program using scattering and absorption parameters of the different grades of the brain glial tumors. The parameters were obtained by the Mie calculations for three main types of scatterers: myelinated axon fibers, cell nuclei and mitochondria. It was revealed that diffuse-reflected light, measured at the perifocal areas of the glial brain tumors, shows a significant difference relative to the signal, measured at the normal tissue, which signifies the possibility to provide diagnostically useful information on the tissue state, and to determine the borders of the tumor, thus to reduce the recurrence appearance. Differences in the values of ratios of diffuse reflectance from active growth parts of tumors and normal white matter can be useful for determination of the degree of tumor progress during the spectroscopic analysis.

  1. Differential effects on glial activation by a direct versus an indirect thrombin inhibitor.

    Science.gov (United States)

    Marangoni, M Natalia; Braun, David; Situ, Annie; Moyano, Ana L; Kalinin, Sergey; Polak, Paul; Givogri, Maria I; Feinstein, Douglas L

    2016-08-15

    Thrombin is a potent regulator of brain function in health and disease, modulating glial activation and brain inflammation. Thrombin inhibitors, several of which are in clinical use as anti-coagulants, can reduce thrombin-dependent neuroinflammation in pathological conditions. However, their effects in a healthy CNS are largely unknown. In adult healthy mice, we compared the effects of treatment by the direct thrombin inhibitor dabigatran etexilate (DE), to those of warfarin, which acts by preventing vitamin K recycling essential for coagulation. After 4weeks, warfarin increased both astrocyte GFAP and microglia Iba-1 staining throughout the CNS; whereas DE reduced expression of both markers. Warfarin, but not DE, reduced sulfatide levels; and warfarin showed longer lasting changes in cerebellar gene expression. DE also reduced glial activation in a mouse model of Alzheimer's disease, although no changes in amyloid plaque burden were observed. These results suggest that treatment with direct thrombin inhibitors may be preferable to those agents which reduce vitamin K levels and have the potential to increase glial activation. PMID:27397090

  2. Multiparty Quantum Remote Secret Conference

    CERN Document Server

    Li, X H; Deng, F G; Zhou, P; Liang, Y J; Zhou, H Y; Li, Xi-Han; Li, Chun-Yan; Deng, Fu-Guo; Zhou, Ping; Liang, Yu-Jie; Zhou, Hong-Yu

    2007-01-01

    We present two schemes for multiparty quantum remote secret conference in which each legitimate conferee can read out securely the secret message announced by another one, but a vicious eavesdropper can get nothing about it. The first one is based on the same key shared efficiently and securely by all the parties with Greenberger-Horne-Zeilinger (GHZ) states, and each conferee sends his secret message to the others with one-time pad crypto-system. The other one is based on quantum encryption with a quantum key, a sequence of GHZ states shared among all the conferees and used repeatedly after confirming their security. Both these schemes are optimal as their intrinsic efficiency for qubits approaches the maximal value.

  3. Secrets and Disclosures: How Young Children Handle Secrets

    Science.gov (United States)

    Anagnostaki, Lida; Wright, Michael J.; Papathanasiou, Athanasia

    2013-01-01

    The authors examined the influence of content and verbal cues on young children's understanding of secret information and of its disclosure. Participants were 209 5- and 6-year-old children in an experiment where a puppet, named Zinc, was the protagonist. Children were asked to whom Zinc would disclose a list of pieces of information, some of…

  4. Efficient Transduction of Feline Neural Progenitor Cells for Delivery of Glial Cell Line-Derived Neurotrophic Factor Using a Feline Immunodeficiency Virus-Based Lentiviral Construct

    Directory of Open Access Journals (Sweden)

    X. Joann You

    2011-01-01

    Full Text Available Work has shown that stem cell transplantation can rescue or replace neurons in models of retinal degenerative disease. Neural progenitor cells (NPCs modified to overexpress neurotrophic factors are one means of providing sustained delivery of therapeutic gene products in vivo. To develop a nonrodent animal model of this therapeutic strategy, we previously derived NPCs from the fetal cat brain (cNPCs. Here we use bicistronic feline lentiviral vectors to transduce cNPCs with glial cell-derived neurotrophic factor (GDNF together with a GFP reporter gene. Transduction efficacy is assessed, together with transgene expression level and stability during induction of cellular differentiation, together with the influence of GDNF transduction on growth and gene expression profile. We show that GDNF overexpressing cNPCs expand in vitro, coexpress GFP, and secrete high levels of GDNF protein—before and after differentiation—all qualities advantageous for use as a cell-based approach in feline models of neural degenerative disease.

  5. Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for molecules associated with metabolism, signaling and regulation in central nervous system mixed glial cell cultures

    Directory of Open Access Journals (Sweden)

    Studzinski Diane

    2009-01-01

    Full Text Available Abstract Background Cytokines secreted by immune cells and activated glia play central roles in both the pathogenesis of and protection from damage to the central nervous system (CNS in multiple sclerosis (MS. Methods We have used gene array analysis to identify the initial direct effects of cytokines on CNS glia by comparing changes in early gene expression in CNS glial cultures treated for 6 hours with cytokines typical of those secreted by Th1 and Th2 lymphocytes and monocyte/macrophages (M/M. Results In two previous papers, we summarized effects of these cytokines on immune-related molecules, and on neural and glial related proteins, including neurotrophins, growth factors and structural proteins. In this paper, we present the effects of the cytokines on molecules involved in metabolism, signaling and regulatory mechanisms in CNS glia. Many of the changes in gene expression were similar to those seen in ischemic preconditioning and in early inflammatory lesions in experimental autoimmune encephalomyelitis (EAE, related to ion homeostasis, mitochondrial function, neurotransmission, vitamin D metabolism and a variety of transcription factors and signaling pathways. Among the most prominent changes, all three cytokine mixtures markedly downregulated the dopamine D3 receptor, while Th1 and Th2 cytokines downregulated neuropeptide Y receptor 5. An unexpected finding was the large number of changes related to lipid metabolism, including several suggesting a switch from diacylglycerol to phosphatidyl inositol mediated signaling pathways. Using QRT-PCR we validated the results for regulation of genes for iNOS, arginase and P glycoprotein/multi-drug resistance protein 1 (MDR1 seen at 6 hours with microarray. Conclusion Each of the three cytokine mixtures differentially regulated gene expression related to metabolism and signaling that may play roles in the pathogenesis of MS, most notably with regard to mitochondrial function and neurotransmitter

  6. FOIA: What's a Trade Secret?

    Science.gov (United States)

    Hawker, Curtis

    The Freedom of Information Act (FOIA) was amended in 1974 in order to restrict government control and to facilitate the public's access to information. However, part of the FOIA bans federal officials from disclosing "trade secrets" and commercial or financial information obtained in confidential circumstances. This exemption has resulted in a…

  7. The secret of the universe.

    Science.gov (United States)

    Asimov, I.

    The author turns his attention to such questions as: How near is the nearest star? How heavy is the Sun? How does the Doppler effect work? and countless others. In addition, he provides an explanation of how mankind first became engaged in business and commerce, and advances his own unique theory on the secret of the universe.

  8. Raspberry Pi for secret agents

    CERN Document Server

    Sjogelid, Stefan

    2015-01-01

    This book is an easy-to-follow guide with practical examples in each chapter. Suitable for the novice and expert alike, each topic provides a fast and easy way to get started with exciting applications and also guides you through setting up the Raspberry Pi as a secret agent toolbox.

  9. Etomidate reduces glutamate uptake in rat cultured glial cells: involvement of PKA

    Science.gov (United States)

    Räth, M; Föhr, K J; Weigt, H U; Gauss, A; Engele, J; Georgieff, M; Köster, S; Adolph, O

    2008-01-01

    Background and purpose: Glutamate is the main excitatory neurotransmitter in the vertebrate CNS. Removal of the transmitter from the synaptic cleft by glial and neuronal glutamate transporters (GLTs) has an important function in terminating glutamatergic neurotransmission and neurological disorders. Five distinct excitatory amino-acid transporters have been characterized, among which the glial transporters excitatory amino-acid transporter 1 (EAAT1) (glutamate aspartate transporter) and EAAT2 (GLT1) are most important for the removal of extracellular glutamate. The purpose of this study was to describe the effect of the commonly used anaesthetic etomidate on glutamate uptake in cultures of glial cells. Experimental approach: The activity of the transporters was determined electrophysiologically using the whole cell configuration of the patch-clamp recording technique. Key results: Glutamate uptake was suppressed by etomidate (3–100 μM) in a time- and concentration-dependent manner with a half-maximum effect occurring at 2.4±0.6 μM. Maximum inhibition was approximately 50% with respect to the control. Etomidate led to a significant decrease of Vmax whereas the Km of the transporter was unaffected. In all cases, suppression of glutamate uptake was reversible within a few minutes upon washout. Furthermore, both GF 109203X, a nonselective inhibitor of PKs, and H89, a selective blocker of PKA, completely abolished the inhibitory effect of etomidate. Conclusion and implications: Inhibition of glutamate uptake by etomidate at clinically relevant concentrations may affect glutamatergic neurotransmission by increasing the glutamate concentration in the synaptic cleft and may compromise patients suffering from acute or chronic neurological disorders such as CNS trauma or epilepsy. PMID:19002104

  10. Magnolol protects against trimethyltin-induced neuronal damage and glial activation in vitro and in vivo.

    Science.gov (United States)

    Kim, Da Jung; Kim, Yong Sik

    2016-03-01

    Trimethyltin (TMT), an organotin with potent neurotoxic effects by selectively damaging to hippocampus, is used as a tool for creating an experimental model of neurodegeneration. In the present study, we investigated the protective effects of magnolol, a natural biphenolic compound, on TMT-induced neurodegeneration and glial activation in vitro and in vivo. In HT22 murine neuroblastoma cells, TMT induced necrotic/apoptotic cell death and oxidative stress, including intracellular reactive oxygen species (ROS), protein carbonylation, induction of heme oxygenase-1 (HO-1), and activation of all mitogen-activated protein kinases (MAPKs) family proteins. However, magnolol treatment significantly suppressed neuronal cell death by inhibiting TMT-mediated ROS generation and activation of JNK and p38 MAPKs. In BV-2 microglial cells, magnolol efficiently attenuated TMT-induced microglial activation via suppression of ROS generation and activation of JNK, p38 MAPKs, and nuclear factor-κB (NF-κB) signaling. In an in vivo mouse study, TMT induced massive neuronal damage and enhanced oxidative stress at day 2. We also observed a concomitant increase in glial cells and inducible nitric oxide synthase (iNOS) expression on the same day. These features of TMT toxicity were reversed by treatment of magnolol. We observed that p-JNK and p-p38 MAPK levels were increased in the mouse hippocampus at day 1 after TMT treatment and that magnolol blocked TMT-induced JNK and p38 MAPK activation. Magnolol administration prevented TMT-induced hippocampal neurodegeneration and glial activation, possibly through the regulation of TMT-mediated ROS generation and MAPK activation. PMID:26756313

  11. The glial scar-monocyte interplay: a pivotal resolution phase in spinal cord repair.

    Directory of Open Access Journals (Sweden)

    Ravid Shechter

    Full Text Available The inflammatory response in the injured spinal cord, an immune privileged site, has been mainly associated with the poor prognosis. However, recent data demonstrated that, in fact, some leukocytes, namely monocytes, are pivotal for repair due to their alternative anti-inflammatory phenotype. Given the pro-inflammatory milieu within the traumatized spinal cord, known to skew monocytes towards a classical phenotype, a pertinent question is how parenchymal-invading monocytes acquire resolving properties essential for healing, under such unfavorable conditions. In light of the spatial association between resolving (interleukin (IL-10 producing monocytes and the glial scar matrix chondroitin sulfate proteoglycan (CSPG, in this study we examined the mutual relationship between these two components. By inhibiting the de novo production of CSPG following spinal cord injury, we demonstrated that this extracellular matrix, mainly known for its ability to inhibit axonal growth, serves as a critical template skewing the entering monocytes towards the resolving phenotype. In vitro cell culture studies demonstrated that this matrix alone is sufficient to induce such monocyte polarization. Reciprocal conditional ablation of the monocyte-derived macrophages concentrated at the lesion margins, using diphtheria toxin, revealed that these cells have scar matrix-resolving properties. Replenishment of monocytic cell populations to the ablated mice demonstrated that this extracellular remodeling ability of the infiltrating monocytes requires their expression of the matrix-degrading enzyme, matrix metalloproteinase 13 (MMP-13, a property that was found here to be crucial for functional recovery. Altogether, this study demonstrates that the glial scar-matrix, a known obstacle to regeneration, is a critical component skewing the encountering monocytes towards a resolving phenotype. In an apparent feedback loop, monocytes were found to regulate scar resolution. This

  12. Investigation of protein secretion and secretion stress in Ashbya gossypii

    OpenAIRE

    Aguiar, Tatiana Quinta; Ribeiro, Orquídea; Arvas, Mikko; Wiebe, Marilyn G.; Penttilä, Merja; Domingues, Lucília

    2014-01-01

    Background Ashbya gossypii is a filamentous Saccharomycete used for the industrial production of riboflavin that has been recently explored as a host system for recombinant protein production. To gain insight into the protein secretory pathway of this biotechnologically relevant fungus, we undertook genome-wide analyses to explore its secretome and its transcriptional responses to protein secretion stress. Results A computational pipeline was used to predict the inventory of proteins putative...

  13. Drug carrier systems based on collagen-alginate composite structures for improving the performance of GDNF-secreting HEK293 cells.

    Science.gov (United States)

    Lee, M; Lo, A C; Cheung, P T; Wong, D; Chan, B P

    2009-02-01

    Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor. Development of drug delivery technologies facilitating controlled release of GDNF is critical to applying GDNF in treating neurodegenerative diseases. We previously developed 3D collagen microspheres and demonstrated enhanced GDNF secretion after encapsulation of HEK293 cells, which were transduced to overexpress GDNF in these microspheres. However, the entrapped HEK293 cells were able to migrate out of the collagen microspheres, making it undesirable for clinical applications. In this report, we investigate two new carrier designs, namely collagen-alginate composite gel and collagen microspheres embedded in alginate gel in preventing cell leakage, maintaining cell growth and controlling GDNF secretion in the HEK293 cells. We demonstrated that inclusion of alginate gel in both designs is efficient in preventing cell leakage to the surrounding yet permitting the GDNF secretion, although the cellular growth rate is reduced in an alginate concentration dependent manner. Differential patterns of GDNF secretion in the two designs were demonstrated. The collagen-alginate composite gel maintains a more or less constant GDNF secretion over time while the collagen microspheres embedded in alginate gel continue to increase the secretion level of GDNF over time. This study contributes towards the development of cell-based GDNF delivery devices for the future therapeutics of neurodegenerative diseases. PMID:19059641

  14. Current ideas on central chemoreception by neurons and glial cells in the retrotrapezoid nucleus

    OpenAIRE

    Mulkey, Daniel K.; Wenker, Ian C.; Kréneisz, Orsolya

    2010-01-01

    Central chemoreception is the mechanism by which CO2/pH-sensitive neurons (i.e., chemoreceptors) regulate breathing in response to changes in tissue pH. A region of the brain stem called the retrotrapezoid nucleus (RTN) is thought to be an important site of chemoreception (23), and recent evidence suggests that RTN chemoreception involves two interrelated mechanisms: H+-mediated activation of pH-sensitive neurons (38) and purinergic signaling (19), possibly from pH-sensitive glial cells. A th...

  15. Differential activation of spinal cord glial cells in murine models of neuropathic and cancer pain

    DEFF Research Database (Denmark)

    Hald, Andreas; Nedergaard, S; Hansen, RR;

    2009-01-01

    of spinal cord glial activation in three different murine pain models to investigate if microglial activation is a general prerequisite for astrocyte activation in pain models. We found that two different types of cancer induced pain resulted in severe spinal astrogliosis without activation of microglia......Activation of spinal cord microglia and astrocytes is a common phenomenon in nerve injury pain models and is thought to exacerbate pain perception. Following a nerve injury, a transient increase in the presence of microglia takes place while the increased numbers of astrocytes stay elevated...

  16. Botulinum neurotoxin type A modulates vesicular release of glutamate from satellite glial cells

    OpenAIRE

    da Silva, Larissa Bittencourt; Poulsen, Jeppe Nørgaard; Arendt-Nielsen, Lars; Gazerani, Parisa

    2015-01-01

    This study investigated the presence of cell membrane docking proteins synaptosomal-associated protein, 25 and 23 kD (SNAP-25 and SNAP-23) in satellite glial cells (SGCs) of rat trigeminal ganglion; whether cultured SGCs would release glutamate in a time- and calcium-dependent manner following calcium-ionophore ionomycin stimulation; and if botulinum neurotoxin type A (BoNTA), in a dose-dependent manner, could block or decrease vesicular release of glutamate. SGCs were isolated from the trige...

  17. Primary Glial and Neuronal Tumors of the Ovary or Peritoneum: A Clinicopathologic Study of 11 Cases.

    Science.gov (United States)

    Liang, Li; Olar, Adriana; Niu, Na; Jiang, Yi; Cheng, Wenjun; Bian, Xiu-Wu; Yang, Wentao; Zhang, Jing; Yemelyanova, Anna; Malpica, Anais; Zhang, Zhihong; Fuller, Gregory N; Liu, Jinsong

    2016-06-01

    Primary glial and neuronal tumors of the ovary or peritoneum are rare neuroectodermal-type tumors similar to their counterparts in the central nervous system. We retrospectively reviewed 11 cases. These cases included 4 ependymomas, 6 astrocytic tumors, and 1 neurocytoma. Patients' age ranged from 9 to 50 years (mean, 26 y; median, 24 y). All ependymal tumors with detailed clinical history (n=3) were not associated with any other ovarian neoplasm. In contrast, all astrocytic tumors were associated with immature teratoma (n=4), mature cystic teratoma (n=1), or mixed germ cell tumor (n=1). The neurocytoma arose in association with mature teratomatous components in a patient with a history of treated mixed germ cell tumor. Immunohistochemical staining showed that 7 of 7 ependymal and astrocytic tumors (100%) were positive for glial fibrillary acidic protein, and 2 of 2 ependymomas (100%) were positive for both estrogen and progesterone receptors. The neurocytoma was positive for synaptophysin and negative for S100 protein, glial fibrillary acidic protein, and SALL4. No IDH1-R132H mutation was detected in 2 of 2 (0%) astrocytomas by immunohistochemistry. Next-generation sequencing was performed on additional 2 ependymomas and 2 astrocytomas but detected no mutations in a panel of 50 genes that included IDH1, IDH2, TP53, PIK3CA, EGFR, BRAF, and PTEN. Follow-up information was available for 8 patients, with the follow-up period ranging from 4 to 59 months (mean, 15 mo; median, 8.5 mo), of which 3 had no evidence of disease and 5 were alive with disease. In conclusion, primary glial and neuronal tumors of the ovary can arise independently or in association with other ovarian germ cell tumor components. Pathologists should be aware of these rare tumors and differentiate them from other ovarian neoplasms. Even though an IDH1 or IDH2 mutation is found in the majority of WHO grade II and III astrocytomas, and in secondary glioblastomas arising from them, such mutations were

  18. Experimentally induced diabetes causes glial activation, glutamate toxicity and cellular damage leading to changes in motor function

    Directory of Open Access Journals (Sweden)

    Aarti eNagayach

    2014-10-01

    Full Text Available Behavioural impairments are the most empirical consequence of diabetes mellitus documented in both humans and animal models, but the underlying causes are still poorly understood. As the cerebellum plays a major role in coordination and execution of the motor functions, we investigated the possible involvement of glial activation, cellular degeneration and glutamate transportation in the cerebellum of rats, rendered diabetic by a single injection of streptozotocin (STZ; 45mg/ kg body weight; intraperitoneally. Motor function alterations were studied using Rotarod test (motor coordination and grip strength (muscle activity at 2nd, 4th, 6th, 8th, 10th and 12th week post diabetic confirmation. Scenario of glial (astroglia and microglia activation, cell death and glutamate transportation was gauged using immunohistochemistry, histological study and image analysis. Cellular degeneration was clearly demarcated in the diabetic cerebellum. Glial cells were showing sequential and marked activation following diabetes in terms of both morphology and cell number. Bergmann glial cells were hypertrophied and distorted. Active caspase-3 positive apoptotic cells were profoundly present in all three cerebellar layers. Reduced co-labelling of GLT-1 and GFAP revealed the altered glutamate transportation in cerebellum following diabetes. These results, exclusively derived from histology, immunohistochemistry and cellular quantification, provide first insight over the associative reciprocity between the glial activation, cellular degeneration and reduced glutamate transportation, which presumably lead to the behavioural alterations following STZ-induced diabetes.

  19. Dynamic changes of glial fibrillary acidic protein and nestin in the hippocampus of adult rat brain following ischemic vascular dementia

    Institute of Scientific and Technical Information of China (English)

    Tianping Yu; Peng Zhang; Xiong Zhang; Linhui Wang; Mingyuan Tian; Yu Li

    2011-01-01

    Vascular dementia produced by permanent ligation of bilateral common carotid arteries involves progressive deterioration of intellectual and cognitive function in rats, which are closely associated with the hippocampus. This study used immunohistochemical analysis to detect the expression of glial fibrillary acidic protein and nestin in the hippocampus in a vascular dementia model. The results revealed that both glial fibrillary acidic protein and nestin expression were increased 1 day after permanent ligation of the bilateral common carotid arteries, compared with a sham-operated group. The expression of glial fibrillary acidic protein peaked at 7 days post-surgery. The expression of nestin was a little weaker than that of glial fibrillary acidic protein, and peaked at 14 days (P<0.01). The expression of both proteins slightly decreased at 21 and 28 days, accompanied by recovery of cerebral blood flow. In conclusion, this study demonstrated that glial fibrillary acidic protein and nestin exhibited dynamic expression in the rat hippocampus after permanent ligation of bilateral common carotid arteries. This finding suggests that dynamic alterations in protein expression play an important role in the pathogenesis of vascular dementia.

  20. A transient wave of BMP signaling in the retina is necessary for Müller glial differentiation.

    Science.gov (United States)

    Ueki, Yumi; Wilken, Matthew S; Cox, Kristen E; Chipman, Laura B; Bermingham-McDonogh, Olivia; Reh, Thomas A

    2015-02-01

    The primary glial cells in the retina, the Müller glia, differentiate from retinal progenitors in the first postnatal week. CNTF/LIF/STAT3 signaling has been shown to promote their differentiation; however, another key glial differentiation signal, BMP, has not been examined during this period of Müller glial differentiation. In the course of our analysis of the BMP signaling pathway, we observed a transient wave of Smad1/5/8 signaling in the inner nuclear layer at the end of the first postnatal week, from postnatal day (P) 5 to P9, after the end of neurogenesis. To determine the function of this transient wave, we blocked BMP signaling during this period in vitro or in vivo, using either a BMP receptor antagonist or noggin (Nog). Either treatment leads to a reduction in expression of the Müller glia-specific genes Rlbp1 and Glul, and the failure of many of the Müller glia to repress the bipolar/photoreceptor gene Otx2. These changes in normal Müller glial differentiation result in permanent disruption of the retina, including defects in the outer limiting membrane, rosette formation and a reduction in functional acuity. Our results thus show that Müller glia require a transient BMP signal at the end of neurogenesis to fully repress the neural gene expression program and to promote glial gene expression. PMID:25605781

  1. PYTHON IMPLEMENTATION OF VISUAL SECRET SHARING SCHEMES

    OpenAIRE

    Ruxandra Olimid

    2011-01-01

    Visual secret sharing schemes (VSS) represent an important concept of visual cryptography. They permit the sharing of a secret image between multiple participants so that only authorized groups can recover the secret. This paper considers the software implementation of some black-and-white secret images VSS in Python programming language. PIL (Python Imaging Library) provides strong image processing capabilities, making the library suitable for this kind of implementation. We present samples ...

  2. A Complex of Nuclear Factor I-X3 and STAT3 Regulates Astrocyte and Glioma Migration through the Secreted Glycoprotein YKL-40*

    OpenAIRE

    Singh, Sandeep K.; Bhardwaj, Reetika; Wilczynska, Katarzyna M.; Dumur, Catherine I.; Kordula, Tomasz

    2011-01-01

    Nuclear factor I-X3 (NFI-X3) is a newly identified splice variant of NFI-X that regulates expression of several astrocyte-specific markers, such as glial fibrillary acidic protein. Here, we identified a set of genes regulated by NFI-X3 that includes a gene encoding a secreted glycoprotein YKL-40. Although YKL-40 expression is up-regulated in glioblastoma multiforme, its regulation and functions in nontransformed cells of the central nervous system are widely unexplored. We find that expressio...

  3. Some Economics of Trade Secret Law

    OpenAIRE

    Friedman, David D; William M. Landes; Posner, Richard A

    1991-01-01

    Despite the practical importance of trade secrets to the business community, the law of trade secrets is a neglected orphan in economic analysis. This paper sketches an approach to the economics of trade secret law that connects it more closely both to other areas of intellectual property and to broader issues in the positive economic theory of the common law.

  4. The retinoic acid signaling pathway regulates anterior/posterior patterning in the nerve cord and pharynx of amphioxus, a chordate lacking neural crest

    Science.gov (United States)

    Escriva, Hector; Holland, Nicholas D.; Gronemeyer, Hinrich; Laudet, Vincent; Holland, Linda Z.

    2002-01-01

    Amphioxus, the closest living invertebrate relative of the vertebrates, has a notochord, segmental axial musculature, pharyngeal gill slits and dorsal hollow nerve cord, but lacks neural crest. In amphioxus, as in vertebrates, exogenous retinoic acid (RA) posteriorizes the embryo. The mouth and gill slits never form, AmphiPax1, which is normally downregulated where gill slits form, remains upregulated and AmphiHox1 expression shifts anteriorly in the nerve cord. To dissect the role of RA signaling in patterning chordate embryos, we have cloned the single retinoic acid receptor (AmphiRAR), retinoid X receptor (AmphiRXR) and an orphan receptor (AmphiTR2/4) from amphioxus. AmphiTR2/4 inhibits AmphiRAR-AmphiRXR-mediated transactivation in the presence of RA by competing for DR5 or IR7 retinoic acid response elements (RAREs). The 5' untranslated region of AmphiTR2/4 contains an IR7 element, suggesting possible auto- and RA-regulation. The patterns of AmphiTR2/4 and AmphiRAR expression during embryogenesis are largely complementary: AmphiTR2/4 is strongly expressed in the cerebral vesicle (homologous to the diencephalon plus anterior midbrain), while AmphiRAR expression is high in the equivalent of the hindbrain and spinal cord. Similarly, while AmphiTR2/4 is expressed most strongly in the anterior and posterior thirds of the endoderm, the highest AmphiRAR expression is in the middle third. Expression of AmphiRAR is upregulated by exogenous RA and completely downregulated by the RA antagonist BMS009. Moreover, BMS009 expands the pharynx posteriorly; the first three gill slit primordia are elongated and shifted posteriorly, but do not penetrate, and additional, non-penetrating gill slit primordia are induced. Thus, in an organism without neural crest, initiation and penetration of gill slits appear to be separate events mediated by distinct levels of RA signaling in the pharyngeal endoderm. Although these compounds have little effect on levels of AmphiTR2/4 expression, RA

  5. Stimulation of incretin secreting cells

    Science.gov (United States)

    Pais, Ramona; Gribble, Fiona M.; Reimann, Frank

    2016-01-01

    The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide-1 (GLP-1) are secreted from enteroendocrine cells in the gut and regulate physiological and homeostatic functions related to glucose control, metabolism and food intake. This review provides a systematic summary of the molecular mechanisms underlying secretion from incretin cells, and an understanding of how they sense and interact with lumen and vascular factors and the enteric nervous system through transporters and G-protein coupled receptors (GPCRs) present on their surface to ultimately culminate in hormone release. Some of the molecules described below such as sodium coupled glucose transporter 1 (SGLT1), G-protein coupled receptor (GPR) 119 and GPR40 are targets of novel therapeutics designed to enhance endogenous gut hormone release. Synthetic ligands at these receptors aimed at treating obesity and type 2 diabetes are currently under investigation. PMID:26885360

  6. Stimulation of incretin secreting cells.

    Science.gov (United States)

    Pais, Ramona; Gribble, Fiona M; Reimann, Frank

    2016-02-01

    The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide-1 (GLP-1) are secreted from enteroendocrine cells in the gut and regulate physiological and homeostatic functions related to glucose control, metabolism and food intake. This review provides a systematic summary of the molecular mechanisms underlying secretion from incretin cells, and an understanding of how they sense and interact with lumen and vascular factors and the enteric nervous system through transporters and G-protein coupled receptors (GPCRs) present on their surface to ultimately culminate in hormone release. Some of the molecules described below such as sodium coupled glucose transporter 1 (SGLT1), G-protein coupled receptor (GPR) 119 and GPR40 are targets of novel therapeutics designed to enhance endogenous gut hormone release. Synthetic ligands at these receptors aimed at treating obesity and type 2 diabetes are currently under investigation. PMID:26885360

  7. Electronic enhancement of tear secretion

    Science.gov (United States)

    Brinton, Mark; Lim Chung, Jae; Kossler, Andrea; Kook, Koung Hoon; Loudin, Jim; Franke, Manfred; Palanker, Daniel

    2016-02-01

    Objective. To study electrical stimulation of the lacrimal gland and afferent nerves for enhanced tear secretion, as a potential treatment for dry eye disease. We investigate the response pathways and electrical parameters to safely maximize tear secretion. Approach. We evaluated the tear response to electrical stimulation of the lacrimal gland and afferent nerves in isofluorane-anesthetized rabbits. In acute studies, electrical stimulation was performed using bipolar platinum foil electrodes, implanted beneath the inferior lacrimal gland, and a monopolar electrode placed near the afferent ethmoid nerve. Wireless microstimulators with bipolar electrodes were implanted beneath the lacrimal gland for chronic studies. To identify the response pathways, we applied various pharmacological inhibitors. To optimize the stimulus, we measured tear secretion rate (Schirmer test) as a function of pulse amplitude (1.5-12 mA), duration (0.1-1 ms) and repetition rate (10-100 Hz). Main results. Stimulation of the lacrimal gland increased tear secretion by engaging efferent parasympathetic nerves. Tearing increased with stimulation amplitude, pulse duration and repetition rate, up to 70 Hz. Stimulation with 3 mA, 500 μs pulses at 70 Hz provided a 4.5 mm (125%) increase in Schirmer score. Modulating duty cycle further increased tearing up to 57%, compared to continuous stimulation in chronically implanted animals (36%). Ethmoid (afferent) nerve stimulation increased tearing similar to gland stimulation (3.6 mm) via a reflex pathway. In animals with chronically implanted stimulators, a nearly 6 mm increase (57%) was achieved with 12-fold less charge density per pulse (0.06-0.3 μC mm-2 with 170-680 μs pulses) than the damage threshold (3.5 μC mm-2 with 1 ms pulses). Significance. Electrical stimulation of the lacrimal gland or afferent nerves may be used as a treatment for dry eye disease. Clinical trials should validate this approach in patients with aqueous tear deficiency, and

  8. Unconventional secretion by autophagosome exocytosis

    OpenAIRE

    Pfeffer, Suzanne R

    2010-01-01

    In this issue, Duran et al. (2010. J. Cell Biol. doi: 10.1083/jcb.200911154) and Manjithaya et al. (2010. J. Cell Biol. doi: 10.1083/jcb.200911149) use yeast genetics to reveal a role for autophagosome intermediates in the unconventional secretion of an acyl coenzyme A (CoA)–binding protein that lacks an endoplasmic reticulum signal sequence. Medium-chain acyl CoAs are also required and may be important for substrate routing to this pathway.

  9. Insulin secretion: mechanisms of regulation

    Directory of Open Access Journals (Sweden)

    Radosavljević Tatjana

    2004-01-01

    Full Text Available Regulation of insulin secretion Beta cells are unique endocrine cells. They respond positively, in terms of insulin secretion, not only to changes in the extracellular glucose concentration, but also to activators of the phospholipase C (cholecystokinin or acetylcholine, and to activators of adenylate cyclase (glucagon, glucagon-like peptide-1, or gastric inhibitory polypeptide. Major messengers which mediate glucose action for insulin release are Ca2%, adenosine triphosphate (ATP and diacylglycerol (DAG. Major pathways of insulin release stimulation There are four major pathways involved in stimulation of insulin release. The first pathway is KATP channel-dependent pathway in which increased blood glucose concentrations and increased b-cell metabolism result in a change in intracellular ATP/ADP ratio. This is a contributory factor in closure of ATP-dependent K% channels, depolarization of b-cell membrane, in increased voltage-dependent L-type Ca2%channel activity. Increased Ca2% influx results in increased intracellular Ca2% and stimulated insulin release. KATP channel-independent pathway augments Ca2%-stimulated insulun secretion of KATP channel-dependent pathway. Major potentiation of release results from hormonal and peptidergic activation of receptors linked to adenylyl cyclase. Adenylyl cyclase activity is stimulated by hormones such as vasoactive intestinal peptide (VIP, glucagon-like peptide-1 (GLP-1, and so on. These hormones, acting via G protein, stimulate adenylyl cyclase, thus causing a rise in cyclic adenosine monophosphate (cAMP and activation of protein kinase A (PKA. Increased activity of PKA results in potentiation of insulin secretion.

  10. Haloperidol secreted in breast milk.

    OpenAIRE

    Whalley, L.J.; Blain, P G; Prime, J K

    1981-01-01

    A nursing mother was given haloperidol 5 mg twice daily for puerperal psychosis and continued to breast feed under hospital supervision. Despite considerable amounts of haloperidol being secreted in the breast milk (up to 23.5 micrograms/l), the infant was apparently not sedated, fed well, and continued to thrive. The findings suggest that maternal ingestion of haloperidol for short periods has no deleterious effect on the infant's development.

  11. Possible role of glial cells in the relationship between thyroid dysfunction and mental disorders

    Directory of Open Access Journals (Sweden)

    Mami eNoda

    2015-06-01

    Full Text Available It is widely accepted that there is a close relationship between the endocrine system and the central nervous system (CNS. Among hormones closely related to the nervous system, thyroid hormones (THs are critical for the development and function of the CNS; not only for neuronal cells but also for glial development and differentiation. Any impairment of TH supply to the developing CNS causes severe and irreversible changes in the overall architecture and function of human brain, leading to various neurological dysfunctions. In adult brain, impairment of THs, such as hypothyroidism and hyperthyroidism, can cause psychiatric disorders such as schizophrenia, bipolar disorder, anxiety and depression. Though hypothyroidism impairs synaptic transmission and plasticity, its effect on glial cells and cellular mechanisms are unknown. This mini-review article summarizes how THs are transported to the brain, metabolized in astrocytes and affect microglia and oligodendrocytes, showing an example of glioendocrine system. It may help to understand physiological and/or pathophysiological functions of THs in the CNS and how hypo- and hyper-thyroidism may cause mental disorders.

  12. Comparison of contrast in brightness mode and strain ultrasonography of glial brain tumours

    International Nuclear Information System (INIS)

    Image contrast between normal tissue and brain tumours may sometimes appear to be low in intraoperative ultrasound. Ultrasound imaging of strain is an image modality that has been recently explored for intraoperative imaging of the brain. This study aims to investigate differences in image contrast between ultrasound brightness mode (B-mode) images and ultrasound strain magnitude images of brain tumours. Ultrasound radiofrequency (RF) data was acquired during surgery in 15 patients with glial tumours. The data were subsequently processed to provide strain magnitude images. The contrast in the B-mode images and the strain images was determined in assumed normal brain tissue and tumour tissue at selected regions of interest (ROI). Three measurements of contrast were done in the ultrasound data for each patient. The B-mode and strain contrasts measurements were compared using the paired samples t- test. The statistical analysis of a total of 45 measurements shows that the contrasts in the strain magnitude images are significantly higher than in the conventional ultrasound B-mode images (P < 0.0001). The results indicate that ultrasound strain imaging provides better discrimination between normal brain tissue and glial tumour tissue than conventional ultrasound B-mode imaging. Ultrasound imaging of tissue strain therefore holds the potential of becoming a valuable adjunct to conventional intraoperative ultrasound imaging in brain tumour surgery

  13. Minocycline inhibits glial proliferation in the H-Tx rat model of congenital hydrocephalus

    Directory of Open Access Journals (Sweden)

    Miller Janet M

    2010-05-01

    Full Text Available Abstract Background Reactive astrocytosis and microgliosis are important features of the pathophysiology of hydrocephalus, and persistent glial "scars" that form could exacerbate neuroinflammation, impair cerebral perfusion, impede neuronal regeneration, and alter biomechanical properties. The purpose of this study was to determine the efficacy of minocycline, an antibiotic known for its anti-inflammatory properties, to reduce gliosis in the H-Tx rat model of congenital hydrocephalus. Methods Minocycline (45 mg/kg/day i.p. in 5% sucrose at a concentration of 5-10 mg/ml was administered to hydrocephalic H-Tx rats from postnatal day 15 to day 21, when ventriculomegaly had reached moderate to severe stages. Treated animals were compared to age-matched non-hydrocephalic and untreated hydrocephalic littermates. The cerebral cortex (both gray matter laminae and white matter was processed for immunohistochemistry (glial fibrillary acidic protein, GFAP, for astrocytes and ionized calcium binding adaptor molecule, Iba-1, for microglia and analyzed by qualitative and quantitative light microscopy. Results The mean number of GFAP-immunoreactive astrocytes was significantly higher in untreated hydrocephalic animals compared to both types of controls (p p p Conclusions Overall, these data suggest that minocycline treatment is effective in reducing the gliosis that accompanies hydrocephalus, and thus may provide an added benefit when used as a supplement to ventricular shunting.

  14. Ciliary neurotrophic factor protects striatal neurons against excitotoxicity by enhancing glial glutamate uptake.

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    Corinne Beurrier

    Full Text Available Ciliary neurotrophic factor (CNTF is a potent neuroprotective cytokine in different animal models of glutamate-induced excitotoxicity, although its action mechanisms are still poorly characterized. We tested the hypothesis that an increased function of glial glutamate transporters (GTs could underlie CNTF-mediated neuroprotection. We show that neuronal loss induced by in vivo striatal injection of the excitotoxin quinolinic acid (QA was significantly reduced (by approximately 75% in CNTF-treated animals. In striatal slices, acute QA application dramatically inhibited corticostriatal field potentials (FPs, whose recovery was significantly higher in CNTF rats compared to controls (approximately 40% vs. approximately 7%, confirming an enhanced resistance to excitotoxicity. The GT inhibitor DL-threo-beta-benzyloxyaspartate greatly reduced FP recovery in CNTF rats, supporting the role of GT in CNTF-mediated neuroprotection. Whole-cell patch-clamp recordings from striatal medium spiny neurons showed no alteration of basic properties of striatal glutamatergic transmission in CNTF animals, but the increased effect of a low-affinity competitive glutamate receptor antagonist (gamma-D-glutamylglycine also suggested an enhanced GT function. These data strongly support our hypothesis that CNTF is neuroprotective via an increased function of glial GTs, and further confirms the therapeutic potential of CNTF for the clinical treatment of progressive neurodegenerative diseases involving glutamate overflow.

  15. Agenesis of the Corpus Callosum Due to Defective Glial Wedge Formation in Lhx2 Mutant Mice.

    Science.gov (United States)

    Chinn, Gregory A; Hirokawa, Karla E; Chuang, Tony M; Urbina, Cecilia; Patel, Fenil; Fong, Jeanette; Funatsu, Nobuo; Monuki, Edwin S

    2015-09-01

    Establishment of the corpus callosum involves coordination between callosal projection neurons and multiple midline structures, including the glial wedge (GW) rostrally and hippocampal commissure caudally. GW defects have been associated with agenesis of the corpus callosum (ACC). Here we show that conditional Lhx2 inactivation in cortical radial glia using Emx1-Cre or Nestin-Cre drivers results in ACC. The ACC phenotype was characterized by aberrant ventrally projecting callosal axons rather than Probst bundles, and was 100% penetrant on 2 different mouse strain backgrounds. Lhx2 inactivation in postmitotic cortical neurons using Nex-Cre mice did not result in ACC, suggesting that the mutant phenotype was not autonomous to the callosal projection neurons. Instead, ACC was associated with an absent hippocampal commissure and a markedly reduced to absent GW. Expression studies demonstrated strong Lhx2 expression in the normal GW and in its radial glial progenitors, with absence of Lhx2 resulting in normal Emx1 and Sox2 expression, but premature exit from the cell cycle based on EdU-Ki67 double labeling. These studies define essential roles for Lhx2 in GW, hippocampal commissure, and corpus callosum formation, and suggest that defects in radial GW progenitors can give rise to ACC. PMID:24781987

  16. Nogo receptor 1 is expressed in both primary cultured glial cells and neurons

    Science.gov (United States)

    Ukai, Junichi; Imagama, Shiro; Ohgomori, Tomohiro; Ito, Zenya; Ando, Kei; Ishiguro, Naoki; Kadomatsu, Kenji

    2016-01-01

    ABSTRACT Nogo receptor (NgR) is common in myelin-derived molecules, i.e., Nogo, MAG, and OMgp, and plays important roles in both axon fasciculation and the inhibition of axonal regeneration. In contrast to NgR’s roles in neurons, its roles in glial cells have been poorly explored. Here, we found a dynamic regulation of NgR1 expression during development and neuronal injury. NgR1 mRNA was consistently expressed in the brain from embryonic day 18 to postnatal day 25. In contrast, its expression significantly decreased in the spinal cord during development. Primary cultured neurons, microglia, and astrocytes expressed NgR1. Interestingly, a contusion injury in the spinal cord led to elevated NgR1 mRNA expression at the injury site, but not in the motor cortex, 14 days after injury. Consistent with this, astrocyte activation by TGFβ1 increased NgR1 expression, while microglia activation rather decreased NgR1 expression. These results collectively suggest that NgR1 expression is enhanced in a milieu of neural injury. Our findings may provide insight into the roles of NgR1 in glial cells.

  17. GABA and glutamate uptake and metabolism in retinal glial (Müller cells

    Directory of Open Access Journals (Sweden)

    Andreas eBringmann

    2013-04-01

    Full Text Available Müller cells, the principal glial cells of the retina, support the synaptic activity by the uptake and metabolization of extracellular neurotransmitters. Müller cells express uptake and exchange systems for various neurotransmitters including glutamate and -aminobutyric acid (GABA. Müller cells remove the bulk of extracellular glutamate in the inner retina and contribute to the glutamate clearance around photoreceptor terminals. By the uptake of glutamate, Müller cells are involved in the shaping and termination of the synaptic activity, particularly in the inner retina. Reactive Müller cells are neuroprotective, e.g., by the clearance of excess extracellular glutamate, but may also contribute to neuronal degeneration by a malfunctioning or even reversal of glial glutamate transporters, or by a downregulation of the key enzyme, glutamine synthetase. This review summarizes the present knowledge about the role of Müller cells in the clearance and metabolization of extracellular glutamate and GABA. Some major pathways of GABA and glutamate metabolism in Müller cells are described; these pathways are involved in the glutamate-glutamine cycle of the retina, in the defense against oxidative stress via the production of glutathione, and in the production of substrates for the neuronal energy metabolism.

  18. Possible role of glial cells in the relationship between thyroid dysfunction and mental disorders.

    Science.gov (United States)

    Noda, Mami

    2015-01-01

    It is widely accepted that there is a close relationship between the endocrine system and the central nervous system (CNS). Among hormones closely related to the nervous system, thyroid hormones (THs) are critical for the development and function of the CNS; not only for neuronal cells but also for glial development and differentiation. Any impairment of TH supply to the developing CNS causes severe and irreversible changes in the overall architecture and function of the human brain, leading to various neurological dysfunctions. In the adult brain, impairment of THs, such as hypothyroidism and hyperthyroidism, can cause psychiatric disorders such as schizophrenia, bipolar disorder, anxiety and depression. Although impact of hypothyroidism on synaptic transmission and plasticity is known, its effect on glial cells and related cellular mechanisms remain enigmatic. This mini-review article summarizes how THs are transported into the brain, metabolized in astrocytes and affect microglia and oligodendrocytes, demonstrating an example of glioendocrine system. Neuroglial effects may help to understand physiological and/or pathophysiological functions of THs in the CNS and how hypo- and hyper-thyroidism may cause mental disorders. PMID:26089777

  19. Effects of X-irradiation on glial cells in the developing rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Ferrer, I.; Borras, D. (Barcelona Univ. (Spain) Hospitalet de Llobregat. Unidad Neuropatologia)

    1994-08-01

    Sprague-Dawley rats were given a single dose of 2Gy X-rays when 1 or 3 days of age. Dying cells in the germinal layer of the telencephalon reached peak values 6h after irradiation; dead cells were cleared 48h later. These effects were almost abolished with the injection of cyclohexamide (1 [mu]g/g body weight) given at the time of irradiation. PCNA-immunoreactive cells (cells in late G[sub 1] and S phases of the cell cycle) and PCNA-negative cells were sensitive to X-rays. Long-term effects on glial cell populations in the subcortical white matter of the cingulum were examined in irradiated rats, killed at postnatal day 30 (P30), by means of glial fibrillary acidic protein, vimentin and S-100 immunohistochemistry, as well as with anti-TGF-[alpha] (transformerly growth factor) antibodies that are used as putative oligodendrogial cell markers in the white matter of rat. (author).

  20. Modeling glial contributions to seizures and epileptogenesis: cation-chloride cotransporters in Drosophila melanogaster.

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    Zeid M Rusan

    Full Text Available Flies carrying a kcc loss-of-function mutation are more seizure-susceptible than wild-type flies. The kcc gene is the highly conserved Drosophila melanogaster ortholog of K+/Cl- cotransporter genes thought to be expressed in all animal cell types. Here, we examined the spatial and temporal requirements for kcc loss-of-function to modify seizure-susceptibility in flies. Targeted RNA interference (RNAi of kcc in various sets of neurons was sufficient to induce severe seizure-sensitivity. Interestingly, kcc RNAi in glia was particularly effective in causing seizure-sensitivity. Knockdown of kcc in glia or neurons during development caused a reduction in seizure induction threshold, cell swelling, and brain volume increase in 24-48 hour old adult flies. Third instar larval peripheral nerves were enlarged when kcc RNAi was expressed in neurons or glia. Results suggest that a threshold of K+/Cl- cotransport dysfunction in the nervous system during development is an important determinant of seizure-susceptibility in Drosophila. The findings presented are the first attributing a causative role for glial cation-chloride cotransporters in seizures and epileptogenesis. The importance of elucidating glial cell contributions to seizure disorders and the utility of Drosophila models is discussed.

  1. Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte lineage maturation

    Directory of Open Access Journals (Sweden)

    Gokhan Solen

    2010-02-01

    Full Text Available Abstract Background Long non-protein-coding RNAs (ncRNAs are emerging as important regulators of cellular differentiation and are widely expressed in the brain. Results Here we show that many long ncRNAs exhibit dynamic expression patterns during neuronal and oligodendrocyte (OL lineage specification, neuronal-glial fate transitions, and progressive stages of OL lineage elaboration including myelination. Consideration of the genomic context of these dynamically regulated ncRNAs showed they were part of complex transcriptional loci that encompass key neural developmental protein-coding genes, with which they exhibit concordant expression profiles as indicated by both microarray and in situ hybridization analyses. These included ncRNAs associated with differentiation-specific nuclear subdomains such as Gomafu and Neat1, and ncRNAs associated with developmental enhancers and genes encoding important transcription factors and homeotic proteins. We also observed changes in ncRNA expression profiles in response to treatment with trichostatin A, a histone deacetylase inhibitor that prevents the progression of OL progenitors into post-mitotic OLs by altering lineage-specific gene expression programs. Conclusion This is the first report of long ncRNA expression in neuronal and glial cell differentiation and of the modulation of ncRNA expression by modification of chromatin architecture. These observations explicitly link ncRNA dynamics to neural stem cell fate decisions, specification and epigenetic reprogramming and may have important implications for understanding and treating neuropsychiatric diseases.

  2. Titanium dioxide nanoparticles inhibit proliferation and induce morphological changes and apoptosis in glial cells

    International Nuclear Information System (INIS)

    Titanium dioxide nanoparticles (TiO2 NPs) are widely used in the chemical, electrical and electronic industries. TiO2 NPs can enter directly into the brain through the olfactory bulb and be deposited in the hippocampus region. We determined the effect of TiO2 NPs on rat and human glial cells, C6 and U373, respectively. We evaluated proliferation by crystal violet staining, internalization of TiO2 NPs, and cellular morphology by TEM analysis, as well as F-actin distribution by immunostaining and cell death by detecting active caspase-3 and DNA fragmentation. TiO2 NPs inhibited proliferation and induced morphological changes that were related with a decrease in immuno-location of F-actin fibers. TiO2 NPs were internalized and formation of vesicles was observed. TiO2 NPs induced apoptosis after 96 h of treatment. Hence, TiO2 NPs had a cytotoxic effect on glial cells, suggesting that exposure to TiO2 NPs could cause brain injury and be hazardous to health.

  3. Activation of Satellite Glial Cells in Rat Trigeminal Ganglion after Upper Molar Extraction

    International Nuclear Information System (INIS)

    The neurons in the trigeminal ganglion (TG) are surrounded by satellite glial cells (SGCs), which passively support the function of the neurons, but little is known about the interactions between SGCs and TG neurons after peripheral nerve injury. To examine the effect of nerve injury on SGCs, we investigated the activation of SGCs after neuronal damage due to the extraction of the upper molars in rats. Three, 7, and 10 days after extraction, animals were fixed and the TG was removed. Cryosections of the ganglia were immunostained with antibodies against glial fibrillary acidic protein (GFAP), a marker of activated SGCs, and ATF3, a marker of damaged neurons. After tooth extraction, the number of ATF3-immunoreactive (IR) neurons enclosed by GFAP-IR SGCs had increased in a time-dependent manner in the maxillary nerve region of the TG. Although ATF3-IR neurons were not detected in the mandibular nerve region, the number of GFAP-IR SGCs increased in both the maxillary and mandibular nerve regions. Our results suggest that peripheral nerve injury affects the activation of TG neurons and the SGCs around the injured neurons. Moreover, our data suggest the existence of a neuronal interaction between maxillary and mandibular neurons via SGC activation

  4. Glial response to 17β-estradiol in neonatal rats with excitotoxic brain injury.

    Science.gov (United States)

    Pansiot, Julien; Pham, Hoa; Dalous, Jeremie; Chevenne, Didier; Colella, Marina; Schwendimann, Leslie; Fafouri, Assia; Mairesse, Jérôme; Moretti, Raffaella; Schang, Anne-Laure; Charriaut-Marlangue, Christiane; Gressens, Pierre; Baud, Olivier

    2016-08-01

    White-matter injury is the most common cause of the adverse neurodevelopmental outcomes observed in preterm infants. Only few options exist to prevent perinatal brain injury associated to preterm delivery. 17β-estradiol (E2) is the predominant estrogen in circulation and has been shown to be neuroprotective in vitro and in vivo. However, while E2 has been found to modulate inflammation in adult models of brain damage, how estrogens influence glial cells response in the developing brain needs further investigations. Using a model of ibotenate-induced brain injury, we have refined the effects of E2 in the developing brain. E2 provides significant neuroprotection both in the cortical plate and the white matter in neonatal rats subjected to excitotoxic insult mimicking white matter and cortical damages frequently observed in very preterm infants. E2 promotes significant changes in microglial phenotypes balance in response to brain injury and the acceleration of oligodendrocyte maturation. Maturational effects of E2 on myelination process were observed both in vivo and in vitro. Altogether, these data demonstrate that response of glial cells to E2 could be responsible for its neuroprotective properties in neonatal excitotoxic brain injury. PMID:27222132

  5. Role of spinal glial cells in bee-toxin-induced spontaneous pain, hyperalgesia, and inflammation

    Directory of Open Access Journals (Sweden)

    Yao LU

    2012-08-01

    Full Text Available Objective To observe the effects of intrathecal injection of fluorocitrate, a glial metabolism inhibitor, on bee-toxin-induced spontaneous pain, hyperalgesia and inflammatory response. Methods Forty adult male SD rats with intrathecal catheterization were randomly divided into five groups (8 each: (1 bee-toxin alone group; (2 vehicle (solvent group; (3 low dose (1nmol fluorocitrate group; (4 middle dose (10nmol fluorocitrate group; (5 high dose (50nmol fluorocitrate group. After the measurement of rat paw withdrawal mechanical threshold (PWMT and paw volume (PV, the drug or vehicle was administered intrathecally. Twenty minutes later, bee-toxin (0.2mg/50μl was intraplantarly injected into the left hind paw of every rat, and spontaneous flinching reflexes (SFR were observed instantly for 1 hour. Two hours later, PWMT and PV were measured again. Results Intraplantar injection of bee-toxin into one hind paw of rat induced persistent SFR lasting for 1 hour, with PWMT decreased and PV increased in the injected paw. Compared with control group, pretreatment with intrathecal injection of fluorocitrate produced a significant inhibition of bee-toxin-induced persistent SFR (P < 0.05, P < 0.01, decreased the PWMT in a dose-dependent manner (P < 0.05, but it had no effect on bee-toxin-induced paw edema. Conclusion Activation of spinal glial cells may participate in bee-toxin-induced spontaneous pain and mechanical hyperalgesia, but not inflammatory response.

  6. Mutant GlialCAM Causes Megalencephalic Leukoencephalopathy with Subcortical Cysts, Benign Familial Macrocephaly, and Macrocephaly with Retardation and Autism

    Science.gov (United States)

    López-Hernández, Tania; Ridder, Margreet C.; Montolio, Marisol; Capdevila-Nortes, Xavier; Polder, Emiel; Sirisi, Sònia; Duarri, Anna; Schulte, Uwe; Fakler, Bernd; Nunes, Virginia; Scheper, Gert C.; Martínez, Albert; Estévez, Raúl; van der Knaap, Marjo S.

    2011-01-01

    Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a leukodystrophy characterized by early-onset macrocephaly and delayed-onset neurological deterioration. Recessive MLC1 mutations are observed in 75% of patients with MLC. Genetic-linkage studies failed to identify another gene. We recently showed that some patients without MLC1 mutations display the classical phenotype; others improve or become normal but retain macrocephaly. To find another MLC-related gene, we used quantitative proteomic analysis of affinity-purified MLC1 as an alternative approach and found that GlialCAM, an IgG-like cell adhesion molecule that is also called HepaCAM and is encoded by HEPACAM, is a direct MLC1-binding partner. Analysis of 40 MLC patients without MLC1 mutations revealed multiple different HEPACAM mutations. Ten patients with the classical, deteriorating phenotype had two mutations, and 18 patients with the improving phenotype had one mutation. Most parents with a single mutation had macrocephaly, indicating dominant inheritance. In some families with dominant HEPACAM mutations, the clinical picture and magnetic resonance imaging normalized, indicating that HEPACAM mutations can cause benign familial macrocephaly. In other families with dominant HEPACAM mutations, patients had macrocephaly and mental retardation with or without autism. Further experiments demonstrated that GlialCAM and MLC1 both localize in axons and colocalize in junctions between astrocytes. GlialCAM is additionally located in myelin. Mutant GlialCAM disrupts the localization of MLC1-GlialCAM complexes in astrocytic junctions in a manner reflecting the mode of inheritance. In conclusion, GlialCAM is required for proper localization of MLC1. HEPACAM is the second gene found to be mutated in MLC. Dominant HEPACAM mutations can cause either macrocephaly and mental retardation with or without autism or benign familial macrocephaly. PMID:21419380

  7. Poly-thymidine oligonucleotides mediate activation of murine glial cells primarily through TLR7, not TLR8.

    Directory of Open Access Journals (Sweden)

    Min Du

    Full Text Available The functional role of murine TLR8 in the inflammatory response of the central nervous system (CNS remains unclear. Murine TLR8 does not appear to respond to human TLR7/8 agonists, due to a five amino acid deletion in the ectodomain. However, recent studies have suggested that murine TLR8 may be stimulated by alternate ligands, which include vaccinia virus DNA, phosphothioate oligodeoxynucleotides (ODNs or the combination of phosphothioate poly-thymidine oligonucleotides (pT-ODNs with TLR7/8 agonists. In the current study, we analyzed the ability of pT-ODNs to induce activation of murine glial cells in the presence or absence of TLR7/8 agonists. We found that TLR7/8 agonists induced the expression of glial cell activation markers and induced the production of multiple proinflammatory cytokines and chemokines in mixed glial cultures. In contrast, pT-ODNs alone induced only low level expression of two cytokines, CCL2 and CXCL10. The combination of pT-ODNs along with TLR7/8 agonists induced a synergistic response with substantially higher levels of proinflammatory cytokines and chemokines compared to CL075. This enhancement was not due to cellular uptake of the agonist, indicating that the pT-ODN enhancement of cytokine responses was due to effects on an intracellular process. Interestingly, this response was also not due to synergistic stimulation of both TLR7 and TLR8, as the loss of TLR7 abolished the activation of glial cells and cytokine production. Thus, pT-ODNs act in synergy with TLR7/8 agonists to induce strong TLR7-dependent cytokine production in glial cells, suggesting that the combination of pT-ODNs with TLR7 agonists may be a useful mechanism to induce pronounced glial activation in the CNS.

  8. Effect of the control proliferation of astrocyte on the formation of glial scars by antisense GFAP retrovirus

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Astrocytes play an important role in the formation of glial scars.In order to investigate the effect of inhibiting GFAP gene expression on normal,reactive astrocytes and on glial scar formation,the efficiency of the recombinant antisense GFAP retrovirus (PLBskG) on the growth,cell cycle,morphology and GFAP gene expression of astrocytes in vitro and on the formation of glial scars in vivo has been studied by cell growth curves,flow cytometry,immunocytochemistry,in situ hybridization,RT-PCR and Southern blot.The results confirm the recombinant retrovirus (PLBskG) produced growth suppression and G1 arrest of the normal and injured astrocytes.The infected cells become round or ellipoid.The cell processes become fine or retracted.The intensity of staining of GFAP is reduced.Expression of GFAP mRNA is down regulated.However,in the control experiment,no obvious effects on the morphology or synthesis of GFAP on cultured normal and scratched astrocytes infected by primary retrovirus vector (PLXSN) have been observed.The supernatant of PLBskG has been injected into an injured site by microinjection in vivo.The number and process lengths of GFAP positive cells are obviously reduced around the injured site.The formation of the glial scar is inhibited,showing that the recombinant antisense GFAP retrovirus can effectively inhibit the growth and GFAP expression of normal and injured astrocytes in vitro and the formation of glial scar in vivo.It is suggested that GFAP plays an important role in glial scar formation.

  9. Evidence of female-specific glial deficits in the hippocampus in a mouse model of prenatal stress.

    LENUS (Irish Health Repository)

    Behan, Aine T

    2012-02-01

    Prenatal stress (PS) has been associated with an increased incidence of numerous neuropsychiatric disorders, including depression, anxiety, schizophrenia, and autism. To determine the effects of PS on hippocampal-dependent behaviour hippocampal morphology, we examined behavioural responses and hippocampal cytoarchitecture of a maternal restraint stress paradigm of PS in C57BL6 mice. Female offspring only showed a reduction in hippocampal glial count in the pyramidal layer following PS. Additionally, only PS females showed increased depressive-like behaviour with cognitive deficits predominantly in female offspring when compared to males. This data provides evidence for functional female-specific glial deficits within the hippocampus as a consequence of PS.

  10. Evidence of female-specific glial deficits in the hippocampus in a mouse model of prenatal stress.

    LENUS (Irish Health Repository)

    Behan, Aine T

    2011-01-01

    Prenatal stress (PS) has been associated with an increased incidence of numerous neuropsychiatric disorders, including depression, anxiety, schizophrenia, and autism. To determine the effects of PS on hippocampal-dependent behaviour hippocampal morphology, we examined behavioural responses and hippocampal cytoarchitecture of a maternal restraint stress paradigm of PS in C57BL6 mice. Female offspring only showed a reduction in hippocampal glial count in the pyramidal layer following PS. Additionally, only PS females showed increased depressive-like behaviour with cognitive deficits predominantly in female offspring when compared to males. This data provides evidence for functional female-specific glial deficits within the hippocampus as a consequence of PS.

  11. Secret sharing scheme with inherited characteristic

    Institute of Scientific and Technical Information of China (English)

    Ye Zhenjun; Meng Fanzhen

    2006-01-01

    To assure the shareholders can look for their "legal" attorneys to renew the secret, once the secret sharing scheme is initialized, a secret sharing scheme with inherited characteristic is constructed. In this scheme, each shareholder can produce a new share by his algorithm, which is equivalent to the primary one. Together with other shares, the primary secret can be renewed. Since this scheme is constructed not by replacing the primary share with a new share produced by the dealer in his primitive secret sharing scheme, so no matter how much shares the shareholder produces, these shares can not be gathered together to renew the secret in this scheme. Compared with the existing secret sharing schemes, this scheme provides more agility for the shareholders by investing each of them a function but not affect its security.

  12. LcrG secretion is not required for blocking of Yops secretion in Yersinia pestis

    Directory of Open Access Journals (Sweden)

    Matson Jyl S

    2008-02-01

    Full Text Available Abstract Background LcrG, a negative regulator of the Yersinia type III secretion apparatus has been shown to be primarily a cytoplasmic protein, but is secreted at least in Y. pestis. LcrG secretion has not been functionally analyzed and the relevance of LcrG secretion on LcrG function is unknown. Results An LcrG-GAL4AD chimera, originally constructed for two-hybrid analyses to analyze LcrG protein interactions, appeared to be not secreted but the LcrG-GAL4AD chimera retained the ability to regulate Yops secretion. This result led to further investigation to determine the significance of LcrG secretion on LcrG function. Additional analyses including deletion and substitution mutations of amino acids 2–6 in the N-terminus of LcrG were constructed to analyze LcrG secretion and LcrG's ability to control secretion. Some changes to the N-terminus of LcrG were found to not affect LcrG's secretion or LcrG's secretion-controlling activity. However, substitution of poly-isoleucine in the N-terminus of LcrG did eliminate LcrG secretion but did not affect LcrG's secretion controlling activity. Conclusion These results indicate that secretion of LcrG, while observable and T3SS mediated, is not relevant for LcrG's ability to control secretion.

  13. Weegee’s City Secrets

    Directory of Open Access Journals (Sweden)

    Alan TRACHTENBERG

    2010-03-01

    Full Text Available En tant que photographe indépendant de meurtres, d’accidents, d’incendies, mais aussi de moments de loisirs dans la ville — de scènes de violence et de plaisir — Weegee travaillait essentiellement la nuit et utilisait un flash puissant associé à son appareil-photo de presse. Ses « secrets pour réaliser des photographies avec un flash » consistent à donner des conseils pratiques et techniques pour débutants. Mais au cœur de la rhétorique de ses « secrets » se trouvent des réflexions subtiles et convaincantes révélant la relation entre la lumière et l’obscurité, et plus particulièrement la manière dont la lumière du flash permet de rendre visible l’obscurité. Dans le récit de Weegee, le flash confère à la photographie le pouvoir d’écrire — d’écrire avec la lumière, un mode de représentation singulièrement approprié pour enregistrer des instants de vie dans les rues nocturnes de la ville.As a freelance photographer of crime, accidents, fires, and also of the recreational life of the city—scenes of violence and of pleasure—Weegee worked mainly at night and employed a powerful photoflash attachment to his press camera. His "secrets of shooting with photoflash" consist of practical technical advice for beginners. But within the rhetoric of his "secrets" there lie cogent and subtle reflections on the relation of light to darkness, especially on the way the flash of light makes darkness visible. In Weegee’s account, the photoflash gives photography the power of writing—writing with light, a mode of picturing uniquely suited to recording instants of life on city streets at night.

  14. Secrets of the Oracle Database

    CERN Document Server

    Debes, Norbert

    2009-01-01

    Secrets of the Oracle Database is the definitive guide to undocumented and partially documented features of the Oracle database server. Covering useful but little-known features from Oracle9i Database through Oracle Database 11g, this book will improve your efficiency as an Oracle database administrator or developer. Norbert Debes shines the light of day on features that help you master more difficult administrative, tuning, and troubleshooting tasks than you ever thought possible. Finally, in one place, you have at your fingertips knowledge that previously had to be acquired through years of

  15. Magnetic resonance diffusion and perfusion for differentiation and grading the diffuse glial brain tumors

    International Nuclear Information System (INIS)

    Full text: The aim is to investigate the role and importance of diffusion and perfusion magnetic resonance techniques in the diagnosis, differentiation and grading of diffuse glial brain tumors, and to determine whether there is a statistically significant difference in ADC and rCBV values of different types of gliomas according to their histopathologic grade and to calculate thresholds values for distinguishing high- from low-gradeglioma. Standard protocol, including SAG T1, AX T2, AX T2 FlAIR, COR T2 FlAIR, 3D T1 + C, in combination with diffusion and perfusion sequences. 46 patients with glial tumors, histologically verified are included. Grade distribution in three groups: II gr WHO-11 in number; III gr WHO-9; IV gr WHO- 26 in number. Calculation of the minimum value of the ADC and the maximum value of rCBV for each glioma. To understand the relationship between the minimum and maximum values of ADC rCBV and tumor grade were analyzed values in the three groups by the Mann-Whitney U test. Make a ROC (receiver operating characteristic) analysis to determine the optimal thresholds minADC, maxrCBV for tumor grading (with the best combination of sensitivity and specificity for differentiating WHO IIgr low-grade from III, IV gr WHO highgrade glioma. There were statistically significant differences in values of rCBVmax ADCmin between glial tumors II gr and III gr, II gr and IV gr but not III gr and IV gr WHO. The threshold values of ADC and rCBV for differentiation of low from high-grade glioma, were respectively: ADC = 1,1x10-3 mm2 / sec (with 91.1% accuracy, sensitivity 97.06%, specificity 72,73%; PPV 91,67%; NPV 88,89%); rCBV = 1,6 (with 91.11% accuracy, sensitivity 100%, specificity 63,64%; PPV 89,47%; NPV 100%). Functional MR sequences such as diffusion and perfusion can provide important additional information and improve glioma grading

  16. Glial cell activity is maintained during prolonged inflammatory challenge in rats

    Directory of Open Access Journals (Sweden)

    B.C. Borges

    2012-08-01

    Full Text Available We evaluated the expression of glial fibrillary acidic protein (GFAP, glutamine synthetase (GS, ionized calcium binding adaptor protein-1 (Iba-1, and ferritin in rats after single or repeated lipopolysaccharide (LPS treatment, which is known to induce endotoxin tolerance and glial activation. Male Wistar rats (200-250 g received ip injections of LPS (100 µg/kg or saline for 6 days: 6 saline (N = 5, 5 saline + 1 LPS (N = 6 and 6 LPS (N = 6. After the sixth injection, the rats were perfused and the brains were collected for immunohistochemistry. After a single LPS dose, the number of GFAP-positive cells increased in the hypothalamic arcuate nucleus (ARC; 1 LPS: 35.6 ± 1.4 vs control: 23.1 ± 2.5 and hippocampus (1 LPS: 165.0 ± 3.0 vs control: 137.5 ± 2.5, and interestingly, 6 LPS injections further increased GFAP expression in these regions (ARC = 52.5 ± 4.3; hippocampus = 182.2 ± 4.1. We found a higher GS expression only in the hippocampus of the 6 LPS injections group (56.6 ± 0.8 vs 46.7 ± 1.9. Ferritin-positive cells increased similarly in the hippocampus of rats treated with a single (49.2 ± 1.7 vs 28.1 ± 1.9 or repeated (47.6 ± 1.1 vs 28.1 ± 1.9 LPS dose. Single LPS enhanced Iba-1 in the paraventricular nucleus (PVN: 92.8 ± 4.1 vs 65.2 ± 2.2 and hippocampus (99.4 ± 4.4 vs 73.8 ± 2.1, but had no effect in the retrochiasmatic nucleus (RCA and ARC. Interestingly, 6 LPS increased the Iba-1 expression in these hypothalamic and hippocampal regions (RCA: 57.8 ± 4.6 vs 36.6 ± 2.2; ARC: 62.4 ± 6.0 vs 37.0 ± 2.2; PVN: 100.7 ± 4.4 vs 65.2 ± 2.2; hippocampus: 123.0 ± 3.8 vs 73.8 ± 2.1. The results suggest that repeated LPS treatment stimulates the expression of glial activation markers, protecting neuronal activity during prolonged inflammatory challenges.

  17. Glial cell activity is maintained during prolonged inflammatory challenge in rats

    Energy Technology Data Exchange (ETDEWEB)

    Borges, B.C.; Rorato, R.; Antunes-Rodrigues, J.; Elias, L.L.K. [Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto SP (Brazil)

    2012-05-04

    We evaluated the expression of glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), ionized calcium binding adaptor protein-1 (Iba-1), and ferritin in rats after single or repeated lipopolysaccharide (LPS) treatment, which is known to induce endotoxin tolerance and glial activation. Male Wistar rats (200-250 g) received ip injections of LPS (100 µg/kg) or saline for 6 days: 6 saline (N = 5), 5 saline + 1 LPS (N = 6) and 6 LPS (N = 6). After the sixth injection, the rats were perfused and the brains were collected for immunohistochemistry. After a single LPS dose, the number of GFAP-positive cells increased in the hypothalamic arcuate nucleus (ARC; 1 LPS: 35.6 ± 1.4 vs control: 23.1 ± 2.5) and hippocampus (1 LPS: 165.0 ± 3.0 vs control: 137.5 ± 2.5), and interestingly, 6 LPS injections further increased GFAP expression in these regions (ARC = 52.5 ± 4.3; hippocampus = 182.2 ± 4.1). We found a higher GS expression only in the hippocampus of the 6 LPS injections group (56.6 ± 0.8 vs 46.7 ± 1.9). Ferritin-positive cells increased similarly in the hippocampus of rats treated with a single (49.2 ± 1.7 vs 28.1 ± 1.9) or repeated (47.6 ± 1.1 vs 28.1 ± 1.9) LPS dose. Single LPS enhanced Iba-1 in the paraventricular nucleus (PVN: 92.8 ± 4.1 vs 65.2 ± 2.2) and hippocampus (99.4 ± 4.4 vs 73.8 ± 2.1), but had no effect in the retrochiasmatic nucleus (RCA) and ARC. Interestingly, 6 LPS increased the Iba-1 expression in these hypothalamic and hippocampal regions (RCA: 57.8 ± 4.6 vs 36.6 ± 2.2; ARC: 62.4 ± 6.0 vs 37.0 ± 2.2; PVN: 100.7 ± 4.4 vs 65.2 ± 2.2; hippocampus: 123.0 ± 3.8 vs 73.8 ± 2.1). The results suggest that repeated LPS treatment stimulates the expression of glial activation markers, protecting neuronal activity during prolonged inflammatory challenges.

  18. Usefulness of short TE proton MR spectroscopy in grading brain glial tumors

    International Nuclear Information System (INIS)

    To determine the usefulness of in-vivo proton MR spectroscopy (MRS) with short TE for grading glial brain tumors. For the purpose of tumor grading, 32 patients with pathologically confirmed glial tumors were examined by proton MRS. This and MRI were performed on a 1.5T superconductive MR scanner. T2-weighted FSE images (TR/TE=3D4000/100 msec) were used to obtain anatomical reference images. The stimulated-echo acquisition mode (STEAM:TR/TE/MT=3D3000/30/13.7 msec) was used to acquire MRS data from the localized single-voxel (2x2x2 cm3) in both hemispheres. Residual water resonance in the spectra was removed using a CHESS pulse sequence. Prior to baseline correction, MRS raw-data, free induction decay signals were zero-filled, apodized by an exponential function with 8 Hz line-broadening, and fourier transformed. To normalize signal intensities of metabolites such as N-acetyl aspartate (NAA), total chloline (Cho), myo-inositol ml), and lactate (Lac), the creatine (Cr) peak was used as a standard. The concentration ratios of Cho/Cr, mI/Cr, α-Glx, Lac, and NAA/Cr changed lineaarly according to tumor grade. Increased Cho, mI, αGIx, and Lac levels were clearly seen in all grades. The most dramatic increases, observed in either Grade III or IV, were 78% and 228% for Cho (p less than 0.001), 106% and 61% for mI (p less than 0.001), 32% and 5% for α-Glx, and 727% and 450% for Lac (p less than 0.001), respectively. Increase of concentration ratio of Lac/Cr observed only in Grade III and Grade IV. The concentration ratios of NAA/Cr decreased gradually as tumor grade increased (p less than 0.001). The metabolic changes seen on proton MR spectroscopy using short TE might be useful for grading glial brain tumors. (author)

  19. The Proteome of Native Adult Müller Glial Cells From Murine Retina.

    Science.gov (United States)

    Grosche, Antje; Hauser, Alexandra; Lepper, Marlen Franziska; Mayo, Rebecca; von Toerne, Christine; Merl-Pham, Juliane; Hauck, Stefanie M

    2016-02-01

    To date, the proteomic profiling of Müller cells, the dominant macroglia of the retina, has been hampered because of the absence of suitable enrichment methods. We established a novel protocol to isolate native, intact Müller cells from adult murine retinae at excellent purity which retain in situ morphology and are well suited for proteomic analyses. Two different strategies of sample preparation - an in StageTips (iST) and a subcellular fractionation approach including cell surface protein profiling were used for quantitative liquid chromatography-mass spectrometry (LC-MSMS) comparing Müller cell-enriched to depleted neuronal fractions. Pathway enrichment analyses on both data sets enabled us to identify Müller cell-specific functions which included focal adhesion kinase signaling, signal transduction mediated by calcium as second messenger, transmembrane neurotransmitter transport and antioxidant activity. Pathways associated with RNA processing, cellular respiration and phototransduction were enriched in the neuronal subpopulation. Proteomic results were validated for selected Müller cell genes by quantitative real time PCR, confirming the high expression levels of numerous members of the angiogenic and anti-inflammatory annexins and antioxidant enzymes (e.g. paraoxonase 2, peroxiredoxin 1, 4 and 6). Finally, the significant enrichment of antioxidant proteins in Müller cells was confirmed by measurements on vital retinal cells using the oxidative stress indicator CM-H2DCFDA. In contrast to photoreceptors or bipolar cells, Müller cells were most efficiently protected against H2O2-induced reactive oxygen species formation, which is in line with the protein repertoire identified in the proteomic profiling. Our novel approach to isolate intact glial cells from adult retina in combination with proteomic profiling enabled the identification of novel Müller glia specific proteins, which were validated as markers and for their functional impact in glial

  20. Decreased glial reactivity could be involved in the antipsychotic-like effect of cannabidiol.

    Science.gov (United States)

    Gomes, Felipe V; Llorente, Ricardo; Del Bel, Elaine A; Viveros, Maria-Paz; López-Gallardo, Meritxell; Guimarães, Francisco S

    2015-05-01

    NMDA receptor hypofunction could be involved, in addition to the positive, also to the negative symptoms and cognitive deficits found in schizophrenia patients. An increasing number of data has linked schizophrenia with neuroinflammatory conditions and glial cells, such as microglia and astrocytes, have been related to the pathogenesis of schizophrenia. Cannabidiol (CBD), a major non-psychotomimetic constituent of Cannabis sativa with anti-inflammatory and neuroprotective properties induces antipsychotic-like effects. The present study evaluated if repeated treatment with CBD (30 and 60 mg/kg) would attenuate the behavioral and glial changes observed in an animal model of schizophrenia based on the NMDA receptor hypofunction (chronic administration of MK-801, an NMDA receptor antagonist, for 28 days). The behavioral alterations were evaluated in the social interaction and novel object recognition (NOR) tests. These tests have been widely used to study changes related to negative symptoms and cognitive deficits of schizophrenia, respectively. We also evaluated changes in NeuN (a neuronal marker), Iba-1 (a microglia marker) and GFAP (an astrocyte marker) expression in the medial prefrontal cortex (mPFC), dorsal striatum, nucleus accumbens core and shell, and dorsal hippocampus by immunohistochemistry. CBD effects were compared to those induced by the atypical antipsychotic clozapine. Repeated MK-801 administration impaired performance in the social interaction and NOR tests. It also increased the number of GFAP-positive astrocytes in the mPFC and the percentage of Iba-1-positive microglia cells with a reactive phenotype in the mPFC and dorsal hippocampus without changing the number of Iba-1-positive cells. No change in the number of NeuN-positive cells was observed. Both the behavioral disruptions and the changes in expression of glial markers induced by MK-801 treatment were attenuated by repeated treatment with CBD or clozapine. These data reinforces the proposal

  1. Increased Th2 cytokine secretion, eosinophilic airway inflammation, and airway hyperresponsiveness in neurturin-deficient mice.

    Science.gov (United States)

    Michel, Tatiana; Thérésine, Maud; Poli, Aurélie; Domingues, Olivia; Ammerlaan, Wim; Brons, Nicolaas H C; Hentges, François; Zimmer, Jacques

    2011-06-01

    Neurotrophins such as nerve growth factor and brain-derived neurotrophic factor have been described to be involved in the pathogenesis of asthma. Neurturin (NTN), another neurotrophin from the glial cell line-derived neurotrophic factor family, was shown to be produced by human immune cells: monocytes, B cells, and T cells. Furthermore, it was previously described that the secretion of inflammatory cytokines was dramatically stimulated in NTN knockout (NTN(-/-)) mice. NTN is structurally similar to TGF-β, a protective cytokine in airway inflammation. This study investigates the implication of NTN in a model of allergic airway inflammation using NTN(-/-) mice. The bronchial inflammatory response of OVA-sensitized NTN(-/-) mice was compared with wild-type mice. Airway inflammation, Th2 cytokines, and airway hyperresponsiveness (AHR) were examined. NTN(-/-) mice showed an increase of OVA-specific serum IgE and a pronounced worsening of inflammatory features. Eosinophil number and IL-4 and IL-5 concentration in the bronchoalveolar lavage fluid and lung tissue were increased. In parallel, Th2 cytokine secretion of lung draining lymph node cells was also augmented when stimulated by OVA in vitro. Furthermore, AHR was markedly enhanced in NTN(-/-) mice after sensitization and challenge when compared with wild-type mice. Administration of NTN before challenge with OVA partially rescues the phenotype of NTN(-/-) mice. These findings provide evidence for a dampening role of NTN on allergic inflammation and AHR in a murine model of asthma. PMID:21508262

  2. Prefrontal changes in the glutamate-glutamine cycle and neuronal/glial glutamate transporters in depression with and without suicide

    NARCIS (Netherlands)

    Zhao, J; Verwer, R W H; van Wamelen, D J; Qi, X-R; Gao, S-F; Lucassen, P J; Swaab, D F

    2016-01-01

    There are indications for changes in glutamate metabolism in relation to depression or suicide. The glutamate-glutamine cycle and neuronal/glial glutamate transporters mediate the uptake of the glutamate and glutamine. The expression of various components of the glutamate-glutamine cycle and the neu

  3. QUANTIFICATION OF GLIAL FIBRILLARY ACIDIC PROTEIN: COMPARISON OF SLOT-IMMUNOBINDING ASSAYS WITH A NOVEL SANDWICH ELISA

    Science.gov (United States)

    Detailed protocols are presented for assaying glial fibrillary acidic protein (GFAP), an astrocyte localized protein rich serves as a quantitative marker of toxicant- induced injury to the central nervous system. wo different solid-phase assay procedures are described: 1) a nitro...

  4. The contribution of spinal glial cells to chronic pain behaviour in the monosodium iodoacetate model of osteoarthritic pain

    Directory of Open Access Journals (Sweden)

    Sagar Devi

    2011-11-01

    Full Text Available Abstract Background Clinical studies of osteoarthritis (OA suggest central sensitization may contribute to the chronic pain experienced. This preclinical study used the monosodium iodoacetate (MIA model of OA joint pain to investigate the potential contribution of spinal sensitization, in particular spinal glial cell activation, to pain behaviour in this model. Experimental OA was induced in the rat by the intra-articular injection of MIA and pain behaviour (change in weight bearing and distal allodynia was assessed. Spinal cord microglia (Iba1 staining and astrocyte (GFAP immunofluorescence activation were measured at 7, 14 and 28 days post MIA-treatment. The effects of two known inhibitors of glial activation, nimesulide and minocycline, on pain behaviour and activation of microglia and astrocytes were assessed. Results Seven days following intra-articular injection of MIA, microglia in the ipsilateral spinal cord were activated (p Conclusions Here we provide evidence for a contribution of spinal glial cells to pain behaviour, in particular distal allodynia, in this model of osteoarthritic pain. Our data suggest there is a potential role of glial cells in the central sensitization associated with OA, which may provide a novel analgesic target for the treatment of OA pain.

  5. A Glial K/Cl Transporter Controls Neuronal Receptive Ending Shape by Chloride Inhibition of an rGC.

    Science.gov (United States)

    Singhvi, Aakanksha; Liu, Bingqian; Friedman, Christine J; Fong, Jennifer; Lu, Yun; Huang, Xin-Yun; Shaham, Shai

    2016-05-01

    Neurons receive input from the outside world or from other neurons through neuronal receptive endings (NREs). Glia envelop NREs to create specialized microenvironments; however, glial functions at these sites are poorly understood. Here, we report a molecular mechanism by which glia control NRE shape and associated animal behavior. The C. elegans AMsh glial cell ensheathes the NREs of 12 neurons, including the thermosensory neuron AFD. KCC-3, a K/Cl transporter, localizes specifically to a glial microdomain surrounding AFD receptive ending microvilli, where it regulates K(+) and Cl(-) levels. We find that Cl(-) ions function as direct inhibitors of an NRE-localized receptor-guanylyl-cyclase, GCY-8, which synthesizes cyclic guanosine monophosphate (cGMP). High cGMP mediates the effects of glial KCC-3 on AFD shape by antagonizing the actin regulator WSP-1/NWASP. Components of this pathway are broadly expressed throughout the nervous system, suggesting that ionic regulation of the NRE microenvironment may be a conserved mechanism by which glia control neuron shape and function. PMID:27062922

  6. Hydrocortisone stimulates the development of oligodendrocytes in primary glial cultures and affects glucose metabolism and lipid synthesis in these cultures

    NARCIS (Netherlands)

    Warringa, R.A.J.; Hoeben, R.C.; Koper, W.J.; Sykes, J.E.C.; Golde, L.M.G. van; Lopes-Cardozo, M.

    1987-01-01

    Cultures of glial cells were prepared from the brains of one-week-old rat pups. After one day in culture, serum was omitted from the medium and replaced by a combination of growth-stimulating hormones and other factors that enhanced the percentage of oligodendrocytes in the cultures. We investigated

  7. Detection of human immunodeficiency virus DNA in cultured human glial cells by means of the polymerase chain reaction

    DEFF Research Database (Denmark)

    Teglbjærg, Lars Stubbe; Hansen, J-ES; Dalbøge, H;

    1991-01-01

    This report describes the use of the polymerase chain reaction (PCR) for the detection of viral genomic sequences in latently infected cells. Infection with human immunodeficiency virus in cultures of human glial cells was demonstrated, using nucleic acid amplification followed by dot blot hybrid...... where viral replication is absent, or where genomic copies are present at such low numbers that they are otherwise undetectable....

  8. Sonographic nomogram of the leptomeninges (pia-glial plate) and its usefulness for evaluating bacterial meningitis in infants

    OpenAIRE

    Jequier, Sigrid; Jéquier, J C

    1999-01-01

    To our knowledge, the upper limits of the thickness of normal meninges on neurosonograms are not known. We therefore established a nomogram for sonographic measurements of the leptomeninges (pia-glial plate) and assessed its usefulness in neurosonographic examinations of children with bacterial meningitis.

  9. DIAGNOSTIC VALUE OF THE DEJA VU PHENOMENON IN THE CLINICAL PICTURE OF GLIAL BRAIN TUMORS

    Directory of Open Access Journals (Sweden)

    Pavel Nikolaevich Vlasov

    2009-12-01

    This investigation was undertaken to study the implication of the DV phenomenon in the clinical picture of glial brain tumors (GBT. One hundred and sixty-one subjects (mean age 29,2±6,4 years; males 47%, including 129 healthy individuals and 32 patients with GBT, were examined. In the clinical picture of GBT with seizures, DV is a common symptom that is encountered in the involvement of predominantly the right temporal lobe and accompanied by generalized convulsive attacks and olfactory hallucinations. DV in GBT occurs more than once daily; its duration is a few (as many as 5 minutes; DV is characterized by a negative emotional tinge and attended by fear

  10. In Vivo Reprogramming for CNS Repair: Regenerating Neurons from Endogenous Glial Cells.

    Science.gov (United States)

    Li, Hedong; Chen, Gong

    2016-08-17

    Neuroregeneration in the CNS has proven to be difficult despite decades of research. The old dogma that CNS neurons cannot be regenerated in the adult mammalian brain has been overturned; however, endogenous adult neurogenesis appears to be insufficient for brain repair. Stem cell therapy once held promise for generating large quantities of neurons in the CNS, but immunorejection and long-term functional integration remain major hurdles. In this Perspective, we discuss the use of in vivo reprogramming as an emerging technology to regenerate functional neurons from endogenous glial cells inside the brain and spinal cord. Besides the CNS, in vivo reprogramming has been demonstrated successfully in the pancreas, heart, and liver and may be adopted in other organs. Although challenges remain for translating this technology into clinical therapies, we anticipate that in vivo reprogramming may revolutionize regenerative medicine by using a patient's own internal cells for tissue repair. PMID:27537482

  11. Enterocolitis induced by autoimmune targeting of enteric glial cells: A possible mechanism in Crohn's disease?

    Science.gov (United States)

    Cornet, Anne; Savidge, Tor C.; Cabarrocas, Julie; Deng, Wen-Lin; Colombel, Jean-Frederic; Lassmann, Hans; Desreumaux, Pierre; Liblau, Roland S.

    2001-11-01

    Early pathological manifestations of Crohn's disease (CD) include vascular disruption, T cell infiltration of nerve plexi, neuronal degeneration, and induction of T helper 1 cytokine responses. This study demonstrates that disruption of the enteric glial cell network in CD patients represents another early pathological feature that may be modeled after CD8+ T cell-mediated autoimmune targeting of enteric glia in double transgenic mice. Mice expressing a viral neoself antigen in astrocytes and enteric glia were crossed with specific T cell receptor transgenic mice, resulting in apoptotic depletion of enteric glia to levels comparable in CD patients. Intestinal and mesenteric T cell infiltration, vasculitis, T helper 1 cytokine production, and fulminant bowel inflammation were characteristic hallmarks of disease progression. Immune-mediated damage to enteric glia therefore may participate in the initiation and/or the progression of human inflammatory bowel disease.

  12. Postnatal roles of glial cell line-derived neurotrophic factor family members in nociceptors plasticity

    Institute of Scientific and Technical Information of China (English)

    Sacha A. Malin; Brian M. Davis

    2008-01-01

    The neurotrophin and glial cell line-derived neurotrophic factor (GDNF) family of growth factors have been extensively studied because of their proven ability to regulate development of the peripheral nervous system. The neurotrophin family,which includes nerve growth factor (NGF), NT-3, NT4/5 and BDNF, is also known for its ability to regulate the function of adult sensory neurons. Until recently, little was known concerning the role of the GNDF-family (that includes GDNF, artemin, neurturin and persephin) in adult sensory neuron function. Here we describe recent data that indicates that the GDNF family can regulate sensory neuron function, that some of its members are elevated in inflammatory pain models and that application of these growth factors produces pain in vivo. Finally we discuss how these two families of growth factors may converge on a single membrane receptor, TRPV 1, to produce long-lasting hyperalgesia.

  13. Immunohistochemical visualization of neurons and specific glial cells for stereological application in the porcine neocortex

    DEFF Research Database (Denmark)

    Lyck, Lise; Jelsing, Jacob; Jensen, Pia Søndergaard;

    2006-01-01

    The pig is becoming an increasingly used non-primate model in basic experimental studies of human neurological diseases. In spite of the widespread use of immunohistochemistry and cell type specific markers, the application of immunohistochemistry in the pig brain has not been systematically...... described. Therefore, to facilitate future stereological studies of the neuronal and glial cell populations in experimental neurological diseases in the pig, we established a battery of immunohistochemical protocols for staining of perfusion fixed porcine brain tissue processed as free floating cryostat......-, vibratome- or paraffin sections. Antibodies against NeuN, GFAP, S100-protein, MBP, CNPase, CD11b, CD68 (KP1), CD45 and Ki67 were evaluated, and all except CD68 and CD45 resulted in staining of high quality in either type of tissue. Each staining was evaluated with respect to specificity and sensitivity in...

  14. Glial cell line-derived neurotrophic factor (GDNF therapy for Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Shingo,Tetsuro

    2007-04-01

    Full Text Available Many studies using animals clarify that glial cell line-derived neurotrophic factor (GDNF has strong neuroprotective and neurorestorative effects on dopaminergic neurons. Several pilot studies clarified the validity of continuous intraputaminal GDNF infusion to patients with Parkinson's disease (PD, although a randomized controlled trial of GDNF therapy published in 2006 resulted in negative outcomes, and controversy remains about the efficacy and safety of the treatment. For a decade, our laboratory has investigated the efficacy and the most appropriate method of GDNF administration using animals, and consequently we have obtained some solid data that correspond to the results of clinical trials. In this review, we present an outline of our studies and other key studies related to GDNF, the current state of the research, problems to be overcome, and predictions regarding the use of GDNF therapy for PD in the future.

  15. Human glial chimeric mice reveal astrocytic dependence of JC virus infection

    DEFF Research Database (Denmark)

    Kondo, Yoichi; Windrem, Martha S; Zou, Lisa;

    2014-01-01

    with humanized white matter by engrafting human glial progenitor cells (GPCs) into neonatal immunodeficient and myelin-deficient mice. Intracerebral delivery of JCV resulted in infection and subsequent demyelination of these chimeric mice. Human GPCs and astrocytes were infected more readily than...... oligodendrocytes, and viral replication was noted primarily in human astrocytes and GPCs rather than oligodendrocytes, which instead expressed early viral T antigens and exhibited apoptotic death. Engraftment of human GPCs in normally myelinated and immunodeficient mice resulted in humanized white matter that was...... chimeric for human astrocytes and GPCs. JCV effectively propagated in these mice, which indicates that astroglial infection is sufficient for JCV spread. Sequencing revealed progressive mutation of the JCV capsid protein VP1 after infection, suggesting that PML may evolve with active infection. These...

  16. Glial cells of the central nervous system of Bothrops jararaca (Reptilia, Ofidae: an ultrastructural study

    Directory of Open Access Journals (Sweden)

    Eduardo F. Bondan

    2015-07-01

    Full Text Available Abstract Although ultrastructural characteristics of mature neuroglia in the central nervous system (CNS are very well described in mammals, much less is known in reptiles, especially serpents. In this context, two specimens of Bothrops jararaca were euthanized for morphological analysis of CNS glial cells. Samples from telencephalon, mesencephalon and spinal cord were collected and processed for light and transmission electron microscopy investigation. Astrocytes, oligodendrocytes, microglial cells and ependymal cells, as well as myelin sheaths, presented similar ultrastructural features to those already observed in mammals and tended to maintain their general aspect all over the distinct CNS regions observed. Morphological similarities between reptilian and mammalian glia are probably linked to their evolutionary conservation throughout vertebrate phylogeny.

  17. Removal of Duodenum Elicits GLP-1 Secretion

    DEFF Research Database (Denmark)

    Muscogiuri, Giovanna; Mezza, Teresa; Prioletta, Annamaria;

    2013-01-01

    ) secretion (P = 0.0004), while both fasting and postprandial glucose levels increased (P = 0.0001); GLP-1 and glucagon responses to the mixed meal increased significantly after surgery (P = 0.02 and 0.031). While changes in GIP levels did not correlate with insulin, glucagon, and glucose levels, the increase...... in GLP-1 secretion was inversely related to the postsurgery decrease in insulin secretion (R(2) = 0.56; P = 0.012) but not to the increased glucagon secretion, which correlated inversely with the reduction of insulin (R(2) = 0.46; P = 0.03) and C-peptide (R(2) = 0.37; P = 0.04). Given that the...... and a remarkable increase in GLP-1 levels, which was not translated into increased insulin secretion. Rather, the hypoinsulinemia may have caused an increase in glucagon secretion....

  18. Phenotype overlap in glial cell populations: astroglia, oligodendroglia and NG-2(+ cells

    Directory of Open Access Journals (Sweden)

    Robert eFern

    2015-05-01

    Full Text Available The extent to which NG-2(+ cells form a distinct population separate from astrocytes is central to understanding whether this important cell class is wholly an oligodendrocyte precursor cell (OPC or has additional functions akin to those classically ascribed to astrocytes. Early immuno-staining studies indicate that NG-2(+ cells do not express the astrocyte marker GFAP, but orthogonal reconstructions of double-labelled confocal image stacks here reveal a significant degree of co-expression in individual cells within post-natal day 10 (P10 rat optic nerve (RON and rat cortex. Extensive scanning of various antibody/fixation/embedding approaches identified a protocol for selective post-embedded immuno-gold labelling. This first ultrastructural characterization of identified NG-2(+ cells revealed populations of both OPCs and astrocytes in P10 RON. NG-2(+ astrocytes had classic features including the presence of glial filaments but low levels of glial filament expression were also found in OPCs and myelinating oligodendrocytes. P0 RONs contained few OPCs but positively identified astrocytes were observed to ensheath pre-myelinated axons in a fashion previously described as a definitive marker of the oligodendrocyte lineage. Astrocyte ensheathment was also apparent in P10 RONs, was absent from developing nodes of Ranvier and was never associated with compact myelin. Astrocyte processes were also shown to encapsulate some oligodendrocyte somata. The data indicate that common criteria for delineating astrocytes and oligodendroglia are insufficiently robust and that astrocyte features ascribed to OPCs are likely to arise from misidentification.

  19. Prolonged minocycline treatment impairs motor neuronal survival and glial function in organotypic rat spinal cord cultures.

    Directory of Open Access Journals (Sweden)

    Josephine Pinkernelle

    Full Text Available BACKGROUND: Minocycline, a second-generation tetracycline antibiotic, exhibits anti-inflammatory and neuroprotective effects in various experimental models of neurological diseases, such as stroke, Alzheimer's disease, amyotrophic lateral sclerosis and spinal cord injury. However, conflicting results have prompted a debate regarding the beneficial effects of minocycline. METHODS: In this study, we analyzed minocycline treatment in organotypic spinal cord cultures of neonatal rats as a model of motor neuron survival and regeneration after injury. Minocycline was administered in 2 different concentrations (10 and 100 µM at various time points in culture and fixed after 1 week. RESULTS: Prolonged minocycline administration decreased the survival of motor neurons in the organotypic cultures. This effect was strongly enhanced with higher concentrations of minocycline. High concentrations of minocycline reduced the number of DAPI-positive cell nuclei in organotypic cultures and simultaneously inhibited microglial activation. Astrocytes, which covered the surface of the control organotypic cultures, revealed a peripheral distribution after early minocycline treatment. Thus, we further analyzed the effects of 100 µM minocycline on the viability and migration ability of dispersed primary glial cell cultures. We found that minocycline reduced cell viability, delayed wound closure in a scratch migration assay and increased connexin 43 protein levels in these cultures. CONCLUSIONS: The administration of high doses of minocycline was deleterious for motor neuron survival. In addition, it inhibited microglial activation and impaired glial viability and migration. These data suggest that especially high doses of minocycline might have undesired affects in treatment of spinal cord injury. Further experiments are required to determine the conditions for the safe clinical administration of minocycline in spinal cord injured patients.

  20. Advanced MR diagnostic imaging in pediatric glial cell tumors: from morphological to pathophysiological evaluation

    International Nuclear Information System (INIS)

    Full text: Introduction: The conventional MR imaging is important, and in most cases necessary imaging tool for studying the macroscopic structure, for localization and distribution of a glial brain tumor. It is an integral part of the optimal MR protocol, which further comprises a diffusion, perfusion techniques, techniques for the permeability and oxygenation assessment, as well as MR spectroscopy to the metabolism assessment. What you will learn: Glial brain tumors in children - incidence, histology, classification, diagnosis; Nature and principles of MR diffusion, perfusion, techniques for permeability and oxygenation assessment, MR spectroscopy; Contemporary techniques allowing to obtain not only MR morphological information but also to evaluate the tumor the pathophysiology: the cellular atypia, cellularity, tumor neovascularization, oxygen consumption, metabolism, status of the blood-brain barrier. This assessment determines the biological potential of the tumor, treatment options and prognosis. Discussion: The findings from conventional MR examinations, incl. administration of gadolinium contrast agents are associated with the degree of glioma and can be useful for their classification. Taking into account that from 20% to 45 % of the unenhanced supratentorial gliomas are malignant, some low-grade gliomas enhance (ganglioglioma, pilocytic astrocytoma, oligodendroglioma), 9% of malignant gliomas have no contrast enhancement, and in general, the contrast enhancement is not seen as a reliable indicator for the infiltration extent. The contemporary MR techniques improve the assessment of the pathophysiology of the tumor which is relevant to its histology and biological potential. Conclusion: Modern MR techniques besides purely diagnostic advantages (determine the extent and distribution of glioma), enable: differentiation of tumor recurrence from radiation necrosis; identification of optimal locations for biopsy or operative resection; prognosis, planning and

  1. Fine Astrocyte Processes Contain Very Small Mitochondria: Glial Oxidative Capability May Fuel Transmitter Metabolism.

    Science.gov (United States)

    Derouiche, Amin; Haseleu, Julia; Korf, Horst-Werner

    2015-12-01

    The peripheral astrocyte process (PAP) is the glial compartment largely handling inactivation of transmitter glutamate, and supplying glutamate to the axon terminal. It is not clear how these energy demanding processes are fueled, and whether the PAP exhibits oxidative capability. Whereas the GFAP-positive perinuclear cytoplasm and stem process are rich in mitochondria, the PAP is often considered too narrow to contain mitochondria and might thus not rely on oxidative metabolism. Applying high resolution light microscopy, we investigate here the presence of mitochondria in the PAPs of freshly dissociated, isolated astrocytes. We provide an overview of the subcellular distribution and the approximate size of astrocytic mitochondria. A substantial proportion of the astrocyte's mitochondria are contained in the PAPs and, on the average, they are smaller there than in the stem processes. The majority of mitochondria in the stem and peripheral processes are surprisingly small (0.2-0.4 µm), spherical and not elongate, or tubular, which is supported by electron microscopy. The density of mitochondria is two to several times lower in the PAPs than in the stem processes. Thus, PAPs do not constitute a mitochondria free glial compartment but contain mitochondria in large numbers. No juxtaposition of mitochondria-containing PAPs and glutamatergic synapses has been reported. However, the issue of sufficient ATP concentrations in perisynaptic PAPs can be seen in the light of (1) the rapid, activity dependent PAP motility, and (2) the recently reported activity-dependent mitochondrial transport and immobilization leading to spatial, subcellular organisation of glutamate uptake and oxidative metabolism. PMID:25894677

  2. Inhibitory effect of synthetic small interfering RNAs on glial fibrillary acidic expression in astrocytes

    Institute of Scientific and Technical Information of China (English)

    Mingzhu Zhang; Qing Zhao; Xin Tang; Guangrong Yu

    2008-01-01

    BACKGROUND: Glial fibrillary acidic protein (GFAP) expression highly correlates with spinal glial scar formation, and is regarded as an important target for scar therapy. Efficient inhibition of expression could benefit recovery from spinal cord injury. OBJECTIVE: To investigate the inhibitory effects of synthetic small interfering RNAs (siRNAs) on astrocytie GFAP expression in rats. DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment at the cellular and molecular level was performed at the First Hospital of Dalian Medical University between June 2005 and February 2006. MATERIALS: A total of 100 seven-day-old, Sprague Dawley rats were selected. GAPDH siRNA was purchased from Ambion, USA, And TransMessengerTM Transfection Reagent from DAKO, Carpinteria, CA. METHODS: Rat astrocytes were isolated and cultured. Three pairs of 21-nucleotide (nt) siRNAs specific to rats GFAP mRNA, 401,404 and 854, were synthesized and transfected in primary astrocytes at 1, 2, 3, and 4 g/L using TransMessengerTM Transfection Reagent. Non-transfected astrocytes served as the blank group. Cells transfected with siRNA were regarded as the negative control group, with GAPDH siRNA as the positive control group, and 401 siRNA, 404 siRNA, and 854 siRNA as experimental groups. MAIN OUTCOME MEASURES: GFAP mRNA and protein expression were assessed by RT-PCR and Western blot, respectively, at 24, 48, and 72 hours of culture. RESULTS: GFAP mRNA expression in the positive control group was significantly less than the negative control group (P0.05). GFAP protein expression was remarkably less in siRNA-transfected astroeytes compared to the blank control (P < 0.01). CONCLUSION: Transfected siRNAs could significantly inhibit GFAP gene expression in astrocytes after 72 hours in culture.

  3. Decreased glial and synaptic glutamate uptake in the striatum of HIV-1 gp120 transgenic mice.

    Science.gov (United States)

    Melendez, Roberto I; Roman, Cristina; Capo-Velez, Coral M; Lasalde-Dominicci, Jose A

    2016-06-01

    The mechanisms leading to the neurocognitive deficits in humans with immunodeficiency virus type 1 (HIV-1) are not well resolved. A number of cell culture models have demonstrated that the HIV-envelope glycoprotein 120 (gp120) decreases the reuptake of glutamate, which is necessary for learning, memory, and synaptic plasticity. However, the impact of brain HIV-1 gp120 on glutamate uptake systems in vivo remains unknown. Notably, alterations in brain glutamate uptake systems are implicated in a number of neurodegenerative and neurocognitive disorders. We characterized the kinetic properties of system XAG (sodium-dependent) and systems xc- (sodium-independent) [3H]-L-glutamate uptake in the striatum and hippocampus of HIV-1 gp120 transgenic mice, an established model of HIV neuropathology. We determined the kinetic constant Vmax (maximal velocity) and Km (affinity) of both systems XAG and xc- using subcellular preparations derived from neurons and glial cells. We show significant (30-35 %) reductions in the Vmax of systems XAG and xc- in both neuronal and glial preparations derived from the striatum, but not from the hippocampus of gp120 mice relative to wild-type (WT) controls. Moreover, immunoblot analysis showed that the protein expression of glutamate transporter subtype-1 (GLT-1), the predominant brain glutamate transporter, was significantly reduced in the striatum but not in the hippocampus of gp120 mice. These extensive and region-specific deficits of glutamate uptake likely contribute to the development and/or severity of HIV-associated neurocognitive disorders. Understanding the role of striatal glutamate uptake systems in HIV-1 gp120 may advance the development of new therapeutic strategies to prevent neuronal damage and improve cognitive function in HIV patients. PMID:26567011

  4. Double immunofluorescence shows coexpression of Bcl-x with GFAP in a variety of glial lesions.

    Science.gov (United States)

    Tan, Kong-Bing; Magdalene Koh, Hui-Keng; Tan, Soo-Yong

    2006-12-01

    Bcl-x is an important member of the bcl-2 family of proteins that has been shown to be expressed by both native nervous system tissue and several nervous system tumors. Its anti-apoptotic activity is believed to contribute to nervous system tumorigenesis. We seek to compare the staining characteristics of Bcl-x and GFAP in various neuronal and glial lesions, both neoplastic and non-neoplastic. We also use a double immunofluorescence technique to assess for coexpression of Bcl-x and GFAP by the same lesional cells. Forty cases of brain tumors and reactive brain conditions were reviewed. The former included astrocytomas, GBMs, ependymomas, oligodendrogliomas, gangliogliomas, subependymomas and neurocytomas. The latter included cases of gliosis, cerebritis and mesial temporal sclerosis. Immunohistochemistry for Bcl-x and GFAP was performed. Double immunofluorescent labeling using antibodies to both GFAP and Bcl-x was also carried out. Expression of Bcl-x closely follows that of GFAP with strong expression in both reactive astrocytes and astrocytomas. There is more focal expression in other gliomas. Immunostaining for Bcl-x is generally more intense and distinct, compared to that for GFAP. Expression of both GFAP and Bcl-x is more focal in oligodendrogliomas, with staining of mainly intervening astrocytic processes. Double immunolabelling confirms the coexpression of Bcl-x and GFAP in various gliomas and reactive brain conditions. As immunostaining for Bcl-x is generally more distinct and intense than that for GFAP, it may serve as a useful alternative to help highlight glial cells in selected diagnostic settings. PMID:16773221

  5. Connexin and pannexin hemichannels in brain glial cells: properties, pharmacology and roles

    Directory of Open Access Journals (Sweden)

    Christian eGiaume

    2013-07-01

    Full Text Available Functional interaction between neurons and glia is an exciting field that has expanded tremendously during the past decade. Such partnership has multiple impacts on neuronal activity and survival. Indeed, numerous findings indicate that glial cells interact tightly with neurons in physiological as well as pathological situations. One typical feature of glial cells is their high expression level of gap junction protein subunits, named connexins (Cxs, thus the membrane channels they form may contribute to neuroglial interaction that impacts neuronal activity and survival. While the participation of gap junction channels in neuroglia interactions has been regularly reviewed in the past, the other channel function of Cxs, i.e. hemichannels located at the cell surface, has only recently received attention. While gap junction channels provide the basis for a unique direct cell-to-cell communication, Cx hemichannels allow the exchange of ions and signaling molecules between the cytoplasm and the extracellular medium, thus supporting autocrine and paracrine communication through a process referred to as gliotransmission, as well as uptake and release of metabolites. More recently, another family of proteins, termed pannexins (Panxs, has been identified. These proteins share similar membrane topology but no sequence homology with Cxs. They form multimeric membrane channels with pharmacology somewhat overlapping with that of Cx hemichannels. Such duality has led to several controversies in the literature concerning the identification of the molecular channel constituents (Cxs versus Panxs in glia. In the present review, we up-date and discuss the knowledge of Cx hemichannels and Panx channels in glia, their properties and pharmacology, as well as the understanding of their contribution to neuroglia interactions in healthy and diseased brain.

  6. Physiology of Epithelial Chloride and Fluid Secretion

    OpenAIRE

    Frizzell, Raymond A.; Hanrahan, John W.

    2012-01-01

    Epithelial salt and water secretion serves a variety of functions in different organ systems, such as the airways, intestines, pancreas, and salivary glands. In cystic fibrosis (CF), the volume and/or composition of secreted luminal fluids are compromised owing to mutations in the gene encoding CFTR, the apical membrane anion channel that is responsible for salt secretion in response to cAMP/PKA stimulation. This article examines CFTR and related cellular transport processes that underlie epi...

  7. Pancreatic Bicarbonate Secretion Involves Two Proton Pumps*

    OpenAIRE

    Novak, Ivana; Wang, Jing; Henriksen, Katrine L; Haanes, Kristian A.; Krabbe, Simon; Nitschke, Roland; Hede, Susanne E.

    2010-01-01

    Pancreas secretes fluid rich in digestive enzymes and bicarbonate. The alkaline secretion is important in buffering of acid chyme entering duodenum and for activation of enzymes. This secretion is formed in pancreatic ducts, and studies to date show that plasma membranes of duct epithelium express H+/HCO3− transporters, which depend on gradients created by the Na+/K+-ATPase. However, the model cannot fully account for high-bicarbonate concentrations, and other active transporters, i.e. pumps,...

  8. Glial reaction in the hippocampus after global cardiogenic ischemia Reação glial no hipocampo após isquemia global cardiogênica

    Directory of Open Access Journals (Sweden)

    Emerson Fachin Martins

    2001-03-01

    Full Text Available Many experimental surgerical procedures have been perfomed in the analyse of the phenomenon of brain trophism and plasticity, however undesirable intercorrence can occour leading to specific changes in the results that should be taken into attention. To study this issue we have promoted a transient cardiogenic interruption of the blood flow together with a transient occlusion of the bilateral common carotid arteries (2VO in rats and analysed the state of activation of astrocyte and microglia by means of the glial fibrillary acidic protein (GFAP and OX42 immunohistochemistry, respectively. Rats were submitted to incomplete global cerebral ischemia (IGCI by occlusion of the bilateral carotid arteries for 30 minutes. During the IGCI surgical, some rats received a higher dose of the chloral hydrate anaesthesia which promoted a cardiogenic interruption of the blood flow (CIBF for a period of 10 minutes followed by and prompt reperfusion. During that period, animals were submited to a cardiac massage and ventilated. Sham operation were made in control animals. Rats were killed and their brains processed 14 days after the surgery. The animals that have received a IGCI showed a slight astroglial and microglial reaction in all subfields of the hippocampal formation, however the animal submitted to CIBF showed a massive infiltration of the reactive astrocyte and microglia in CA1 subfield. This results demonstrated that a transient occlusion of the bilateral common carotid arteries leads to activation of glial cells in the hippocampus, however this response can be remarkable changed in animal developing a transient systemic hypoperfusion during surgery. Thus, an accurated monitoration of the hemodinamic condition of the animal has to be done in experimental models of brain ischemia and the results have to be analysed in view of this aspect.Muitos procedimentos experimentais são desenvolvidos para analisar o fenômeno do trofismo e plasticidade cerebral

  9. Temporomandibular joint inflammation activates glial and immune cells in both the trigeminal ganglia and in the spinal trigeminal nucleus

    Directory of Open Access Journals (Sweden)

    Jasmin Luc

    2010-12-01

    Full Text Available Abstract Background Glial cells have been shown to directly participate to the genesis and maintenance of chronic pain in both the sensory ganglia and the central nervous system (CNS. Indeed, glial cell activation has been reported in both the dorsal root ganglia and the spinal cord following injury or inflammation of the sciatic nerve, but no data are currently available in animal models of trigeminal sensitization. Therefore, in the present study, we evaluated glial cell activation in the trigeminal-spinal system following injection of the Complete Freund's Adjuvant (CFA into the temporomandibular joint, which generates inflammatory pain and trigeminal hypersensitivity. Results CFA-injected animals showed ipsilateral mechanical allodynia and temporomandibular joint edema, accompanied in the trigeminal ganglion by a strong increase in the number of GFAP-positive satellite glial cells encircling neurons and by the activation of resident macrophages. Seventy-two hours after CFA injection, activated microglial cells were observed in the ipsilateral trigeminal subnucleus caudalis and in the cervical dorsal horn, with a significant up-regulation of Iba1 immunoreactivity, but no signs of reactive astrogliosis were detected in the same areas. Since the purinergic system has been implicated in the activation of microglial cells during neuropathic pain, we have also evaluated the expression of the microglial-specific P2Y12 receptor subtype. No upregulation of this receptor was detected following induction of TMJ inflammation, suggesting that any possible role of P2Y12 in this paradigm of inflammatory pain does not involve changes in receptor expression. Conclusions Our data indicate that specific glial cell populations become activated in both the trigeminal ganglia and the CNS following induction of temporomandibular joint inflammation, and suggest that they might represent innovative targets for controlling pain during trigeminal nerve sensitization.

  10. Arginase 2 deletion reduces neuro-glial injury and improves retinal function in a model of retinopathy of prematurity.

    Directory of Open Access Journals (Sweden)

    Subhadra P Narayanan

    Full Text Available BACKGROUND: Retinopathy of prematurity (ROP is a major cause of vision impairment in low birth weight infants. While previous work has focused on defining the mechanisms of vascular injury leading to retinal neovascularization, recent studies show that neurons are also affected. This study was undertaken to determine the role of the mitochondrial arginine/ornithine regulating enzyme arginase 2 (A2 in retinal neuro-glial cell injury in the mouse model of ROP. METHODS AND FINDINGS: Studies were performed using wild type (WT and A2 knockout (A2-/- mice exposed to Oxygen Induced Retinopathy (OIR. Neuronal injury and apoptosis were assessed using immunohistochemistry, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling and Western blotting. Electroretinography (ERG was used to assess retinal function. Neuro-glial injury in WT ROP mice was evident by TUNEL labeling, retinal thinning, decreases in number of rod bipolar cells and glial cell activation as compared with room air controls. Significant reduction in numbers of TUNEL positive cells, inhibition of retinal thinning, preservation of the rod bipolar cells and prevention of glial activation were observed in the A2-/- retinas. Retinal function was markedly impaired in the WT OIR mice as shown by decreases in amplitude of the b-wave of the ERG. This defect was significantly reduced in A2-/- mice. Levels of the pro-apoptotic proteins p53, cleaved caspase 9, cytochrome C and the mitochondrial protein Bim were markedly increased in WT OIR retinas compared to controls, whereas the pro-survival Mitochondrial protein BCL-xl was reduced. These alterations were largely blocked in the A2-/- OIR retina. CONCLUSIONS: Our data implicate A2 in neurodegeneration during ROP. Deletion of A2 significantly improves neuronal survival and function, possibly through the regulation of mitochondrial membrane permeability mediated apoptosis during retinal ischemia. These molecular events are associated with

  11. Random Secretion of Growth Hormone in Humans

    Science.gov (United States)

    Prank, Klaus; Kloppstech, Mirko; Nowlan, Steven J.; Sejnowski, Terrence J.; Brabant, Georg

    1996-08-01

    In normal humans, growth hormone (GH) is secreted from a gland located adjacent to the brain (pituitary) into the blood in distinct pulses, but in patients bearing a tumor within the pituitary (acromegaly) GH is excessively secreted in an irregular manner. It has been hypothesized that GH secretion in the diseased state becomes random. This hypothesis is supported by demonstrating that GH secretion in patients with acromegaly cannot be distinguished from a variety of linear stochastic processes based on the predictability of the fluctuations of GH concentration in the bloodstream.

  12. DYNAMIC AND VERIFIABLE SECRET SHARING AMONG WEIGHTED PARTICIPANTS

    Institute of Scientific and Technical Information of China (English)

    Yanshuo ZHANG; Zhuojun LIU

    2007-01-01

    A secret sharing scheme permits a secret to be shared among participants in such a way that only qualified subsets of participants can recover the secret. Secret sharing is useful in management of cryptographic keys. Based on identity, we analyze the secret sharing scheme among weighted participants. Then we present a dynamic scheme about secret sharing among weighted participants. At last, we analyze the secret sharing scheme among weighted participants, which can make all weighted participants verifiable and dynamic.

  13. Noninvasive clearance of airway secretions.

    Science.gov (United States)

    Hardy, K A; Anderson, B D

    1996-06-01

    Airway clearance techniques are indicated for specific diseases that have known clearance abnormalities (Table 2). Murray and others have commented that such techniques are required only for patients with a daily sputum production of greater than 30 mL. The authors have observed that patients with diseases known to cause clearance abnormalities can have sputum clearance with some techniques, such as positive expiratory pressure, autogenic drainage, and active cycle of breathing techniques, when PDPV has not been effective. Hasani et al has shown that use of the forced exhalatory technique in patients with nonproductive cough still resulted in movement of secretions proximally from all regions of the lung in patients with airway obstruction. It is therefore reasonable to consider airway clearance techniques for any patient who has a disease known to alter mucous clearance, including CF, dyskinetic cilia syndromes, and bronchiectasis from any cause. Patients with atelectasis from mucous plugs and hypersecretory states, such as asthma and chronic bronchitis, patients with pain secondary to surgical procedures, and patients with neuromuscular disease, weak cough, and abnormal patency of the airway may also benefit from the application of airway clearance techniques. Infants and children up to 3 years of age with airway clearance problems need to be treated with PDPV. Manual percussion with hands alone or a flexible face mask or cup and small mechanical vibrator/percussors, such as the ultrasonic devices, can be used. The intrapulmonary percussive ventilator shows growing promise in this area. The high-frequency oscillator is not supplied with vests of appropriate sizes for tiny babies and has not been studied in this group. Young patients with neuromuscular disease may require assisted ventilation and airway oscillations can be applied. CPAP alone has been shown to improve achievable flow rates that will increase air-liquid interactions for patients with these diseases

  14. Lack of connexin43-mediated Bergmann glial gap junctional coupling does not affect cerebellar long-term depression, motor coordination, or eyeblink conditioning

    Directory of Open Access Journals (Sweden)

    Mika Tanaka

    2008-04-01

    Full Text Available Bergmann glial cells are specialized astrocytes in the cerebellum. In the mature cerebellar molecular layer, Bergmann glial processes are closely associated with Purkinje cells, enclosing Purkinje cell dendritic synapses with a glial sheath. There is intensive gap junctional coupling between Bergmann glial processes, but their significance in cerebellar functions is not known. Connexin43 (Cx43, a major component of astrocytic gap junction channels, is abundantly expressed in Bergmann glial cells. To examine the role of Cx43-mediated gap junctions between Bergmann glial cells in cerebellar functions, we generated Cx43 conditional knockout mice with the S100b-Cre transgenic line (Cx43fl/fl:S100b-Cre, which exhibited a significant loss of Cx43 in the Bergmann glial cells and astrocytes in the cerebellum with a postnatal onset. The Cx43fl/fl:S100b-Cre mice had normal cerebellar architecture. Although gap junctional coupling between the Bergmann glial cells measured by spreading of microinjected Lucifer yellow was virtually abolished in Cx43fl/fl:S100b-Cre mice, electrophysiologic analysis revealed that cerebellar long-term depression could be induced and maintained normally in thier cerebellar slices. In addition, at the behavioral level, Cx43fl/fl:S100b-Cre mice had normal motor coordination in the rotarod task and normal conditioned eyelid response. Our findings suggest that Cx43-mediated gap junctional coupling between Bergmann glial cells is not necessary for the neuron-glia interactions required for cerebellum-dependent motor coordination and motor learning.

  15. Family Secrets: The Bioethics of Genetic Testing

    Science.gov (United States)

    Markowitz, Dina G.; DuPre, Michael J.; Holt, Susan; Chen, Shaw-Ree; Wischnowski, Michael

    2006-01-01

    This article discusses "Family Secrets," a problem-based learning (PBL) curriculum module that focuses on the bioethical implications of genetic testing. In high school biology classrooms throughout New York State, students are using "Family Secrets" to learn about DNA testing; Huntington's disease (HD); and the ethical, legal, and social…

  16. Cortactin enhances exosome secretion without altering cargo.

    Science.gov (United States)

    Gangoda, Lahiru; Mathivanan, Suresh

    2016-07-18

    The role of cortactin, a regulator of late endosomal trafficking, in the biogenesis and secretion of exosomes is poorly understood. In this issue, Sinha et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201601025) elucidate the role of cortactin as a positive regulator of late endosomal docking and exosome secretion. PMID:27432895

  17. Entanglement Enhances Security in Secret Sharing

    OpenAIRE

    Demkowicz-Dobrzanski, Rafal; De, Aditi Sen; Sen, Ujjwal; Lewenstein, Maciej

    2008-01-01

    We analyze tolerable quantum bit error rates in secret sharing protocols, and show that using entangled encoding states is advantageous in the case when the eavesdropping attacks are local. We also provide a criterion for security in secret sharing -- a parallel of the Csiszar-Korner criterion in single-receiver cryptography.

  18. Decrypted secrets methods and maxims of cryptology

    CERN Document Server

    Bauer, Friedrich L

    2006-01-01

    A reference work on cryptology offering technical and biographical details. This book reviews secret codes and their uses - the foundations of cryptography. It also deals with the process of covertly decrypting a secret code - cryptanalysis, and gives particular advice on assessing methods.

  19. On Secret Sharing with Nonlinear Product Reconstruction

    DEFF Research Database (Denmark)

    Cascudo Pueyo, Ignacio; Cramer, Ronald; Mirandola, Diego;

    2015-01-01

    Multiplicative linear secret sharing is a fundamental notion in the area of secure multiparty computation and, since recently, in the area of two-party cryptography as well. In a nutshell, this notion guarantees that the product of two secrets is obtained as a linear function of the vector consis...

  20. "The Secret Garden": A Literary Journey.

    Science.gov (United States)

    Jordan, Anne Devereaux

    1998-01-01

    Outlines the life of Frances Hodgson Burnett, author of "The Secret Garden." Argues that it not only tells an enthralling tale, but takes readers on a journey through the history of English literature. Discusses the gothic tradition and romanticism of "The Secret Garden." Lists classic elements in the book and offers five ideas for stimulating…

  1. Studying the glial cell response to biomaterials and surface topography for improving the neural electrode interface

    Science.gov (United States)

    Ereifej, Evon S.

    Neural electrode devices hold great promise to help people with the restoration of lost functions, however, research is lacking in the biomaterial design of a stable, long-term device. Current devices lack long term functionality, most have been found unable to record neural activity within weeks after implantation due to the development of glial scar tissue (Polikov et al., 2006; Zhong and Bellamkonda, 2008). The long-term effect of chronically implanted electrodes is the formation of a glial scar made up of reactive astrocytes and the matrix proteins they generate (Polikov et al., 2005; Seil and Webster, 2008). Scarring is initiated when a device is inserted into brain tissue and is associated with an inflammatory response. Activated astrocytes are hypertrophic, hyperplastic, have an upregulation of intermediate filaments GFAP and vimentin expression, and filament formation (Buffo et al., 2010; Gervasi et al., 2008). Current approaches towards inhibiting the initiation of glial scarring range from altering the geometry, roughness, size, shape and materials of the device (Grill et al., 2009; Kotov et al., 2009; Kotzar et al., 2002; Szarowski et al., 2003). Literature has shown that surface topography modifications can alter cell alignment, adhesion, proliferation, migration, and gene expression (Agnew et al., 1983; Cogan et al., 2005; Cogan et al., 2006; Merrill et al., 2005). Thus, the goals of the presented work are to study the cellular response to biomaterials used in neural electrode fabrication and assess surface topography effects on minimizing astrogliosis. Initially, to examine astrocyte response to various materials used in neural electrode fabrication, astrocytes were cultured on platinum, silicon, PMMA, and SU-8 surfaces, with polystyrene as the control surface. Cell proliferation, viability, morphology and gene expression was measured for seven days in vitro. Results determined the cellular characteristics, reactions and growth rates of astrocytes

  2. Serum Glial Fibrillary Acidic Protein Predicts Tissue Glial Fibrillary Acidic Protein Break-Down Products and Therapeutic Efficacy after Penetrating Ballistic-Like Brain Injury.

    Science.gov (United States)

    Boutté, Angela M; Deng-Bryant, Ying; Johnson, David; Tortella, Frank C; Dave, Jitendra R; Shear, Deborah A; Schmid, Kara E

    2016-01-01

    Acute traumatic brain injury (TBI) is associated with neurological dysfunction, changes in brain proteins, and increased serum biomarkers. However, the relationship between these brain proteins and serum biomarkers, and the ability of these serum biomarkers to indicate a neuroprotective/therapeutic response, remains elusive. Penetrating ballistic-like brain injury (PBBI) was used to systematically analyze several key TBI biomarkers, glial fibrillary acidic protein (GFAP) and its break-down products (BDPs)-ubiquitin C-terminal hydrolase-L1 (UCH-L1), α-II spectrin, and α-II spectrin BDPs (SBDPs)-in brain tissues and serum during an extended acute-subacute time-frame. In addition, neurological improvement and serum GFAP theranostic value was evaluated after neuroprotective treatment. In brain tissues, total GFAP increased more than three-fold 2 to 7 d after PBBI. However, this change was primarily due to GFAP-BDPs which increased to 2.7-4.8 arbitrary units (AU). Alpha-II spectrin was nearly ablated 3 d after PBBI, but somewhat recovered after 7 d. In conjunction with α-II spectrin loss, SBDP-145/150 increased approximately three-fold 2 to 7 d after PBBI (vs. sham, p<0.05). UCH-L1 protein levels were slightly decreased 7 d after PBBI but otherwise were unaffected. Serum GFAP was elevated by 3.2- to 8.8-fold at 2 to 4 h (vs. sham; p<0.05) and the 4 h increase was strongly correlated to 3 d GFAP-BDP abundance (r=0.66; p<0.05). Serum GFAP showed such a strong injury effect that it also was evaluated after therapeutic intervention with cyclosporin A (CsA). Administration of 2.5 mg/kg CsA significantly reduced serum GFAP elevation by 22.4-fold 2 h after PBBI (vs. PBBI+vehicle; p<0.05) and improved neurological function 1 d post-injury. Serum biomarkers, particularly GFAP, may be correlative tools of brain protein changes and feasible theranostic markers of TBI progression and recovery. PMID:25789543

  3. Radioimmunoassay in the detection of insulin secretion

    International Nuclear Information System (INIS)

    Some antihypertensive drugs have been shown to cause clinically significant alteration in the endocrine function. This study was conducted to investigate the effect of a new antihypertensive drug, rilmenidine on insulin secretion, which is an important determinant for glucose metabolism. In-vitro method was used to study the direct effect of rilmenidine on glucose induced insulin secretion using isolated rat pancreas. Insulin was assayed using radioimmunoassay. Concentrations of rilmenidine used were based on the peak plasma concentration achieved with an oral standard dose of 1 mg. This study showed that rilmenidine at low concentration was able to stimulate insulin secretion whereas at higher concentration inhibited the insulin secretion. This probably was due to its effect on the imidazoline receptor and the alpha2 adrenoceptor known to induce and inhibit insulin secretion respectively. (Author)

  4. Characterization of a secreted Chlamydia protease

    DEFF Research Database (Denmark)

    Shaw, Allan C; Vandahl, Brian; Larsen, Martin Røssel;

    2002-01-01

    Chlamydiae are obligate intracellular bacteria that are important human pathogens. The Chlamydia genomes contain orthologues to secretion apparatus proteins from other intracellular bacteria, but only a few secreted proteins have been identified. Most likely, effector proteins are secreted in order...... this paper verifies the applicability of the described method for the identification of secreted proteins. We extend the findings by Zhong et al. by proteome studies of expression and turnover of C. trachomatis CPAF showing that the degradation of C. trachomatis D CPAF in the host cell is very limited...... to promote infection. Effector proteins cannot be identified by motif or similarity searches. As a new strategy for identification of secreted proteins we have compared 2D-PAGE profiles of [35S]-labelled Chlamydia proteins from whole lysates of infected cells to 2D-PAGE profiles of proteins from...

  5. Kif11 dependent cell cycle progression in radial glial cells is required for proper neurogenesis in the zebrafish neural tube.

    Science.gov (United States)

    Johnson, Kimberly; Moriarty, Chelsea; Tania, Nessy; Ortman, Alissa; DiPietrantonio, Kristina; Edens, Brittany; Eisenman, Jean; Ok, Deborah; Krikorian, Sarah; Barragan, Jessica; Golé, Christophe; Barresi, Michael J F

    2014-03-01

    Radial glia serve as the resident neural stem cells in the embryonic vertebrate nervous system, and their proliferation must be tightly regulated to generate the correct number of neuronal and glial cell progeny in the neural tube. During a forward genetic screen, we recently identified a zebrafish mutant in the kif11 loci that displayed a significant increase in radial glial cell bodies at the ventricular zone of the spinal cord. Kif11, also known as Eg5, is a kinesin-related, plus-end directed motor protein responsible for stabilizing and separating the bipolar mitotic spindle. We show here that Gfap+ radial glial cells express kif11 in the ventricular zone and floor plate. Loss of Kif11 by mutation or pharmacological inhibition with S-trityl-L-cysteine (STLC) results in monoastral spindle formation in radial glial cells, which is characteristic of mitotic arrest. We show that M-phase radial glia accumulate over time at the ventricular zone in kif11 mutants and STLC treated embryos. Mathematical modeling of the radial glial accumulation in kif11 mutants not only confirmed an ~226× delay in mitotic exit (likely a mitotic arrest), but also predicted two modes of increased cell death. These modeling predictions were supported by an increase in the apoptosis marker, anti-activated Caspase-3, which was also found to be inversely proportional to a decrease in cell proliferation. In addition, treatment with STLC at different stages of neural development uncovered two critical periods that most significantly require Kif11 function for stem cell progression through mitosis. We also show that loss of Kif11 function causes specific reductions in oligodendroglia and secondary interneurons and motorneurons, suggesting these later born populations require proper radial glia division. Despite these alterations to cell cycle dynamics, survival, and neurogenesis, we document unchanged cell densities within the neural tube in kif11 mutants, suggesting that a mechanism of

  6. Cyclic AMP-induced K+ secretion occurs independently of Cl− secretion in rat distal colon

    OpenAIRE

    Sandle, Geoffrey I.; Rajendran, Vazhaikkurichi M

    2012-01-01

    cAMP induces both active Cl− and active K+ secretion in mammalian colon. It is generally assumed that a mechanism for K+ exit is essential to maintain cells in the hyperpolarized state, thus favoring a sustained Cl− secretion. Both Kcnn4c and Kcnma1 channels are located in colon, and this study addressed the questions of whether Kcnn4c and/or Kcnma1 channels mediate cAMP-induced K+ secretion and whether cAMP-induced K+ secretion provides the driving force for Cl− secretion. Forskolin (FSK)-en...

  7. Glial cell line-derived neurotrophic factor gene delivery via a polyethylene imine grafted chitosan carrier

    Directory of Open Access Journals (Sweden)

    Peng YS

    2014-06-01

    Full Text Available Yu-Shiang Peng,1,* Po-Liang Lai,2,* Sydney Peng,1 His-Chin Wu,3 Siang Yu,1 Tsan-Yun Tseng,4 Li-Fang Wang,5 I-Ming Chu1 1Department of Chemical Engineering, National Tsing Hua University, Hsinchu, 2Department of Orthopedic Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, 3Department of Materials Engineering, Tatung University, Taipei, 4Graduate School of Biotechnology and Bioengineering, College of Engineering, Yuan Ze University, Chung-Li, 5Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan *Yu-Shiang Peng and Po-Liang Lai contributed equally to this work Abstract: Parkinson’s disease is known to result from the loss of dopaminergic neurons. Direct intracerebral injections of high doses of recombinant glial cell line-derived neurotrophic factor (GDNF have been shown to protect adult nigral dopaminergic neurons. Because GDNF does not cross the blood–brain barrier, intracerebral gene transfer is an ideal option. Chitosan (CHI is a naturally derived material that has been used for gene transfer. However, the low water solubility often leads to decreased transfection efficiency. Grafting of highly water-soluble polyethylene imines (PEI and polyethylene glycol onto polymers can increase their solubility. The purpose of this study was to design a non-viral gene carrier with improved water solubility as well as enhanced transfection efficiency for treating Parkinsonism. Two molecular weights (Mw =600 and 1,800 g/mol of PEI were grafted onto CHI (PEI600-g-CHI and PEI1800-g-CHI, respectively by opening the epoxide ring of ethylene glycol diglycidyl ether (EX-810. This modification resulted in a non-viral gene carrier with less cytotoxicity. The transfection efficiency of PEI600-g-CHI/deoxyribonucleic acid (DNA polyplexes was significantly higher than either PEI1800-g-CHI/DNA or CHI/DNA polyplexes. The maximal GDNF expression of PEI600-g-CHI/DNA was at the

  8. Identification of protein secretion systems and novel secreted proteins in Rhizobium leguminosarum bv. viciae

    Directory of Open Access Journals (Sweden)

    Krehenbrink Martin

    2008-01-01

    Full Text Available Abstract Background Proteins secreted by bacteria play an important role in infection of eukaryotic hosts. Rhizobia infect the roots of leguminous plants and establish a mutually beneficial symbiosis. Proteins secreted during the infection process by some rhizobial strains can influence infection and modify the plant defence signalling pathways. The aim of this study was to systematically analyse protein secretion in the recently sequenced strain Rhizobium leguminosarum bv. viciae 3841. Results Similarity searches using defined protein secretion systems from other Gram-negative bacteria as query sequences revealed that R. l. bv. viciae 3841 has ten putative protein secretion systems. These are the general export pathway (GEP, a twin-arginine translocase (TAT secretion system, four separate Type I systems, one putative Type IV system and three Type V autotransporters. Mutations in genes encoding each of these (except the GEP were generated, but only mutations affecting the PrsDE (Type I and TAT systems were observed to affect the growth phenotype and the profile of proteins in the culture supernatant. Bioinformatic analysis and mass fingerprinting of tryptic fragments of culture supernatant proteins identified 14 putative Type I substrates, 12 of which are secreted via the PrsDE, secretion system. The TAT mutant was defective for the symbiosis, forming nodules incapable of nitrogen fixation. Conclusion None of the R. l. bv. viciae 3841 protein secretion systems putatively involved in the secretion of proteins to the extracellular space (Type I, Type IV, Type V is required for establishing the symbiosis with legumes. The PrsDE (Type I system was shown to be the major route of protein secretion in non-symbiotic cells and to secrete proteins of widely varied size and predicted function. This is in contrast to many Type I systems from other bacteria, which typically secrete specific substrates encoded by genes often localised in close proximity to

  9. Focal Transplantation of Human iPSC-Derived Glial-Rich Neural Progenitors Improves Lifespan of ALS Mice

    Directory of Open Access Journals (Sweden)

    Takayuki Kondo

    2014-08-01

    Full Text Available Transplantation of glial-rich neural progenitors has been demonstrated to attenuate motor neuron degeneration and disease progression in rodent models of mutant superoxide dismutase 1 (SOD1-mediated amyotrophic lateral sclerosis (ALS. However, translation of these results into a clinical setting requires a renewable human cell source. Here, we derived glial-rich neural progenitors from human iPSCs and transplanted them into the lumbar spinal cord of ALS mouse models. The transplanted cells differentiated into astrocytes, and the treated mouse group showed prolonged lifespan. Our data suggest a potential therapeutic mechanism via activation of AKT signal. The results demonstrated the efficacy of cell therapy for ALS by the use of human iPSCs as cell source.

  10. A competitive advantage by neonatally engrafted human glial progenitors yields mice whose brains are chimeric for human glia

    DEFF Research Database (Denmark)

    Windrem, Martha S; Schanz, Steven J; Morrow, Carolyn;

    2014-01-01

    Neonatally transplanted human glial progenitor cells (hGPCs) densely engraft and myelinate the hypomyelinated shiverer mouse. We found that, in hGPC-xenografted mice, the human donor cells continue to expand throughout the forebrain, systematically replacing the host murine glia. The differentiat......Neonatally transplanted human glial progenitor cells (hGPCs) densely engraft and myelinate the hypomyelinated shiverer mouse. We found that, in hGPC-xenografted mice, the human donor cells continue to expand throughout the forebrain, systematically replacing the host murine glia. The...... differentiation of the donor cells is influenced by the host environment, such that more donor cells differentiated as oligodendrocytes in the hypomyelinated shiverer brain than in myelin wild-types, in which hGPCs were more likely to remain as progenitors. Yet in each recipient, both the number and relative...

  11. Indomethacin decreases gastroduodenal mucosal bicarbonate secretion in humans

    DEFF Research Database (Denmark)

    Mertz-Nielsen, A; Hillingsø, Jens; Bukhave, K;

    1995-01-01

    BACKGROUND: Cyclooxygenase inhibitors reduce mucosal bicarbonate secretion in the duodenum, but the evidence for their effect on bicarbonate secretion in the stomach remains controversial. We have, therefore, studied how indomethacin influences gastroduodenal bicarbonate secretion and luminal rel...

  12. Label-free distinguishing between neurons and glial cells based on two-photon excited fluorescence signal of neuron perinuclear granules

    Science.gov (United States)

    Du, Huiping; Jiang, Liwei; Wang, Xingfu; Liu, Gaoqiang; Wang, Shu; Zheng, Liqin; Li, Lianhuang; Zhuo, Shuangmu; Zhu, Xiaoqin; Chen, Jianxin

    2016-08-01

    Neurons and glial cells are two critical cell types of brain tissue. Their accurate identification is important for the diagnosis of psychiatric disorders such as depression and schizophrenia. In this paper, distinguishing between neurons and glial cells by using the two-photon excited fluorescence (TPEF) signals of intracellular intrinsic sources was performed. TPEF microscopy combined with TUJ-1 and GFAP immunostaining and quantitative image analysis demonstrated that the perinuclear granules of neurons in the TPEF images of brain tissue and the primary cultured cortical cells were a unique characteristic of neurons compared to glial cells which can become a quantitative feature to distinguish neurons from glial cells. With the development of miniaturized TPEF microscope (‘two-photon fiberscopes’) imaging devices, TPEF microscopy can be developed into an effective diagnostic and monitoring tool for psychiatric disorders such as depression and schizophrenia.

  13. Effect of interleukin-1β on spinal cord nociceptive transmission of normal and monoarthritic rats after disruption of glial function

    OpenAIRE

    Constandil, Luis; Hernández, Alejandro; Pelissier, Teresa; Arriagada, Osvaldo; Espinoza, Karla; Burgos, Hector; Laurido, Claudio

    2009-01-01

    Introduction Cytokines produced by spinal cord glia after peripheral injuries have a relevant role in the maintenance of pain states. Thus, while IL-1β is overexpressed in the spinal cords of animals submitted to experimental arthritis and other chronic pain models, intrathecal administration of IL-1β to healthy animals induces hyperalgesia and allodynia and enhances wind-up activity in dorsal horn neurons. Methods To investigate the functional contribution of glial cells in the spinal cord n...

  14. Time-Lapse Imaging of the Dynamics of CNS Glial-Axonal Interactions In Vitro and Ex Vivo

    OpenAIRE

    Kalliopi Ioannidou; Anderson, Kurt I; David Strachan; Edgar, Julia M.; Barnett, Susan C.

    2012-01-01

    Background Myelination is an exquisite and dynamic example of heterologous cell-cell interaction, which consists of the concentric wrapping of multiple layers of oligodendrocyte membrane around neuronal axons. Understanding the mechanism by which oligodendrocytes ensheath axons may bring us closer to designing strategies to promote remyelination in demyelinating diseases. The main aim of this study was to follow glial-axonal interactions over time both in vitro and ex vivo to visualize th...

  15. Genetic deletion of afadin causes hydrocephalus by destruction of adherens junctions in radial glial and ependymal cells in the midbrain.

    Directory of Open Access Journals (Sweden)

    Hideaki Yamamoto

    Full Text Available Adherens junctions (AJs play a role in mechanically connecting adjacent cells to maintain tissue structure, particularly in epithelial cells. The major cell-cell adhesion molecules at AJs are cadherins and nectins. Afadin binds to both nectins and α-catenin and recruits the cadherin-β-catenin complex to the nectin-based cell-cell adhesion site to form AJs. To explore the role of afadin in radial glial and ependymal cells in the brain, we generated mice carrying a nestin-Cre-mediated conditional knockout (cKO of the afadin gene. Newborn afadin-cKO mice developed hydrocephalus and died neonatally. The afadin-cKO brain displayed enlarged lateral ventricles and cerebral aqueduct, resulting from stenosis of the caudal end of the cerebral aqueduct and obliteration of the ventral part of the third ventricle. Afadin deficiency further caused the loss of ependymal cells from the ventricular and aqueductal surfaces. During development, radial glial cells, which terminally differentiate into ependymal cells, scattered from the ventricular zone and were replaced by neurons that eventually covered the ventricular and aqueductal surfaces of the afadin-cKO midbrain. Moreover, the denuded ependymal cells were only occasionally observed in the third ventricle and the cerebral aqueduct of the afadin-cKO midbrain. Afadin was co-localized with nectin-1 and N-cadherin at AJs of radial glial and ependymal cells in the control midbrain, but these proteins were not concentrated at AJs in the afadin-cKO midbrain. Thus, the defects in the afadin-cKO midbrain most likely resulted from the destruction of AJs, because AJs in the midbrain were already established before afadin was genetically deleted. These results indicate that afadin is essential for the maintenance of AJs in radial glial and ependymal cells in the midbrain and is required for normal morphogenesis of the cerebral aqueduct and ventral third ventricle in the midbrain.

  16. Zirconium oxide ceramic foam: a promising supporting biomaterial for massive production of glial cell line-derived neurotrophic factor*

    OpenAIRE

    Liu, Zhong-Wei; Li, Wen-qiang; Wang, Jun-kui; Ma, Xian-cang; Liang, Chen; Liu, Peng; Chu, Zheng; Dang, Yong-hui

    2014-01-01

    This study investigated the potential application of a zirconium oxide (ZrO2) ceramic foam culturing system to the production of glial cell line-derived neurotrophic factor (GDNF). Three sets of ZrO2 ceramic foams with different pore densities of 10, 20, and 30 pores per linear inch (PPI) were prepared to support a 3D culturing system. After primary astrocytes were cultured in these systems, production yields of GDNF were evaluated. The biomaterial biocompatibility, cell proliferation and act...

  17. Neonatal Neural Progenitor Cells and Their Neuronal and Glial Cell Derivatives Are Fully Permissive for Human Cytomegalovirus Infection▿

    OpenAIRE

    Luo, Min Hua; Philip H. Schwartz; Fortunato, Elizabeth A.

    2008-01-01

    Congenital human cytomegalovirus (HCMV) infection causes central nervous system structural abnormalities and functional disorders, affecting both astroglia and neurons with a pathogenesis that is only marginally understood. To better understand HCMV's interactions with such clinically important cell types, we utilized neural progenitor cells (NPCs) derived from neonatal autopsy tissue, which can be differentiated down either glial or neuronal pathways. Studies were performed using two viral i...

  18. Reexpression of glial fibrillary acidic protein rescues the ability of astrocytoma cells to form processes in response to neurons

    OpenAIRE

    1994-01-01

    Astroglial cells play an important role in orchestrating the migration and positioning of neurons during central nervous system development. Primary astroglia, as well as astrocytoma cells will extend long stable processes when co-cultured with granule neurons. In order to determine the function of the glial fibrillary acidic protein (GFAP), the major intermediate filament protein in astroglia and astrocytoma cells, we suppressed the expression of GFAP by stable transfection of an anti- sense...

  19. Glial alterations from early to late stages in a model of Alzheimer's disease: Evidence of autophagy involvement in Aβ internalization.

    Science.gov (United States)

    Pomilio, Carlos; Pavia, Patricio; Gorojod, Roxana Mayra; Vinuesa, Angeles; Alaimo, Agustina; Galvan, Veronica; Kotler, Monica Lidia; Beauquis, Juan; Saravia, Flavia

    2016-02-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disease without effective therapy. Brain amyloid deposits are classical histopathological hallmarks that generate an inflammatory reaction affecting neuronal and glial function. The identification of early cell responses and of brain areas involved could help to design new successful treatments. Hence, we studied early alterations of hippocampal glia and their progression during the neuropathology in PDAPP-J20 transgenic mice, AD model, at 3, 9, and 15 months (m) of age. At 3 m, before deposits formation, microglial Iba1+ cells from transgenic mice already exhibited signs of activation and larger soma size in the hilus, alterations appearing later on stratum radiatum. Iba1 immunohistochemistry revealed increased cell density and immunoreactive area in PDAPP mice from 9 m onward selectively in the hilus, in coincidence with prominent amyloid Congo red + deposition. At pre-plaque stages, GFAP+ astroglia showed density alterations while, at an advanced age, the presence of deposits was associated with important glial volume changes and apparently being intimately involved in amyloid degradation. Astrocytes around plaques were strongly labeled for LC3 until 15 m in Tg mice, suggestive of increased autophagic flux. Moreover, β-Amyloid fibrils internalization by astrocytes in in vitro conditions was dependent on autophagy. Co-localization of Iba1 with ubiquitin or p62 was exclusively found in microglia contacting deposits from 9 m onward, suggesting torpid autophagy. Our work characterizes glial changes at early stages of the disease in PDAPP-J20 mice, focusing on the hilus as an especially susceptible hippocampal subfield, and provides evidence that glial autophagy could play a role in amyloid processing at advanced stages. PMID:26235241

  20. MYELIN BASIC PROTEIN-PRIMED T CELLS INDUCE NEUROTROPHINS IN GLIAL CELLS VIA α5β3 INTEGRIN

    OpenAIRE

    Roy, Avik; Liu, Xiaojuan; Pahan, Kalipada

    2007-01-01

    Increasing the level of neurotrophins within the CNS may have therapeutic efficacy in patients with various neurological diseases. Earlier we have demonstrated that myelin basic protein (MBP)-primed T cells induce the expression of various proinflammatory molecules in glial cells via cell-to-cell contact. Here we describe that after Th2 polarization by gemfibrozil or other drugs, MBP-primed T cells induced the expression of neurotrophic molecules such as, brain-derived neurotrophic factor (BD...

  1. Radiosensitivity of glial progenitor cells of the perinatal and adult rat optic nerve studied by an in vitro clonogenic assay

    International Nuclear Information System (INIS)

    The cellular basis of radiation-induced demyelination and white matter necrosis of the central nervous system (CNS), is poorly understood. Glial cells responsible for myelination in the CNS might be the target cells of this type of damage. Glial cells with stem cell properties derived from the perinatal and adult rat CNS can be cultured in vitro. These cells are able to differentiate into oligodendrocytes or type-2 astrocytes (O-2A) depending on the culture conditions. Growth factors produced by monolayers of type-1 astrocytes inhibit premature differentiation of O-2A progenitor cells and allow colony formation. A method which employs these monolayers of type-1 astrocytes to culture O-2A progenitor cells has been adapted to allow the analysis of colonies of surviving cells after X-irradiation. In vitro survival curves were obtained for glial progenitor cells derived from perinatal and adult optic nerves. The intrinsic radiosensitivity of perinatal and adult O-2A progenitor cells showed a large difference. Perinatal O-2A progenitor cells are quite radiosensitive, in contrast to adult O-2A progenitor cells. For both cell types an inverse relationship was found between the dose and the size of colonies derived from surviving cells. Surviving O-2A progenitor cells maintain their ability to differentiate into oligo-dendrocytes or type-2 astrocytes. This system to assess radiation-induced damage to glial progenitor cells in vitro systems to have a great potential in unraveling the cellular basis of radiation-induced demyelinating syndromes of the CNS. (author). 28 refs.; 4 figs.; 1 tab

  2. Differences in DNA methylation between human neuronal and glial cells are concentrated in enhancers and non-CpG sites

    OpenAIRE

    Kozlenkov, Alexey; Roussos, Panos; Timashpolsky, Alisa; Barbu, Mihaela; Rudchenko, Sergei; Bibikova, Marina; Klotzle, Brandy; Byne, William; Lyddon, Rebecca; Di Narzo, Antonio Fabio; Hurd, Yasmin L.; Eugene V Koonin; Dracheva, Stella

    2013-01-01

    We applied Illumina Human Methylation450K array to perform a genomic-scale single-site resolution DNA methylation analysis in neuronal and nonneuronal (primarily glial) nuclei separated from the orbitofrontal cortex of postmortem human brain. The findings were validated using enhanced reduced representation bisulfite sequencing. We identified thousands of sites differentially methylated (DM) between neuronal and nonneuronal cells. The DM sites were depleted within CpG-island–containing promot...

  3. The neuregulin, glial growth factor 2, diminishes autoimmune demyelination and enhances remyelination in a chronic relapsing model for multiple sclerosis

    OpenAIRE

    Cannella, Barbara; Hoban, Carolyn J; Gao, Yan-Ling; Garcia-Arenas, Renee; Lawson, Deborah; Marchionni, Mark; Gwynne, David; Raine, Cedric S.

    1998-01-01

    Glial growth factor 2 (GGF2) is a neuronal signal that promotes the proliferation and survival of the oligodendrocyte, the myelinating cell of the central nervous system (CNS). The present study examined whether recombinant human GGF2 (rhGGF2) could effect clinical recovery and repair to damaged myelin in chronic relapsing experimental autoimmune encephalomyelitis (EAE) in the mouse, a major animal model for the human demyelinating disease, multiple sclerosis. Mice with EAE were treated with ...

  4. Chronic psychosocial stress and citalopram modulate the expression of the glial proteins GFAP and NDRG2 in the hippocampus

    OpenAIRE

    Araya-Callís, Carolina; Hiemke, Christoph; Abumaria, Nashat; Flugge, Gabriele

    2012-01-01

    Rationale It has been suggested that there are causal relationships between alterations in brain glia and major depression. Objectives To investigate whether a depressive-like state induces changes in brain astrocytes, we used chronic social stress in male rats, an established preclinical model of depression. Expression of two astrocytic proteins, the intermediate filament component glial fibrillary acidic protein (GFAP) and the cytoplasmic protein N-myc downregulated gene 2 (NDRG2), was anal...

  5. Effects of atorvastatin on plasma matrix metalloproteinase-9 concentration after glial tumor resection; a randomized, double blind, placebo controlled trial

    OpenAIRE

    Mohebbi, Niayesh; Khoshnevisan, Alireza; Naderi, Soheil; Abdollahzade, Sina; Salamzadeh, Jamshid; Javadi, Mohammadreza; Mojtahedzadeh, Mojtaba; GHOLAMI, KHEIROLLAH.

    2014-01-01

    Background Neurosurgical procedures such as craniotomy and brain tumor resection could potentially lead to unavoidable cerebral injuries. Matrix metalloproteinase-9 (MMP-9) is up-regulated in neurological injuries. Statins have been suggested to reduce MMP- 9 level and lead to neuroprotection. Atorvastatin preoperatively administered to evaluate its neuroprotective effects and outcome assessment in neurosurgical-induced brain injuries after glial tumor resection. In this prospective, randomiz...

  6. First evidence for glial pathology in late life minor depression: S100B is increased in males with minor depression

    OpenAIRE

    Polyakova, Maryna; Sander, Christian; Arelin, Katrin; Lampe, Leonie; Luck, Tobias; Luppa, Melanie; Kratzsch, Jürgen; Hoffmann, Karl-Titus; Riedel-Heller, Steffi; Villringer, Arno; Schoenknecht, Peter; Schroeter, Matthias L.

    2015-01-01

    Minor depression is diagnosed when a patient suffers from 2 to 4 depressive symptoms for at least 2 weeks. Though minor depression is a widespread phenomenon, its pathophysiology has hardly been studied. To get a first insight into the pathophysiological mechanisms underlying this disorder we assessed serum levels of biomarkers for plasticity, glial and neuronal function: brain-derived neurotrophic factor (BDNF), S100B and neuron specific enolase (NSE). 27 subjects with minor depressive episo...

  7. First evidence for glial pathology in late life minor depression: S100B is increased in males with minor depression

    OpenAIRE

    Maryna Polyakova; Tobias Luck; Juergen Kratzsch; Karl-Titus Hoffmann; Arno Villringer

    2015-01-01

    Minor depression is diagnosed when a patient suffers from two to four depressive symptoms for at least two weeks. Though minor depression is a widespread phenomenon, its pathophysiology has hardly been studied. To get a first insight into the pathophysiological mechanisms underlying this disorder we assessed serum levels of biomarkers for plasticity, glial and neuronal function: brain-derived neurotrophic factor (BDNF), S100B and neuron specific enolase (NSE). 27 subjects with minor depressiv...

  8. Neural progenitor cells isolated from the subventricular zone present hemichannel activity and form functional gap junctions with glial cells

    Science.gov (United States)

    Talaverón, Rocío; Fernández, Paola; Escamilla, Rosalba; Pastor, Angel M.; Matarredona, Esperanza R.; Sáez, Juan C.

    2015-01-01

    The postnatal subventricular zone (SVZ) lining the walls of the lateral ventricles contains neural progenitor cells (NPCs) that generate new olfactory bulb interneurons. Communication via gap junctions between cells in the SVZ is involved in NPC proliferation and in neuroblast migration towards the olfactory bulb. SVZ NPCs can be expanded in vitro in the form of neurospheres that can be used for transplantation purposes after brain injury. We have previously reported that neurosphere-derived NPCs form heterocellular gap junctions with host glial cells when they are implanted after mechanical injury. To analyze functionality of NPC-glial cell gap junctions we performed dye coupling experiments in co-cultures of SVZ NPCs with astrocytes or microglia. Neurosphere-derived cells expressed mRNA for at least the hemichannel/gap junction channel proteins connexin 26 (Cx26), Cx43, Cx45 and pannexin 1 (Panx1). Dye coupling experiments revealed that gap junctional communication occurred among neurosphere cells (incidence of coupling: 100%). Moreover, hemichannel activity was also detected in neurosphere cells as evaluated in time-lapse measurements of ethidium bromide uptake. Heterocellular coupling between NPCs and glial cells was evidenced in co-cultures of neurospheres with astrocytes (incidence of coupling: 91.0 ± 4.7%) or with microglia (incidence of coupling: 71.9 ± 6.7%). Dye coupling in neurospheres and in co-cultures was inhibited by octanol, a gap junction blocker. Altogether, these results suggest the existence of functional hemichannels and gap junction channels in postnatal SVZ neurospheres. In addition, they demonstrate that SVZ-derived NPCs can establish functional gap junctions with astrocytes or microglia. Therefore, cell-cell communication via gap junctions and hemichannels with host glial cells might subserve a role in the functional integration of NPCs after implantation in the damaged brain. PMID:26528139

  9. Satellite glial cells can promote the extension of neuronal axons in vitro

    Institute of Scientific and Technical Information of China (English)

    Jiu-Hong Zhao; Yi-Di Huang; Xi-Nan Yi; Quan-Peng Zhang; Xian-Fang Zhang; Xu Dong; Gang Luo; Hai-Ying Zhang; Kun-Ju Wang; Mei-Li Lao

    2015-01-01

    Objective: To study the influence of satellite glial cells (SGCs) on the outgrowth of neuronal neurite and the role of Slit1 protein and the contact with neurons in this process, in vitro. Methods: Neurons culture and SGC-neuron co-culture were used as the cell models. The length of axons and dendrites were measured via immunofluorescence to observe the influence of SGCs on the outgrowth of neuronal neurite. The Slit1 protein was added into SGC-neuron co-culture model. The length of dendrites was measured via immunofluorescence at different point times. Result: The anatomical relationship between neurons and SGCs changed as culture period expand. At 12 h after culture, SGCs all surrounded neurons; by 72 h after culture, SGCs were all off neurons. SGCs can promote the growth of neuronal axos, but inhibit the growth of its dendrites; when SGCs closely contact with neurons, the effect of Slit1 on promoting the dendritic growth is not obvious, but when SGCs were off neurons, the effect of Slit1 on promoting the dendritic growth is significant. Conclusion: SGCs can promote the growth of neuronal axos, but inhibit the growth of its dendrites; Slit- Robo signaling pathways and contact with neurons play a role in this process.

  10. Molecular cloning and primary structure of human glial fibrillary acidic protein

    Energy Technology Data Exchange (ETDEWEB)

    Reeves, S.A.; Helman, L.J.; Allison, A.; Israel, M.A. (National Cancer Institute, Bethesda, MD (USA))

    1989-07-01

    Glial fibrillary acidic protein (GFAP) is an intermediate-filament (IF) protein that is highly specific for cells of astroglial lineage, although its tissue-specific role is speculative. Determination of the primary structure of this protein should be of importance for understanding the functional role it plays in astroglia. Therefore, the authors isolated a cDNA clone encoding this protein and determined its nucleotide sequence. The predicted amino acid sequence indicates that GFAP shares structural similarities-particularly in the central rod domain and to a lesser degree in the carboxyl-terminal domain-with other IF proteins found in nonepithelial cell types. Considerable sequence divergence in the amino-terminal region of GFAP suggests that the tissue-specific functions of this IF protein might be mediated through this region of the molecule. In contrast, conservation of structural characteristics and a moderate degree of sequence conservation in the carboxyl-terminal region suggest functional similarities. Blot hybridization analysis using the GFAP cDNA as a probe failed to detect GFAP mRNA in both normal and neoplastic human tissues in which IF proteins other than GFAP are known to be expressed.

  11. Combined treatment with ribavirin and tiazofurin attenuates response of glial cells in experimental autoimmune encephalomyelitis

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    Nedeljković Nadežda

    2012-01-01

    Full Text Available Experimental autoimmune encephalomyelitis (EAE is an animal model of multiple sclerosis (MS, a human inflammatory and demyelinating disease. Microglia and astrocytes are glial cells of the central nervous system (CNS that play a dual role in MS and EAE pathology. The aim of this study was to examine the effect of combined treatment with two nucleoside analogues, ribavirin and tiazofurin, on microglia and astrocytes in actively induced EAE. Therapeutic treatment with a combination of these two nucleoside analogues reduced disease severity, mononuclear cell infiltration and demyelination. The obtained histological results indicate that ribavirin and tiazofurin changed activated microglia into an inactive type and attenuated astrocyte reactivity at the end of the treatment period. Since reduction of reactive microgliosis and astrogliosis correlated with EAE suppression, the present study also suggests that the obtained beneficial effect of ribavirin and tiazofurin could be a consequence of their action inside as well as outside the CNS. [Acknowledgments. This work was supported by the Serbian Ministry of Education and Science, Project No: III41014.

  12. High Resolution Dissection of Reactive Glial Nets in Alzheimer’s Disease

    Science.gov (United States)

    Bouvier, David S.; Jones, Emma V.; Quesseveur, Gaël; Davoli, Maria Antonietta; A. Ferreira, Tiago; Quirion, Rémi; Mechawar, Naguib; Murai, Keith K.

    2016-01-01

    Fixed human brain samples in tissue repositories hold great potential for unlocking complexities of the brain and its alteration with disease. However, current methodology for simultaneously resolving complex three-dimensional (3D) cellular anatomy and organization, as well as, intricate details of human brain cells in tissue has been limited due to weak labeling characteristics of the tissue and high background levels. To expose the potential of these samples, we developed a method to overcome these major limitations. This approach offers an unprecedented view of cytoarchitecture and subcellular detail of human brain cells, from cellular networks to individual synapses. Applying the method to AD samples, we expose complex features of microglial cells and astrocytes in the disease. Through this methodology, we show that these cells form specialized 3D structures in AD that we refer to as reactive glial nets (RGNs). RGNs are areas of concentrated neuronal injury, inflammation, and tauopathy and display unique features around β-amyloid plaque types. RGNs have conserved properties in an AD mouse model and display a developmental pattern coinciding with the progressive accumulation of neuropathology. The method provided here will help reveal novel features of the healthy and diseased human brain, and aid experimental design in translational brain research. PMID:27090093

  13. A model of space-fractional-order diffusion in the glial scar.

    Science.gov (United States)

    Prodanov, Dimiter; Delbeke, Jean

    2016-08-21

    Implantation of neuroprosthetic electrodes induces a stereotypical state of neuroinflammation, which is thought to be detrimental for the neurons surrounding the electrode. Mechanisms of this type of neuroinflammation are still poorly understood. Recent experimental and theoretical results point to a possible role of the diffusing species in this process. The paper considers a model of anomalous diffusion occurring in the glial scar around a chronic implant in two simple geometries - a separable rectilinear electrode and a cylindrical electrode, which are solvable exactly. We describe a hypothetical extended source of diffusing species and study its concentration profile in steady-state conditions. Diffusion transport is assumed to obey a fractional-order Fick law, derivable from physically realistic assumptions using a fractional calculus approach. Presented fractional-order distribution morphs into integer-order diffusion in the case of integral fractional exponents. The model demonstrates that accumulation of diffusing species can occur and the scar properties (i.e. tortuosity, fractional order, scar thickness) and boundary conditions can influence such accumulation. The observed shape of the concentration profile corresponds qualitatively with GFAP profiles reported in the literature. The main difference with respect to the previous studies is the explicit incorporation of the apparatus of fractional calculus without assumption of an ad hoc tortuosity parameter. The approach can be adapted to other studies of diffusion in biological tissues, for example of biomolecules or small drug molecules. PMID:27179458

  14. Glial fibrillary acidic protein (GFAP: modulation by growth factors and its implication in astrocyte differentiation

    Directory of Open Access Journals (Sweden)

    F.C.A. Gomes

    1999-05-01

    Full Text Available Intermediate filament (IF proteins constitute an extremely large multigene family of developmentally and tissue-regulated cytoskeleton proteins abundant in most vertebrate cell types. Astrocyte precursors of the CNS usually express vimentin as the major IF. Astrocyte maturation is followed by a switch between vimentin and glial fibrillary acidic protein (GFAP expression, with the latter being recognized as an astrocyte maturation marker. Levels of GFAP are regulated under developmental and pathological conditions. Upregulation of GFAP expression is one of the main characteristics of the astrocytic reaction commonly observed after CNS lesion. In this way, studies on GFAP regulation have been shown to be useful to understand not only brain physiology but also neurological disease. Modulators of GFAP expression include several hormones such as thyroid hormone, glucocorticoids and several growth factors such as FGF, CNTF and TGFß, among others. Studies of the GFAP gene have already identified several putative growth factor binding domains in its promoter region. Data obtained from transgenic and knockout mice have provided new insights into IF protein functions. This review highlights the most recent studies on the regulation of IF function by growth factors and hormones.

  15. Acquisition of glial cells missing 2 enhancers contributes to a diversity of ionocytes in zebrafish.

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    Takanori Shono

    Full Text Available Glial cells missing 2 (gcm2 encoding a GCM-motif transcription factor is expressed in the parathyroid in amniotes. In contrast, gcm2 is expressed in pharyngeal pouches (a homologous site of the parathyroid, gills, and H(+-ATPase-rich cells (HRCs, a subset of ionocytes on the skin surface of the teleost fish zebrafish. Ionocytes are specialized cells that are involved in osmotic homeostasis in aquatic vertebrates. Here, we showed that gcm2 is essential for the development of HRCs and Na(+-Cl(- co-transporter-rich cells (NCCCs, another subset of ionocytes in zebrafish. We also identified gcm2 enhancer regions that control gcm2 expression in ionocytes of zebrafish. Comparisons of the gcm2 locus with its neighboring regions revealed no conserved elements between zebrafish and tetrapods. Furthermore, We observed gcm2 expression patterns in embryos of the teleost fishes Medaka (Oryzias latipes and fugu (Fugu niphobles, the extant primitive ray-finned fishes Polypterus (Polypterus senegalus and sturgeon (a hybrid of Huso huso × Acipenser ruhenus, and the amphibian Xenopus (Xenopus laevis. Although gcm2-expressing cells were observed on the skin surface of Medaka and fugu, they were not found in Polypterus, sturgeon, or Xenopus. Our results suggest that an acquisition of enhancers for the expression of gcm2 contributes to a diversity of ionocytes in zebrafish during evolution.

  16. Modulation of excitatory neurotransmission by neuronal/glial signalling molecules: interplay between purinergic and glutamatergic systems.

    Science.gov (United States)

    Köles, László; Kató, Erzsébet; Hanuska, Adrienn; Zádori, Zoltán S; Al-Khrasani, Mahmoud; Zelles, Tibor; Rubini, Patrizia; Illes, Peter

    2016-03-01

    Glutamate is the main excitatory neurotransmitter of the central nervous system (CNS), released both from neurons and glial cells. Acting via ionotropic (NMDA, AMPA, kainate) and metabotropic glutamate receptors, it is critically involved in essential regulatory functions. Disturbances of glutamatergic neurotransmission can be detected in cognitive and neurodegenerative disorders. This paper summarizes the present knowledge on the modulation of glutamate-mediated responses in the CNS. Emphasis will be put on NMDA receptor channels, which are essential executive and integrative elements of the glutamatergic system. This receptor is crucial for proper functioning of neuronal circuits; its hypofunction or overactivation can result in neuronal disturbances and neurotoxicity. Somewhat surprisingly, NMDA receptors are not widely targeted by pharmacotherapy in clinics; their robust activation or inhibition seems to be desirable only in exceptional cases. However, their fine-tuning might provide a promising manipulation to optimize the activity of the glutamatergic system and to restore proper CNS function. This orchestration utilizes several neuromodulators. Besides the classical ones such as dopamine, novel candidates emerged in the last two decades. The purinergic system is a promising possibility to optimize the activity of the glutamatergic system. It exerts not only direct and indirect influences on NMDA receptors but, by modulating glutamatergic transmission, also plays an important role in glia-neuron communication. These purinergic functions will be illustrated mostly by depicting the modulatory role of the purinergic system on glutamatergic transmission in the prefrontal cortex, a CNS area important for attention, memory and learning. PMID:26542977

  17. Treatment with glial derived neurotropic factor (GDNF attenuates oxidative damages of spinal

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    Tao Li

    2016-05-01

    Full Text Available Spinal cord injury (SCI is a serious and debilitating issue being suffered by wide population worldwide. Extensive treatment approaches have been tested and being verified for their efficacy. Owing to the nature of central nervous system (CNS, the resident stem cells would be triggered in response to any sort of trauma with nerve factors as their communication signals. Apart from physical injuries, damages due to oxidative stress also need to be addressed while CNS repair mechanism takes place. This study looks at the potential of glial derived nerve factor (GDNF in addressing the SCI in regard to oxidative damages. A total of 60 Wistar rats were clustered into five groups and GDNF at various concentrations was tested in each group. Assessments in terms of oxidative stress parameters were noted and analyzed accordingly. It was noted that GDNF had reduced oxidative damages and increased the levels of anti-oxidants in dose-dependent manner (p < 0.05. Though treatment with 10 mg/mL and 20 mg/mL showed significant changes as compared to control group, these treatment modalities remained insignificant among each other. In conclusion, we demonstrated that GDNF exerted a neuro-protective effect on CNS by inducing anti-oxidants and reducing the levels of oxidative stress in SCI induced rat models.

  18. Comparative Analysis of Human, Mouse, and Pig Glial Fibrillary Acidic Protein Gene Structures.

    Science.gov (United States)

    Eun, Kiyoung; Hwang, Seon-Ung; Jeon, Hye-Min; Hyun, Sang-Hwan; Kim, Hyunggee

    2016-01-01

    Comparing the coding and regulatory sequences of genes in different species provides information on whether proteins translated from genes have conserved functions or gene expressions are regulated by analogical mechanisms. Herein, we compared the coding and regulatory sequences of glial fibrillary acidic protein (GFAP) from humans, mice, and pigs. The GFAP gene encodes a class III intermediate filament protein expressed specifically in astrocytes of the central nervous system. On comparing the mRNA, regulatory region (promoter), and protein sequences of GFAP gene in silico, we found that GFAP mRNA 3'-untranslated region (3'-UTR), promoter, and amino acid sequences showed higher similarities between humans and pigs than between humans and mice. In addition, the promoter-luciferase reporter gene assay revealed that the pig GFAP promoter functioned in human astrocytes. Notably, the 1.8-kb promoter fragment upstream from transcription initiation site showed strongest transcriptional activity compared to 5.2-kb DNA fragment or other regions of GFAP promoter. We also found that pig GFAP mRNA and promoter activity increased in pig fibroblasts by human IL-1β treatment. Taken together, these results suggest that the regulatory mechanisms and functions of pig genes might be more similar to those of humans than mice, indicating that pigs, particularly miniature pigs, are a useful model for studying human biological and pathological events. PMID:26913554

  19. Steroid modulation of neurogenesis: Focus on radial glial cells in zebrafish.

    Science.gov (United States)

    Pellegrini, Elisabeth; Diotel, Nicolas; Vaillant-Capitaine, Colette; Pérez Maria, Rita; Gueguen, Marie-Madeleine; Nasri, Ahmed; Cano Nicolau, Joel; Kah, Olivier

    2016-06-01

    Estrogens are known as steroid hormones affecting the brain in many different ways and a wealth of data now document effects on neurogenesis. Estrogens are provided by the periphery but can also be locally produced within the brain itself due to local aromatization of circulating androgens. Adult neurogenesis is described in all vertebrate species examined so far, but comparative investigations have brought to light differences between vertebrate groups. In teleost fishes, the neurogenic activity is spectacular and adult stem cells maintain their mitogenic activity in many proliferative areas within the brain. Fish are also quite unique because brain aromatase expression is limited to radial glia cells, the progenitor cells of adult fish brain. The zebrafish has emerged as an interesting vertebrate model to elucidate the cellular and molecular mechanisms of adult neurogenesis, and notably its modulation by steroids. The main objective of this review is to summarize data related to the functional link between estrogens production in the brain and neurogenesis in fish. First, we will demonstrate that the brain of zebrafish is an endogenous source of steroids and is directly targeted by local and/or peripheral steroids. Then, we will present data demonstrating the progenitor nature of radial glial cells in the brain of adult fish. Next, we will emphasize the role of estrogens in constitutive neurogenesis and its potential contribution to the regenerative neurogenesis. Finally, the negative impacts on neurogenesis of synthetic hormones used in contraceptive pills production and released in the aquatic environment will be discussed. PMID:26151741

  20. Role of glial cells in innate immunity and their role in CNS demyelination.

    Science.gov (United States)

    Sriram, Subramaniam

    2011-10-28

    The adaptive and innate arms of the immune system are the two pillars of host defense against environmental pathogens. Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS which is considered to be autoimmune and is thought to result from breakdown in the usual checks and balances of the adaptive immune response. The major pathological outcome of the disease is "the MS plaque" a unique feature of CNS demyelination characterized by the destruction of oligodendrocytes with loss of myelin and underlying axons. The MS plaque is not seen in other inflammatory disorders of the CNS. The prevailing opinion suggests that MS is mediated by the activation of an adaptive immune response which targets neural antigens. Currently, the role of an innate immune in the development of the lesions in MS has remained unclear. We explore the potential cellular elements of the innate immune system and in particular glial cells, which are likely candidates in inducing the specific pathological picture that is evident in MS. Activated microglia and the release of molecules which are detrimental to oligodendrocyte have been suggested as mechanisms by which innate immunity causes demyelination in MS. However a microglia/macrophage centric model does not explain the specificity of lesion development in MS. We propose that activation pathways of receptors of the innate immune system present on oligodendrocytes and astrocytes rather than microglia are central to the pathogenesis of demyelination seen in MS. PMID:21907419

  1. Regulation of Glial Cell Functions by PPAR-γ Natural and Synthetic Agonists

    Directory of Open Access Journals (Sweden)

    Luisa Minghetti

    2008-04-01

    Full Text Available In the recent years, the peroxisome proliferator-activated receptor-γ (PPAR-γ, a well known target for type II diabetes treatment, has received an increasing attention for its therapeutic potential in inflammatory and degenerative brain disorders. PPAR-γ agonists, which include naturally occurring compounds (such as long chain fatty acids and the cyclopentenone prostaglandin 15-deoxy Δ12,14 prostaglandin J2, and synthetic agonists (among which the thiazolidinediones and few nonsteroidal anti-inflammatory drugs have shown anti-inflammatory and protective effects in several experimental models of Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, multiple sclerosis and stroke, as well as in few clinical studies. The pleiotropic effects of PPAR-γ agonists are likely to be mediated by several mechanisms involving anti-inflammatory activities on peripheral immune cells (macrophages and lymphocytes, as well as direct effects on neural cells including cerebral vascular endothelial cells, neurons, and glia. In the present article, we will review the recent findings supporting a major role for PPAR-γ agonists in controlling neuroinflammation and neurodegeneration through their activities on glial cells, with a particular emphasis on microglial cells as major macrophage population of the brain parenchyma and main actors in brain inflammation.

  2. Prospective therapies for high-grade glial tumours: A literature review

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    Sayed Samed Talibi

    2014-09-01

    Full Text Available After three decades of intensive research, cytoreductive surgery remains the gold standard of treatment of malignant gliomas. Survivorship at both 1-year and 5-years has not drastically changed in the UK. Concomitant chemo- and radiotherapy has enhanced the efficiency of surgery, enabling more aggressive tumour resection whilst also preserving the surrounding healthy brain parenchyma. More accurate imaging techniques have also played a role in tumour identification, key to this has been pre- and intra-operative contrast enhancement and compounds that have a high affinity in binding to glioma cells. Intra-operative imaging has heralded the ability to give the operating surgeon continuous feedback to assess the completeness of resection. Research is shifting into investigating the complex cellular and molecular glial tumour-genesis, and has led to the development of efficacious chemotherapy agents and trial novel therapies. Oncolytic virotherapy has shown promise in clinical trials and gene therapy in-vitro studies. Surgery however remains the primary therapeutic option for the management of malignant gliomas removing the mass of proliferating malignant tumour cells and decompression of the space-occupying lesion.

  3. Characterization of Olfactory Ensheathing Glial Cells Cultured on Polyurethane/Polylactide Electrospun Nonwovens

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    Jakub Grzesiak

    2015-01-01

    Full Text Available The aim of this research was to evaluate novel biomaterials for neural regeneration. The investigated materials were composed of polyurethane (PU and polylactide (PLDL blended at three different w/w ratios, that is, 5/5, 6/4, and 8/2 of PU/PLDL. Ultrathin fibrous scaffolds were prepared using electrospinning. The scaffolds were investigated for their applicability for nerve regeneration by culturing rat olfactory ensheathing glial cells. Cells were cultured on the materials for seven days, during which cellular morphology, phenotype, and metabolic activity were analysed. SEM analysis of the fabricated fibrous scaffolds showed fibers of a diameter mainly lower than 600 μm with unimportant volume of protrusions situated along the fibers, with nonsignificant differences between all analysed materials. Cells cultured on the materials showed differences in their morphology and metabolic activity, depending on the blend composition. The most proper morphology, with numerous p75+ and GFAP+ cells present, was observed in the sample 6/4, whereas the highest metabolic activity was measured in the sample 5/5. However, none of the investigated samples showed cytotoxicity or negatively influenced cellular morphology. Therefore, the novel electrospun fibrous materials may be considered for regenerative medicine applications, and especially when contacting with highly sensitive nervous cells.

  4. Proliferative reactive gliosis is compatible with glial metabolic support and neuronal function

    Directory of Open Access Journals (Sweden)

    Fero Matthew

    2011-10-01

    Full Text Available Abstract Background The response of mammalian glial cells to chronic degeneration and trauma is hypothesized to be incompatible with support of neuronal function in the central nervous system (CNS and retina. To test this hypothesis, we developed an inducible model of proliferative reactive gliosis in the absence of degenerative stimuli by genetically inactivating the cyclin-dependent kinase inhibitor p27Kip1 (p27 or Cdkn1b in the adult mouse and determined the outcome on retinal structure and function. Results p27-deficient Müller glia reentered the cell cycle, underwent aberrant migration, and enhanced their expression of intermediate filament proteins, all of which are characteristics of Müller glia in a reactive state. Surprisingly, neuroglial interactions, retinal electrophysiology, and visual acuity were normal. Conclusion The benign outcome of proliferative reactive Müller gliosis suggests that reactive glia display context-dependent, graded and dynamic phenotypes and that reactivity in itself is not necessarily detrimental to neuronal function.

  5. Molecular cloning and primary structure of human glial fibrillary acidic protein

    International Nuclear Information System (INIS)

    Glial fibrillary acidic protein (GFAP) is an intermediate-filament (IF) protein that is highly specific for cells of astroglial lineage, although its tissue-specific role is speculative. Determination of the primary structure of this protein should be of importance for understanding the functional role it plays in astroglia. Therefore, the authors isolated a cDNA clone encoding this protein and determined its nucleotide sequence. The predicted amino acid sequence indicates that GFAP shares structural similarities-particularly in the central rod domain and to a lesser degree in the carboxyl-terminal domain-with other IF proteins found in nonepithelial cell types. Considerable sequence divergence in the amino-terminal region of GFAP suggests that the tissue-specific functions of this IF protein might be mediated through this region of the molecule. In contrast, conservation of structural characteristics and a moderate degree of sequence conservation in the carboxyl-terminal region suggest functional similarities. Blot hybridization analysis using the GFAP cDNA as a probe failed to detect GFAP mRNA in both normal and neoplastic human tissues in which IF proteins other than GFAP are known to be expressed

  6. Administration of the Glial Condition Medium in the Nucleus Accumbens Prolong Maintenance and Intensify Reinstatement of Morphine-Seeking Behavior.

    Science.gov (United States)

    Arezoomandan, Reza; Khodagholi, Fariba; Haghparast, Abbas

    2016-04-01

    Accumulating evidence suggested that glial cells are involved in synaptic plasticity and behavioral changes induced by drugs abuse. The role of these cells in maintenance and reinstatement of morphine (MRP) conditioned place preference (CPP) remains poorly characterized. The aim of present study was to investigate the direct role of glial cells in nucleus accumbens (NAc) in the maintenance and reinstatement of MRP-seeking behavior. CPP induced with injection of MRP (5 mg/kg, s.c. for 3 days), lasted for 7 days after cessation of MRP treatment and priming dose of MRP (1 mg/kg, s.c.) reinstated the extinguished MRP-induced CPP. The astrocyte-conditioned medium (ACM) and neuroglia conditioned medium (NCM) exposed to MRP (10 and 100 µM) have been microinjected into the NAc. Intra-NAc administration of ACM during extinction period failed to change the maintenance of MRP-CPP, but MRP 100-treated ACM could slightly increase the magnitude of reinstatement. In contrast to ACM, intra-NAc administration of MRP 100-treated NCM caused slower extinction by 3 days and significantly increased the magnitude of reinstatement. Our findings suggest the involvement of glial cells activation in the maintenance and reinstatement of MRP-seeking behaviors, and provides new evidence that these cells might be a potential target for the treatment of MRP addiction. PMID:26547198

  7. Globular Glial Mixed Four Repeat Tau and TDP-43 Proteinopathy with Motor Neuron Disease and Frontotemporal Dementia.

    Science.gov (United States)

    Takeuchi, Ryoko; Toyoshima, Yasuko; Tada, Mari; Tanaka, Hidetomo; Shimizu, Hiroshi; Shiga, Atsushi; Miura, Takeshi; Aoki, Kenju; Aikawa, Akane; Ishizawa, Shin; Ikeuchi, Takeshi; Nishizawa, Masatoyo; Kakita, Akiyoshi; Takahashi, Hitoshi

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) may be accompanied by frontotemporal dementia (FTD). We report a case of glial mixed tau and TDP-43 proteinopathies in a Japanese patient diagnosed clinically as having ALS-D. Autopsy revealed loss of lower motor neurons and degeneration of the pyramidal tracts in the spinal cord and brain stem. The brain showed frontotemporal lobar degeneration (FTLD), the most severe neuronal loss and gliosis being evident in the precentral gyrus. Although less severe, such changes were also observed in other brain regions, including the basal ganglia and substantia nigra. AT8 immunostaining revealed that predominant occurrence of astrocytic tau lesions termed globular astrocytic inclusions (GAIs) was a feature of the affected regions. These GAIs were Gallyas-Braak negative. Neuronal and oligodendrocytic tau lesions were comparatively scarce. pS409/410 immunostaining also revealed similar neuronal and glial TDP-43 lesions. Interestingly, occasional co-localization of tau and TDP-43 was evident in the GAIs. Immunoblot analyses revealed band patterns characteristic of a 4-repeat (4R) tauopathy, corticobasal degeneration and a TDP-43 proteinopathy, ALS/FTLD-TDP Type B. No mutations were found in the MAPT or TDP-43 genes. We consider that this patient harbored a distinct, sporadic globular glial mixed 4R tau and TDP-43 proteinopathy associated with motor neuron disease and FTD. PMID:25787090

  8. Membrane-bound catechol-O-methyl transferase in cortical neurons and glial cells is intracellularly oriented

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    Björn H Schott

    2010-10-01

    Full Text Available Catechol-O-methyl transferase (COMT is involved in the inactivation of dopamine in brain regions in which the dopamine transporter (DAT1 is sparsely expressed. The membrane-bound isoform of COMT (MB-COMT is the predominantly expressed form in the mammalian central nervous system (CNS. It has been a matter of debate whether in neural cells of the CNS the enzymatic domain of MB-COMT is oriented towards the cytoplasmic or the extracellular compartment. Here we used live immunocytochemistry on cultured neocortical neurons and glial cells to investigate the expression and membrane orientation of native COMT and of transfected MB-COMT fused to green fluorescent protein (GFP. After live staining, COMT immunoreactivity was reliably detected in both neurons and glial cells after permeabilization, but not on unpermeabilized cells. Similarly, autofluorescence of COMT-GFP fusion protein and antibody fluorescence showed overlap only in permeabilized neurons. Our data provide converging evidence for an intracellular membrane orientation of MB-COMT in neurons and glial cells, suggesting the presence of a DAT1-independent postsynaptic uptake mechanism for dopamine, prior to its degradation via COMT.

  9. Partial involvement of NMDA receptors and glial cells in the nociceptive behaviors induced by intrathecally administered histamine.

    Science.gov (United States)

    Mizoguchi, Hirokazu; Komatsu, Takaaki; Iwata, Yoko; Watanabe, Chizuko; Watanabe, Hiroyuki; Orito, Tohru; Katsuyama, Soh; Yonezawa, Akihiko; Onodera, Kenji; Sakurada, Tsukasa; Sakurada, Shinobu

    2011-05-16

    The involvement of spinal glial cells in the nociceptive behaviors induced by 800 pmol of histamine was determined in mice. Histamine at 800 pmol injected intrathecally (i.t.) produced nociceptive behaviors, consisting of scratching, biting and licking. The nociceptive behaviors induced by histamine were significantly suppressed by i.t. co-administration with tachykinin NK(1) receptor antagonist CP99,994 or competitive antagonist for N-methyl-d-aspartate (NMDA) receptor d-(-)-2-amino-5-phosphonovaleric acid (d-APV). The i.t. pretreatment with the glial cell inhibitor dl-fluorocitric acid or minocycline failed to affect the nociceptive behaviors induced by histamine. However, in mice pretreated i.t. with dl-fluorocitric acid or minocycline, the nociceptive behaviors induced by histamine were significantly suppressed by i.t. co-administration with CP99,994 but not d-APV. In Western blot analysis using lumbar spinal cords, i.t. treatment with 800 pmol of histamine increased the phosphorylation of the NR1 subunit of NMDA receptors. The increased phosphorylation of the NR1 subunit of NMDA receptors by histamine was abolished by i.t. pretreatment with dl-fluorocitric acid or minocycline. The present results suggest that histamine at 800 pmol elicits nociceptive behaviors through activation of the neuronal NK(1) receptor and the NR1 subunit-containing NMDA receptors on glial cells in the spinal cord. PMID:21352890

  10. Applying secret sharing for HIS backup exchange.

    Science.gov (United States)

    Kuroda, Tomohiro; Kimura, Eizen; Matsumura, Yasushi; Yamashita, Yoshinori; Hiramatsu, Haruhiko; Kume, Naoto; Sato, Atsushi

    2013-01-01

    To secure business continuity is indispensable for hospitals to fulfill its social responsibility under disasters. Although to back up the data of the hospital information system (HIS) at multiple remote sites is a key strategy of business continuity plan (BCP), the requirements to treat privacy sensitive data jack up the cost for the backup. The secret sharing is a method to split an original secret message up so that each individual piece is meaningless, but putting sufficient number of pieces together to reveal the original message. The secret sharing method eases us to exchange HIS backups between multiple hospitals. This paper evaluated the feasibility of the commercial secret sharing solution for HIS backup through several simulations. The result shows that the commercial solution is feasible to realize reasonable HIS backup exchange platform when template of contract between participating hospitals is ready. PMID:24110653

  11. Cell Secretion: Current Structural and Biochemical Insights

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    Saurabh Trikha

    2010-01-01

    Full Text Available Essential physiological functions in eukaryotic cells, such as release of hormones and digestive enzymes, neurotransmission, and intercellular signaling, are all achieved by cell secretion. In regulated (calcium-dependent secretion, membrane-bound secretory vesicles dock and transiently fuse with specialized, permanent, plasma membrane structures, called porosomes or fusion pores. Porosomes are supramolecular, cup-shaped lipoprotein structures at the cell plasma membrane that mediate and control the release of vesicle cargo to the outside of the cell. The sizes of porosomes range from 150nm in diameter in acinar cells of the exocrine pancreas to 12nm in neurons. In recent years, significant progress has been made in our understanding of the porosome and the cellular activities required for cell secretion, such as membrane fusion and swelling of secretory vesicles. The discovery of the porosome complex and the molecular mechanism of cell secretion are summarized in this article.

  12. Insulin and Glucagon Secretion In Vitro

    Science.gov (United States)

    Rajan, Arun S.

    1998-01-01

    Long-duration space flight is associated with many physiological abnormalities in astronauts. In particular, altered regulation of the hormones insulin and glucagon may contribute to metabolic disturbances such as increased blood sugar levels, which if persistently elevated result in toxic effects. These changes are also observed in the highly prevalent disease diabetes, which affects 16 million Americans and consumes over $100 billion in annual healthcare costs. By mimicking the microgravity environment of space in the research laboratory using a NASA-developed bioreactor, one can study the physiology of insulin and glucagon secretion and determine if there are alterations in these cellular processes. The original specific objectives of the project included: (1) growing ('cell culture') of pancreatic islet beta and alpha cells that secrete insulin and glucagon respectively, in the NASA bioreactor; (2) examination of the effects of microgravity on insulin and glucagon secretion; and (3) study of molecular mechanisms of insulin and glucagon secretion if altered by microgravity.

  13. Pancreatic bicarbonate secretion involves two proton pumps

    DEFF Research Database (Denmark)

    Novak, Ivana; Wang, Jing; Henriksen, Katrine L.;

    2011-01-01

    Pancreas secretes fluid rich in digestive enzymes and bicarbonate. The alkaline secretion is important in buffering of acid chyme entering duodenum and for activation of enzymes. This secretion is formed in pancreatic ducts, and studies to date show that plasma membranes of duct epithelium express...... non-gastric H(+)-K(+)-ATPases. We measured intracellular pH and secretion in small ducts isolated from rat pancreas and showed their sensitivity to H(+)-K(+) pump inhibitors and ion substitutions. Gastric and non-gastric H(+)-K(+) pumps were demonstrated on RNA and protein levels, and pumps were...... H(+)/HCO(3)(-) transporters, which depend on gradients created by the Na(+)/K(+)-ATPase. However, the model cannot fully account for high-bicarbonate concentrations, and other active transporters, i.e. pumps, have not been explored. Here we show that pancreatic ducts express functional gastric and...

  14. Attention-deficit hyperactivity disorder (ADHD and glial integrity: S100B, cytokines and kynurenine metabolism - effects of medication

    Directory of Open Access Journals (Sweden)

    Schwarz Markus J

    2010-05-01

    Full Text Available Abstract Background Children with attention-deficit/hyperactivity disorder (ADHD show a marked temporal variability in their display of symptoms and neuropsychological performance. This could be explained in terms of an impaired glial supply of energy to support neuronal activity. Method We pursued one test of the idea with measures of a neurotrophin reflecting glial integrity (S100B and the influences of 8 cytokines on the metabolism of amino-acids, and of tryptophan/kynurenine to neuroprotective or potentially toxic products that could modulate glial function. Serum samples from 21 medication-naïve children with ADHD, 21 typically-developing controls, 14 medicated children with ADHD and 7 healthy siblings were analysed in this preliminary exploration of group differences and associations. Results There were no marked group differences in levels of S100B, no major imbalance in the ratios of pro- to anti-inflammatory interleukins nor in the metabolism of kynurenine to toxic metabolites in ADHD. However, four trends are described that may be worthy of closer examination in a more extensive study. First, S100B levels tended to be lower in ADHD children that did not show oppositional/conduct problems. Second, in medicated children raised interleukin levels showed a trend to normalisation. Third, while across all children the sensitivity to allergy reflected increased levels of IL-16 and IL-10, the latter showed a significant inverse relationship to measures of S100B in the ADHD group. Fourthly, against expectations healthy controls tended to show higher levels of toxic 3-hydroxykynurenine (3 HK than those with ADHD. Conclusions Thus, there were no clear signs (S100B that the glial functions were compromised in ADHD. However, other markers of glial function require examination. Nonetheless there is preliminary evidence that a minor imbalance of the immunological system was improved on medication. Finally, if lower levels of the potentially toxic 3

  15. Standpoints and protection of business secrets

    OpenAIRE

    Brane Bertoncelj

    2001-01-01

    The human impact on an information system where data bases, containing business secretes, are stored is one of the most unreliable and unforeseeable factors. For this reason, it must not be underestimated. The results of this study indicate a correlation between behavioural intention and protection of business secretes. There is a statistically significant correlation between behavioural intention and behavioural supervision. This means that an increased level of perceived supervision over o...

  16. Peptides and neurotransmitters that affect renin secretion

    Science.gov (United States)

    Ganong, W. F.; Porter, J. P.; Bahnson, T. D.; Said, S. I.

    1984-01-01

    Substance P inhibits renin secretion. This polypeptide is a transmitter in primary afferent neurons and is released from the peripheral as well as the central portions of these neurons. It is present in afferent nerves from the kidneys. Neuropeptide Y, which is a cotransmitter with norepinephrine and epinephrine, is found in sympathetic neurons that are closely associated with and presumably innervate the juxtagolmerular cells. Its effect on renin secretion is unknown, but it produces renal vasoconstriction and natriuresis. Vasoactive intestinal polypeptide (VIP) is a cotransmitter with acetylocholine in cholinergic neurons, and this polypeptide stimulates renin secretion. We cannot find any evidence for its occurence in neurons in the kidneys, but various stimuli increase plasma VIP to levels comparable to those produced by doses of exogenous VIP which stimulated renin secretion. Neostigmine increases plasma VIP and plasma renin activity, and the VIP appears to be responsible for the increase in renin secretion, since the increase is not blocked by renal denervation or propranolol. Stimulation of various areas in the brain produces sympathetically mediated increases in plasma renin activity associated with increases in blood pressure. However, there is pharmacological evidence that the renin response can be separated from the blood pressure response. In anaesthetized dogs, drugs that increase central serotonergic discharge increase renin secretion without increasing blood pressure. In rats, activation of sertonergic neurons in the dorsal raphe nucleus increases renin secretion by a pathway that projects from this nucleus to the ventral hypothalamus, and from there to the kidneys via the sympathetic nervous system. The serotonin releasing drug parachloramphetamine also increases plasma VIP, but VIP does not appear to be the primary mediator of the renin response. There is preliminary evidence that the serotonergic neurons in the dorsal raphe nucleus are part of the

  17. Development of secreted proteins as biotherapeutic agents.

    Science.gov (United States)

    Bonin-Debs, Angelika L; Boche, Irene; Gille, Hendrik; Brinkmann, Ulrich

    2004-04-01

    As one of the most important classes of proteins, secreted factors account for about one-tenth of the human genome, 3000 - 4000 in total, including factors of signalling pathways, blood coagulation and immune defence, as well as digestive enzymes and components of the extracellular matrix. Secreted proteins are a rich source of new therapeutics and drug targets, and are currently the focus of major drug discovery programmes throughout the industry. Many of the most important novel drugs developed in biotechnology have resulted from the application of secreted proteins as therapeutics. Secreted proteins often circulate throughout the body and, therefore, have access to most organs and tissues. Because of that, many of the factors are themselves therapeutic agents. This paper gives an overview on the features and functions of human secreted proteins and peptides, as well as strategies by which to discover additional therapeutic proteins from the human 'secretome'. Furthermore, a variety of examples are provided for the therapeutic use of recombinant secreted proteins as 'biologicals', including features and applications of recombinant antibodies, erythropoietin, insulin, interferon, plasminogen activators, growth hormone and colony-stimulating factors. PMID:15102604

  18. The cargo and the transport system: secreted proteins and protein secretion in Trichoderma reesei (Hypocrea jecorina).

    Science.gov (United States)

    Saloheimo, Markku; Pakula, Tiina M

    2012-01-01

    Trichoderma reesei (Hypocrea jecorina) is an efficient cell factory for protein production that is exploited by the enzyme industry. Yields of over 100 g secreted protein l(-1) from industrial fermentations have been reported. In this review we discuss the spectrum of proteins secreted by T. reesei and the studies carried out on its protein secretion system. The major enzymes secreted by T. reesei under production conditions are those degrading plant polysaccharides, the most dominant ones being the major cellulases, as demonstrated by the 2D gel analysis of the secretome. According to genome analysis, T. reesei has fewer genes encoding enzymes involved in plant biomass degradation compared with other fungi with sequenced genomes. We also discuss other T. reesei secreted enzymes and proteins that have been studied, such as proteases, laccase, tyrosinase and hydrophobins. Investigation of the T. reesei secretion pathway has included molecular characterization of the pathway components functioning at different stages of the secretion process as well as analysis of the stress responses caused by impaired folding or trafficking in the pathway or by expression of heterologous proteins. Studies on the transcriptional regulation of the secretory pathway have revealed similarities, but also interesting differences, with other organisms, such as a different induction mechanism of the unfolded protein response and the repression of genes encoding secreted proteins under secretion stress conditions. PMID:22053009

  19. γ-aminobutyric acid secreted from islet β-cells modulates exocrine secretion in rat pancreas

    Institute of Scientific and Technical Information of China (English)

    Yong-Deuk Park; Zheng-Yun Cui; Guang Wu; Hyung-Seo Park; Hyoung-Jin Park

    2006-01-01

    AIM: To investigate the role of endogenous γ-aminobutyric acid (GABA) in pancreatic exocrine secretion.METHODS: The isolated, vascularly perfused rat pancreas was employed in this study to eliminate the possible influences of extrinsic nerves and hormones.Cholecystokinin (CCK; 10 pmol/L) was intra-arterially given to stimulate exocrine secretion of the pancreas.RESULTS: Glutamine, a major precursor of GABA, which was given intra-arterially at concentrations of 1, 4 and 10 mmol/L, dose-dependently elevated the CCK-stimulated secretions of fluid and amylase in the normal pancreas.Bicuculline (10 μmol/L), a GABAA receptor antagonist,blocked the enhancing effect of glutamine (4 mmol/L) on the CCK-stimulated exocrine secretions. Glutamine, at concentrations of 1, 4 and 10 mmol/L, dose-dependently increased the GABA concentration in portal effluent of the normal pancreas. The effects of glutamine on the CCK-stimulated exocrine secretion as well as the GABA secretion were markedly reduced in the streptozotocintreated pancreas.CONCLUSION: GABA could be secreted from β-cells into the islet-acinar portal system after administration of glutainine, and could enhance the CCK-stimulated exocrine secretion through GABAA receptors. Thus,GABA in islet β-cells is a hormone modulating pancreatic exocrine secretion.

  20. Magnetic resonance diffusion and perfusion imaging in differentiation and grading the diffuse glial brain neoplasms

    International Nuclear Information System (INIS)

    Gliomas are the most common primary brain tumors. They are heterogenous group of tumors, which have infiltrative growth and relative resistance to radio-and chemotherapy. Gliomas are estimated from the WHO classification by means of grades from I go IV. Grade I (localized, 'special' gliomas) and grade II (diffuse gliomas) are considered low-grade, while grade III, IV are high-grade. Although histologically benign, the majority of grade II tumors will transform into malignant grades III and IV during the interval 5-10 years from the initial diagnosis. Glial tumor grading is based on a histo-pathological analysis of the most malignant tumour region, and takes into account the number of mitoses, nuclear atypia, microvascular proliferation and presence of necrosis. These grade are important, because they determine the therapeutic approach and the prognosis in patients with gliomas. Conventional MR images provide important information about contrast-enhancement, oedema, distant tumoral focuses, hemorrhage, necrosis, mass effect and etc, which are very useful in assessment of the tumor aggressiveness and hence tumor grade. Contrast-enhancement reflects the blood-brain-barrier status and could not be a reliable marker of malignancy. Modern physiological MR techniques like MR diffusion and MR perfusion imaging provide information about tumor physiology like microvascularity, angiogenesis and cellularity, all of which are also important in defining the tumor grade. Diffusion weighted imaging estimates the tumor structure-cellularity and water content. Perfusion weighted imaging shows capillary density and neovascularization. (authors) Key words: DIFFUSE GLIOMAS. GLIOMA GRADE. DIFFUSION WEIGHTED AND PERFUSION WEIGHTED MAGNETIC RESONANCE IMAGING

  1. The autophagic- lysosomal pathway determines the fate of glial cells under manganese- induced oxidative stress conditions.

    Science.gov (United States)

    Gorojod, R M; Alaimo, A; Porte Alcon, S; Pomilio, C; Saravia, F; Kotler, M L

    2015-10-01

    Manganese (Mn) overexposure is frequently associated with the development of a neurodegenerative disorder known as Manganism. The Mn-mediated generation of reactive oxygen species (ROS) promotes cellular damage, finally leading to apoptotic cell death in rat astrocytoma C6 cells. In this scenario, the autophagic pathway could play an important role in preventing cytotoxicity. In the present study, we found that Mn induced an increase in the amount and total volume of acidic vesicular organelles (AVOs), a process usually related to the activation of the autophagic pathway. Particularly, the generation of enlarged AVOs was a ROS- dependent event. In this report we demonstrated for the first time that Mn induces autophagy in glial cells. This conclusion emerged from the results obtained employing a battery of autophagy markers: a) the increase in LC3-II expression levels, b) the formation of autophagic vesicles labeled with monodansylcadaverine (MDC) or LC3 and, c) the increase in Beclin 1/ Bcl-2 and Beclin 1/ Bcl-X(L) ratio. Autophagy inhibition employing 3-MA and mAtg5(K130R) resulted in decreased cell viability indicating that this event plays a protective role in Mn- induced cell death. In addition, mitophagy was demonstrated by an increase in LC3 and TOM-20 colocalization. On the other hand, we proposed the occurrence of lysosomal membrane permeabilization (LMP) based in the fact that cathepsins B and D activities are essential for cell death. Both cathepsin B inhibitor (Ca-074 Me) or cathepsin D inhibitor (Pepstatin A) completely prevented Mn- induced cytotoxicity. In addition, low dose of Bafilomycin A1 showed a similar effect, a finding that adds evidence about the lysosomal role in Mn cytotoxicity. Finally, in vivo experiments demonstrated that Mn induces injury and alters LC3 expression levels in rat striatal astrocytes. In summary, our results demonstrated that autophagy is activated to counteract the harmful effect caused by Mn. These data is valuable to

  2. Extrasynaptic neurotransmission in the modulation of brain function. Focus on the striatal neuronal-glial networks

    Directory of Open Access Journals (Sweden)

    Kjell eFuxe

    2012-06-01

    Full Text Available Extrasynaptic neurotransmission is an important short distance form of volume transmission (VT and describes the extracellular diffusion of transmitters and modulators after synaptic spillover or extrasynaptic release in the local circuit regions binding to and activating mainly extrasynaptic neuronal and glial receptors in the neuroglial networks of the brain. Receptor-receptor interactions in G protein-coupled receptor (GPCR heteromers play a major role, on dendritic spines and nerve terminals including glutamate synapses, in the integrative processes of the extrasynaptic signaling. Heteromeric complexes between GPCR and ion-channel receptors play a special role in the integration of the synaptic and extrasynaptic signals. Changes in extracellular concentrations of the classical synaptic neurotransmitters glutamate and GABA found with microdialysis is likely an expression of the activity of the neuron-astrocyte unit of the brain and can be used as an index of VT-mediated actions of these two neurotransmitters in the brain. Thus, the activity of neurons may be functionally linked to the activity of astrocytes, which may release glutamate and GABA to the extracellular space where extrasynaptic glutamate and GABA receptors do exist. Wiring transmission (WT and VT are fundamental properties of all neurons of the CNS but the balance between WT and VT varies from one nerve cell population to the other. The focus is on the striatal cellular networks, and the WT and VT and their integration via receptor heteromers are described in the GABA projection neurons, the glutamate, dopamine, 5-hydroxytryptamine (5-HT and histamine striatal afferents, the cholinergic interneurons and different types of GABA interneurons. In addition, the role in these networks of VT signaling of the energy-dependent modulator adenosine and of endocannabinoids mainly formed in the striatal projection neurons will be underlined to understand the communication in the striatal

  3. HDAC1 regulates the proliferation of radial glial cells in the developing Xenopus tectum.

    Science.gov (United States)

    Tao, Yi; Ruan, Hangze; Guo, Xia; Li, Lixin; Shen, Wanhua

    2015-01-01

    In the developing central nervous system (CNS), progenitor cells differentiate into progeny to form functional neural circuits. Radial glial cells (RGs) are a transient progenitor cell type that is present during neurogenesis. It is thought that a combination of neural trophic factors, neurotransmitters and electrical activity regulates the proliferation and differentiation of RGs. However, it is less clear how epigenetic modulation changes RG proliferation. We sought to explore the effect of histone deacetylase (HDAC) activity on the proliferation of RGs in the visual optic tectum of Xenopus laevis. We found that the number of BrdU-labeled precursor cells along the ventricular layer of the tectum decrease developmentally from stage 46 to stage 49. The co-labeling of BrdU-positive cells with brain lipid-binding protein (BLBP), a radial glia marker, showed that the majority of BrdU-labeled cells along the tectal midline are RGs. BLBP-positive cells are also developmentally decreased with the maturation of the brain. Furthermore, HDAC1 expression is developmentally down-regulated in tectal cells, especially in the ventricular layer of the tectum. Pharmacological blockade of HDACs using Trichostatin A (TSA) or Valproic acid (VPA) decreased the number of BrdU-positive, BLBP-positive and co-labeling cells. Specific knockdown of HDAC1 by a morpholino (HDAC1-MO) decreased the number of BrdU- and BLBP-labeled cells and increased the acetylation level of histone H4 at lysine 12 (H4K12). The visual deprivation-induced increase in BrdU- and BLBP-positive cells was blocked by HDAC1 knockdown at stage 49 tadpoles. These data demonstrate that HDAC1 regulates radial glia cell proliferation in the developing optical tectum of Xenopus laevis. PMID:25789466

  4. Possible role of glial cells in the onset and progression of Lyme neuroborreliosis

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    Jacobs Mary B

    2009-08-01

    Full Text Available Abstract Background Lyme neuroborreliosis (LNB may present as meningitis, cranial neuropathy, acute radiculoneuropathy or, rarely, as encephalomyelitis. We hypothesized that glia, upon exposure to Borrelia burgdorferi, the Lyme disease agent, produce inflammatory mediators that promote the acute cellular infiltration of early LNB. This inflammatory context could potentiate glial and neuronal apoptosis. Methods We inoculated live B. burgdorferi into the cisterna magna of rhesus macaques and examined the inflammatory changes induced in the central nervous system (CNS, and dorsal root nerves and ganglia (DRG. Results ELISA of the cerebrospinal fluid (CSF showed elevated IL-6, IL-8, CCL2, and CXCL13 as early as one week post-inoculation, accompanied by primarily lymphocytic and monocytic pleocytosis. In contrast, onset of the acquired immune response, evidenced by anti-B. burgdorferi C6 serum antibodies, was first detectable after 3 weeks post-inoculation. CSF cell pellets and CNS tissues were culture-positive for B. burgdorferi. Histopathology revealed signs of acute LNB: severe multifocal leptomeningitis, radiculitis, and DRG inflammatory lesions. Immunofluorescence staining and confocal microscopy detected B. burgdorferi antigen in the CNS and DRG. IL-6 was observed in astrocytes and neurons in the spinal cord, and in neurons in the DRG of infected animals. CCL2 and CXCL13 were found in microglia as well as in endothelial cells, macrophages and T cells. Importantly, the DRG of infected animals showed significant satellite cell and neuronal apoptosis. Conclusion Our results support the notion that innate responses of glia to B. burgdorferi initiate/mediate the inflammation seen in acute LNB, and show that neuronal apoptosis occurs in this context.

  5. Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned

    Directory of Open Access Journals (Sweden)

    Viktoria eGudi

    2014-03-01

    Full Text Available Although astrogliosis and microglia activation are characteristic features of multiple sclerosis (MS and other central nervous system (CNS lesions the exact functions of these events are not fully understood. Animal models help to understand the complex interplay between the different cell types of the CNS and uncover general mechanisms of damage and repair of myelin sheaths. The so called cuprizone model is a toxic model of demyelination in the CNS white and grey matter, which lacks an autoimmune component. Cuprizone induces apoptosis of mature oligodendrocytes that leads to a robust demyelination and profound activation of both astrocytes and microglia with regional heterogeneity between different white and grey matter regions. Although not suitable to study autoimmune mediated demyelination, this model is extremely helpful to elucidate basic cellular and molecular mechanisms during de- and particularly remyelination independently of interactions with peripheral immune cells. Phagocytosis and removal of damaged myelin seems to be one of the major roles of microglia in this model and it is well known that removal of myelin debris is a prerequisite of successful remyelination. Furthermore, microglia provide several signals that support remyelination.The role of astrocytes during de- and remyelination is not well defined. Both supportive and destructive functions have been suggested. Using the cuprizone model we could demonstrate that there is an important crosstalk between astrocytes and microglia. In this review we focus on the role of glial reactions and interaction in the cuprizone model. Advantages and limitations of as well as its potential therapeutic relevance for the human disease MS are critically discussed in comparison to other animal models.

  6. Role of glutamate receptors and glial cells in the pathophysiology of treatment-resistant depression.

    Science.gov (United States)

    Kim, Yong-Ku; Na, Kyoung-Sae

    2016-10-01

    Treatment-resistant depression (TRD) causes substantial socioeconomic burden. Although a consensus on the definition of TRD has not yet been reached, it is certain that classic monoaminergic antidepressants are ineffective for TRD. One decade ago, many researchers found ketamine, an N-methyl-d-aspartate receptor (NMDAR) antagonist, to be an alternative to classic monoaminergic antidepressants. The major mechanisms of action of ketamine rapidly induce synaptogenesis in the brain-derived neurotrophic factor (BDNF) pathway. Although excessive glutamatergic neurotransmission and consequent excitotoxicity were considered a major cause of TRD, recent evidence suggests that the extrasynaptic glutamatergic receptor signal pathway mainly contributes to the detrimental effects of TRD. Glial cells such as microglia and astrocytes, early life adversity, and glucocorticoid receptor dysfunction participate in complex cross-talk. An appropriate reuptake of glutamate at the astrocyte is crucial for preventing 'spill-over' of synaptic glutamate and binding to the extrasynaptic NMDA receptor. Excessive microglial activation and the inflammatory process cause astrocyte glutamatergic dysfunction, which in turn activates microglial function. Early life adversity and glucocorticoid receptor dysfunction result in vulnerability to stress in adulthood. A maladaptive response to stress leads to increased glutamatergic release and pro-inflammatory cytokines, which then activate microglia. However, since the role of inflammatory mediators such as pro-inflammatory cytokines is not specific for depression, more disease-specific mechanisms should be identified. Last, although much research has focused on ketamine as an alternative antidepressant for TRD, its long-lasting effectiveness and adverse events have not been rigorously demonstrated. Additionally, evidence suggests that substantial brain abnormalities develop in ketamine abusers. Thus, more investigations for ketamine and other novel

  7. Exercise therapy normalizes BDNF upregulation and glial hyperactivity in a mouse model of neuropathic pain.

    Science.gov (United States)

    Almeida, Cayo; DeMaman, Aline; Kusuda, Ricardo; Cadetti, Flaviane; Ravanelli, Maria Ida; Queiroz, André L; Sousa, Thais A; Zanon, Sonia; Silveira, Leonardo R; Lucas, Guilherme

    2015-03-01

    Treatment of neuropathic pain is a clinical challenge likely because of the time-dependent changes in many neurotransmitter systems, growth factors, ionic channels, membrane receptors, transcription factors, and recruitment of different cell types. Conversely, an increasing number of reports have shown the ability of extended and regular physical exercise in alleviating neuropathic pain throughout a wide range of mechanisms. In this study, we investigate the effect of swim exercise on molecules associated with initiation and maintenance of nerve injury-induced neuropathic pain. BALB/c mice were submitted to partial ligation of the sciatic nerve followed by a 5-week aerobic exercise program. Physical training reversed mechanical hypersensitivity, which lasted for an additional 4 weeks after exercise interruption. Swim exercise normalized nerve injury-induced nerve growth factor, and brain-derived neurotrophic factor (BDNF) enhanced expression in the dorsal root ganglion, but had no effect on the glial-derived neurotrophic factor. However, only BDNF remained at low levels after exercise interruption. In addition, exercise training significantly reduced the phosphorylation status of PLCγ-1, but not CREB, in the spinal cord dorsal horn in response to nerve injury. Finally, prolonged swim exercise reversed astrocyte and microglia hyperactivity in the dorsal horn after nerve lesion, which remained normalized after training cessation. Together, these results demonstrate that exercise therapy induces long-lasting analgesia through various mechanisms associated with the onset and advanced stages of neuropathy. Moreover, the data support further studies to clarify whether appropriate exercise intensity, volume, and duration can also cause long-lasting pain relief in patients with neuropathic pain. PMID:25687543

  8. Lower glial metabolite levels in brains of young children with prenatal nicotine exposure.

    Science.gov (United States)

    Chang, Linda; Cloak, Christine C; Jiang, Caroline S; Hoo, Aaron; Hernandez, Antonette B; Ernst, Thomas M

    2012-03-01

    Many pregnant women smoke cigarettes during pregnancy, but the effect of nicotine on the developing human brain is not well understood, especially in young children. This study aims to determine the effects of prenatal nicotine exposure (PNE) on brain metabolite levels in young (3-4 years old) children, using proton magnetic resonance spectroscopy ((1)H MRS). Twenty-six children with PNE and 24 nicotine-unexposed children (controls) were evaluated with a structured examination, a battery of neuropsychological tests, and MRI/(1)H MRS (without sedation). Concentrations of N-acetyl compounds (NA), total creatine (tCR), choline-containing compounds (CHO), myo-inositol (MI), and glutamate+glutamine (GLX) were measured in four brain regions. Children with PNE had similar performance to controls on neuropsychological testing. However, compared to controls, the PNE group had lower MI (repeated measures ANOVA-p = 0.03) and tCr levels (repeated measures ANOVA-p = 0.003), especially in the basal ganglia of the girls (-19.3%, p = 0.01). In contrast, GLX was elevated in the anterior cingulate cortex of the PNE children (+9.4%, p = 0.03), and those with the highest GLX levels had the poorest performance on vocabulary (r = -0.67; p metabolite concentrations. These findings suggest that PNE may lead to subclinical abnormalities in glial development, especially in the basal ganglia, and regionally specific changes in other neurometabolites. These alterations were not influenced by the amount of nicotine exposure prenatally. However, the effects of PNE on energy metabolism may be sex specific, with greater alterations in girls. PMID:21912896

  9. Neuroprotection and reduction of glial reaction by cannabidiol treatment after sciatic nerve transection in neonatal rats.

    Science.gov (United States)

    Perez, Matheus; Benitez, Suzana U; Cartarozzi, Luciana P; Del Bel, Elaine; Guimarães, Francisco S; Oliveira, Alexandre L R

    2013-11-01

    In neonatal rats, the transection of a peripheral nerve leads to an intense retrograde degeneration of both motor and sensory neurons. Most of the axotomy-induced neuronal loss is a result of apoptotic processes. The clinical use of neurotrophic factors is difficult due to side effects and elevated costs, but other molecules might be effective and more easily obtained. Among them, some are derived from Cannabis sativa. Cannabidiol (CBD) is the major non-psychotropic component found on the surface of such plant leaves. The present study aimed to investigate the neuroprotective potential of CBD. Thus, 2-day-old Wistar rats were divided into the following experimental groups: sciatic nerve axotomy + CBD treatment (CBD group), axotomy + vehicle treatment (phosphate buffer group) and a control group (no-treatment group). The results were analysed by Nissl staining, immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling at 5 days post-lesion. Neuronal counting revealed both motor and sensory neuron rescue following treatment with CBD (15 and 30 mg/kg). Immunohistochemical analysis (obtained by synaptophysin staining) revealed 30% greater synaptic preservation within the spinal cord in the CBD-treated group. CBD administration decreased the astroglial and microglial reaction by 30 and 27%, respectively, as seen by glial fibrillary acidic protein and ionised calcium binding adaptor molecule 1 immunolabeling quantification. In line with such results, the terminal deoxynucleotidyl transferase dUTP nick end labeling reaction revealed a reduction of apoptotic cells, mostly located in the spinal cord intermediate zone, where interneurons promote sensory-motor integration. The present results show that CBD possesses neuroprotective characteristics that may, in turn, be promising for future clinical use. PMID:23981015

  10. Molecular signatures of cell cycle transcripts in the pathogenesis of Glial tumors

    Directory of Open Access Journals (Sweden)

    Bhattacharya Rabindra

    2004-01-01

    Full Text Available Abstract Background Astrocytic brain tumors are among the most lethal and morbid tumors of adults, often occurring during the prime of life. These tumors form an interesting group of cancer to understand the molecular mechanism of pathogenesis. Histological grading of Astrocytoma based on WHO classification does not provide complete information on the proliferation potential and biological behavior of the tumors. It is known that cancer results from the disruption of the orderly regulated cycle of replication and division. In the present study, we made an attempt to identify the cell cycle signatures and their involvement in the clinical aggressiveness of gliomas. Methods The variation in expression of various cell cycle genes was studied in different stages of glial tumor progression (low and high grades, and the results were compared with their corresponding expression levels in the normal brain tissue. Macroarray analysis was used for the purpose. Results Macroarray analysis of 114 cell cycle genes in different grades of glioma indicated differential expression pattern in 34% of the gene transcripts, when compared to the normal tissue. Majority of the transcripts belong to the intracellular kinase networks, cell cycle regulating kinases, transcription factors and transcription activators. Conclusion Based on the observation in the expression pattern in low grade and high grade gliomas, it can be suggested that the upregulation of cell cycle activators are seen as an early event in glioma; however, in malignancy it is not the cell cycle activators alone, which are involved in tumorigenesis. Understanding the molecular details of cell cycle regulation and checkpoint abnormalities in cancer could offer an insight into potential therapeutic strategies.

  11. Anti-obesity sodium tungstate treatment triggers axonal and glial plasticity in hypothalamic feeding centers.

    Directory of Open Access Journals (Sweden)

    Marta Amigó-Correig

    Full Text Available This study aims at exploring the effects of sodium tungstate treatment on hypothalamic plasticity, which is known to have an important role in the control of energy metabolism.Adult lean and high-fat diet-induced obese mice were orally treated with sodium tungstate. Arcuate and paraventricular nuclei and lateral hypothalamus were separated and subjected to proteomic analysis by DIGE and mass spectrometry. Immunohistochemistry and in vivo magnetic resonance imaging were also performed.Sodium tungstate treatment reduced body weight gain, food intake, and blood glucose and triglyceride levels. These effects were associated with transcriptional and functional changes in the hypothalamus. Proteomic analysis revealed that sodium tungstate modified the expression levels of proteins involved in cell morphology, axonal growth, and tissue remodeling, such as actin, CRMP2 and neurofilaments, and of proteins related to energy metabolism. Moreover, immunohistochemistry studies confirmed results for some targets and further revealed tungstate-dependent regulation of SNAP25 and HPC-1 proteins, suggesting an effect on synaptogenesis as well. Functional test for cell activity based on c-fos-positive cell counting also suggested that sodium tungstate modified hypothalamic basal activity. Finally, in vivo magnetic resonance imaging showed that tungstate treatment can affect neuronal organization in the hypothalamus.Altogether, these results suggest that sodium tungstate regulates proteins involved in axonal and glial plasticity. The fact that sodium tungstate could modulate hypothalamic plasticity and networks in adulthood makes it a possible and interesting therapeutic strategy not only for obesity management, but also for other neurodegenerative illnesses like Alzheimer's disease.

  12. Flavonoids Induce the Synthesis and Secretion of Neurotrophic Factors in Cultured Rat Astrocytes: A Signaling Response Mediated by Estrogen Receptor

    Directory of Open Access Journals (Sweden)

    Sherry L. Xu

    2013-01-01

    Full Text Available Neurotrophic factors are playing vital roles in survival, growth, and function of neurons. Regulation of neurotrophic factors in the brain has been considered as one of the targets in developing drug or therapy against neuronal disorders. Flavonoids, a family of multifunctional natural compounds, are well known for their neuronal beneficial effects. Here, the effects of flavonoids on regulating neurotrophic factors were analyzed in cultured rat astrocytes. Astrocyte is a major secreting source of neurotrophic factors in the brain. Thirty-three flavonoids were screened in the cultures, and calycosin, isorhamnetin, luteolin, and genistein were identified to be highly active in inducing the synthesis and secretion of neurotrophic factors, including nerve growth factor (NGF, glial-derived neurotrophic factor (GDNF, and brain-derived neurotrophic factor (BDNF. The inductions were in time- and dose-dependent manners. In cultured astrocytes, the phosphorylation of estrogen receptor was triggered by application of flavonoids. The phosphorylation was blocked by an inhibitor of estrogen receptor, which in parallel reduced the flavonoid-induced expression of neurotrophic factors. The results proposed the role of flavonoids in protecting brain diseases, and therefore these flavonoids could be developed for health food supplement for patients suffering from neurodegenerative diseases.

  13. Quantum Ramp Secret Sharing Scheme and Quantum Operations

    Science.gov (United States)

    Xiao, Heling; Wang, Huifeng; Wang, Bin

    2016-09-01

    In order to improve the efficiency of quantum secret sharing, quantum ramp secret sharing schemes were proposed (Ogawa et al., Phys. Rev. A 72, 032318 [2005]), which had a trade-off between security and coding efficiency. In quantum ramp secret sharing, partial information about the secret is allowed to leak to a set of participants, called an intermediate set, which cannot fully reconstruct the secret. This paper revisits the size of a share in the quantum ramp secret scheme based on a relation between the quantum operations and the coherent information. We also propose an optimal quantum ramp secret sharing scheme.

  14. Meaningful Share Generation for Increased Number of Secrets in Visual Secret-Sharing Scheme

    Directory of Open Access Journals (Sweden)

    Mustafa Ulutas

    2010-01-01

    Full Text Available This paper presents a new scheme for hiding two halftone secret images into two meaningful shares created from halftone cover images. Meaningful shares are more desirable than noise-like (meaningless shares in Visual Secret Sharing because they look natural and do not attract eavesdroppers' attention. Previous works in the field focus on either increasing number of secrets or creating meaningful shares for one secret image. The method outlined in this paper both increases the number of secrets and creates meaningful shares at the same time. While the contrast ratio of shares is equal to that of Extended Visual Cryptography, two secrets are encoded into two shares as opposed to one secret in the Extended Visual Cryptography. Any two natural-looking images can be used as cover unlike the Halftone Visual Cryptography method where one cover should be the negative of the other cover image and can only encode one secret. Effectiveness of the proposed method is verified by an experiment.

  15. Shared Secrets versus Secrets Kept Private Are Linked to Better Adolescent Adjustment

    Science.gov (United States)

    Frijns, Tom; Finkenauer, Catrin; Keijsers, Loes

    2013-01-01

    It is a household notion that secrecy is bad while sharing is good. But what about shared secrets? The present research adopts a functional analysis of sharing secrets, arguing that it should negate harmful consequences generally associated with secrecy and serves important interpersonal functions in adolescence. A survey study among 790 Dutch…

  16. Biochemical Methods to Analyze Wnt Protein Secretion.

    Science.gov (United States)

    Glaeser, Kathrin; Boutros, Michael; Gross, Julia Christina

    2016-01-01

    Wnt proteins act as potent morphogens in various aspects of embryonic development and adult tissue homeostasis. However, in addition to its physiological importance, aberrant Wnt signaling has been linked to the onset and progression of different types of cancer. On the cellular level, the secretion of Wnt proteins involves trafficking of lipid-modified Wnts from the endoplasmic reticulum (ER) to Golgi and further compartments via the Wnt cargo receptor evenness interrupted. Others and we have recently shown that Wnt proteins are secreted on extracellular vesicles (EVs) such as microvesicles and exosomes. Although more details about specific regulation of Wnt secretion steps are emerging, it remains largely unknown how Wnt proteins are channeled into different release pathways such as lipoprotein particles, EVs and cytonemes. Here, we describe protocols to purify and quantify Wnts from the supernatant of cells by either assessing total Wnt proteins in the supernatant or monitoring Wnt proteins on EVs. Purified Wnts from the supernatant as well as total cellular protein content can be investigated by immunoblotting. Additionally, the relative activity of canonical Wnts in the supernatant can be assessed by a dual-luciferase Wnt reporter assay. Quantifying the amount of secreted Wnt proteins and their activity in the supernatant of cells allows the investigation of intracellular trafficking events that regulate Wnt secretion and the role of extracellular modulators of Wnt spreading. PMID:27590148

  17. Dynamics of protein secretion during adipocyte differentiation.

    Science.gov (United States)

    Ojima, Koichi; Oe, Mika; Nakajima, Ikuyo; Muroya, Susumu; Nishimura, Takanori

    2016-08-01

    The major functions of adipocytes include both lipid storage and the production of secretory factors. However, the type of proteins released from mouse 3T3-L1 cells during adipocyte differentiation remains poorly understood. We examined the dynamics of secreted proteins during adipocyte differentiation using mass spectrometry (MS) combined with an iTRAQ (®) labeling method that enables the simultaneous analysis of relative protein expression levels. A total of 215 proteins were identified and quantified from approximately 10 000 MS/MS spectra. Of these, approximately 38% were categorized as secreted proteins based on gene ontology classification. Adipokine secretion levels were increased with the progression of differentiation. By contrast, levels of fibril collagen components, such as subunits of type I and III collagens, were decreased during differentiation. Basement membrane components attained their peak levels at day 4 when small lipid droplets accumulated in differentiated 3T3-L1 cells. Simultaneously, peak levels of collagen microfibril components that comprise type V and VI collagen subunits were also observed. Our data demonstrated that extracellular matrix components were predominantly released during the early and middle stages of adipocyte differentiation, with a subsequent increase in the secretion of adipokines. This suggests that 3T3-L1 cells secrete adipokines after their ECM is constructed during adipocyte differentiation. PMID:27516960

  18. Post-proliferative immature radial glial cells female-specifically express aromatase in the medaka optic tectum.

    Directory of Open Access Journals (Sweden)

    Akio Takeuchi

    Full Text Available Aromatase, the key enzyme responsible for estrogen biosynthesis, is present in the brain of all vertebrates. Much evidence has accumulated that aromatase is highly and exclusively expressed in proliferating mature radial glial cells in the brain of teleost fish even in adulthood, unlike in other vertebrates. However, the physiological significance of this expression remains unknown. We recently found that aromatase is female-specifically expressed in the optic tectum of adult medaka fish. In the present study, we demonstrated that, contrary to the accepted view of the teleost brain, female-specific aromatase-expressing cells in the medaka optic tectum represent a transient subset of post-proliferative immature radial glial cells in the neural stem cell lineage. This finding led us to hypothesize that female-specific aromatase expression and consequent estrogen production causes some sex difference in the life cycle of tectal cells. As expected, the female tectum exhibited higher expression of genes indicative of cell proliferation and radial glial maturation and lower expression of an anti-apoptotic gene than did the male tectum, suggesting a female-biased acceleration of the cell life cycle. Complicating the interpretation of this result, however, is the additional observation that estrogen administration masculinized the expression of these genes in the optic tectum, while simultaneously stimulating aromatase expression. Taken together, these results provide evidence that a unique subpopulation of neural stem cells female-specifically express aromatase in the optic tectum and suggest that this aromatase expression and resultant estrogen synthesis have an impact on the life cycle of tectal cells, whether stimulatory or inhibitory.

  19. Rat ciliary neurothrophic factor (CNTF): gene structure and regulation of mRNA levels in glial cell cultures.

    OpenAIRE

    Carroll, Patrick; Sendtner, Michael; Meyer, Michael; Thoenen, Hans

    2009-01-01

    The structure of the rat ciliary neurotrophic factor (CNTF) gene and the regulation ofCNTF mRNA levels in cultured glial cells were investigated. The rat mRNA is encoded by a simple two-exon transcription unit. Sequence analysis of the region upstream of the transcription start-site did not reveal a typical TATA-box consensus sequence. Low levels of CNTF mRNA were detected in cultured Schwann cells, and CNTF mRNA was not increased by a variety of treatments. Three-week-old astrocyteenriched c...

  20. Basic fibroblast growth factor contributes to a shift in the angioregulatory activity of retinal glial (Muller cells.

    Directory of Open Access Journals (Sweden)

    Yousef Yafai

    Full Text Available Basic fibroblast growth factor (bFGF is a pleiotropic cytokine with pro-angiogenic and neurotrophic effects. The angioregulatory role of this molecule may become especially significant in retinal neovascularization, which is a hallmark of a number of ischemic eye diseases. This study was undertaken to reveal expression characteristics of bFGF, produced by retinal glial (Müller cells, and to determine conditions under which glial bFGF may stimulate the proliferation of retinal microvascular endothelial cells. Immunofluorescence labeling detected bFGF in Müller cells of the rat retina and in acutely isolated Müller cells with bFGF levels, which increased after ischemia-reperfusion in postischemic retinas. In patients with proliferative diabetic retinopathy or myopia, the immunoreactivity of bFGF co-localized to glial fibrillary acidic protein (GFAP-positive cells in surgically excised retinal tissues. RT-PCR and ELISA analyses indicated that cultured Müller cells produce bFGF, which is elevated under hypoxia or oxidative stress, as well as under stimulation with various growth factors and cytokines, including pro-inflammatory factors. When retinal endothelial cells were cultured in the presence of media from hypoxia (0.2%-conditioned Müller cells, a distinct picture of endothelial cell proliferation emerged. Media from 24-h cultured Müller cells inhibited proliferation, whereas 72-h conditioned media elicited a stimulatory effect. BFGF-neutralizing antibodies suppressed the enhanced endothelial cell proliferation to a similar extent as anti-VEGF antibodies. Furthermore, phosphorylation of extracellular signal-regulated kinases (ERK-1/-2 in retinal endothelial cells was increased when the cells were cultured in 72-h conditioned media, while neutralizing bFGF attenuated the activation of this signaling pathway. These data provide evidence that retinal (glial Müller cells are major sources of bFGF in the ischemic retina. Müller cells under

  1. Efficient Differentiation of Embryonic Stem Cells into Neurons in Glial Cell-conditioned Medium under Attaching Conditions

    Institute of Scientific and Technical Information of China (English)

    Hai-Bin TIAN; Zeng-Liang BAI; Hong WANG; Jian-Quan CHEN; Guo-Xiang CHENG

    2005-01-01

    Embryonic stem (ES) cells can differentiate into neurons in vitro, which provides hope for the treatment of some neurodegenerative diseases through cell transplantation. However, it remains a challenge to efficiently induce ES cells to differentiate into neurons. Here, we show that murine ES cells can efficiently differentiate into neurons when cultured in glial cell- conditioned medium (GCM) under attaching conditions without the formation of embryoid bodies. In comparison with murine embryonic fibroblast-conditioned medium, we found that GCM has a positive effect on limiting the generation of non-neuronal cells, such as astrocytes. In addition, compared with suspension conditions, attaching conditions delay the differentiation process of ES cells.

  2. Neuroimaging findings of the post-treatment effects of radiation and chemotherapy of malignant primary glial neoplasms.

    Science.gov (United States)

    Mamlouk, M D; Handwerker, J; Ospina, J; Hasso, A N

    2013-08-01

    Post-treatment radiation and chemotherapy of malignant primary glial neoplasms present a wide spectrum of tumor appearances and treatment-related entities. Radiologic findings of these post-treatment effects overlap, making it difficult to distinguish treatment response and failure. The purposes of this article are to illustrate and contrast the imaging appearances of recurrent tumor from necrosis and to discuss other radiologic effects of cancer treatments. It is critical for radiologists to recognize these treatment-related effects to help direct clinical management. PMID:24007728

  3. Intraspinal transplantation of motoneuron-like cell combined with delivery of polymer-based glial cell line-derived neurotrophic factor for repair of spinal cord contusion injury

    Institute of Scientific and Technical Information of China (English)

    Alireza Abdanipour; Taki Tiraihi; Taher Taheri

    2014-01-01

    To evaluate the effects of glial cell line-derived neurotrophic factor transplantation combined with adipose-derived stem cells-transdifferentiated motoneuron delivery on spinal cord con-tusion injury, we developed rat models of spinal cord contusion injury, 7 days later, injected adipose-derived stem cells-transdifferentiated motoneurons into the epicenter, rostral and caudal regions of the impact site and simultaneously transplanted glial cell line-derived neuro-trophic factor-gelfoam complex into the myelin sheath. Motoneuron-like cell transplantation combined with glial cell line-derived neurotrophic factor delivery reduced cavity formations and increased cell density in the transplantation site. The combined therapy exhibited superior promoting effects on recovery of motor function to transplantation of glial cell line-derived neurotrophic factor, adipose-derived stem cells or motoneurons alone. These ifndings suggest that motoneuron-like cell transplantation combined with glial cell line-derived neurotrophic factor delivery holds a great promise for repair of spinal cord injury.

  4. Standpoints and protection of business secrets

    Directory of Open Access Journals (Sweden)

    Brane Bertoncelj

    2001-06-01

    Full Text Available The human impact on an information system where data bases, containing business secretes, are stored is one of the most unreliable and unforeseeable factors. For this reason, it must not be underestimated. The results of this study indicate a correlation between behavioural intention and protection of business secretes. There is a statistically significant correlation between behavioural intention and behavioural supervision. This means that an increased level of perceived supervision over one's own behaviour is related to behavioural intention. A great majority of participants would not divulge a business secret due to internal moral factors, i.e., they possess the appropriate capabilities to determine the advantages of social moral values over personal values.

  5. Proton pump inhibitors inhibit pancreatic secretion

    DEFF Research Database (Denmark)

    Wang, Jing; Barbuskaite, Dagne; Tozzi, Marco;

    2015-01-01

    localizations in duct cell monolayers (Capan-1) and human pancreas, and notably the gastric pumps are localized on the luminal membranes. In Capan-1 cells, PPIs inhibited recovery of intracellular pH from acidosis. Furthermore, in rats treated with PPIs, pancreatic secretion was inhibited but concentrations of......The mechanism by which pancreas secretes high HCO3- has not been fully resolved. This alkaline secretion, formed in pancreatic ducts, can be achieved by transporting HCO3- from serosa to mucosa or by moving H+ in the opposite direction. The aim of the present study was to determine whether H......+/K+-ATPases are expressed and functional in human pancreatic ducts and whether proton pump inhibitors (PPIs) have effect on those. Here we show that the gastric HKα1 and HKβ subunits (ATP4A; ATP4B) and non-gastric HKα2 subunits (ATP12A) of H+/K+-ATPases are expressed in human pancreatic cells. Pumps have similar...

  6. Indirect effects of TiO2 nanoparticle on neuron-glial cell interactions.

    Science.gov (United States)

    Hsiao, I-Lun; Chang, Chia-Cheng; Wu, Chung-Yi; Hsieh, Yi-Kong; Chuang, Chun-Yu; Wang, Chu-Fang; Huang, Yuh-Jeen

    2016-07-25

    Although, titanium dioxide nanoparticles (TiO2NPs) are nanomaterials commonly used in consumer products, little is known about their hazardous effects, especially on central nervous systems. To examine this issue, ALT astrocyte-like, BV-2 microglia and differentiated N2a neuroblastoma cells were exposed to 6 nm of 100% anatase TiO2NPs. A lipopolysaccharide (LPS) was pre-treated to activate glial cells before NP treatment for mimicking NP exposure under brain injury. We found that ALT and BV-2 cells took up more NPs than N2a cells and caused lower cell viability. TiO2NPs induced IL-1β in the three cell lines and IL-6 in N2a. LPS-activated BV-2 took up more TiO2NPs than normal BV-2 and released more intra/extracellular reactive oxygen species (ROS), IL-1β, IL-6 and MCP-1 than did activated BV-2. Involvement of clathrin- and caveolae-dependent endocytosis in ALT and clathrin-dependent endocytosis and phagocytosis in BV-2 both had a slow NP translocation rate to lysosome, which may cause slow ROS production (after 24 h). Although TiO2NPs did not directly cause N2a viability loss, by indirect NP exposure to the bottom chamber of LPS-activated BV-2 in the Transwell system, they caused late apoptosis and loss of cell viability in the upper N2a chamber due to H2O2 and/or TNF-α release from BV-2. However, none of the adverse effects in N2a or BV-2 cells was observed when TiO2NPs were exposed to ALT-N2a or ALT-BV-2 co-culture. These results demonstrate that neuron damage can result from TiO2NP-mediated ROS and/or cytokines release from microglia, but not from astrocytes. PMID:27216632

  7. Assesment of perfusion in glial tumors with arterial spin labeling; comparison with dynamic susceptibility contrast method

    Energy Technology Data Exchange (ETDEWEB)

    Cebeci, H, E-mail: hcebeci16@gmail.com [Department of Radiology, Uludag University Medical School, Bursa (Turkey); Aydin, O [Department of Radiology, Uludag University Medical School, Bursa (Turkey); Ozturk-Isik, E; Gumus, C [Department of Biomedical Engineering, Yeditepe University, Istanbul (Turkey); Inecikli, F [Department of Radiology, Kanuni Sultan Suleyman Educational and Research Hospital, Istanbul (Turkey); Bekar, A; Kocaeli, H [Department of Neurosurgery, Uludag University Medical School, Bursa (Turkey); Hakyemez, B [Department of Radiology, Uludag University Medical School, Bursa (Turkey)

    2014-10-15

    Highlights: • We compared the perfusion parameters obtained with both DSC and ASL perfusion imaging methods. • In ASL perfusion imaging, we also created quantitative CBF maps. • All patients included in the study had histopathological diagnose. • All MR examinations are done with 3T MR imaging system. - Abstract: Purpose: Arterial spin labeling perfusion imaging (ASL-PI) is a non-invasive perfusion imaging method that can be used for evaluation and quantification of cerebral blood flow (CBF). Aim of our study was to evaluating the efficiency of ASL in histopathological grade estimation of glial tumors and comparing findings with dynamic susceptibility contrast perfusion imaging (DSC-PI) method. Methods: This study involved 33 patients (20 high-grade and 13 low-grade gliomas). Multiphase multislice pulsed ASL MRI sequence and a first-passage gadopentetate dimeglumine T2*-weighted gradient-echo single-shot echo-planar sequence were acquired for all the patients. For each patient, perfusion relative signal intensity (rSI), CBF and relative CBF (rCBF) on ASL-PI and relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) values on DSC-PI were determined. The relative signal intensity of each tumor was determined as the maximal SI within the tumor divided by SI within symetric region in the contralateral hemisphere on ASL-PI. rCBV and rCBF were calculated by deconvolution of an arterial input function. Relative values of the lesions were obtained by dividing the values to the normal appearing symmetric region on the contralateral hemisphere. For statistical analysis, Mann–Whitney ranksum test was carried out. Receiver operating characteristic curve (ROC) analysis was performed to assess the relationship between the rCBF-ASL, rSI-ASL, rCBV and rCBF ratios and grade of gliomas. Their cut-off values permitting best discrimination was calculated. The correlation between rCBV, rCBF, rSI-ASL and rCBF-ASL and glioma grade was assessed using

  8. Assesment of perfusion in glial tumors with arterial spin labeling; comparison with dynamic susceptibility contrast method

    International Nuclear Information System (INIS)

    Highlights: • We compared the perfusion parameters obtained with both DSC and ASL perfusion imaging methods. • In ASL perfusion imaging, we also created quantitative CBF maps. • All patients included in the study had histopathological diagnose. • All MR examinations are done with 3T MR imaging system. - Abstract: Purpose: Arterial spin labeling perfusion imaging (ASL-PI) is a non-invasive perfusion imaging method that can be used for evaluation and quantification of cerebral blood flow (CBF). Aim of our study was to evaluating the efficiency of ASL in histopathological grade estimation of glial tumors and comparing findings with dynamic susceptibility contrast perfusion imaging (DSC-PI) method. Methods: This study involved 33 patients (20 high-grade and 13 low-grade gliomas). Multiphase multislice pulsed ASL MRI sequence and a first-passage gadopentetate dimeglumine T2*-weighted gradient-echo single-shot echo-planar sequence were acquired for all the patients. For each patient, perfusion relative signal intensity (rSI), CBF and relative CBF (rCBF) on ASL-PI and relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) values on DSC-PI were determined. The relative signal intensity of each tumor was determined as the maximal SI within the tumor divided by SI within symetric region in the contralateral hemisphere on ASL-PI. rCBV and rCBF were calculated by deconvolution of an arterial input function. Relative values of the lesions were obtained by dividing the values to the normal appearing symmetric region on the contralateral hemisphere. For statistical analysis, Mann–Whitney ranksum test was carried out. Receiver operating characteristic curve (ROC) analysis was performed to assess the relationship between the rCBF-ASL, rSI-ASL, rCBV and rCBF ratios and grade of gliomas. Their cut-off values permitting best discrimination was calculated. The correlation between rCBV, rCBF, rSI-ASL and rCBF-ASL and glioma grade was assessed using

  9. Biodegradable chitin conduit tubulation combined with bone marrow mesenchymal stem cell transplantation for treatment of spinal cord injury by reducing glial scar and cavity formation

    Directory of Open Access Journals (Sweden)

    Feng Xue

    2015-01-01

    Full Text Available We examined the restorative effect of modified biodegradable chitin conduits in combination with bone marrow mesenchymal stem cell transplantation after right spinal cord hemisection injury. Immunohistochemical staining revealed that biological conduit sleeve bridging reduced glial scar formation and spinal muscular atrophy after spinal cord hemisection. Bone marrow mesenchymal stem cells survived and proliferated after transplantation in vivo, and differentiated into cells double-positive for S100 (Schwann cell marker and glial fibrillary acidic protein (glial cell marker at 8 weeks. Retrograde tracing showed that more nerve fibers had grown through the injured spinal cord at 14 weeks after combination therapy than either treatment alone. Our findings indicate that a biological conduit combined with bone marrow mesenchymal stem cell transplantation effectively prevented scar formation and provided a favorable local microenvironment for the proliferation, migration and differentiation of bone marrow mesenchymal stem cells in the spinal cord, thus promoting restoration following spinal cord hemisection injury.

  10. Biodegradable chitin conduit tubulation combined with bone marrow mesenchymal stem cell transplantation for treatment of spinal cord injury by reducing glial scar and cavity formation

    Institute of Scientific and Technical Information of China (English)

    Feng Xue; Er-jun Wu; Pei-xun Zhang; Li-ya A; Yu-hui Kou; Xiao-feng Yin; Na Han

    2015-01-01

    We examined the restorative effect of modiifed biodegradable chitin conduits in combination with bone marrow mesenchymal stem cell transplantation after right spinal cord hemisection injury. Immunohistochemical staining revealed that biological conduit sleeve bridging reduced glial scar formation and spinal muscular atrophy after spinal cord hemisection. Bone marrow mesenchymal stem cells survived and proliferated after transplantationin vivo, and differentiated into cells double-positive for S100 (Schwann cell marker) and glial ifbrillary acidic protein (glial cell marker) at 8 weeks. Retrograde tracing showed that more nerve ifbers had grown through the injured spinal cord at 14 weeks after combination therapy than either treatment alone. Our ifndings indicate that a biological conduit combined with bone marrow mesenchymal stem cell transplantation effectively prevented scar formation and provided a favorable local microenvi-ronment for the proliferation, migration and differentiation of bone marrow mesenchymal stem cells in the spinal cord, thus promoting restoration following spinal cord hemisection injury.

  11. Magnolol treatment reversed the glial pathology in an unpredictable chronic mild stress-induced rat model of depression.

    Science.gov (United States)

    Li, Lu-Fan; Yang, Jie; Ma, Shi-Ping; Qu, Rong

    2013-07-01

    Growing evidence indicates that glia atrophy contributes to the pathophysiology and the pathogenesis of major depressive disorder. Magnolol is the main constituent identified in the bark of Magnolia officinalis, which has been used for the treatment of mental disorders, including depression, in Asian countries. In this study, we investigated the antidepressant-like effect and the possible mechanisms of magnolol in rats subjected to unpredictable chronic mild stress (UCMS). The ameliorative effect of magnolol on depression symptoms was investigated through behavior tests, including sucrose preference test, open-field test and forced-swimming test. In addition, the levels of glial fibrillary acidic protein (GFAP), an astrocyte marker, in the hippocampus and prefrontal cortex were determined by immunohistochemistry, Western blot, and reverse transcription-polymerase chain reaction (RT-PCR). Exposure to UCMS resulted in a decrease of behavioral activity, whereas magnolol (20, 40 mg/kg) and fluoxetine (20mg/kg) administration significantly reversed the depressive-like behaviors (P<0.05).Moreover, treatment with magnolol effectively increased GFAP mRNA and protein levels in UCMS rats. These results confirmed the antidepressant-like effect of magnolol, which maybe primarily mediated by reversing the glial atrophy in the UCMS rat brain. PMID:23632393

  12. Endomorphin analog analgesics with reduced abuse liability, respiratory depression, motor impairment, tolerance, and glial activation relative to morphine.

    Science.gov (United States)

    Zadina, James E; Nilges, Mark R; Morgenweck, Jenny; Zhang, Xing; Hackler, Laszlo; Fasold, Melita B

    2016-06-01

    Opioids acting at the mu opioid receptor (MOR) are the most effective analgesics, however adverse side effects severely limit their use. Of particular importance, abuse liability results in major medical, societal, and economic problems, respiratory depression is the cause of fatal overdoses, and tolerance complicates treatment and increases the risk of side effects. Motor and cognitive impairment are especially problematic for older adults. Despite the host of negative side effects, opioids such as morphine are commonly used for acute and chronic pain conditions. Separation of analgesia from unwanted effects has long been an unmet goal of opioid research. Novel MOR agonist structures may prove critical for greater success. Here we tested metabolically stable analogs of the endomorphins, endogenous opioids highly selective for the MOR. Compared to morphine, the analogs showed dramatically improved analgesia-to-side-effect ratios. At doses providing equal or greater antinociception than morphine in the rat, the analogs showed reduced a) respiratory depression, b) impairment of motor coordination, c) tolerance and hyperalgesia, d) glial p38/CGRP/P2X7 receptor signaling, and e) reward/abuse potential in both conditioned place preference and self-administration tests. Differential effects on glial activation indicate a mechanism for the relative lack of side effects by the analogs compared to morphine. The results suggest that endomorphin analogs described here could provide gold standard pain relief mediated by selective MOR activation, but with remarkably safer side effect profiles compared to opioids like morphine. PMID:26748051

  13. A preliminary investigation into the impact of a pesticide combination on human neuronal and glial cell lines in vitro.

    Directory of Open Access Journals (Sweden)

    Michael D Coleman

    Full Text Available Many pesticides are used increasingly in combinations during crop protection and their stability ensures the presence of such combinations in foodstuffs. The effects of three fungicides, pyrimethanil, cyprodinil and fludioxonil, were investigated together and separately on U251 and SH-SY5Y cells, which can be representative of human CNS glial and neuronal cells respectively. Over 48h, all three agents showed significant reductions in cellular ATP, at concentrations that were more than tenfold lower than those which significantly impaired cellular viability. The effects on energy metabolism were reflected in their marked toxic effects on mitochondrial membrane potential. In addition, evidence of oxidative stress was seen in terms of a fall in cellular thiols coupled with increases in the expression of enzymes associated with reactive species formation, such as GSH peroxidase and superoxide dismutase. The glial cell line showed significant responsiveness to the toxin challenge in terms of changes in antioxidant gene expression, although the neuronal SH-SY5Y line exhibited greater vulnerability to toxicity, which was reflected in significant increases in caspase-3 expression, which is indicative of the initiation of apoptosis. Cyprodinil was the most toxic agent individually, although oxidative stress-related enzyme gene expression increases appeared to demonstrate some degree of synergy in the presence of the combination of agents. This report suggests that the impact of some pesticides, both individually and in combinations, merits further study in terms of their impact on human cellular health.

  14. Scalable Mechanisms for Rational Secret Sharing

    CERN Document Server

    Dani, Varsha; Saia, Jared

    2012-01-01

    We consider the classical secret sharing problem in the case where all agents are selfish but rational. In recent work, Kol and Naor show that, when there are two players, in the non-simultaneous communication model, i.e. when rushing is possible, there is no Nash equilibrium that ensures both players learn the secret. However, they describe a mechanism for this problem, for any number of players, that is an epsilon-Nash equilibrium, in that no player can gain more than epsilon utility by deviating from it. Unfortunately, the Kol and Naor mechanism, and, to the best of our knowledge, all previous mechanisms for this problem require each agent to send O(n) messages in expectation, where n is the number of agents. This may be problematic for some applications of rational secret sharing such as secure multi-party computation and simulation of a mediator. We address this issue by describing mechanisms for rational secret sharing that are designed for large n. Both of our results hold for n > 2, and are Nash equil...

  15. Potassium secretion in mammalian distal colon

    DEFF Research Database (Denmark)

    Sørensen, Mads Vaarby

    2009-01-01

    -/- and the CFTR-/- mouse, we could functionally isolate the cAMP-activated K+ conductance as the BK channel. In addition we found the cAMP-activated K+ conductance to be further up-regulated by aldosterone. Taken together, these results show cAMP-activated K+ secretion occurs via a regulated specific...

  16. The Best Kept Secret in Gifted Education

    Science.gov (United States)

    Alvino, James

    2004-01-01

    It is perhaps one of the best-kept secrets in educating gifted high school youth, and yet for 45 years, Hugh O'Brian Youth Leadership (HOBY) has been going strong, "Motivating Tomorrow's Leaders Today." After spending nine inspirational days in 1958 with Albert Schweitzer (Nobel Prize physician and philosopher) at his clinic in the African jungle,…

  17. Secrets of Mlearning Failures: Confronting Reality

    Science.gov (United States)

    Cochrane, Thomas

    2012-01-01

    Having implemented and evaluated over 35 mlearning projects in a variety of contexts in higher education over the past 6 years the researcher is ready to share the untold secret: not all mlearning projects succeed! This article critiques three of the researcher's mlearning projects that can be classed as "failures" and compares them to successful…

  18. Acetylcholine regulates ghrelin secretion in humans

    NARCIS (Netherlands)

    F. Broglio (Fabio); E. Ghigo (Ezio); C. Gottero; F. Prodam; S. Destefanis; A. Benso; C. Gauna (Carlotta); L.J. Hofland (Leo); E. Arvat; A-J. van der Lely (Aart-Jan); P.M. van Koetsveld (Peter)

    2004-01-01

    textabstractGhrelin secretion has been reportedly increased by fasting and energy restriction but decreased by food intake, glucose, insulin, and somatostatin. However, its regulation is still far from clarified. The cholinergic system mediates some ghrelin actions, e.g. stimulatio

  19. Secret Symmetries in AdS/CFT

    CERN Document Server

    de Leeuw, Marius; Moriyama, Sanefumi; Regelskis, Vidas; Torrielli, Alessandro

    2012-01-01

    We discuss special quantum group (secret) symmetries of the integrable system associated to the AdS/CFT correspondence. These symmetries have by now been observed in a variety of forms, including the spectral problem, the boundary scattering problem, n-point amplitudes, the pure-spinor formulation and quantum affine deformations.

  20. Effects of photoreceptor metabolism on interstitial and glial cell pH in bee retina: evidence of a role for NH4+.

    Science.gov (United States)

    Coles, J A; Marcaggi, P; Véga, C; Cotillon, N

    1996-09-01

    1. Measurements were made with pH microelectrodes in superfused slices of the retina of the honey-bee drone. In the dark, the mean +/- S.E.M. pH values in the three compartments of the tissue were: neurones (photoreceptors), 6.99 +/- 0.04; glial cells (outer pigment cells), 7.31 +/- 0.03; extracellular space, 6.60 +/- 0.03. 2. Stimulation of the photoreceptors with light caused transient pH changes: a decrease in the photoreceptors (pHn) and in the glial cells (pHg), and an increase in the interstitial clefts (pHo). 3. The effects of inhibition and activation of aerobic metabolism showed that part, perhaps all, of the light-induced delta pHo resulted from the increased aerobic metabolism in the photoreceptors. 4. Addition of 2 mM NH4+ to the superfusate produced changes in pHo and pHg of the same sign as and similar amplitude to those caused by light stimulation. Manipulation of transmembrane pH gradients had similar effects on changes in pHo induced by light or by exogenous NH4+. 5. Measurements with NH(4+)-sensitive microelectrodes showed that stimulation of aerobic metabolism in the photoreceptors increased [NH4+]o and also that exogenous NH4+/NH3 was taken up by cells, presumably the glial cells. 6. We conclude that within seconds of an increase in the aerobic metabolism in the photoreceptors, they release an increased amount of NH4+/NH3 which affects pHo and enters glial cells. Other evidence suggests that in drone retina the glial cells supply the neurones with amino acids as substrates of energy metabolism; the present results suggest that fixed nitrogen is returned to the glial cells as NH4+/NH3. PMID:8887745