1,721,097 research outputs found
Role of the Thyroid System in Myelination and Neural Connectivity
No full textThe role of thyroid hormone on brain development is dramatically illustrated by "cretinism," a severe mental retardation due to iodine deficiency and maternal hypothyroidism during gestation. In the last decades, the molecular bases of the cellular action of thyroid hormone in the nervous tissue have been at least partially elucidated, and the emerged picture is much more complex than expected. In this article, the main mechanisms determining thyroid hormone availability, nuclear and membrane receptor occupancy and downstream action, gene expression, and nongenomic mechanism are reviewed, focusing on myelination and myelin turnover
Cellular approaches to central nervous system remyelination stimulation: thyroid hormone to promote myelin repair via endogenous stem and precursor cells
No full textBrain and spinal cord repair is a very difficult task in view of the extremely limited repair capability of the mature central nervous system (CNS). Thus, cellular therapies are regarded as a new frontier for both acute and chronic neurological diseases characterized by neuron or oligodendroglia degeneration. Although cell replacement has been considered as the primary goal of such approaches, in recent years greater attention has been devoted to the possibility that new undifferentiated cells in damaged nervous tissue might also act in autocrine-paracrine fashion, regulating the micro-environment through the release of growth factor and cytokines, also regulating immune response and local inflammation. In this review, repair of demyelinating disease using endogenous cells will be discussed in view of the critical role played by thyroid hormones (THs) during developmental myelination, focusing on the following points: 1) endogenous stem and precursor cells during demyelinating diseases; 2) TH homeostasis in the CNS; 3) cellular and molecular mechanism regulated by TH during developmental myelination and 4) a working hypothesis to develop a rationale for the use of THs to improve remyelination through endogenous stem and precursor cells in the course of demyelinating disease
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
IN VIVO AND IN VITRO STUDY ON MICROGLIA ACTIVATION OF CHF5074, A NONSTEROIDAL ANTI-INFLAMMATORY DERIVATIVE WITH GAMMA-SECRETASE MODULATORYACTIVITY
No full textBackground: CHF5074, nonsteroidal anti-inflammatory derivative with g
-secretase modulatory activity has been shown to inhibit brain plaque deposition
and to attenuate or reverse memory deficit in different transgenic
mouse models of Alzheimer disease (AD). The recent discovery of modulation
Rho-GTPase-dependent signaling suggests that the range of biological
actions exerted by this drug may be wider than expected. Since neuroinflammation
is considered a major pathogenetic mechanism in AD, we investigated
the possible regulation of microglia activation by CHF5074 in vivo
and in vitro. Methods: The Tg2576 transgenic mouse carrying a transgene
coding for the 695-amino acid isoform of human APP derived from a large
Swedish family with early-onset AD was used for in vivo study. CHF5074
60 mg/kg was administered for 2 months to female transgenic and wild-type
mice of 7 months of age (n 1⁄4 12/group). Activated microglia was measured
by Iba1 immunohistochemistry, area fraction and cell number evaluation. In
vitro experiments were carried out on microglia enriched rat primary
cultures, activated by LPS 0.1mM for 8 h, and CHF5074 pretreatment was
performed at 1, 3 and 10mM one hour before LPS administration. TNFalfa,
IL-6, IL-12 and RANTES were measured by ELISA in the cell culture
medium. Results: In vivo, quantification of immunoreactivity indicated that
compared to transgenic controls, wild-type animals had much lower activated
microglia (cell count and area fraction, P<0.05). Compared to
Tg2576 control mice, activated microglia in the cerebral cortex was significantly
(P < 0.05) reduced by CHF5074 treatment. In vitro experiments indicated
that RANTES up-regulation by LPS was significantly attenuated by
CHF5074 3 and 10 mM. Conclusions: This results of this study showed that
CHF5074 significantly inhibits neuroinflammatory activity mediated by microglia.
RANTES (regulated upon activation, normal T cell expressed and
secreted) regulation could support a specific role in microglia-astrocyte
cross-talk
Nerve growth factor promotes differentiation and protects the oligodendrocyte precursor cells from in vitro hypoxia/ischemia
Full text linkIntroduction: Nerve growth factor (NGF) is a pleiotropic molecule acting on different cell types in physiological and pathological conditions. However, the effect of NGF on the survival, differentiation and maturation of oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), the cells responsible for myelin formation, turnover, and repair in the central nervous system (CNS), is still poorly understood and heavily debated. Methods: Here we used mixed neural stem cell (NSC)-derived OPC/astrocyte cultures to clarify the role of NGF throughout the entire process of OL differentiation and investigate its putative role in OPC protection under pathological conditions. Results: We first showed that the gene expression of all the neurotrophin receptors (TrkA, TrkB, TrkC, and p75(NTR)) dynamically changes during the differentiation. However, only TrkA and p75(NTR) expression depends on T3-differentiation induction, as Ngf gene expression induction and protein secretion in the culture medium. Moreover, in the mixed culture, astrocytes are the main producer of NGF protein, and OPCs express both TrkA and p75(NTR). NGF treatment increases the percentage of mature OLs, while NGF blocking by neutralizing antibody and TRKA antagonist impairs OPC differentiation. Moreover, both NGF exposure and astrocyte-conditioned medium protect OPCs exposed to oxygenglucose deprivation (OGD) from cell death and NGF induces an increase of AKT/pAKT levels in OPCs nuclei by TRKA activation. Discussion: This study demonstrated that NGF is implicated in OPC differentiation, maturation, and protection in the presence of metabolic challenges, also suggesting implications for the treatment of demyelinating lesions and diseases
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