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‣ Análise da expressão de neurotrofinas durante a regeneração de nervo periférico de rato por enxerto venoso; Analysis of the expression of neurotrophins during regeneration of peripheral nerves in rats with vein graft

Ahmed, Farooque Jamaluddin
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 15/02/2013 Português
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Análise da expressão de neurotrofinas durante a regeneração de nervo periférico de rato por enxerto venoso Enxertos de veias têm sido empregados para preencher lacunas em nervos periféricos transeccionados para melhor recuperação funcional. No entanto, vários inconvenientes, como a constrição do enxerto secundário foram observados. Uma nova alternativa para esta técnica foi desenvolvida. Simplesmente invertendo a veia de dentro para fora, chamado do Inside- out vein graft. As neurotrofinas são uma família de fatores neurotróficos conhecidos por desempenhar um papel significativo na regeneração de nervos periféricos. A família da neurotrofina é constituído por fator de crescimento nervoso (NGF), fator neurotrófico derivado do cérebro (BDNF), Neurotrofina-3 (NT-3) e Neurotrofina-4 (NT-4). No campo da neurobiologia, vários autores têm utilizado a técnica de PCR a fim de obter mais informações sobre os nervos regenerados. Neste estudo, foi utilizada a técnica de biologia molecular para explorar o papel e o nível das neurotrofinas durante a regeneração de nervos periféricos com enxerto de veia. O nervo isquiático de ratos foi seccionado e reparado com enxerto de veia invertida (IOVG) e técnicas de enxerto de veia padrão (SVG). No grupo controle...

‣ Neurotrophins induce release of neurotrophins by the regulated secretory pathway

Krüttgen, Alex; Möller, J. Carsten; Heymach, John V.; Shooter, Eric M.
Fonte: The National Academy of Sciences Publicador: The National Academy of Sciences
Tipo: Artigo de Revista Científica
Publicado em 04/08/1998 Português
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Recent studies have established that neurotrophin synthesis and secretion are regulated by activity and that these factors are involved in activity-dependent processes in the nervous system. Neurotrophins also are known to induce increases in intracellular calcium, a trigger for regulated secretion. This finding raises the possibility that neurotrophins themselves may stimulate regulated secretion of neurotrophins. To address this question, we studied the release of neurotrophins from transfected PC12 cells, a widely used model for neuronal secretion and neurotrophin signal transduction. We found that neurotrophins induced the regulated secretion of brain-derived neurotrophic factor, neurotrophin-3 (NT-3), and neurotrophin-4/5. The effect of brain-derived neurotrophic factor on release of NT-3 could be abolished by REX, a p75 blocking antibody, but not by K252a, an inhibitor of neurotrophin tyrosine kinase receptor (Trk) signaling. The nerve growth factor effect on release of NT-3 could be blocked only by simultaneous application of REX and K252a, suggesting that they are mediated by TrkA as well as p75. Our data show that neurotrophins are able to induce the regulated secretion of neurotrophins and suggest a signal-transducing role for both TrkA and p75 in this process. The neurotrophin-induced release of neurotrophins may be relevant for activity-dependent processes such as synaptic plasticity and memory formation.

‣ Neurotrophin release by neurotrophins: Implications for activity-dependent neuronal plasticity

Canossa, Marco; Griesbeck, Oliver; Berninger, Benedikt; Campana, Gabriele; Kolbeck, Roland; Thoenen, Hans
Fonte: The National Academy of Sciences of the USA Publicador: The National Academy of Sciences of the USA
Tipo: Artigo de Revista Científica
Publicado em 25/11/1997 Português
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Neurotrophins, secreted in an activity-dependent manner, are thought to be involved in the activity-dependent refinement of synaptic connections. Here we demonstrate that in hippocampal neurons and the rat pheochromocytoma cell line PC12 application of exogenous neurotrophins induces secretion of neurotrophins, an effect that is mediated by the activation of tyrosine kinase neurotrophin receptors (Trks). Like activity-dependent secretion of neurotrophins, neurotrophin-induced neurotrophin secretion requires mobilization of calcium from intracellular stores. Because neurotrophins are likely to be released from both dendrites and axons, neurotrophin-induced neurotrophin release represents a potential positive feedback mechanism, contributing to the reinforcement and stabilization of synaptic connections.

‣ Neurotrophins and the immune system

Vega, José A; García-Suárez, Olivia; Hannestad, Jonas; Pérez-Pérez, Marta; Germanà, Antonino
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /07/2003 Português
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The neurotrophins are a family of polypeptide growth factors that are essential for the development and maintenance of the vertebrate nervous system. In recent years, data have emerged indicating that neurotrophins could have a broader role than their name might suggest. In particular, the putative role of NGF and its receptor TrkA in immune system homeostasis has become a much studied topic, whereas information on the other neurotrophins is scarce in this regard. This paper reviews what is known about the expression and possible functions of neurotrophins and their receptors in different immune tissues and cells, as well as recent data obtained from studies of transgenic mice in our laboratory. Results from studies to date support the idea that neurotrophins may regulate some immune functions. They also play an important role in the development of the thymus and in the survival of thymocytes.

‣ The interaction of neurotrophins with the p75NTR common neurotrophin receptor: a comprehensive molecular modeling study.

Shamovsky, I. L.; Ross, G. M.; Riopelle, R. J.; Weaver, D. F.
Fonte: Cold Spring Harbor Laboratory Press Publicador: Cold Spring Harbor Laboratory Press
Tipo: Artigo de Revista Científica
Publicado em /11/1999 Português
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Neurotrophins are a family of proteins with pleiotropic effects mediated by two distinct receptor types, namely the Trk family, and the common neurotrophin receptor p75NTR. Binding of four mammalian neurotrophins, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5), to p75NTR is studied by molecular modeling based on X-ray structures of the neurotrophins and the extracellular domain of p55TNFR, a homologue of p75NTR. The model of neurotrophin/receptor interactions suggests that the receptor binding domains of neurotrophins (loops I and IV) are geometrically and electrostatically complementary to a putative binding site of p75NTR, formed by the second and part of the third cysteine-rich domains. Geometric match of neurotrophin/receptor binding domains in the complexes, as characterized by shape complementarity statistic Sc, is comparable to known protein/protein complexes. All charged residues within the loops I and IV of the neurotrophins, previously determined as being critical for p75NTR binding, directly participate in receptor binding in the framework of the model. Principal residues of the binding site of p75NTR include Asp47, Lys56, Asp75, Asp76, Asp88, and Glu89. The additional involvement of Arg80 and Glu53 is specific for NGF and BDNF...

‣ Neurotrophins modulate monocyte chemotaxis without affecting macrophage function

Samah, B; Porcheray, F; Gras, G
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /03/2008 Português
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Neurotrophins nerve growth factor (NGF), brain-derived growth factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) and their high-affinity tyrosine protein kinase receptor (Trk) family, TrkA, TrkB, TrkC, and low-affinity p75NTR receptor, are key molecules implicated in the development of the central nervous system. Increasing evidence suggests that they also have physiological and pathological roles outside the nervous system. In this study we examined the expression of neurotrophins and their receptors in human activated macrophages and to what extent neurotrophins themselves modulate macrophage activation, in a model of primary adult monocyte-derived macrophage. Our data indicate that macrophages express neurotrophin and neurotrophin receptor genes differentially, and respond to cell stimulation by specific inductions. Neurotrophins did not modify the antigen-presenting capacities of macrophages or their production of proinflammatory cytokines, but somehow skewed their activation phenotype. In contrast, NGF clearly increased CXCR-4 expression in macrophage and their chemotactic response to low CXCL-12 concentration. The differential effect of specific macrophage stimuli on neurotrophin expression, in particular NGF and NT-3...

‣ MYELIN BASIC PROTEIN-PRIMED T CELLS INDUCE NEUROTROPHINS IN GLIAL CELLS VIA α5β3 INTEGRIN

Roy, Avik; Liu, Xiaojuan; Pahan, Kalipada
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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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 (BDNF) and neurotrophin-3 (NT-3) but not proinflammatory molecules in microglia and astroglia via cell-to-cell contact. MBP-primed Th2 cells expressed α5 and β3 integrins and functional blocking antibodies against both α5 and β3 integrins inhibited the ability of MBP-primed Th2 cells to induce glial neurotrophins. On the other hand, glial cells expressed PDGF-Rβ and neutralization of this glial receptor abrogated the ability of Th2 cells to induce neurotrophins in glia. Activation of glial cAMP response element-binding protein (CREB) by MBP-primed Th2 cell contact and inhibition of contact-mediated expression of neurotrophins by antisense knockdown of glial CREB suggest that MBP-primed Th2 cell-glia contact induces the expression of neurotrophins through glial activation of CREB. Accordingly...

‣ Fates of neurotrophins after retrograde axonal transport: Phosphorylation of p75NTR is a sorting signal for delayed degradation

Butowt, Rafal; von Bartheld, Christopher S.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 26/08/2009 Português
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Neurotrophins can mediate survival or death of neurons. Opposing functions of neurotrophins are based on binding of these ligands to two distinct types of receptors: trk receptors and p75NTR. Previous work showed that target-derived NGF induces cell death, while BDNF and NT-3 enhance survival of neurons in the isthmo-optic nucleus of avian embryos. To determine the fate of retrogradely transported neurotrophins and test whether their sorting differs between neurotrophins mediating survival- or death-signaling pathways, we traced receptor-binding, sorting and degradation kinetics of target-applied radiolabeled neurotrophins that bind in this system to trk receptors (BDNF, NT-3) or only to p75NTR (NGF). At the ultrastructural level, the p75NTR-bound NGF accumulates with a significant delay in multivesicular bodies and organelles of the degradation pathway upon arrival in the cell body when compared with trk-bound BDNF or NT-3. This delayed lysosomal accumulation was restricted to target-derived NGF, but was not seen when NGF was supplied to the soma in vitro. The kinase inhibitors K252a and Gö6976 alter the kinetics of organelle accumulation: phosphorylation of p75NTR is a sorting signal for delayed sequestering of p75NTR-bound NGF in multivesicular bodies and delayed degradation in lysosomes when compared to trk-bound neurotrophins. Mutagenesis and mass spectrometry studies indicate that p75NTR is phosphorylated by conventional protein kinase C on serine-266. We conclude that in addition to the known phosphorylation of trks...

‣ Analysis of neurotrophins in human serum by immunoaffinity capillary electrophoresis (ICE) following traumatic head injury

Kalish, Heather; Phillips, Terry M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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Neurotrophins, including brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4), and β-nerve growth factor (β-NGF), play an active role in the development, maintenance and survival of cells of the central nervous system (CNS). Previous research has indicated that a decrease in concentrations of these neurotrophins is often associated with cell death and ultimately patient demise. However, much of the research conducted analyses of samples taken directly from the CNS, i.e., of samples that are not readily available in clinical trauma centers. In an attempt to obtain a method for evaluating neurotrophins in a more readily accessible matrix, i.e., serum, a precise and accurate immunoaffinity capillary electrophoresis (ICE) method was developed and applied to measure neurotrophins in serum from patients with various degrees of head injury. The five neurotrophins of interest were extracted and concentrated by specific immunochemically immobilized antibodies, bound directly to the capillary wall, and eluted and separated in approximately 10 min. NT-3, BDNF, CNTF and β-NGF showed a marked decrease in concentration as the severity of the head injury increased: mild versus severe: 91% decrease for NT-3; 93 % decrease for BDNF; 93 % decrease for CNTF; and a 87 % decrease for β-NGF. This decrease in concentration is consistent with the neuroprotective roles that neurotrophins play in the maintenance and survival of neuronal cells. The results obtained by the ICE method were closely comparable with those generated by a commercially available ELISA method.

‣ Cardiovascular Actions of Neurotrophins

CAPORALI, ANDREA; EMANUELI, COSTANZA
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/2009 Português
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Neurotrophins were christened in consideration of their actions on the nervous system and, for a long time, they were the exclusive interest of neuroscientists. However, more recently, this family of proteins has been shown to possess essential cardiovascular functions. During cardiovascular development, neurotrophins and their receptors are essential factors in the formation of the heart and critical regulator of vascular development. Postnatally, neurotrophins control the survival of endothelial cells, vascular smooth muscle cells, and cardiomyocytes and regulate angiogenesis and vasculogenesis, by autocrine and paracrine mechanisms. Recent studies suggest the capacity of neurotrophins, via their tropomyosin-kinase receptors, to promote therapeutic neovascularization in animal models of hindlimb ischemia. Conversely, the neurotrophin low-affinity p75NTR receptor induces apoptosis of endothelial cells and vascular smooth muscle cells and impairs angiogenesis. Finally, nerve growth factor looks particularly promising in treating microvascular complications of diabetes or reducing cardiomyocyte apoptosis in the infarcted heart. These seminal discoveries have fuelled basic and translational research and thus opened a new field of investigation in cardiovascular medicine and therapeutics. Here...

‣ Role of Neurotrophins on Postnatal Neurogenesis in the Thalamus: Prenatal Exposure to Ethanol

Mooney, Sandra M.; Miller, Michael W.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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A second wave of neuronal generation occurs in the ventrobasal nucleus of the rat thalamus (VB) during the first three postnatal weeks. The present study tested the hypotheses (1) that postnatal neurogenesis in the VB is neurotrophin-regulated and (2) that ethanol-induced changes in this proliferation are mediated by neurotrophins. The first studies examined the effects of neurotrophins on the numbers of cycling cells in ex vivo preparations of the VB from three-day-old rats. The proportion of cycling (Ki-67-positive) VB cells was higher in cultured thalamic slices treated with neurotrophins than in controls. Interestingly, this increase occurred with nerve growth factor (NGF) alone or with a combination of NGF and brain-derived neurotrophic factor (BDNF), but not with BDNF alone. Based on these data, the VBs from young offspring of pregnant rats fed an ethanol-containing or an isocaloric non-alcoholic liquid diet were examined between postnatal day (P) 1 and P31. Studies used enzyme-linked immunosorbent assays and immunoblots to explore the effects of ethanol on the expression of neurotrophins, their receptors, and representative signaling proteins. Ethanol altered the expression of neurotrophins and receptors throughout the first postnatal month. Expression of NGF increased...

‣ The Role of Neurotrophins in Multiple Sclerosis—Pathological and Clinical Implications

Kalinowska-Lyszczarz, Alicja; Losy, Jacek
Fonte: Molecular Diversity Preservation International (MDPI) Publicador: Molecular Diversity Preservation International (MDPI)
Tipo: Artigo de Revista Científica
Publicado em 22/10/2012 Português
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Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS) with unknown etiology. It was recently suggested that autoimmunity, which had long been considered to be destructive in MS, might also play a protective role in the CNS of MS patients. Neurotrophins are polypeptides belonging to the neurotrophic factor family. While neurotrophins mediate cell survival and proliferation in the nervous system, they are also expressed within peripheral blood mononuclear cells fraction (PBMCs) of immunological system. In MS additional neurotrophic support from PBMCs might compensate relative neurotrophins deficiency in the damaged CNS tissue that needs to be repaired. Failure to produce the adequate neurotrophins concentrations might result in decreased protection of the CNS, consequently leading to increased atrophy, which is the main determinant of MS patients’ end-point disability. There are several lines of evidence, both from clinical research and animal models, suggesting that neurotrophins play a pivotal role in neuroprotective and neuroregenerative processes that are often defective in the course of MS. It seems that neuroprotective strategies might be used as potentially valuable add-on therapies...

‣ Regulatory networks between neurotrophins and miRNAs in brain diseases and cancers

Shi, Jian
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Português
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Neurotrophins are involved in many physiological and pathological processes in the nervous system. They regulate and modify signal transduction, transcription and translation in neurons. It is recently demonstrated that the neurotrophin expression is regulated by microRNAs (miRNAs), changing our views on neurotrophins and miRNAs. Generally, miRNAs regulate neurotrophins and their receptors in at least two ways: (1) miRNAs bind directly to the 3′ untranslated region (UTR) of isoform-specific mRNAs and post-transcriptionally regulate their expression; (2) miRNAs bind to the 3′ UTR of the regulatory factors of neurotrophins and regulate their expression. On the other hand, neurotrophins can regulate miRNAs. The results of BNDF research show that neurotrophins regulate miRNAs in at least three ways: (1) ERK stimulation enhances the activation of TRBP (HIV-1 TAR RNA-binding protein) and Dicer, leading to the upregulation of miRNA biogenesis; (2) ERK-dependent upregulation of Lin28a (RNA-binding proteins) blocks select miRNA biogenesis; (3) transcriptional regulation of miRNA expression through activation of transcription factors, including CREB and NF-κB. These regulatory processes integrate positive and negative regulatory loops in neurotrophin and miRNA signaling pathways...

‣ Orthodontic tooth movement and neurotrophins in the rat dento-alveolar complex.

Moses, James
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2010 Português
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During orthodontic tooth movement, stress is applied on the dento-alveolar complex, initiating a biological response. This response results in the remodelling of the periodontal ligament and the alveolar bone. When a force is placed on a tooth, the periodontal ligament is stretched and compressed depending on the direction of force. On the side where the ligament is stretched, a response resulting in bone deposition is initiated. On the opposite side, where the periodontal ligament is compressed, a response resulting in the resorption of bone begins. These responses are believed to be modulated by factors that are derived from the immune or nervous systems. When stress is placed on the periodontal ligament, it is believed that nerve fibres and neuroreceptors within the tissue are distorted, leading to the release of neurotrophins and a common concomitant clinical response of pain and pressure. These neurotrophins may interact with cells within the dentoalveolar complex, including fibroblasts, endothelial and alveolar bone cells, resulting in the initiation of bone resorption via the activation of intracellular secondary messengers, which leads to cellular proliferation and differentiation. Neurotrophin levels may play a role in the modulation of cellular activity in the periodontal ligament during orthodontic movement. They are a family of protein polypeptides which are important in neural cell differentiation and survival. One relatively well studied member of the family...

‣ TNF-α and its receptors modulate complex behaviours and neurotrophins in transgenic mice; TNF-alpha and its receptors modulate complex behaviours and neurotrophins in transgenic mice

Camara, M.; Corrigan, F.; Jaehne, E.; Jawahar, M.; Anscomb, H.; Koerner, H.; Baune, B.
Fonte: Pergamon-Elsevier Science Ltd Publicador: Pergamon-Elsevier Science Ltd
Tipo: Artigo de Revista Científica
Publicado em //2013 Português
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UNLABELLED: Tumour necrosis factor-α (TNF-α) plays an important role not only in immunity but also in the normal functioning of the central nervous system (CNS). At physiological levels, studies have shown TNF-α is essential to maintain synaptic scaling and thus influence learning and memory formation while also playing a role in modulating pathological states of anxiety and depression. TNF-α signals mainly through its two receptors, TNF-R1 and TNF-R2, however the exact role that these receptors play in TNF-α mediated behavioural phenotypes is yet to be determined. METHODS: We have assessed TNF(-/-), TNF-R1(-/-) and TNF-R2(-/-) mice against C57BL/6 wild-type (WT) mice from 12 weeks of age in order to evaluate measures of spatial memory and learning in the Barnes maze (BM) and Y-maze, as well as other behaviours such as exploration, social interaction, anxiety and depression-like behaviour in a battery of tests. We have also measured hippocampal and prefrontal cortex levels of the neurotrophins nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) as well as used immunohistochemical analyses to measure number of proliferating cells (Ki67) and immature neurons (DCX) within the dentate gyrus. RESULTS: We have shown that young adult TNF(-/-) and TNF-R1(-/-) mice displayed impairments in learning and memory in the BM and Y-maze...

‣ Neurotrophine und aktivitätsabhängige synaptische Plastizität: Untersuchungen zum Ort und Mechanismus der regulierten Neurotrophin-Freisetzung in adenoviral transduzierten hippokampalen Primärkulturen; Neurotrophins and activity-dependent plasticity: Investigations into the site and mechanism of regulated neurotrophin secretion in adenovirally transduced hippocampal primary cultures

Gärtner, Annette
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
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Eine modulatorische Rolle von Neurotrophinen (NT) in Prozessen aktivitätsabhängiger synaptischer Plastizität wurde in zahlreichen Untersuchungen gezeigt. NT bewirken diese Effekte über prä- und postsynaptische Mechanismen. Ein Ziel dieser Arbeit war es, die NT-Verfügbarkeit zu definierten Zeiten und an definierten Orten zu untersuchen, und die zugrundeliegenden Mechanismen aufzuklären. Um NT reproduzierbar nachweisen zu können wurden sie mittels adenoviraler Vektoren oder Sindbisviren überexprimiert. Für eine Transduktion dissoziierter Neuronen wurden Adenoviren bevorzugt, da Neuronen ohne zytotoxische Effekte Transgene bis zu zwei Wochen exprimieren konnten, während für einen lokalen Gentransfer in hippokampale Schnittkulturen die Verwendung von Sindbisviren erfolgreicher war, da sie selektiv Neuronen transduzieren. Im zweiten Teil der Arbeit wurden die Orte der NT-Freisetzung mit ultrastrastruktureller Auflösung identifiziert. Dazu verwendeten wir NT6myc, welches spezifisch an die Heparansulfatproteoglykane der Zelloberfläche bindet und sofort nach seiner Freisetzung an der Oberfläche adheriert, und mittels immunogoldzytochemischer Methoden nachgewiesen wurde. Die KCl-induzierte NT6myc-Freisetzung erfolgte vorwiegend aus neuronalen Ausläufern. Allerdings konnte keine ortsspezifische Freisetzung entlang der Ausläufer nachgewiesen werden. Weiterhin wurden die Speicher- und Freisetzungskompartimente von NT charakterisiert. Alle untersuchten NT waren in hippokampalen Neuronen gleich verteilt: die Immunoreaktivität war im Soma akkumuliert und homogen in punktförmigen Strukturen über die neuronalen Ausläufer verteilt. Auf EM-Ebene wurde die NT in glatten Membranstrukturen unterschiedlicher Formen und Größen lokalisiert. Im letzten Teil der Arbeit wurden NT mit definierten elektrischen Stimuli freigesetzt...

‣ Neurotrophins in the developing and regenerating visual system

von Bartheld, C.S.
Fonte: Murcia : F. Hernández Publicador: Murcia : F. Hernández
Tipo: Artigo de Revista Científica Formato: application/pdf
Português
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The neurotrophins NGF, BDNF, NT-3 and NT-4 have a wide range of effects in the development and regeneration of neural circuits in the visual system of vertebrates. This review focuses on the localization and functions of neurotrophins in the retina, lateral geniculate nucleus, suprachiasmatic nucleus, superior colliculus/optic tectum, and isthmic nuclei. Research of the past 20 years has shown that neurotrophins and their receptors are localized in numerous visual centers from the retina to the visual cortex, and that neurotrophins influence proliferation, neurite outgrowth and survival of cells in the visual system in vitro and in vivo. A relationship between electrical activity and neurotrophic functions has been established in several visual centers in the CNS, and neurotrophins have been implicated in synaptic plasticity in the visual cortex. Besides functions of neurotrophins as retrograde, target-derived trophic factors, recent data indicate that neurotrophins may have anterograde, afferent as well as local, paracrine actions in the retina, optic nerve and the visual cortex. Some neurotrophins appear to regulate proliferation and survival of glial cells in the optic pathways. Neurotrophins increase the survival of retinal ganglion cells after axotomy or ischemia and they promote the regeneration of retinal ganglion cell axons in some vertebrates. Neurotrophins also rescue photoreceptors from degeneration. These findings implicate the neurotrophins not only as important regulators during development...

‣ Unexpected presence of the neurotrophins NGF and BDNF and the neurotrophin receptor p75 in the tendon cells of the human Achilles tendon

Bagge, Johan; Lorentzon, Ronny; Alfredson, Hàkan; Forsgren, Sture
Fonte: Murcia : F. Hernández Publicador: Murcia : F. Hernández
Tipo: Artigo de Revista Científica Formato: application/pdf
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Neurotrophins are substances that have been shown to be important in growth and remodelling phases in different types of tissue. There is no information concerning the possible occurrences of neurotrophins and their receptors in tendons. In this study, sections of both chronic painful (tendinosis) and pain-free (nontendinosis) human Achilles tendons were immunohistochemically stained with antibodies against the neurotrophins NGF and BDNF, and their receptors TrkA, TrkB and p75. There were marked immunoreactions for NGF and BDNF in the tendon cells (tenocytes) of both tendinosis and non-tendinosis specimens. The tenocytes were also reactive for the receptor p75, but not for the receptors TrkA and TrkB. In addition, p75 immunoreactions were seen in nerve fascicles and in the walls of arterioles. This is the first study to identify neurotrophins in the tenocytes of human tendon. It is clear from this study that the local cells of tendons are sources of neurotrophins. The neurotrophins may play an important role in the tendon through their interaction with the receptor p75 in the tenocytes. These interactions may regulate tropic modulatory, and apoptotic effects. In conclusion, the observations show a new concept concerning production and function of neurotrophins...

‣ Prolonged recycling of internalized neurotrophins in the nerve terminal

Weible, Michael; Bartlett, Selena; Reynolds, Anna; Hendry, Ian
Fonte: Wiley-Liss Inc Publicador: Wiley-Liss Inc
Tipo: Artigo de Revista Científica
Português
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Background: Neurons require contact with their target tissue in order to survive and make correct connections. The retrograde axonal transport of neurotrophins occurs after receptor-mediated endocytosis into vesicles at the nerve terminal. However, the me

‣ The role of neurotrophins and neurotrophin receptors in the pathogenesis of neurodegeneration and neuroregeneration

Marco Salazar, Paola
Fonte: [Barcelona] : Universitat Autònoma de Barcelona, Publicador: [Barcelona] : Universitat Autònoma de Barcelona,
Tipo: Tesis i dissertacions electròniques; info:eu-repo/semantics/doctoralThesis; info:eu-repo/semantics/publishedVersion Formato: application/pdf
Publicado em //2014 Português
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Las neurotrofinas son una familia de factores de crecimiento polipeptídicos estructuralmente relacionados que influyen en el desarrollo, mantenimiento, supervivencia, reparación y muerte de las células neuronales y no neuronales en el sistema nervioso. Los miembros pertenecientes a este grupo que incluyen NGF, BDNF, NT-3 y NT 4/5, ejercen sus funciones intracelulares mediante la unión a dos tipos de receptores transmembrana muy diferentes; los receptores de tirosin quinasa (Trk A, B y C) y el receptor de neurotrofina p75 (p75NTR), un miembro perteneciente a la superfamilia del factor de necrosis tumoral (TNF). Las neurotrofinas son objeto de estudio de la investigación actual debido a su participación tanto en condiciones fisiológicas como patológicas. Estudios previos publicados señalan las neurotrofinas como agentes terapéuticos prometedores. En esta tesis, se llevó a cabo un estudio inmunohistoquímico de todas estas neurotrofinas (a excepción de NT4 / 5) y sus receptores en el sistema nervioso de diferentes modelos transgénicos murinos en dos escenarios diferentes: neurodegeneración del sistema nervioso central y neuroregeneración en el sistema nervioso periférico. Con el fin de dilucidar los mecanismos neurodegenerativos asociados a la patogénesis de las enfermedades priónicas...