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Anne Grete Byskov - One of the best experts on this subject based on the ideXlab platform.
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human primordial germ cells migrate along Nerve Fibers and schwann cells from the dorsal hind gut mesentery to the gonadal ridge
Molecular Human Reproduction, 2010Co-Authors: Kjeld Møllgård, Melissa C Lutterodt, Yding C Andersen, P E Hoyer, Ase Jespersen, Anne Grete ByskovAbstract:The aim of this study was to investigate the spatiotemporal development of autonomic Nerve Fibers and primordial germ cells (PGCs) along their migratory route from the dorsal mesentery to the gonadal ridges in human embryos using immunohistochemical markers and electron microscopy. Autonomic Nerve Fibers in the dorsal mesentery, the pre-aortic and para-aortic plexuses and in the gonadal ridge were stained for b III tubulin, neuron specific enolase and the glia fibrillary acidic protein. Electron microscopy demonstrated the presence of neurofilaments and neurotubules in these Nerve Fibers and their intimate contact with PGCs. PGCs expressed GAGE, MAGE-A4, OCT4 and c-Kit. Serial paraffin sections showed that most PGCs were located inside bundles of autonomic Nerve Fibers with the majority adjacent to the most peripheral Fibers (close to Schwann cells). We also show that both Nerve Fibers and PGCs arrive at the gonadal ridge between 29 and 33 days pc. In conclusion, our data suggest that PGCs in human embryos preferentially migrate along autonomic Nerve Fibers from the dorsal mesentery to the developing gonad where they are delivered via a fine Nerve plexus.
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Human primordial germ cells migrate along Nerve Fibers and Schwann cells from the dorsal hind gut mesentery to the gonadal ridge
Molecular human reproduction, 2010Co-Authors: Kjeld Møllgård, Melissa C Lutterodt, P E Hoyer, Ase Jespersen, C. Yding Andersen, Anne Grete ByskovAbstract:The aim of this study was to investigate the spatiotemporal development of autonomic Nerve Fibers and primordial germ cells (PGCs) along their migratory route from the dorsal mesentery to the gonadal ridges in human embryos using immunohistochemical markers and electron microscopy. Autonomic Nerve Fibers in the dorsal mesentery, the pre-aortic and para-aortic plexuses and in the gonadal ridge were stained for beta III tubulin, neuron specific enolase and the glia fibrillary acidic protein. Electron microscopy demonstrated the presence of neurofilaments and neurotubules in these Nerve Fibers and their intimate contact with PGCs. PGCs expressed GAGE, MAGE-A4, OCT4 and c-Kit. Serial paraffin sections showed that most PGCs were located inside bundles of autonomic Nerve Fibers with the majority adjacent to the most peripheral Fibers (close to Schwann cells). We also show that both Nerve Fibers and PGCs arrive at the gonadal ridge between 29 and 33 days pc. In conclusion, our data suggest that PGCs in human embryos preferentially migrate along autonomic Nerve Fibers from the dorsal mesentery to the developing gonad where they are delivered via a fine Nerve plexus.
Kjeld Møllgård - One of the best experts on this subject based on the ideXlab platform.
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human primordial germ cells migrate along Nerve Fibers and schwann cells from the dorsal hind gut mesentery to the gonadal ridge
Molecular Human Reproduction, 2010Co-Authors: Kjeld Møllgård, Melissa C Lutterodt, Yding C Andersen, P E Hoyer, Ase Jespersen, Anne Grete ByskovAbstract:The aim of this study was to investigate the spatiotemporal development of autonomic Nerve Fibers and primordial germ cells (PGCs) along their migratory route from the dorsal mesentery to the gonadal ridges in human embryos using immunohistochemical markers and electron microscopy. Autonomic Nerve Fibers in the dorsal mesentery, the pre-aortic and para-aortic plexuses and in the gonadal ridge were stained for b III tubulin, neuron specific enolase and the glia fibrillary acidic protein. Electron microscopy demonstrated the presence of neurofilaments and neurotubules in these Nerve Fibers and their intimate contact with PGCs. PGCs expressed GAGE, MAGE-A4, OCT4 and c-Kit. Serial paraffin sections showed that most PGCs were located inside bundles of autonomic Nerve Fibers with the majority adjacent to the most peripheral Fibers (close to Schwann cells). We also show that both Nerve Fibers and PGCs arrive at the gonadal ridge between 29 and 33 days pc. In conclusion, our data suggest that PGCs in human embryos preferentially migrate along autonomic Nerve Fibers from the dorsal mesentery to the developing gonad where they are delivered via a fine Nerve plexus.
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Human primordial germ cells migrate along Nerve Fibers and Schwann cells from the dorsal hind gut mesentery to the gonadal ridge
Molecular human reproduction, 2010Co-Authors: Kjeld Møllgård, Melissa C Lutterodt, P E Hoyer, Ase Jespersen, C. Yding Andersen, Anne Grete ByskovAbstract:The aim of this study was to investigate the spatiotemporal development of autonomic Nerve Fibers and primordial germ cells (PGCs) along their migratory route from the dorsal mesentery to the gonadal ridges in human embryos using immunohistochemical markers and electron microscopy. Autonomic Nerve Fibers in the dorsal mesentery, the pre-aortic and para-aortic plexuses and in the gonadal ridge were stained for beta III tubulin, neuron specific enolase and the glia fibrillary acidic protein. Electron microscopy demonstrated the presence of neurofilaments and neurotubules in these Nerve Fibers and their intimate contact with PGCs. PGCs expressed GAGE, MAGE-A4, OCT4 and c-Kit. Serial paraffin sections showed that most PGCs were located inside bundles of autonomic Nerve Fibers with the majority adjacent to the most peripheral Fibers (close to Schwann cells). We also show that both Nerve Fibers and PGCs arrive at the gonadal ridge between 29 and 33 days pc. In conclusion, our data suggest that PGCs in human embryos preferentially migrate along autonomic Nerve Fibers from the dorsal mesentery to the developing gonad where they are delivered via a fine Nerve plexus.
Patrick W Mantyh - One of the best experts on this subject based on the ideXlab platform.
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sensory and sympathetic Nerve Fibers undergo sprouting and neuroma formation in the painful arthritic joint of geriatric mice
Arthritis Research & Therapy, 2012Co-Authors: Juan Miguel Jimenezandrade, Patrick W MantyhAbstract:Although the prevalence of arthritis dramatically increases with age, the great majority of preclinical studies concerning the mechanisms that drive arthritic joint pain have been performed in young animals. One mechanism hypothesized to contribute to arthritic pain is ectopic Nerve sprouting; however, neuroplasticity is generally thought to be greater in young versus old Nerves. Here we explore whether sensory and sympathetic Nerve Fibers can undergo a significant ectopic Nerve remodeling in the painful arthritic knee joint of geriatric mice. Vehicle (saline) or complete Freund's adjuvant (CFA) was injected into the knee joint of 27- to 29-month-old female mice. Pain behaviors, macrophage infiltration, neovascularization, and the sprouting of sensory and sympathetic Nerve Fibers were then assessed 28 days later, when significant knee-joint pain was present. Knee joints were processed for immunohistochemistry by using antibodies raised against CD68 (monocytes/macrophages), PECAM (endothelial cells), calcitonin gene-related peptide (CGRP; sensory Nerve Fibers), neurofilament 200 kDa (NF200; sensory Nerve Fibers), tyrosine hydroxylase (TH; sympathetic Nerve Fibers), and growth-associated protein 43 (GAP43; Nerve Fibers undergoing sprouting). At 4 weeks after initial injection, CFA-injected mice displayed robust pain-related behaviors (which included flinching, guarding, impaired limb use, and reduced weight bearing), whereas animals injected with vehicle alone displayed no significant pain-related behaviors. Similarly, in the CFA-injected knee joint, but not in the vehicle-injected knee joint, a remarkable increase was noted in the number of CD68+ macrophages, density of PECAM+ blood vessels, and density and formation of neuroma-like structures by CGRP+, NF200+, and TH+ Nerve Fibers in the synovium and periosteum. Sensory and sympathetic Nerve Fibers that innervate the aged knee joint clearly maintain the capacity for robust Nerve sprouting and formation of neuroma-like structures after inflammation/injury. Understanding the factors that drive this neuroplasticity, whether this pathologic reorganization of Nerve Fibers contributes to chronic joint pain, and how the phenotype of sensory and sympathetic Nerves changes with age may provide pharmacologic insight and targets for better controlling aging-related joint pain.
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breast cancer induced bone remodeling skeletal pain and sprouting of sensory Nerve Fibers
The Journal of Pain, 2011Co-Authors: Aaron P Bloom, Juan Miguel Jimenezandrade, Reid N Taylor, Gabriela Castanedacorral, Magdalena J Kaczmarska, Katie T Freeman, Kathleen A Coughlin, Joseph R Ghilardi, Michael A Kuskowski, Patrick W MantyhAbstract:Abstract Breast cancer metastasis to bone is frequently accompanied by pain. What remains unclear is why this pain tends to become more severe and difficult to control with disease progression. Here we test the hypothesis that with disease progression, sensory Nerve Fibers that innervate the breast cancer bearing bone undergo a pathological sprouting and reorganization, which in other nonmalignant pathologies has been shown to generate and maintain chronic pain. Injection of human breast cancer cells (MDA-MB-231-BO) into the femoral intramedullary space of female athymic nude mice induces sprouting of calcitonin gene-related peptide (CGRP + ) sensory Nerve Fibers. Nearly all CGRP + Nerve Fibers that undergo sprouting also coexpress tropomyosin receptor kinase A (TrkA + ) and growth-associated protein-43 (GAP43 + ). This ectopic sprouting occurs in periosteal sensory Nerve Fibers that are in close proximity to breast cancer cells, tumor-associated stromal cells, and remodeled cortical bone. Therapeutic treatment with an antibody that sequesters Nerve growth factor (NGF), administered when the pain and bone remodeling were first observed, blocks this ectopic sprouting and attenuates cancer pain. The present data suggest that the breast cancer cells and tumor-associated stromal cells express and release NGF, which drives bone pain and the pathological reorganization of nearby CGRP + /TrkA + /GAP43 + sensory Nerve Fibers. Perspective Therapies that block breast cancer pain by reducing the tumor-induced pathological sprouting and reorganization of sensory Nerve Fibers may provide insight into the evolving mechanisms that drive breast cancer pain and lead to more effective therapies for attenuating this chronic pain state.
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the majority of myelinated and unmyelinated sensory Nerve Fibers that innervate bone express the tropomyosin receptor kinase a
Neuroscience, 2011Co-Authors: Gabriela Castanedacorral, Juan Miguel Jimenezandrade, Aaron P Bloom, Reid N Taylor, Magdalena J Kaczmarska, Joseph R Ghilardi, William G Mantyh, Patrick W MantyhAbstract:Abstract Although skeletal pain is a leading cause of chronic pain and disability, relatively little is known about the specific populations of Nerve Fibers that innervate the skeleton. Recent studies have reported that therapies blocking Nerve growth factor (NGF) or its cognate receptor, tropomyosin receptor kinase A (TrkA) are efficacious in attenuating skeletal pain. A potential factor to consider when assessing the analgesic efficacy of targeting NGF-TrkA signaling in a pain state is the fraction of NGF-responsive TrkA+ nociceptors that innervate the tissue from which the pain is arising, as this innervation and the analgesic efficacy of targeting NGF-TrkA signaling may vary considerably from tissue to tissue. To explore this in the skeleton, tissue slices and whole mount preparations of the normal, adult mouse femur were analyzed using immunohistochemistry and confocal microscopy. Analysis of these preparations revealed that 80% of the unmyelinated/thinly myelinated sensory Nerve Fibers that express calcitonin gene-related peptide (CGRP) and innervate the periosteum, mineralized bone and bone marrow also express TrkA. Similarly, the majority of myelinated sensory Nerve Fibers that express neurofilament 200 kDa (NF200) which innervate the periosteum, mineralized bone and bone marrow also co-express TrkA. In the normal femur, the relative density of CGRP+, NF200+ and TrkA+ sensory Nerve Fibers per unit volume is: periosteum>bone marrow>mineralized bone>cartilage with the respective relative densities being 100:2:0.1:0. The observation that the majority of sensory Nerve Fibers innervating the skeleton express TrkA+, may in part explain why therapies that block NGF/TrkA pathway are highly efficacious in attenuating skeletal pain.
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a phenotypically restricted set of primary afferent Nerve Fibers innervate the bone versus skin therapeutic opportunity for treating skeletal pain
Bone, 2010Co-Authors: Juan Miguel Jimenezandrade, Aaron P Bloom, William G Mantyh, Alice S Ferng, Gregory Dussor, Todd W Vanderah, Patrick W MantyhAbstract:Although musculoskeletal pain is one of the most common causes of chronic pain and physical disability in both developing and developed countries, relatively little is known about the Nerve Fibers and mechanisms that drive skeletal pain. Small diameter sensory Nerve Fibers, most of which are C-fiber nociceptors, can be separated into two broad populations: the peptide-rich and peptide-poor Nerve Fibers. Peptide-rich Nerve Fibers express substance P (SP) and calcitonin gene-related peptide (CGRP). In contrast, the peptide-poor Nerve Fibers bind to isolectin B4 (IB(4)) and express the purinergic receptor P(2)X(3) and Mas-related G protein-coupled receptor member d (Mrgprd). In the present report, we used mice in which the Mrgprd(+) Nerve Fibers express genetically encoded axonal tracers to determine the peptide-rich and peptide-poor sensory Nerve Fibers that innervate the glabrous skin of the hindpaw as compared to the bone marrow, mineralized bone and periosteum of the femur. Whereas the skin is richly innervated by CGRP(+), SP(+), P(2)X(3)(+) and Mrgprd(+) sensory Nerve Fibers, the bone marrow, mineralized bone and periosteum receive a significant innervation by SP(+) and CGRP(+), but not Mrgprd(+) and P(2)X(3)(+) Nerve Fibers. This lack of redundancy in the populations of C-Fibers that innervate the bone may present a unique therapeutic opportunity for targeting skeletal pain as the peptide-rich and peptide-poor sensory Nerve Fibers generally express a different repertoire of receptors and channels to detect noxious stimuli. Thus, therapies that target the specific types of C-Nerve Fibers that innervate the bone may be uniquely effective in attenuating skeletal pain as compared to skin pain.
P E Hoyer - One of the best experts on this subject based on the ideXlab platform.
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human primordial germ cells migrate along Nerve Fibers and schwann cells from the dorsal hind gut mesentery to the gonadal ridge
Molecular Human Reproduction, 2010Co-Authors: Kjeld Møllgård, Melissa C Lutterodt, Yding C Andersen, P E Hoyer, Ase Jespersen, Anne Grete ByskovAbstract:The aim of this study was to investigate the spatiotemporal development of autonomic Nerve Fibers and primordial germ cells (PGCs) along their migratory route from the dorsal mesentery to the gonadal ridges in human embryos using immunohistochemical markers and electron microscopy. Autonomic Nerve Fibers in the dorsal mesentery, the pre-aortic and para-aortic plexuses and in the gonadal ridge were stained for b III tubulin, neuron specific enolase and the glia fibrillary acidic protein. Electron microscopy demonstrated the presence of neurofilaments and neurotubules in these Nerve Fibers and their intimate contact with PGCs. PGCs expressed GAGE, MAGE-A4, OCT4 and c-Kit. Serial paraffin sections showed that most PGCs were located inside bundles of autonomic Nerve Fibers with the majority adjacent to the most peripheral Fibers (close to Schwann cells). We also show that both Nerve Fibers and PGCs arrive at the gonadal ridge between 29 and 33 days pc. In conclusion, our data suggest that PGCs in human embryos preferentially migrate along autonomic Nerve Fibers from the dorsal mesentery to the developing gonad where they are delivered via a fine Nerve plexus.
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Human primordial germ cells migrate along Nerve Fibers and Schwann cells from the dorsal hind gut mesentery to the gonadal ridge
Molecular human reproduction, 2010Co-Authors: Kjeld Møllgård, Melissa C Lutterodt, P E Hoyer, Ase Jespersen, C. Yding Andersen, Anne Grete ByskovAbstract:The aim of this study was to investigate the spatiotemporal development of autonomic Nerve Fibers and primordial germ cells (PGCs) along their migratory route from the dorsal mesentery to the gonadal ridges in human embryos using immunohistochemical markers and electron microscopy. Autonomic Nerve Fibers in the dorsal mesentery, the pre-aortic and para-aortic plexuses and in the gonadal ridge were stained for beta III tubulin, neuron specific enolase and the glia fibrillary acidic protein. Electron microscopy demonstrated the presence of neurofilaments and neurotubules in these Nerve Fibers and their intimate contact with PGCs. PGCs expressed GAGE, MAGE-A4, OCT4 and c-Kit. Serial paraffin sections showed that most PGCs were located inside bundles of autonomic Nerve Fibers with the majority adjacent to the most peripheral Fibers (close to Schwann cells). We also show that both Nerve Fibers and PGCs arrive at the gonadal ridge between 29 and 33 days pc. In conclusion, our data suggest that PGCs in human embryos preferentially migrate along autonomic Nerve Fibers from the dorsal mesentery to the developing gonad where they are delivered via a fine Nerve plexus.
Melissa C Lutterodt - One of the best experts on this subject based on the ideXlab platform.
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human primordial germ cells migrate along Nerve Fibers and schwann cells from the dorsal hind gut mesentery to the gonadal ridge
Molecular Human Reproduction, 2010Co-Authors: Kjeld Møllgård, Melissa C Lutterodt, Yding C Andersen, P E Hoyer, Ase Jespersen, Anne Grete ByskovAbstract:The aim of this study was to investigate the spatiotemporal development of autonomic Nerve Fibers and primordial germ cells (PGCs) along their migratory route from the dorsal mesentery to the gonadal ridges in human embryos using immunohistochemical markers and electron microscopy. Autonomic Nerve Fibers in the dorsal mesentery, the pre-aortic and para-aortic plexuses and in the gonadal ridge were stained for b III tubulin, neuron specific enolase and the glia fibrillary acidic protein. Electron microscopy demonstrated the presence of neurofilaments and neurotubules in these Nerve Fibers and their intimate contact with PGCs. PGCs expressed GAGE, MAGE-A4, OCT4 and c-Kit. Serial paraffin sections showed that most PGCs were located inside bundles of autonomic Nerve Fibers with the majority adjacent to the most peripheral Fibers (close to Schwann cells). We also show that both Nerve Fibers and PGCs arrive at the gonadal ridge between 29 and 33 days pc. In conclusion, our data suggest that PGCs in human embryos preferentially migrate along autonomic Nerve Fibers from the dorsal mesentery to the developing gonad where they are delivered via a fine Nerve plexus.
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Human primordial germ cells migrate along Nerve Fibers and Schwann cells from the dorsal hind gut mesentery to the gonadal ridge
Molecular human reproduction, 2010Co-Authors: Kjeld Møllgård, Melissa C Lutterodt, P E Hoyer, Ase Jespersen, C. Yding Andersen, Anne Grete ByskovAbstract:The aim of this study was to investigate the spatiotemporal development of autonomic Nerve Fibers and primordial germ cells (PGCs) along their migratory route from the dorsal mesentery to the gonadal ridges in human embryos using immunohistochemical markers and electron microscopy. Autonomic Nerve Fibers in the dorsal mesentery, the pre-aortic and para-aortic plexuses and in the gonadal ridge were stained for beta III tubulin, neuron specific enolase and the glia fibrillary acidic protein. Electron microscopy demonstrated the presence of neurofilaments and neurotubules in these Nerve Fibers and their intimate contact with PGCs. PGCs expressed GAGE, MAGE-A4, OCT4 and c-Kit. Serial paraffin sections showed that most PGCs were located inside bundles of autonomic Nerve Fibers with the majority adjacent to the most peripheral Fibers (close to Schwann cells). We also show that both Nerve Fibers and PGCs arrive at the gonadal ridge between 29 and 33 days pc. In conclusion, our data suggest that PGCs in human embryos preferentially migrate along autonomic Nerve Fibers from the dorsal mesentery to the developing gonad where they are delivered via a fine Nerve plexus.