Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurotrophins are target-derived trophic factors essential for the survival and maintenance of neurons. Among these, nerve growth factor (NGF) and neurotrophin-3 (NT-3) are particularly important for sensory neurons. The actions of neurotrophins are through the p75 low-affinity receptor and the high-affinity receptor tyrosine kinase (trk). Each neurotrophin has its preferred receptor, i.e. trkA for NGF, and trkC for NT-3. The primary sensory neurons in the dorsal root ganglion are classified into two categories, namely, the large and small sensory neurons based on their size. The large sensory neurons with the expression of trkC depend on NT-3 for development and subserve the function of position sensations. Some of the small sensory neurons express trkA and are NGF-dependent. They are responsible for nociceptive sensation, the detection of painful and thermal stimuli. A more intriguing observation is the bidirectional interactions between nociceptive nerves and their target, the skin. The peripheral processes of small sensory neurons innervate the epidermis of the skin as 'free nerve endings'. In denervated skin, there is a drastic reduction in the epidermal thickness, a finding corroborated by the phenomenon of trophic change, the shining and thinning of the skin, in the disorders of peripheral nerves. The performance of animals with peripheral nerve disorders improved after administration of neurotrophic factors. Based on these results, the therapeutic potentials of neurotrophic factors in human are under investigation.
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PMID:Trophic interactions between sensory nerves and their targets. 1008 38

Cerebrospinal fluid (CSF) is secreted by the choroid plexuses located in the lateral, third and fourth ventricles. The fluid flows through the ventricular system, passing over all the regions of germinal activity. CSF contains growth factors and other neurotrophic factors, which are important for cell survival and proliferation. It has been shown that nerve growth factor deprivation induces apoptosis in the developing cerebral cortex. In this study, disruption of normal CSF flow on neural cell survival in the developing cortex has been investigated. Draining CSF from the ventricles of the brain during development increases the number of neural cell deaths and thinning of the cerebral cortex compared with normal ones. These data from our study indicate that normal CSF circulation is important for the survival of cells in the developing cerebral cortex and thus of CSF in the normal chick cerebral cortex development.
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PMID:The role of cerebrospinal fluid on neural cell survival in the developing chick cerebral cortex: an in vivo study. 1683 7

The central nervous system (CNS) of vertebrates originates from neuroepithelial cells located within the embryonic neural tube. Coincidental with the processes of proliferation, migration and differentiation in the developing CNS, cell death is also a major phenomenon during normal development. The investigation of neural cell death in development has focused on the role of target-derived survival factors such as nerve growth factor (NGF). In this study, the effects of anti-NGF antibody on neural cell death in the cerebral cortex have been investigated. Injection of anti-NGF antibody into the cisterna magnum of mouse pups increased the number of neural cell deaths and resulted in thinning of the cerebral cortex compared with a control group. It is concluded that endogenous NGF is essential for cortical cell survival in the cerebral cortex of the newborn mouse. Moreover, this method may be applied to the other factors and different CNS regions, allowing identification of molecules and signals involved in neural cell survival.
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PMID:Neural cell death is induced by neutralizing antibody to nerve growth factor: an in vivo study. 1770 5

The axonal transport of organelles is critical for the development, maintenance, and survival of neurons, and its dysfunction has been implicated in several neurodegenerative diseases. Retrograde axon transport is mediated by the motor protein dynein. In this study, using embryonic chicken dorsal root ganglion neurons, we investigate the effects of Ciliobrevin D, a pharmacological dynein inhibitor, on the transport of axonal organelles, axon extension, nerve growth factor (NGF)-induced branching and growth cone expansion, and axon thinning in response to actin filament depolymerization. Live imaging of mitochondria, lysosomes, and Golgi-derived vesicles in axons revealed that both the retrograde and anterograde transport of these organelles was inhibited by treatment with Ciliobrevin D. Treatment with Ciliobrevin D reversibly inhibits axon extension and transport, with effects detectable within the first 20 min of treatment. NGF induces growth cone expansion, axonal filopodia formation and branching. Ciliobrevin D prevented NGF-induced formation of axonal filopodia and branching but not growth cone expansion. Finally, we report that the retrograde reorganization of the axonal cytoplasm which occurs on actin filament depolymerization is inhibited by treatment with Ciliobrevin D, indicating a role for microtubule based transport in this process, as well as Ciliobrevin D accelerating Wallerian degeneration. This study identifies Ciliobrevin D as an inhibitor of the bidirectional transport of multiple axonal organelles, indicating this drug may be a valuable tool for both the study of dynein function and a first pass analysis of the role of axonal transport.
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PMID:The dynein inhibitor Ciliobrevin D inhibits the bidirectional transport of organelles along sensory axons and impairs NGF-mediated regulation of growth cones and axon branches. 2540 3

There is intense interest in developing novel methods for the sustained delivery of low levels of clinical therapeutics. MAX8 is a peptide-based beta-hairpin hydrogel that has unique shear thinning properties that allow for immediate rehealing after the removal of shear forces, making MAX8 an excellent candidate for injectable drug delivery at a localized injury site. The current studies examined the feasibility of using MAX8 as a delivery system for nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), two neurotrophic growth factors currently used in experimental treatments of spinal cord injuries. Experiments determined that encapsulation of NGF and BDNF within MAX8 did not negatively impact gel formation or rehealing and that shear thinning did not result in immediate growth factor release. ELISA, microscopy, rheology, and Western blotting experiments collectively demonstrate the functional capabilities of the therapeutic-loaded hydrogels to (i) maintain a protective environment against in vitro degradation of encapsulated therapeutics for at least 28 days; and (ii) allow for sustained release of NGF and BDGF capable of initiating neurite-like extensions of PC12 cells, most likely due to NGF/BDGF signaling pathways. Importantly, while the 21 day release profiles could be tuned by adjusting the MAX8 hydrogel concentration, the initial shear thinning of the hydrogel (e.g., during injection) does not induce significant premature loss of the encapsulated therapeutic, most likely due to effective trapping of growth factors within structurally robust domains that are maintained during the application of shear forces. Together, our data suggests that MAX8 allows for greater dosage control and sustained therapeutic growth factor delivery, potentially alleviating side effects and improving the efficacy of current therapies.
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PMID:Beta Hairpin Peptide Hydrogels as an Injectable Solid Vehicle for Neurotrophic Growth Factor Delivery. 2622 9

It is consistently reported that in inflammatory arthritis (IA), pain may continue despite well-controlled inflammation, most likely due to interactions between joint pathology and pain pathway alterations. Nervous system alterations have been described, but much remains to be understood about neuronal and central non-neuronal changes in IA. Using a rat model of IA induced by intra-articular complete Freund's adjuvant injection, this study includes a thorough characterization of joint pathology and objectives to identify peripheral innervation changes and alterations in the spinal dorsal horn (DH) that could alter DH excitatory balancing. Male and female rats displayed long-lasting pain-related behavior, but, in agreement with our previous studies, other pathological alterations emerged only at later times. Cartilage vascularization, thinning, and decreased proteoglycan content were not detectable in the ipsilateral cartilage until 4 weeks after complete Freund's adjuvant. Sympathetic and peptidergic nociceptive fibers invaded the ipsilateral cartilage alongside blood vessels, complex innervation changes were observed in the surrounding skin, and ipsilateral nerve growth factor protein expression was increased. In the DH, we examined innervation by peptidergic and nonpeptidergic nociceptors, inhibitory terminal density, the KCl cotransporter KCC2, microgliosis, and astrocytosis. Here, we detected the presence of microgliosis and, interestingly, an apparent loss of inhibitory terminals and decreased expression of KCC2. In conclusion, we found evidence of anatomical, inflammatory, and neuronal alterations in the peripheral and central nervous systems in a model of IA. Together, these suggest that there may be a shift in the balance between incoming and outgoing excitation, and modulatory inhibitory tone in the DH.
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PMID:Peripheral and central nervous system alterations in a rat model of inflammatory arthritis. 3206 63