Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The impact of increased levels of skin-derived nerve growth factor (NGF) neurotrophin on sensory and sympathetic innervation to the mouse mystacial pad and postero-orbital vibrissae was determined. Consistent with an approximate doubling of neuron number in trigeminal and superior cervical ganglia, many components of the sensory and sympathetic innervation were substantially enhanced. Although the increased number of neurons raised the possibility that all types of innervation were increased, immunohistochemical analysis indicated that enhanced NGF production had a differential effect upon sensory innervation, primarily increasing unmyelinated innervation. This increased innervation occurred in specific locations known to be innervated by small, unmyelinated fibers, suggesting that NGF modulated sensory innervation density, but not targeting. In contrast, sympathetic innervation was not only increased but also was distributed to some aberrant locations. In the intervibrissal fur of the mystacial pad, both the number of sensory axons and branches appeared increased, whereas in vibrissal follicle sinus complexes, only branching increased. In some areas, sensory ending density was lower than expected based upon the size of the source nerve bundles suggesting that many axons and branches were surviving but failing to form functional endings. Furthermore, the immunochemical profile of innervation was altered in some sensory populations as demonstrated by the coexistence of RT-97 neurofilament labeling in calcitonin gene-related peptide (CGRP) positive axons, by the loss of substance P colocalization in some CGRP axons, and by an absence of neuropeptide Y labeling in tyrosine hydroxylase positive sympathetic axons. Collectively, these results indicate that the NGF mediated increase in neuron number may be selective for particular sets of innervation and that increases among some populations may result from phenotypic switching.
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PMID:Overexpression of nerve growth factor in skin causes preferential increases among innervation to specific sensory targets. 937 9

Trauma to a peripheral nerve is followed by anatomical remodelling proximal to the lesion, including sprouting of perivascular axons to form baskets of noradrenergic terminals ("rings") around large diameter primary afferent somata in the dorsal root ganglia containing lesioned neurons and sprouting of Abeta axons terminating deep in the dorsal horn into Lamina II. These abnormal structural associations may contribute to the changes in sensory processing that lead to neuropathic pain. The trigger for sprouting of sympathetic axons is probably a neurotrophin (such as nerve growth factor) concentrated locally. Nerve growth factor messenger RNA is known to be increased in dorsal root ganglia after sciatic nerve transection and increased local nerve growth factor elicits collateral sprouting of intact sympathetic terminals into adjacent denervated skin. Nociceptive terminals containing calcitonin gene-related peptide, with or without substance P, also sprout in response to raised concentrations of nerve growth factor. We have found that axons of small sensory neurons immunoreactive for these peptides also form rings around large diameter dorsal root ganglion cells of adult rats after sciatic nerve transection, concurrently with the development of rings of noradrenergic terminals.
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PMID:Axonal sprouts containing calcitonin gene-related peptide and substance P form pericellular baskets around large diameter neurons after sciatic nerve transection in the rat. 957 89

In rats with streptozotocin-induced diabetes, we measured increased (by 61%; P < 0.05) mRNA for nerve growth factor (NGF) in the iris together with increased (by 82%; P < 0.05) mRNA for preprotachykinin (the substance P precursor) in the trigeminal ganglion, suggesting that increased NGF was driving increased substance P gene expression. In other diabetic rats, these changes were prevented by treatment with either an antioxidant (butylated hydroxytoluene; 1% by diet) or an aldose reductase inhibitor (ARI) (sorbinil; 25 mg/kg/day p.o.) and the sorbinil treatment was associated with significant inhibition of polyol pathway intermediates in both lens and sciatic nerve. This suggests that polyol pathway activity in the lens may translate to oxidative stress-driving stimulation of NGF gene expression in the iris. The change is selective for NFG, because expression of the analogous neurotrophin, neurotrophin-3 (NT-3), was unaltered in the same irises. These changes suggest that oxidative stress and/or inflammation can drive up NGF expression in diabetes--a mechanism that might participate in iritis.
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PMID:Stimulation of nerve growth-factor and substance P expression in the iris-trigeminal axis of diabetic rats--involvement of oxidative stress and effects of aldose reductase inhibition. 974 8

To determine whether growth factors of the neurotrophin family are able to regulate the phenotype of striatal projection neurons, cell lines overexpressing brain-derived neurotrophic factor, neurotrophin-3 or neurotrophin-4/5 were intrastriatally grafted. Striatal projection neurons were examined for the regulation of their soma areas and for the expression of glutamate decarboxylase 67, preprotachykinin A, preproenkephalin and prodynorphin messenger RNAs by in situ hybridization. Brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-4/5 differentially regulated the soma area of projection neurons at different distances from the graft, but did not modify their messenger RNA levels. Neurotrophin-3 induced an increase in the soma area of preproenkephalin- and preprotachykinin A-positive neurons, brain-derived neurotrophic factor increased the soma area of only preprotachykinin A-positive neurons, while neurotrophin-4/5 did not produce any effect. Because atrophy and neuronal loss are hallmarks of Huntington's disease, we next examined whether neurotrophins prevent degenerative changes in a quinolinate model of Huntington's disease. Seven days after intrastriatal quinolinate injection, we observed a halo of cell loss around the injection sites, reduced soma area of glutamate decarboxylase 67-, preproenkephalin- and preprotachykinin A-positive neurons bordering the lesion, and a decrease in the messenger RNA levels of glutamate decarboxylase 67 and these neuropeptides. Grafting of cell lines expressing brain-derived neurotrophic factor, neurotrophin-3 or neurotrophin-4/5 reduced the size of the lesion for preproenkephalin-, preprotachykinin- and glutamate decarboxylase 67-, but not for prodynorphin-positive neurons. Moreover, the three neurotrophins prevented the atrophy of all projection neurons, and the lesion-induced decrease in preproenkephalin and preprotachykinin A messenger RNA levels. We conclude that neurotrophins differentially regulate the phenotype of striatal projection neurons and prevent degenerative changes. The higher efficiency of neurotrophin-3 suggests a potential therapeutic application of this molecule in neurological disorders affecting striatal projection neurons, such as Huntington's disease.
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PMID:Brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-4/5 differentially regulate the phenotype and prevent degenerative changes in striatal projection neurons after excitotoxicity in vivo. 1039 33

Diabetes-induced embryo malformations and growth retardation are correlated with a variety of biochemical changes including oxidative stress. In this study, we show that the morphological alterations are correlated with progressive and selective changes of mRNA expression in specific neurotrophic factors. At embryological stage E-17, diabetes affected both embryo growth and NGF mRNA expression, which was reduced by as much as 90 and 56% in target tissues of sensory system such as tongue and intestine, respectively. The reduction in retina and heart was around 50%. Conversely, the mRNA expression of low-affinity neurotrophin receptor p75 was increased. At birth, BDNF mRNA expression was affected with a significant generalized reduction,while in vibrissae we observed a reduction of BDNF and p75 mRNAs and an increase of NGF. At postnatal day 14, pups from diabetic mothers showed reduced muscle levels of IGF-I, while we observed a partial impairment of substance P axonal transport at postnatal day 28. Treatment of diabetic mothers with silybin, a flavonoid with antioxidant properties, prevented most of the changes in neurotrophic factor expression and substance P axonal transport with no effects on hyperglycemia and embryo growth retardation. These results indicate that oxidative stress may influence neurotrophic factor synthesis in target territories during development. In addition, these data suggest that nervous system abnormalities observed in diabetic embryopathy may also derive by insufficient neurotrophic factor biosynthesis involving sequentially NGF in the embryo and BDNF and IGF-I in the early postnatal days. Insulin treatment of diabetic mothers normalized hyperglycemia and body growth, with consequent regular embryonic and postnatal development.
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PMID:Progressive and selective changes in neurotrophic factor expression and substance p axonal transport induced by perinatal diabetes: protective action of antioxidant treatment. 1044 Sep 1

Recently it has been observed that a subpopulation of gut endocrine cells in vertebrates express Trk-like proteins, suggesting that neurotrophins could regulate the synthesis and storage of amines and peptides of these cells. Nevertheless, the peptides and amines present in the endocrine cells that express Trks have not been characterized. In this study we used immunohistochemistry to investigate the occurrence of Trk-like proteins (TrkA-like, TrkB-like and TrkC-like) and the possible co-localization of these with peptides and/or biogenic amines in the endocrine cells of the stomach of three teleost (bass, gilt-head and scorpionfish). No TrkA-like immunoreactivity (IR) was detected in the stomach of these species, whereas TrkB-like IR and TrkC-like IR were observed in numerous cells of the gastric epithelium. TrkB-like immunoreactive cells were present in all three species examined, and were particularly abundant in the blind sac. Conversely, TrkC-like immunoreactive cells were found only in the bass stomach, apparently co-localized with TrkB-like IR. TrkB-like IR was found co-localized with somatostatin IR in scorpionfish, and with somatostatin and CGRP IR in gilt-head and bass. Gastric endocrine cells expressing 5-HT, glucagon, insulin, met-, leu-enkephalin, substance P, PYY, VIP, CCK, NPY, bombesin and motilin were unreactive for Trk-like proteins. The present results provide direct evidence for the occurrence of Trk-like neurotrophin receptor proteins in a subpopulation of the teleostean gastric endocrine cells and suggest that neurotrophins could regulate, as in neurons, the expression of some neuropeptides such as somatostatin and CGRP.
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PMID:Co-localization of Trk neurotrophin receptors and regulatory peptides in the endocrine cells of the teleostean stomach. 1052 80

The expression of 34 transmitter-related genes has been examined in the cholinergic neurones of rat striatal brain slices, with the aim of correlating gene expression with functional activity. The mRNAs encoding types I, II/IIA, and III alpha subunits of the voltage-sensitive sodium channels were detected, suggesting the presence of these three types of sodium channel. Similarly, mRNAs encoding all four alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-type glutamate receptor subunits and the NR1 and NR2A, 2B, and 2D subunits of the NMDA-type glutamate receptors were detected, suggesting that various combinations of these subunits mediate the cellular response to synaptically released glutamate. Other mRNAs detected included the NK1 and NK3 tachykinin receptors, all four known adenosine receptors, and the GABA-synthesising enzyme glutamate decarboxylase. Subpopulations of these cholinergic neurones have been identified on the basis of the expression of the NK3 tachykinin receptor in 5% and the trkC neurotrophin receptor in 12% of the cells investigated.
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PMID:Correlating physiology with gene expression in striatal cholinergic neurones. 1064 37

Alterations of nerve growth factor (NGF) expression have been demonstrated during peripheral nerve disease and the impaired expression or synthesis and transportation of NGF has been correlated with the pathogenesis of several peripheral neuropathies. Since exogenous NGF administration seems to cause undesired side-effects, therapeutical strategies based on the regulation of endogenous synthesis of NGF could prove useful in the clinical treatment of these disorders. The aim of the present study was to analyse the effects of exogenous peripheral administration of the neuropeptide cholecystokinin-8 (CCK-8) on endogenous NGF synthesis, NGF mRNA and distribution of peripheral neuropeptides which are known to be regulated by this neurotrophin. To address these questions we studied the effects of capsaicin (CAPS) before and after the administration of CCK-8 on NGF levels, NGF mRNA expression and localization, and the concentration of substance P (SP) and calcitonin gene-related peptide (CGRP) in peripheral tissue These studies demonstrate that administration of the CCK-8 induces an increase of NGF protein and mRNA in peripheral tissue. NGF level in paw skin of CAPS/CCK-8-treated mice is 3 fold higher than in controls (1241+/-110 pg gr(-1) of tissue wet weight versus 414+/-110 pg gr(-1) of controls) and nearly 6 fold higher than in CAPS-treated mice (1241+/-110 pg gr(-1) versus 248+/-27 pg gr(-1)). The increase of NGF is correlated with the recovery of impaired nocifensive behaviour and with an overexpression of SP and CGRP. The evidence that CCK-8 promotes the recovery of sensory deficits suggests a potential clinical use for this neuropeptide in peripheral neuropathies.
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PMID:Cholecystokinin-8 enhances nerve growth factor synthesis and promotes recovery of capsaicin-induced sensory deficit. 1068 99

In the rat small intestine, neurotrophin-3 immunoreactivity was identified in ganglion cells and in processes mostly innervating the mucosa and occasionally the muscle layer and vasculature. The vast majority of neurotrophin-3 immunoreactive neurons contained vasoactive intestinal polypeptide (VIP), but not substance P or related tachykinin (SP/TK). Neurotrophin receptors visualized by pan-trk immunoreactivity were found in numerous ganglion cells of both plexuses and in nerve processes in the intestinal wall. Pan-trk submucosal neurons contained VIP (36%) or SP/TK-IR (47%). Pan-trk myenteric neurons contained VIP-IR (57%) or SP/TK (27%). Our data suggest that neurotrophin-3 and neurotrophin receptors may be involved in the maintenance of enteric neuronal circuits, transmission and phenotypic expression.
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PMID:Neurotrophin-3 and neurotrophin receptor immunoreactivity in peptidergic enteric neurons. 1107 30

Intrastriatal injection of quinolinate has been proven to be a very useful animal model to study the pathogenesis and treatment of Huntington's disease. To determine whether growth factors of the neurotrophin family are able to prevent the degeneration of striatal projection neurons, cell lines expressing brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or neurotrophin-4/5 (NT-4/5) were grafted in the adult rat striatum before quinolinate injection. Three days after lesioning, ongoing cell death was assessed by in situ detection of DNA fragmentation. In animals grafted with the control cell line, quinolinate injection induced a gradual cell loss that was differentially prevented by intrastriatal grafting of BDNF-, NT-3-, or NT-415-secreting cells. Seven days after lesioning, we characterized striatal projection neurons that were protected by neurotrophins. Quinolinate injection, alone or in combination with the control cell line, induced a selective loss of striatal projection neurons. Grafting of a BDNF-secreting cell line pre-vented the loss of all types of striatal projection neurons analyzed. Glutamic acid decarboxylase 67-, preproenkephalin-, and preprotachykinin A- but not prodynorphin-expressing neurons were protected by grafting of NT-3- or NT-4/5-secreting cells but with less efficiency than the BDNF-secreting cells. Our findings show that neurotrophins are able to promote the survival of striatal projection neurons in vivo and suggest that BDNF might be beneficial for the treatment of striatonigral degenerative disorders, including Huntington's disease.
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PMID:Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 prevent the death of striatal projection neurons in a rodent model of Huntington's disease. 1118 72


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