Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effect of dopamine on the in vivo expression of brain-derived neurotrophic factor (BDNF) in the striatum of mouse. BDNF mRNA expression in the striatum, which was quantified with the reverse transcriptase polymerase chain reaction, was up-regulated from 2 h after oral administration of levodopa, a precursor of dopamine. The increase was sustained for 16 h. Co-administration of haloperidol partially inhibited dopamine-induced BDNF enhancement. These data suggest that dopaminergic stimulation directly promotes the expression of BDNF in the striatum in vivo.
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PMID:Dopaminergic stimulation up-regulates the in vivo expression of brain-derived neurotrophic factor (BDNF) in the striatum. 135 75

Neurotrophic support to peripheral sensory neurons is provided by 2 factors of related sequence, NGF and brain-derived neurotrophic factor (BDNF). NGF is present in peripheral target tissues, while BDNF has only been reported in the CNS. We now report the biological characterization and molecular cloning of a cDNA for BDNF from human platelets. BDNF in human platelets has biological activities very similar to those of BDNF obtained from adult porcine brain in neuron-enriched cultures prepared from peripheral ganglia of chick embryos at 8-12 d of incubation. BDNF from human platelets promoted the survival and neurite outgrowth of placodal and neural crest-derived sensory neurons, but not to parasympathetic or sympathetic neurons. Activity of the factor was additive to that of NGF in dorsal root ganglia (DRG) neuron cultures and is equivalent to porcine brain BDNF in nodose ganglion neuron cultures. On SDS-PAGE, BDNF from human platelets is recovered at an apparent molecular weight equivalent to porcine brain BDNF (13,000 D). A BDNF cDNA fragment was amplified from human platelet RNA by using a coupled reverse transcriptase-polymerase chain reaction. Molecular cloning and DNA sequence analysis of the amplified cDNA fragment revealed complete identity for the deduced amino acid sequences of human and porcine BDNF [amino acid (aa) 10-108 of the mature factor]. Thus, human platelets might provide an important source of BDNF for regenerating peripheral sensory neurons at the site of nerve injury.
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PMID:Human platelets contain brain-derived neurotrophic factor. 223 Sep 38

Chemoreceptor neurons innervating the rat carotid body were used as a model system to define target regulation of visceral sensory development in fetal and newborn animals. In vitro, chemoafferents were selectively supported by coculture with the carotid body or by treatment with trkB ligands [brain-derived neurotrophic factor (BDNF) and neurotrophin-4], whereas nerve growth factor and neurotrophin 3 had no effect. In vivo, chemoafferent neurons died following carotid body removal at birth, indicating a predominant role of peripheral, rather than central, targets in mediating survival at this stage. However, in the absence of target tissues, a large proportion of carotid body afferents could be rescued by implants containing BDNF. Moreover, BDNF mRNA was detected in the newborn carotid body by reverse transcriptase polymerase chain reaction. These data provide the first demonstration that BDNF can substitute for peripheral target support of sensory neuron survival in vivo and indicate that trkB ligands may be particularly important for development of visceral afferents involved in cardiorespiratory control.
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PMID:BDNF supports mammalian chemoafferent neurons in vitro and following peripheral target removal in vivo. 781 97

The nerve growth factor (NGF) family of neurotrophins exerts effects by binding to products of the trk family of proto-oncogenes. We examined the expression of both trk and neurotrophin mRNA during the entire range of development of quail dorsal root ganglia (DRG) and sympathetic ganglia (SG) using in situ hybridization and reverse transcriptase-polymerase chain reaction (RT-PCR). TrkC mRNA was present in neurons or their precursors from the time of formation of DRG (stage 18, embryonic day 2.5 [E2.5]) and throughout development. The number of labeled cells changed, however, from a majority to a minority at later developmental stages. Expression of trkA mRNA was not detected in DRG until stage 30 (E6) by in situ hybridization, although results with RT-PCR were positive at stage 23 (E3.5). Labeling was always detected on a majority of neurons or their precursors. SG exhibited low levels of trkC mRNA during the later stages of development, whereas trkA mRNA was present from stage 34 onward in most neurons. We have also shown that NGF, neurotrophin-3 (NT-3), and brain-derived neurotrophic factor (BDNF) mRNA were present at all stages examined (stages 23 through 45 for DRG, stages 35-36 and 45 for SG). In DRG, NGF mRNA expression was limited to support cells, whereas NT-3 and BDNF mRNA were detected in both neurons and support cells. These results suggest that neurotrophins could serve a local function in developing ganglia, which can be correlated with the presence of their respective receptors.
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PMID:Expression of trk and neurotrophin mRNA in dorsal root and sympathetic ganglia of the quail during development. 786 Nov 16

The precursor cells that form the enteric nervous system (ENS) are multipotent when they arrive in the gut from the neural crest. Their differentiation thus depends on signals from the enteric microenvironment. Crest-derived cells were isolated from the fetal rat bowel by immunoselection at E14 with NC-1/HNK-1 antibodies and secondary antibodies coupled to magnetic beads. NC-1/HNK-1-immunoreactive cells were enriched approximately 36-fold. The NC-1/HNK-1-selected population and the residual population were plated at equal cell density and maintained in a defined medium for 6-7 d. The total number of cells found in the cultures of the residual cells was three- to fourfold that in cultures of immunoselected cells. Neurotrophin-3 (NT-3), but not nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), or neurotrophin-4/5 (NT-4/5), was found to increase the proportion of neurons (neurofilament-immunoreactive or neuron-specific enolase-immunoreactive) or glia (S-100-immunoreactive) (from 6.6 +/- 0.9% to 15.2 +/- 1.4%; p < 0.001). This effect was concentration dependent (from 1 to 40 ng/ml) and observed only in the cultures of immunoselected cells. NT-3 also enhanced neurite outgrowth. NT-3 increased neither cell number nor bromodeoxyuridine incorporation and thus was not mitogenic. Exposure of immunoselected cells to NT-3 rapidly and transiently induced the appearance of nuclear Fos immunoreactivity. Transcripts coding for TrkC, the transducing receptor for NT-3, were identified in the fetal rat gut (E14-E16) and in the immunoselected population of cells using reverse transcriptase and the polymerase chain reaction. It is concluded that NT-3 specifically promotes the differentiation of enteric crest-derived cells as neurons or glia and may thus play a role in the development and/or maintenance of the ENS.
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PMID:Neurotrophin-3 induces neural crest-derived cells from fetal rat gut to develop in vitro as neurons or glia. 796 61

Nerve growth factor causes mediator release from rat peritoneal mass cells in the presence of lysophosphatidylserine. We have investigated the neurotrophin and receptor specificity involved in this response. Nerve growth factor produced a dose-dependent release of [14C]serotonin in the presence of lysophosphatidylserine with an EC50 of approximately 1 nM. Incubation with brain-derived neurotrophic factor and neurotrophin-3 did not produce a response. Northern blot analysis with probes for low affinity nerve growth factor receptor (p75), trkA, trkB, and trkC demonstrated a detectable signal for trkA only. Western blots of trkA immunoprecipitates from mast cell culture lysates, probed with anti-phosphotyrosine antibodies, demonstrated expression of functional TrkA protein. To determine whether p75, trkB, or trkC mRNA was present in amounts below the limit of detection for Northern analysis, a sensitive reverse transcriptase polymerase chain reaction protocol was used; again rat peritoneal mast cells demonstrated only trkA. The predominant form of trkA message expressed in rat peritoneal mast cells was smaller than the neuronal form. An 18-nucleotide exon (coding for 6 amino acids in the extracellular domain) in the neuronal message was not found in the predominant mast cell trkA message. PC12 cells, a rat pheochromocytoma cell line, and dissociated rat sympathetic neurons showed both trkA and p75, but not trkB or trkC. Anterior pituitary expressed both trkB and trkC, but not trkA. To confirm the lack of expression of p75 on mast cells, 125I-nerve growth factor was chemically cross-linked to mast cells or PC12 cells and then immunoprecipitated with a monoclonal antibody specific for p75, 192-IgG; no p75 was detected. Thus, mediator release from rat peritoneal mast cells by nerve growth factor was specific and not a general property of neurotrophins, and the response was modulated through the trkA proto-oncogene. To our knowledge, this is the first description of a bone marrow-derived cell type that expresses trkA at both the mRNA and protein levels. These data provide further evidence that p75 is not necessary for nerve growth factor signal transduction.
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PMID:Mediator release from mast cells by nerve growth factor. Neurotrophin specificity and receptor mediation. 832 66

The neurotrophin tyrosine kinase receptors trkA, trkB, and trkC have been isolated and sequenced from several mammalian species. Their cognate ligands nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT-4), and neurotrophin-3 (NT-3) act as survival and trophic factors for neurons in the peripheral nervous system (PNS). In this study we have focused on the isolation and expression of the chicken trkA homologue. In addition to a near full-length cDNA sequence described, including an extracellular six amino-acid motif earlier found in neuronal TrkA in human and rat, a novel insert of 150 base pairs (bp) between subdomains IX and X in the otherwise well-conserved intracellular kinase domain is reported. Phylogenetic analysis showed the relationship between chicken trkA and the mammalian trkA receptors. Comparisons of the extracellular domains showed some amino-acid motifs of putative NGF binding function to be well conserved in chicken TrkA. The early expression of trkA mRNA, including the alternatively spliced insert form, was localized by in situ hybridization. As early as embryonal day 3 (E3), trkA mRNA is expressed in the condensing dorsal root ganglia, and at E4 distinct trkA mRNA expression appears in the primary sympathetic chain ganglia. Finally, using a reverse transcriptase-polymerase chain reaction (RT-PCR) approach, we found that among several tested growth factors only fibroblast growth factor-2 (FGF-2) upregulated trkA mRNA expression in E9 sympathetic ganglion explants. This upregulation of trkA was corroborated by subsequent NGF-stimulated fiber outgrowth.
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PMID:Molecular cloning of the chicken trkA and its expression in early peripheral ganglia. 889 7

Application of neurotrophic factors (NFs) to the cut stump of motor nerves of neonatal rats confers neuroprotection from trauma-induced neuronal death. To test whether motoneurons are capable of responding to endogenously produced NFs, facial motoneurons were genetically modified in vivo to express several NFs and then tested for their response to peripheral nerve damage. Replication-defective adenoviral vectors [Adv. Rous sarcoma virus (RSV)-nf] representing three families of NFs were constructed that carried genes for brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), glial cell-derived neurotrophic factor (GDNF), and nerve growth factor. Media from cultured cells transduced with Adv. RSV-nf contained NFs that supported the survival of cultured chick sensory neurons in the same manner as recombinant NF standards. When Adv.RSV-nf or an adenoviral vector containing the beta-galactosidase gene (Adv.RSV-beta-gal) were injected into the facial muscles of neonatal rats the vectors were retrogradely transported to the facial nucleus where the NFs or beta-gal were expressed. A fraction (approximately 10%) of the neurons were transduced as demonstrated by reverse transcriptase-PCR, histochemistry, and immunocytochemistry. In the case of Adv.RSV-BDNF, Adv.RSV-CNTF, and Adv.RSV-GDNF, a significant portion of the facial nucleus neurons was protected, 16.5, 18.2, and 53.3%, respectively, from death after axotomy, showing that neurons are capable of transporting the Adv. RSV-nf, expressing the recombinant NF genes, and responding to the NFs. In the case of Adv.RSV-GDNF, a greater number of facial nucleus motoneurons survived than were transduced, indicating that neighboring untransduced neurons were protected by the GDNF expressed by the transduced neurons by a paracrine mechanism.
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PMID:Targeted transduction of CNS neurons with adenoviral vectors carrying neurotrophic factor genes confers neuroprotection that exceeds the transduced population. 925 62

Expression of neurotrophins in pure microglia cultured from embryonic rat brain and the effects of lipopolysaccharide (LPS) on the expression were investigated. In untreated cultures, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin (NT)-4/5 mRNAs were detected by use of reverse transcriptase-polymerase chain reaction but NT-3 mRNA was not. LPS stimulation caused a marked increase in BDNF mRNA expression in addition to a slight increment of the NT-4/5 mRNA level; however, the NGF mRNA level was not affected. LPS also increased BDNF-like immunoreactivity in cultured microglia, an action consistent with an elevation of BDNF mRNA. These results demonstrate that LPS stimulates synthesis of BDNF and probably NT-4/5, specific ligands for tyrosine kinase receptor TrkB, suggesting that activated microglia, which appear in the damaged brain, participate in neuronal regeneration via production of such neurotrophins.
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PMID:Lipopolysaccharide enhances synthesis of brain-derived neurotrophic factor in cultured rat microglia. 945 17

In a previous study we have shown that a subpopulation of primary sensory neurons contain brain-derived neurotrophic factor immunoreactivity. In the present study we investigated the distribution of brain-derived neurotrophic factor and its mRNA in cranial and spinal ganglia at different segmental levels, using immunohistochemical and quantitative reverse transcriptase-polymerase chain reaction techniques. Our results show that there is no significant difference in the percentage of brain-derived neurotrophic factor-immunoreactive neurons in spinal ganglia of different segmental levels. In contrast, more brain-derived neurotrophic factor-immunoreactive neurons were found in placode-derived than neural crest-derived ganglia. The percentage of brain-derived neurotrophic factor-immunoreactive neurons is consistent with the percentage of neurons lost after deletion of brain-derived neurotrophic factor or trkB genes. However, there is no correlation between brain-derived neurotrophic factor mRNA levels and the number of brain-derived neurotrophic factor immunoreactive neurons in these ganglia, suggesting that some neurons synthesize brain-derived neurotrophic factor while others accumulate the factor following its retrograde transport within nerve fibers. In particular, the proportion of brain-derived neurotrophic factor that is derived from extraganglionic sources in the placode-derived ganglia appears greater than that in the neural crest-derived ganglia.
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PMID:Distribution of brain-derived neurotrophic factor in cranial and spinal ganglia. 945 33


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