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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tissue responses to injury are regulated by neurotrophins and neurotrophin receptor levels and can involve both retrograde and paracrine/autocrine trophic signaling. To determine how neurotrophins may contribute to the injury response, the timing and the extent of the up-regulation of neurotrophins and their receptors was examined in a model system which is particularly well suited for the analysis of trophic signaling pathways in response to injury. Injury to the occlusal surfaces of rat molar cusps induces a localized increase in nerve growth factor (NGF) expression in the dental pulp within 4-6 h. Radiolabeled NGF was transported in a receptor-mediated fashion from the teeth to a subset of neurons in the trigeminal ganglion within 15 h, indicating that these neurons possess NGF receptors (trk A and/or p75NTR). To test for NGF responses in the tooth sensory afferent neurons, levels of expression of neurotrophins and their receptors were examined by in situ hybridization in the trigeminal ganglion at 0, 4, 12, 20, 28 and 52 h post-injury. Within the maxillary division of the trigeminal ganglion, trk A expression was elevated at 4 h post-injury, with a maximum increase (2-fold) after 52 h. p75NTR was increased by 28 h post-injury and was increased 1.35-fold by 52 h. BDNF mRNA was increased 12 h after injury (1.8-fold), and 2.5-3-fold at 52 h post-injury. The trk B expression was increased only late after injury (28 and 52 h). To determine the receptor/neurotrophin phenotype of trigeminal neurons with projections to the molar teeth, these neurons were double-labeled with the retrograde tracer fluoro-gold and probes for either BDNF or trk B. The results show that tooth-innervating trigeminal neurons express BDNF, but not trk B. The timing of mRNA expression after injury and the phenotype of identified trigeminal neurons suggests a complex signaling cascade in which NGF at the injury site regulates NGF receptor expression at the levels of the cell body as well as increases in BDNF expression. Upregulated BDNF may act in a paracrine fashion on neighboring trigeminal cells expressing trk B. This signaling cascade may be a common feature of the response to mild peripheral inflammatory injuries within nociceptive pathways.
Brain Res Mol Brain Res 1998 Oct 30
PMID:Neurotrophin receptor expression is induced in a subpopulation of trigeminal neurons that label by retrograde transport of NGF or fluoro-gold following tooth injury. 979 12

Previous results from our laboratory indicate that two nights of voluntary wheel running upregulates brain-derived neurotrophic factor (BDNF) mRNA expression in the hippocampus. In order to investigate the time-course of the BDNF response and to examine how physical activity preferentially activates particular transcriptional pathways, the effects of 6 and 12 h of voluntary wheel running on BDNF and exons I-IV mRNA expression were investigated in rats. Hippocampal full-length BDNF mRNA expression was rapidly influenced by physical activity, showing significant increases in expression levels as soon as 6 h of voluntary wheel running. Moreover, there was a strong positive correlation between distance run and BDNF mRNA expression. Exon I mRNA expression was significantly upregulated after 6 h of running and was maintained or enhanced by 12 h of voluntary running. Exon II had a slower time-course and was significantly upregulated after 12 h, selectively in the CA1 hippocampal region. Exon III and Exon IV showed no significant increase in expression level after 6 or 12 h of running in the paradigm studied. It is significant that the rapid neurotrophin response is demonstrated for a physiologically relevant stimulus, as opposed to the extreme conditions of seizure paradigms. Furthermore, exercise-induced upregulation of BDNF may help increase the brain's resistance to damage and neurodegeneration that occurs with aging.
Brain Res Mol Brain Res 1998 Oct 30
PMID:Exercise-induced regulation of brain-derived neurotrophic factor (BDNF) transcripts in the rat hippocampus. 979 93

Epithelial expression of the 75-kDa low-affinity neurotrophin receptor (p75NTR) is inversely associated with the malignant progression of the human prostate. To elucidate the function of p75NTR in the prostate, the human prostate epithelial tumor cell line TSU-pr1, which does not express p75NTR, was stably and transiently transfected with the cDNA for the receptor. The stably transfected cells were assessed for levels of p75NTR expression and categorized into low, intermediate, and high receptor-expressing clones by immunocytochemical and immunoblot analyses. Incorporation of [3H]thymidine was used to assess nerve growth factor (NGF)-induced changes in cell proliferation. TSU-pr1 epithelial cells transfected with a neomycin-resistance vector alone demonstrated a dose-dependent increase in the rate of NGF-stimulated [3H]thymidine uptake. Expression of p75NTR decreased the dose-dependent NGF-mediated proliferation of the TSU-pr1 prostate epithelial cells. The greater the degree of expression of p75NTR in the transfected clones, the less the stimulatory effect of exogenous NGF on cell proliferation. Furthermore, the ratio of p75NTR to tropomyosin receptor kinase for each clone was inversely correlated with the ability of NGF to stimulate growth of the TSU-pr1 transfectants. To determine whether p75NTR-mediated growth inhibition of prostate epithelia occurs by induction of programmed cell death, transiently transfected clones were analyzed by an in situ DNA nick-translation assay. NGF deprivation and anti-NGF treatment of transiently transfected TSU-pr1 cells significantly increased the proportion of epithelial cells undergoing programmed cell death by approximately fourfold above control levels. Conversely, addition of NGF was able to rescue p75NTR-expressing clones from undergoing programmed cell death at levels not significantly different from those of mock-transfected clones. These results demonstrate that p75NTR is a negative regulator of human prostate epithelial cell growth by induction of programmed cell death. Hence, loss of p75NTR expression in human prostate epithelia eliminates a growth-inhibitory pathway, thereby contributing to the malignant progression of the prostate.
Mol Carcinog 1998 Oct
PMID:Expression of p75NTR in a human prostate epithelial tumor cell line reduces nerve growth factor-induced cell growth by activation of programmed cell death. 980 64

The expression of the mRNAs of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and the neurotrophin receptor, TrkB, was studied in the rat hippocampus by in situ hybridization following normothermic (37 degreesC) and protective hypothermic (33 degreesC) transient cerebral ischemia of 15 min duration. In the resistant dentate gyrus, normothermic ischemia transiently induced NGF mRNA at around 8 h of recovery, while the NT3 mRNA levels were depressed over at least a 24-h recovery period. The levels of BDNF and TrkB were transiently and markedly elevated with a maximal expression at 24 h of recovery. Intraischemic hypothermia reduced the induction of NGF mRNA, while the increase of BDNF mRNA expression occurred earlier during recovery, and the post-ischemic NT3 mRNA depression was not affected. Also, the expression of TrkB mRNA was enhanced, and occurred concomitantly with the elevation of BDNF mRNA. In contrast, there were no changes in neurotrophin and TrkB mRNA in the CA3 and CA1 regions. The expression of BDNF mRNA at 24 h after normothermic ischemia, was attenuated by intraischemic hypothermia. We conclude that, the expressions of NGF, BDNF, NT3 or TrkB mRNA in ischemia-sensitive hippocampal subregions are not increased by protective hypothermia. In contrast, hypothermia induces neurotrophin mRNA alterations in the ischemia-resistant dentate gyrus that may convey protection to sensitive regions.
Brain Res Mol Brain Res 1998 Dec 10
PMID:The effect of hypothermia on the expression of neurotrophin mRNA in the hippocampus following transient cerebral ischemia in the rat. 983 92

Neurotrophins have specificity toward distinct subpopulations of dorsal root ganglion (DRG) neurons with different neurotrophin receptors. It has been suggested that neurotrophins also play important roles in mature DRG neurons after injury. In the present study, we examined the expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 (NT-3) mRNAs in the DRG after a peripheral nerve injury. The data showed that following a spinal nerve ligation, the level of NGF mRNA increased 4 times over the normal level and was maintained at a high level for a period of 3 weeks. The induction of BDNF mRNA was brief (lasting less than 3 days) and lesser in quantity ( approximately 1. 7 times increase) compared to NGF expression. The expression of NT-3 mRNA was not detected either in normal or nerve injured rats. Results suggest that different neurotrophins play different functional roles in the DRG after spinal nerve injury.
Brain Res Mol Brain Res 1999 Feb 05
PMID:Expression of neurotrophin mRNAs in the dorsal root ganglion after spinal nerve injury. 993 85

We analyzed the distribution of mRNAs encoding the low-affinity neurotrophin receptor (p75) in the CNS of adult and neonatal opossum (Monodelphis demestica) by in situ hybridization with oligodeoxynucleotide probes complementary to cloned rat sequences. During the first 2 postnatal weeks high levels of p75 message were present in the mantle zone throughout the neural tube, in basal forebrain neurons, in motoneurons, and in cerebellar cell layers. Transcript expression decreased with age. In adult CNS only a few cells in the basal forebrain expressed high levels of p75 mRNA. Nerve growth factor upregulated p75 mRNA signals in dorsal root ganglia of cultured 7 day old whole-CNS preparations. Our results indicate the usefulness of rat p75 oligodexynucleotide probes to identify homologous species of transcripts in the CNS of a non-eutherian mammal.
Brain Res Mol Brain Res 1999 Feb 19
PMID:Detection of p75 mRNA in developing marsupial CNS by cross-hybridization with rat oligonucleotide probes. 1003 15

We examined the distribution of the high affinity neurotrophin receptors (trkA, trkB, and trkC) in the rat geniculate ganglion. Previous work had shown that during early (prenatal) development, trkB and its two ligands, BDNF and NT-4/5, were most important for survival of almost all neurons. Using nested polymerase chain reaction (PCR), we showed that trkA, trkB, and trkC transcripts were expressed, and the mRNAs for trkB and trkC were more abundant than that for trkA. We modified and improved the method for direct reverse transcription in situ PCR and localized trkB mRNA in approximately one third of the neurons in the ganglion. Immunohistochemical data confirmed that approximately the same fraction of neurons was immunoreactive with antibody vs. trkB, and an approximately equal fraction was immunoreactive with trkC antibody. These results are consistent with the notion that both BDNF/trkB and NT-3/trkC play important roles in maintenance of the geniculate ganglion neurons and possibly the peripheral taste system in the young postnatal rat.
Brain Res Mol Brain Res 1999 May 07
PMID:Neurotrophin receptors in the geniculate ganglion. 1032 Jul 78

In the present work, we examined the time-dependent changes in trkA, trkB and trkC mRNA levels induced by the injection of glutamate receptor agonists into the striatum. Changes in trk mRNAs induced by quinolinate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), kainate or 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) were analyzed by a ribonuclease protection assay. All high-affinity neurotrophin receptors showed differential regulation after intrastriatal injury. Up-regulation of trkA expression was observed in kainate- or ACPD-injected striata at 10 and 24 h, respectively, whereas quinolinate injection induced down-regulation between 4 and 6 h after injury. Interestingly, all the excitatory amino acid receptor agonists induced up-regulation of trkB-kinase mRNA levels. This increase was maximal between 2 and 4 h after injection except in kainate injected striata, which showed the peak of expression at 10 h. In contrast, no changes in trkC mRNA expression were observed after striatal excitotoxic injury. In conclusion, our results show that trk receptor mRNA levels are differentially regulated by excitatory amino acid receptor agonists in the striatum, suggesting that changes in the levels of neurotrophin receptors might be involved either in synaptic plasticity processes or in neuronal protection in the striatal excitotoxic paradigm.
Brain Res Mol Brain Res 1999 Jun 08
PMID:The neurotrophin receptors trkA, trkB and trkC are differentially regulated after excitotoxic lesion in rat striatum. 1036 45

Our recent studies revealed that brain-derived neurotrophic factor (BDNF) rapidly enhances tyrosine phosphorylation and dephosphorylation of the NMDA receptor subunit, NR2B, in the postsynaptic density (PSD), potentially regulating synaptic plasticity. To explore the molecular mechanisms underlying synaptic NR2B signaling, we examined the protein tyrosine phosphatase, PTP1D; BDNF reportedly increases association of PTP1D with tyrosine phosphorylated proteins in cortical neurons and PC 12 cells. We now report that PTP1D is an intrinsic component of the rat cerebrocortical PSD, based on Western blot analysis using specific anti-PTP1D antibodies. In addition, NR2B was co-immunoprecipitated with PTP1D using anti-NR2B antibodies or anti-PTP1D antibodies, indicating physical association of the subunit with PTP1D. Moreover, treatment of the purified PSD with BDNF for 5 min elicited a two-fold increase in the association of NR2B with PTP1D. The BDNF action appeared to be specific, since nerve growth factor, another member of the neurotrophin gene family, did not alter the association. Finally, an overlay assay revealed that BDNF caused a two-fold increase in binding of blotted PSD NR2B proteins to PTP1D-SH2 domains, revealing molecular mechanisms mediating the PTP1D-NR2B binding. Taken together, our results raise the possibility that PTP1D participates in BDNF-mediated NR2B signaling cascades at the postsynaptic site, thereby regulating synaptic plasticity.
Brain Res Mol Brain Res 1999 Jun 18
PMID:Brain-derived neurotrophic factor enhances association of protein tyrosine phosphatase PTP1D with the NMDA receptor subunit NR2B in the cortical postsynaptic density. 1038 39

Vascular endothelial cells are among the first cells that ventricular zone neuroblasts encounter during early development. The ventricular zone cells promote angiogenesis by the invading vasculature, with the release of endothelial mitogens. Yet the feedback support of young neurons by endothelial cells (ECs) has not hitherto been explored. We therefore asked whether ECs might participate in neuronal recruitment, by providing neurotrophic support to newly generated neurons. We used the neurogenic subependymal zone (SZ) of the adult rat forebrain as a model system, because of its well-characterized and relatively homogeneous population of neuronal precursor cells. We found that explants of the adult rat SZ raised on ECs generated more neurons, which survived longer, than explants raised on astrocytes, fibroblasts, or laminin. This endothelial trophic effect was humoral, in that it was also noted in SZ explants raised in noncontiguous coculture with ECs grown on porous inserts. RT-PCR for neurotrophin family members revealed that cultures of both human brain- and umbilical cord-derived ECs produced brain-derived neurotrophic factor (BDNF) mRNA, but no detectable NGF, NT-3, or NT-4 mRNA. ELISA revealed that BDNF protein was secreted by ECs into the medium at >1 ng/ml. The neurotrophic effect of ECs could be replaced by added BDNF, and was blocked by addition of 5 microg/ml trkB-Fc to endothelial-SZ cocultures. Thus, endothelial cells can act as sources of secreted BDNF, through which the capillary microvasculature may act to support neuronal recruitment and survival in the CNS.
Mol Cell Neurosci 1999 Jun
PMID:Endothelial trophic support of neuronal production and recruitment from the adult mammalian subependyma. 1038 30


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