Disease relevance of Ntf3

• PNT-1 also promoted survival of a greater number of embryonic dorsal root ganglion neurons than any of the other neurotrophins alone, and its effects were equivalent to a combination of NGF, BDNF, and NT-3 [1].
• BDNF and NT-3 decreased body weights, an effect that was sustained over the infusion period [2].
• BDNF and NT-3 afforded neuronal protection even when administered 8 or 4 h, respectively, after the onset of hypoglycemia [3].
• Epileptiform activity evoked by hippocampal stimulation and exceeding 70 s lead to a concomitant and transient increase of brain- derived neurotrophic factor, nerve growth factor, trkB and trkC messenger RNA expression in dentate granule cells after both focal and generalized seizures [4].
• Endothelins play a role in the regulation of astrocytic functions in brain pathologies such as hyperplasia and neurotrophic factor production [5].

Psychiatry related information on Ntf3

• 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 [6].
• The results show that NT-3, but no other neurotrophin, prevents the degeneration of noradrenergic neurons of the locus coeruleus in a 6-hydroxydopamine lesion model that resembles the pattern of cell loss found in Alzheimer's disease [7].
• Supranigral infusions of BDNF and NT-3 alter circadian rhythms, spontaneous motor activity, body weights, and amphetamine-induced behaviors including locomotion and contraversive rotations [2].
• BDNF and NT3 extend the critical period for developmental climbing fibre plasticity [8].
• Proprioception and mechanoception are lost after gene deletion of neurotrophin-3 or its high-affinity receptor, TrkC [9].

High impact information on Ntf3

• Thus trkB encodes an essential component of a functional receptor for BDNF and NT-3, but not for NGF [10].
• However, both BDNF and NT-3, but not NGF, bind to full-length and truncated forms of a receptor-like tyrosine kinase, trkB, for which no ligand had previously been identified [10].
• The trk tyrosine kinase proto-oncogene product gp140prototrk binds nerve growth factor (NGF) and is rapidly and selectively activated by this neurotrophic factor [11].
• Dorsal horn neurons were found to be synaptically driven by peripheral nerve stimulation in rats treated with NGF, NT3 and GDNF, demonstrating functional reconnection [12].
• Transplantation approaches using cellular bridges, fetal central nervous system cells, fibroblasts expressing neurotrophin-3 (ref. 6), hybridoma cells expressing inhibitory protein-blocking antibodies, or olfactory nerves ensheathing glial cells transplanted into the acutely injured spinal cord have produced axonal regrowth or functional benefits [13].

Chemical compound and disease context of Ntf3

• Here we report on the ability of NT-3 to regulate the expression of the LNGFR in C6 glioma cells [14].
• Here, we identify T lymphoma invasion and metastasis (Tiam) 1 as the Rac1-specific guanine-nucleotide exchange factor involved in NT3-induced Schwann cell migration [15].
• We measured chronic changes in the levels of BDNF, nerve growth factor (NGF) and neurotrophin-3 (NT-3) in the adult hippocampus using enzyme-linked immunosorbent assay (ELISA) after a unilateral intracerebroventricular administration of kainic acid (KA), a model of temporal lobe epilepsy [16].
• PURPOSE: Neuronal cells undergo apoptosis when the supply of neurotrophic factor is limited by injury, trauma, or neurodegenerative disease [17].
• When the ischemic rats were treated with dexamethasone, the elevation of brain-derived neurotrophic factor mRNA and the reduction of neurotrophin-3 mRNA level were prevented within the first 24 hrs, and hippocampal CA1 neurons were protected from ischemia-induced cell loss 7 days after brain ischemia [18].

Biological context of Ntf3

• Saturation binding in embryonic spinal sensory neurons demonstrated a greater number of high-affinity binding sites for PNT-1 than for its parental molecule NT-3 [1].
• In this study, we examined whether the upregulation of neurotrophic factors in reactive astrocytes and cultured astrocytes is a consequence of separation from their neuronal counterparts, and whether neurotrophic factor levels can be regulated by placing astrocytes into coculture with neurons [19].
• Taken together, our results indicate that BDNF and NT-3 have broadly similar effects in promoting the survival and differentiated phenotype of both dopaminergic and GABAergic neurons of the developing substantia nigra [20].
• We show that reintroduction of rat hippocampal neurons to rat hippocampal astrocytes in vitro leads to a time dependent downregulation in astrocytes of the neurotrophic factors CNTF, NGF, and neurotrophin 3 (NT-3) [19].
• NT-3 increased neither cell number nor bromodeoxyuridine incorporation and thus was not mitogenic [21].

Anatomical context of Ntf3

• In the denervated gastrocnemius muscle, the level of BDNF mRNA increased, NT-3 mRNA did not change, while NT-4 mRNA decreased [22].
• In bioassays, BDNF and NT-3, but not NGF, at physiological concentrations induced neurite outgrowth from the statoacoustic ganglion explants [23].
• Brain-derived neurotrophic factor and neurotrophin 3 mRNAs in the peripheral target fields of developing inner ear ganglia [23].
• Development of survival responsiveness to brain-derived neurotrophic factor, neurotrophin 3 and neurotrophin 4/5, but not to nerve growth factor, in cultured motoneurons from chick embryo spinal cord [24].
• NT-3 mRNA expression in the adult rat brain is largely confined to the hippocampus [25].

Associations of Ntf3 with chemical compounds

• The effects of BDNF and NT-3 on dopamine uptake activity showed no additivity [20].
• Changes in neurotrophic factor expression and receptor activation following exposure of hippocampal neuron/astrocyte cocultures to kainic acid [19].
• GAD activity was increased by BDNF (1.8-fold) and NT-3 (threefold) treatment, but not by NT-4/5, whereas GABA content was increased to a similar extent by all three neurotrophins [20].
• The data presented are the first demonstration that one neurotrophin regulates the expression of another and provide evidence that NT-3 production in granule neurons is regulated by both BDNF and T3 [26].
• Tyrosine phosphorylation of phospholipase C-gamma increased rapidly after NT-3, suggesting that this enzyme becomes activated [27].

Enzymatic interactions of Ntf3

• In addition, NT-3 was able to phosphorylate the BDNF receptor, TrkB but only at higher concentration (50 ng/ml) [28].
• However, we found the TrkC receptor constitutively phosphorylated even in the absence of added ligand suggesting an interaction of TrkC with endogenously produced NT-3 [28].
• Tyrosine phosphorylation of the p13 Suc1-associated neurotrophic factor-induced tyrosine-phosphorylated target protein in response to bFGF was strongly inhibited by Shb overexpression, without correlating with the corresponding rate of neurite outgrowth [29].

Regulatory relationships of Ntf3

• Exposure of immunoselected cells to NT-3 rapidly and transiently induced the appearance of nuclear Fos immunoreactivity [21].
• BDNF- and NT-3-induced somatostatin release depended upon extra- and intracellular Ca(2+) since it was completely abolished in the presence of the Ca(2+) chelators BAPTA (bis-(alpha-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid) or BAPTA-AM (bis-(alpha-aminophenoxy)-ethane-N,N,N',N'-tetraacetoxymethylester), respectively [30].
• These results suggest that endothelin is an extracellular signal that stimulates astrocytic neurotrophin-3 production in brain pathologies [5].
• Taken together, these results suggest that NT3 induce NSCs to differentiate into OLPs by enhancing the expression of Olig-1 through an Erk1/2-dependent pathway [31].
• BDNF and NT-3 stimulated neurite outgrowth of calbindin D neurons to a much smaller degree [32].

Other interactions of Ntf3

• Neurotrophin-3: a neurotrophic factor related to NGF and BDNF [33].
• The expression of NT-3 and NT-4 and their receptors in the trigeminal system prior to target field innervation suggests that these NTFs have also other functions than being the target-derived trophic factors [34].
• Inhibitors of ERK activation that block inhibition by NGF had no effect on inhibition by NT-3 [35].
• 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 [21].
• BDNF and synapsin I mRNAs were lower and NT-3 levels were higher in the lumbar hemicord ipsilateral to the BTX-A injection [36].

Analytical, diagnostic and therapeutic context of Ntf3

• In this study, we have used in situ hybridization to examine expression of this novel neurotrophic factor during postnatal development [25].
• Comparable densities were found in groups that underwent axotomy and either sham injection (533+/-51; n=5), injection of vehicle (588+/-19; n=10), or NT-3 treatment (634+/-62; n=6) [37].
• Immunoprecipitation of p21ras from 32P-prelabeled cells showed that NT-3 increased the level of the GTP-bound form of the protein threefold over the control within 5 min [27].
• After a single subcutaneous injection of para-chloroamphetamine (PCA; 9 mg/ml) that lesions the majority of serotonergic axons in the rat cortex, we injected adenoviral vectors containing cDNAs for brain-derived neurotrophic factor (Adv.BDNF), neurotrophin-3 (Adv.NT-3), or nerve growth factor (Adv.NGF) into the rat frontal cortex [38].
• Rapid stimulatory effects of brain-derived neurotrophic factor and neurotrophin-3 on somatostatin release and intracellular calcium rise in primary hypothalamic cell cultures [30].

References