Disease relevance of Ntf5

• Thus, NT-4/5 may have therapeutic value in preventing hearing impairment caused by damage to primary auditory afferent neurons [1].
• Messenger RNA for trkB, the high-affinity receptor for BDNF and neurotrophin-4 (NT-4), was increased between 3 and 6 h bilaterally in the dentate gyrus following a lateral fluid-percussion brain injury of moderate severity (2.0-2.1 atm) [2].
• Sequestration of endogenous BDNF/neurotrophin 4 by intraspinal TrkB-Fc fusion protein administration does not, in noninflamed animals, change basal pain sensitivity nor the mechanical hypersensitivity induced by peripheral capsaicin administration, a measure of C fiber-mediated central sensitization [3].
• We investigated the retrograde axonal transport of 125I-labeled neurotrophins (NGF, BDNF, NT-3, and NT-4) from the sciatic nerve to dorsal root ganglion (DRG) sensory neurons and spinal motor neurons in normal rats or after neuronal injury [4].
• Prompted by a previous uinexpected finding that NT-4/5, as well as NGF sensitizes single nociceptors to noxious heat, we have explored the relative potency of all neurotrophins in eliciting thermal hyperalgesia [5].

Psychiatry related information on Ntf5

• 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].
• NT-4/5 was only effective at the onset, but no longer at the peak of the critical period suggesting a switch in neurotrophin dependency for these cortical cell classes [7].

High impact information on Ntf5

• We found that BDNF and neurotrophin-4/5 depolarized neurons just as rapidly as the neurotransmitter glutamate, even at a more than thousand-fold lower concentration [8].
• Muscle-derived neurotrophin-4 as an activity-dependent trophic signal for adult motor neurons [9].
• The production of neurotrophin-4 (NT-4) in rat skeletal muscle was found to depend on muscle activity [9].
• NT-4 immunoreactivity was detected in slow, type I muscle fibers [9].
• 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 [10].

Chemical compound and disease context of Ntf5

• Like NGF, agonists of tyrosine kinaseB (trkB) receptors (NT-4/5 and BDN F) induced thermal hyperalgesia in the first 5 h after treatment (NT-4/5 > BDNF) but the effect had worn off by 24 h [5].
• Neuronal vulnerability to glutamate toxicity was significantly reduced in cultures pretreated with NT-4/5 [11].
• Our data show that NT-4 completely prevents malonate-induced toxicity, whereas BDNF or NT-3 had no neuroprotective effect [12].
• Moreover, neurons pretreated with NT-4/5 were more resistant to toxicity induced by calcium ionophore A23187, demonstrating that NT-4/5 increases neuronal resistance to calcium-mediated injury [11].
• These findings reveal a new population of striatal cells, calretinin neurons, that are relatively resistant to quinolinic acid toxicity and that neurotrophin-4/5 and transforming growth factor-alpha partially protect against the phenotypic degeneration of striatal cell populations in an in vivo animal model of Huntington's disease [13].

Biological context of Ntf5

• NT-4 protein is shown to elicit neurite outgrowth from explanted embryonic trigeminal ganglia and to promote neuronal survival of dissociated trigeminal ganglion neurons when cultured during the phase of cell death [14].
• Brain-derived neurotrophic factor and neurotrophin-4/5 modify neurotransmitter-related gene expression in the 6-hydroxydopamine-lesioned rat striatum [15].
• Furthermore, NT4 transfection of one explant of axonally connected corticocortical cocultures evoked significantly larger numbers of NPY neurons in both explants [16].
• The neurotrophins BDNF, NT-3 and NT-4/5, but not NGF, up-regulate the cholinergic phenotype of developing motor neurons [17].
• In contrast, with BDNF or NT4 repetitive action potential trains were not observed [18].

Anatomical context of Ntf5

• Levels of NT-4 mRNA in the whisker pad decrease between embryonic day 13 (E13) and E20, correlating in time with the onset of naturally occurring neuronal death in the innervating trigeminal ganglion [14].
• The nucleus contained NT3 and cytosol contained NT4 [19].
• The cytoplasm of conjunctival stratified squamous cells and goblet cell lateral membranes contained NGF, BDNF, and NT4 [19].
• BDNF and NT-4 differentiate two pathways in the modulation of neuropeptide protein levels in postnatal hippocampal interneurons [20].
• Among the other factors tested, we also found that NT-4 and GDNF increased the number of surviving neurons in a dose-dependent manner, whereas NGF, BDNF and NT-3 showed no survival promoting effect on corticospinal motor neurons [21].

Associations of Ntf5 with chemical compounds

• In contrast to BDNF, the action of NT4 was independent of calcium influx through NMDA receptors and L-type calcium channels [16].
• NT-4/5 treatment elicited the greatest increase (7-fold) in the number of TH-positive neurons, as well as a 2.6-fold increase in dopamine content [22].
• BDNF, NT-3, or NT-4/5 also produced dose-dependent elevations of 2-3-fold in GABA uptake activity [22].
• Neurotrophin-4/5 enhances survival of cultured spiral ganglion neurons and protects them from cisplatin neurotoxicity [1].
• BDNF and NT-4/5 also circumvented glutamate-induced oxidative death in DIV 1-2 granule neurons [23].

Physical interactions of Ntf5

• A rapid activation of TrkB (1-8 h) was also observed in the spinal cord after axotomy,while the amount of TrkB co-precipitating with NT-4 was markedly lower after axotomy [24].

Regulatory relationships of Ntf5

• CNTF also enhanced the neurotrophin-4/5-mediated increase of ChAT activity, but not the nerve growth factor (NGF)-mediated one [25].
• Indeed, TrkB-expressing inhibitory SGS neurons responded to cortical NT-4/5 infusion with somatic growth [7].
• In addition, neurotrophin-4 prevented the morphine-induced increase in glial fibrillary acidic protein [26].
• Our findings suggest that subpopulations of cortical GABAergic and calbindin-expressing neurons respond to NT-4/5 during development [27].
• Neurotrophin-4 also influenced the morphology of tyrosine hydroxylase-positive neurons [28].

Other interactions of Ntf5

• Moreover, neurons treated with NT-4/5 display a very high level of NPY mRNA expression in somata and in the dendritic trees [29].
• Neurotrophin-4 (NT-4) and glial cell line-derived neurotrophic factor (GDNF) promote the survival of corticospinal motor neurons of neonatal rats in vitro [21].
• Neurotrophin-4/5 alone also normalized expression of messenger RNA encoding the 67 x 10(3) mol. wt isoform of glutamate decarboxylase, while none of the neurotrophins had a significant effect on preproenkephalin messenger RNA expression.(ABSTRACT TRUNCATED AT 250 WORDS)[15]
• Muscle cells express full-length TrkB, the cognate receptor for BDNF and NT-4 [30].
• Direct activation of this receptor by anti-TrkB antibodies mimicked the BDNF/NT-4 inhibition of agrin-induced AChR clustering [30].

Analytical, diagnostic and therapeutic context of Ntf5

• The cellular localization of mRNA for neurotrophin-4 (NT-4), a novel neurotrophic factor, in the developing whisker follicles and skin of the embryonic rat is demonstrated by in situ hybridization [14].
• Here we report that neurotrophin-4/5 (NT-4/5), a member of the nerve growth factor family, promoted survival of postnatal rat SGNs up to threefold in dissociated cell cultures [1].
• NT-4 and BDNF administered intraocularly at the time of axotomy exert a neuroprotective effect on axotomy-induced RGC death, thus increasing the population of surviving RGCs and delaying the onset of RGC of axotomy-induced RGC death by approximately 3 days [31].
• Effects of brain-derived neurotrophic factor and neurotrophin-4 on isolated cultured retinal ganglion cells: evaluation by flow cytometry [32].
• Intramuscular injections of recombinant NT-4/5 into the SOL muscle of rat neonates significantly accelerated the normal fast-to-slow MyHC isoform transformation [33].

References