Brain-derived neurotrophic factor suppresses programmed death of cerebellar granule cells through a posttranslational mechanism

1997 ◽  
Vol 30 (1-2) ◽  
pp. 101-124 ◽  
Author(s):  
Kazuhiko Suzuki ◽  
Tatsuro Koike
Keyword(s):  
Neurotrophic Factor ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Brain Derived Neurotrophic Factor ◽  
Cerebellar Granule ◽  
Programmed Death

scholarly journals Gangliosides Activate Trk Receptors by Inducing the Release of Neurotrophins

2002 ◽  
Vol 277 (51) ◽  
pp. 49466-49472 ◽  
Author(s):  
Stuart J. Rabin ◽  
Alessia Bachis ◽  
Italo Mocchetti
Keyword(s):  
Neurotrophic Factor ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Tumor Necrosis Factor Receptor ◽  
Brain Derived Neurotrophic Factor ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Scatchard Analysis ◽  
Trk Receptors ◽  
Neurotrophin 3

We used NIH-3T3 fibroblasts expressing the different Trk receptors to examine whether GM1 ganglioside and its semisynthetic derivative LIGA20 activate various neurotrophin receptors. GM1 induced autophosphorylation of TrkC more potently than TrkA or TrkB receptors. In contrast, LIGA20 activated TrkB tyrosine phosphorylation only. Therefore, Scatchard analysis was performed to determine whether GM1 binds to TrkC. GM1 failed to displace neurotrophin-3 binding, suggesting that this ganglioside does not act as a ligand for Trk receptors. In addition, GM1 failed to induce autophosphorylation of a chimeric receptor consisting of the extracellular domain of the tumor necrosis factor receptor and the intracellular domain of TrkA, suggesting that GM1 does not affect the tyrosine kinase domain. We next determined whether GM1 induces the release of neurotrophins from fibroblast cells. GM1 induced a rapid and significant increase in the amount of neurotrophin-3, but not other neurotrophins. This effect was independent of the presence of Trk because K252a did not prevent GM1-mediated release of neurotrophin-3. Moreover, GM1-mediated TrkC autophosphorylation was blocked by TrkC-IgG (but not TrkB-IgG) receptor bodies, further suggesting that GM1 activates TrkC by inducing the release of neurotrophin-3. This hypothesis was also tested in cultured cerebellar granule cells. GM1 induced neurotrophin-3 (but not brain-derived neurotrophic factor or nerve growth factor) release. In contrast, LIGA20 increased the secretion of brain-derived neurotrophic factor. Our data show that gangliosides may activate different Trk receptors by differentially affecting the release of neurotrophins.

scholarly journals Cytoarchitecture and brain-derived neurotrophic factor immunolocalisation in the cerebellar cortex of African grasscutter (Thryonomys Swinderianus)

2016 ◽  
Vol 33 (03) ◽  
pp. 146-154 ◽  
Author(s):  
C. Ibe ◽  
S. Ojo ◽  
S. Salami ◽  
J. Ayo ◽  
U. Nlebedum ◽  
...  
Keyword(s):  
Cerebellar Cortex ◽  
Neurotrophic Factor ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Brain Derived Neurotrophic Factor ◽  
Granule Cell Layer ◽  
Germinal Layer ◽  
Anterograde Axonal Transport ◽  
Similar Report ◽  
Purkinje Neurones

Abstract Introduction: The study described the lamina organization and immunolocalisation of brain-derived neurotrophic factor in the cerebellar cortex of the African grasscutter, at defined postnatal periods. Materials and Method: Brain samples extracted from African grasscutter neonates on postnatal day 3, juveniles on postnatal day 72 and adults on postnatal day 450 were prepared for routine histology and immunohistochemistry, using antibody specific to brain-derived neurotrophic factor. Results: On postnatal day 3, all the laminae typical of the concentric lamina organisation of the mammalian cerebellar cortex were evident, but, and external germinal layer was also observed. On postnatal day 72, and thereafter, the external germinal layer was no more evident. On postnatal day 3, the tree-like arrangement (Arbor vitae) of the cerebellum was not very striking, as the interlobular fissures were incomplete. On postnatal day 72, the Arbor vitae were better presented, as more lobules had been completely separated by interlobular fissures; although, there were some incompletely separated lobules, presented with interlobular fissural lines. On postnatal day 450, the lobules were distinct as the interlobular fissures separated all the vermal and hemispheric lobules. In all the postnatal periods, the granule cell layer was the most populated, while the Purkinje layer was a single cell line of Purkinje neurones. At all postnatal periods, strong immunoreactivity to brain-derived neurotrophic factor was observed in the Purkinje layer; the cell bodies and dendrites of all Purkinje neurones were immunoreactive; while the nuclei in neonate Purkinje neurons where not immunoreactive, the nuclei in the adults were immunoreactive. The cerebellar granule cells were not brain-derived neurotrophic factor immunoreactive, suggestive of their non-synthesis or loss of the synthesized protein, by anterograde axonal transport, to paracrine function. Conclusion: These findings and others were related to some behaviours of the African grasscutter, and compared with similar report in other rodents.

scholarly journals Transgenic Brain-Derived Neurotrophic Factor Modulates a Developing Cerebellar Inhibitory Synapse

1999 ◽  
Vol 6 (3) ◽  
pp. 276-283
Author(s):  
Shaowen Bao ◽  
Lu Chen ◽  
Xiaoxi Qiao ◽  
Richard F. Thompson
Keyword(s):  
Transgenic Mouse ◽  
Neurotrophic Factor ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Wild Type Mouse ◽  
Brain Derived Neurotrophic Factor ◽  
Brain Regions ◽  
Inhibitory Synapses ◽  
Gabaergic Synapse ◽  
Subunit Expression

Brain-derived neurotrophic factor (BDNF) has been shown to promote synapse formation and maturation in neurons of many brain regions, including inhibitory synapses. In the cerebellum, the Golgi cell-granule cell GABAergic synaptic responses undergo developmental transition from slow-decaying to fast-decaying kinetics, which parallels a developmental increase of GABAAreceptor α6 subunit expression in the cerebellar granule cells. In culture, BDNF accelerates the expression of GABAA receptor α6 subunit expression in granule cells. Here we examined synaptic GABAA response kinetics in BDNF transgenic mice. The mutant mouse, which carries a BDNF transgene driven by a β-actin promoter, overexpresses BDNF (two- to fivefold increase compared with wild types) in all brain regions. Recordings of the spontaneous GABAA responses indicate that the decay time constant of the GABAergic responses decreases during early postnatal development; this transition is accelerated in the BDNF transgenic mouse. The amplitude of the spontaneous GABAA responses was also larger in the transgenic mouse than in the wild-type mouse. However, the frequency of the spontaneous GABAA responses were not different between the two groups. Our results suggest that BDNF may modulate GABAergic synapse maturation in the cerebellum.

Sign in / Sign up

Export Citation Format

Share Document