Timing of Neuronal Death following Successive Blockade of Protein Synthesis and Axoplasmic Transport in the Axonal Target Territory

Blaser, P.F.; Clarke, Peter G. H.

doi:10.1159/000111671

Cited by 6 publications

(6 citation statements)

References 19 publications

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“…The second trophic factor must be provided by the target cells and must be retrogradely transported by ION axons. The first explanation is consistent with findings that reduction of protein synthesis at E15 in the retina does not induce cell death in the ION and that a reserve of trophic substances in the retina may sustain the ION for 1 day (Blaser et al, 1991;Blaser and Clarke, 1992). The notion of a second trophic factor is supported by the switch in the ION's response to tetrodotoxin in the retina from increased survival to complete degeneration at about E17 (Péquignot and Clarke, 1992), which appears to coincide with the time point when the ION neurons lose dependence on retrogradely transported BDNF, but now appear to depend on a (second?)…”

Section: Critical Period Of Retrograde Trophic Signaling For the Ionsupporting

confidence: 86%

Target‐derived BDNF (brain‐derived neurotrophic factor) is essential for the survival of developing neurons in the isthmo‐optic nucleus

Bartheld

Johnson

2001

J of Comparative Neurology

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Neurons in the peripheral nervous system depend on single neurotrophic factors, whereas those in the brain are thought to utilize many different trophic factors. This study examined whether some neurons in the brain critically depend on a single trophic factor during development. Neurons in the isthmo-optic nucleus (ION) of chick embryos respond to exogenous brain-derived neurotrophic factor (BDNF). Relatively high concentrations of endogenous BDNF were present in the ION of 14-18-day-old chick embryos. ION target cells in the retina were immunolabeled for BDNF but showed surprisingly low levels of BDNF mRNA. These data suggest that ION target cells derive some BDNF from other retinal sources. No BDNF mRNA was detected in the ION itself. ION neurons had a very efficient retrograde transport system for BDNF and exogenous BDNF arrived in the ION intact. When the ION was deprived of endogenous trkB ligands by injection of trkB fusion proteins in the eye, cell death of ION neurons was enhanced, and this effect was mimicked by BDNF-specific blocking antibodies in the eye. TrkB fusion proteins in the retina induced cell death of ION neurons prior to visible effects on ION target cells in the retina. Immunolabel for endogenous BDNF was sparse in pyknotic ION neurons, suggesting that ION neurons with low BDNF content were eliminated by apoptosis. These data show that BDNF is an essential target-derived trophic factor for developing ION neurons and thereby validate the neurotrophic hypothesis for at least one neuronal population in the brain.

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Section: Critical Period Of Retrograde Trophic Signaling For the Ionsupporting

confidence: 86%

Target‐derived BDNF (brain‐derived neurotrophic factor) is essential for the survival of developing neurons in the isthmo‐optic nucleus

Bartheld

Johnson

2001

J of Comparative Neurology

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“…However, our results cannot have been contaminated by multistage retrograde effects via the isthmo-optic nucleus, because these would occur too late. Intraocular injections of colchicine or TTX in chick embryos take at least 24 hr to produce noticeable effects in the isthmo-optic nucleus (Pequignot and Clarke, 199 1;Blaser and Clarke, 1992) which appeared normal in all of the present embryos.…”

Section: Discussionmentioning

confidence: 66%

Rapid onset of neuronal death induced by blockade of either axoplasmic transport or action potentials in afferent fibers during brain development

1992

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We have investigated how neurons in the optic tecta of embryonic day 16 chick embryos depend for survival on their afferents from the retina. To distinguish between activity-mediated effects and other, "trophic," ones, we compared the effects on the tectal neurons of blocking intraocular axoplasmic transport (with colchicine) or action potentials (by means of TTX). Both interventions rapidly induced the appearance of dying (pyknotic) neurons in the tectum, with major increases in their number occurring within 13 hr post-colchicine and within 9 hr post-TTX. Following both drugs, the dying neurons were morphologically similar, and in both cases the cell death depended on protein synthesis. However, the effects of colchicine and of TTX could be dissociated, since the most superficial tectal neurons became pyknotic only in response to colchicine, and, with a sufficiently short survival time (9 hr), the deep cells of the stratum griseum centrale became pyknotic only in response to TTX. We hence argue that the survival of the tectal neurons depends on their ongoing maintenance by substances released from retinotectal axon terminals, the release being activity dependent in the case of the deep neurons but independent of activity in the case of the superficial ones.

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“…Second, because drugs or other biochemical agents can be injected into the vitreous chamber of the eye, their effects are, to a large extent, quarantined from the rest of the CNS and the rest of the body (cf. Blaser and Clarke, 1992). Thus no obvious systemic side-effects were seen in any of the neonatal rats that received intraocular cycloheximide injections.…”

Section: Discussionmentioning

confidence: 84%

The Effect of Cycloheximide and Ganglioside GM1 on the Viability of Retinotectally Projecting Ganglion Cells Following Ablation of the Superior Colliculus in Neonatal Rats

Harvey

Cui

Robertson

1994

Eur J of Neuroscience

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The time-course and extent of death of retinal ganglion cells (RGCs) following ablation of the superior colliculus (SC) in neonatal Wistar rats has recently been described [Harvey, A. R. and Robertson, D. (1992) J. Comp. Neurol., 325, 83-94]. Normal and pyknotic nuclei of retinotectally projecting ganglion cells were visualized using the fluorescent retrograde tracer diamidino yellow (DY), which had been injected into the SC at P2 (day of birth = P0), 2 days prior to tectal removal. The present report sets out to determine whether cycloheximide, an inhibitor of protein synthesis, or ganglioside GM1 reduced this lesion-induced RGC death. All surgery was carried out under ether anaesthesia; DY was injected into the left SC at P2 and the injected area was removed at P4. Cycloheximide (20-500 ng) was injected into the vitreous chamber of the right eye immediately after the lesion and again 11-12 h later. In some rats, cycloheximide administration was delayed until 12 h after the SC ablation. Control rats received SC lesions alone or lesions plus sham eye injections of saline. Different doses of GM1 were applied i.p. or intraocularly. Rats were perfused 24 h after the SC lesion, at the time of peak RGC death. Retinae of lesion only or sham eye injected rats contained approximately 11% pyknotic RGCs and the density of normal RGCs was approximately 3400/mm2. The rate of pyknosis in cycloheximide treated retinae was reduced to approximately 3%. Normal RGC density in these retinae was approximately 5500/mm2, similar to that found in retinae of unlesioned animals.(ABSTRACT TRUNCATED AT 250 WORDS)

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Timing of Neuronal Death following Successive Blockade of Protein Synthesis and Axoplasmic Transport in the Axonal Target Territory

Cited by 6 publications

References 19 publications

Target‐derived BDNF (brain‐derived neurotrophic factor) is essential for the survival of developing neurons in the isthmo‐optic nucleus

Target‐derived BDNF (brain‐derived neurotrophic factor) is essential for the survival of developing neurons in the isthmo‐optic nucleus

Rapid onset of neuronal death induced by blockade of either axoplasmic transport or action potentials in afferent fibers during brain development

The Effect of Cycloheximide and Ganglioside GM1 on the Viability of Retinotectally Projecting Ganglion Cells Following Ablation of the Superior Colliculus in Neonatal Rats

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