Combined effects of deafferentation and de-efferentation on isthmo-optic neurons during the period of their naturally occurring cell death

Abstract

We have studied the effects on the chick embryo's isthmo-optic nucleus of de-efferentation alone or in combination with deafferentation. De-efferentation was achieved by pharmacological destruction of the axonal target cells in the retina at E13, or by colchicine-blockade of axoplasmic transport in the intraocular parts of the isthmo-optic axons at E13; deafferentation was by a tectal lesion at E11 or E12. De-efferentation alone causes all the isthmo-optic neurons to die, and mostly by the "endocytic-autophagic" mode of cell death, which is characterized by pronounced endocytosis (of an intravascularly injected label) and by intense, clumped activity of two lysosomal enzymes (acid phosphatase and N-acetyl-beta-glucosaminidase). Deafferentation plus de-efferentation caused there to be less endocytic-autophagic dying cells in the isthmo-optic nucleus than after de-efferentation alone, but all the neurons still died. Our interpretation is that deafferentation switched many of the isthmo-optic neurons to a completely different (nonendocytic, nonautophagic) mode of cell death.

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

“…That the retrograde effects of colchicine appli cation arc due to the perikaryon being deprived of neuro trophic support owing to the blockade of axoplasmic transport is virtually certain in the case of sympathetic neurons, since to survive they require NGF, which they can normally obtain only via colchicine-sensitive retro grade transport [14,15], and since systemically adminis tered NGF counteracts the toxic effects of colchicine (or other tubulin-binding substances) on sympathetic neu rons [16,17]. In the ION, the same is likely to be true, although our only evidence is that the neuronal death provoked in the ION by an intraocular injection of col chicine is of a particular morphologic type that occurs reliably when the ION is prevented (by any of several means: early retinal ablation, late destruction of the reti nal target cells, or blockade of axoplasmic transport) from receiving retrograde maintenance, but not when the ION neurons die from other causes such as deafferentation [7][8][9].…”

“…As at younger ages [7][8][9], in embryos that received a single colchicine injection at E16.0, the contralateral ION showed the first signs of degeneration about 24 h later, and became markedly degenerate by 30 h after colchicine injection. By 36 h after colchicine injection, it contained only 2,000-3,000 neurons, compared with 9,000-10,000 on the control side (table 1A).…”

Regulation of endothelial monocyte-activating polypeptide II release by apoptosis

“…23). It has been hypothesized that these large numbers of apoptotic cells correspond to the overproduction of neuronal cells and their incorrect projection to their target sites (24). The developing eye is another example where a colocalization of EMAP II mRNA and TUNEL staining was observed (Fig.…”

Developmental cell death: morphological diversity and multiple mechanisms

“…This latter conclusion is supported by recent experiments on the isthmo-optic nucleus in the avian brain, where it was known that deprivation of retrograde maintenance from the axonal target caused autophagic cell death (characterized also by endocytosis) whereas preventing the arrival of afferents caused a nonautophagic type (possibly type 1) (Clarke 1984(Clarke , 1985bHornung et al 1989). If the two operations are combined, the autophagy (and associated endocytosis) are suppressed (Clarke and Egloff 1988).…”