A fine structural study of the formation of temporary swellings (Herring bodies) and reversible degeneration of neurosecretory axons following microiontophoretic ejection of vinblastine into the hypothalamo-neurohypophysial tract of the frog (Rana pipiens)

Abstract

The microiontophoretic ejection of vinblastine into the median eminence effectively blocked axonal transport in the hypothalamoneurohypophysial system of the frog. Proximal to the ejection site, large axon swellings (Herring bodies) were found that contained mainly abundant neurosecretory granulated vesicles and axonal smooth endoplasmic reticulum. At advanced post ejection times, autophagic events were obvious. Subsequently, preexperimental conditions were reestablished, indicative of the resumption of axonal transport. Distal to the ejection site, i.e. in the neural lobe, the relatively long block of axonal transport subsequent to the vinblastine ejection caused most axons to degenerate and to be phagocytized by pituicytes. The degenerative process was reversible since upon reestablishment of the axonal transport regeneration of the neurosecretory fibers occurred.

A mouse model of familial amyotrophic lateral sclerosis expressing a mutant superoxide dismutase 1 shows evidence of disordered transport in the vasopressin hypothalamo‐neurohypophysial axis

“…These anatomical elements undergo morphological changes that correlate with the onset of appropriate physiological stimuli, including osmotic changes, parturition and lactation (Tweedle & Hatton 1987; Beagley & Hatton 1992). Similar morphological phenomena are also observed when axonal transport of neurosecretory granules (NSG) is damaged (Dellmann & Rodriguez 1970; Dellmann & Sikora‐VanMeter 1982; Chang & Dellmann 1984), thus providing a very valuable model for investigation of pathological processes.…”

“…(1981) showed that lesions of the periventricular tissue around the preoptic recess in the rat brain provoked increased numbers of swellings, containing dense bodies and lamellar dense bodies indicative of enhanced crinophagy. Similarly, Chang & Dellmann (1984) demonstrated that interruption of axonal transport in the frog hypothalamo‐neurohypophysial axis, by microiontophoretic injection of the antimitotic drug vinblastine into the median eminence, induced the appearance of Herring bodies, in which autophagic events became evident at longer postinjection times. In our transgenic mouse model, classification of large swellings based on ultrastructural criteria revealed a higher amount of swellings with characteristics like those reported in the studies mentioned.…”

“…presence of autophagic vacuoles, dense bodies and empty vesicles), an increase in NSG size has been observed under both normal conditions (Dellmann & Rodriguez 1970) and experimentally‐induced axon degeneration (Dellmann et al . 1968; Chang & Dellmann 1984). It is noteworthy that neither clearly recognizable degenerating axons nor increased phagocytic activity of pituicytes, both events being indicative of neuronal degeneration (Zambrano & De Robertis 1968; Chang & Dellmann 1984), were specifically detected in the SOD1 mutant animals.…”

“…1968; Chang & Dellmann 1984). It is noteworthy that neither clearly recognizable degenerating axons nor increased phagocytic activity of pituicytes, both events being indicative of neuronal degeneration (Zambrano & De Robertis 1968; Chang & Dellmann 1984), were specifically detected in the SOD1 mutant animals. In this respect, two possible explanations are conceivable.…”

“…acute chemical treatments (Rodriguez Echandia et al . 1977; Chang & Dellmann 1984) or axonal transection (Dellmann & Owsley 1969). Consistent with the latter idea, some of the modifications in the hypothalamo‐neurohypophysial axis of G86R mice occur during the presymptomatic phase, which suggests a slow and persistent damage of the tract.…”