Nerve destruction by colchicine in mice and golden hamsters

Angevine, Jay B.

doi:10.1002/jez.1401360209

Cited by 50 publications

(10 citation statements)

References 34 publications

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“…Colchicine also apparently binds to components of plasma and nuclear membranes as well as to free tubulin (29)(30)(31). Although some studies using doses of colchicine similar to those of the present study report only reversible effects (22,32), several other papers suggest lasting morphological changes in neurons and glia (23,(33)(34)(35)(36).…”

Section: Discussionsupporting

confidence: 57%

Preferential neurotoxicity of colchicine for granule cells of the dentate gyrus of the adult rat.

Goldschmidt¹,

Steward²

1980

Proc. Natl. Acad. Sci. U.S.A.

132

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Injections of 5-7 ,ug (6-9 nmol) of colchicine into the dentate gyrus of the hippocampus of mature rats result in widespread destruction of dentate granule cells with little, if any, damage to other cell populations, including hippocampal pyramidal cells. Selective destruction of dentate granule cells is also observed after intraventricular injections. The destructive effects of colchicine appear as soon as 12 hr after the injection and lead to the disappearance of the granule cells over a period of days. Whereas the effects on nongranule cell populations in the hippocampus appear to be reversed by approximately 11 days after injection, the granule cells are almost completely absent at long intervals after injection. At the long postinjection survival intervals the disappearance of the granule cells is accompanied by elimination of their terminal projections, the mossy fibers, as revealed by Timm staining for heavy metals. Because the preferential neurotoxic effects of colchicine do not result in morbidity or obvious behavioral debilitation, the toxicity may prove useful for studying the functional consequences of removing specific cell populations in the central nervous system.In recent years, the ablation technique for studying brain function has received much criticism due to the lack of selectivity of the electrolytic or aspiration techniques traditionally used. This lack of selectivity is a particular problem when one attempts to dissociate the effects of the removal of specific neurons from the interruption of fibers having distant origins and terminations (fibers of passage), or when one attempts to ascribe the effects of lesions to the removal of one specific population of cells contained within a structure composed of heterogeneous cell types. Because of these problems, considerable recent interest has been generated by drugs or other treatments that are selective in their toxic effects on given neuronal populations or that can destroy neuronal cell bodies without interrupting fibers of passage. Several means of inducing more or less selective lesions have been described, including x-irradiation during development (1-3) and injections of toxic analogs of presumed neurotransmitters, including norepinephrine and dopamine (4-8), serotonin (9), and glutamic acid (10-12). These selective methods have provided new insights into the behavioral, biochemical, and physiological changes associated with the removal of specific cell populations in situations in which more traditional methods for producing lesions have largely reached the limits of their usefulness (13)(14)(15)(16)(17)(18)(19). Because of the tremendous potential of methods with a selective neurotoxic effect, particularly when these effects can be wrought in mature animals, we were intrigued by an apparently selective toxicity of colchicine for granule cells of the dentate gyrus of the hippocampal formation. The present study describes this effect.The publication costs of this article were defrayed in part by page charge payment. This article...

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Section: Discussionsupporting

confidence: 57%

Preferential neurotoxicity of colchicine for granule cells of the dentate gyrus of the adult rat.

Goldschmidt¹,

Steward²

1980

Proc. Natl. Acad. Sci. U.S.A.

132

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“…The apparent degeneration of some neurones several weeks after local application of colchicine is puzzling. Although injection of the drug into peripheral nerves or chronic application can cause pronounced Wallerian degeneration (Angevine, 1957;Albuquerque et al 1972; see also Singer & Steinberg, 1972), there was little physiological or anatomical evidence of this occurring during the first week after drug treatment in the present experiments. The percentage of neurones antidromically driven by the treated branch was only marginally reduced compared to normal ganglia, and axons at, or distal to, the site of colchicine application did not show frank signs of degeneration in electron microscopical sections during this period.…”

contrasting

confidence: 51%

“…The animals tolerated this procedure well and, although three animals died in the immediate post-operative period, those that survived appeared normal and did not show signs of colchicine intoxication (Angevine, 1957). After an interval of 4-7 days (or longer in some animals), the ganglia were removed with suitable lengths of the 6-2 cervical sympathetic trunk, and the inferior and superior post-ganglionic branches, for stimulation and recording with glass suction electrodes (Purves, 1975).…”

Section: Effects Of Colchjcine On Neurones Methodsmentioning

confidence: 99%

Functional and structural changes in mammalian sympathetic neurones following colchicine application to post‐ganglionic nerves.

Purves¹

1976

The Journal of Physiology

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SUMMARY1. The -effects of post-ganglionic colchicine application on neurones of the guinea-pig superior cervical ganglion were studied with intracellular recording and electron microscopy.2. Local colchicine application for 30 mmn to one of the major postganglionic nerves caused several electrophysiological changes after 4-7 days in many neurones whose axons run in this nerve. These changes include: (a) a reduction in the amplitude of synaptic potentials elicited by supramaximal preganglionic stimulation; (6) a decrease in the number of preganglionic fibres innervating individual neurones; (c) the development of regenerative responses mn dendrites; and (d) the failure of antidromic action potentials to fully invade the neuronal soma. These functional changes occurred in the absence of impaired impulse conduction or axon degeneration, and were not observed in nearby neurones whose axons ran in an untreated post-ganglionic nerve. The effects of colchicine are similar to the changes produced by axotomy.3. Counts of synapses in thin sections from the region of the ganglion where the affected neurones were located showed a reduction, compared to the number of synapses in other regions of the colchicine treated ganglia, or normal control ganglia. This finding indicates that synaptic depression after colchicine treatment, like that after axotomy, is due primarily to a loss of synaptic contacts from the dendrites of affected nerve cells. Unusual profiles containing numerous vesicular and tubular organelles frequently seen after interruption of the axons were also observed in thin sections after colchicine treatment.4. The similarity of the electrophysiological and ultrastructural effects of colchicine treatment and axon interruption offers further support for the view that synaptic contacts on sympathetic neurones are normally regulated by an interaction of the neuronal soma with its axonal extension to the periphery. 6PHY 259

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“…If, on the other hand, the fast and slow transport are driven by distinct mechanisms, then the microtubule is not the only structure affected by colchicine, and which mechanism is mediated by the microtubules cannot be unambiguously decided. I n all of these experiments the simplistic interpretation of the colchicine effects may be questioned since the drug shows a powerful cytotoxicity (Angevine, 1957)-although our treated crayfish showed no evidence of impaired neural function.…”

Section: Discussionmentioning

confidence: 86%

Studies on the mechanism of axoplasmic transport in the crayfish cord

1969

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SUMMARYFollowing the injection of "H-leucine into a crayfish ganglion, tritiumlabeled proteins were detected remaining in the ganglion and moving a t a slow linear rate caudad along the nerve cord. The rate of movement increased linearly with temperature between 5 and 20°C, but ceased a t 3°C. The movement was also blocked for a distance around a colchicineinjected ganglion. Both of these observations would be compatible with the involvement of microtubules in slow axoplasmic transport. However, in both instances normal-appearing microtubules were observed by electron microscopy. Gel electropherograms of the denatured labeled proteins showed that the transported proteins are complex and may correspond to most of the axoplasmic proteins including the microtubules.

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Nerve destruction by colchicine in mice and golden hamsters

Cited by 50 publications

References 34 publications

Preferential neurotoxicity of colchicine for granule cells of the dentate gyrus of the adult rat.

Preferential neurotoxicity of colchicine for granule cells of the dentate gyrus of the adult rat.

Functional and structural changes in mammalian sympathetic neurones following colchicine application to post‐ganglionic nerves.

Studies on the mechanism of axoplasmic transport in the crayfish cord

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