@article{ab62b7c8e2c648c5b7a17a0ac04ba219,
title = "Rapid reorganization of the axonal cytoskeleton induced by a gamma diketone",
abstract = "Microtubules and neurofilaments are the major components of nerve fiber axoplasm and are evenly distributed longitudinally. Rearrangement of this distribution can be induced by a number of chemicals, including 2,5-hexanedione (2,5-HD). Utilizing 2,5-HD, this study explores the earliest time points of observable rearrangement of the cytoskeletal elements. Intrafascicular injections into the sciatic nerve shows central accumulation of microtubules and peripheral relocation of neurofilaments within 1 min of injection, suggesting a direct effect of the toxin of these components.",
keywords = "2,5-hexandione, microtubules, neurofilaments, reorganization",
author = "Zagoren, {Joy C.} and Politis, {Michael J.} and Spencer, {Peter S.}",
note = "Funding Information: in nerves injected with saline or 2,4-hexanedione. Changesin the textureo f axoplasmo f myelinatefdib - ers were evidentb y light-microscopeex aminatioans early as 30 s after 2,5-HD injection. Ultrastructural analysisr evealeda disorientatioonf neurofilaments in scatterende rvef ibersand, at 1 min post-injection, this phenomenonw as widespread( Fig. 1). Mitochondria,m icrotubuleasn d smoothe ndoplasmirce - ticulum were observedin a central region of axoplasm largely devoid of neurofilamentbs ut con-tainingf ine filamentoums ateriaol f unknownid entity. Neurofilamentcso ngregateidn disorganizeda r-ray along the perimeteor f the axon. This abnormal arrangemenotf axoplasmw as observedin fibers at all later timepointsS. chwannc ells and endoneurial fibroblastas ppeareudn changed. These resultss uggestt hata componenotf the cy-toskeletaol rganizatioonf neuronsis specificallya nd selectivelay ffectedb y exposureto 2,5-HD. It is possible that the side-armos f neurotubuleasn d neurofi-lamentsa re affecteds incethe comparablcey toskele- 1 DeCaprio,A , P. andW eberP, ,, Conversioon fl ysineE -ami-no groupst o substitutepdy rroled erivativebsy 2,5-hexane-dione.A possiblem echanismof proteinb inding.T oxicolog- ist, 1 (19811) 34. 2 Ellisman,M . H. and Porter,K . R., Microtrabeculasrt ruc-tureo f the axoplasmimc atrix:V isualizatioon f cross-linking structureas nd their distributionJ,. Cell Biol., 87 (1980) 464-479. 3 Griffin,J . W., Price,D . L., HoffmanP, . N. andC ork,L . C., The axonacl ytoskeletona:lt erationosf organizatioann da x-onal transportin modelso f neurofibrillaryp athologyJ,. Neuropath. exp. Neurol., 40( 19813) 16. 4 Politis,M . J., PellegrinoR, . G. and SpencerP, . S., Ultra-structuraslt udieso f thed ying-bacpkr ocessV. . Axonaln eu- tal elementso f Schwannc ells and fibroblastsa ppear to lack theses pecializationas;n dc ytoskeletarel orga-nizationis not observedin thesec ells.I nterruptionof a networko f side-armsn ormallyr esponsiblefo r the orderlyd istributiono f axoplasmiecl ementms ighta c-count for the congregatioonf cytoskeletaell ements inducedb y 2,5-HD. In summaryt,h eses tudiesd emonstratteh e rapid and spontaneourse organizatioonf axoplasmin re-sponset o contactw ith 2,5-HD, an agentc apableo f forming pyrrolesw ith intracellulapr rotein1s. Addi-tionals tudiesa renow requiredto identifyt heprotein target(so) f 2,5-HD; such informationm ayilluminate not only moleculamr echanismusn derlyingth emain-tenanceo f axoplasmioc rganizationb,u t also the se-quenceo f early eventsw hichc ulminatein the onset of axonald egeneration, The authorsw ishto thankM s. Laurell Edwardsf or typingt he manuscriptS. upportedin part by NIOSH Grant 00851a ndShell InternationaRle search.",
year = "1983",
month = jun,
day = "27",
doi = "10.1016/0006-8993(83)90807-7",
language = "English (US)",
volume = "270",
pages = "162--164",
journal = "Brain research",
issn = "0006-8993",
publisher = "Elsevier",
number = "1",
}