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4928350 
Journal Article 
MORPHOLOGICAL ASSESSMENT OF ETHYL CHOLINE MUSTARD AZIRIDINIUM-INDUCED NEUROTOXICITY IN RAT-BRAIN REAGGREGATE CULTURES 
Jones, HB; Pillar, AM; Prince, AK 
1993 
Yes 
Acta Neuropathologica
ISSN: 0001-6322
EISSN: 1432-0533 
SPRINGER VERLAG 
NEW YORK 
86 
154-162 
English 
Foetal rat brain reaggregate cultures have been employed to investigate the morphological changes associated with the neurotoxic action of ethylcholine mustard aziridinium (ECMA). In a companion study we provided evidence for apparent selective cholinergic neurotoxicity. Exposure of 9-day-old cultures to 12.5 muM ECMA for 3 days produced dilatation of selected axon preterminals and terminals in the outer core tissue layer. Axoplasm in these dilated terminals was electron lucent and contained a flocculent, plasma-like material with remnants of the smooth endoplasmic reticulum. Their synaptic vesicle content was much reduced or, absent. Microglial cells were engaged in phagocytosis of these effete structures and a few necrotic neurons were enveloped by glial processes. Exposure to 50 muM ECMA produced widespread necrosis with some surviving neurons, surrounded by the still-persisting capsular layer. Treatment with 100 muM ECMA generated a greater extent of tissue necrosis, with only a few surviving neurons and glial cells being contained within the necrotic tissue mass. Reaggregates frequently disintegrated following capsule loss. Our results indicate that the initial morphological manifestation of ECMA-induced toxicity is dilatation of axon terminals, that are probably of cholinergic origin and are targeted due to their possession of the high-affinity choline transport system which is unique to these neurons. 
ETHYLCHOLINE MUSTARD AZIRIDINIUM (ECMA, AF64A); BRAIN REAGGREGATE CULTURES; ULTRASTRUCTURE