title: Morphological assessment of ethyl choline mustard aziridinium-induced neurotoxicity in rat brain reaggregate cultures.
abstract: 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 microM 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 microM ECMA produced widespread necrosis with some surviving neurons, surrounded by the still-persisting capsular layer. Treatment with 100 microM 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.
authors.affiliation: Toxicology and Pathology Group, Smith Kline and French, Welwyn, Hertfordshire, UK.
authors.forename: H B
authors.initials: HB
authors.lastname: Jones
authors.forename: A M
authors.initials: AM
authors.lastname: Pillar
authors.forename: A K
authors.initials: AK
authors.lastname: Prince
mesh_terms: D000818:Animals; D001388:Aziridines / Q000633:toxicity*; D001921:Brain / Q000473:pathology*; D002478:Cells, Cultured; D002794:Choline / Q000031:analogs & derivatives* / Q000633:toxicity; D005260:Female; D008854:Microscopy, Electron; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology; D009457:Neuroglia / Q000187:drug effects / Q000648:ultrastructure; D009466:Neuromuscular Blocking Agents / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure; D011247:Pregnancy; D017729:Presynaptic Terminals / Q000187:drug effects / Q000648:ultrastructure; D051381:Rats; D013572:Synaptic Vesicles / Q000187:drug effects / Q000648:ultrastructure
chemical_list: D001388:Aziridines; D009466:Neuromuscular Blocking Agents; C044894:ethylcholine aziridinium; D002794:Choline