title: Computational analysis of the effects of antineoplastic agents on axonal transport.
abstract: Axonal transport plays a crucial role in neuronal morphogenesis, survival, and function. Despite its importance, however, the molecular mechanisms of axonal transport remain mostly unknown because a simple and quantitative assay system for axonal transport has been lacking. In order to better characterize the molecular mechanisms involved in axonal transport, we here developed a computer-assisted monitoring system. Using lipophilic fluorochrome chloromethylbenzamido dialkylcarbocyanine (CM-DiI) as a labeling dye, we have successfully labeled membranous organelles in cultured chick dorsal root ganglia neurons. We confirmed that sodium azide, an ATPase inhibitor, and nocodazole, a microtubule-destabilizing agent, markedly suppressed anterograde and retrograde axonal transport of CM-DiI-labeled particles. We further tested the effects of several anti-neoplastic drugs on axonal transport. Paclitaxel, vincristine, cisplatin, and oxaliplatin, all of which are known to be neurotoxic and to cause neurological symptoms, suppressed anterograde and retrograde axonal transport. Another series of anti-neoplastic drugs, including methotrexate and 5-fluorouracil, did not affect the axonal transport. This is the first report of an automated monitoring system for axonal transport. This system will be useful for toxicity assays, characterizing axonal transport, or screening drugs that may modify neuronal functions.
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Japan. goshima@med.yokohama-cu.ac.jp
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Goshima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Usui
authors.forename: Takahito
authors.initials: T
authors.lastname: Shiozawa
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Hida
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kuraoka
authors.forename: Sayumi
authors.initials: S
authors.lastname: Takeshita
authors.forename: Naoya
authors.initials: N
authors.lastname: Yamashita
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ichikawa
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kamiya
authors.forename: Takahisa
authors.initials: T
authors.lastname: Gotoh
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Gotoh
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001370:Axonal Transport / Q000187:drug effects* / Q000502:physiology; D002232:Carbocyanines / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D002945:Cisplatin / Q000494:pharmacology; D019295:Computational Biology; D005456:Fluorescent Dyes / Q000378:metabolism; D005472:Fluorouracil / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology; D009474:Neurons / Q000187:drug effects; D015739:Nocodazole / Q000494:pharmacology; D015388:Organelles / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D017239:Paclitaxel / Q000494:pharmacology; D019810:Sodium Azide / Q000494:pharmacology; D012984:Software; D014750:Vincristine / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; C101089:CM-DiI; D002232:Carbocyanines; D005456:Fluorescent Dyes; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D014750:Vincristine; D019810:Sodium Azide; D017239:Paclitaxel; D002945:Cisplatin; D015739:Nocodazole; D005472:Fluorouracil