title: Paclitaxel causes degeneration of both central and peripheral axon branches of dorsal root ganglia in mice.
abstract: Peripheral neuropathy is a common and dose-limiting side effect of many cancer chemotherapies. The taxane agents, including paclitaxel (Taxol(®)), are effective chemotherapeutic drugs but cause degeneration of predominantly large myelinated afferent sensory fibers of the peripheral nervous system in humans and animal models. Dorsal root ganglia (DRG) neurons are sensory neurons that have unipolar axons each with two branches: peripheral and central. While taxane agents induce degeneration of peripheral axons, whether they also cause degeneration of central nervous system axons is not clear. Using a mouse model of paclitaxel-induced neuropathy, we investigated the effects of paclitaxel on the central branches of sensory axons.
  
  
  
  We observed that in the spinal cords of paclitaxel-intoxicated mice, degenerated axons were present in the dorsal columns, where the central branches of DRG axons ascend rostrally. In the peripheral nerves, degenerated myelinated fibers were present in significantly greater numbers in distal segments than in proximal segments indicating that this model exhibits the distal-to-proximal degeneration pattern generally observed in human peripheral nerve disorders.
  
  
  
  We conclude that paclitaxel causes degeneration of both the peripheral and central branches of DRG axons, a finding that has implications for the site and mode of action of chemotherapy agents on the nervous system.
authors.affiliation: Neuromuscular Division, Department of Neurology, Johns Hopkins University School of Medicine, The John G. Rangos Sr. Building, Room 239, 855 N. Wolfe Street, Baltimore, MD, 21205, USA.|Harvard University, Boston, MA, USA.
authors.forename: Aniqa
authors.initials: A
authors.lastname: Tasnim
authors.affiliation: Neuromuscular Division, Department of Neurology, Johns Hopkins University School of Medicine, The John G. Rangos Sr. Building, Room 239, 855 N. Wolfe Street, Baltimore, MD, 21205, USA.|University of Maryland Medical School, Baltimore, MD, USA.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Rammelkamp
authors.affiliation: Neuromuscular Division, Department of Neurology, Johns Hopkins University School of Medicine, The John G. Rangos Sr. Building, Room 239, 855 N. Wolfe Street, Baltimore, MD, 21205, USA.
authors.forename: Amy B
authors.initials: AB
authors.lastname: Slusher
authors.affiliation: Johns Hopkins Drug Discovery Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Wozniak
authors.affiliation: Neuromuscular Division, Department of Neurology, Johns Hopkins University School of Medicine, The John G. Rangos Sr. Building, Room 239, 855 N. Wolfe Street, Baltimore, MD, 21205, USA.|Johns Hopkins Drug Discovery Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Slusher
authors.affiliation: Neuromuscular Division, Department of Neurology, Johns Hopkins University School of Medicine, The John G. Rangos Sr. Building, Room 239, 855 N. Wolfe Street, Baltimore, MD, 21205, USA. mfarah2@jhmi.edu.
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Farah
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001369:Axons / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology; D017239:Paclitaxel / Q000633:toxicity*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000473:pathology; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D017239:Paclitaxel
keywords: Activated macrophages; Axonal degeneration; Neuropathy