title: Myelin structure is unaltered in chemotherapy-induced peripheral neuropathy.
abstract: OBJECTIVE
  Alterations in mRNA for myelin proteins are reported in animal models of chemotherapy-induced peripheral neuropathies (CIPN); however, ultrastructural changes in aldehyde-fixed and plastic-embedded myelin are not evident by electron microscopy. Therefore, we used X-ray diffraction (XRD) to investigate more subtle changes in myelin sheath structure from unfixed nerves.
  
  
  METHODS
  We used in vivo chronic animal models of CIPN in female Wistar rats, administering cisplatin (CDDP 2mg/kg, i.p. twice/week), paclitaxel (PT 10mg/kg, i.v. once/week) or bortezomib (0.20mg/kg, i.v. three times/week) over a total period of 4weeks. Animal weights were monitored, and tail nerve conduction velocity (NCV) was determined at the end of the treatments to assess the occurrence of peripheral neuropathy. Sciatic nerves were collected and the myelin structure was analyzed using electron microscopy (EM) and XRD.
  
  
  RESULTS
  All the rats treated with the chemotherapy agents developed peripheral neuropathy, as indicated by a decrease in NCV values; however, light and electron microscopy indicated no severe pathological alterations of the myelin morphology. XRD also did not demonstrate significant differences between sciatic nerves in treated vs. control rats with respect to myelin period, relative amount of myelin, membrane structure, and regularity of membrane packing.
  
  
  CONCLUSIONS
  These results indicate that experimental peripheral neuropathy caused by CDDP, PT, and bortezomib-which are among the most widely used chemotherapy agents-does not significantly affect the structure of internodal myelin in peripheral nerve.
authors.affiliation: Department of Neuroscience and Biomedical Technologies, University of Milan-Bicocca, Monza, Italy. a.gilardini@gmail.com
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gilardini
authors.forename: Robin L
authors.initials: RL
authors.lastname: Avila
authors.forename: Norberto
authors.initials: N
authors.lastname: Oggioni
authors.forename: Virginia
authors.initials: V
authors.lastname: Rodriguez-Menendez
authors.forename: Mario
authors.initials: M
authors.lastname: Bossi
authors.forename: Annalisa
authors.initials: A
authors.lastname: Canta
authors.forename: Guido
authors.initials: G
authors.lastname: Cavaletti
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Kirschner
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D046529:Microscopy, Electron, Transmission; D009185:Myelin Proteins / Q000378:metabolism* / Q000648:ultrastructure; D009186:Myelin Sheath / Q000473:pathology / Q000648:ultrastructure; D009431:Neural Conduction / Q000187:drug effects; D009900:Optic Nerve / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D014961:X-Ray Diffraction
chemical_list: D000970:Antineoplastic Agents; D009185:Myelin Proteins