title: Aberrant activation of CDK5 is involved in the pathogenesis of OPIDN.
abstract: Exposure to triorthocresyl phosphate (TOCP) may result in a late neurological complication, i.e. organophosphate-induced delayed neuropathy (OPIDN). The aim of this study was to examine changes in levels of cyclin-dependent kinase 5 (CDK5) and of its activator, p35/p25, in the spinal cord of hens treated by TOCP. After exposure to a single dose of TOCP, groups of adult hens were examined in 3, 5, 7, 9, 14, and 18 days after exposure. CDK5, p35/p25 expression and distribution in the lumbar spinal cord were evaluated by immunohistochemistry and Western blotting. The hens showed signs of OPIDN around day 9 after exposure. The number of p (phosphorylated) -CDK5 and p35 positive cells increased significantly. Co-localization and mislocalization of p-CDK5 and p35/p25 was identified and became evident in neurons around the 9th day. Meanwhile, CDK5, p-CDK5, p35, p25 protein levels and p25/p35 ratio were increased, and peaked around the 9th day, then decreased. Some hens' unilateral common peroneal was treated by roscovitine 3 days after TOCP exposure. Axonal transport of these nerves was faster than of their opposite side and of those simply treated by TOCP. These findings indicate aberrant activation of CDK5 may be involved in the pathogenesis of OPIDN.
authors.affiliation: Institute of Neurosciences, The Fourth Military Medical University, Xi'an, China.
authors.forename: Ying-Peng
authors.initials: YP
authors.lastname: Wang
authors.forename: Dan-Lei
authors.initials: DL
authors.lastname: Mou
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Song
authors.forename: Zhi-Ren
authors.initials: ZR
authors.lastname: Rao
authors.forename: Duan
authors.initials: D
authors.lastname: Li
authors.forename: Gong
authors.initials: G
authors.lastname: Ju
mesh_terms: D000818:Animals; D002645:Chickens; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005260:Female; D006735:Horseradish Peroxidase; D007150:Immunohistochemistry; D009422:Nervous System Diseases / Q000139:chemically induced / Q000201:enzymology*; D014317:Tritolyl Phosphates / Q000633:toxicity*
chemical_list: D014317:Tritolyl Phosphates; D006735:Horseradish Peroxidase; D051360:Cyclin-Dependent Kinase 5; C025541:tri-o-cresyl phosphate