title: Oxidative Stress Mediated Hippocampal Neuron Apoptosis Participated in Carbon Disulfide-Induced Rats Cognitive Dysfunction.
abstract: Occupational exposure to carbon disulfide (CS2) exhibits central nervous systems toxicity. But the mechanism is unclear. The present study was designed to investigate the relationship between the CNS damage and cognitive dysfunction caused by CS2, and eventually reveal the possible oxidative-related mechanism of hippocampus pathological changes in CS2exposed rats. Male Wistar rats were administrated with CS2at dosage of 200, 400 and 600 mg/kg for consecutive 20 days, respectively. Cognitive performances were evaluated by Morris water maze tests. Thionin and immunohistochemical analysis were used to investigate the hippocampal neuron damage, and the expression of apoptosis related proteins (cleaved-caspase 3, Bax and Bcl-2) were detected to explore the possible mechanisms of neuronal loss. Oxidative stress parameters were checked by commercial assay kits. Rats exposed to CS2displayed cognitive dysfunction manifested as decreased spatial learning ability and memory lesion. Pathological changes and significant neuron loss were observed in hippocampus, especially in CA1 and CA3 sub-regions. Mitochondria-dependent apoptosis pathway was implicated in the CS2-induced neuronal loss which was demonstrated by the up-regulation of cleaved-caspase 3 and Bax accompanied with down-regulation of Bcl-2. Furthermore, extensive oxidative stress induced by CS2was also revealed by the measurement of ROS, RNS, MDA, GSH&GSSG and antioxidant enzymes (CAT, T-SOD, and GSH-Px). Our study suggested that oxidative stress mediated hippocampal neuron apoptosis might play an important role in CS2induced CNS damage and cognitive dysfunction.
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Gleniece
authors.initials: G
authors.lastname: Irving
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Xujing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Han
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Yongpeng
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Yilin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zeng
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Fuyong
authors.initials: F
authors.lastname: Song
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Xiulan
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong, 250012, China. keqinx@sdu.edu.cn.
authors.forename: Keqin
authors.initials: K
authors.lastname: Xie
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002246:Carbon Disulfide / Q000633:toxicity*; D060825:Cognitive Dysfunction / Q000139:chemically induced / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002246:Carbon Disulfide
keywords: Apoptosis; Carbon disulfide; Central nervous system damage; Cognitive dysfunction; Oxidative stress