Immobilization stress induces cell death through production of reactive oxygen species in the mouse cerebral cortex.
Prolonged stress has been shown to impair brain function and increase vulnerability to neuronal injury. To elucidate the in vivo response of neuronal cells to induced stress, we immobilized mice by binding their legs. Levels of reactive oxygen species (ROS) in the cerebral cortex were increased after stress induction. NADPH oxidase, interleukin-1beta (IL-1beta) and cyclooxygenase 2 mRNA (COX-2) expression levels were upregulated, and Fas levels were also increased. The increased expression of these factors was associated with neuronal death, which was confirmed by TUNEL and NeuN staining. OX42 staining was also evident around the TUNEL-stained lesions. From these findings, it appears that immobilization stress induces neuronal death in the mouse cerebral cortex, a process mediated by NADPH oxidase, IL-1beta, COX-2, ROS and Fas. However, this could be inhibited by pretreating the animals with antioxidants such as ebselen or pyrrolidine dithiocarbamate.
Lee
Young Jun
YJ
Laboratory of Cell Biology, Ajou University Institute for Medical Sciences, Suwon 442-721, South Korea.
Choi
Bunsoon
B
Lee
Eunjoo Hwang
EH
Choi
Kyeong Sook
KS
Sohn
Seonghyang
S
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001393:Azoles / Q000627:therapeutic use; D039481:CD11b Antigen / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D007103:Immobilization / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D054833:Isoindoles; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D016566:Organoselenium Compounds / Q000627:therapeutic use; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013312:Stress, Physiological / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
D000975:Antioxidants; D001393:Azoles; D039481:CD11b Antigen; D007375:Interleukin-1; D054833:Isoindoles; D016566:Organoselenium Compounds; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D019014:fas Receptor; C042986:ebselen; D051546:Cyclooxygenase 2; D019255:NADPH Oxidases; D010751:Phosphopyruvate Hydratase