Neuro-inflammatory response in rats chronically exposed to (137)Cesium.
After the Chernobyl nuclear accident, behavioural disorders and central nervous system diseases were frequently observed in populations living in the areas contaminated by (137)Cs. Until now, these neurological disturbances were not elucidated, but the presence of a neuro-inflammatory response could be one explanation. Rats were exposed for 3 months to drinking water contaminated with (137)Cs at a dose of 400Bqkg(-1), which is similar to that ingested by the population living in contaminated areas in the former USSR countries. Pro-inflammatory and anti-inflammatory cytokine genes were assessed by real-time PCR in the frontal cortex and the hippocampus. At this level of exposure, gene expression of TNF-alpha and IL-6 increased in the hippocampus and gene expression of IL-10 increased in the frontal cortex. Concentration of TNF-alpha, measured by ELISA assays, was also increased in the hippocampus. The central NO-ergic pathway was also studied: iNOS gene expression and cNOS activity were significantly increased in the hippocampus. In conclusion, this study showed for the first time that sub-chronic exposure with post-accidental doses of (137)Cs leads to molecular modifications of pro- and anti-inflammatory cytokines and NO-ergic pathway in the brain. This neuro-inflammatory response could contribute to the electrophysiological and biochemical alterations observed after chronic exposure to (137)Cs.
Lestaevel
Philippe
P
Institut de Radioprotection et de Sûreté Nucléaire, Service de Radiobiologie et d'Epidémiologie, BP 17, 92262 Fontenay-aux-Roses, France. philippe.lestaevel@irsn.fr
Grandcolas
Line
L
Paquet
François
F
Voisin
Philippe
P
Aigueperse
Jocelyne
J
Gourmelon
Patrick
P
D000818:Animals; D002588:Cesium Radioisotopes / Q000633:toxicity*; D047852:Chernobyl Nuclear Accident; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004790:Enzyme Induction; D004797:Enzyme-Linked Immunosorbent Assay; D005625:Frontal Lobe / Q000201:enzymology / Q000378:metabolism / Q000528:radiation effects*; D015870:Gene Expression / Q000528:radiation effects*; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism / Q000528:radiation effects*; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D009443:Neuritis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D002588:Cesium Radioisotopes; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat