Kinetics of the neuroinflammation-oxidative stress correlation in rat brain following the injection of fibrillar amyloid-beta onto the hippocampus in vivo.
The purpose of this study was to describe-following the injection of a single intracerebral dose of fibrillar amyloid-beta(1-40) in vivo-some correlations between proinflammatory cytokines and oxidative stress indicators in function of time, as well as how these variables fit in a regression model. We found a positive, significant correlation between interleukin (IL)-1beta or IL-6 and the activity of the glutathione peroxidase enzyme (GSH-Px), but IL-1beta or IL-6 maintained a strong, negative correlation with the lipid peroxidation (LPO). The first 12 h marked a positive correlation between IL-6 and tumor necrosis factor-alpha (TNF-alpha), but starting from the 36 h, this relationship became negative. We found also particular patterns of behavior through the time for IL-1beta, nitrites and IL-6, with parallel or sequential interrelationships. Results shows clearly that, in vivo, the fibrillar amyloid-beta (Abeta) disrupts the oxidative balance and initiate a proinflammatory response, which in turn feeds the oxidative imbalance in a coordinated, sequential way. This work contributes to our understanding of the positive feedbacks, focusing the "cytokine cycle" along with the oxidative stress mediators in a complex, multicellular, and interactive environment.
Rosales-Corral
Sergio
S
Centro de Investigación Biomédica de Occidente del Instituto Mexicano del Seguro Social, Sierra Mojada 800, Colonia Independencia, CP 44340 Guadalajara, Jalisco, Mexico. sarco60@yahoo.com
Tan
Dun-Xian
DX
Reiter
Russel J
RJ
Valdivia-Velázquez
Miguel
M
Acosta-Martínez
J Pablo
JP
Ortiz
Genaro G
GG
D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D004789:Enzyme Activation / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D018836:Inflammation Mediators / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D007700:Kinetics; D016014:Linear Models; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric
D016229:Amyloid beta-Peptides; D018836:Inflammation Mediators; D007375:Interleukin-1; D007378:Interleukins; D009573:Nitrites; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C090308:amyloid beta-protein (40-1); D005979:Glutathione Peroxidase