Premium
P3–287: Effects of lovastatin on secretion of MCP–1 and nitric oxide by cultured adult mouse astrocytes stimulated with IL–1B or TNF–A
Author(s) -
Husemann Jens,
Anankov Roman,
Hossein Ruhella,
Silverstein Samuel
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.1556
Subject(s) - lovastatin , tumor necrosis factor alpha , neuroinflammation , nitric oxide , pharmacology , inflammation , astrocyte , secretion , microglia , interleukin 6 , medicine , interleukin , chemistry , cytokine , immunology , endocrinology , central nervous system , cholesterol
rhesus monkeys and the effects on fA toxicity and recruitment of microglia examined. To determine the possible mechanism of microglia contribution to fA toxicity, generation of reactive oxygen species (ROS) in response to fA was investigated in microglia isolated from aged rhesus cortex. Results: fA resulted in significantly larger stereologically determined volume of damage in aged rhesus cortex when compared with injections of vehicle. Co-injection of MIF with fA or delivery of MIF via Alzet pump resulted in a dose-dependent reduction in the number of microglia and the volume of damage caused by fA determined using unbiased stereological methods. Microglia isolated from the aged rhesus cortex displayed robust production of ROS following stimulation with fA . Significantly, MIF resulted in a dose dependent reduction in the production of ROS by aged rhesus microglia following fA stimulation. Conclusions: These observations indicate that fA , which is deposited in plaques in Alzheimer’s disease, is likely to exert toxic effects on aging neurons in the primate. Microglia appear to make a major contribution to the age-related vulnerability of neurons to fA toxicity in the primate brain, most likely through enhanced production of reactive oxygen species. The absence of microglia activation following low dose fA injections in the young rhesus and inhibition of toxicity of such injections in the aged rhesus following MIF treatment suggest that aged primate microglia may display an enhanced response to fA stimulation.