Rosiglitazone prevents the memory deficits induced by amyloid-beta oligomers via inhibition of inflammatory responses

Rosiglitazone has been known to attenuate neurodegeneration in Alzheimer's disease (AD), but the underlying mechanisms remain unclear. In this study, Morris water maze test, ELISA and electrophysiological methods were used to examine the role and underling mechanisms of rosiglitazone on A beta 42 oligomer-induced memory impairments. We found that rosiglitazone attenuated A beta 42 oligomer-induced memory impairments in rats in a dose-dependent manner. The levels of inflammatory cytokines interleukin-1 beta (IL-1 beta) and interferon gamma (IFN gamma) were significantly increased 7 days after injection of A beta 42 oligomers into the rat hippocampus. Inhibition of microglia activation prevented A beta 42 oligomer-induced increases in IL-1 beta and IFN gamma levels. Rosiglitazone completely prevented the increase in the levels of IL-1 beta and IFN gamma induced by A beta 42 oligomers. Treatment of hippocampal slices with the inflammatory cytokine IL-1 beta or IFN gamma significantly inhibited the production of long-term potentiation (LTP) in the dentate gyrus. Rosiglitazone prevented the inhibitory effects of inflammatory cytokines on LTP. Thus, inhibition of inflammatory responses may be part of the mechanisms of action of rosiglitazone on preventing memory deficits induced by A beta 42 oligmers. (C) 2014 Elsevier Ireland Ltd. All rights reserved.