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

Abstract

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 Aβ42 oligomer-induced memory impairments. We found that rosiglitazone attenuated Aβ42 oligomer-induced memory impairments in rats in a dose-dependent manner. The levels of inflammatory cytokines interleukin-1 beta (IL-1β) and interferon gamma (IFNγ) were significantly increased 7 days after injection of Aβ42 oligomers into the rat hippocampus. Inhibition of microglia activation prevented Aβ42 oligomer-induced increases in IL-1β and IFNγ levels. Rosiglitazone completely prevented the increase in the levels of IL-1β and IFNγ induced by Aβ42 oligomers. Treatment of hippocampal slices with the inflammatory cytokine IL-1β or IFNγ 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 Aβ42 oligmers.

Keywords: Alzheimer's disease; Amyloid-beta 42 oligomers; Inflammatory cytokines; Long-term potentiation; Rosiglitazone.