Effects of pyrrolidine dithiocarbamate on beta-amyloid (25-35)-induced inflammatory responses and memory deficits in the rat

It has been well established that neuroinflammation is involved in Alzheimer disease (AD) pathogenesis. Accumulation and aggregation of beta-amyloid (A beta) peptide in the brains of patients with AD result in activation of glial cells which, in turn, initiates neuroinflammatory responses that involve reactive oxygen intermediates and release of inflammatory cytokines. In this study, bilateral intracerebroventricular (icv) injections of A beta (25-35) in the rat resulted in impairment in learning and spatial memory and increased immunoreactive staining of AD-related neuropathological markers (A beta, APP) and inflammatory mediators (OX-6, COX-2) in CA1 and dentate gyrus regions of the hippocampus. Pyrrolidine dithiocarbamate (PDTC) given intraperitoneally 30 min before A beta injection and daily for 7 days postsurgery significantly prevented A beta-induced neuropathological and neuroinflammatory responses, as well as the learning and spatial memory deficits. The potential of PDTC for reducing cognitive and neuropathological deficits may provide preliminary evidence for a new approach of AD treatment. (c) 2006 Elsevier Inc. All rights reserved.