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 (Abeta) 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 (i.c.v.) injections of Abeta (25-35) in the rat resulted in impairment in learning and spatial memory and increased immunoreactive staining of AD-related neuropathological markers (Abeta, 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 Abeta injection and daily for 7 days postsurgery significantly prevented Abeta-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.
Cheng
Guanliang
G
Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario N6A 5C1, Canada.
Whitehead
Shawn N
SN
Hachinski
Vladimir
V
Cechetto
David F
DF
D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000633:toxicity; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy*; D007276:Injections, Intraventricular; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013859:Thiocarbamates / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid