Chronic neuroinflammation in rats reproduces components of the neurobiology of Alzheimer's disease.
Inflammatory processes may play a critical role in the pathogenesis of the degenerative changes and cognitive impairments associated with Alzheimer's disease (AD). In the present study, lipopolysaccharide (LPS) from the cell wall of gram-negative bacteria was used to produce chronic, global inflammation within the brain of young rats. Chronic infusion of LPS (0.25 microgram/h) into the 4th ventricle for four weeks produced (1) an increase in the number of glial fibrillary acidic protein-positive activated astrocytes and OX-6-positive reactive microglia distributed throughout the brain, with the greatest increase occurring within the temporal lobe, particularly the hippocampus, (2) an induction in interleukin-1 beta, tumor necrosis factor-alpha and beta-amyloid precursor protein mRNA levels within the basal forebrain region and hippocampus, (3) the degeneration of hippocampal CA3 pyramidal neurons, and (4) a significant impairment in spatial memory as determined by decreased spontaneous alternation behavior on a T-maze.
Hauss-Wegrzyniak
B
B
Arizona Research Laboratories, University of Arizona, Tucson 85724, USA.
Dobrzanski
P
P
Stoehr
J D
JD
Wenk
G L
GL
D000544:Alzheimer Disease / Q000276:immunology* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000276:immunology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D005968:Glutamate Decarboxylase / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008070:Lipopolysaccharides; D018782:Maze Learning; D017628:Microglia / Q000378:metabolism; D009443:Neuritis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000201:enzymology; D016548:Prosencephalon / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016564:Amyloid beta-Protein Precursor; D005904:Glial Fibrillary Acidic Protein; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase