Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Alzheimer Disease / immunology*
-
Alzheimer Disease / metabolism
-
Amyloid beta-Protein Precursor / genetics
-
Animals
-
Astrocytes / metabolism
-
Choline O-Acetyltransferase / genetics
-
Gene Expression Regulation, Enzymologic / drug effects
-
Gene Expression Regulation, Enzymologic / immunology
-
Glial Fibrillary Acidic Protein / genetics
-
Glutamate Decarboxylase / genetics
-
Interleukin-1 / genetics
-
Interleukin-6 / genetics
-
Lipopolysaccharides
-
Maze Learning
-
Microglia / metabolism
-
Neuritis / chemically induced
-
Neuritis / immunology*
-
Neuritis / metabolism
-
Neurons / chemistry
-
Neurons / enzymology
-
Prosencephalon / immunology
-
Prosencephalon / metabolism
-
RNA, Messenger / analysis
-
Rats
-
Rats, Inbred F344
-
Tumor Necrosis Factor-alpha / genetics
Substances
-
Amyloid beta-Protein Precursor
-
Glial Fibrillary Acidic Protein
-
Interleukin-1
-
Interleukin-6
-
Lipopolysaccharides
-
RNA, Messenger
-
Tumor Necrosis Factor-alpha
-
Choline O-Acetyltransferase
-
Glutamate Decarboxylase